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Sample records for evaluate drugdrug interactions

  1. Evaluation of drug-drug interactions among patients with chronic ...

    African Journals Online (AJOL)

    Introduction: The risk of drug-drug interactions (DDIs) is high in patients with chronic kidney disease (CKD) necessitating dose adjustments or the avoidance of drug combinations. This study aimed to evaluate DDIs among patients with CKD in the University of Nigeria Teaching Hospital (UNTH), Enugu, South-East Nigeria.

  2. Hepatic transporter drug-drug interactions: an evaluation of approaches and methodologies.

    Science.gov (United States)

    Williamson, Beth; Riley, Robert J

    2017-12-01

    Drug-drug interactions (DDIs) continue to account for 5% of hospital admissions and therefore remain a major regulatory concern. Effective, quantitative prediction of DDIs will reduce unexpected clinical findings and encourage projects to frontload DDI investigations rather than concentrating on risk management ('manage the baggage') later in drug development. A key challenge in DDI prediction is the discrepancies between reported models. Areas covered: The current synopsis focuses on four recent influential publications on hepatic drug transporter DDIs using static models that tackle interactions with individual transporters and in combination with other drug transporters and metabolising enzymes. These models vary in their assumptions (including input parameters), transparency, reproducibility and complexity. In this review, these facets are compared and contrasted with recommendations made as to their application. Expert opinion: Over the past decade, static models have evolved from simple [I]/k i models to incorporate victim and perpetrator disposition mechanisms including the absorption rate constant, the fraction of the drug metabolised/eliminated and/or clearance concepts. Nonetheless, models that comprise additional parameters and complexity do not necessarily out-perform simpler models with fewer inputs. Further, consideration of the property space to exploit some drug target classes has also highlighted the fine balance required between frontloading and back-loading studies to design out or 'manage the baggage'.

  3. Drug repurposing based on drug-drug interaction.

    Science.gov (United States)

    Zhou, Bin; Wang, Rong; Wu, Ping; Kong, De-Xin

    2015-02-01

    Given the high risk and lengthy procedure of traditional drug development, drug repurposing is gaining more and more attention. Although many types of drug information have been used to repurpose drugs, drug-drug interaction data, which imply possible physiological effects or targets of drugs, remain unexploited. In this work, similarity of drug interaction was employed to infer similarity of the physiological effects or targets for the drugs. We collected 10,835 drug-drug interactions concerning 1074 drugs, and for 700 of them, drug similarity scores based on drug interaction profiles were computed and rendered using a drug association network with 589 nodes (drugs) and 2375 edges (drug similarity scores). The 589 drugs were clustered into 98 groups with Markov Clustering Algorithm, most of which were significantly correlated with certain drug functions. This indicates that the network can be used to infer the physiological effects of drugs. Furthermore, we evaluated the ability of this drug association network to predict drug targets. The results show that the method is effective for 317 of 561 drugs that have known targets. Comparison of this method with the structure-based approach shows that they are complementary. In summary, this study demonstrates the feasibility of drug repurposing based on drug-drug interaction data. © 2014 John Wiley & Sons A/S.

  4. Evaluation of Drug-Drug Interaction Potential Between Sacubitril/Valsartan (LCZ696) and Statins Using a Physiologically Based Pharmacokinetic Model.

    Science.gov (United States)

    Lin, Wen; Ji, Tao; Einolf, Heidi; Ayalasomayajula, Surya; Lin, Tsu-Han; Hanna, Imad; Heimbach, Tycho; Breen, Christopher; Jarugula, Venkateswar; He, Handan

    2017-05-01

    Sacubitril/valsartan (LCZ696) has been approved for the treatment of heart failure. Sacubitril is an in vitro inhibitor of organic anion-transporting polypeptides (OATPs). In clinical studies, LCZ696 increased atorvastatin C max by 1.7-fold and area under the plasma concentration-time curve by 1.3-fold, but had little or no effect on simvastatin or simvastatin acid exposure. A physiologically based pharmacokinetics modeling approach was applied to explore the underlying mechanisms behind the statin-specific LCZ696 drug interaction observations. The model incorporated OATP-mediated clearance (CL int,T ) for simvastatin and simvastatin acid to successfully describe the pharmacokinetic profiles of either analyte in the absence or presence of LCZ696. Moreover, the model successfully described the clinically observed drug effect with atorvastatin. The simulations clarified the critical parameters responsible for the observation of a low, yet clinically relevant, drug-drug interaction DDI between sacubitril and atorvastatin and the lack of effect with simvastatin acid. Atorvastatin is administered in its active form and rapidly achieves C max that coincide with the low C max of sacubitril. In contrast, simvastatin requires a hydrolysis step to the acid form and therefore is not present at the site of interactions at sacubitril concentrations that are inhibitory. Similar models were used to evaluate the drug-drug interaction risk for additional OATP-transported statins which predicted to maximally result in a 1.5-fold exposure increase. Copyright © 2017. Published by Elsevier Inc.

  5. Potential drug-drug interactions on in-patient medication ...

    African Journals Online (AJOL)

    Potential drug-drug interactions on in-patient medication prescriptions at Mbarara Regional Referral Hospital (MRRH) in western Uganda: prevalence, clinical importance and associated factors. SJ Lubinga, E Uwiduhaye ...

  6. Identification of clinically significant drug-drug interactions in cardiac ...

    African Journals Online (AJOL)

    Purpose: To identify clinically significant potential drug-drug interactions in cardiac intensive care units of two tertiary care ... hypertension, hyperlipidemia, diabetes or other diseases .... May result in digoxin toxicity (nausea, vomiting, cardiac.

  7. Antifungal therapy: drug-drug interactions at your fingertips

    NARCIS (Netherlands)

    Lempers, V.J.; Bruggemann, R.J.

    2016-01-01

    The Information Age has revolutionized the ability of healthcare professionals (HCPs) to oversee a substantial body of clinically relevant information literally at one's fingertips. In the field of clinical pharmacology, this may be particularly useful for managing drug-drug interactions (DDIs). A

  8. Evaluation of Potential Drug-Drug Interaction Between Delayed-Release Dimethyl Fumarate and a Commonly Used Oral Contraceptive (Norgestimate/Ethinyl Estradiol) in Healthy Women.

    Science.gov (United States)

    Zhu, Bing; Nestorov, Ivan; Zhao, Guolin; Meka, Venkata; Leahy, Mark; Kam, Jeanelle; Sheikh, Sarah I

    2017-11-01

    Delayed-release dimethyl fumarate (DMF) is an oral therapy for relapsing multiple sclerosis with anti-inflammatory and neuroprotective properties. This 2-period crossover study was conducted to evaluate the potential for drug-drug interaction between DMF (240 mg twice daily) and a combined oral contraceptive (OC; norgestimate 250 μg, ethinyl estradiol 35 μg). Forty-six healthy women were enrolled; 32 completed the study. After the lead-in period (OC alone), 41 eligible participants were randomized 1:1 to sequence 1 (OC and DMF coadministration in period 1; OC alone in period 2) or sequence 2 (regimens reversed). Mean concentration profiles of plasma norelgestromin (primary metabolite of norgestimate) and ethinyl estradiol were superimposable following OC alone and OC coadministered with DMF, with 90% confidence intervals of geometric mean ratios for area under the plasma concentration-time curve over the dosing interval and peak plasma concentration contained within the 0.8-1.25 range. Low serum progesterone levels during combined treatment confirmed suppression of ovulation. The pharmacokinetics of DMF (measured via its primary active metabolite, monomethyl fumarate) were consistent with historical data when DMF was administered alone. No new safety concerns were identified. These results suggest that norgestimate/ethinyl estradiol-based OCs may be used with DMF without dose modification. © 2017, The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

  9. Drug-drug interactions involving lysosomes: mechanisms and potential clinical implications.

    Science.gov (United States)

    Logan, Randall; Funk, Ryan S; Axcell, Erick; Krise, Jeffrey P

    2012-08-01

    Many commercially available, weakly basic drugs have been shown to be lysosomotropic, meaning they are subject to extensive sequestration in lysosomes through an ion trapping-type mechanism. The extent of lysosomal trapping of a drug is an important therapeutic consideration because it can influence both activity and pharmacokinetic disposition. The administration of certain drugs can alter lysosomes such that their accumulation capacity for co-administered and/or secondarily administered drugs is altered. In this review the authors explore what is known regarding the mechanistic basis for drug-drug interactions involving lysosomes. Specifically, the authors address the influence of drugs on lysosomal pH, volume and lipid processing. Many drugs are known to extensively accumulate in lysosomes and significantly alter their structure and function; however, the therapeutic and toxicological implications of this remain controversial. The authors propose that drug-drug interactions involving lysosomes represent an important potential source of variability in drug activity and pharmacokinetics. Most evaluations of drug-drug interactions involving lysosomes have been performed in cultured cells and isolated tissues. More comprehensive in vivo evaluations are needed to fully explore the impact of this drug-drug interaction pathway on therapeutic outcomes.

  10. Evaluation of a Potential Metabolism-Mediated Drug-Drug Interaction Between Atomoxetine and Bupropion in Healthy Volunteers.

    Science.gov (United States)

    Todor, Ioana; Popa, Adina; Neag, Maria; Muntean, Dana; Bocsan, Corina; Buzoianu, Anca; Vlase, Laurian; Gheldiu, Ana-Maria; Briciu, Corina

    2016-01-01

    To evaluate the impact of bupropion on the pharmacokinetic profile of atomoxetine and its main active metabolite (glucuronidated form), 4-hydroxyatomoxetine-O-glucuronide, in healthy volunteers. An open-label, non-randomized, two-period, sequential clinical trial was conducted as follows: during Period I (Reference), each volunteer received a single oral dose of 25 mg atomoxetine, whilst during Period II (Test), a combination of 25 mg atomoxetine and 300 mg bupropion was administered to all volunteers, after a pretreatment regimen with bupropion for 7 days. Next, after determining atomoxetine and 4-hydroxyatomoxetine-O-glucuronide plasma concentrations, their pharmacokinetic parameters were calculated using a noncompartmental method and subsequently compared to determine any statistically significant differences between the two periods. Bupropion intake influenced all the pharmacokinetic parameters of both atomoxetine and its metabolite. For atomoxetine, Cmax increased from 226±96.1 to 386±137 ng/mL and more importantly, AUC0-∞ was significantly increasedfrom 1580±1040 to 8060±4160 ng*h/mL, while the mean t1/2 was prolonged after bupropion pretreatment. For 4-hydroxyatomoxetine-O-glucuronide, Cmax and AUC0-∞  were decreased from 707±269 to 212±145 ng/mL and from 5750±1240 to 3860±1220 ng*h/mL, respectively. These results demonstrated that the effect of bupropion on CYP2D6 activity was responsible for an increased systemic exposure to atomoxetine (5.1-fold) and also for a decreased exposure to its main metabolite (1.5-fold). Additional studies are required in order to evaluate the clinical relevance of this pharmacokinetic drug interaction.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

  11. Clopidogrel paclitaxel drug-drug interaction

    DEFF Research Database (Denmark)

    Agergaard, K; Mau-Sørensen, M; Stage, T B

    2017-01-01

    register. Peripheral sensory neuropathy was retrospectively evaluated from medical charts and compared to that of 88 age and sex matched controls treated with paclitaxel and low dose aspirin. By a cumulative dose of 1500 mg paclitaxel, 35% of the patients had developed severe neuropathy. The overall hazard...... ratio between clopidogrel use and severe paclitaxel neuropathy was 1.7 (95% CI, 0.9-3.0). Among those receiving a high dose paclitaxel regimen, the hazard ratio was 2.3 (95% CI, 1.1-4.5). Our study indicates that clopidogrel is associated with a clinically relevant increased risk of neuropathy......Paclitaxel is mainly eliminated by CYP2C8 in the liver. CYP2C8 is strongly inhibited by the clopidogrel metabolite acyl-β-D-glucuronide. To determine if this interaction has clinical relevance, we identified 48 patients treated with clopidogrel and paclitaxel using databases and a prescription...

  12. Indolealkylamines: biotransformations and potential drug-drug interactions.

    Science.gov (United States)

    Yu, Ai-Ming

    2008-06-01

    Indolealkylamine (IAA) drugs are 5-hydroxytryptamine (5-HT or serotonin) analogs that mainly act on the serotonin system. Some IAAs are clinically utilized for antimigraine therapy, whereas other substances are notable as drugs of abuse. In the clinical evaluation of antimigraine triptan drugs, studies on their biotransformations and pharmacokinetics would facilitate the understanding and prevention of unwanted drug-drug interactions (DDIs). A stable, principal metabolite of an IAA drug of abuse could serve as a useful biomarker in assessing intoxication of the IAA substance. Studies on the metabolism of IAA drugs of abuse including lysergic acid amides, tryptamine derivatives and beta-carbolines are therefore emerging. An important role for polymorphic cytochrome P450 2D6 (CYP2D6) in the metabolism of IAA drugs of abuse has been revealed by recent studies, suggesting that variations in IAA metabolism, pharmaco- or toxicokinetics and dynamics can arise from distinct CYP2D6 status, and CYP2D6 polymorphism may represent an additional risk factor in the use of these IAA drugs. Furthermore, DDIs with IAA agents could occur additively at the pharmaco/toxicokinetic and dynamic levels, leading to severe or even fatal serotonin toxicity. In this review, the metabolism and potential DDIs of these therapeutic and abused IAA drugs are described.

  13. Observational study of drug-drug interactions in oncological inpatients

    Directory of Open Access Journals (Sweden)

    María Sacramento Díaz-Carrasco

    2018-01-01

    Full Text Available Objective: To determine the prevalence of potential clinically relevant drug- drug interactions in adult oncological inpatients, as well as to describe the most frequent interactions. A standard database was used. Method: An observational, transversal, and descriptive study including patients admitted to the Oncology Service of a reference hospital. All prescriptions were collected twice a week during a month. They were analysed using Lexicomp® database, recording all interactions classified with a level of risk: C, D or X. Results: A total of 1 850 drug-drug interactions were detected in 218 treatments. The prevalence of treatments with at least one clinically relevant interaction was 95%, being 94.5% for those at level C and 26.1% for levels D and X. The drugs most commonly involved in the interactions detected were opioid analgesics, antipsychotics (butyrophenones, benzodiazepines, pyrazolones, glucocorticoids and heparins, whereas interactions with antineoplastics were minimal, highlighting those related to paclitaxel and between metamizole and various antineoplastics. Conclusions: The prevalence of clinically relevant drug-drug interactions rate was very high, highlighting the high risk percentage of them related to level of risk X. Due to the frequency of onset and potential severity, highlighted the concomitant use of central nervous system depressants drugs with risk of respiratory depression, the risk of onset of anticholinergic symptoms when combining morphine or haloperidol with butylscopolamine, ipratropium bromide or dexchlorpheniramine and the multiple interactions involving metamizole.

  14. Compliance with national guidelines for the management of drug-drug interactions in Dutch community pharmacies.

    NARCIS (Netherlands)

    Buurma, H.; Schalekamp, T.; Egberts, A.C.G.; Smet, P.A.G.M. de

    2007-01-01

    BACKGROUND: Pharmacists contribute to the detection and prevention of drug therapy-related problems, including drug-drug interactions. Little is known about compliance with pharmacy practice guidelines for the management of drug-drug interaction alerts. OBJECTIVE: To measure the compliance of

  15. Clinical risk management in Dutch community pharmacies: the case of drug-drug interactions.

    NARCIS (Netherlands)

    Buurma, H.; Smet, P.A.G.M. de; Egberts, A.C.G.

    2006-01-01

    BACKGROUND: The prevention of drug-drug interactions requires a systematic approach for which the concept of clinical risk management can be used. The objective of our study was to measure the frequency, nature and management of drug-drug interaction alerts as these occur in daily practice of Dutch

  16. Potential drug-drug and drug-disease interactions in well-functioning community-dwelling older adults.

    Science.gov (United States)

    Hanlon, J T; Perera, S; Newman, A B; Thorpe, J M; Donohue, J M; Simonsick, E M; Shorr, R I; Bauer, D C; Marcum, Z A

    2017-04-01

    There are few studies examining both drug-drug and drug-disease interactions in older adults. Therefore, the objective of this study was to describe the prevalence of potential drug-drug and drug-disease interactions and associated factors in community-dwelling older adults. This cross-sectional study included 3055 adults aged 70-79 without mobility limitations at their baseline visit in the Health Aging and Body Composition Study conducted in the communities of Pittsburgh PA and Memphis TN, USA. The outcome factors were potential drug-drug and drug-disease interactions as per the application of explicit criteria drawn from a number of sources to self-reported prescription and non-prescription medication use. Over one-third of participants had at least one type of interaction. Approximately one quarter (25·1%) had evidence of had one or more drug-drug interactions. Nearly 10·7% of the participants had a drug-drug interaction that involved a non-prescription medication. % The most common drug-drug interaction was non-steroidal anti-inflammatory drugs (NSAIDs) affecting antihypertensives. Additionally, 16·0% had a potential drug-disease interaction with 3·7% participants having one involving non-prescription medications. The most common drug-disease interaction was aspirin/NSAID use in those with history of peptic ulcer disease without gastroprotection. Over one-third (34·0%) had at least one type of drug interaction. Each prescription medication increased the odds of having at least one type of drug interaction by 35-40% [drug-drug interaction adjusted odds ratio (AOR) = 1·35, 95% confidence interval (CI) = 1·27-1·42; drug-disease interaction AOR = 1·30; CI = 1·21-1·40; and both AOR = 1·45; CI = 1·34-1·57]. A prior hospitalization increased the odds of having at least one type of drug interaction by 49-84% compared with those not hospitalized (drug-drug interaction AOR = 1·49, 95% CI = 1·11-2·01; drug-disease interaction AOR = 1·69, CI = 1·15-2

  17. Predicting drug?drug interactions through drug structural similarities and interaction networks incorporating pharmacokinetics and pharmacodynamics knowledge

    OpenAIRE

    Takeda, Takako; Hao, Ming; Cheng, Tiejun; Bryant, Stephen H.; Wang, Yanli

    2017-01-01

    Drug?drug interactions (DDIs) may lead to adverse effects and potentially result in drug withdrawal from the market. Predicting DDIs during drug development would help reduce development costs and time by rigorous evaluation of drug candidates. The primary mechanisms of DDIs are based on pharmacokinetics (PK) and pharmacodynamics (PD). This study examines the effects of 2D structural similarities of drugs on DDI prediction through interaction networks including both PD and PK knowledge. Our a...

  18. Drug-Drug Interaction Extraction via Convolutional Neural Networks

    Directory of Open Access Journals (Sweden)

    Shengyu Liu

    2016-01-01

    Full Text Available Drug-drug interaction (DDI extraction as a typical relation extraction task in natural language processing (NLP has always attracted great attention. Most state-of-the-art DDI extraction systems are based on support vector machines (SVM with a large number of manually defined features. Recently, convolutional neural networks (CNN, a robust machine learning method which almost does not need manually defined features, has exhibited great potential for many NLP tasks. It is worth employing CNN for DDI extraction, which has never been investigated. We proposed a CNN-based method for DDI extraction. Experiments conducted on the 2013 DDIExtraction challenge corpus demonstrate that CNN is a good choice for DDI extraction. The CNN-based DDI extraction method achieves an F-score of 69.75%, which outperforms the existing best performing method by 2.75%.

  19. Prolonged Drug-Drug Interaction between Terbinafine and Perphenazine.

    Science.gov (United States)

    Park, Young-Min

    2012-12-01

    I report here an elderly woman receiving perphenazine together with terbinafine. After 1 week of terbinafine treatment she experienced extrapyramidal symptoms and, in particular, akathisia. Her symptoms did not disappear for 6 weeks, and so at 2 weeks prior to this most recent admission she had stopped taking terbinafine. However, these symptoms persisted for 3 weeks after discontinuing terbinafine. It is well known that terbinafine inhibits CYP2D6 and that perphenazine is metabolized mainly by CYP2D6. Thus, when terbinafine and perphenazine are coadministrated, the subsequent increase in the concentration of perphenazine may induce extrapyramidal symptoms. Thus, terbinafine therapy may be associated with the induction and persistence of extrapyramidal symptoms, including akathisia. This case report emphasizes the importance of monitoring drug-drug interactions in patients undergoing terbinafine and perphenazine therapy.

  20. Potential Drug-Drug Interactions among Patients prescriptions collected from Medicine Out-patient Setting.

    Science.gov (United States)

    Farooqui, Riffat; Hoor, Talea; Karim, Nasim; Muneer, Mehtab

    2018-01-01

    To identify and evaluate the frequency, severity, mechanism and common pairs of drug-drug interactions (DDIs) in prescriptions by consultants in medicine outpatient department. This cross sectional descriptive study was done by Pharmacology department of Bahria University Medical & Dental College (BUMDC) in medicine outpatient department (OPD) of a private hospital in Karachi from December 2015 to January 2016. A total of 220 prescriptions written by consultants were collected. Medications given with patient's diagnosis were recorded. Drugs were analyzed for interactions by utilizing Medscape drug interaction checker, drugs.com checker and stockley`s drug interactions index. Two hundred eleven prescriptions were selected while remaining were excluded from the study because of unavailability of the prescribed drugs in the drug interaction checkers. In 211 prescriptions, two common diagnoses were diabetes mellitus (28.43%) and hypertension (27.96%). A total of 978 medications were given. Mean number of medications per prescription was 4.6. A total of 369 drug-drug interactions were identified in 211 prescriptions (175%). They were serious 4.33%, significant 66.12% and minor 29.53%. Pharmacokinetic and pharmacodynamic interactions were 37.94% and 51.21% respectively while 10.84% had unknown mechanism. Number wise common pairs of DDIs were Omeprazole-Losartan (S), Gabapentine- Acetaminophen (M), Losartan-Diclofenac (S). The frequency of DDIs is found to be too high in prescriptions of consultants from medicine OPD of a private hospital in Karachi. Significant drug-drug interactions were more and mostly caused by Pharmacodynamic mechanism. Number wise evaluation showed three common pairs of drugs involved in interactions.

  1. Statin drug-drug interactions in a Romanian community pharmacy.

    Science.gov (United States)

    Badiu, Raluca; Bucsa, Camelia; Mogosan, Cristina; Dumitrascu, Dan

    2016-01-01

    Statins are frequently prescribed for patients with dyslipidemia and have a well-established safety profile. However, when associated with interacting dugs, the risk of adverse effects, especially muscular toxicity, is increased. The objective of this study was to identify, characterize and quantify the prevalence of the potential drug-drug interactions (pDDIs) of statins in reimbursed prescriptions from a community pharmacy in Bucharest. We analyzed the reimbursed prescriptions including statins collected during one month in a community pharmacy. The online program Medscape Drug Interaction Checker was used for checking the drug interactions and their classification based on severity: Serious - Use alternative, Significant - Monitor closely and Minor. 132 prescriptions pertaining to 125 patients were included in the analysis. Our study showed that 25% of the patients who were prescribed statins were exposed to pDDIs: 37 Serious and Significant interactions in 31 of the statins prescriptions. The statins involved were atorvastatin, simvastatin and rosuvastatin. Statin pDDIs have a high prevalence and patients should be monitored closely in order to prevent the development of adverse effects that result from statin interactions.

  2. Using Nonexperts for Annotating Pharmacokinetic Drug-Drug Interaction Mentions in Product Labeling: A Feasibility Study.

    Science.gov (United States)

    Hochheiser, Harry; Ning, Yifan; Hernandez, Andres; Horn, John R; Jacobson, Rebecca; Boyce, Richard D

    2016-04-11

    Because vital details of potential pharmacokinetic drug-drug interactions are often described in free-text structured product labels, manual curation is a necessary but expensive step in the development of electronic drug-drug interaction information resources. The use of nonexperts to annotate potential drug-drug interaction (PDDI) mentions in drug product label annotation may be a means of lessening the burden of manual curation. Our goal was to explore the practicality of using nonexpert participants to annotate drug-drug interaction descriptions from structured product labels. By presenting annotation tasks to both pharmacy experts and relatively naïve participants, we hoped to demonstrate the feasibility of using nonexpert annotators for drug-drug information annotation. We were also interested in exploring whether and to what extent natural language processing (NLP) preannotation helped improve task completion time, accuracy, and subjective satisfaction. Two experts and 4 nonexperts were asked to annotate 208 structured product label sections under 4 conditions completed sequentially: (1) no NLP assistance, (2) preannotation of drug mentions, (3) preannotation of drug mentions and PDDIs, and (4) a repeat of the no-annotation condition. Results were evaluated within the 2 groups and relative to an existing gold standard. Participants were asked to provide reports on the time required to complete tasks and their perceptions of task difficulty. One of the experts and 3 of the nonexperts completed all tasks. Annotation results from the nonexpert group were relatively strong in every scenario and better than the performance of the NLP pipeline. The expert and 2 of the nonexperts were able to complete most tasks in less than 3 hours. Usability perceptions were generally positive (3.67 for expert, mean of 3.33 for nonexperts). The results suggest that nonexpert annotation might be a feasible option for comprehensive labeling of annotated PDDIs across a broader

  3. Drug-drug interactions in prescriptions for hospitalized elderly with Acute Coronary Syndrome

    Directory of Open Access Journals (Sweden)

    Tiago Aparecido Maschio de Lima

    2017-11-01

    Full Text Available The objective was to determine the rate of potential drug-drug interactions in prescriptions for elderly diagnosed with Acute Coronary Syndrome in a teaching hospital. This is an exploratory, descriptive study that analyzed 607 prescriptions through databases to identify and classify the interactions based on intensity (major, moderate or minor, the mechanism (pharmacokinetic or pharmacodynamics and documentation relevance. We detected 10,162 drug-drug interactions, distributed in 554 types of different combinations within the prescribed drugs, and 99% of prescriptions presented at least one and a maximum of 53 interactions; highlighting the prevalence of major and moderates ones. There was a correlation between the number of drug-drug interactions and the number of prescribed drugs and the hospitalization time. This study contributes for the delimitation of a prevalence pattern in drug-drug interactions in prescriptions for Acute Coronary Syndrome, besides subsidizing the importance of the effective implementation of the Clinical Pharmacy in teaching hospitals.

  4. P-glycoprotein interaction with risperidone and 9-OH-risperidone studied in vitro, in knock-out mice and in drug-drug interaction experiments

    DEFF Research Database (Denmark)

    Ejsing, Thomas B.; Pedersen, Anne D.; Linnet, Kristian

    2005-01-01

    P-glycoprotein, risperidone, nortriptyline, cyclosporine A, drug-drug interaction, blood-brain barrier, knock-out mice......P-glycoprotein, risperidone, nortriptyline, cyclosporine A, drug-drug interaction, blood-brain barrier, knock-out mice...

  5. Drug-drug interactions involving antidepressants: focus on desvenlafaxine.

    Science.gov (United States)

    Low, Yvette; Setia, Sajita; Lima, Graca

    2018-01-01

    Psychiatric and physical conditions often coexist, and there is robust evidence that associates the frequency of depression with single and multiple physical conditions. More than half of patients with depression may have at least one chronic physical condition. Therefore, antidepressants are often used in cotherapy with other medications for the management of both psychiatric and chronic physical illnesses. The risk of drug-drug interactions (DDIs) is augmented by complex polypharmacy regimens and extended periods of treatment required, of which possible outcomes range from tolerability issues to lack of efficacy and serious adverse events. Optimal patient outcomes may be achieved through drug selection with minimal potential for DDIs. Desvenlafaxine is a serotonin-norepinephrine reuptake inhibitor approved for the treatment of adults with major depressive disorder. Pharmacokinetic studies of desvenlafaxine have shown a simple metabolic profile unique among antidepressants. This review examines the DDI profiles of antidepressants, particularly desvenlafaxine, in relation to drugs of different therapeutic areas. The summary and comparison of information available is meant to help clinicians in making informed decisions when using desvenlafaxine in patients with depression and comorbid chronic conditions.

  6. QSAR Modeling and Prediction of Drug-Drug Interactions.

    Science.gov (United States)

    Zakharov, Alexey V; Varlamova, Ekaterina V; Lagunin, Alexey A; Dmitriev, Alexander V; Muratov, Eugene N; Fourches, Denis; Kuz'min, Victor E; Poroikov, Vladimir V; Tropsha, Alexander; Nicklaus, Marc C

    2016-02-01

    Severe adverse drug reactions (ADRs) are the fourth leading cause of fatality in the U.S. with more than 100,000 deaths per year. As up to 30% of all ADRs are believed to be caused by drug-drug interactions (DDIs), typically mediated by cytochrome P450s, possibilities to predict DDIs from existing knowledge are important. We collected data from public sources on 1485, 2628, 4371, and 27,966 possible DDIs mediated by four cytochrome P450 isoforms 1A2, 2C9, 2D6, and 3A4 for 55, 73, 94, and 237 drugs, respectively. For each of these data sets, we developed and validated QSAR models for the prediction of DDIs. As a unique feature of our approach, the interacting drug pairs were represented as binary chemical mixtures in a 1:1 ratio. We used two types of chemical descriptors: quantitative neighborhoods of atoms (QNA) and simplex descriptors. Radial basis functions with self-consistent regression (RBF-SCR) and random forest (RF) were utilized to build QSAR models predicting the likelihood of DDIs for any pair of drug molecules. Our models showed balanced accuracy of 72-79% for the external test sets with a coverage of 81.36-100% when a conservative threshold for the model's applicability domain was applied. We generated virtually all possible binary combinations of marketed drugs and employed our models to identify drug pairs predicted to be instances of DDI. More than 4500 of these predicted DDIs that were not found in our training sets were confirmed by data from the DrugBank database.

  7. Comparative analysis of three drug-drug interaction screening systems against probable clinically relevant drug-drug interactions: a prospective cohort study.

    Science.gov (United States)

    Muhič, Neža; Mrhar, Ales; Brvar, Miran

    2017-07-01

    Drug-drug interaction (DDI) screening systems report potential DDIs. This study aimed to find the prevalence of probable DDI-related adverse drug reactions (ADRs) and compare the clinical usefulness of different DDI screening systems to prevent or warn against these ADRs. A prospective cohort study was conducted in patients urgently admitted to medical departments. Potential DDIs were checked using Complete Drug Interaction®, Lexicomp® Online™, and Drug Interaction Checker®. The study team identified the patients with probable clinically relevant DDI-related ADRs on admission, the causality of which was assessed using the Drug Interaction Probability Scale (DIPS). Sensitivity, specificity, and positive and negative predictive values of screening systems to prevent or warn against probable DDI-related ADRs were evaluated. Overall, 50 probable clinically relevant DDI-related ADRs were found in 37 out of 795 included patients taking at least two drugs, most common of them were bleeding, hyperkalemia, digitalis toxicity, and hypotension. Complete Drug Interaction showed the best sensitivity (0.76) for actual DDI-related ADRs, followed by Lexicomp Online (0.50), and Drug Interaction Checker (0.40). Complete Drug Interaction and Drug Interaction Checker had positive predictive values of 0.07; Lexicomp Online had 0.04. We found no difference in specificity and negative predictive values among these systems. DDI screening systems differ significantly in their ability to detect probable clinically relevant DDI-related ADRs in terms of sensitivity and positive predictive value.

  8. Managing Drug-Drug Interaction Between Ombitasvir, Paritaprevir/Ritonavir, Dasabuvir, and Mycophenolate Mofetil.

    Science.gov (United States)

    Lemaitre, Florian; Ben Ali, Zeineb; Tron, Camille; Jezequel, Caroline; Boglione-Kerrien, Christelle; Verdier, Marie-Clémence; Guyader, Dominique; Bellissant, Eric

    2017-08-01

    No drug-drug interaction study has been conducted to date for the combination of ombitasvir, paritaprevir/ritonavir, dasabuvir (3D), and mycophenolic acid (MPA). We here report the case of a hepatitis C virus-infected patient treated with 3D and MPA for vasculitis. In light of the threat of drug-drug interaction, the concentration of MPA was measured before, during, and 15 days after the end of the 3D treatment. Similar values were found at all 3 time points, thus indicating that there is probably no need to adapt MPA dosage to 3D.

  9. Drug-Drug and Herb-Drug Interaction-A Comment | Esimone ...

    African Journals Online (AJOL)

    Clinically relevant drug-drug interactions may be pharmacodynamic or pharmacokinetic. And herbal medicinal products are becoming increasingly popular. Drug interactions can be in vivo or in vitro. Pharmacodynamic outcomes take such forms as Additive, Synergistic, Antagonistic or Indifferent. The paper reviews and ...

  10. Venetoclax (ABT-199) Might Act as a Perpetrator in Pharmacokinetic Drug-Drug Interactions.

    Science.gov (United States)

    Weiss, Johanna; Gajek, Thomas; Köhler, Bruno Christian; Haefeli, Walter Emil

    2016-02-24

    Venetoclax (ABT-199) represents a specific B-cell lymphoma 2 (Bcl-2) inhibitor that is currently under development for the treatment of lymphoid malignancies. So far, there is no published information on its interaction potential with important drug metabolizing enzymes and drug transporters, or its efficacy in multidrug resistant (MDR) cells. We therefore scrutinized its drug-drug interaction potential in vitro. Inhibition of cytochrome P450 enzymes (CYPs) was quantified by commercial kits. Inhibition of drug transporters (P-glycoprotein (P-gp, ABCB1), breast cancer resistance protein (BCRP), and organic anion transporting polypeptides (OATPs)) was evaluated by the use of fluorescent probe substrates. Induction of drug transporters and drug metabolizing enzymes was quantified by real-time RT-PCR. The efficacy of venetoclax in MDR cells lines was evaluated with proliferation assays. Venetoclax moderately inhibited P-gp, BCRP, OATP1B1, OATP1B3, CYP3A4, and CYP2C19, whereas CYP2B6 activity was increased. Venetoclax induced the mRNA expression of CYP1A1, CYP1A2, UGT1A3, and UGT1A9. In contrast, expression of ABCB1 was suppressed, which might revert tumor resistance towards antineoplastic P-gp substrates. P-gp over-expression led to reduced antiproliferative effects of venetoclax. Effective concentrations for inhibition and induction lay in the range of maximum plasma concentrations of venetoclax, indicating that it might act as a perpetrator drug in pharmacokinetic drug-drug interactions.

  11. Prevalence of potential drug-drug interactions in cancer patients treated with oral anticancer drugs

    NARCIS (Netherlands)

    van Leeuwen, R. W. F.; Brundel, D. H. S.; Neef, C.; van Gelder, T.; Mathijssen, R. H. J.; Burger, D. M.; Jansman, F. G. A.

    2013-01-01

    Background: Potential drug-drug interactions (PDDIs) in patients with cancer are common, but have not previously been quantified for oral anticancer treatment. We assessed the prevalence and seriousness of potential PDDIs among ambulatory cancer patients on oral anticancer treatment. Methods: A

  12. Statin-associated rhabdomyolysis triggered by drug-drug interaction with itraconazole

    DEFF Research Database (Denmark)

    Dybro, Anne Mette; Damkier, Per; Rasmussen, Torsten Bloch

    2016-01-01

    -associated rhabdomyolysis, probably caused by a drug-drug interaction between simvastatin and itraconazole. The patient made full recovery. Three commonly used statins-simvastatin, atorvastatin and lovastatin-are metabolised by the liver enzyme CYP3A4. Several potent inhibitors of this enzyme are known, for example, azole...

  13. Prevalence of potential drug-drug interactions in cancer patients treated with oral anticancer drugs

    NARCIS (Netherlands)

    R.W.F. van Leeuwen (Roelof); D.H.S. Brundel (D. H S); C. Neef (Cees); T. van Gelder (Teun); A.H.J. Mathijssen (Ron); D.M. Burger (David); F.G.A. Jansman (Frank)

    2013-01-01

    textabstractBackground: Potential drug-drug interactions (PDDIs) in patients with cancer are common, but have not previously been quantified for oral anticancer treatment. We assessed the prevalence and seriousness of potential PDDIs among ambulatory cancer patients on oral anticancer treatment.

  14. Drug-drug interactions in patients treated for cancer : a prospective study on clinical interventions

    NARCIS (Netherlands)

    van Leeuwen, R. W. F.; Jansman, F. G. A.; van den Bemt, P. M. L. A.; de Man, F.; Piran, F.; Vincenten, I.; Jager, A.; Rijneveld, A. W.; Brugma, J. D.; Mathijssen, R. H. J.; van Gelder, T.

    Background: Drug-drug interactions (DDIs) are of major concern in oncology, since cancer patients typically take many concomitant medications. Retrospective studies have been conducted to determine the prevalence of DDIs. However, prospective studies on DDIs needing interventions in cancer patients

  15. Clinical management of drug-drug interactions in HCV therapy: Challenges and solutions

    NARCIS (Netherlands)

    Burger, D.M.; Back, D.; Buggisch, P.; Buti, M.; Craxi, A.; Foster, G.; Klinker, H.; Larrey, D.; Nikitin, I.; Pol, S. van der; Puoti, M.; Romero-Gomez, M.; Wedemeyer, H.; Zeuzem, S.

    2013-01-01

    Hepatitis C virus (HCV) infected patients often take multiple co-medications to treat adverse events related to HCV therapy, or to manage other co-morbidities. Drug-drug interactions associated with this polypharmacy are relatively new to the field of HCV pharmacotherapy. With the advent of the

  16. [Drug-Drug Interactions with Consideration of Pharmacogenetics].

    Science.gov (United States)

    Ozawa, Shogo

    2018-01-01

     Elderly patients often suffer from a variety of diseases and therefore may be prescribed several kinds of drugs. Interactions between these drugs may cause problems in some patients. Guidelines for drug interactions were released on July 8, 2014 "Drug Interaction Guideline for Drug Development and Labeling Recommendations (Final Draft)". These guidelines include the theoretical basis for evaluating the mechanisms of drug interaction, the possible extent of drug interactions, and take into consideration special populations (e.g., infants, children, elderly patients, patients with hepatic or renal dysfunction, and subjects with minor deficient alleles for drug metabolizing enzymes and drug transporters). In this symposium article, I discuss this last special population: altered drug metabolism and drug interactions in subjects with minor alleles of genes encoding deficient drug metabolizing enzymes. I further discuss a drug label for eliglustat (Cerdelga) with instructions for patients with ultra-rapid, extensive, intermediate, and poor metabolizer phenotypes that arise from different CYP2D6 gene alleles.

  17. Drug-drug interactions of antifungal agents and implications for patient care.

    Science.gov (United States)

    Gubbins, Paul O; Amsden, Jarrett R

    2005-10-01

    Drug interactions in the gastrointestinal tract, liver and kidneys result from alterations in pH, ionic complexation, and interference with membrane transport proteins and enzymatic processes involved in intestinal absorption, enteric and hepatic metabolism, renal filtration and excretion. Azole antifungals can be involved in drug interactions at all the sites, by one or more of the above mechanisms. Consequently, azoles interact with a vast array of compounds. Drug-drug interactions associated with amphotericin B formulations are predictable and result from the renal toxicity and electrolyte disturbances associated with these compounds. The echinocandins are unknown cytochrome P450 substrates and to date are relatively devoid of significant drug-drug interactions. This article reviews drug interactions involving antifungal agents that affect other agents and implications for patient care are highlighted.

  18. Evaluation of Pharmacokinetic and Pharmacodynamic Drug-Drug Interaction of Sacubitril/Valsartan (LCZ696) and Sildenafil in Patients With Mild-to-Moderate Hypertension.

    Science.gov (United States)

    Hsiao, H-L; Langenickel, T H; Petruck, J; Kode, K; Ayalasomayajula, S; Schuehly, U; Greeley, M; Pal, P; Zhou, W; Prescott, M F; Sunkara, G; Rajman, I

    2018-03-01

    Sacubitril/valsartan (LCZ696) is indicated for the treatment of patients with heart failure and reduced ejection fraction (HFrEF). Since patients with HFrEF may receive sacubitril/valsartan and sildenafil, both increasing cyclic guanosine monophosphate, the present study evaluated the pharmacokinetic and pharmacodynamic drug interaction potential between sacubitril/valsartan and sildenafil. In this open-label, three-period, single sequence study, patients with mild-to-moderate hypertension (153.8 ± 8.2 mmHg mean systolic blood pressure (SBP)) received a single dose of sildenafil 50 mg, sacubitril/valsartan 400 mg once daily for 5 days, and sacubitril/valsartan and sildenafil coadministration. When coadministered with sildenafil, the AUC and C max of valsartan decreased by 29% and 39%, respectively. Coadministration of sacubitril/valsartan and sildenafil resulted in a greater decrease in BP (-5/-4/-4 mmHg mean ambulatory SBP/DBP/MAP (mean arterial pressure)) than with sacubitril/valsartan alone. Both treatments were generally safe and well tolerated in this study; however, the additional BP reduction suggests that sildenafil should be administered cautiously in patients receiving sacubitril/valsartan. Unique identifier: NCT01601470. © 2017 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  19. Drug-drug interactions among recently hospitalised patients--frequent but mostly clinically insignificant

    DEFF Research Database (Denmark)

    Glintborg, Bente; Andersen, Stig Ejdrup; Dalhoff, Kim

    2005-01-01

    OBJECTIVE: Patients use and store considerable amounts of drugs. The aim of the present study was to identify potential drug-drug interactions between drugs used by patients recently discharged from the hospital and, subsequently, to estimate the clinical implications of these interactions. METHODS......: Patients were visited within 1 week following their discharge from hospital and interviewed about their drug use. Stored products were inspected. We used a bibliography (Hansten and Horn; Wolters Kluwer Health, St. Louis, Mo., 2004) to identify and classify potential drug-drug interactions. RESULTS......: eight per patient; range: 1-24). With respect to those drugs used daily or on demand, 476 potential interactions were identified (126 patients); none were class 1 (always avoid drug combination) and 25 were class 2 (usually avoid combination; 24 patients). Eleven of the potential class 2 interactions...

  20. A survey of attitudes, practices, and knowledge regarding drug-drug interactions among medical residents in Iran

    NARCIS (Netherlands)

    Nabovati, Ehsan; Vakili-Arki, Hasan; Taherzadeh, Zhila; Saberi, Mohammad Reza; Abu-Hanna, Ameen; Eslami, Saeid

    2017-01-01

    Background When prescribing medications, physicians should recognize clinically relevant potential drug-drug interactions (DDIs). To improve medication safety, it is important to understand prescribers' knowledge and opinions pertaining to DDIs. Objective To determine the current DDI information

  1. Pharmacokinetic drug-drug interaction and their implication in clinical management

    OpenAIRE

    Palleria, Caterina; DI PAOLO, Antonello; Giofrè, Chiara; Caglioti, Chiara; Leuzzi, Giacomo; Siniscalchi, Antonio; De Sarro, Giovambattista; Gallelli, Luca

    2013-01-01

    Drug-drug interactions (DDIs) are one of the commonest causes of medication error in developed countries, particularly in the elderly due to poly-therapy, with a prevalence of 20-40%. In particular, poly-therapy increases the complexity of therapeutic management and thereby the risk of clinically important DDIs, which can both induce the development of adverse drug reactions or reduce the clinical efficacy. DDIs can be classify into two main groups: pharmacokinetic and pharmacodynamic. In thi...

  2. Evaluations of in vitro metabolism, drug-drug interactions mediated by reversible and time-dependent inhibition of CYPs, and plasma protein binding of MMB4 DMS.

    Science.gov (United States)

    Hong, S Peter; Lusiak, Bozena D; Burback, Brian L; Johnson, Jerry D

    2013-01-01

    1,1'-Methylenebis[4-[(hydroxyimino)methyl]-pyridinium] (MMB4) dimethanesulfonate (DMS) is a bisquaternary pyridinium aldoxime that reactivates acetylcholinesterase inhibited by organophosphorus nerve agent. Drug metabolism and plasma protein binding for MMB4 DMS were examined using various techniques and a wide range of species. When (14)C-MMB4 DMS was incubated in liver microsomes, 4-pyridine aldoxime (4-PA) and an additional metabolite were detected in all species tested. Identity of the additional metabolite was postulated to be isonicotinic acid (INA) based on liquid chromatography with a tandem mass spectrometry analysis, which was confirmed by comparison with authentic INA. Formation of INA was dependent on species, with the highest level found in monkey liver microsomes. The MMB4 DMS exhibited reversible inhibition in a concentration-dependent manner toward cytochrome P450 1A2 (CYP1A2), CYP2C9, CYP2C19, CYP2D6, and CYP3A4 in human liver microsomes showing the highest inhibition for CYP2D6. Human recombinant CYPs were used to evaluate inhibitory curves more adequately and determine detailed kinetic constants for reversible inhibition and potential time-dependent inhibition (TDI). The MMB4 DMS exhibited reversible inhibition toward human-recombinant CYP2D6 with an inhibition constant (K i) value of 66.6 µmol/L. Based on the k inact/K I values, MMB4 DMS was found to exhibit the most potent TDI toward CYP2D6. The MMB4 DMS at 5 different concentrations was incubated in plasma for 5 hours using an equilibrium dialysis device. For all species tested, there were no concentration-dependent changes in plasma protein binding, ranging from 10% to 17%. These results suggest that MMB4 was not extensively bound to plasma protein, and there were no overt species-related differences in the extent of MMB4 bound to plasma protein.

  3. Global patient safety and antiretroviral drug-drug interactions in the resource-limited setting.

    Science.gov (United States)

    Seden, Kay; Khoo, Saye H; Back, David; Byakika-Kibwika, Pauline; Lamorde, Mohammed; Ryan, Mairin; Merry, Concepta

    2013-01-01

    Scale-up of HIV treatment services may have contributed to an increase in functional health facilities available in resource-limited settings and an increase in patient use of facilities and retention in care. As more patients are reached with medicines, monitoring patient safety is increasingly important. Limited data from resource-limited settings suggest that medication error and antiretroviral drug-drug interactions may pose a significant risk to patient safety. Commonly cited causes of medication error in the developed world include the speed and complexity of the medication use cycle combined with inadequate systems and processes. In resource-limited settings, specific factors may contribute, such as inadequate human resources and high disease burden. Management of drug-drug interactions may be complicated by limited access to alternative medicines or laboratory monitoring. Improving patient safety by addressing the issue of antiretroviral drug-drug interactions has the potential not just to improve healthcare for individuals, but also to strengthen health systems and improve vital communication among healthcare providers and with regulatory agencies.

  4. Consistency of psychotropic drug-drug interactions listed in drug monographs.

    Science.gov (United States)

    Liu, Xinyue; Hatton, Randy C; Zhu, Yanmin; Hincapie-Castillo, Juan M; Bussing, Regina; Barnicoat, Marie; Winterstein, Almut G

    With an increasing prevalence of psychotropic polypharmacy, clinicians depend on drug-drug interaction (DDI) references to ensure safe regimens, but the consistency of such information is frequently questioned. To evaluate the consistency of psychotropic DDIs documented in Clinical Pharmacology (CP), Micromedex (MM), and Lexicomp (LC) and summarize consistent psychotropic DDIs. In May 2016, we extracted severe or major psychotropic DDIs for 102 psychotropic drugs, including central nervous system (CNS) stimulants, antidepressants, an antimanic agent (lithium), antipsychotics, anticonvulsants, and anxiolytics-sedatives-hypnotics from CP, MM, and LC. We then summarized the psychotropic DDIs that were included in all 3 references and with evidence quality of "excellent" or "good" based on MM. We identified 1496, 938, and 1006 unique severe or major psychotropic DDIs from CP, MM, and LC, respectively. Common adverse effects related to psychotropic DDIs include increased or decreased effectiveness, CNS depression, neurotoxicity, QT prolongation, serotonin syndrome, and multiple adverse effects. Among these interactions, only 371 psychotropic DDIs were documented in all 3 references, 59 of which had "excellent" or "good" quality of evidence based on MM. The consistency of psychotropic DDI documentation across CP, MM, and LC is poor. DDI documentations need standards that would encourage consistency among drug information references. The list of the 59 DDIs may be useful in the assessment of psychotropic polypharmacy and highlighting DDI alerts in clinical practice. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  5. Detection of Potential Drug-Drug Interactions for Outpatients across Hospitals

    Directory of Open Access Journals (Sweden)

    Yu-Ting Yeh

    2014-01-01

    Full Text Available The National Health Insurance Administration (NHIA has adopted smart cards (or NHI-IC cards as health cards to carry patients’ medication histories across hospitals in Taiwan. The aims of this study are to enhance a computerized physician order entry system to support drug-drug interaction (DDI checking based on a patient’s medication history stored in his/her NHI-IC card. For performance evaluation, we developed a transaction tracking log to keep track of every operation on NHI-IC cards. Based on analysis of the transaction tracking log from 1 August to 31 October 2007, physicians read patients’ NHI-IC cards in 71.01% (8,246 of patient visits; 33.02% (2,723 of the card reads showed at least one medicine currently being taken by the patient, 82.94% of which were prescribed during the last visit. Among 10,036 issued prescriptions, seven prescriptions (0.09% contained at least one drug item that might interact with the currently-taken medicines stored in NHI-IC cards and triggered pop-up alerts. This study showed that the capacity of an NHI-IC card is adequate to support DDI checking across hospitals. Thus, the enhanced computerized physician order entry (CPOE system can support better DDI checking when physicians are making prescriptions and provide safer medication care, particularly for patients who receive medication care from different hospitals.

  6. Detection of potential drug-drug interactions for outpatients across hospitals.

    Science.gov (United States)

    Yeh, Yu-Ting; Hsu, Min-Hui; Chen, Chien-Yuan; Lo, Yu-Sheng; Liu, Chien-Tsai

    2014-01-27

    The National Health Insurance Administration (NHIA) has adopted smart cards (or NHI-IC cards) as health cards to carry patients' medication histories across hospitals in Taiwan. The aims of this study are to enhance a computerized physician order entry system to support drug-drug interaction (DDI) checking based on a patient's medication history stored in his/her NHI-IC card. For performance evaluation, we developed a transaction tracking log to keep track of every operation on NHI-IC cards. Based on analysis of the transaction tracking log from 1 August to 31 October 2007, physicians read patients' NHI-IC cards in 71.01% (8,246) of patient visits; 33.02% (2,723) of the card reads showed at least one medicine currently being taken by the patient, 82.94% of which were prescribed during the last visit. Among 10,036 issued prescriptions, seven prescriptions (0.09%) contained at least one drug item that might interact with the currently-taken medicines stored in NHI-IC cards and triggered pop-up alerts. This study showed that the capacity of an NHI-IC card is adequate to support DDI checking across hospitals. Thus, the enhanced computerized physician order entry (CPOE) system can support better DDI checking when physicians are making prescriptions and provide safer medication care, particularly for patients who receive medication care from different hospitals.

  7. High-Throughput Cytochrome P450 Cocktail Inhibition Assay for Assessing Drug-Drug and Drug-Botanical Interactions.

    Science.gov (United States)

    Li, Guannan; Huang, Ke; Nikolic, Dejan; van Breemen, Richard B

    2015-11-01

    Detection of drug-drug interactions is essential during the early stages of drug discovery and development, and the understanding of drug-botanical interactions is important for the safe use of botanical dietary supplements. Among the different forms of drug interactions that are known, inhibition of cytochrome P450 (P450) enzymes is the most common cause of drug-drug or drug-botanical interactions. Therefore, a rapid and comprehensive mass spectrometry-based in vitro high-throughput P450 cocktail inhibition assay was developed that uses 10 substrates simultaneously against nine CYP isoforms. Including probe substrates for CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and two probes targeting different binding sites of CYP3A4/5, this cocktail simultaneously assesses at least as many P450 enzymes as previous assays while remaining among the fastest due to short incubation times and rapid analysis using ultrahigh pressure liquid chromatography-tandem mass spectrometry. The method was validated using known inhibitors of each P450 enzyme and then shown to be useful not only for single-compound testing but also for the evaluation of potential drug-botanical interactions using the botanical dietary supplement licorice (Glycyrrhiza glabra) as an example. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  8. Impact of the CYP2C8 *3 polymorphism on the drug-drug interaction between gemfibrozil and pioglitazone.

    Science.gov (United States)

    Aquilante, Christina L; Kosmiski, Lisa A; Bourne, David W A; Bushman, Lane R; Daily, Elizabeth B; Hammond, Kyle P; Hopley, Charles W; Kadam, Rajendra S; Kanack, Alexander T; Kompella, Uday B; Le, Merry; Predhomme, Julie A; Rower, Joseph E; Sidhom, Maha S

    2013-01-01

    The objective of this study was to determine the extent to which the CYP2C8*3 allele influences pharmacokinetic variability in the drug-drug interaction between gemfibrozil (CYP2C8 inhibitor) and pioglitazone (CYP2C8 substrate). In this randomized, two phase crossover study, 30 healthy Caucasian subjects were enrolled based on CYP2C8*3 genotype (n = 15, CYP2C8*1/*1; n = 15, CYP2C8*3 carriers). Subjects received a single 15 mg dose of pioglitazone or gemfibrozil 600 mg every 12 h for 4 days with a single 15 mg dose of pioglitazone administered on the morning of day 3. A 48 h pharmacokinetic study followed each pioglitazone dose and the study phases were separated by a 14 day washout period. Gemfibrozil significantly increased mean pioglitazone AUC(0,∞) by 4.3-fold (P gemfibrozil administration was significantly influenced by CYP2C8 genotype. Specifically, CYP2C8*3 carriers had a 5.2-fold mean increase in pioglitazone AUC(0,∞) compared with a 3.3-fold mean increase in CYP2C8*1 homozygotes (P = 0.02). CYP2C8*3 is associated with decreased pioglitazone plasma exposure in vivo and significantly influences the pharmacokinetic magnitude of the gemfibrozil-pioglitazone drug-drug interaction. Additional studies are needed to evaluate the impact of CYP2C8 genetics on the pharmacokinetics of other CYP2C8-mediated drug-drug interactions. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  9. Clinically relevant potential drug-drug interactions among outpatients: A nationwide database study.

    Science.gov (United States)

    Jazbar, Janja; Locatelli, Igor; Horvat, Nejc; Kos, Mitja

    2018-06-01

    Adverse drug events due to drug-drug interactions (DDIs) represent a considerable public health burden, also in Slovenia. A better understanding of the most frequently occurring potential DDIs may enable safer pharmacotherapy and minimize drug-related problems. The aim of this study was to evaluate the prevalence and predictors of potential DDIs among outpatients in Slovenia. An analysis of potential DDIs was performed using health claims data on prescription drugs from a nationwide database. The Lexi-Interact Module was used as the reference source of interactions. The influence of patient-specific predictors on the risk of potential clinically relevant DDIs was evaluated using logistic regression model. The study population included 1,179,803 outpatients who received 15,811,979 prescriptions. The total number of potential DDI cases identified was 3,974,994, of which 15.6% were potentially clinically relevant. Altogether, 9.3% (N = 191,213) of the total population in Slovenia is exposed to clinically relevant potential DDIs, and the proportion is higher among women and the elderly. After adjustment for cofactors, higher number of medications and older age are associated with higher odds of clinically relevant potential DDIs. The burden of DDIs is highest with drug combinations that increase risk of bleeding, enhance CNS depression or anticholinergic effects or cause cardiovascular complications. The current study revealed that 1 in 10 individuals in the total Slovenian population is exposed to clinically relevant potential DDIs yearly. Taking into account the literature based conservative estimate that approximately 1% of potential DDIs result in negative health outcomes, roughly 1800 individuals in Slovenia experience an adverse health outcome each year as a result of clinically relevant potential interactions alone. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Clinical assessment of drug-drug interactions of tasimelteon, a novel dual melatonin receptor agonist.

    Science.gov (United States)

    Ogilvie, Brian W; Torres, Rosarelis; Dressman, Marlene A; Kramer, William G; Baroldi, Paolo

    2015-09-01

    Tasimelteon ([1R-trans]-N-[(2-[2,3-dihydro-4-benzofuranyl] cyclopropyl) methyl] propanamide), a novel dual melatonin receptor agonist that demonstrates specificity and high affinity for melatonin receptor types 1 and 2 (MT1 and MT2 receptors), is the first treatment approved by the US Food and Drug Administration for Non-24-Hour Sleep-Wake Disorder. Tasimelteon is rapidly absorbed, with a mean absolute bioavailability of approximately 38%, and is extensively metabolized primarily by oxidation at multiple sites, mainly by cytochrome P450 (CYP) 1A2 and CYP3A4/5, as initially demonstrated by in vitro studies and confirmed by the results of clinical drug-drug interactions presented here. The effects of strong inhibitors and moderate or strong inducers of CYP1A2 and CYP3A4/5 on the pharmacokinetics of tasimelteon were evaluated in humans. Coadministration with fluvoxamine resulted in an approximately 6.5-fold increase in tasimelteon's area under the curve (AUC), whereas cigarette smoking decreased tasimelteon's exposure by approximately 40%. Coadministration with ketoconazole resulted in an approximately 54% increase in tasimelteon's AUC, whereas rifampin pretreatment resulted in a decrease in tasimelteon's exposure of approximately 89%. © 2015 The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

  11. ORIGINAL ARTICLES Prevalence of drug-drug interactions of ...

    African Journals Online (AJOL)

    2008-02-02

    Feb 2, 2008 ... Table II. Frequency of level 2 interactions between ARVs and the other drugs. Interacting ARVs and other drugs. N. %*. Didanosine + ketoconazole. 1. 0.91. Didanosine + ofloxacin. 1. 0.91. Didanosine + ciprofloxacin. 2. 1.82. Didanosine + iraconazole. 3. 2.73. Didanosine + ketoconazole. 2. 1.82. Efavirenz ...

  12. Position-aware deep multi-task learning for drug-drug interaction extraction.

    Science.gov (United States)

    Zhou, Deyu; Miao, Lei; He, Yulan

    2018-05-01

    A drug-drug interaction (DDI) is a situation in which a drug affects the activity of another drug synergistically or antagonistically when being administered together. The information of DDIs is crucial for healthcare professionals to prevent adverse drug events. Although some known DDIs can be found in purposely-built databases such as DrugBank, most information is still buried in scientific publications. Therefore, automatically extracting DDIs from biomedical texts is sorely needed. In this paper, we propose a novel position-aware deep multi-task learning approach for extracting DDIs from biomedical texts. In particular, sentences are represented as a sequence of word embeddings and position embeddings. An attention-based bidirectional long short-term memory (BiLSTM) network is used to encode each sentence. The relative position information of words with the target drugs in text is combined with the hidden states of BiLSTM to generate the position-aware attention weights. Moreover, the tasks of predicting whether or not two drugs interact with each other and further distinguishing the types of interactions are learned jointly in multi-task learning framework. The proposed approach has been evaluated on the DDIExtraction challenge 2013 corpus and the results show that with the position-aware attention only, our proposed approach outperforms the state-of-the-art method by 0.99% for binary DDI classification, and with both position-aware attention and multi-task learning, our approach achieves a micro F-score of 72.99% on interaction type identification, outperforming the state-of-the-art approach by 1.51%, which demonstrates the effectiveness of the proposed approach. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Common drug-drug interactions in antifungal treatments for superficial fungal infections.

    Science.gov (United States)

    Gupta, Aditya K; Versteeg, Sarah G; Shear, Neil H

    2018-04-01

    Antifungal agents can be co-administered alongside several other medications for a variety of reasons such as the presence of comorbidities. Pharmacodynamic interactions such as synergistic and antagonistic interactions could be the result of co-administered medications. Pharmacokinetic interactions could also transpire through the inhibition of metabolizing enzymes and drug transport systems, altering the absorption, metabolism and excretion of co-administered medications. Both pharmacodynamic and pharmacokinetic interactions can result in hospitalization due to serious adverse effects associated with antifungal agents, lower therapeutic doses required to achieve desired antifungal activity, and prevent antifungal resistance. Areas covered: The objective of this review is to summarize pharmacodynamic and pharmacokinetic interactions associated with common antifungal agents used to treat superficial fungal infections. Pharmacodynamic and pharmacokinetic interactions that impact the therapeutic effects of antifungal agents and drugs that are influenced by the presence of antifungal agents was the context to which these antifungal agents were addressed. Expert opinion: The potential for drug-drug interactions is minimal for topical antifungals as opposed to oral antifungals as they have minimal exposure to other co-administered medications. Developing non-lipophilic antifungals that have unique metabolizing pathways and are topical applied are suggested properties that could help limit drug-drug interactions associated with future treatments.

  14. A Novel Design for Drug-Drug Interaction Alerts Improves Prescribing Efficiency.

    Science.gov (United States)

    Russ, Alissa L; Chen, Siying; Melton, Brittany L; Johnson, Elizabette G; Spina, Jeffrey R; Weiner, Michael; Zillich, Alan J

    2015-09-01

    Drug-drug interactions (DDIs) are common in clinical care and pose serious risks for patients. Electronic health records display DDI alerts that can influence prescribers, but the interface design of DDI alerts has largely been unstudied. In this study, the objective was to apply human factors engineering principles to alert design. It was hypothesized that redesigned DDI alerts would significantly improve prescribers' efficiency and reduce prescribing errors. In a counterbalanced, crossover study with prescribers, two DDI alert designs were evaluated. Department of Veterans Affairs (VA) prescribers were video recorded as they completed fictitious patient scenarios, which included DDI alerts of varying severity. Efficiency was measured from time-stamped recordings. Prescribing errors were evaluated against predefined criteria. Efficiency and prescribing errors were analyzed with the Wilcoxon signed-rank test. Other usability data were collected on the adequacy of alert content, prescribers' use of the DDI monograph, and alert navigation. Twenty prescribers completed patient scenarios for both designs. Prescribers resolved redesigned alerts in about half the time (redesign: 52 seconds versus original design: 97 seconds; p<.001). Prescribing errors were not significantly different between the two designs. Usability results indicate that DDI alerts might be enhanced by facilitating easier access to laboratory data and dosing information and by allowing prescribers to cancel either interacting medication directly from the alert. Results also suggest that neither design provided adequate information for decision making via the primary interface. Applying human factors principles to DDI alerts improved overall efficiency. Aspects of DDI alert design that could be further enhanced prior to implementation were also identified.

  15. Drug-drug interaction may explain failed antibiotic effectiveness - an ...

    African Journals Online (AJOL)

    The in vivo effect of co-administration of the NSAIDs (acetyl salicylic acid (ASA), piroxicam, indomethacin and paracetamol) with ciprofloxacin against Staphylococcus aureus in Swiss mice, rendered neutropenic by pre-treatment with cyclophosphamide, was evaluated using animal model. Using the murine thigh model, ...

  16. A review of drug-drug interactions in older HIV-infected patients.

    Science.gov (United States)

    Chary, Aarthi; Nguyen, Nancy N; Maiton, Kimberly; Holodniy, Mark

    2017-12-01

    The number of older HIV-infected people is growing due to increasing life expectancies resulting from the use of antiretroviral therapy (ART). Both HIV and aging increase the risk of other comorbidities, such as cardiovascular disease, osteoporosis, and some malignancies, leading to greater challenges in managing HIV with other conditions. This results in complex medication regimens with the potential for significant drug-drug interactions and increased morbidity and mortality. Area covered: We review the metabolic pathways of ART and other medications used to treat medical co-morbidities, highlight potential areas of concern for drug-drug interactions, and where feasible, suggest alternative approaches for treating these conditions as suggested from national guidelines or articles published in the English language. Expert commentary: There is limited evidence-based data on ART drug interactions, pharmacokinetics and pharmacodynamics in the older HIV-infected population. Choosing and maintaining effective ART regimens for older adults requires consideration of side effect profile, individual comorbidities, interactions with concurrent prescriptions and non-prescription medications and supplements, dietary patterns with respect to dosing, pill burden and ease of dosing, cost and affordability, patient preferences, social situation, and ART resistance history. Practitioners must remain vigilant for potential drug interactions and intervene when there is a potential for harm.

  17. Data-driven prediction of adverse drug reactions induced by drug-drug interactions.

    Science.gov (United States)

    Liu, Ruifeng; AbdulHameed, Mohamed Diwan M; Kumar, Kamal; Yu, Xueping; Wallqvist, Anders; Reifman, Jaques

    2017-06-08

    The expanded use of multiple drugs has increased the occurrence of adverse drug reactions (ADRs) induced by drug-drug interactions (DDIs). However, such reactions are typically not observed in clinical drug-development studies because most of them focus on single-drug therapies. ADR reporting systems collect information on adverse health effects caused by both single drugs and DDIs. A major challenge is to unambiguously identify the effects caused by DDIs and to attribute them to specific drug interactions. A computational method that provides prospective predictions of potential DDI-induced ADRs will help to identify and mitigate these adverse health effects. We hypothesize that drug-protein interactions can be used as independent variables in predicting ADRs. We constructed drug pair-protein interaction profiles for ~800 drugs using drug-protein interaction information in the public domain. We then constructed statistical models to score drug pairs for their potential to induce ADRs based on drug pair-protein interaction profiles. We used extensive clinical database information to construct categorical prediction models for drug pairs that are likely to induce ADRs via synergistic DDIs and showed that model performance deteriorated only slightly, with a moderate amount of false positives and false negatives in the training samples, as evaluated by our cross-validation analysis. The cross validation calculations showed an average prediction accuracy of 89% across 1,096 ADR models that captured the deleterious effects of synergistic DDIs. Because the models rely on drug-protein interactions, we made predictions for pairwise combinations of 764 drugs that are currently on the market and for which drug-protein interaction information is available. These predictions are publicly accessible at http://avoid-db.bhsai.org . We used the predictive models to analyze broader aspects of DDI-induced ADRs, showing that ~10% of all combinations have the potential to induce ADRs

  18. Pharmacodynamics and common drug-drug interactions of the third-generation antiepileptic drugs.

    Science.gov (United States)

    Stefanović, Srđan; Janković, Slobodan M; Novaković, Milan; Milosavljević, Marko; Folić, Marko

    2018-02-01

    Anticonvulsants that belong to the third generation are considered as 'newer' antiepileptic drugs, including: eslicarbazepine acetate, lacosamide, perampanel, brivaracetam, rufinamide and stiripentol. Areas covered: This article reviews pharmacodynamics (i.e. mechanisms of action) and clinically relevant drug-drug interactions of the third-generation antiepileptic drugs. Expert opinion: Newer antiepileptic drugs have mechanisms of action which are not shared with the first and the second generation anticonvulsants, like inhibition of neurotransmitters release, blocking receptors for excitatory amino acids and new ways of sodium channel inactivation. New mechanisms of action increase chances of controlling forms of epilepsy resistant to older anticonvulsants. Important advantage of the third-generation anticonvulsants could be their little propensity for interactions with both antiepileptic and other drugs observed until now, making prescribing much easier and safer. However, this may change with new studies specifically designed to discover drug-drug interactions. Although the third-generation antiepileptic drugs enlarged therapeutic palette against epilepsy, 20-30% of patients with epilepsy is still treatment-resistant and need new pharmacological approach. There is great need to explore all molecular targets that may directly or indirectly be involved in generation of seizures, so a number of candidate compounds for even newer anticonvulsants could be generated.

  19. Variable Linezolid Exposure in Intensive Care Unit Patients-Possible Role of Drug-Drug Interactions.

    Science.gov (United States)

    Töpper, Christoph; Steinbach, Cathérine L; Dorn, Christoph; Kratzer, Alexander; Wicha, Sebastian G; Schleibinger, Michael; Liebchen, Uwe; Kees, Frieder; Salzberger, Bernd; Kees, Martin G

    2016-10-01

    Standard doses of linezolid may not be suitable for all patient groups. Intensive care unit (ICU) patients in particular may be at risk of inadequate concentrations. This study investigated variability of drug exposure and its potential sources in this population. Plasma concentrations of linezolid were determined by high-performance liquid chromatography in a convenience sample of 20 ICU patients treated with intravenous linezolid 600 mg twice daily. Ultrafiltration applying physiological conditions (pH 7.4/37°C) was used to determine the unbound fraction. Individual pharmacokinetic (PK) parameters were estimated by population PK modeling. As measures of exposure to linezolid, area under the concentration-time curve (AUC) and trough concentrations (Cmin) were calculated and compared with published therapeutic ranges (AUC 200-400 mg*h/L, Cmin 2-10 mg/L). Coadministered inhibitors or inducers of cytochrome P450 and/or P-glycoprotein were noted. Data from 18 patients were included into the PK evaluation. Drug exposure was highly variable (median, range: AUC 185, 48-618 mg*h/L, calculated Cmin 2.92, 0.0062-18.9 mg/L), and only a minority of patients had values within the target ranges (6 and 7, respectively). AUC and Cmin were linearly correlated (R = 0.98), and classification of patients (underexposed/within therapeutic range/overexposed) according to AUC or Cmin was concordant in 15 cases. Coadministration of inhibitors was associated with a trend to higher drug exposure, whereas 3 patients treated with levothyroxine showed exceedingly low drug exposure (AUC ∼60 mg*h/L, Cmin linezolid is highly variable and difficult to predict in ICU patients, and therapeutic drug monitoring seems advisable. PK drug-drug interactions might partly be responsible and should be further investigated; protein binding appears to be stable and irrelevant.

  20. Detecting drug-drug interactions using a database for spontaneous adverse drug reactions : an example with diuretics and non-steroidal anti-inflammatory drugs

    NARCIS (Netherlands)

    van Puijenbroek, E P; Egberts, A C; Heerdink, E R; Leufkens, H G

    2000-01-01

    OBJECTIVE: Drug-drug interactions are relatively rarely reported to spontaneous reporting systems (SRSs) for adverse drug reactions. For this reason, the traditional approach for analysing SRS has major limitations for the detection of drug-drug interactions. We developed a method that may enable

  1. Development of description framework of pharmacodynamics ontology and its application to possible drug-drug interaction reasoning.

    Science.gov (United States)

    Imai, Takeshi; Hayakawa, Masayo; Ohe, Kazuhiko

    2013-01-01

    Prediction of synergistic or antagonistic effects of drug-drug interaction (DDI) in vivo has been of considerable interest over the years. Formal representation of pharmacological knowledge such as ontology is indispensable for machine reasoning of possible DDIs. However, current pharmacology knowledge bases are not sufficient to provide formal representation of DDI information. With this background, this paper presents: (1) a description framework of pharmacodynamics ontology; and (2) a methodology to utilize pharmacodynamics ontology to detect different types of possible DDI pairs with supporting information such as underlying pharmacodynamics mechanisms. We also evaluated our methodology in the field of drugs related to noradrenaline signal transduction process and 11 different types of possible DDI pairs were detected. The main features of our methodology are the explanation capability of the reason for possible DDIs and the distinguishability of different types of DDIs. These features will not only be useful for providing supporting information to prescribers, but also for large-scale monitoring of drug safety.

  2. Large-scale structural and textual similarity-based mining of knowledge graph to predict drug-drug interactions

    KAUST Repository

    Abdelaziz, Ibrahim; Fokoue, Achille; Hassanzadeh, Oktie; Zhang, Ping; Sadoghi, Mohammad

    2017-01-01

    Drug-Drug Interactions (DDIs) are a major cause of preventable Adverse Drug Reactions (ADRs), causing a significant burden on the patients’ health and the healthcare system. It is widely known that clinical studies cannot sufficiently and accurately identify DDIs for new drugs before they are made available on the market. In addition, existing public and proprietary sources of DDI information are known to be incomplete and/or inaccurate and so not reliable. As a result, there is an emerging body of research on in-silico prediction of drug-drug interactions. In this paper, we present Tiresias, a large-scale similarity-based framework that predicts DDIs through link prediction. Tiresias takes in various sources of drug-related data and knowledge as inputs, and provides DDI predictions as outputs. The process starts with semantic integration of the input data that results in a knowledge graph describing drug attributes and relationships with various related entities such as enzymes, chemical structures, and pathways. The knowledge graph is then used to compute several similarity measures between all the drugs in a scalable and distributed framework. In particular, Tiresias utilizes two classes of features in a knowledge graph: local and global features. Local features are derived from the information directly associated to each drug (i.e., one hop away) while global features are learnt by minimizing a global loss function that considers the complete structure of the knowledge graph. The resulting similarity metrics are used to build features for a large-scale logistic regression model to predict potential DDIs. We highlight the novelty of our proposed Tiresias and perform thorough evaluation of the quality of the predictions. The results show the effectiveness of Tiresias in both predicting new interactions among existing drugs as well as newly developed drugs.

  3. Large-scale structural and textual similarity-based mining of knowledge graph to predict drug-drug interactions

    KAUST Repository

    Abdelaziz, Ibrahim

    2017-06-12

    Drug-Drug Interactions (DDIs) are a major cause of preventable Adverse Drug Reactions (ADRs), causing a significant burden on the patients’ health and the healthcare system. It is widely known that clinical studies cannot sufficiently and accurately identify DDIs for new drugs before they are made available on the market. In addition, existing public and proprietary sources of DDI information are known to be incomplete and/or inaccurate and so not reliable. As a result, there is an emerging body of research on in-silico prediction of drug-drug interactions. In this paper, we present Tiresias, a large-scale similarity-based framework that predicts DDIs through link prediction. Tiresias takes in various sources of drug-related data and knowledge as inputs, and provides DDI predictions as outputs. The process starts with semantic integration of the input data that results in a knowledge graph describing drug attributes and relationships with various related entities such as enzymes, chemical structures, and pathways. The knowledge graph is then used to compute several similarity measures between all the drugs in a scalable and distributed framework. In particular, Tiresias utilizes two classes of features in a knowledge graph: local and global features. Local features are derived from the information directly associated to each drug (i.e., one hop away) while global features are learnt by minimizing a global loss function that considers the complete structure of the knowledge graph. The resulting similarity metrics are used to build features for a large-scale logistic regression model to predict potential DDIs. We highlight the novelty of our proposed Tiresias and perform thorough evaluation of the quality of the predictions. The results show the effectiveness of Tiresias in both predicting new interactions among existing drugs as well as newly developed drugs.

  4. Target mediated drug disposition with drug-drug interaction, Part II: competitive and uncompetitive cases.

    Science.gov (United States)

    Koch, Gilbert; Jusko, William J; Schropp, Johannes

    2017-02-01

    We present competitive and uncompetitive drug-drug interaction (DDI) with target mediated drug disposition (TMDD) equations and investigate their pharmacokinetic DDI properties. For application of TMDD models, quasi-equilibrium (QE) or quasi-steady state (QSS) approximations are necessary to reduce the number of parameters. To realize those approximations of DDI TMDD models, we derive an ordinary differential equation (ODE) representation formulated in free concentration and free receptor variables. This ODE formulation can be straightforward implemented in typical PKPD software without solving any non-linear equation system arising from the QE or QSS approximation of the rapid binding assumptions. This manuscript is the second in a series to introduce and investigate DDI TMDD models and to apply the QE or QSS approximation.

  5. The potential drug-drug interaction between proton pump inhibitors and warfarin

    DEFF Research Database (Denmark)

    Henriksen, Daniel Pilsgaard; Stage, Tore Bjerregaard; Hansen, Morten Rix

    2015-01-01

    BACKGROUND: Proton pump inhibitors (PPIs) have been suggested to increase the effect of warfarin, and clinical guidelines recommend careful monitoring of international normalized ratio (INR) when initiating PPI among warfarin users. However, this drug-drug interaction is sparsely investigated...... in a clinical setting. The aim was to assess whether initiation of PPI treatment among users of warfarin leads to increased INR values. METHODS: The study was an observational self-controlled study from 1998 to 2012 leveraging data on INR measurements on patients treated with warfarin from primary care...... and outpatient clinics and their use of prescription drugs. Data were analyzed in 2015. We assessed INR, warfarin dose, and dose/INR ratio before and after initiating PPI treatment using the paired student's t-test. RESULTS: We identified 305 warfarin users initiating treatment with PPIs. The median age was 71...

  6. Pharmacokinetic drug-drug interaction and their implication in clinical management.

    Science.gov (United States)

    Palleria, Caterina; Di Paolo, Antonello; Giofrè, Chiara; Caglioti, Chiara; Leuzzi, Giacomo; Siniscalchi, Antonio; De Sarro, Giovambattista; Gallelli, Luca

    2013-07-01

    Drug-drug interactions (DDIs) are one of the commonest causes of medication error in developed countries, particularly in the elderly due to poly-therapy, with a prevalence of 20-40%. In particular, poly-therapy increases the complexity of therapeutic management and thereby the risk of clinically important DDIs, which can both induce the development of adverse drug reactions or reduce the clinical efficacy. DDIs can be classify into two main groups: pharmacokinetic and pharmacodynamic. In this review, using Medline, PubMed, Embase, Cochrane library and Reference lists we searched articles published until June 30 2012, and we described the mechanism of pharmacokinetic DDIs focusing the interest on their clinical implications.

  7. Pharmacokinetic drug-drug interaction and their implication in clinical management

    Directory of Open Access Journals (Sweden)

    Palleria Caterina

    2013-01-01

    Full Text Available Drug-drug interactions (DDIs are one of the commonest causes of medication error in developed countries, particularly in the elderly due to poly-therapy, with a prevalence of 20-40%. In particular, poly-therapy increases the complexity of therapeutic management and thereby the risk of clinically important DDIs, which can both induce the development of adverse drug reactions or reduce the clinical efficacy. DDIs can be classify into two main groups: pharmacokinetic and pharmacodynamic. In this review, using Medline, PubMed, Embase, Cochrane library and Reference lists we searched articles published until June 30 2012, and we described the mechanism of pharmacokinetic DDIs focusing the interest on their clinical implications.

  8. Core drug-drug interaction alerts for inclusion in pediatric electronic health records with computerized prescriber order entry.

    Science.gov (United States)

    Harper, Marvin B; Longhurst, Christopher A; McGuire, Troy L; Tarrago, Rod; Desai, Bimal R; Patterson, Al

    2014-03-01

    The study aims to develop a core set of pediatric drug-drug interaction (DDI) pairs for which electronic alerts should be presented to prescribers during the ordering process. A clinical decision support working group composed of Children's Hospital Association (CHA) members was developed. CHA Pharmacists and Chief Medical Information Officers participated. Consensus was reached on a core set of 19 DDI pairs that should be presented to pediatric prescribers during the order process. We have provided a core list of 19 high value drug pairs for electronic drug-drug interaction alerts to be recommended for inclusion as high value alerts in prescriber order entry software used with a pediatric patient population. We believe this list represents the most important pediatric drug interactions for practical implementation within computerized prescriber order entry systems.

  9. Potential drug-drug interactions with direct oral anticoagulants in elderly hospitalized patients.

    Science.gov (United States)

    Forbes, Heather L; Polasek, Thomas M

    2017-10-01

    To determine the prevalence and nature of potential drug-drug interactions (DDIs) with direct oral anticoagulants (DOACs) in elderly hospitalized patients. This was a retrospective observational study. Inclusion criteria were: aged over 65 years; taking apixaban, rivaroxaban or dabigatran; and admitted to the Repatriation General Hospital between April 2014 and July 2015. A list of clinically relevant 'perpetrator' drugs was compiled from product information, the Australian Medicines Handbook, the Australian National Prescribing Service resources, and local health network guidelines. The prevalence and nature of potential DDIs with DOACs was determined by comparing inpatient drug charts with the list of perpetrator drugs. There were 122 patients in the study with a mean age of 82 years. Most patients had nonvalvular atrial fibrillation and were taking DOACs to prevent thrombotic stroke (83%). Overall, 45 patients (37%) had a total of 54 potential DDIs. Thirty-five patients had potential pharmacodynamic DDIs with antidepressants, nonsteroidal anti-inflammatory drugs and antiplatelets (35/122, 29%). Nineteen patients had potential pharmacokinetic DDIs (19/122, 16%). Of these, 68% (13/19) were taking drugs that increase DOAC plasma concentrations (amiodarone, erythromycin, diltiazem or verapamil) and 32% (6/19) were taking drugs that decrease DOAC plasma concentrations (carbamazepine, primidone or phenytoin). There were no cases of patients taking contraindicated interacting drugs. Potential DDIs with DOACs in elderly hospital inpatients are relatively common, particularly interactions that may increase the risk of bleeding. The risk-benefit ratio of DOACs in elderly patients on polypharmacy should always be carefully considered.

  10. Computational prediction of drug-drug interactions based on drugs functional similarities.

    Science.gov (United States)

    Ferdousi, Reza; Safdari, Reza; Omidi, Yadollah

    2017-06-01

    Therapeutic activities of drugs are often influenced by co-administration of drugs that may cause inevitable drug-drug interactions (DDIs) and inadvertent side effects. Prediction and identification of DDIs are extremely vital for the patient safety and success of treatment modalities. A number of computational methods have been employed for the prediction of DDIs based on drugs structures and/or functions. Here, we report on a computational method for DDIs prediction based on functional similarity of drugs. The model was set based on key biological elements including carriers, transporters, enzymes and targets (CTET). The model was applied for 2189 approved drugs. For each drug, all the associated CTETs were collected, and the corresponding binary vectors were constructed to determine the DDIs. Various similarity measures were conducted to detect DDIs. Of the examined similarity methods, the inner product-based similarity measures (IPSMs) were found to provide improved prediction values. Altogether, 2,394,766 potential drug pairs interactions were studied. The model was able to predict over 250,000 unknown potential DDIs. Upon our findings, we propose the current method as a robust, yet simple and fast, universal in silico approach for identification of DDIs. We envision that this proposed method can be used as a practical technique for the detection of possible DDIs based on the functional similarities of drugs. Copyright © 2017. Published by Elsevier Inc.

  11. A novel algorithm for analyzing drug-drug interactions from MEDLINE literature.

    Science.gov (United States)

    Lu, Yin; Shen, Dan; Pietsch, Maxwell; Nagar, Chetan; Fadli, Zayd; Huang, Hong; Tu, Yi-Cheng; Cheng, Feng

    2015-11-27

    Drug-drug interaction (DDI) is becoming a serious clinical safety issue as the use of multiple medications becomes more common. Searching the MEDLINE database for journal articles related to DDI produces over 330,000 results. It is impossible to read and summarize these references manually. As the volume of biomedical reference in the MEDLINE database continues to expand at a rapid pace, automatic identification of DDIs from literature is becoming increasingly important. In this article, we present a random-sampling-based statistical algorithm to identify possible DDIs and the underlying mechanism from the substances field of MEDLINE records. The substances terms are essentially carriers of compound (including protein) information in a MEDLINE record. Four case studies on warfarin, ibuprofen, furosemide and sertraline implied that our method was able to rank possible DDIs with high accuracy (90.0% for warfarin, 83.3% for ibuprofen, 70.0% for furosemide and 100% for sertraline in the top 10% of a list of compounds ranked by p-value). A social network analysis of substance terms was also performed to construct networks between proteins and drug pairs to elucidate how the two drugs could interact.

  12. Drug-drug interactions as a result of co-administering Δ9-THC and CBD with other psychotropic agents.

    Science.gov (United States)

    Rong, Carola; Carmona, Nicole E; Lee, Yena L; Ragguett, Renee-Marie; Pan, Zihang; Rosenblat, Joshua D; Subramaniapillai, Mehala; Shekotikhina, Margarita; Almatham, Fahad; Alageel, Asem; Mansur, Rodrigo; Ho, Roger C; McIntyre, Roger S

    2018-01-01

    To determine, via narrative, non-systematic review of pre-clinical and clinical studies, whether the effect of cannabis on hepatic biotransformation pathways would be predicted to result in clinically significant drug-drug interactions (DDIs) with commonly prescribed psychotropic agents. Areas covered: A non-systematic literature search was conducted using the following databases: PubMed, PsycInfo, and Scopus from inception to January 2017. The search term cannabis was cross-referenced with the terms drug interactions, cytochrome, cannabinoids, cannabidiol, and medical marijuana. Pharmacological, molecular, and physiologic studies evaluating the pharmacokinetics of Δ 9 -tetrahydrocannabinol (Δ 9 -THC) and cannabidiol (CBD), both in vitro and in vivo, were included. Bibliographies were also manually searched for additional citations that were relevant to the overarching aim of this paper. Expert opinion: Δ 9 -Tetrahydrocannabinol and CBD are substrates and inhibitors of cytochrome P450 enzymatic pathways relevant to the biotransformation of commonly prescribed psychotropic agents. The high frequency and increasing use of cannabis invites the need for healthcare providers to familiarize themselves with potential DDIs in persons receiving select psychotropic agents, and additionally consuming medical marijuana and/or recreational marijuana.

  13. Knowledge Integration and Use-Case Analysis for a Customized Drug-Drug Interaction CDS Service

    Science.gov (United States)

    Kam, Hye Jin; Park, Man Young; Kim, Woojae; Yoon, Duk Yong; Ahn, Eun Kyoung; Park, Rae Woong

    Clinical decision support systems (CDSSs) are thought to reduce adverse drug events (ADEs) by monitoring drug-drug interactions(DDIs). However, clinically improper or excessive alerts can result in high alert overrides. A tailored CDS service, which is appropriate for clinicians and their ordering situations, is required to increase alert acceptance. In this study, we conducted a 12-week pilot project adopting a tailed CDSS at an emergency department. The new CDSS was conducted via a stepwise integration of additional new rules. The alert status with changes in acceptance rate was analyzed. The most frequent DDI alerts were related to prescriptions of anti-inflammatory drugs. The percentages of alert overrides for each stage were 98.0%, 96.0%, 96.9%, and 98.1%, respectively. 91.5% of overridden alerts were related to discharge medications. To reduce the potential hazards of ADEs, the development of an effective customized DDI CDSS is required, via in-depth analysis on alert patterns and overridden reasons.

  14. Cumulative organic anion transporter-mediated drug-drug interaction potential of multiple components in salvia miltiorrhiza (danshen) preparations.

    Science.gov (United States)

    Wang, Li; Venitz, Jürgen; Sweet, Douglas H

    2014-12-01

    To evaluate organic anion transporter-mediated drug-drug interaction (DDI) potential for individual active components of Danshen (Salvia miltiorrhiza) vs. combinations using in vitro and in silico approaches. Inhibition profiles for single Danshen components and combinations were generated in stably-expressing human (h)OAT1 and hOAT3 cells. Plasma concentration-time profiles for compounds were estimated from in vivo human data using an i.v. two-compartment model (with first-order elimination). The cumulative DDI index was proposed as an indicator of DDI potential for combination products. This index was used to evaluate the DDI potential for Danshen injectables from 16 different manufacturers and 14 different lots from a single manufacturer. The cumulative DDI index predicted in vivo inhibition potentials, 82% (hOAT1) and 74% (hOAT3), comparable with those observed in vitro, 72 ± 7% (hOAT1) and 81 ± 10% (hOAT3), for Danshen component combinations. Using simulated unbound Cmax values, a wide range in cumulative DDI index between manufacturers, and between lots, was predicted. Many products exhibited a cumulative DDI index > 1 (50% inhibition). Danshen injectables will likely exhibit strong potential to inhibit hOAT1 and hOAT3 function in vivo. The proposed cumulative DDI index might improve prediction of DDI potential of herbal medicines or pharmaceutical preparations containing multiple components.

  15. Clinical Drug-Drug Pharmacokinetic Interaction Potential of Sucralfate with Other Drugs: Review and Perspectives.

    Science.gov (United States)

    Sulochana, Suresh P; Syed, Muzeeb; Chandrasekar, Devaraj V; Mullangi, Ramesh; Srinivas, Nuggehally R

    2016-10-01

    Sucralfate, a complex of aluminium hydroxide with sulfated sucrose, forms a strong gastrointestinal tract (GIT) mucosal barrier with excellent anti-ulcer property. Because sucralfate does not undergo any significant oral absorption, sucralfate resides in the GIT for a considerable length of time. The unabsorbed sucralfate may alter the pharmacokinetics of the oral drugs by impeding its absorption and reducing the oral bioavailability. Because of the increased use of sucralfate, it was important to provide a reappraisal of the published clinical drug-drug interaction studies of sucralfate with scores of drugs. This review covers several category of drugs such as non-steroidal anti-inflammatory drugs, fluoroquinolones, histamine H2-receptor blockers, macrolides, anti-fungals, anti-diabetics, salicylic acid derivatives, steroidal anti-inflammatory drugs and provides pharmacokinetic data summary along with study design, objectives and key remarks. While the loss of oral bioavailability was significant for the fluoroquinolone class, it generally varied for other classes of drugs, suggesting that impact of the co-administration of sucralfate is manageable in clinical situations. Given the technology advancement in formulation development, it may be in order feasible to develop appropriate formulation strategies to either avoid or minimize the absorption-related issues when co-administered with sucralfate. It is recommended that consideration of both in vitro and preclinical studies may be in order to gauge the level of interaction of a drug with sucralfate. Such data may aid in the development of appropriate strategies to navigate the co-administration of sucralfate with other drugs in this age of polypharmacy.

  16. Improved Predictions of Drug-Drug Interactions Mediated by Time-Dependent Inhibition of CYP3A.

    Science.gov (United States)

    Yadav, Jaydeep; Korzekwa, Ken; Nagar, Swati

    2018-05-07

    Time-dependent inactivation (TDI) of cytochrome P450s (CYPs) is a leading cause of clinical drug-drug interactions (DDIs). Current methods tend to overpredict DDIs. In this study, a numerical approach was used to model complex CYP3A TDI in human-liver microsomes. The inhibitors evaluated included troleandomycin (TAO), erythromycin (ERY), verapamil (VER), and diltiazem (DTZ) along with the primary metabolites N-demethyl erythromycin (NDE), norverapamil (NV), and N-desmethyl diltiazem (NDD). The complexities incorporated into the models included multiple-binding kinetics, quasi-irreversible inactivation, sequential metabolism, inhibitor depletion, and membrane partitioning. The resulting inactivation parameters were incorporated into static in vitro-in vivo correlation (IVIVC) models to predict clinical DDIs. For 77 clinically observed DDIs, with a hepatic-CYP3A-synthesis-rate constant of 0.000 146 min -1 , the average fold difference between the observed and predicted DDIs was 3.17 for the standard replot method and 1.45 for the numerical method. Similar results were obtained using a synthesis-rate constant of 0.000 32 min -1 . These results suggest that numerical methods can successfully model complex in vitro TDI kinetics and that the resulting DDI predictions are more accurate than those obtained with the standard replot approach.

  17. A linguistic rule-based approach to extract drug-drug interactions from pharmacological documents.

    Science.gov (United States)

    Segura-Bedmar, Isabel; Martínez, Paloma; de Pablo-Sánchez, César

    2011-03-29

    A drug-drug interaction (DDI) occurs when one drug influences the level or activity of another drug. The increasing volume of the scientific literature overwhelms health care professionals trying to be kept up-to-date with all published studies on DDI. This paper describes a hybrid linguistic approach to DDI extraction that combines shallow parsing and syntactic simplification with pattern matching. Appositions and coordinate structures are interpreted based on shallow syntactic parsing provided by the UMLS MetaMap tool (MMTx). Subsequently, complex and compound sentences are broken down into clauses from which simple sentences are generated by a set of simplification rules. A pharmacist defined a set of domain-specific lexical patterns to capture the most common expressions of DDI in texts. These lexical patterns are matched with the generated sentences in order to extract DDIs. We have performed different experiments to analyze the performance of the different processes. The lexical patterns achieve a reasonable precision (67.30%), but very low recall (14.07%). The inclusion of appositions and coordinate structures helps to improve the recall (25.70%), however, precision is lower (48.69%). The detection of clauses does not improve the performance. Information Extraction (IE) techniques can provide an interesting way of reducing the time spent by health care professionals on reviewing the literature. Nevertheless, no approach has been carried out to extract DDI from texts. To the best of our knowledge, this work proposes the first integral solution for the automatic extraction of DDI from biomedical texts.

  18. An attention-based effective neural model for drug-drug interactions extraction.

    Science.gov (United States)

    Zheng, Wei; Lin, Hongfei; Luo, Ling; Zhao, Zhehuan; Li, Zhengguang; Zhang, Yijia; Yang, Zhihao; Wang, Jian

    2017-10-10

    Drug-drug interactions (DDIs) often bring unexpected side effects. The clinical recognition of DDIs is a crucial issue for both patient safety and healthcare cost control. However, although text-mining-based systems explore various methods to classify DDIs, the classification performance with regard to DDIs in long and complex sentences is still unsatisfactory. In this study, we propose an effective model that classifies DDIs from the literature by combining an attention mechanism and a recurrent neural network with long short-term memory (LSTM) units. In our approach, first, a candidate-drug-oriented input attention acting on word-embedding vectors automatically learns which words are more influential for a given drug pair. Next, the inputs merging the position- and POS-embedding vectors are passed to a bidirectional LSTM layer whose outputs at the last time step represent the high-level semantic information of the whole sentence. Finally, a softmax layer performs DDI classification. Experimental results from the DDIExtraction 2013 corpus show that our system performs the best with respect to detection and classification (84.0% and 77.3%, respectively) compared with other state-of-the-art methods. In particular, for the Medline-2013 dataset with long and complex sentences, our F-score far exceeds those of top-ranking systems by 12.6%. Our approach effectively improves the performance of DDI classification tasks. Experimental analysis demonstrates that our model performs better with respect to recognizing not only close-range but also long-range patterns among words, especially for long, complex and compound sentences.

  19. Drug-drug Interactions of Statins Potentially Leading to Muscle-Related Side Effects in Hospitalized Patients.

    Science.gov (United States)

    Bucsa, Camelia; Farcas, Andreea; Leucuta, D; Mogosan, Cristina; Bojita, M; Dumitrascu, D L

    2015-01-01

    The associations of drugs that may interact with the statins resulting in elevated serum concentration of the statins are an important risk factor for statin induced muscle disorders. We aimed to determine the prevalence of these associations in all hospitalized patients that had been prescribed statins before/during hospitalization and to find out how often they are associated with muscle-related side effects. This prospective, non-interventional study performed in two internal medicine departments included patients with statin therapy before/during hospitalization. Data on each patient demographic characteristics, co-morbidities and treatment was collected from medical charts and interviews. We evaluated patients' therapy for the targeted associations using Thomson Micromedex Drug Interactions checker and we ranked the identified drug-drug interactions (DDIs) accordingly. Each patient with statin treatment before admission was additionally interviewed in order to identify muscular symptoms. In 109 patients on statin treatment we found 35 potential (p) DDIs of statins in 30 (27.5%) patients, most of which were in the therapy before admission (27 pDDIs). The pDDIs were moderate (20 pDDIs) and major (15 pDDIs). Of the total number of pDDIs, 24 were targeting the muscular system. The drugs most frequently involved in the statins' pDDIs were amiodarone and fenofibrate. Two of the patients with pDDIs reported muscle pain, both having additional risk factors for statin induced muscular effects. The prevalence of statins' pDDIs was high in our study, mostly in the therapy before admission, with only a small number of pDDIs resulting in clinical outcome.

  20. Predicting and understanding comprehensive drug-drug interactions via semi-nonnegative matrix factorization.

    Science.gov (United States)

    Yu, Hui; Mao, Kui-Tao; Shi, Jian-Yu; Huang, Hua; Chen, Zhi; Dong, Kai; Yiu, Siu-Ming

    2018-04-11

    Drug-drug interactions (DDIs) always cause unexpected and even adverse drug reactions. It is important to identify DDIs before drugs are used in the market. However, preclinical identification of DDIs requires much money and time. Computational approaches have exhibited their abilities to predict potential DDIs on a large scale by utilizing pre-market drug properties (e.g. chemical structure). Nevertheless, none of them can predict two comprehensive types of DDIs, including enhancive and degressive DDIs, which increases and decreases the behaviors of the interacting drugs respectively. There is a lack of systematic analysis on the structural relationship among known DDIs. Revealing such a relationship is very important, because it is able to help understand how DDIs occur. Both the prediction of comprehensive DDIs and the discovery of structural relationship among them play an important guidance when making a co-prescription. In this work, treating a set of comprehensive DDIs as a signed network, we design a novel model (DDINMF) for the prediction of enhancive and degressive DDIs based on semi-nonnegative matrix factorization. Inspiringly, DDINMF achieves the conventional DDI prediction (AUROC = 0.872 and AUPR = 0.605) and the comprehensive DDI prediction (AUROC = 0.796 and AUPR = 0.579). Compared with two state-of-the-art approaches, DDINMF shows it superiority. Finally, representing DDIs as a binary network and a signed network respectively, an analysis based on NMF reveals crucial knowledge hidden among DDIs. Our approach is able to predict not only conventional binary DDIs but also comprehensive DDIs. More importantly, it reveals several key points about the DDI network: (1) both binary and signed networks show fairly clear clusters, in which both drug degree and the difference between positive degree and negative degree show significant distribution; (2) the drugs having large degrees tend to have a larger difference between positive degree

  1. Comparison of three commercial knowledge bases for detection of drug-drug interactions in clinical decision support.

    Science.gov (United States)

    Fung, Kin Wah; Kapusnik-Uner, Joan; Cunningham, Jean; Higby-Baker, Stefanie; Bodenreider, Olivier

    2017-07-01

    To compare 3 commercial knowledge bases (KBs) used for detection and avoidance of potential drug-drug interactions (DDIs) in clinical practice. Drugs in the DDI tables from First DataBank (FDB), Micromedex, and Multum were mapped to RxNorm. The KBs were compared at the clinical drug, ingredient, and DDI rule levels. The KBs were evaluated against a reference list of highly significant DDIs from the Office of the National Coordinator for Health Information Technology (ONC). The KBs and the ONC list were applied to a prescription data set to simulate their use in clinical decision support. The KBs contained 1.6 million (FDB), 4.5 million (Micromedex), and 4.8 million (Multum) clinical drug pairs. Altogether, there were 8.6 million unique pairs, of which 79% were found only in 1 KB and 5% in all 3 KBs. However, there was generally more agreement than disagreement in the severity rankings, especially in the contraindicated category. The KBs covered 99.8-99.9% of the alerts of the ONC list and would have generated 25 (FDB), 145 (Micromedex), and 84 (Multum) alerts per 1000 prescriptions. The commercial KBs differ considerably in size and quantity of alerts generated. There is less variability in severity ranking of DDIs than suggested by previous studies. All KBs provide very good coverage of the ONC list. More work is needed to standardize the editorial policies and evidence for inclusion of DDIs to reduce variation among knowledge sources and improve relevance. Some DDIs considered contraindicated in all 3 KBs might be possible candidates to add to the ONC list. Published by Oxford University Press on behalf of the American Medical Informatics Association 2017. This work is written by US Government employees and is in the public domain in the United States.

  2. Information needs for making clinical recommendations about potential drug-drug interactions: a synthesis of literature review and interviews.

    Science.gov (United States)

    Romagnoli, Katrina M; Nelson, Scott D; Hines, Lisa; Empey, Philip; Boyce, Richard D; Hochheiser, Harry

    2017-02-22

    Drug information compendia and drug-drug interaction information databases are critical resources for clinicians and pharmacists working to avoid adverse events due to exposure to potential drug-drug interactions (PDDIs). Our goal is to develop information models, annotated data, and search tools that will facilitate the interpretation of PDDI information. To better understand the information needs and work practices of specialists who search and synthesize PDDI evidence for drug information resources, we conducted an inquiry that combined a thematic analysis of published literature with unstructured interviews. Starting from an initial set of relevant articles, we developed search terms and conducted a literature search. Two reviewers conducted a thematic analysis of included articles. Unstructured interviews with drug information experts were conducted and similarly coded. Information needs, work processes, and indicators of potential strengths and weaknesses of information systems were identified. Review of 92 papers and 10 interviews identified 56 categories of information needs related to the interpretation of PDDI information including drug and interaction information; study design; evidence including clinical details, quality and content of reports, and consequences; and potential recommendations. We also identified strengths/weaknesses of PDDI information systems. We identified the kinds of information that might be most effective for summarizing PDDIs. The drug information experts we interviewed had differing goals, suggesting a need for detailed information models and flexible presentations. Several information needs not discussed in previous work were identified, including temporal overlaps in drug administration, biological plausibility of interactions, and assessment of the quality and content of reports. Richly structured depictions of PDDI information may help drug information experts more effectively interpret data and develop recommendations

  3. Preferences of Patients and Pharmacists with Regard to the Management of Drug-Drug Interactions : A Choice-Based Conjoint Analysis

    NARCIS (Netherlands)

    Heringa, Mette; Floor-Schreudering, Annemieke; Wouters, Hans; De Smet, Peter A G M; Bouvy, Marcel L

    INTRODUCTION: The management of drug-drug interactions (DDIs) is a complex process in which risk-benefit assessments should be combined with the patient's perspective. OBJECTIVE: The aim of this study was to determine patients' and pharmacists' preferences regarding DDI management. METHODS: We

  4. Diclofenac sex-divergent drug-drug interaction with Sunitinib: pharmacokinetics and tissue distribution in male and female mice.

    Science.gov (United States)

    Chew, Chii Chii; Ng, Salby; Chee, Yun Lee; Koo, Teng Wai; Liew, Ming Hui; Chee, Evelyn Li-Ching; Modamio, Pilar; Fernández, Cecilia; Mariño, Eduardo L; Segarra, Ignacio

    2017-08-01

    Coadministration of diclofenac and sunitinib, tyrosine kinase inhibitor, led to sex-divergent pharmacokinetic drug-drug interaction outcomes. Male and female mice were administered 60 mg/kg PO sunitinib alone (control groups) or with 30 mg/kg PO diclofenac. Sunitinib concentration in plasma, brain, kidney and liver were determined by HPLC and non-compartmental pharmacokinetic parameters calculated. In male mice, diclofenac decreased AUC 0→∞ 38% in plasma (p diclofenac increased the liver uptake efficiency in male (27%, p diclofenac with probable clinical translatability due to potential different effects in male and female patients requiring careful selection of the NSAID and advanced TDM to implement a personalized treatment.

  5. Target-mediated drug disposition with drug-drug interaction, Part I: single drug case in alternative formulations.

    Science.gov (United States)

    Koch, Gilbert; Jusko, William J; Schropp, Johannes

    2017-02-01

    Target-mediated drug disposition (TMDD) describes drug binding with high affinity to a target such as a receptor. In application TMDD models are often over-parameterized and quasi-equilibrium (QE) or quasi-steady state (QSS) approximations are essential to reduce the number of parameters. However, implementation of such approximations becomes difficult for TMDD models with drug-drug interaction (DDI) mechanisms. Hence, alternative but equivalent formulations are necessary for QE or QSS approximations. To introduce and develop such formulations, the single drug case is reanalyzed. This work opens the route for straightforward implementation of QE or QSS approximations of DDI TMDD models. The manuscript is the first part to introduce DDI TMDD models with QE or QSS approximations.

  6. Drug-drug interactions and adverse drug reactions in polypharmacy among older adults: an integrative review.

    Science.gov (United States)

    Rodrigues, Maria Cristina Soares; Oliveira, Cesar de

    2016-09-01

    to identify and summarize studies examining both drug-drug interactions (DDI) and adverse drug reactions (ADR) in older adults polymedicated. an integrative review of studies published from January 2008 to December 2013, according to inclusion and exclusion criteria, in MEDLINE and EMBASE electronic databases were performed. forty-seven full-text studies including 14,624,492 older adults (≥ 60 years) were analyzed: 24 (51.1%) concerning ADR, 14 (29.8%) DDI, and 9 studies (19.1%) investigating both DDI and ADR. We found a variety of methodological designs. The reviewed studies reinforced that polypharmacy is a multifactorial process, and predictors and inappropriate prescribing are associated with negative health outcomes, as increasing the frequency and types of ADRs and DDIs involving different drug classes, moreover, some studies show the most successful interventions to optimize prescribing. DDI and ADR among older adults continue to be a significant issue in the worldwide. The findings from the studies included in this integrative review, added to the previous reviews, can contribute to the improvement of advanced practices in geriatric nursing, to promote the safety of older patients in polypharmacy. However, more research is needed to elucidate gaps. identificar e sintetizar estudos que examinam as interações medicamentosas (IM) e reações adversas a medicamentos (RAM) em idosos polimedicados. revisão integrativa de estudos publicados de janeiro de 2008 a dezembro de 2013, de acordo com critérios de inclusão e exclusão, nas bases de dados eletrônicas MEDLINE e EMBASE. foram analisados 47 estudos de texto completo, incluindo 14,624,492 idosos (≥ 60 anos): 24 (51,1%) sobre RAM, 14 (29,8%) sobre IM e 9 estudos (19,1%) que investigaram tanto IM como RAM. Encontramos uma variedade de desenhos metodológicos. Os estudos revisados reforçaram que a polifarmácia é um processo multifatorial, e os preditores e a prescrição inadequada estão associados a

  7. The role of drug profiles as similarity metrics: applications to repurposing, adverse effects detection and drug-drug interactions.

    Science.gov (United States)

    Vilar, Santiago; Hripcsak, George

    2017-07-01

    Explosion of the availability of big data sources along with the development in computational methods provides a useful framework to study drugs' actions, such as interactions with pharmacological targets and off-targets. Databases related to protein interactions, adverse effects and genomic profiles are available to be used for the construction of computational models. In this article, we focus on the description of biological profiles for drugs that can be used as a system to compare similarity and create methods to predict and analyze drugs' actions. We highlight profiles constructed with different biological data, such as target-protein interactions, gene expression measurements, adverse effects and disease profiles. We focus on the discovery of new targets or pathways for drugs already in the pharmaceutical market, also called drug repurposing, in the interaction with off-targets responsible for adverse reactions and in drug-drug interaction analysis. The current and future applications, strengths and challenges facing all these methods are also discussed. Biological profiles or signatures are an important source of data generation to deeply analyze biological actions with important implications in drug-related studies. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. Pharmacogenetics of drug-drug interaction and drug-drug-gene interaction : A systematic review on CYP2C9, CYP2C19 and CYP2D6

    NARCIS (Netherlands)

    Bahar, Muh Akbar; Setiawan, Didik; Hak, Eelko; Wilffert, Bob

    Currently, most guidelines on drug-drug interaction (DDI) neither consider the potential effect of genetic polymorphism in the strength of the interaction nor do they account for the complex interaction caused by the combination of DDI and drug-gene interaction (DGI) where there are multiple

  9. Colchicine in Pericardial Disease: from the Underlying Biology and Clinical Benefits to the Drug-Drug Interactions in Cardiovascular Medicine.

    Science.gov (United States)

    Schenone, Aldo L; Menon, Venu

    2018-06-14

    This is an in-depth review on the mechanism of action, clinical utility, and drug-drug interactions of colchicine in the management of pericardial disease. Recent evidence about therapeutic targets on pericarditis has demonstrated that NALP3 inflammasome blockade is the cornerstone in the clinical benefits of colchicine. Such benefits extend from acute and recurrent pericarditis to transient constriction and post-pericardiotomy syndrome. Despite the increased utilization of colchicine in cardiovascular medicine, safety concerns remains unsolved regarding the long-term use of colchicine in the cardiac patient. Moreover, recent evidence has demonstrated that numerous cardiovascular medications, ranging from antihypertensive medication to antiarrhythmics, are known to interact with the CYP3A4 and/or P-gp system increasing the toxicity potential of colchicine. The use of adjunctive colchicine in the management of inflammatory pericardial diseases is standard of care in current practice. It is advised that a careful medication reconciliation with emphasis on pharmacokinetic is completed before prescribing colchicine in order to avoid harmful interaction by finding an alternative regimen or adjusting colchicine dosing.

  10. Detecting drug-drug interactions using a database for spontaneous adverse drug reactions: an example with diuretics and non-steroidal anti-inflammatory drugs.

    Science.gov (United States)

    van Puijenbroek, E P; Egberts, A C; Heerdink, E R; Leufkens, H G

    2000-12-01

    Drug-drug interactions are relatively rarely reported to spontaneous reporting systems (SRSs) for adverse drug reactions. For this reason, the traditional approach for analysing SRS has major limitations for the detection of drug-drug interactions. We developed a method that may enable signalling of these possible interactions, which are often not explicitly reported, utilising reports of adverse drug reactions in data sets of SRS. As an example, the influence of concomitant use of diuretics and non-steroidal anti-inflammatory drugs (NSAIDs) on symptoms indicating a decreased efficacy of diuretics was examined using reports received by the Netherlands Pharmacovigilance Foundation Lareb. Reports received between 1 January 1990 and 1 January 1999 of patients older than 50 years were included in the study. Cases were defined as reports with symptoms indicating a decreased efficacy of diuretics, non-cases as all other reports. Exposure categories were the use of NSAIDs or diuretics versus the use of neither of these drugs. The influence of the combined use of both drugs was examined using logistic regression analysis. The odds ratio of the statistical interaction term of the combined use of both drugs was increased [adjusted odds ratio 2.0, 95% confidence interval (CI) 1.1-3.7], which may indicate an enhanced effect of concomitant drug use. The findings illustrate that spontaneous reporting systems have a potential for signal detection and the analysis of possible drug-drug interactions. The method described may enable a more active approach in the detection of drug-drug interactions after marketing.

  11. A review of pharmacokinetic drug-drug interactions with the anthelmintic medications albendazole and mebendazole.

    Science.gov (United States)

    Pawluk, Shane Ashley; Roels, Craig Allan; Wilby, Kyle John; Ensom, Mary H H

    2015-04-01

    Medications indicated for helminthes and other parasitic infections are frequently being used in mass populations in endemic areas. Currently, there is a lack of guidance for clinicians on how to appropriately manage drug interactions when faced with patients requiring short-term anthelmintic therapy with albendazole or mebendazole while concurrently taking other agents. The objective of this review was to systematically summarize and evaluate published literature on the pharmacokinetics of albendazole or mebendazole when taken with other interacting medications. A search of MEDLINE (1946 to October 2014), EMBASE (1974 to October 2014), International Pharmaceutical Abstracts (1970 to October 2014), Google, and Google Scholar was conducted for articles describing the pharmacokinetics of albendazole or mebendazole when given with other medications (and supplemented by a bibliographic review of all relevant articles). Altogether, 17 articles were included in the review. Studies reported data on pharmacokinetic parameters for albendazole or mebendazole when taken with cimetidine, dexamethasone, ritonavir, phenytoin, carbamazepine, phenobarbital, ivermectin, praziquantel, diethylcarbamazine, azithromycin, and levamisole. Cimetidine increased the elimination half-life of albendazole and maximum concentration (Cmax) of mebendazole; dexamethasone increased the area under the plasma concentration-time curve (AUC) of albendazole; levamisole decreased the Cmax of albendazole; anticonvulsants (phenytoin, phenobarbital, carbamazepine) decreased the AUC of albendazole; praziquantel increased the AUC of albendazole; and ritonavir decreased the AUC of both albendazole and mebendazole. No major interactions were found with ivermectin, azithromycin, or diethylcarbamazine. Future research is required to clarify the clinical relevance of the interactions observed.

  12. Retrospective use of PBPK modelling to understand a clinical drug-drug interaction between dextromethorphan and GSK1034702.

    Science.gov (United States)

    Hobbs, Michael J; Bloomer, Jackie; Dear, Gordon

    2017-08-01

    1. In a clinical trial, a strong drug-drug interaction (DDI) was observed between dextromethorphan (DM, the object or victim drug) and GSK1034702 (the precipitant or perpetrator drug), following single and repeat doses. This study determined the inhibition parameters of GSK1034702 in vitro and applied PBPK modelling approaches to simulate the clinical observations and provide mechanistic hypotheses to understand the DDI. 2. In vitro assays were conducted to determine the inhibition parameters of human CYP2D6 by GSK1034702. PBPK models were populated with the in vitro parameters and DDI simulations conducted and compared to the observed data from a clinical study with DM and GSK1034702. 3. GSK1034702 was a potent direct and metabolism-dependent inhibitor of human CYP2D6, with inhibition parameters of: IC 50  =   1.6 μM, K inact  = 3.7 h -1 and K I  = 0.8 μM. Incorporating these data into PBPK models predicted a DDI after repeat, but not single, 5 mg doses of GSK1034702. 4. The DDI observed with repeat administration of GSK1034702 (5 mg) can be attributed to metabolism-dependent inhibition of CYP2D6. Further, in vitro data were generated and several potential mechanisms proposed to explain the interaction observed following a single dose of GSK1034702.

  13. Reduced Effectiveness of Interruptive Drug-Drug Interaction Alerts after Conversion to a Commercial Electronic Health Record.

    Science.gov (United States)

    Wright, Adam; Aaron, Skye; Seger, Diane L; Samal, Lipika; Schiff, Gordon D; Bates, David W

    2018-05-15

    Drug-drug interaction (DDI) alerts in electronic health records (EHRs) can help prevent adverse drug events, but such alerts are frequently overridden, raising concerns about their clinical usefulness and contribution to alert fatigue. To study the effect of conversion to a commercial EHR on DDI alert and acceptance rates. Two before-and-after studies. 3277 clinicians who received a DDI alert in the outpatient setting. Introduction of a new, commercial EHR and subsequent adjustment of DDI alerting criteria. Alert burden and proportion of alerts accepted. Overall interruptive DDI alert burden increased by a factor of 6 from the legacy EHR to the commercial EHR. The acceptance rate for the most severe alerts fell from 100 to 8.4%, and from 29.3 to 7.5% for medium severity alerts (P fell by 50.5%, and acceptance of Tier 1 alerts rose from 9.1 to 12.7% (P < 0.01). Changing from a highly tailored DDI alerting system to a more general one as part of an EHR conversion decreased acceptance of DDI alerts and increased alert burden on users. The decrease in acceptance rates cannot be fully explained by differences in the clinical knowledge base, nor can it be fully explained by alert fatigue associated with increased alert burden. Instead, workflow factors probably predominate, including timing of alerts in the prescribing process, lack of differentiation of more and less severe alerts, and features of how users interact with alerts.

  14. Strategy for the Prediction of Steady-State Exposure of Digoxin to Determine Drug-Drug Interaction Potential of Digoxin With Other Drugs in Digitalization Therapy.

    Science.gov (United States)

    Srinivas, Nuggehally R

    2016-01-20

    Digoxin, a narrow therapeutic index drug, is widely used in congestive heart failure. However, the digitalization therapy involves dose titration and can exhibit drug-drug interaction. Ctrough versus area under the plasma concentration versus time curve in a dosing interval of 24 hours (AUC0-24h) and Cmax versus AUC0-24h for digoxin were established by linear regression. The predictions of digoxin AUC0-24h values were performed using published Ctrough or Cmax with appropriate regression lines. The fold difference, defined as the quotient of the observed/predicted AUC0-24h values, was evaluated. The mean square error and root mean square error, correlation coefficient (r), and goodness of the fold prediction were used to evaluate the models. Both Ctrough versus AUC0-24h (r = 0.9215) and Cmax versus AUC0-24h models for digoxin (r = 0.7781) showed strong correlations. Approximately 93.8% of the predicted digoxin AUC0-24h values were within 0.76-fold to 1.25-fold difference for Ctrough model. In sharp contrast, the Cmax model showed larger variability with only 51.6% of AUC0-24h predictions within 0.76-1.25-fold difference. The r value for observed versus predicted AUC0-24h for Ctrough (r = 0.9551; n = 177; P < 0.001) was superior to the Cmax (r = 0.6134; n = 275; P < 0.001) model. The mean square error and root mean square error (%) for the Ctrough model were 11.95% and 16.2% as compared to 67.17% and 42.3% obtained for the Cmax model. Simple linear regression models for Ctrough/Cmax versus AUC0-24h were derived for digoxin. On the basis of statistical evaluation, Ctrough was superior to Cmax model for the prediction of digoxin AUC0-24h and can be potentially used in a prospective setting for predicting drug-drug interaction or lack of it.

  15. 6-mercaptopurine and daunorubicin double drug liposomes-preparation, drug-drug interaction and characterization.

    Science.gov (United States)

    Agrawal, Vineet; Paul, Manash K; Mukhopadhyay, Anup K

    2005-01-01

    This article addresses and investigates the dual incorporation of daunorubicin (DR) and 6-mercaptopurine (6-MP) in liposomes for better chemotherapy. These drugs are potential candidates for interaction due to the quinone (H acceptor) and hydroxyl (H donor) groups on DR and 6-MP, respectively. Interactions between the two drugs in solution were monitored by UV/Vis and fluorescence spectroscopy. Interaction between the two drugs inside the liposomes was evaluated by HPLC (for 6-MP) and by fluorescence spectroscopy (for daunorubicin) after phospholipase-mediated liposome lysis. Our results provide evidence for the lack of interaction between the two drugs in solution and in liposomes. The entrapment efficiencies of 6-MP in the neutral Phosphatidyl choline (PC):Cholesterol (Chol):: 2:1 and anionic PC:Chol:Cardiolipin (CL) :: 4:5:1 single and double drug liposomes were found to be 0.4% and 1.5% (on average), respectively. The entrapment efficiencies of DR in the neutral and anionic double drug liposomes were found to be 55% and 31%, respectively. The corresponding entrapment of daunorubicin in the single drug liposomes was found to be 62% on average. Our thin layer chromatography (TLC) and transmission electron microscopy (TEM) results suggest stability of lipid and liposomes, thus pointing plausible existence of double drug liposomes. Cytotoxicity experiments were performed by using both single drug and double drug liposomes. By comparing the results of phase contrast and fluorescence microscopy, it was observed that the double drug liposomes were internalized in the jurkat and Hut78 (highly resistant cell line) leukemia cells as viewed by the fluorescence of daunorubicin. The cytotoxicity was dose dependent and had shown a synergistic effect when double drug liposome was used.

  16. Analysis of Potential Drug-Drug Interactions and Its Clinical Manifestation of Pediatric Prescription on 2 Pharmacies in Bandung

    Directory of Open Access Journals (Sweden)

    Melisa I. Barliana

    2013-09-01

    Full Text Available The potential of Drug-Drug Interactions (DDI in prescription have high incidence around the world, including Indonesia. However, scientific evidence regarding DDI in Indonesia is not available. Therefore, in this study we have conducted survey in 2 pharmacies in Bandung against pediatric prescription given by pediatrician. These prescriptions then analyzed the potential for DDI contained in the prescription and clinical manifestation. The analysis showed that in pharmacy A, there are 33 prescriptions (from a total of 155 prescriptions that have potential DDI, or approximately 21.19% (2 prescriptions have the potential DDI major categories, 23 prescriptions categorized as moderate, and 8 prescriptions as minor. In Pharmacy B, there are 6 prescriptions (from a total of 40 prescriptions or 15% of potential DDI (4 prescriptions categorized as moderate and 2 prescriptions as minor. This result showed that potential DDI happened less than 50% in pediatric prescription from both pharmacies. However, this should get attention because DDI should not happen in a prescription considering its clinical manifestations caused by DDI. Moreover, current pharmaceutical care refers to patient oriented than product oriented. In addition, further study for the pediatric prescription on DDI incidence in large scale need to be investigated.

  17. Drug-drug interactions and adverse drug reactions in polypharmacy among older adults: an integrative review 1

    Science.gov (United States)

    Rodrigues, Maria Cristina Soares; de Oliveira, Cesar

    2016-01-01

    ABSTRACT Objective: to identify and summarize studies examining both drug-drug interactions (DDI) and adverse drug reactions (ADR) in older adults polymedicated. Methods: an integrative review of studies published from January 2008 to December 2013, according to inclusion and exclusion criteria, in MEDLINE and EMBASE electronic databases were performed. Results: forty-seven full-text studies including 14,624,492 older adults (≥ 60 years) were analyzed: 24 (51.1%) concerning ADR, 14 (29.8%) DDI, and 9 studies (19.1%) investigating both DDI and ADR. We found a variety of methodological designs. The reviewed studies reinforced that polypharmacy is a multifactorial process, and predictors and inappropriate prescribing are associated with negative health outcomes, as increasing the frequency and types of ADRs and DDIs involving different drug classes, moreover, some studies show the most successful interventions to optimize prescribing. Conclusions: DDI and ADR among older adults continue to be a significant issue in the worldwide. The findings from the studies included in this integrative review, added to the previous reviews, can contribute to the improvement of advanced practices in geriatric nursing, to promote the safety of older patients in polypharmacy. However, more research is needed to elucidate gaps. PMID:27598380

  18. Characterization of the mechanism of drug-drug interactions from PubMed using MeSH terms.

    Science.gov (United States)

    Lu, Yin; Figler, Bryan; Huang, Hong; Tu, Yi-Cheng; Wang, Ju; Cheng, Feng

    2017-01-01

    Identifying drug-drug interaction (DDI) is an important topic for the development of safe pharmaceutical drugs and for the optimization of multidrug regimens for complex diseases such as cancer and HIV. There have been about 150,000 publications on DDIs in PubMed, which is a great resource for DDI studies. In this paper, we introduced an automatic computational method for the systematic analysis of the mechanism of DDIs using MeSH (Medical Subject Headings) terms from PubMed literature. MeSH term is a controlled vocabulary thesaurus developed by the National Library of Medicine for indexing and annotating articles. Our method can effectively identify DDI-relevant MeSH terms such as drugs, proteins and phenomena with high accuracy. The connections among these MeSH terms were investigated by using co-occurrence heatmaps and social network analysis. Our approach can be used to visualize relationships of DDI terms, which has the potential to help users better understand DDIs. As the volume of PubMed records increases, our method for automatic analysis of DDIs from the PubMed database will become more accurate.

  19. Characterization of the mechanism of drug-drug interactions from PubMed using MeSH terms.

    Directory of Open Access Journals (Sweden)

    Yin Lu

    Full Text Available Identifying drug-drug interaction (DDI is an important topic for the development of safe pharmaceutical drugs and for the optimization of multidrug regimens for complex diseases such as cancer and HIV. There have been about 150,000 publications on DDIs in PubMed, which is a great resource for DDI studies. In this paper, we introduced an automatic computational method for the systematic analysis of the mechanism of DDIs using MeSH (Medical Subject Headings terms from PubMed literature. MeSH term is a controlled vocabulary thesaurus developed by the National Library of Medicine for indexing and annotating articles. Our method can effectively identify DDI-relevant MeSH terms such as drugs, proteins and phenomena with high accuracy. The connections among these MeSH terms were investigated by using co-occurrence heatmaps and social network analysis. Our approach can be used to visualize relationships of DDI terms, which has the potential to help users better understand DDIs. As the volume of PubMed records increases, our method for automatic analysis of DDIs from the PubMed database will become more accurate.

  20. Optimization of drug-drug interaction alert rules in a pediatric hospital's electronic health record system using a visual analytics dashboard.

    Science.gov (United States)

    Simpao, Allan F; Ahumada, Luis M; Desai, Bimal R; Bonafide, Christopher P; Gálvez, Jorge A; Rehman, Mohamed A; Jawad, Abbas F; Palma, Krisha L; Shelov, Eric D

    2015-03-01

    To develop and evaluate an electronic dashboard of hospital-wide electronic health record medication alerts for an alert fatigue reduction quality improvement project. We used visual analytics software to develop the dashboard. We collaborated with the hospital-wide Clinical Decision Support committee to perform three interventions successively deactivating clinically irrelevant drug-drug interaction (DDI) alert rules. We analyzed the impact of the interventions on care providers' and pharmacists' alert and override rates using an interrupted time series framework with piecewise regression. We evaluated 2 391 880 medication alerts between January 31, 2011 and January 26, 2014. For pharmacists, the median alert rate prior to the first DDI deactivation was 58.74 alerts/100 orders (IQR 54.98-60.48) and 25.11 alerts/100 orders (IQR 23.45-26.57) following the three interventions (pdashboard facilitated safe rapid-cycle reductions in alert burden that were temporally associated with lower pharmacist override rates in a subgroup of DDIs not directly affected by the interventions; meanwhile, the pharmacists' frequency of selecting the 'cancel' option increased. We hypothesize that reducing the alert burden enabled pharmacists to devote more attention to clinically relevant alerts. © The Author 2014. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Investigation of bioequivalence of a new fixed-dose combination of nifedipine and candesartan with the corresponding loose combination as well as the drug-drug interaction potential between both drugs under fasting conditions.

    Science.gov (United States)

    Brendel, Erich; Weimann, Boris; Dietrich, Hartmut; Froede, Christoph; Thomas, Dirk

    2013-09-01

    To determine the bioequivalence of a nifedipine and candesartan fixed-dose combination (FDC) with the corresponding loose combination, and to investigate the pharmacokinetic drug-drug interaction potential between both drugs. 49 healthy, white, male subjects received: 60 mg nifedipine and 32 mg candesartan FDC, the loose combination of 60 mg nifedipine GITS and 32 mg candesartan, 60 mg nifedipine GITS alone, or 32 mg candesartan alone in a randomized, non-blinded, 4-period, 4-way crossover design with each dosing following overnight fasting. Treatment periods were separated by washout periods of ≥ 5 days. Plasma samples were collected for 48 hours after dosing and assayed using a validated LC-MS/MS method. Bioequivalence between the FDC and the loose combination as well as the impact of combined treatment with both drugs on candesartan pharmacokinetics was evaluated in 47 subjects, while the corresponding impact of treatment with both drugs on nifedipine pharmacokinetics was assessed in 46 patients. For AUC(0-tlast) and Cmax the 90% confidence intervals (CIs) for the ratios of the FDC vs. the corresponding loose combination were within the acceptance range for bioequivalence of 80 - 125%. When comparing AUC(0-tlast) and Cmax of nifedipine and candesartan after dosing with the loose combination vs. each drug alone, the 90% CIs remained within the range of 80 - 125% indicating the absence of a clinically relevant pharmacokinetic drug-drug interaction. Nifedipine and candesartan as well as the combinations were well tolerated. The FDC containing 60 mg nifedipine and 32 mg candesartan was bioequivalent to the corresponding loose combination following single oral doses under fasting conditions. No clinically relevant pharmacokinetic drug-drug interaction between nifedipine and candesartan was observed.

  2. Drug-drug interaction of microdose and regular-dose omeprazole with a CYP2C19 inhibitor and inducer.

    Science.gov (United States)

    Park, Gab-Jin; Bae, Soo Hyeon; Park, Wan-Su; Han, Seunghoon; Park, Min-Ho; Shin, Seok-Ho; Shin, Young G; Yim, Dong-Seok

    2017-01-01

    A microdose drug-drug interaction (DDI) study may be a valuable tool for anticipating drug interaction at therapeutic doses. This study aimed to compare the magnitude of DDIs at microdoses and regular doses to explore the applicability of a microdose DDI study. Six healthy male volunteer subjects were enrolled into each DDI study of omeprazole (victim) and known perpetrators: fluconazole (inhibitor) and rifampin (inducer). For both studies, the microdose (100 μg, cold compound) and the regular dose (20 mg) of omeprazole were given at days 0 and 1, respectively. On days 2-9, the inhibitor or inducer was given daily, and the microdose and regular dose of omeprazole were repeated at days 8 and 9, respectively. Full omeprazole pharmacokinetic samplings were performed at days 0, 1, 8, and 9 of both studies for noncompartmental analysis. The magnitude of the DDI, the geometric mean ratios (with perpetrator/omeprazole only) of maximum concentration (C max ) and area under the curve to the last measurement (AUC t ) of the microdose and the regular dose were compared. The geometric mean ratios in the inhibition study were: 2.17 (micro) and 2.68 (regular) for C max , and 4.07 (micro), 4.33 (regular) for AUC t . For the induction study, they were 0.26 (micro) and 0.21 (regular) for C max , and 0.16 (micro) and 0.15 (regular) for AUC t . There were no significant statistical differences in the magnitudes of DDIs between microdose and regular-dose conditions, regardless of induction or inhibition. Our results may be used as partial evidence that microdose DDI studies may replace regular-dose studies, or at least be used for DDI-screening purposes.

  3. Projecting ADME Behavior and Drug-Drug Interactions in Early Discovery and Development: Application of the Extended Clearance Classification System.

    Science.gov (United States)

    El-Kattan, Ayman F; Varma, Manthena V; Steyn, Stefan J; Scott, Dennis O; Maurer, Tristan S; Bergman, Arthur

    2016-12-01

    To assess the utility of Extended Clearance Classification System (ECCS) in understanding absorption, distribution, metabolism, and elimination (ADME) attributes and enabling victim drug-drug interaction (DDI) predictions. A database of 368 drugs with relevant ADME parameters, main metabolizing enzymes, uptake transporters, efflux transporters, and highest change in exposure (%AUC) in presence of inhibitors was developed using published literature. Drugs were characterized according to ECCS using ionization, molecular weight and estimated permeability. Analyses suggested that ECCS class 1A drugs are well absorbed and systemic clearance is determined by metabolism mediated by CYP2C, esterases, and UGTs. For class 1B drugs, oral absorption is high and the predominant clearance mechanism is hepatic uptake mediated by OATP transporters. High permeability neutral/basic drugs (class 2) showed high oral absorption, with metabolism mediated generally by CYP3A, CYP2D6 and UGTs as the predominant clearance mechanism. Class 3A/4 drugs showed moderate absorption with dominant renal clearance involving OAT/OCT2 transporters. Class 3B drugs showed low to moderate absorption with hepatic uptake (OATPs) and/or renal clearance as primary clearance mechanisms. The highest DDI risk is typically seen with class 2/1B/3B compounds manifested by inhibition of either CYP metabolism or active hepatic uptake. Class 2 showed a wider range in AUC change likely due to a variety of enzymes involved. DDI risk for class 3A/4 is small and associated with inhibition of renal transporters. ECCS provides a framework to project ADME profiles and further enables prediction of victim DDI liabilities in drug discovery and development.

  4. A quantitative systems pharmacology approach, incorporating a novel liver model, for predicting pharmacokinetic drug-drug interactions.

    Science.gov (United States)

    Cherkaoui-Rbati, Mohammed H; Paine, Stuart W; Littlewood, Peter; Rauch, Cyril

    2017-01-01

    All pharmaceutical companies are required to assess pharmacokinetic drug-drug interactions (DDIs) of new chemical entities (NCEs) and mathematical prediction helps to select the best NCE candidate with regard to adverse effects resulting from a DDI before any costly clinical studies. Most current models assume that the liver is a homogeneous organ where the majority of the metabolism occurs. However, the circulatory system of the liver has a complex hierarchical geometry which distributes xenobiotics throughout the organ. Nevertheless, the lobule (liver unit), located at the end of each branch, is composed of many sinusoids where the blood flow can vary and therefore creates heterogeneity (e.g. drug concentration, enzyme level). A liver model was constructed by describing the geometry of a lobule, where the blood velocity increases toward the central vein, and by modeling the exchange mechanisms between the blood and hepatocytes. Moreover, the three major DDI mechanisms of metabolic enzymes; competitive inhibition, mechanism based inhibition and induction, were accounted for with an undefined number of drugs and/or enzymes. The liver model was incorporated into a physiological-based pharmacokinetic (PBPK) model and simulations produced, that in turn were compared to ten clinical results. The liver model generated a hierarchy of 5 sinusoidal levels and estimated a blood volume of 283 mL and a cell density of 193 × 106 cells/g in the liver. The overall PBPK model predicted the pharmacokinetics of midazolam and the magnitude of the clinical DDI with perpetrator drug(s) including spatial and temporal enzyme levels changes. The model presented herein may reduce costs and the use of laboratory animals and give the opportunity to explore different clinical scenarios, which reduce the risk of adverse events, prior to costly human clinical studies.

  5. A quantitative systems pharmacology approach, incorporating a novel liver model, for predicting pharmacokinetic drug-drug interactions.

    Directory of Open Access Journals (Sweden)

    Mohammed H Cherkaoui-Rbati

    Full Text Available All pharmaceutical companies are required to assess pharmacokinetic drug-drug interactions (DDIs of new chemical entities (NCEs and mathematical prediction helps to select the best NCE candidate with regard to adverse effects resulting from a DDI before any costly clinical studies. Most current models assume that the liver is a homogeneous organ where the majority of the metabolism occurs. However, the circulatory system of the liver has a complex hierarchical geometry which distributes xenobiotics throughout the organ. Nevertheless, the lobule (liver unit, located at the end of each branch, is composed of many sinusoids where the blood flow can vary and therefore creates heterogeneity (e.g. drug concentration, enzyme level. A liver model was constructed by describing the geometry of a lobule, where the blood velocity increases toward the central vein, and by modeling the exchange mechanisms between the blood and hepatocytes. Moreover, the three major DDI mechanisms of metabolic enzymes; competitive inhibition, mechanism based inhibition and induction, were accounted for with an undefined number of drugs and/or enzymes. The liver model was incorporated into a physiological-based pharmacokinetic (PBPK model and simulations produced, that in turn were compared to ten clinical results. The liver model generated a hierarchy of 5 sinusoidal levels and estimated a blood volume of 283 mL and a cell density of 193 × 106 cells/g in the liver. The overall PBPK model predicted the pharmacokinetics of midazolam and the magnitude of the clinical DDI with perpetrator drug(s including spatial and temporal enzyme levels changes. The model presented herein may reduce costs and the use of laboratory animals and give the opportunity to explore different clinical scenarios, which reduce the risk of adverse events, prior to costly human clinical studies.

  6. Hypericum perforatum: pharmacokinetic, mechanism of action, tolerability, and clinical drug-drug interactions.

    Science.gov (United States)

    Russo, Emilio; Scicchitano, Francesca; Whalley, Benjamin J; Mazzitello, Carmela; Ciriaco, Miriam; Esposito, Stefania; Patanè, Marinella; Upton, Roy; Pugliese, Michela; Chimirri, Serafina; Mammì, Maria; Palleria, Caterina; De Sarro, Giovambattista

    2014-05-01

    Hypericum perforatum (HP) belongs to the Hypericaceae family and is one of the oldest used and most extensively investigated medicinal herbs. The medicinal form comprises the leaves and flowering tops of which the primary ingredients of interest are naphthodianthrones, xanthones, flavonoids, phloroglucinols (e.g. hyperforin), and hypericin. Although several constituents elicit pharmacological effects that are consistent with HP's antidepressant activity, no single mechanism of action underlying these effects has thus far been found. Various clinical trials have shown that HP has a comparable antidepressant efficacy as some currently used antidepressant drugs in the treatment of mild/moderate depression. Interestingly, low-hyperforin-content preparations are effective in the treatment of depression. Moreover, HP is also used to treat certain forms of anxiety. However, HP can induce various cytochrome P450s isozymes and/or P-glycoprotein, of which many drugs are substrates and which are the main origin of HP-drug interactions. Here, we analyse the existing evidence describing the clinical consequence of HP-drug interactions. Although some of the reported interactions are based on findings from in vitro studies, the clinical importance of which remain to be demonstrated, others are based on case reports where causality can, in some cases, be determined to reveal clinically significant interactions that suggest caution, consideration, and disclosure of potential interactions prior to informed use of HP. Copyright © 2013 John Wiley & Sons, Ltd.

  7. Polypharmacy and the risk of drug-drug interactions among Danish elderly

    DEFF Research Database (Denmark)

    Rosholm, J U; Bjerrum, L; Hallas, J

    1998-01-01

    OBJECTIVE: To analyze the use of all subsidized prescription drugs with special attention to the elderly (> or = 70 years of age), including their use of drug combination generally accepted as carrying a risk of severe interactions. DESIGN: Descriptive prevalence study. SETTING: Odense...... accepted as carrying a risk of severe interactions. RESULTS: Among persons less than 70 years, 67.9% used none, 16.5% used one drug and 15.6% used two or more prescription drugs. The corresponding prevalences for the elderly were 35.7%, 15.9% and 48.4%. The 26,337 elderly patients with at least two drugs...... used 21,293 different combinations. Of the elderly patients who had purchased > or = two drugs, 4.4% had combinations of drugs carrying a risk of severe interactions. CONCLUSIONS: Most elderly use drugs and usually several drugs concomitantly. The elderly form a heterogeneous group of drug users. Drug...

  8. Entecavir Interacts with Influx Transporters hOAT1, hCNT2, hCNT3, but Not with hOCT2: The Potential for Renal Transporter-Mediated Cytotoxicity and Drug-Drug Interactions

    Czech Academy of Sciences Publication Activity Database

    Mandíková, J.; Volková, M.; Pávek, P.; Navrátilová, L.; Hyršová, L.; Janeba, Zlatko; Pavlík, J.; Bárta, P.; Trejtnar, F.

    2016-01-01

    Roč. 6, Jan 5 (2016), č. článku 304. ISSN 1663-9812 Institutional support: RVO:61388963 Keywords : antivirals * nephrotoxicity * renal disposition * drug-drug interactions Subject RIV: CC - Organic Chemistry Impact factor: 4.400, year: 2016 http://journal.frontiersin.org/article/10.3389/fphar.2015.00304/full

  9. Possible drug-drug interaction between pregabalin and clozapine in patients with schizophrenia

    DEFF Research Database (Denmark)

    Schjerning, O; Lykkegaard, S; Damkier, P

    2015-01-01

    INTRODUCTION: Pregabalin is an antiepileptic drug with anti-anxiety properties and is approved for treatment of generalized anxiety disorder. Anxiety is common in patients with schizophrenia and pregabalin has been suggested as an off-label add-on treatment. METHODS: Pregabalin was added...... patient was less clear. DISCUSSION: This short report discusses the possible mechanism of a pregabalin-clozapine interaction....

  10. Drug-drug interactions as a determinant of elevated lithium serum levels in daily clinical practice

    NARCIS (Netherlands)

    Wilting, [No Value; Movig, KL; Moolenaar, M; Hekster, YA; Brouwers, [No Value; Heerdink, ER; Nolen, WA; Egberts, AC

    Objective: Lithium is a drug with a narrow therapeutic window. Concomitantly used medication is a potentially influencing factor of lithium serum concentrations. We conducted a multicentre retrospective case-control study with the aim of investigating lithium-related drug interactions as

  11. Drug-drug interactions between anti-retroviral therapies and drugs of abuse in HIV systems.

    Science.gov (United States)

    Kumar, Santosh; Rao, P S S; Earla, Ravindra; Kumar, Anil

    2015-03-01

    Substance abuse is a common problem among HIV-infected individuals. Importantly, addictions as well as moderate use of alcohol, smoking, or other illicit drugs have been identified as major reasons for non-adherence to antiretroviral therapy (ART) among HIV patients. The literature also suggests a decrease in the response to ART among HIV patients who use these substances, leading to failure to achieve optimal virological response and increased disease progression. This review discusses the challenges with adherence to ART as well as observed drug interactions and known toxicities with major drugs of abuse, such as alcohol, smoking, methamphetamine, cocaine, marijuana, and opioids. The lack of adherence and drug interactions potentially lead to decreased efficacy of ART drugs and increased ART, and drugs of abuse-mediated toxicity. As CYP is the common pathway in metabolizing both ART and drugs of abuse, we discuss the possible involvement of CYP pathways in such drug interactions. We acknowledge that further studies focusing on common metabolic pathways involving CYP and advance research in this area would help to potentially develop novel/alternate interventions and drug dose/regimen adjustments to improve medication outcomes in HIV patients who consume drugs of abuse.

  12. Pharmacokinetic drug-drug interaction between erlotinib and paracetamol: A potential risk for clinical practice.

    Science.gov (United States)

    Karbownik, Agnieszka; Szałek, Edyta; Sobańska, Katarzyna; Grabowski, Tomasz; Wolc, Anna; Grześkowiak, Edmund

    2017-05-01

    Erlotinib is a tyrosine kinase inhibitor available for the treatment of non-small cell lung cancer. Paracetamol is an analgesic agent, commonly used in cancer patients. Because these drugs are often co-administered, there is an increasing issue of interaction between them. The aim of the study was to investigate the effect of paracetamol on the pharmacokinetic parameters of erlotinib, as well as the influence of erlotinib on the pharmacokinetics of paracetamol. The rabbits were divided into three groups: the rabbits receiving erlotinib (I ER ), the group receiving paracetamol (II PR ), and the rabbits receiving erlotinib+paracetamol (III ER+PR ). A single dose of erlotinib was administered orally (25mg) and was administered intravenously (35mg/kg). Plasma concentrations of erlotinib, its metabolite (OSI420), paracetamol and its metabolites - glucuronide and sulphate were measured with the validated method. During paracetamol co-administration we observed increased erlotinib maximum concentration (C max ) and area under the plasma concentration-time curve from time zero to infinity (AUC 0-∞ ) by 87.7% and 31.1%, respectively. In turn, erlotinib lead to decreased paracetamol AUC 0-∞ by 35.5% and C max by 18.9%. The mean values of paracetamol glucuronide/paracetamol ratios for C max were 32.2% higher, whereas paracetamol sulphate/paracetamol ratios for C max and AUC 0-∞ were 37.1% and 57.1% lower in the II PR group, when compared to the III ER+PR group. Paracetamol had significant effect on the enhanced plasma exposure of erlotinib. Additionally, erlotinib contributed to the lower concentrations of paracetamol. Decreased glucuronidation and increased sulphation of paracetamol after co-administration of erlotinib were also observed. Copyright © 2017. Published by Elsevier B.V.

  13. Potential drug-drug interactions in a Brazilian teaching hospital: age-related differences?

    Directory of Open Access Journals (Sweden)

    Daniela Oliveira Melo

    2016-07-01

    Full Text Available This study proposes to measure frequency and to characterize the profile of potential drug interactions (pDDI in a general medicine ward of a teaching hospital. Data about identification and clinical status of patients were extracted from medical records between March to August 2006. The occurrence of pDDI was analyzed using the database monographs Micromedex® DrugReax® System. From 5,336 prescriptions with two or more drugs, 3,097 (58.0% contained pDDI. The frequency of major and well document pDDI was 26.5%. Among 647 patients, 432 (66.8% were exposed to at least one pDDI and 283 (43.7% to major pDDI. The multivariate analysis identified that factors related to higher rates of major pDDI were the same age (p< 0.0001, length of stay (p< 0.0001, prevalence of hypertension [OR=3.42 (p< 0.0001] and diabetes mellitus [OR=2.1 (p< 0.0001], cardiovascular diseases (p< 0.0001 and the number of prescribed drugs (Spearman’s correlation=0.640622, p< 0.0001. Between major pDDI, the main risk was hemorrhage (50.3%, the most frequent major pDDI involved combination of anticoagulants and antiplatelet drugs. Among moderate pDDI, 3,866 (90.8% involved medicines for the treatment of chronic non-communicable diseases, mainly hypertension. In HU-USP, the profile of pDDI was similar among adults and elderly (the most frequent pDDI and major pDDI were same, the difference was only the frequency in either group. The efforts of the clinical pharmacists should be directed to elderly patients with cardiovascular compromise, mainly in use of anticoagulants and antiplatelet drugs. Furthermore, hospital managers should increase the integration between levels of health care to promote safety patient after discharge.Keywords: Drug interactions. Aged. Internal Medicine. Hospitals, University. RESUMOInterações medicamentosas potenciais em um hospital escolar brasileiro: diferenças relacionadas à idade?O estudo tem por objetivo descrever o perfil de intera

  14. Inhibitory effects of drugs on the metabolic activity of mouse and human aldehyde oxidases and influence on drug-drug interactions.

    Science.gov (United States)

    Takaoka, Naoki; Sanoh, Seigo; Okuda, Katsuhiro; Kotake, Yaichiro; Sugahara, Go; Yanagi, Ami; Ishida, Yuji; Tateno, Chise; Tayama, Yoshitaka; Sugihara, Kazumi; Kitamura, Shigeyuki; Kurosaki, Mami; Terao, Mineko; Garattini, Enrico; Ohta, Shigeru

    2018-04-17

    As aldehyde oxidase (AOX) plays an emerging role in drug metabolism, understanding its significance for drug-drug interactions (DDI) is important. Therefore, we tested 10 compounds for species-specific and substrate-dependent differences in the inhibitory effect of AOX activity using genetically engineered HEK293 cells over-expressing human AOX1, mouse AOX1 or mouse AOX3. The IC 50 values of 10 potential inhibitors of the three AOX enzymes were determined using phthalazine and O 6 -benzylguanine as substrates. 17β-Estradiol, menadione, norharmane and raloxifene exhibited marked differences in inhibitory effects between the human and mouse AOX isoforms when the phthalazine substrate was used. Some of the compounds tested exhibited substrate-dependent differences in their inhibitory effects. Docking simulations with human AOX1 and mouse AOX3 were conducted for six representative inhibitors. The rank order of the minimum binding energy reflected the order of the corresponding IC 50 values. We also evaluated the potential DDI between an AOX substrate (O 6 -benzylguanine) and an inhibitor (hydralazine) using chimeric mice with humanized livers. Pretreatment of hydralazine increased the maximum plasma concentration (C max ) and the area under the plasma concentration-time curve (AUC 0-24 ) of O 6 -benzylguanine compared to single administration. Our in vitro data indicate species-specific and substrate-dependent differences in the inhibitory effects on AOX activity. Our in vivo data demonstrate the existence of a DDI which may be of relevance in the clinical context. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Analysis of drug-drug interactions among patients receiving antiretroviral regimens using data from a large open-source prescription database.

    Science.gov (United States)

    Patel, Nimish; Borg, Peter; Haubrich, Richard; McNicholl, Ian

    2018-06-14

    Results of a study of contraindicated concomitant medication use among recipients of preferred antiretroviral therapy (ART) regimens are reported. A retrospective study was conducted to evaluate concomitant medication use in a cohort of previously treatment-naive, human immunodeficiency virus (HIV)-infected U.S. patients prescribed preferred ART regimens during the period April 2014-March 2015. Data were obtained from a proprietary longitudinal prescription database; elements retrieved included age, sex, and prescription data. The outcome of interest was the frequency of drug-drug interactions (DDIs) associated with concomitant use of contraindicated medications. Data on 25,919 unique treatment-naive patients who used a preferred ART regimen were collected. Overall, there were 384 instances in which a contraindicated medication was dispensed for concurrent use with a recommended ART regimen. Rates of contraindicated concomitant medication use differed significantly by ART regimen; the highest rate (3.2%) was for darunavir plus ritonavir plus emtricitabine-tenofovir disoproxil fumarate (DRV plus RTV plus FTC/TDF), followed by elvitegravir-cobicistat-emtricitabine-tenofovir disoproxil fumarate (EVG/c/FTC/TDF)(2.8%). The highest frequencies of DDIs were associated with ART regimens that included a pharmacoenhancing agent: DRV plus RTV plus FTC/TDF (3.2%) and EVG/c/FTC/TDF (2.8%). In a large population of treatment-naive HIV-infected patients, ART regimens that contained a pharmacoenhancing agent were involved most frequently in contraindicated medication-related DDIs. All of the DDIs could have been avoided by using therapeutic alternatives within the same class not associated with a DDI. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  16. An Evidence-Based Assessment of the Clinical Significance of Drug-Drug Interactions Between Disease-Modifying Antirheumatic Drugs and Non-Antirheumatic Drugs According to Rheumatologists and Pharmacists

    NARCIS (Netherlands)

    van Roon, Eric N.; van den Bemt, Patricia M. L. A.; Jansen, Tim L. Th. A.; Houtman, Nella M.; van de Laar, Mart A. F. J.; Brouwers, Jacobus R. B. J.

    Background: Clinically relevant drug-drug interactions (DDIs) must be recognized in a timely manner and managed appropriately to prevent adverse drug reactions or therapeutic failure. Because the evidence for most DDIs is based on case reports or poorly documented clinical information, there is a

  17. A drug-drug interaction study to assess the effect of the CYP1A2 inhibitor fluvoxamine on the pharmacokinetics of dovitinib (TKI258) in patients with advanced solid tumors

    NARCIS (Netherlands)

    de Weger, Vincent A; Goel, Sanjay; von Moos, Roger; Schellens, Jan H M; Mach, Nicholas; Tan, Eugene; Anand, Suraj; Scott, Jeffrey W; Lassen, Ulrik N

    PURPOSE: Dovitinib is an orally available multi tyrosine kinase inhibitor which inhibits VEGFR 1-3, FGFR 1-3, and PDGFR. This study was performed to investigate the potential drug-drug interaction of dovitinib with the CYP1A2 inhibitor fluvoxamine in patients with advanced solid tumors. METHODS:

  18. A drug-drug interaction study to assess the effect of the CYP1A2 inhibitor fluvoxamine on the pharmacokinetics of dovitinib (TKI258) in patients with advanced solid tumors

    DEFF Research Database (Denmark)

    de Weger, Vincent A; Goel, Sanjay; von Moos, Roger

    2018-01-01

    PURPOSE: Dovitinib is an orally available multi tyrosine kinase inhibitor which inhibits VEGFR 1-3, FGFR 1-3, and PDGFR. This study was performed to investigate the potential drug-drug interaction of dovitinib with the CYP1A2 inhibitor fluvoxamine in patients with advanced solid tumors. METHODS: ...

  19. Drug-drug interaction and doping, part 1: an in vitro study on the effect of non-prohibited drugs on the phase I metabolic profile of toremifene.

    Science.gov (United States)

    Mazzarino, Monica; de la Torre, Xavier; Fiacco, Ilaria; Palermo, Amelia; Botrè, Francesco

    2014-05-01

    The present study was designed to provide preliminary information on the potential impact of metabolic drug-drug interaction on the effectiveness of doping control strategies currently followed by the anti-doping laboratories to detect the intake of banned agents. In vitro assays based on the use of human liver microsomes and recombinant CYP isoforms were designed and performed to characterize the phase I metabolic profile of the prohibited agent toremifene, selected as a prototype drug of the class of selective oestrogen receptor modulators, both in the absence and in the presence of medicaments (fluconazole, ketoconazole, itraconazole, miconazole, cimetidine, ranitidine, fluoxetine, paroxetine, nefazodone) not included in the World Anti-Doping Agency list of prohibited substances and methods and frequently administered to athletes. The results show that the in vitro model developed in this study was adequate to simulate the in vivo metabolism of toremifene, confirming the results obtained in previous studies. Furthermore, our data also show that ketoconazole, itraconazole, miconazole and nefazodone cause a marked modification in the production of the metabolic products (i.e. hydroxylated and carboxylated metabolites) normally selected by the anti-doping laboratories as target analytes to detect toremifene intake; moderate variations were registered in the presence of fluconazole, paroxetine and fluoxetine; while no significant modifications were measured in the presence of ranitidine and cimetidine. This evidence imposes that the potential effect of drug-drug interactions is duly taken into account in anti-doping analysis, also for a broader significance of the analytical results. Copyright © 2014 John Wiley & Sons, Ltd.

  20. Analysis of clinical drug-drug interaction data to predict uncharacterized interaction magnitudes between antiretroviral drugs and co-medications.

    Science.gov (United States)

    Stader, Felix; Kinvig, Hannah; Battegay, Manuel; Khoo, Saye; Owen, Andrew; Siccardi, Marco; Marzolini, Catia

    2018-04-23

    Despite their high potential for drug-drug-interactions (DDI), clinical DDI studies of antiretroviral drugs (ARVs) are often lacking, because the full range of potential interactions cannot feasibly or pragmatically be studied, with some high-risk DDI studies also ethically difficult to undertake. Thus, a robust method to screen and to predict the likelihood of DDIs is required.We developed a method to predict DDIs based on two parameters: the degree of metabolism by specific enzymes such as CYP3A and the strength of an inhibitor or inducer. These parameters were derived from existing studies utilizing paradigm substrates, inducers and inhibitors of CYP3A, to assess the predictive performance of this method by verifying predicted magnitudes of changes in drug exposure against clinical DDI studies involving ARVs.The derived parameters were consistent with the FDA classification of sensitive CYP3A substrates and the strength of CYP3A inhibitors and inducers. Characterized DDI magnitudes (n = 68) between ARVs and co-medications were successfully quantified meaning 53%, 85% and 98% of the predictions were within 1.25-fold (0.80 - 1.25), 1.5-fold (0.66 - 1.48) and 2-fold (0.66 - 1.94) of the observed clinical data. In addition, the method identifies CYP3A substrates likely to be highly or conversely minimally impacted by CYP3A inhibitors or inducers, thus categorizing the magnitude of DDIs.The developed effective and robust method has the potential to support a more rational identification of dose adjustment to overcome DDIs being particularly relevant in a HIV-setting giving the treatments complexity, high DDI risk and limited guidance on the management of DDIs. Copyright © 2018 American Society for Microbiology.

  1. Clopidogrel-Proton Pump Inhibitor Drug-Drug Interaction and Risk of Adverse Clinical Outcomes Among PCI-Treated ACS Patients: A Meta-analysis.

    Science.gov (United States)

    Serbin, Michael A; Guzauskas, Gregory F; Veenstra, David L

    2016-08-01

    Uncertainty regarding clopidogrel effectiveness attenuation because of a drug-drug interaction with proton pump inhibitors (PPI) has led to conflicting guidelines on concomitant therapy. In particular, the effect of this interaction in patients who undergo a percutaneous coronary intervention (PCI), a population known to have increased risk of adverse cardiovascular events, has not been systematically evaluated. To synthesize the evidence of the effect of clopidogrel-PPI drug interaction on adverse cardiovascular outcomes in a PCI patient population. We conducted a systematic literature review for studies reporting clinical outcomes in patients who underwent a PCI and were initiated on clopidogrel with or without a PPI. Studies were included in the analysis if they reported at least 1 of the clinical outcomes of interest (major adverse cardiovascular event [MACE], cardiovascular death, all-cause death, myocardial infarction, stroke, stent thrombosis, and bleed events). We excluded studies that were not exclusive to PCI patients or had no PCI subgroup analysis and/or did not report at least a 6-month follow-up. Statistical and clinical heterogeneity were evaluated and HRs and 95% CIs for adverse clinical events were pooled using the DerSimonian and Laird random-effects meta-analysis method. We identified 12 studies comprising 50,277 PCI patients that met our inclusion and exclusion criteria. Our analysis included retrospective analyses of randomized controlled trials (2), health registries (3), claims databases (2), and institutional records (5); no prospective studies of PCI patients were identified. On average, patients were in their mid-60s, male, and had an array of comorbidities, including hyperlipidemia, diabetes, hypertension, and smoking history. Concomitant therapy following PCI resulted in statistically significant increases in composite MACE (HR = 1.28; 95% CI = 1.24-1.32), myocardial infarction (HR = 1.51; 95% CI = 1.40-1.62), and stroke (HR = 1.46; 95

  2. Pharmacogenetics of drug-drug interaction and drug-drug-gene interaction: a systematic review on CYP2C9, CYP2C19 and CYP2D6.

    Science.gov (United States)

    Bahar, Muh Akbar; Setiawan, Didik; Hak, Eelko; Wilffert, Bob

    2017-05-01

    Currently, most guidelines on drug-drug interaction (DDI) neither consider the potential effect of genetic polymorphism in the strength of the interaction nor do they account for the complex interaction caused by the combination of DDI and drug-gene interaction (DGI) where there are multiple biotransformation pathways, which is referred to as drug-drug-gene interaction (DDGI). In this systematic review, we report the impact of pharmacogenetics on DDI and DDGI in which three major drug-metabolizing enzymes - CYP2C9, CYP2C19 and CYP2D6 - are central. We observed that several DDI and DDGI are highly gene-dependent, leading to a different magnitude of interaction. Precision drug therapy should take pharmacogenetics into account when drug interactions in clinical practice are expected.

  3. Critical drug-drug interactions for use in electronic health records systems with computerized physician order entry: review of leading approaches.

    Science.gov (United States)

    Classen, David C; Phansalkar, Shobha; Bates, David W

    2011-06-01

    Medications represent the most common intervention in health care, despite their benefits; they also lead to an estimated 1.5 million adverse drug events and tens of thousands of hospital admissions each year. Although some are not preventable given what is known today, many types are, and one key cause which is preventable is drug-drug interactions (DDIs). Most electronic health record systems include programs that can check and prevent these types of interactions as a routine part of medication ordering. Studies suggest that these systems as implemented often do not effectively screen for these DDIs. A major reason for this deficiency is the lack of any national standard for the critical DDIs that should be routinely operationlized in these complex systems. We review the leading critical DDI lists from multiple sources including several leading health systems, a leading commercial content provider, the Leapfrog CPOE Testing Standard, and the new Office of the National Coordinator (ONC) DDI List. Implementation of strong DDI checking is one of the important steps in terms of realizing the benefits of electronic prescribing with respect to safety. Hopefully, the ONC list will make it easier for organizations to ensure they are including the most important interactions, and the Leapfrog List may help these organizations develop an operational DDI list that can be practically implemented. In addition, this review has identified 7 common DDIs that can be the starting point for all organizations in this area of medication safety.

  4. A mechanistic framework for in vitro-in vivo extrapolation of liver membrane transporters: prediction of drug-drug interaction between rosuvastatin and cyclosporine.

    Science.gov (United States)

    Jamei, M; Bajot, F; Neuhoff, S; Barter, Z; Yang, J; Rostami-Hodjegan, A; Rowland-Yeo, K

    2014-01-01

    The interplay between liver metabolising enzymes and transporters is a complex process involving system-related parameters such as liver blood perfusion as well as drug attributes including protein and lipid binding, ionisation, relative magnitude of passive and active permeation. Metabolism- and/or transporter-mediated drug-drug interactions (mDDIs and tDDIs) add to the complexity of this interplay. Thus, gaining meaningful insight into the impact of each element on the disposition of a drug and accurately predicting drug-drug interactions becomes very challenging. To address this, an in vitro-in vivo extrapolation (IVIVE)-linked mechanistic physiologically based pharmacokinetic (PBPK) framework for modelling liver transporters and their interplay with liver metabolising enzymes has been developed and implemented within the Simcyp Simulator(®). In this article an IVIVE technique for liver transporters is described and a full-body PBPK model is developed. Passive and active (saturable) transport at both liver sinusoidal and canalicular membranes are accounted for and the impact of binding and ionisation processes is considered. The model also accommodates tDDIs involving inhibition of multiple transporters. Integrating prior in vitro information on the metabolism and transporter kinetics of rosuvastatin (organic-anion transporting polypeptides OATP1B1, OAT1B3 and OATP2B1, sodium-dependent taurocholate co-transporting polypeptide [NTCP] and breast cancer resistance protein [BCRP]) with one clinical dataset, the PBPK model was used to simulate the drug disposition of rosuvastatin for 11 reported studies that had not been used for development of the rosuvastatin model. The simulated area under the plasma concentration-time curve (AUC), maximum concentration (C max) and the time to reach C max (t max) values of rosuvastatin over the dose range of 10-80 mg, were within 2-fold of the observed data. Subsequently, the validated model was used to investigate the impact of

  5. Risk of Clinically Relevant Pharmacokinetic-based Drug-drug Interactions with Drugs Approved by the U.S. Food and Drug Administration Between 2013 and 2016.

    Science.gov (United States)

    Yu, Jingjing; Zhou, Zhu; Tay-Sontheimer, Jessica; Levy, Rene H; Ragueneau-Majlessi, Isabelle

    2018-03-23

    A total of 103 drugs (including 14 combination drugs) were approved by the U.S. Food and Drug Administration from 2013 to 2016. Pharmacokinetic-based drug interaction profiles were analyzed using the University of Washington Drug Interaction Database and the clinical relevance of these observations was characterized based on information from New Drug Application reviews. CYP3A was identified as a major contributor to clinical drug-drug interactions (DDIs), involved in approximately 2/3 of all interactions. Transporters (alone or with enzymes) were found to participate in about half of all interactions, although most of these were weak-to-moderate interactions. When considered as victims, eight new molecular entities (NMEs; cobimetinib, ibrutnib, isavuconazole, ivabradine, naloxegol, paritaprevir, simeprevir, and venetoclax) were identified as sensitive substrates of CYP3A, two NMEs (pirfenidone and tasimelteon) were sensitive substrates of CYP1A2, one NME (dasabuvir) was a sensitive substrate of CYP2C8, one NME (eliglustat) was a sensitive substrate of CYP2D6, and one NME (grazoprevir) was a sensitive substrate of OATP1B1/3 (with changes in exposure greater than 5-fold when co-administered with a strong inhibitor). Interestingly, approximately 75% of identified CYP3A substrates were also substrates of P-gp. As perpetrators, most clinical DDIs involved weak-to-moderate inhibition or induction, with only two drugs (Viekira Pak and idelalisib) showing strong inhibition of CYP3A, and one NME (lumacaftor) considered as a strong CYP3A inducer. Among drugs with large changes in exposure (≥ 5-fold), whether as victim or perpetrator, the most represented therapeutic classes were antivirals and oncology drugs, suggesting a significant risk of clinical DDIs in these patient populations. The American Society for Pharmacology and Experimental Therapeutics.

  6. [Predictive factors of clinically significant drug-drug interactions among regimens based on protease inhibitors, non-nucleoside reverse transcriptase inhibitors and raltegravir].

    Science.gov (United States)

    Cervero, Miguel; Torres, Rafael; Jusdado, Juan José; Pastor, Susana; Agud, Jose Luis

    2016-04-15

    To determine the prevalence and types of clinically significant drug-drug interactions (CSDI) in the drug regimens of HIV-infected patients receiving antiretroviral treatment. retrospective review of database. Centre: Hospital Universitario Severo Ochoa, Infectious Unit. one hundred and forty-two participants followed by one of the authors were selected from January 1985 to December 2014. from their outpatient medical records we reviewed information from the last available visit of the participants, in relation to HIV infection, comorbidities, demographics and the drugs that they were receiving; both antiretroviral drugs and drugs not related to HIV infection. We defined CSDI from the information sheet and/or database on antiretroviral drug interactions of the University of Liverpool (http://www.hiv-druginteractions.org) and we developed a diagnostic tool to predict the possibility of CSDI. By multivariate logistic regression analysis and by estimating the diagnostic performance curve obtained, we identified a quick tool to predict the existence of drug interactions. Of 142 patients, 39 (29.11%) had some type of CSDI and in 11.2% 2 or more interactions were detected. In only one patient the combination of drugs was contraindicated (this patient was receiving darunavir/r and quetiapine). In multivariate analyses, predictors of CSDI were regimen type (PI or NNRTI) and the use of 3 or more non-antiretroviral drugs (AUC 0.886, 95% CI 0.828 to 0.944; P=.0001). The risk was 18.55 times in those receiving NNRTI and 27,95 times in those receiving IP compared to those taking raltegravir. Drug interactions, including those defined as clinically significant, are common in HIV-infected patients treated with antiretroviral drugs, and the risk is greater in IP-based regimens. Raltegravir-based prescribing, especially in patients who receive at least 3 non-HIV drugs could avoid interactions. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  7. Drug disposition and drug-drug interaction data in 2013 FDA new drug applications: a systematic review.

    Science.gov (United States)

    Yu, Jingjing; Ritchie, Tasha K; Mulgaonkar, Aditi; Ragueneau-Majlessi, Isabelle

    2014-12-01

    The aim of the present work was to perform a systematic review of drug metabolism, transport, pharmacokinetics, and DDI data available in the NDAs approved by the FDA in 2013, using the University of Washington Drug Interaction Database, and to highlight significant findings. Among 27 NMEs approved, 22 (81%) were well characterized with regard to drug metabolism, transport, or organ impairment, in accordance with the FDA drug interaction guidance (2012) and were fully analyzed in this review. In vitro, a majority of the NMEs were found to be substrates or inhibitors/inducers of at least one drug metabolizing enzyme or transporter. However, in vivo, only half (n = 11) showed clinically relevant drug interactions, with most related to the NMEs as victim drugs and CYP3A being the most affected enzyme. As perpetrators, the overall effects for NMEs were much less pronounced, compared with when they served as victims. In addition, the pharmacokinetic evaluation in patients with hepatic or renal impairment provided useful information for further understanding of the drugs' disposition. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  8. Prevalence of acid-reducing agents (ARA) in cancer populations and ARA drug-drug interaction potential for molecular targeted agents in clinical development.

    Science.gov (United States)

    Smelick, Gillian S; Heffron, Timothy P; Chu, Laura; Dean, Brian; West, David A; Duvall, Scott L; Lum, Bert L; Budha, Nageshwar; Holden, Scott N; Benet, Leslie Z; Frymoyer, Adam; Dresser, Mark J; Ware, Joseph A

    2013-11-04

    Acid-reducing agents (ARAs) are the most commonly prescribed medications in North America and Western Europe. There are currently no data describing the prevalence of their use among cancer patients. However, this is a paramount question due to the potential for significant drug-drug interactions (DDIs) between ARAs, most commonly proton pump inhibitors (PPIs), and orally administered cancer therapeutics that display pH-dependent solubility, which may lead to decreased drug absorption and decreased therapeutic benefit. Of recently approved orally administered cancer therapeutics, >50% are characterized as having pH-dependent solubility, but there are currently no data describing the potential for this ARA-DDI liability among targeted agents currently in clinical development. The objectives of this study were to (1) determine the prevalence of ARA use among different cancer populations and (2) investigate the prevalence of orally administered cancer therapeutics currently in development that may be liable for an ARA-DDI. To address the question of ARA use among cancer patients, a retrospective cross-sectional analysis was performed using two large healthcare databases: Thomson Reuters MarketScan (N = 1,776,443) and the U.S. Department of Veterans Affairs (VA, N = 1,171,833). Among all cancer patients, the total prevalence proportion of ARA use (no. of cancer patients receiving an ARA/total no. of cancer patients) was 20% and 33% for the MarketScan and VA databases, respectively. PPIs were the most commonly prescribed agent, comprising 79% and 65% of all cancer patients receiving a prescription for an ARA (no. of cancer patients receiving a PPI /no. of cancer patients receiving an ARA) for the MarketScan and VA databases, respectively. To estimate the ARA-DDI liability of orally administered molecular targeted cancer therapeutics currently in development, two publicly available databases, (1) Kinase SARfari and (2) canSAR, were examined. For those orally administered

  9. [Rhabdomyolysis and severe hepatotoxicity due to a drug-drug interaction between ritonavir and simvastatin. Could we use the most cost-effective statin in all human immunodeficiency virus-infected patients?].

    Science.gov (United States)

    Bastida, Carla; Also, Maria Antonia; Pericas, Juan Manuel; Letang, Emili; Tuset, Montse; Miró, Josep Maria

    2014-11-01

    Drugs like statins may induce rhabdomyolysis. Simvastatin and lovastatin have a high hepatic metabolism and their potential toxicity could be increased by interactions with other drugs that reduce their metabolism. A case-report is presented of an HIV-infected patient treated with antiretroviral drugs who developed a rhabdomyolysis-induced renal failure and liver toxicity when simvastatin was substituted for atorvastatin. A literature review is also presented. The patient required hospital admission and showed a favorable response after hydration and urine alkalinization. There were 4 additional cases published of which there was one death. Drug-drug interactions can increase the risk of statin induced rhabdomyolysis. In order to evaluate them properly, physicians at all levels of clinical care should be aware of all drugs prescribed to their patients and the contraindicated combinations. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  10. Underlying mechanism of drug-drug interaction between pioglitazone and gemfibrozil: Gemfibrozil acyl-glucuronide is a mechanism-based inhibitor of CYP2C8.

    Science.gov (United States)

    Takagi, Motoi; Sakamoto, Masaya; Itoh, Tomoo; Fujiwara, Ryoichi

    2015-08-01

    While co-administered gemfibrozil can increase the area under the concentration/time curve (AUC) of pioglitazone more than 3-fold, the underlying mechanism of the drug-drug interaction between gemfibrozil and pioglitazone has not been fully understood. In the present study, gemfibrozil preincubation time-dependently inhibited the metabolism of pioglitazone in the cytochrome P450 (CYP)- and UDP-glucuronosyltransferase (UGT)-activated human liver microsomes. We estimated the kinact and K'app values, which are the maximum inactivation rate constant and the apparent dissociation constant, of gemfibrozil to be 0.071 min(-1) and 57.3 μM, respectively. In this study, the kobs, in vivo value was defined as a parameter that indicates the potency of the mechanism-based inhibitory effect at the blood drug concentration in vivo. The kobs, in vivo values of potent mechanism-based inhibitors, clarithromycin and erythromycin, were estimated to be 0.0096 min(-1) and 0.0051 min(-1), respectively. The kobs, in vivo value of gemfibrozil was 0.0060 min(-1), which was comparable to those of clarithromycin and erythromycin, suggesting that gemfibrozil could be a mechanism-based inhibitor as potent as clarithromycin and erythromycin in vivo. Copyright © 2015 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

  11. MRP2 mediated drug-drug interaction: indomethacin increases sulfasalazine absorption in the small intestine, potentially decreasing its colonic targeting.

    Science.gov (United States)

    Dahan, Arik; Amidon, Gordon L

    2010-02-15

    We have recently shown that efflux transport, mediated by multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP), is responsible for sulfasalazine low-permeability in the small intestine, thereby enabling its colonic targeting and therapeutic action. The purpose of the present study was to evaluate the potential pharmacokinetic interaction between indomethacin and sulfasalazine, in the mechanism of efflux transporter competition. The concentration-dependent effects of indomethacin on sulfasalazine intestinal epithelial transport were investigated across Caco-2 cell monolayers, in both apical to basolateral (AP-BL) and BL-AP directions. The interaction was then investigated in the in situ single-pass rat jejunal perfusion model. Sulfasalazine displayed 30-fold higher BL-AP than AP-BL Caco-2 permeability, indicative of net mucosal secretion. Indomethacin significantly increased AP-BL and decreased BL-AP sulfasalazine Caco-2 transport, in a concentration-dependent manner, with IC(50) values of 75 and 196 microM respectively. In the rat model, higher sulfasalazine concentrations resulted in higher intestinal permeability, consistent with saturation of efflux transporter. Without indomethacin, sulfasalazine demonstrated low rat jejunal permeability (vs. metoprolol). Indomethacin significantly increased sulfasalazine P(eff), effectively shifting it from BCS (biopharmaceutics classification system) Class IV to II. In conclusion, the data indicate that concomitant intake of indomethacin and sulfasalazine may lead to increased absorption of sulfasalazine in the small intestine, thereby reducing its colonic concentration and potentially altering its therapeutic effect. Copyright 2009 Elsevier B.V. All rights reserved.

  12. [Enantioselective determinination of R-warfarin/S-warfarin in human plasma using liquid chromatography-tandem mass spectrometry and its application in a drug-drug interaction study].

    Science.gov (United States)

    Jin, Shu; Zhang, Yi-Fan; Chen, Xiao-Yan; Liu, Ke; Zhong, Da-Fang

    2012-01-01

    To study the drug-drug interaction of morinidazole and warfarin and its application, a sensitive and rapid liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the determination of R-warfarin/S-warfarin in human plasma. In a random, two-period crossover study, 12 healthy volunteers received a single oral dose of 5 mg racemic warfarin in the absence and presence of morinidazole. Blood samples were collected according to a pre-designed time schedule. R-warfarin, S-warfarin and methyclothiazide were extracted with ethylether : methylenechloride (3 : 2), then separated on a Astec Chirobiotic V (150 mm x 4.6 mm ID, 5 microm) column using 5 mmol x L(-1) ammonium acetate (pH 4.0) - acetonitrile as mobile phase at a flow-rate of 1.5 mL x min(-1). The mobile phase was splitted and 0.5 mL x min(-1) was introduced into MS. A tandem mass spectrometer equipped with electrospray ionization source was used as detector and operated in the negative ion mode. Quantification was performed using multiple reaction monitoring (MRM). The resolution of warfarin enantiomers is 1.56. The linear calibration curves for R-warfarin and S-warfarin both were obtained in the concentration range of 5 - 1 000 ng x mL(-1). Intra- and inter-day relative standard deviation (RSD) for R-warfarin and S-warfarin over the entire concentration range across three validation runs was both less than 10%, and relative error (RE) ranged from -4.9% to 0.7%, separately. The method herein described is effective and convenient, and suitable for the study of metabolic interaction between morinidazole and warfarin. The results showed that coadministration of warfarin with morinidazole did not affect the pharmacokinetics of either R-warfarin or S-warfarin.

  13. Prevalence of potentially serious drug-drug interactions among South African elderly private health sector patients using the Mimica Matanović/Vlahović-Palčevski protocol.

    Science.gov (United States)

    van Heerden, Julandi A; Burger, Johanita R; Gerber, Jan J; Vlahović-Palčevski, Vera

    2018-04-01

    To determine the prevalence of potentially serious drug-drug interactions (DDIs) and their relationship with gender and age, among elderly in South Africa. A cross-sectional study was conducted using pharmaceutical claims data for 2013, for a total of 103 420 medical scheme beneficiaries' ≥65 years. All medications dispensed within one calendar month where the days' supply of medication dispensed overlapped, were grouped as one prescription. DDIs per prescription were then identified using the Mimica Matanović/Vlahović-Palčevski DDI protocol. Results were interpreted using effect sizes, that is Cramér's V, Cohen's d and Cohen's ƒ 2 . A total of 331 659 DDIs were identified on 235 870 (25.8%, N = 912 713) prescriptions (mean 0.36 (SD 0.7) (95% CI, 0.36 to 0.37)). Women encountered 63.5% of all DDIs. Effect sizes for the association between DDIs and age group (Cramér's V = 0.06), and gender (Cramér's V = 0.05) was negligible. There was no difference between men and women regarding the mean number of DDIs identified per prescription (Cohen's d = 0.10). The number of medicine per prescription (ƒ 2 = 0.51) was the biggest predictor of the DDIs. The most frequent interacting drug combinations were between central nervous system medicines (30.6%). Our study is the first to report the prevalence of potentially serious DDIs among an elderly population in the South African private health sector utilising the Mimica Matanović/Vlahović-Palčevski DDI protocol. Overall, we identified DDIs in approximately 26% of the prescriptions in our study. Age and gender were not found to be predictors of potentially serious DDIs. © 2017 Royal Pharmaceutical Society.

  14. Extent of poly-pharmacy, occurrence and associated factors of drug-drug interaction and potential adverse drug reactions in Gondar Teaching Referral Hospital, North West Ethiopia

    Directory of Open Access Journals (Sweden)

    Endalkachew Admassie

    2013-01-01

    Full Text Available The aim of this study was to assess the extent of poly-pharmacy, occurrence, and associated factors for the occurrence of drug-drug interaction (DDI and potential adverse drug reaction (ADR in Gondar University Teaching Referral Hospital. Institutional-based retrospective cross-sectional study. This study was conducted on prescriptions of both in and out-patients for a period of 3 months at Gondar University Hospital. Both bivariate analysis and multivariate logistic regression were used to identify risk factors for the occurrence of DDI and possible ADRs. All the statistical calculations were performed using SPSS; software. A total of 12,334 prescriptions were dispensed during the study period of which, 2,180 prescriptions were containing two or more drugs per prescription. A total of 21,210 drugs were prescribed and the average number of drugs per prescription was 1.72. Occurrences of DDI of all categories (Major, Moderate, and Minor were analyzed and DDI were detected in 711 (32.6% prescriptions. Sex was not found to be a risk factor for the occurrence of DDI and ADR, while age and number of medications per prescription were found to be significant risk factors for the occurrence of DDI and ADR. The mean number of drugs per prescription was 1.72 and hence with regard to the WHO limit of drugs per prescription, Gondar hospital was able to maintain the limit and prescriptions containing multiple drugs supposed to be taken systemically. Numbers of drugs per prescription as well as older age were found to be predisposing factors for the occurrence of DDI and potential ADRs while sex was not a risk factor.

  15. Drug-drug interactions with sodium-glucose cotransporters type 2 (SGLT2) inhibitors, new oral glucose-lowering agents for the management of type 2 diabetes mellitus.

    Science.gov (United States)

    Scheen, André J

    2014-04-01

    Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. They are proposed as a novel approach for the management of type 2 diabetes mellitus. They have proven their efficacy in reducing glycated haemoglobin, without inducing hypoglycaemia, as monotherapy or in combination with various other glucose-lowering agents, with the add-on value of promoting some weight loss and lowering arterial blood pressure. As they may be used concomitantly with many other drugs, we review the potential drug-drug interactions (DDIs) regarding the three leaders in the class (dapagliglozin, canagliflozin and empagliflozin). Most of the available studies were performed in healthy volunteers and have assessed the pharmacokinetic interferences with a single administration of the SGLT2 inhibitor. The exposure [assessed by peak plasma concentrations (Cmax) and area under the concentration-time curve (AUC)] to each SGLT2 inhibitor tested was not significantly influenced by the concomitant administration of other glucose-lowering agents or cardiovascular agents commonly used in patients with type 2 diabetes. Reciprocally, these medications did not influence the pharmacokinetic parameters of dapagliflozin, canagliflozin or empagliflozin. Some modest changes were not considered as clinically relevant. However, drugs that could specifically interfere with the metabolic pathways of SGLT2 inhibitors [rifampicin, inhibitors or inducers of uridine diphosphate-glucuronosyltransferase (UGT)] may result in significant changes in the exposure of SGLT2 inhibitors, as shown for dapagliflozin and canagliflozin. Potential DDIs in patients with type 2 diabetes receiving chronic treatment with an SGLT2 inhibitor deserve further attention, especially in individuals treated with several medications or in more fragile patients with hepatic and/or renal impairment.

  16. Prediction of Drug-Drug Interactions with Bupropion and Its Metabolites as CYP2D6 Inhibitors Using a Physiologically-Based Pharmacokinetic Model.

    Science.gov (United States)

    Xue, Caifu; Zhang, Xunjie; Cai, Weimin

    2017-12-21

    The potential of inhibitory metabolites of perpetrator drugs to contribute to drug-drug interactions (DDIs) is uncommon and underestimated. However, the occurrence of unexpected DDI suggests the potential contribution of metabolites to the observed DDI. The aim of this study was to develop a physiologically-based pharmacokinetic (PBPK) model for bupropion and its three primary metabolites-hydroxybupropion, threohydrobupropion and erythrohydrobupropion-based on a mixed "bottom-up" and "top-down" approach and to contribute to the understanding of the involvement and impact of inhibitory metabolites for DDIs observed in the clinic. PK profiles from clinical researches of different dosages were used to verify the bupropion model. Reasonable PK profiles of bupropion and its metabolites were captured in the PBPK model. Confidence in the DDI prediction involving bupropion and co-administered CYP2D6 substrates could be maximized. The predicted maximum concentration (C max ) area under the concentration-time curve (AUC) values and C max and AUC ratios were consistent with clinically observed data. The addition of the inhibitory metabolites into the PBPK model resulted in a more accurate prediction of DDIs (AUC and C max ratio) than that which only considered parent drug (bupropion) P450 inhibition. The simulation suggests that bupropion and its metabolites contribute to the DDI between bupropion and CYP2D6 substrates. The inhibitory potency from strong to weak is hydroxybupropion, threohydrobupropion, erythrohydrobupropion, and bupropion, respectively. The present bupropion PBPK model can be useful for predicting inhibition from bupropion in other clinical studies. This study highlights the need for caution and dosage adjustment when combining bupropion with medications metabolized by CYP2D6. It also demonstrates the feasibility of applying the PBPK approach to predict the DDI potential of drugs undergoing complex metabolism, especially in the DDI involving inhibitory

  17. Consumer Mobile Apps for Potential Drug-Drug Interaction Check: Systematic Review and Content Analysis Using the Mobile App Rating Scale (MARS).

    Science.gov (United States)

    Kim, Ben Yb; Sharafoddini, Anis; Tran, Nam; Wen, Emily Y; Lee, Joon

    2018-03-28

    General consumers can now easily access drug information and quickly check for potential drug-drug interactions (PDDIs) through mobile health (mHealth) apps. With aging population in Canada, more people have chronic diseases and comorbidities leading to increasing numbers of medications. The use of mHealth apps for checking PDDIs can be helpful in ensuring patient safety and empowerment. The aim of this study was to review the characteristics and quality of publicly available mHealth apps that check for PDDIs. Apple App Store and Google Play were searched to identify apps with PDDI functionality. The apps' general and feature characteristics were extracted. The Mobile App Rating Scale (MARS) was used to assess the quality. A total of 23 apps were included for the review-12 from Apple App Store and 11 from Google Play. Only 5 of these were paid apps, with an average price of $7.19 CAD. The mean MARS score was 3.23 out of 5 (interquartile range 1.34). The mean MARS scores for the apps from Google Play and Apple App Store were not statistically different (P=.84). The information dimension was associated with the highest score (3.63), whereas the engagement dimension resulted in the lowest score (2.75). The total number of features per app, average rating, and price were significantly associated with the total MARS score. Some apps provided accurate and comprehensive information about potential adverse drug effects from PDDIs. Given the potentially severe consequences of incorrect drug information, there is a need for oversight to eliminate low quality and potentially harmful apps. Because managing PDDIs is complex in the absence of complete information, secondary features such as medication reminder, refill reminder, medication history tracking, and pill identification could help enhance the effectiveness of PDDI apps. ©Ben YB Kim, Anis Sharafoddini, Nam Tran, Emily Y Wen, Joon Lee. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 28.03.2018.

  18. Usefulness of Two-Compartment Model-Assisted and Static Overall Inhibitory-Activity Method for Prediction of Drug-Drug Interaction.

    Science.gov (United States)

    Iga, Katsumi; Kiriyama, Akiko

    2017-12-01

    Our study of drug-drug interaction (DDI) started with the clarification of unusually large DDI observed between ramelteon (RAM) and fluvoxamine (FLV). The main cause of this DDI was shown to be the extremely small hepatic availability of RAM (vF h ). Traditional DDI prediction assuming the well-stirred hepatic extraction kinetic ignores the relative increase of vF h by DDI, while we could solve this problem by use of the tube model. Ultimately, we completed a simple and useful method for prediction of DDI. Currently, DDI prediction becomes more complex and difficult when examining issues such as dynamic changes in perpetrator level, inhibitory metabolites, etc. The regulatory agents recommend DDI prediction by use of some sophisticated methods. However, they seem problematic in requiring plural in vitro data that reduce the flexibility and accuracy of the simulation. In contrast, our method is based on the static and two-compartment models. The two-compartment model has advantages in that it uses common pharmacokinetics (PK) parameters determined from the actual clinical data, guaranteeing the simulation of the reference standard in DDI. Our studies confirmed that dynamic changes in perpetrator level do not make a difference between static and dynamic methods. DDIs perpetrated by FLV and itraconazole were successfully predicted by use of the present method where two DDI predictors [perpetrator-specific inhibitory activities toward CYP isoforms (pA i, CYP s) and victim-specific fractional CYP-isoform contributions to the clearance (vf m, CYP s)] are determined successively as shown in the graphical abstract. Accordingly, this approach will accelerate DDI prediction over the traditional methods.

  19. In Vitro Dissolution of Fluconazole and Dipyridamole in Gastrointestinal Simulator (GIS), Predicting in Vivo Dissolution and Drug-Drug Interaction Caused by Acid-Reducing Agents.

    Science.gov (United States)

    Matsui, Kazuki; Tsume, Yasuhiro; Amidon, Gregory E; Amidon, Gordon L

    2015-07-06

    Weakly basic drugs typically exhibit pH-dependent solubility in the physiological pH range, displaying supersaturation or precipitation along the gastrointestinal tract. Additionally, their oral bioavailabilities may be affected by coadministration of acid-reducing agents that elevate gastric pH. The purpose of this study was to assess the feasibility of a multicompartmental in vitro dissolution apparatus, Gastrointestinal Simulator (GIS), in predicting in vivo dissolution of certain oral medications. In vitro dissolution studies of fluconazole, a BCS class I, and dipyridamole, a BCS class II weak bases (class IIb), were performed in the GIS as well as United States Pharmacopeia (USP) apparatus II and compared with the results of clinical drug-drug interaction (DDI) studies. In both USP apparatus II and GIS, fluconazole completely dissolved within 60 min regardless of pH, reflecting no DDI between fluconazole and acid-reducing agents in a clinical study. On the other hand, seven-fold and 15-fold higher concentrations of dipyridamole than saturation solubility were observed in the intestinal compartments in GIS with gastric pH 2.0. Precipitation of dipyridamole was also observed in the GIS, and the percentage of dipyridamole in solution was 45.2 ± 7.0%. In GIS with gastric pH 6.0, mimicking the coadministration of acid-reducing agents, the concentration of dipyridamole was equal to its saturation solubility, and the percentage of drug in solution was 9.3 ± 2.7%. These results are consistent with the clinical DDI study of dipyridamole with famotidine, which significantly reduced the Cmax and area under the curve. An In situ mouse infusion study combined with GIS revealed that high concentration of dipyridamole in the GIS enhanced oral drug absorption, which confirmed the supersaturation of dipyridamole. In conclusion, GIS was shown to be a useful apparatus to predict in vivo dissolution for BCS class IIb drugs.

  20. Characterization of simvastatin acid uptake by organic anion transporting polypeptide 3A1 (OATP3A1) and influence of drug-drug interaction.

    Science.gov (United States)

    Atilano-Roque, Amandla; Joy, Melanie S

    2017-12-01

    Human organic anion transporting polypeptide 3A1 (OATP3A1) is predominately expressed in the heart. The ability of OATP3A1 to transport statins into cardiomyocytes is unknown, although other OATPs are known to mediate the uptake of statin drugs in liver. The pleiotropic effects and uptake of simvastatin acid were analyzed in primary human cardiomyocytes and HEK293 cells transfected with the OATP3A1 gene. Treatment with simvastatin acid reduced indoxyl sulfate-mediated reactive oxygen species and modulated OATP3A1 expression in cardiomyocytes and HEK293 cells transfected with the OATP3A1 gene. We observed a pH-dependent effect on OATP3A1 uptake, with more efficient simvastatin acid uptake at pH5.5 in HEK293 cells transfected with the OATP3A1 gene. The Michaelis-Menten constant (K m ) for simvastatin acid uptake by OATP3A1 was 0.017±0.002μM and the V max was 0.995±0.027fmol/min/10 5 cells. Uptake of simvastatin acid was significantly increased by known (benzylpenicillin and estrone-3-sulfate) and potential (indoxyl sulfate and cyclosporine) substrates of OATP3A1. In conclusion, the presence of OATP3A1 in cardiomyocytes suggests that this transporter may modulate the exposure of cardiac tissue to simvastatin acid due to its enrichment in cardiomyocytes. Increases in uptake of simvastatin acid by OATP3A1 when combined with OATP substrates suggest the potential for drug-drug interactions that could influence clinical outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Prevalence of possible drug-drug interactions between antiretroviral agents in different age groups in a section of the private health care sector setting in South Africa.

    Science.gov (United States)

    Katende-Kyenda, N L; Lubbe, M S; Serfontein, J H P; Truter, I

    2008-08-01

    The chronic nature of human immunodeficiency virus (HIV) infection requires lifelong highly active antiretroviral (ARV) therapy (HAART) to continuously suppress HIV-1 viral replication, thus reducing morbidity and mortality. HAART is restricted by complex dosing, drug-drug interactions (DDIs) and toxicities. To determine the prevalence of possible DDIs between ARV drugs in different age groups in a section of the private primary health care sector in South Africa. A quantitative, retrospective drug utilization review was performed on 47 085 ARV prescriptions claimed through a national medicine claims database during 2006. Possible DDIs identified were classified according to a clinical significance rating as described by Tatro [Drug Interaction Facts 2005. St Louis, MO: Facts and Comparisons (2005)]. The total number of patients who received prescriptions that were claimed through the medicine claims database was 275 424, of whom 25.11% were males, 28.28% were females and the gender of 46.61% patients was unknown. Of the total number of patients, 3.27% were HIV patients of which an average of 5.23 +/- 3.86 ARV prescriptions (n = 47 085) per patient were claimed for representing 4.73% of the total number of prescriptions claimed during the study period (N = 993 804). HIV patients received an average of 2.36 +/- 0.61 ARVs per prescription. Only 4.95% of the prescriptions had one ARV medicine item, 56.04% two, 37.10% three, 1.75% four and 6 years and 12 and 60 years with patients <40 years and < or =60 years having the highest number of DDIs and patients older than 60 years the lowest. The majority of DDIs between the ARVs presented in significance levels 2 and 4. The most important interactions were between: indinavir (IDV) and ritonavir (n = 199); efavirenz (EFV) and lopinavir/ritonavir (n = 65) and EFV and IDV (n = 60) all interacting at level 2. The importance of using drug utilization study as an identification tool to provide insight into the prescribing and

  2. Simultaneous Assessment of Transporter-Mediated Drug-Drug Interactions Using a Probe Drug Cocktail in Cynomolgus Monkey.

    Science.gov (United States)

    Kosa, Rachel E; Lazzaro, Sarah; Bi, Yi-An; Tierney, Brendan; Gates, Dana; Modi, Sweta; Costales, Chester; Rodrigues, A David; Tremaine, Larry M; Varma, Manthena V

    2018-06-07

    We aim to establish an in vivo preclinical model to enable simultaneous assessment of inhibition potential of an investigational drug on clinically relevant drug transporters, organic anion transporting polypeptide (OATP)1B, breast cancer resistance protein (BCRP), P-glycoprotein (P-gp) and organic anion transporter (OAT)3. Pharmacokinetics of substrate cocktail consisting of pitavastatin (OATP1B substrate), rosuvastatin (OATP1B/BCRP/OAT3), sulfasalazine (BCRP) and talinolol (P-gp) were obtained in cynomolgus monkey - alone or in combination with transporter inhibitors. Single dose rifampicin (30 mg/kg) significantly (pdrugs, with a marked effect on pitavastatin and rosuvastatin (AUC ratio ~21-39). Elacridar, BCRP/P-gp inhibitor, increased the AUC of sulfasalazine, talinolol, as well as rosuvastatin and pitavastatin. An OAT1/3 inhibitor (probenecid) significantly (pdrug-drug interaction risk assessment, before advancing a new molecular entity into clinical development, as well as providing mechanistic insights on transporter-mediated interactions. The American Society for Pharmacology and Experimental Therapeutics.

  3. P-gp, MRP2 and OAT1/OAT3 mediate the drug-drug interaction between resveratrol and methotrexate

    Energy Technology Data Exchange (ETDEWEB)

    Jia, Yongming [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044 (China); Liu, Zhihao; Wang, Changyuan; Meng, Qiang; Huo, Xiaokui; Liu, Qi; Sun, Huijun [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044 (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian 116044 (China); Sun, Pengyuan; Yang, Xiaobo; Ma, Xiaodong [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044 (China); Liu, Kexin, E-mail: kexinliu@dlmedu.edu.cn [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044 (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian 116044 (China)

    2016-09-01

    The purpose of present study was to investigate the effect of resveratrol (Res) on altering methotrexate (MTX) pharmacokinetics and clarify the related molecular mechanism. Res significantly increased rat intestinal absorption of MTX in vivo and in vitro. Simultaneously, Res inhibited MTX efflux transport in MDR1-MDCK and MRP2-MDCK cell monolayers, suggesting that the target of drug interaction was MDR1 and MRP2 in the intestine during the absorption process. Furthermore, there was a significant decrease in renal clearance of MTX after simultaneous intravenous administration. Similarly, MTX uptake was markedly inhibited by Res in rat kidney slices and hOAT1/3-HEK293 cell, indicating that OAT1 and OAT3 were involved in the drug interaction in the kidney. Additionally, concomitant administration of Res decreased cytotoxic effects of MTX in hOAT1/3-HEK293 cells, and ameliorated nephrotoxicity caused by MTX in rats. Conversely, intestinal damage caused by MTX was not exacerbated after Res treatment. In conclusion, Res enhanced MTX absorption in intestine and decreased MTX renal elimination by inhibiting P-gp, MRP2, OAT1 and OAT3 in vivo and in vitro. Res improved MTX-induced renal damage without increasing intestinal toxicity. - Highlights: • DDI between MTX and Res will occur when they are co-administered. • The first targets of the DDI are P-gp and MRP2 located in intestine. • The second targets of the DDI are OAT1 and OAT3 in kidney. • Res improved MTX-induced renal damage without increasing intestinal toxicity.

  4. Drug-Drug Interactions Potential of Icariin and Its Intestinal Metabolites via Inhibition of Intestinal UDP-Glucuronosyltransferases

    Directory of Open Access Journals (Sweden)

    Yun-Feng Cao

    2012-01-01

    Full Text Available Icariin is known as an indicative constituent of the Epimedium genus, which has been commonly used in Chinese herbal medicine to enhance treat impotence and improve sexual function, as well as for several other indications for over 2000 years. In this study, we aimed to investigate the effects of icariin and its intestinal metabolites on the activities of human UDP-glucuronosyltransferase (UGT activities. Using a panel of recombinant human UGT isoforms, we found that icariin exhibited potent inhibition against UGT1A3. It is interesting that the intestinal metabolites of icariin exhibited a different inhibition profile compared with icariin. Different from icariin, icariside II was a potent inhibitor of UGT1A4, UGT1A7, UGT1A9, and UGT2B7, and icaritin was a potent inhibitor of UGT1A7 and UGT1A9. The potential for drug interactions in vivo was also quantitatively predicted and compared. The quantitative prediction of risks indicated that in vivo inhibition against intestinal UGT1A3, UGT1A4, and UGT1A7 would likely occur after oral administration of icariin products.

  5. The burden and management of cytochrome P450 2D6 (CYP2D6)-mediated drug-drug interaction (DDI): co-medication of metoprolol and paroxetine or fluoxetine in the elderly.

    Science.gov (United States)

    Bahar, Muh Akbar; Hak, Eelko; Bos, Jens H J; Borgsteede, Sander D; Wilffert, Bob

    2017-07-01

    Metoprolol and paroxetine/fluoxetine are inevitably co-prescribed because cardiovascular disorders and depression often coexist in the elderly. This leads to CYP2D6-mediated drug-drug interactions (DDI). Because systematic evaluations are lacking, we assessed the burden of metoprolol-paroxetine/fluoxetine interaction in the elderly and how these interactions are managed in Dutch community pharmacies. Dispensing data were collected from the University of Groningen pharmacy database (IADB.nl, 1999-2014) for elderly patients (≥60 years) starting beta-blockers and/or antidepressants. Based on the two main DDI alert systems (G-Standard and Pharmabase), incidences were divided between signalled (metoprolol-fluoxetine/paroxetine) and not-signalled (metoprolol-alternative antidepressants and alternative beta-blockers-paroxetine/fluoxetine) combinations. Incident users were defined as patients starting at least one signalled or a non-signalled combination. G-Standard signalled throughout the study period, whereas Pharmabase stopped after 2005. A total of 1763 patients had 2039 metoprolol-paroxetine/fluoxetine co-prescriptions, despite DDI alert systems, and about 57.3% were signalled. The number of metoprolol-alternative antidepressant combinations (incidences = 3150) was higher than alternative beta-blocker-paroxetine/fluoxetine combinations (incidences = 1872). Metoprolol users are more likely to be co-medicated with an alternative antidepressant (incidences = 2320) than paroxetine/fluoxetine users (incidences = 1232) are. The number of paroxetine/fluoxetine users co-prescribed with alternative beta-blockers was comparable to those co-medicated with metoprolol (about 50%). Less than 5% of patients received a substitute therapy after using metoprolol-paroxetine/fluoxetine. Most of the metoprolol users (90%) received a low dose (mean DDD = 0.47) regardless whether they were prescribed paroxetine/fluoxetine. Despite the signalling software, metoprolol

  6. Metabolic Pathway of Icotinib In Vitro: The Differential Roles of CYP3A4, CYP3A5, and CYP1A2 on Potential Pharmacokinetic Drug-Drug Interaction.

    Science.gov (United States)

    Zhang, TianHong; Zhang, KeRong; Ma, Li; Li, Zheng; Wang, Juan; Zhang, YunXia; Lu, Chuang; Zhu, Mingshe; Zhuang, XiaoMei

    2018-04-01

    Icotinib is the first self-developed small molecule drug in China for targeted therapy of non-small cell lung cancer. To date, systematic studies on the pharmacokinetic drug-drug interaction of icotinib were limited. By identifying metabolite generated in human liver microsomes and revealing the contributions of major cytochromes P450 (CYPs) in the formation of major metabolites, the aim of the present work was to understand the mechanisms underlying pharmacokinetic and pharmacological variability in clinic. A liquid chromatography/UV/high-resolution mass spectrometer method was developed to characterize the icotinib metabolites. The formation of 6 major metabolites was studied in recombinant CYP isozymes and human liver microsomes with specific inhibitors to identify the CYPs responsible for icotinib metabolism. The metabolic pathways observed in vitro are consistent with those observed in human. Results demonstrated that the metabolites are predominantly catalyzed by CYP3A4 (77%∼87%), with a moderate contribution from CYP3A5 (5%∼15%) and CYP1A2 (3.7%∼7.5%). The contribution of CYP2C8, 2C9, 2C19, and 2D6 is insignificant. Based on our observations, to minimize drug-drug interaction risk in clinic, coprescription of icotinib with strong CYP3A inhibitors or inducers must be weighed. CYP1A2, a highly inducible enzyme in the smoking population, may also represent a determinant of pharmacokinetic and pharmacological variability of icotinib, especially in lung cancer patients with smoking history. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  7. Drug-Drug Interactions Between the Anti-Hepatitis C Virus 3D Regimen of Ombitasvir, Paritaprevir/Ritonavir, and Dasabuvir and Eight Commonly Used Medications in Healthy Volunteers.

    Science.gov (United States)

    Polepally, Akshanth R; King, Jennifer R; Ding, Bifeng; Shuster, Diana L; Dumas, Emily O; Khatri, Amit; Chiu, Yi-Lin; Podsadecki, Thomas J; Menon, Rajeev M

    2016-08-01

    The three direct-acting antiviral regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir (3D regimen) is approved for treatment of hepatitis C virus (HCV) genotype 1 infection. Drug-drug interaction (DDI) studies of the 3D regimen and commonly used medications were conducted in healthy volunteers to provide information on coadministering these medications with or without dose adjustments. Three phase I studies evaluated DDIs between the 3D regimen (ombitasvir/paritaprevir/ritonavir 25/150/100 mg once daily + dasabuvir 250 mg twice daily) and hydrocodone bitartrate/acetaminophen (5/300 mg), metformin hydrochloride (500 mg), diazepam (2 mg), cyclobenzaprine hydrochloride (5 mg), carisoprodol (250 mg), or sulfamethoxazole/trimethoprim (SMZ/TMP) (800/160 mg twice daily), all administered orally. DDI magnitude was determined using geometric mean ratios and 90 % confidence intervals for the maximum plasma concentration (C max) and area under the plasma concentration-time curve (AUC). Changes in exposures (C max and AUC geometric mean ratios) of acetaminophen, metformin, sulfamethoxazole, trimethoprim, and diazepam were ≤25 % upon coadministration with the 3D regimen. The C max and AUC of nordiazepam, an active metabolite of diazepam, increased by 10 % and decreased by 44 %, respectively. Exposures of cyclobenzaprine and carisoprodol decreased by ≤40 and ≤46 %, respectively, whereas exposures of hydrocodone increased up to 90 %. Ombitasvir, paritaprevir, ritonavir, and dasabuvir exposures changed by ≤25 %, except for a 37 % decrease in paritaprevir C max with metformin and a 33 % increase in dasabuvir AUC with SMZ/TMP. Acetaminophen, metformin, sulfamethoxazole, and trimethoprim can be coadministered with the 3D regimen without dose adjustment. Higher doses may be needed for diazepam, cyclobenzaprine, and carisoprodol based on clinical monitoring. A 50 % lower dose and/or clinical monitoring should be considered for hydrocodone. No dose

  8. Drug interactions evaluation: An integrated part of risk assessment of therapeutics

    International Nuclear Information System (INIS)

    Zhang, Lei; Reynolds, Kellie S.; Zhao, Ping; Huang, Shiew-Mei

    2010-01-01

    Pharmacokinetic drug interactions can lead to serious adverse events or decreased drug efficacy. The evaluation of a new molecular entity's (NME's) drug-drug interaction potential is an integral part of risk assessment during drug development and regulatory review. Alteration of activities of enzymes or transporters involved in the absorption, distribution, metabolism, or excretion of a new molecular entity by concomitant drugs may alter drug exposure, which can impact response (safety or efficacy). The recent Food and Drug Administration (FDA) draft drug interaction guidance ( (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm072101.pdf)) highlights the methodologies and criteria that may be used to guide drug interaction evaluation by industry and regulatory agencies and to construct informative labeling for health practitioner and patients. In addition, the Food and Drug Administration established a 'Drug Development and Drug Interactions' website to provide up-to-date information regarding evaluation of drug interactions ( (http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm080499.htm)). This review summarizes key elements in the FDA drug interaction guidance and new scientific developments that can guide the evaluation of drug-drug interactions during the drug development process.

  9. A strategy for early-risk predictions of clinical drug-drug interactions involving the GastroPlusTM DDI module for time-dependent CYP inhibitors.

    Science.gov (United States)

    Sohlenius-Sternbeck, Anna-Karin; Meyerson, Gabrielle; Hagbjörk, Ann-Louise; Juric, Sanja; Terelius, Ylva

    2018-04-01

    1. A set of reference compounds for time-dependent inhibition (TDI) of cytochrome P450 with available literature data for k inact and K I was used to predict clinical implications using the GastroPlus TM software. Comparisons were made to in vivo literature interaction data. 2. The predicted AUC ratios (AUC +inhibitor /AUC control ) could be compared with the observed ratios from literature for all compounds with detailed information about in vivo administration, pharmacokinetics and in vivo interactions (N = 21). For this dataset, the difference between predicted and observed AUC ratios for interactions with midazolam was within twofold for all compounds except one (telaprevir, for which non-CYP-mediated metabolism likely plays a role after multiple dosing). 3. The sensitivity, specificity and accuracy of the GastroPlus TM predictions using a binary classification as no-to-weak interaction versus moderate-to-strong interaction for all compounds with available in vivo interaction data, were 80%, 82% and 81%, respectively (N = 31). 4. As a result of our evaluations of the DDI module in GastroPlus TM , we have implemented an early TDI risk assessment decision tree for our drug discovery projects involving in vitro screening and early GastroPlus TM predictions. Shifted IC 50 values are determined and k inact /K I estimated (by using a regression line established with in house-shifted IC 50 values and literature k inact /K I ratios), followed by GastroPlus TM predictions.

  10. Relative contributions of the major human CYP450 to the metabolism of icotinib and its implication in prediction of drug-drug interaction between icotinib and CYP3A4 inhibitors/inducers using physiologically based pharmacokinetic modeling.

    Science.gov (United States)

    Chen, Jia; Liu, Dongyang; Zheng, Xin; Zhao, Qian; Jiang, Ji; Hu, Pei

    2015-06-01

    Icotinib is an anticancer drug, but relative contributions of CYP450 have not been identified. This study was carried out to identify the contribution percentage of CYP450 to icotinib and use the results to develop a physiologically based pharmacokinetic (PBPK) model, which can help to predict drug-drug interaction (DDI). Human liver microsome (HLM) and supersome using relative activity factor (RAF) were employed to determine the relative contributions of the major human P450 to the net hepatic metabolism of icotinib. These values were introduced to develop a PBPK model using SimCYP. The model was validated by the observed data in a Phase I clinical trial in Chinese healthy subjects. Finally, the model was used to simulate the DDI with ketoconazole or rifampin. Final contribution of CYP450 isoforms determined by HLM showed that CYP3A4 provided major contributions to the metabolism of icotinib. The percentage contributions of the P450 to the net hepatic metabolism of icotinib were determined by HLM inhibition assay and RAF. The AUC ratio under concomitant use of ketoconazole and rifampin was 3.22 and 0.55, respectively. Percentage of contribution of CYP450 to icotinib metabolism was calculated by RAF. The model has been proven to fit the observed data and is used in predicting icotinib-ketoconazole/rifampin interaction.

  11. Farmacología en la tercera edad: medicamentos de uso continuo y peligros de la interacción medicamentosa Pharmacology in the elderly: continuous use medicines and drug-drug interaction risks

    Directory of Open Access Journals (Sweden)

    Marcela Filié Haddad

    2009-03-01

    Full Text Available Introducción: Se observó un considerable crecimiento del contingente poblacional de ancianos. Ellos son los mayores usuarios de medicamentos. Los cambios fisiológicos relacionados con el envejecimiento pueden alterar la propiedad farmacocinética y la farmacodinamia. El cuadro de declinación cognitiva, las limitaciones físicas y las enfermedades crónicas asociadas afectan la habilidad de usar adecuadamente los medicamentos. Objetivo: Indicar las principales clases farmacológicas administradas a pacientes geriátricos y los riesgos de la interacción medicamentosa en base a una revisión de literatura. Conclusión: La mayor parte de los ancianos hacen uso continuo de por lo menos tres fármacos, los más prescritos son aquellos destinados a problemas cardiovasculares y trastornos psíquicos.Introduction: It was observed a considerable growth of elderly people. They are who use more medicines. The physiological changes associated with the age advancing can make pharmacokinetic and pharmacodynamic alterations. The cognitive decline, physical limitations and associate chronic pathology affect the medications appropriately use ability. Aims: Based in a literature review, appoint the main pharmacological groups prescribed to the elderly and the drug-drug interaction risks. Conclusion: The most of elderly use continually at least 3 medicines, the most prescribed are to cardiovascular and psychic diseases treatment.

  12. Quantitative Analysis of Complex Drug-Drug Interactions Between Repaglinide and Cyclosporin A/Gemfibrozil Using Physiologically Based Pharmacokinetic Models With In Vitro Transporter/Enzyme Inhibition Data.

    Science.gov (United States)

    Kim, Soo-Jin; Toshimoto, Kota; Yao, Yoshiaki; Yoshikado, Takashi; Sugiyama, Yuichi

    2017-09-01

    Quantitative analysis of transporter- and enzyme-mediated complex drug-drug interactions (DDIs) is challenging. Repaglinide (RPG) is transported into the liver by OATP1B1 and then is metabolized by CYP2C8 and CYP3A4. The purpose of this study was to describe the complex DDIs of RPG quantitatively based on unified physiologically based pharmacokinetic (PBPK) models using in vitro K i values for OATP1B1, CYP3A4, and CYP2C8. Cyclosporin A (CsA) or gemfibrozil (GEM) increased the blood concentrations of RPG. The time profiles of RPG and the inhibitors were analyzed by PBPK models, considering the inhibition of OATP1B1 and CYP3A4 by CsA or OATP1B1 inhibition by GEM and its glucuronide and the mechanism-based inhibition of CYP2C8 by GEM glucuronide. RPG-CsA interaction was closely predicted using a reported in vitro K i,OATP1B1 value in the presence of CsA preincubation. RPG-GEM interaction was underestimated compared with observed data, but the simulation was improved with the increase of f m,CYP2C8 . These results based on in vitro K i values for transport and metabolism suggest the possibility of a bottom-up approach with in vitro inhibition data for the prediction of complex DDIs using unified PBPK models and in vitro f m value of a substrate for multiple enzymes should be considered carefully for the prediction. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  13. Prediction of the overall renal tubular secretion and hepatic clearance of anionic drugs and a renal drug-drug interaction involving organic anion transporter 3 in humans by in vitro uptake experiments.

    Science.gov (United States)

    Watanabe, Takao; Kusuhara, Hiroyuki; Watanabe, Tomoko; Debori, Yasuyuki; Maeda, Kazuya; Kondo, Tsunenori; Nakayama, Hideki; Horita, Shigeru; Ogilvie, Brian W; Parkinson, Andrew; Hu, Zhuohan; Sugiyama, Yuichi

    2011-06-01

    The present study investigated prediction of the overall renal tubular secretion and hepatic clearances of anionic drugs based on in vitro transport studies. The saturable uptake of eight drugs, most of which were OAT3 substrates (rosuvastatin, pravastatin, pitavastatin, valsartan, olmesartan, trichlormethiazide, p-aminohippurate, and benzylpenicillin) by freshly prepared human kidney slices underestimated the overall intrinsic clearance of the tubular secretion; therefore, a scaling factor of 10 was required for in vitro-in vivo extrapolation. We examined the effect of gemfibrozil and its metabolites, gemfibrozil glucuronide and the carboxylic metabolite, gemfibrozil M3, on pravastatin uptake by human kidney slices. The inhibition study using human kidney slices suggests that OAT3 plays a predominant role in the renal uptake of pravastatin. Comparison of unbound concentrations and K(i) values (1.5, 9.1, and 4.0 μM, for gemfibrozil, gemfibrozil glucuronide, and gemfibrozil M3, respectively) suggests that the mechanism of the interaction is due mainly to inhibition by gemfibrozil and gemfibrozil glucuronide. Furthermore, extrapolation of saturable uptake by cryopreserved human hepatocytes predicts clearance comparable with the observed hepatic clearance although fluvastatin and rosuvastatin required a scaling factor of 11 and 6.9, respectively. This study suggests that in vitro uptake assays using human kidney slices and hepatocytes provide a good prediction of the overall tubular secretion and hepatic clearances of anionic drugs and renal drug-drug interactions. It is also recommended that in vitro-in vivo extrapolation be performed in animals to obtain more reliable prediction.

  14. The Consequence of Drug-Drug Interactions Influencing the Interplay between P-Glycoprotein and Cytochrome P450 3a: An Ex Vivo Study with Rat Precision-Cut Intestinal Slices.

    Science.gov (United States)

    Li, Ming; de Graaf, Inge A M; Siissalo, Sanna; de Jager, Marina H; van Dam, Annie; Groothuis, Geny M M

    2016-05-01

    P-glycoprotein (P-gp) and cytochrome P450 3A (CYP3A) are differentially expressed along the intestine and work coordinately to reduce the intracellular concentration of xenobiotics and the absorption of orally taken drugs. Drug-drug interactions (DDIs) based on P-gp/CYP3A interplay are of clinical importance and require preclinical investigation. We investigated the P-gp/Cyp3a interplay and related DDIs with different P-gp inhibitors in the various regions of the rat intestine ex vivo using precision-cut intestinal slices (PCIS) with quinidine (Qi), a dual substrate of P-gp and Cyp3a, as the probe. The results showed that P-gp efflux was the main factor limiting the intracellular Qi content at concentrations below 5µM, whereas both efflux and metabolism were saturated at [Qi] > 50µM. The selective P-gp inhibitors CP100356 [N-(3,4-dimethoxyphenethyl)-4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2[1H]-yl)-6,7-dimethoxyquinazolin-2-amine] and PSC833 [valspodar, 6-[(2S,4R,6E)-4-methyl-2-(methylamino)-3-oxo-6-octenoic acid]-7-l-valine-cyclosporin A] enhanced the Qi accumulation in slices in line with the different P-gp expression in the intestinal regions and, as a result, also enhanced metabolism in the jejunum and ileum. Dual inhibitors of both P-gp and Cyp3a (verapamil and ketoconazole) increased the concentration of Qi in the jejunum and ileum, but less 3-hydroxy-quinidine was produced due to inhibition of Cyp3a. The results indicate that the P-gp/Cyp3a interplay depends on the concentration of the drug and on the intestinal region under study. Furthermore, due to the P-gp/Cyp3a interplay, DDIs can lead to remarkable changes in the intracellular concentration of both the parent drug and the metabolite, which varies among the intestinal regions and depends on the selectivity of the inhibitors, with potentially important implications for disposition and toxicity of drugs and their metabolites. Copyright © 2016 by The American Society for Pharmacology and Experimental

  15. Drug-Drug Multicomponent Solid Forms: Cocrystal, Coamorphous and Eutectic of Three Poorly Soluble Antihypertensive Drugs Using Mechanochemical Approach.

    Science.gov (United States)

    Haneef, Jamshed; Chadha, Renu

    2017-08-01

    The present study deals with the application of mechanochemical approach for the preparation of drug-drug multicomponent solid forms of three poorly soluble antihypertensive drugs (telmisartan, irbesartan and hydrochlorothiazide) using atenolol as a coformer. The resultant solid forms comprise of cocrystal (telmisartan-atenolol), coamorphous (irbesartan-atenolol) and eutectic (hydrochlorothiazide-atenolol). The study emphasizes that solid-state transformation of drug molecules into new forms is a result of the change in structural patterns, diminishing of dimers and creating new facile hydrogen bonding network based on structural resemblance. The propensity for heteromeric or homomeric interaction between two different drugs resulted into diverse solid forms (cocrystal/coamorphous/eutectics) and become one of the interesting aspects of this research work. Evaluation of these solid forms revealed an increase in solubility and dissolution leading to better antihypertensive activity in deoxycorticosterone acetate (DOCA) salt-induced animal model. Thus, development of these drug-drug multicomponent solid forms is a promising and viable approach to addressing the issue of poor solubility and could be of considerable interest in dual drug therapy for the treatment of hypertension.

  16. Evaluation of potential interactions between mycophenolic acid derivatives and proton pump inhibitors.

    Science.gov (United States)

    Gabardi, Steven; Olyaei, Ali

    2012-01-01

    To evaluate the incidence of gastrointestinal (GI) complications in solid organ transplant (SOT) recipients, impact of the complications on transplant outcomes, and the potential interactions between mycophenolic acid (MPA) derivatives and proton pump inhibitors (PPIs). An unrestricted literature search (1980-January 2012) was performed with MEDLINE and EMBASE using the following key words: drug-drug interaction, enteric-coated mycophenolic acid, GI complications, mycophenolate mofetil, solid organ transplant, and proton pump inhibitor, including individual agents within the class. Abstracts from scientific meetings were also evaluated. Additionally, reference citations from identified publications were reviewed. Relevant English-language, original research articles and review articles were evaluated if they focused on any of the topics identified in the search or included substantial content addressing GI complications in SOT recipients or drug interactions. GI complications are frequent among SOT recipients, with some studies showing prevalence rates as high as 70%. Transplant outcomes among renal transplant recipients are significantly impacted by GI complications, especially in patients requiring immunosuppressant dosage reductions or premature discontinuation. To this end, PPI use among patients receiving transplants is common. Recent data demonstrate that PPIs significantly reduce the overall exposure to MPA after oral administration of mycophenolate mofetil. Similar studies show this interaction does not exist between PPIs and enteric-coated mycophenolic acid (EC-MPA). Unfortunately, most of the available data evaluating this interaction are pharmacokinetic analyses that do not investigate the clinical impact of this interaction. A significant interaction exists between PPIs and mycophenolate mofetil secondary to reduced dissolution of mycophenolate mofetil in higher pH environments. EC-MPA is not absorbed in the stomach; therefore, low intragastric acidity

  17. Drug Interaction API

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Interaction API is a web service for accessing drug-drug interactions. No license is needed to use the Interaction API. Currently, the API uses DrugBank for its...

  18. The Spiral-Interactive Program Evaluation Model.

    Science.gov (United States)

    Khaleel, Ibrahim Adamu

    1988-01-01

    Describes the spiral interactive program evaluation model, which is designed to evaluate vocational-technical education programs in secondary schools in Nigeria. Program evaluation is defined; utility oriented and process oriented models for evaluation are described; and internal and external evaluative factors and variables that define each…

  19. Evaluation of drug interaction microcomputer software: Dambro's Drug Interactions.

    Science.gov (United States)

    Poirier, T I; Giudici, R A

    1990-01-01

    Dambro's Drug Interactions was evaluated using general and specific criteria. The installation process, ease of learning and use were rated excellent. The user documentation and quality of the technical support were good. The scope of coverage, clinical documentation, frequency of updates, and overall clinical performance were fair. The primary advantages of the program are the quick searching and detection of drug interactions, and the attempt to provide useful interaction data, i.e., significance and reference. The disadvantages are the lack of current drug interaction information, outdated references, lack of evaluative drug interaction information, and the inability to save or print patient profiles. The program is not a good value for the pharmacist but has limited use as a quick screening tool.

  20. The burden and management of cytochrome P450 2D6 (CYP2D6)-mediated drug–drug interaction (DDI) : Co-medication of metoprolol and paroxetine or fluoxetine in the elderly

    NARCIS (Netherlands)

    Bahar, Muh Akbar; Hak, Eelko; Bos, Jens H. J.; Borgsteede, Sander D.; Wilffert, Bob

    Purpose: Metoprolol and paroxetine/fluoxetine are inevitably co-prescribed because cardiovascular disorders and depression often coexist in the elderly. This leads to CYP2D6-mediated drug-drug interactions (DDI). Because systematic evaluations are lacking, we assessed the burden of

  1. Drug-drug interactions: new trends | Garba | Journal of ...

    African Journals Online (AJOL)

    The PDF file you selected should load here if your Web browser has a PDF reader plug-in installed (for example, a recent version of Adobe Acrobat Reader). If you would like more information about how to print, save, and work with PDFs, Highwire Press provides a helpful Frequently Asked Questions about PDFs.

  2. Prolonged Drug-Drug Interaction between Terbinafine and Perphenazine

    OpenAIRE

    Park, Young-Min

    2012-01-01

    I report here an elderly woman receiving perphenazine together with terbinafine. After 1 week of terbinafine treatment she experienced extrapyramidal symptoms and, in particular, akathisia. Her symptoms did not disappear for 6 weeks, and so at 2 weeks prior to this most recent admission she had stopped taking terbinafine. However, these symptoms persisted for 3 weeks after discontinuing terbinafine. It is well known that terbinafine inhibits CYP2D6 and that perphenazine is metabolized mainly ...

  3. Teaching Program Evaluation on Interactive Television.

    Science.gov (United States)

    McNeil, Keith; Steinhauser, Jim; Newman, Isadore

    This paper describes a five-session course entitled "Program Evaluation," which was taught via interactive television in the summer of 2002 to 68 doctoral and master's students in 5 of 6 locations throughout New Mexico. Students received a 4-hour lecture and then participated in off-line activities directed by the instructor. Problems in distance…

  4. Using Affinity Diagrams to Evaluate Interactive Prototypes

    DEFF Research Database (Denmark)

    Lucero, Andrés

    2015-01-01

    our particular use of affinity diagramming in prototype evaluations. We reflect on a decade’s experience using affinity diagramming across a number of projects, both in industry and academia. Our affinity diagramming process in interaction design has been tailored and consists of four stages: creating...

  5. Cockpit design and evaluation using interactive graphics

    Science.gov (United States)

    Evans, S. M.

    1975-01-01

    A general overview of the characteristics of an interactive graphics system which was developed to assist cockpit engineers design and evaluate work stations was presented. The manikin used in this COMputerized BIomechanical MAN-model (COMBIMAN) was described, as are provisions for generating work stations and assessing interactions between man and environment. The applications of the present system are explained, and critiques of COMBIMAN are presented. The limitations of the existing programs and the requirements of the designers necessitate future revisions and additions to the biomechanical and erogonomic properties of COMBIMAN. Some of these enhancements are discussed.

  6. Development and Evaluation of an Interactive Pen

    Directory of Open Access Journals (Sweden)

    Froilan G. Destreza

    2015-11-01

    Full Text Available Technologies have reached the classroom. It is one of the means of teaching strategies nowadays. Multimedia projectors have become one of the teaching tools the teacher cannot bear without it. The concept of making this tool to be interactive and easier to use was far conceived by the researcher. The researcher’s objective was to develop such tool and evaluate it according to its portability, simplicity, robustness, user-friendliness, effectiveness and efficiency. The respondents of the project were both the students and teachers of Batangas State University ARASOF-Nasugbu. The researcher has developed different prototypes for the interactive pen and tested in different environment and demonstrated the “know-how” of the project. The project was built using a simple infrared light emitting diode (IR LED, infrared tracker, and software which computes, detects and interact with the application program. Evaluation of the project followed the demonstration. The project got a high acceptance according to its portability, simplicity, robustness, user-friendliness, effectiveness and efficiency. The researcher is recommending the full implementation of the project in the Batangas State University ARASOF- Nasugbu and for better enhancement of the project by eliminating the pen.

  7. Soil-structure interaction - an engineering evaluation

    International Nuclear Information System (INIS)

    Hadjian, A.H.

    1976-01-01

    The two methods of analysis for structure interaction, the impedance and the finite element methods, are reviewed with regard to their present capabilities to address the significant factors of the problem. The objective of the paper is to evaluate if an adequate engineering solution to the problem is provided by either approach. Questions related to the reduction of seismic motions with depth scattering of incident waves, the three-dimensionality of the real problem, soil damping, strain dependency of soil properties and the uncertainties associated with all of the above are discussed in sufficient detail. All conclusions made are based on referenced material. It appears that both methods as presently practised have not yet completely solved the problem, the impedance approach has come closer to addressing the more significant issues. Because of this finding, in addition to its simplicity and low cost, the impedance approach is the perfect engineering method for soil-structure interaction. (Auth.)

  8. Nuclear interactive evaluations on distributed processors

    International Nuclear Information System (INIS)

    Dix, G.E.; Congdon, S.P.

    1988-01-01

    BWR [boiling water reactor] nuclear design is a complicated process, involving trade-offs among a variety of conflicting objectives. Complex computer calculations and usually required for each design iteration. GE Nuclear Energy has implemented a system where the evaluations are performed interactively on a large number of small microcomputers. This approach minimizes the time it takes to carry out design iterations even through the processor speeds are low compared with modern super computers. All of the desktop microcomputers are linked to a common data base via an ethernet communications system so that design data can be shared and data quality can be maintained

  9. Drug interactions in primary health care in the George subdistrict ...

    African Journals Online (AJOL)

    2012-02-15

    Feb 15, 2012 ... Drug-drug interactions are a recognised cause of morbidity and mortality ..... or fatal if the interaction increases toxicity or reduces the intended effect of the ... antihypertensive effect of angiotensin-converting enzyme inhibitors ...

  10. In vitro evaluation of the interaction between methanol extract of ...

    African Journals Online (AJOL)

    Antimicrobial interaction studies between methanol extract of lichen (Ramalina farinacea (I) ach. (Fam: Ramalinacea) and tetracycline, against clinical isolates of Staphylococcus aureus was evaluated. Preliminary antimicrobial properties of the extract were evaluated. Antimicrobial interaction studies between the methanol ...

  11. Order effect in interactive information retrieval evaluation

    DEFF Research Database (Denmark)

    Clemmensen, Melanie Landvad; Borlund, Pia

    2016-01-01

    , and the good-subject effect shed light on how and why order effect may affect test participants’ IR system interaction and search behaviour. Research limitations/implications – Insight about order effect has implications for test design of IIR studies and hence the knowledge base generated on the basis...... of such studies. Due to the limited sample of 20 test participants (Library and Information Science (LIS) students) inference statistics is not applicable; hence conclusions can be drawn from this sample of test participants only. Originality/value – Only few studies in LIS focus on order effect and none from...... the perspective of IIR. Keywords Evaluation, Research methods, Information retrieval, User studies, Searching, Information searches...

  12. Participant Interaction in Asynchronous Learning Environments: Evaluating Interaction Analysis Methods

    Science.gov (United States)

    Blanchette, Judith

    2012-01-01

    The purpose of this empirical study was to determine the extent to which three different objective analytical methods--sequence analysis, surface cohesion analysis, and lexical cohesion analysis--can most accurately identify specific characteristics of online interaction. Statistically significant differences were found in all points of…

  13. Evaluation of an Interactive Undergraduate Cosmology Curriculum

    Science.gov (United States)

    White, Aaron; Coble, Kimberly A.; Martin, Dominique; Hayes, Patrycia; Targett, Tom; Cominsky, Lynn R.

    2018-06-01

    The Big Ideas in Cosmology is an immersive set of web-based learning modules that integrates text, figures, and visualizations with short and long interactive tasks as well as labs that allow students to manipulate and analyze real cosmological data. This enables the transformation of general education astronomy and cosmology classes from primarily lecture and book-based courses to a format that builds important STEM skills, while engaging those outside the field with modern discoveries and a more realistic sense of practices and tools used by professional astronomers. Over two semesters, we field-tested the curriculum in general education cosmology classes at a state university in California [N ~ 80]. We administered pre- and post-instruction multiple-choice and open-ended content surveys as well as the CLASS, to gauge the effectiveness of the course and modules. Questions addressed included the structure, composition, and evolution of the universe, including students’ reasoning and “how we know.”Module development and evaluation was supported by NASA ROSES E/PO Grant #NNXl0AC89G, the Illinois Space Grant Consortium, the Fermi E/PO program, Sonoma State University’s Space Science Education and Public Outreach Group, and San Francisco State University. The modules are published by Great River Learning/Kendall-Hunt.

  14. The user in interactive information retrieval evaluation

    DEFF Research Database (Denmark)

    Ingwersen, Peter

    2011-01-01

    ) Request types, test persons, task-based simulations of search situations and relevance or performance measures in IIR; 2) Ultra-Light Interactive IR experiments; 3) Interactive-Light IR studies; and 4) Naturalistic field investigations of IIR. The chapter concludes with a summary section, a reference list...

  15. Interactive segmentation techniques algorithms and performance evaluation

    CERN Document Server

    He, Jia; Kuo, C-C Jay

    2013-01-01

    This book focuses on interactive segmentation techniques, which have been extensively studied in recent decades. Interactive segmentation emphasizes clear extraction of objects of interest, whose locations are roughly indicated by human interactions based on high level perception. This book will first introduce classic graph-cut segmentation algorithms and then discuss state-of-the-art techniques, including graph matching methods, region merging and label propagation, clustering methods, and segmentation methods based on edge detection. A comparative analysis of these methods will be provided

  16. [Pharmacokinetic interactions of telaprevir with other drugs].

    Science.gov (United States)

    Berenguer Berenguer, Juan; González-García, Juan

    2013-07-01

    Telaprevir is a new direct-acting antiviral drug for the treatment of hepatitis C virus (HCV) infection and is both a substrate and an inhibitor of cytochrome P450 (CYP450) isoenzymes. With the introduction of this new drug, assessment of drug-drug interactions has become a key factor in the evaluation of patients under treatment for HCV infection. During the treatment of this infection, many patients require other drugs to mitigate the adverse effects of anti-HCV drugs and to control other comorbidities. Moreover, most patients coinfected with HIV and HCV require antiretroviral therapy during treatment for HCV. Physicians should therefore be familiar with the pharmacokinetic properties of direct-acting antivirals for HCV treatment and their potential drug-drug interactions. The present article reviews the available information to date on the interactions of telaprevir with other drugs and provides recommendations for daily clinical practice. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  17. Evaluation of the potential interaction between tofacitinib and drugs that undergo renal tubular secretion using metformin, an in vivo marker of renal organic cation transporter 2.

    Science.gov (United States)

    Klamerus, Karen J; Alvey, Christine; Li, Lei; Feng, Bo; Wang, Rong; Kaplan, Irina; Shi, Haihong; Dowty, Martin E; Krishnaswami, Sriram

    2014-11-01

    Tofacitinib is a novel, oral Janus kinase inhibitor. The potential for drug-drug interactions (DDIs) between tofacitinib and drugs that undergo renal tubular secretion was evaluated using metformin as a probe transporter substrate, and genotyping for organic cation transporter (OCT) 1, OCT2 and multidrug and toxin extrusion 1 polymorphisms. Twenty-four healthy male subjects completed this open-label, fixed-sequence study. Subjects were administered a single oral metformin 500 mg dose on Days 1 and 4, and multiple oral tofacitinib 30 mg twice daily doses on Days 2, 3, and 4. Subjects underwent serial blood and urine samplings (Days 1 and 4) to estimate metformin pharmacokinetics. A single blood sample for tofacitinib was collected 2 hours after the morning dose (Day 4). The 90% confidence intervals for the ratios of maximum plasma concentration, area under the curve and renal clearance of metformin, with and without tofacitinib, were contained within the 80-125% acceptance range commonly used to establish a lack of DDI. No deaths, serious adverse events (AEs), severe AEs or discontinuations due to AEs were reported. The study confirms tofacitinib is unlikely to impact the pharmacokinetics of drugs that undergo renal tubular secretion, and concurs with its weak in vitro OCT2 inhibitory profile. © 2014, The American College of Clinical Pharmacology.

  18. Evaluation of Interactive Website Design Indicators for e-Entrepreneurship

    OpenAIRE

    Chih-Chao Chung; Li-Chung Chao; Chin-Hui Chen; Shi-Jer Lou

    2016-01-01

    Using an analytic network process (ANP) as an analytical tool, this study aims to construct an ANP evaluation model of interactive website design indicators. Through a review of the literature, interactive website design of e-entrepreneurship is generalized to the following dimensions: (1) Design; (2) Checking; (3) Service; (4) Interactive; and (5) Promotion, including 19 design indicators. The research is conducted for a case company. According to the findings, the model helps the case compa...

  19. 2nd Workshop on Evaluating Child Robot Interaction

    NARCIS (Netherlands)

    Zaga, Cristina; Lohse, M.; Charisi, Vasiliki; Evers, Vanessa; Neerincx, Marc; Kanda, Takayuki; Leite, Iolanda

    Many researchers have started to explore natural interaction scenarios for children. No matter if these children are normally developing or have special needs, evaluating Child-Robot Interaction (CRI) is a challenge. To find methods that work well and provide reliable data is difficult, for example

  20. Predicting transporter-mediated drug interactions: Commentary on: "Pharmacokinetic evaluation of a drug transporter cocktail consisting of digoxin, furosemide, metformin and rosuvastatin" and "Validation of a microdose probe drug cocktail for clinical drug interaction assessments for drug transporters and CYP3A".

    Science.gov (United States)

    Zhang, L; Sparreboom, A

    2017-04-01

    Transporters, expressed in various tissues, govern the absorption, distribution, metabolism, and excretion of drugs, and consequently their inherent safety and efficacy profiles. Drugs may interact with a transporter as a substrate and/or an inhibitor. Understanding transporter-mediated drug-drug interactions (DDIs), in addition to enzyme-mediated DDIs, is an integral part of risk assessment in drug development and regulatory review because the concomitant use of more than one medication in patients is common. © 2016 ASCPT.

  1. Evaluation of self-interaction parameters from binary phase diagrams

    International Nuclear Information System (INIS)

    Ellison, T.L.

    1977-10-01

    The feasibility of calculating Wagner self-interaction parameters from binary phase diagrams was examined. The self-interaction parameters of 22 non-ferrous liquid solutions were calculated utilizing an equation based on the equality of the chemical potentials of a component in two equilibrium phases. Utilization of the equation requires the evaluation of the first and second derivatives of various liquidus and solidus data at infinite dilution of the solute component. Several numerical methods for evaluating the derivatives of tabular data were examined. A method involving power series curve fitting and subsequent differentiation of the power series was found to be the most suitable for the interaction parameter calculations. Comparison of the calculated self-interaction parameters with values obtained from thermodynamic measurements indicates that the Wagner self-interaction parameter can be successfully calculated from binary phase diagrams

  2. Allosteric cross-talk in chromatin can mediate drug-drug synergy

    Science.gov (United States)

    Adhireksan, Zenita; Palermo, Giulia; Riedel, Tina; Ma, Zhujun; Muhammad, Reyhan; Rothlisberger, Ursula; Dyson, Paul J.; Davey, Curt A.

    2017-03-01

    Exploitation of drug-drug synergism and allostery could yield superior therapies by capitalizing on the immensely diverse, but highly specific, potential associated with the biological macromolecular landscape. Here we describe a drug-drug synergy mediated by allosteric cross-talk in chromatin, whereby the binding of one drug alters the activity of the second. We found two unrelated drugs, RAPTA-T and auranofin, that yield a synergistic activity in killing cancer cells, which coincides with a substantially greater number of chromatin adducts formed by one of the compounds when adducts from the other agent are also present. We show that this occurs through an allosteric mechanism within the nucleosome, whereby defined histone adducts of one drug promote reaction of the other drug at a distant, specific histone site. This opens up possibilities for epigenetic targeting and suggests that allosteric modulation in nucleosomes may have biological relevance and potential for therapeutic interventions.

  3. Evaluation of Interactive Website Design Indicators for e-Entrepreneurship

    Directory of Open Access Journals (Sweden)

    Chih-Chao Chung

    2016-04-01

    Full Text Available Using an analytic network process (ANP as an analytical tool, this study aims to construct an ANP evaluation model of interactive website design indicators. Through a review of the literature, interactive website design of e-entrepreneurship is generalized to the following dimensions: (1 Design; (2 Checking; (3 Service; (4 Interactive; and (5 Promotion, including 19 design indicators. The research is conducted for a case company. According to the findings, the model helps the case company review its current execution of interactive website design indicators and the experts’ opinions of the importance of interactive website design indicators. In addition, by comprehensive comparison, it confirms key design indicators and analyzes the managerial implications to help the case company set up precise strategic planning and resource distribution to enhance corporate operational performance and competitiveness.

  4. Frequency, Levels and Predictors of Potential Drug-Drug ...

    African Journals Online (AJOL)

    major or moderate interactions included rifampin + pyrazinamide (14 cases), phenobarbital + diazepam (14), dexamethasone + rifampin (8), amikacin + furosemide (7), furosemide + captopril (7), dexamethasone + phenobarbital (6), phenobarbital + divalproex sodium (6), isoniazid + rifampin (5) amikacin + ibuprofen (5), ...

  5. Prevalence and Characteristics of Polypharmacy and Drug-Drug ...

    African Journals Online (AJOL)

    Polypharmacy is the prescription of multiple medications for a patient which is a common problem worldwide. The aim of this study was to identify the extent of polypharmacy and occurrence of drug–drug interaction in Afincho Ber Health Centre, Addis Ababa. The study was conducted by retrospective crosssectional review ...

  6. Exploring Action Research as an Approach to Interactive (Participatory) Evaluation

    Science.gov (United States)

    Chaudary, Imran Anjum; Imran, Shahida

    2012-01-01

    This investigation seeks to understand "action research" as an approach to "interactive form of evaluation". The first half of the investigation illuminates the approach with the help of the selective body of literature and the second half draws attention to its application in the field with the help of an authentic evaluation…

  7. Bacteria Hunt: Evaluating multi-paradigm BCI interaction

    NARCIS (Netherlands)

    Mühl, C.; Gürkök, Hayrettin; Plass - Oude Bos, D.; Thurlings, Marieke E.; Scherffig, Lasse; Duvinage, Matthieu; Elbakyan, Alexandra A.; Kang, SungWook; Poel, Mannes; Heylen, Dirk K.J.

    The multimodal, multi-paradigm brain-computer interfacing (BCI) game Bacteria Hunt was used to evaluate two aspects of BCI interaction in a gaming context. One goal was to examine the effect of feedback on the ability of the user to manipulate his mental state of relaxation. This was done by having

  8. Age Differences in Voice Evaluation: From Auditory-Perceptual Evaluation to Social Interactions

    Science.gov (United States)

    Lortie, Catherine L.; Deschamps, Isabelle; Guitton, Matthieu J.; Tremblay, Pascale

    2018-01-01

    Purpose: The factors that influence the evaluation of voice in adulthood, as well as the consequences of such evaluation on social interactions, are not well understood. Here, we examined the effect of listeners' age and the effect of talker age, sex, and smoking status on the auditory-perceptual evaluation of voice, voice-related psychosocial…

  9. Psychometric evaluation of the Social Interaction Phobia Scale.

    Science.gov (United States)

    Reilly, Alison R; Carleton, R Nicholas; Weeks, Justin W

    2012-01-01

    The present study evaluated the psychometric properties of a novel measure of social anxiety symptoms, the Social Interaction Phobia Scale (SIPS), as a stand-alone item set, using an undergraduate sample (N=512). The 14-item SIPS has three subscales assessing Social Interaction Anxiety, Fear of Overt Evaluation, and Fear of Attracting Attention. Confirmatory factor analyses replicated the three-factor structure for the SIPS originally reported by Carleton et al. All SIPS scores demonstrated good internal consistency. The convergent validity of the SIPS was supported by strong and positive correlations between all SIPS scores and measures of social anxiety and fear of evaluation; the finding that the relationships between all SIPS scores and a social anxiety measure were stronger than relationships between all SIPS scores and measures of other constructs supported the discriminant validity of the SIPS. Results suggest that the SIPS possesses excellent psychometric properties.

  10. Using GOMS and NASA-TLX to Evaluate Human-Computer Interaction Process in Interactive Segmentation

    NARCIS (Netherlands)

    Ramkumar, A.; Stappers, P.J.; Niessen, W.J.; Adebahr, S; Schimek-Jasch, T; Nestle, U; Song, Y.

    2016-01-01

    HCI plays an important role in interactive medical image segmentation. The Goals, Operators, Methods, and Selection rules (GOMS) model and the National Aeronautics and Space Administration Task Load Index (NASA-TLX) questionnaire are different methods that are often used to evaluate the HCI

  11. Evaluation of the Potential Pharmacokinetic Interaction between Atomoxetine and Fluvoxamine in Healthy Volunteers.

    Science.gov (United States)

    Todor, Ioana; Popa, Adina; Neag, Maria; Muntean, Dana; Bocsan, Corina; Buzoianu, Anca; Vlase, Laurian; Gheldiu, Ana-Maria; Briciu, Corina

    2017-01-01

    Attention deficit hyperactivity disorder (ADHD) is frequently associated with other psychiatric pathologies. Therefore, the present study investigated a possible pharmacokinetic interaction between atomoxetine (ATX), a treatment option for ADHD, and an antidepressant, namely, fluvoxamine (FVX). Designed as an open-label, non-randomized clinical trial, the study included 2 periods. In period 1 (reference), each subject received ATX 25 mg (single-dose), whereas in period 2 (test), all subjects were given a combination of ATX 25 mg + FVX 100 mg, following a 6-day pretreatment regimen with the enzymatic inhibitor. Non-compartmental methods were employed to determine the pharmacokinetic parameters of ATX and its main active metabolite (glucuronidated form), 4-hydroxyatomoxetine-O-glucuronide. The results revealed significant differences between the study periods for Cmax, AUC0-t and AUC0-∞ values corresponding to ATX and its metabolite. Small, but statistically significant increases in AUC values were reported for both parent drug (1,583.05 ± 1,040.29 vs. 2,111.55 ± 1,411.59 ng*h/ml) and 4-hydroxyatomoxetine-O-glucuronide (5,754.71 ± 1,235.5 vs. 6,293.17 ± 1,219.34 ng*h/ml) after combined treatment of ATX and the enzymatic inhibitor. FVX had a modest effect on the pharmacokinetics of ATX and 4-hydroxyatomoxetine-O-glucuronide. The presence or absence of any clinical consequences associated with this pharmacokinetic drug-drug interaction needs to be established in future studies. © 2016 S. Karger AG, Basel.

  12. Patient Counseling about Herbal-Drug Interactions | Hussain ...

    African Journals Online (AJOL)

    The multitude of pharmacologically active compounds obviously increases the likelihood of interactions taking place. Hence, the likelihood of herb-drug interactions is theoretically higher than drug-drug interactions because synthetic drugs usually contain single chemical entity. Case reports and clinical studies have ...

  13. Lower alert rates by clustering of related drug interaction alerts

    NARCIS (Netherlands)

    Heringa, M.; Siderius, Hidde; Schreudering, A.; De Smet, Peter Agm; Bouvy, M.L.

    OBJECTIVE: We aimed to investigate to what extent clustering of related drug interaction alerts (drug-drug and drug-disease interaction alerts) would decrease the alert rate in clinical decision support systems (CDSSs). METHODS: We conducted a retrospective analysis of drug interaction alerts

  14. Evaluation of clustering algorithms for protein-protein interaction networks

    Directory of Open Access Journals (Sweden)

    van Helden Jacques

    2006-11-01

    Full Text Available Abstract Background Protein interactions are crucial components of all cellular processes. Recently, high-throughput methods have been developed to obtain a global description of the interactome (the whole network of protein interactions for a given organism. In 2002, the yeast interactome was estimated to contain up to 80,000 potential interactions. This estimate is based on the integration of data sets obtained by various methods (mass spectrometry, two-hybrid methods, genetic studies. High-throughput methods are known, however, to yield a non-negligible rate of false positives, and to miss a fraction of existing interactions. The interactome can be represented as a graph where nodes correspond with proteins and edges with pairwise interactions. In recent years clustering methods have been developed and applied in order to extract relevant modules from such graphs. These algorithms require the specification of parameters that may drastically affect the results. In this paper we present a comparative assessment of four algorithms: Markov Clustering (MCL, Restricted Neighborhood Search Clustering (RNSC, Super Paramagnetic Clustering (SPC, and Molecular Complex Detection (MCODE. Results A test graph was built on the basis of 220 complexes annotated in the MIPS database. To evaluate the robustness to false positives and false negatives, we derived 41 altered graphs by randomly removing edges from or adding edges to the test graph in various proportions. Each clustering algorithm was applied to these graphs with various parameter settings, and the clusters were compared with the annotated complexes. We analyzed the sensitivity of the algorithms to the parameters and determined their optimal parameter values. We also evaluated their robustness to alterations of the test graph. We then applied the four algorithms to six graphs obtained from high-throughput experiments and compared the resulting clusters with the annotated complexes. Conclusion This

  15. Simplified Human-Robot Interaction: Modeling and Evaluation

    Directory of Open Access Journals (Sweden)

    Balazs Daniel

    2013-10-01

    Full Text Available In this paper a novel concept of human-robot interaction (HRI modeling is proposed. Including factors like trust in automation, situational awareness, expertise and expectations a new user experience framework is formed for industrial robots. Service Oriented Robot Operation, proposed in a previous paper, creates an abstract level in HRI and it is also included in the framework. This concept is evaluated with exhaustive tests. Results prove that significant improvement in task execution may be achieved and the new system is more usable for operators with less experience with robotics; personnel specific for small and medium enterprises (SMEs.

  16. Pharmacokinetic Drug-Drug Interaction Study Between Raltegravir and Atorvastatin 20 mg in Healthy Volunteers

    NARCIS (Netherlands)

    Blonk, M.I.; Beek, M. van; Colbers, A.; Schouwenberg, B.J.; Burger, D.M.

    2015-01-01

    BACKGROUND: Dyslipidemia is highly prevalent among patients with HIV infection and contributes to an increased risk of cardiovascular disease. We investigated the influence of a frequently used statin, atorvastatin, on the pharmacokinetics of the HIV-integrase inhibitor raltegravir and vice versa.

  17. Potential drug-drug interactions in the neurology ward of a tertiary ...

    African Journals Online (AJOL)

    With this type of program, this better patient health outcomes can be achieved. Keywords: ... technological advancements and ... impact in improving-the quality of patient's-life. .... spinal-hematoma if Aspirin and Enoxaparin .... To avoid the.

  18. Clinical Drug-Drug Pharmacokinetic Interaction Potential of Sucralfate with Other Drugs

    DEFF Research Database (Denmark)

    Sulochana, Suresh P; Syed, Muzeeb; Chandrasekar, Devaraj V

    2016-01-01

    of drugs. This review covers several category of drugs such as non-steroidal anti-inflammatory drugs, fluoroquinolones, histamine H2-receptor blockers, macrolides, anti-fungals, anti-diabetics, salicylic acid derivatives, steroidal anti-inflammatory drugs and provides pharmacokinetic data summary along...

  19. Computerized techniques pave the way for drug-drug interaction prediction and interpretation

    Directory of Open Access Journals (Sweden)

    Reza Safdari

    2016-06-01

    Results: Computerized data-mining in pharmaceutical sciences and related databases provide new key transformative paradigms that can revolutionize the treatment of diseases and hence medical care. Given that various aspects of drug discovery and pharmacotherapy are closely related to the clinical and molecular/biological information, the scientifically sound databases (e.g., DDIs, ADRs can be of importance for the success of pharmacotherapy modalities. Conclusion: A better understanding of DDIs not only provides a robust means for designing more effective medicines but also grantees patient safety.

  20. Reliability evaluation of containments including soil-structure interaction

    International Nuclear Information System (INIS)

    Pires, J.; Hwang, H.; Reich, M.

    1985-12-01

    Soil-structure interaction effects on the reliability assessment of containment structures are examined. The probability-based method for reliability evaluation of nuclear structures developed at Brookhaven National Laboratory is extended to include soil-structure interaction effects. In this method, reliability of structures is expressed in terms of limit state probabilities. Furthermore, random vibration theory is utilized to calculate limit state probabilities under random seismic loads. Earthquake ground motion is modeled by a segment of a zero-mean, stationary, filtered Gaussian white noise random process, represented by its power spectrum. All possible seismic hazards at a site, represented by a hazard curve, are also included in the analysis. The soil-foundation system is represented by a rigid surface foundation on an elastic halfspace. Random and other uncertainties in the strength properties of the structure, in the stiffness and internal damping of the soil, are also included in the analysis. Finally, a realistic reinforced concrete containment is analyzed to demonstrate the application of the method. For this containment, the soil-structure interaction effects on; (1) limit state probabilities, (2) structural fragility curves, (3) floor response spectra with probabilistic content, and (4) correlation coefficients for total acceleration response at specified structural locations, are examined in detail. 25 refs., 21 figs., 12 tabs

  1. Microarrays for the evaluation of cell-biomaterial surface interactions

    Science.gov (United States)

    Thissen, H.; Johnson, G.; McFarland, G.; Verbiest, B. C. H.; Gengenbach, T.; Voelcker, N. H.

    2007-01-01

    The evaluation of cell-material surface interactions is important for the design of novel biomaterials which are used in a variety of biomedical applications. While traditional in vitro test methods have routinely used samples of relatively large size, microarrays representing different biomaterials offer many advantages, including high throughput and reduced sample handling. Here, we describe the simultaneous cell-based testing of matrices of polymeric biomaterials, arrayed on glass slides with a low cell-attachment background coating. Arrays were constructed using a microarray robot at 6 fold redundancy with solid pins having a diameter of 375 μm. Printed solutions contained at least one monomer, an initiator and a bifunctional crosslinker. After subsequent UV polymerisation, the arrays were washed and characterised by X-ray photoelectron spectroscopy. Cell culture experiments were carried out over 24 hours using HeLa cells. After labelling with CellTracker ® Green for the final hour of incubation and subsequent fixation, the arrays were scanned. In addition, individual spots were also viewed by fluorescence microscopy. The evaluation of cell-surface interactions in high-throughput assays as demonstrated here is a key enabling technology for the effective development of future biomaterials.

  2. Pharmacoepidemiological assessment of drug interactions with vitamin K antagonists

    DEFF Research Database (Denmark)

    Pottegård, Anton; Christensen, Rene dePont; Wang, Shirley V

    2014-01-01

    PurposeWe present a database of prescription drugs and international normalized ratio (INR) data and the applied methodology for its use to assess drug-drug interactions with vitamin K antagonists (VKAs). We use the putative interaction between VKAs and tramadol as a case study. MethodsWe used...

  3. Drug Interactions in Clinical Practice | Ohaju-Obodo | Nigerian ...

    African Journals Online (AJOL)

    The existence of numerous drugs available today for clinical management of patients require consideration of their potential interactions - alteration of the effects of one drug by the concurrent or prior administration of one or more drugs (drug-drug interactions). There could also be alteration of the effects of a drug by food ...

  4. TargetNet: a web service for predicting potential drug-target interaction profiling via multi-target SAR models.

    Science.gov (United States)

    Yao, Zhi-Jiang; Dong, Jie; Che, Yu-Jing; Zhu, Min-Feng; Wen, Ming; Wang, Ning-Ning; Wang, Shan; Lu, Ai-Ping; Cao, Dong-Sheng

    2016-05-01

    Drug-target interactions (DTIs) are central to current drug discovery processes and public health fields. Analyzing the DTI profiling of the drugs helps to infer drug indications, adverse drug reactions, drug-drug interactions, and drug mode of actions. Therefore, it is of high importance to reliably and fast predict DTI profiling of the drugs on a genome-scale level. Here, we develop the TargetNet server, which can make real-time DTI predictions based only on molecular structures, following the spirit of multi-target SAR methodology. Naïve Bayes models together with various molecular fingerprints were employed to construct prediction models. Ensemble learning from these fingerprints was also provided to improve the prediction ability. When the user submits a molecule, the server will predict the activity of the user's molecule across 623 human proteins by the established high quality SAR model, thus generating a DTI profiling that can be used as a feature vector of chemicals for wide applications. The 623 SAR models related to 623 human proteins were strictly evaluated and validated by several model validation strategies, resulting in the AUC scores of 75-100 %. We applied the generated DTI profiling to successfully predict potential targets, toxicity classification, drug-drug interactions, and drug mode of action, which sufficiently demonstrated the wide application value of the potential DTI profiling. The TargetNet webserver is designed based on the Django framework in Python, and is freely accessible at http://targetnet.scbdd.com .

  5. TargetNet: a web service for predicting potential drug-target interaction profiling via multi-target SAR models

    Science.gov (United States)

    Yao, Zhi-Jiang; Dong, Jie; Che, Yu-Jing; Zhu, Min-Feng; Wen, Ming; Wang, Ning-Ning; Wang, Shan; Lu, Ai-Ping; Cao, Dong-Sheng

    2016-05-01

    Drug-target interactions (DTIs) are central to current drug discovery processes and public health fields. Analyzing the DTI profiling of the drugs helps to infer drug indications, adverse drug reactions, drug-drug interactions, and drug mode of actions. Therefore, it is of high importance to reliably and fast predict DTI profiling of the drugs on a genome-scale level. Here, we develop the TargetNet server, which can make real-time DTI predictions based only on molecular structures, following the spirit of multi-target SAR methodology. Naïve Bayes models together with various molecular fingerprints were employed to construct prediction models. Ensemble learning from these fingerprints was also provided to improve the prediction ability. When the user submits a molecule, the server will predict the activity of the user's molecule across 623 human proteins by the established high quality SAR model, thus generating a DTI profiling that can be used as a feature vector of chemicals for wide applications. The 623 SAR models related to 623 human proteins were strictly evaluated and validated by several model validation strategies, resulting in the AUC scores of 75-100 %. We applied the generated DTI profiling to successfully predict potential targets, toxicity classification, drug-drug interactions, and drug mode of action, which sufficiently demonstrated the wide application value of the potential DTI profiling. The TargetNet webserver is designed based on the Django framework in Python, and is freely accessible at http://targetnet.scbdd.com.

  6. Robust ray-tracing algorithms for interactive dose rate evaluation

    International Nuclear Information System (INIS)

    Perrotte, L.

    2011-01-01

    More than ever, it is essential today to develop simulation tools to rapidly evaluate the dose rate received by operators working on nuclear sites. In order to easily study numerous different scenarios of intervention, computation times of available softwares have to be all lowered. This mainly implies to accelerate the geometrical computations needed for the dose rate evaluation. These computations consist in finding and sorting the whole list of intersections between a big 3D scene and multiple groups of 'radiative' rays meeting at the point where the dose has to be measured. In order to perform all these computations in less than a second, we first propose a GPU algorithm that enables the efficient management of one big group of coherent rays. Then we present a modification of this algorithm that guarantees the robustness of the ray-triangle intersection tests through the elimination of the precision issues due to floating-point arithmetic. This modification does not require the definition of scene-dependent coefficients ('epsilon' style) and only implies a small loss of performance (less than 10%). Finally we propose an efficient strategy to handle multiple ray groups (corresponding to multiple radiative objects) which use the previous results.Thanks to these improvements, we are able to perform an interactive and robust dose rate evaluation on big 3D scenes: all of the intersections (more than 13 million) between 700 000 triangles and 12 groups of 100 000 rays each are found, sorted along each ray and transferred to the CPU in 470 milliseconds. (author) [fr

  7. A Bone-Implant Interaction Mouse Model for Evaluating Molecular Mechanism of Biomaterials/Bone Interaction.

    Science.gov (United States)

    Liu, Wenlong; Dan, Xiuli; Wang, Ting; Lu, William W; Pan, Haobo

    2016-11-01

    The development of an optimal animal model that could provide fast assessments of the interaction between bone and orthopedic implants is essential for both preclinical and theoretical researches in the design of novel biomaterials. Compared with other animal models, mice have superiority in accessing the well-developed transgenic modification techniques (e.g., cell tracing, knockoff, knockin, and so on), which serve as powerful tools in studying molecular mechanisms. In this study, we introduced the establishment of a mouse model, which was specifically tailored for the assessment of bone-implant interaction in a load-bearing bone marrow microenvironment and could potentially allow the molecular mechanism study of biomaterials by using transgenic technologies. The detailed microsurgery procedures for developing a bone defect (Φ = 0.8 mm) at the metaphysis region of the mouse femur were recorded. According to our results, the osteoconductive and osseointegrative properties of a well-studied 45S5 bioactive glass were confirmed by utilizing our mouse model, verifying the reliability of this model. The feasibility and reliability of the present model were further checked by using other materials as objects of study. Furthermore, our results indicated that this animal model provided a more homogeneous tissue-implant interacting surface than the rat at the early stage of implantation and this is quite meaningful for conducting quantitative analysis. The availability of transgenic techniques to mechanism study of biomaterials was further testified by establishing our model on Nestin-GFP transgenic mice. Intriguingly, the distribution of Nestin + cells was demonstrated to be recruited to the surface of 45S5 glass as early as 3 days postsurgery, indicating that Nestin + lineage stem cells may participate in the subsequent regeneration process. In summary, the bone-implant interaction mouse model could serve as a potential candidate to evaluate the early stage tissue

  8. Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, part I.

    Science.gov (United States)

    Armstrong, Scott C; Cozza, Kelly L

    2003-01-01

    Pharmacokinetic drug-drug interactions with morphine, hydromorphone, and oxymorphone are reviewed in this column. Morphine is a naturally occurring opiate that is metabolized chiefly through glucuronidation by uridine diphosphate glucuronosyl transferase (UGT) enzymes in the liver. These enzymes produce an active analgesic metabolite and a potentially toxic metabolite. In vivo drug-drug interaction studies with morphine are few, but they do suggest that inhibition or induction of UGT enzymes could alter morphine and its metabolite levels. These interactions could change analgesic efficacy. Hydromorphone and oxymorphone, close synthetic derivatives of morphine, are also metabolized primarily by UGT enzymes. Hydromorphone may have a toxic metabolite similar to morphine. In vivo drug-drug interaction studies with hydromorphone and oxymorphone have not been done, so it is difficult to make conclusions with these drugs.

  9. Interactive model evaluation tool based on IPython notebook

    Science.gov (United States)

    Balemans, Sophie; Van Hoey, Stijn; Nopens, Ingmar; Seuntjes, Piet

    2015-04-01

    In hydrological modelling, some kind of parameter optimization is mostly performed. This can be the selection of a single best parameter set, a split in behavioural and non-behavioural parameter sets based on a selected threshold or a posterior parameter distribution derived with a formal Bayesian approach. The selection of the criterion to measure the goodness of fit (likelihood or any objective function) is an essential step in all of these methodologies and will affect the final selected parameter subset. Moreover, the discriminative power of the objective function is also dependent from the time period used. In practice, the optimization process is an iterative procedure. As such, in the course of the modelling process, an increasing amount of simulations is performed. However, the information carried by these simulation outputs is not always fully exploited. In this respect, we developed and present an interactive environment that enables the user to intuitively evaluate the model performance. The aim is to explore the parameter space graphically and to visualize the impact of the selected objective function on model behaviour. First, a set of model simulation results is loaded along with the corresponding parameter sets and a data set of the same variable as the model outcome (mostly discharge). The ranges of the loaded parameter sets define the parameter space. A selection of the two parameters visualised can be made by the user. Furthermore, an objective function and a time period of interest need to be selected. Based on this information, a two-dimensional parameter response surface is created, which actually just shows a scatter plot of the parameter combinations and assigns a color scale corresponding with the goodness of fit of each parameter combination. Finally, a slider is available to change the color mapping of the points. Actually, the slider provides a threshold to exclude non behaviour parameter sets and the color scale is only attributed to the

  10. User-evaluated Gestures for Touchless Interactions from a Distance

    NARCIS (Netherlands)

    Fikkert, F.W.; van der Vet, P.E.; Nijholt, Antinus

    2010-01-01

    Very big displays are now commonplace but interactions with them are limited, even poorly understood. Recently, understanding touch-based interactions have received a great deal of attention due to the popularity and low costs of these displays. The direct extension of such interactions, touch less

  11. Modelling operator cognitive interactions in nuclear power plant safety evaluation

    International Nuclear Information System (INIS)

    Senders, J.W.; Moray, N.; Smiley, A.; Sellen, A.

    1985-08-01

    The overall objectives of the study were to review methods which are applicable to the analysis of control room operator cognitive interactions in nuclear plant safety evaluations and to indicate where future research effort in this area should be directed. This report is based on an exhaustive search and review of the literature on NPP (Nuclear Power Plant) operator error, human error, human cognitive function, and on human performance. A number of methods which have been proposed for the estimation of data for probabilistic risk analysis have been examined and have been found wanting. None addresses the problem of diagnosis error per se. Virtually all are concerned with the more easily detected and identified errors of action. None addresses underlying cause and mechanism. It is these mechanisms which must be understood if diagnosis errors and other cognitive errors are to be controlled and predicted. We have attempted to overcome the deficiencies of earlier work and have constructed a model/taxonomy, EXHUME, which we consider to be exhaustive. This construct has proved to be fruitful in organizing our thinking about the kinds of error that can occur and the nature of self-correcting mechanisms, and has guided our thinking in suggesting a research program which can provide the data needed for quantification of cognitive error rates and of the effects of mitigating efforts. In addition a preliminary outline of EMBED, a causal model of error, is given based on general behavioural research into perception, attention, memory, and decision making. 184 refs

  12. [Does implementation of benchmarking in quality circles improve the quality of care of patients with asthma and reduce drug interaction?].

    Science.gov (United States)

    Kaufmann-Kolle, Petra; Szecsenyi, Joachim; Broge, Björn; Haefeli, Walter Emil; Schneider, Antonius

    2011-01-01

    The purpose of this cluster-randomised controlled trial was to evaluate the efficacy of quality circles (QCs) working either with general data-based feedback or with an open benchmark within the field of asthma care and drug-drug interactions. Twelve QCs, involving 96 general practitioners from 85 practices, were randomised. Six QCs worked with traditional anonymous feedback and six with an open benchmark. Two QC meetings supported with feedback reports were held covering the topics "drug-drug interactions" and "asthma"; in both cases discussions were guided by a trained moderator. Outcome measures included health-related quality of life and patient satisfaction with treatment, asthma severity and number of potentially inappropriate drug combinations as well as the general practitioners' satisfaction in relation to the performance of the QC. A significant improvement in the treatment of asthma was observed in both trial arms. However, there was only a slight improvement regarding inappropriate drug combinations. There were no relevant differences between the group with open benchmark (B-QC) and traditional quality circles (T-QC). The physicians' satisfaction with the QC performance was significantly higher in the T-QCs. General practitioners seem to take a critical perspective about open benchmarking in quality circles. Caution should be used when implementing benchmarking in a quality circle as it did not improve healthcare when compared to the traditional procedure with anonymised comparisons. Copyright © 2011. Published by Elsevier GmbH.

  13. Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, Part II.

    Science.gov (United States)

    Armstrong, Scott C; Cozza, Kelly L

    2003-01-01

    Pharmacokinetic drug-drug interactions with codeine, dihydrocodeine, hydrocodone, oxycodone, and buprenorphine are reviewed in this column. These compounds have a very similar chemical structure to morphine. Unlike morphine, which is metabolized chiefly through conjugation reactions with uridine diphosphate glucuronosyl transferase (UGT) enzymes, these five drugs are metabolized both through oxidative reactions by the cytochrome P450 (CYP450) enzyme and conjugation by UGT enzymes. There is controversy as to whether codeine, dihydrocodeine, and hydrocodone are actually prodrugs requiring activation by the CYP450 2D6 enzyme or UGT enzymes. Oxycodone and buprenorphine, however, are clearly not prodrugs and are metabolized by the CYP450 2D6 and 3A4 enzymes, respectively. Knowledge of this metabolism assists in the understanding for the potential of drug-drug interactions with these drugs. This understanding is important so that clinicians can choose the proper dosages for analgesia and anticipate potential drug-drug interactions.

  14. A test to evaluation non-linear soil structure interaction

    International Nuclear Information System (INIS)

    Hagiwara, T.; Kitada, Y.

    2005-01-01

    JNES is planning a new project to study non-linear soil-structure interaction (SSI) effect under large earthquake ground motions equivalent to and/or over a design earthquake ground motion of S2. Concerning the SSI test, it is pointed out that handling of the scale effect of the specimen taking into account the surrounding soil on the earthquake response evaluation to the actual structure is essential issue for the scaled model test. Thus, for the test, the largest specimen possible and the biggest input motion possible are necessary. Taking into account the above issues, new test methodology, which utilizes artificial earthquake ground motion, is considered desirable if it can be performed at a realistic cost. With this motivation, we have studied the test methodology which applying blasting power as for a big earthquake ground motion. The information from a coalmine company in the U.S.A. indicates that the works performed in the surface coalmine to blast a rock covering a coal layer generates a big artificial ground motion, which is similar to earthquake ground motion. Application of this artificial earthquake ground motion for the SSI test is considered very promising because the blasting work is carried out periodically for mining coal so that we can apply artificial motions generated by the work if we construct a building model at a closed point to the blasting work area. The major purposes of the test are to understand (a) basic earthquake response characteristics of a Nuclear Power Plant (NPP) reactor building when a large earthquake strikes the NPP site and (b) nonlinear characteristics of SSI phenomenon during a big earthquake. In the paper of ICONE-13, we will introduce the test method and basic characteristics of measured artificial ground motions generated by the blasting works on an actual site. (authors)

  15. Self-Consistent Criteria for Evaluation of Neutron Interaction

    International Nuclear Information System (INIS)

    Henry, H.F.; Newlon, C.E.; Knight, J.R.

    2007-01-01

    New safe interaction criteria for containers of fissionable materials handled at the Oak Ridge Gaseous Diffusion Plant have been developed on the basis of an interaction theory using the basic concepts of a safe solid angle subtended by interacting containers, and the multiplication factor as determined by two-group theory for an individually safe containers The calculated results agree satisfactorily with experimental data obtained with identical interacting units involving both cylinders and slabs containing highly enriched uranium, the core compositions of which were varied between H/U-235 atomic ratios of 44.3 and 337. The application of the derived interaction criteria to items containing material with low moderation or low U-235 assay, and to containers for which nuclear safety is dependent upon control of the U-235 mass or U-235 concentration is discussed.

  16. Introduction to a Protein Interaction System Used for Quantitative Evaluation of Biomolecular Interactions

    OpenAIRE

    Yamniuk, Aaron

    2013-01-01

    A central goal of molecular biology is the determination of biomolecular function. This comes largely from a knowledge of the non-covalent interactions that biological small and macro-molecules experience. The fundamental mission of the Molecular Interactions Research Group (MIRG) of the ABRF is to show how solution biophysical tools are used to quantitatively characterize molecular interactions, and to educate the ABRF members and scientific community on the utility and limitations of core t...

  17. Students' Evaluation of Classroom Interactions of Their Biology ...

    African Journals Online (AJOL)

    Nekky Umera

    teacher classroom interactions were positively correlated and uncertainty, ... implementation is that, if biology teachers were to display more leadership, helpful and ... Accepted methods to overcome poor academic achievement in science have ... activities and experiences through which teachers; curriculum, materials, and.

  18. Evaluation of Mobile Phones for Large Display Interaction

    OpenAIRE

    Bauer, Jens; Thelen, Sebastian; Ebert, Achim

    2012-01-01

    Large displays have become more and more common in the last few years. While interaction with these displays can be conducted using standard methods such as computer mouse and keyboard, this approach causes issues in multi-user environments, where the various conditions for providing multiple keyboards and mice, together with the facilities to employ them, cannot be met. To solve this problem, interaction using mobile phones was proposed by several authors. Previous solutions were specialized...

  19. Iatrogenic cushing syndrome secondary to a probable interaction between voriconazole and budesonide.

    Science.gov (United States)

    Jones, Whitney; Chastain, Cody A; Wright, Patty W

    2014-07-01

    Oral budesonide is commonly used for the management of Crohn's disease given its high affinity for glucocorticoid receptors and low systemic activity due to extensive first-pass metabolism through hepatic cytochrome P450 (CYP) 3A4. Voriconazole, a second-generation triazole antifungal agent, is both a substrate and potent inhibitor of CYP isoenzymes, specifically CYP2C19, CYP2C9, and CYP3A4; thus, the potential for drug-drug interactions with voriconazole is high. To our knowledge, drug-drug interactions between voriconazole and corticosteroids have not been specifically reported in the literature. We describe a 48-year-old woman who was receiving oral budesonide 9 mg/day for the management of Crohn's disease and was diagnosed with fluconazole-resistant Candida albicans esophagitis; oral voriconazole 200 mg every 12 hours for 3 weeks was prescribed for treatment. Because the patient experienced recurrent symptoms of dysphagia, a second 3-week course of voriconazole therapy was taken. Seven weeks after originally being prescribed voriconazole, she came to her primary care clinic with elevated blood pressure, lower extremity edema, and weight gain; she was prescribed a diuretic and evaluated for renal dysfunction. At a follow-up visit 6 weeks later with her specialty clinic, the patient's blood pressure was elevated, and her physical examination was notable for moon facies, posterior cervical fat pad prominence, and lower extremity pitting edema. Iatrogenic Cushing syndrome due to a drug-drug interaction between voriconazole and budesonide was suspected, and voriconazole was discontinued. Budesonide was continued as previously prescribed for her Crohn's disease. On reevaluation 2 months later, the patient's Cushingoid features had markedly regressed. To our knowledge, this is the first published case report of iatrogenic Cushing syndrome due to a probable interaction between voriconazole and oral budesonide. In patients presenting with Cushingoid features who

  20. Evaluation of a potential transporter-mediated drug interaction between rosuvastatin and pradigastat, a novel DGAT-1 inhibitor.

    Science.gov (United States)

    Kulmatycki, Kenneth; Hanna, Imad; Meyers, Dan; Salunke, Atish; Movva, Aishwarya; Majumdar, Tapan; Natrillo, Adrienne; Vapurcuyan, Arpine; Rebello, Sam; Sunkara, Gangadhar; Chen, Jin

    2015-05-01

    An in vitro drugdrug interaction (DDI) study was performed to assess the potential for pradigastat to inhibit breast cancer resistance protein (BCRP), organic anion-transporting polypeptide (OATP), and organic anion transporter 3 (OAT3) transport activities. To understand the relevance of these in vitro findings, a clinical pharmacokinetic DDI study using rosuvastatin as a BCRP, OATP, and OAT3 probe substrate was conducted. The study used cell lines that stably expressed or over-expressed the respective transporters. The clinical study was an open-label, single sequence study where subjects (n = 36) received pradigastat (100 mg once daily x 3 days thereafter 40 mg once daily) and rosuvastatin (10 mg once daily), alone and in combination. Pradigastat inhibited BCRP-mediated efflux activity in a dose-dependent fashion in a BCRP over-expressing human ovarian cancer cell line with an IC(50) value of 5 μM. Similarly, pradigastat inhibited OATP1B1, OATP1B3 (estradiol 17β glucuronide transport), and OAT3 (estrone 3 sulfate transport) activity in a concentrationdependent manner with estimated IC(50) values of 1.66 ± 0.95 μM, 3.34 ± 0.64 μM, and 0.973 ± 0.11 μM, respectively. In the presence of steady state pradigastat concentrations, AUC(τ, ss) of rosuvastatin was unchanged and its Cmax,ss decreased by 14% (5.30 and 4.61 ng/mL when administered alone and coadministered with pradigastat, respectively). Pradigastat AUC(τ, ss) and C(max, ss) were unchanged when coadministered with rosuvastatin at steady state. Both rosuvastatin and pradigastat were well tolerated. These data indicate no clinically relevant pharmacokinetic interaction between pradigastat and rosuvastatin.

  1. EVALUATING AUSTRALIAN FOOTBALL LEAGUE PLAYER CONTRIBUTIONS USING INTERACTIVE NETWORK SIMULATION

    Directory of Open Access Journals (Sweden)

    Jonathan Sargent

    2013-03-01

    Full Text Available This paper focuses on the contribution of Australian Football League (AFL players to their team's on-field network by simulating player interactions within a chosen team list and estimating the net effect on final score margin. A Visual Basic computer program was written, firstly, to isolate the effective interactions between players from a particular team in all 2011 season matches and, secondly, to generate a symmetric interaction matrix for each match. Negative binomial distributions were fitted to each player pairing in the Geelong Football Club for the 2011 season, enabling an interactive match simulation model given the 22 chosen players. Dynamic player ratings were calculated from the simulated network using eigenvector centrality, a method that recognises and rewards interactions with more prominent players in the team network. The centrality ratings were recorded after every network simulation and then applied in final score margin predictions so that each player's match contribution-and, hence, an optimal team-could be estimated. The paper ultimately demonstrates that the presence of highly rated players, such as Geelong's Jimmy Bartel, provides the most utility within a simulated team network. It is anticipated that these findings will facilitate optimal AFL team selection and player substitutions, which are key areas of interest to coaches. Network simulations are also attractive for use within betting markets, specifically to provide information on the likelihood of a chosen AFL team list "covering the line".

  2. Visualization of acoustic particle interaction and agglomeration: Theory evaluation

    International Nuclear Information System (INIS)

    Hoffmann, T.L.; Koopmann, G.H.

    1997-01-01

    In this paper experimentally observed trajectories of particles undergoing acoustically induced interaction and agglomeration processes are compared to and validated with numerically generated trajectories based on existing agglomeration theories. Models for orthokinetic, scattering, mutual radiation pressure, and hydrodynamic particle interaction are considered in the analysis. The characteristic features of the classical orthokinetic agglomeration hypothesis, such as collision processes and agglomerations due to the relative entrainment motion, are not observed in the digital images. The measured entrainment rates of the particles are found to be consistently lower than the theoretically predicted values. Some of the experiments reveal certain characteristics which may possibly be related to mutual scattering interaction. The study's most significant discovery is the so-called tuning fork agglomeration [T. L. Hoffmann and G. H. Koopmann, J. Acoust. Soc. Am. 99, 2130 endash 2141 (1996)]. It is shown that this phenomenon contradicts the theories for mutual scattering interaction and mutual radiation pressure interaction, but agrees with the acoustic wake effect model in its intrinsic feature of attraction between particles aligned along the acoustic axis. A model by Dianov et al. [Sov. Phys. Acoust. 13 (3), 314 endash 319 (1968)] is used to describe this effect based on asymmetric flow fields around particles under Oseen flow conditions. It is concluded that this model is consistent with the general characteristics of the tuning fork agglomerations, but lacks certain refinements with respect to accurate quantification of the effect. copyright 1997 Acoustical Society of America

  3. Drug interaction databases in medical literature

    DEFF Research Database (Denmark)

    Kongsholm, Gertrud Gansmo; Nielsen, Anna Katrine Toft; Damkier, Per

    2015-01-01

    PURPOSE: It is well documented that drug-drug interaction databases (DIDs) differ substantially with respect to classification of drug-drug interactions (DDIs). The aim of this study was to study online available transparency of ownership, funding, information, classifications, staff training...... available transparency of ownership, funding, information, classifications, staff training, and underlying documentation varies substantially among various DIDs. Open access DIDs had a statistically lower score on parameters assessed....... and the three most commonly used subscription DIDs in the medical literature. The following parameters were assessed for each of the databases: Ownership, classification of interactions, primary information sources, and staff qualification. We compared the overall proportion of yes/no answers from open access...

  4. Standard problems to evaluate soil structure interaction computer codes

    International Nuclear Information System (INIS)

    Miller, C.A.; Costantino, C.J.; Philippacopoulos, A.J.

    1979-01-01

    The seismic response of nuclear power plant structures is often calculated using lumped parameter methods. A finite element model of the structure is coupled to the soil with a spring-dashpot system used to represent the interaction process. The parameters of the interaction model are based on analytic solutions to simple problems which are idealizations of the actual problems of interest. The objective of the work reported in this paper is to compare predicted responses using the standard lumped parameter models with experimental data. These comparisons are shown to be good for a fairly uniform soil system and for loadings which do not result in nonlinear interaction effects such as liftoff. 7 references, 7 figures

  5. Empirical evaluation of neutral interactions in host-parasite networks.

    Science.gov (United States)

    Canard, E F; Mouquet, N; Mouillot, D; Stanko, M; Miklisova, D; Gravel, D

    2014-04-01

    While niche-based processes have been invoked extensively to explain the structure of interaction networks, recent studies propose that neutrality could also be of great importance. Under the neutral hypothesis, network structure would simply emerge from random encounters between individuals and thus would be directly linked to species abundance. We investigated the impact of species abundance distributions on qualitative and quantitative metrics of 113 host-parasite networks. We analyzed the concordance between neutral expectations and empirical observations at interaction, species, and network levels. We found that species abundance accurately predicts network metrics at all levels. Despite host-parasite systems being constrained by physiology and immunology, our results suggest that neutrality could also explain, at least partially, their structure. We hypothesize that trait matching would determine potential interactions between species, while abundance would determine their realization.

  6. Evaluating DEM results with FEM perspectives of load : soil interaction

    NARCIS (Netherlands)

    Tadesse, D.

    2004-01-01

    Keywords: Load - soil interaction, soil structure, soil mechanical properties, FEM (Finite Element Method), Plaxis (Finite Element Code), granular particles, shear stress, DEM (Distinct Element Method),

  7. Towards a standard on evaluation of tactile/haptic interactions

    NARCIS (Netherlands)

    Sinclair, I.; Carter, J.; Kassner, S.; Erp, J.B.F. van; Weber, G.; Elliott, L.; Andrew, I.

    2012-01-01

    Tactile and haptic interaction is becoming increasingly important; ergonomic standards can ensure that systems are designed with sufficient concern for ergonomics and interoperability. ISO (through working group TC159/SC4/WG9) is developing international standards in this subject area, dual-tracked

  8. Mood swings: design and evaluation of affective interactive art

    NARCIS (Netherlands)

    Bialoskorski, Leticia S.S.; Westerink, Joyce H.D.M.; van den Broek, Egon

    2009-01-01

    The field of affective computing is concerned with developing emphatic products, such as affective consumer products, affective games, and affective art. This paper describes Mood Swings, an affective interactive art system, which interprets and visualizes affect expressed by a person. Mood Swings

  9. Nonunion of acetabular fractures: evaluation with interactive multiplanar CT

    International Nuclear Information System (INIS)

    Kuhlman, J.E.; Fishman, E.K.; Ney, D.R.; Brooker, A.F. Jr.; Magid, D.

    1989-01-01

    Nonunions involving fractures of the acetabulum are reportedly rare, with few citings and little discussion in the literature. It is possible that acetabular nonunions go undetected because imaging of the acetabulum is difficult by conventional radiography. We report two cases of fracture nonunion involving the weight-bearing surface of the acetabulum diagnosed with the aid of computed tomography (CT) and a newly developed interactive 2D/3D orthotool that uniquely processes and reformats routine CT data. The interactive 2D/3D orthotool is a sophisticated computer program that allows dynamic viewing of standard multiplanar reconstructions in the axial, coronal, and sagittal planes as well as multiple oblique projections. The 2D/3D orthotool provides on screen correlation of two-dimensional multiplanar images with three-dimensional reconstructions of the pelvis. The authors found this capability ideally suited for studying fractures with off-axis orientation such as those through the acetabular dome, greatly facilitating the diagnosis of nonunion

  10. Evaluating Interactions of Forest Conservation Policies on Avoided Deforestation

    Science.gov (United States)

    Robalino, Juan; Sandoval, Catalina; Barton, David N.; Chacon, Adriana; Pfaff, Alexander

    2015-01-01

    We estimate the effects on deforestation that have resulted from policy interactions between parks and payments and between park buffers and payments in Costa Rica between 2000 and 2005. We show that the characteristics of the areas where protected and unprotected lands are located differ significantly. Additionally, we find that land characteristics of each of the policies and of the places where they interact also differ significantly. To adequately estimate the effects of the policies and their interactions, we use matching methods. Matching is implemented not only to define adequate control groups, as in previous research, but also to define those groups of locations under the influence of policies that are comparable to each other. We find that it is more effective to locate parks and payments away from each other, rather than in the same location or near each other. The high levels of enforcement inside both parks and lands with payments, and the presence of conservation spillovers that reduce deforestation near parks, significantly reduce the potential impact of combining these two policies. PMID:25909323

  11. Evaluating interactions of forest conservation policies on avoided deforestation.

    Science.gov (United States)

    Robalino, Juan; Sandoval, Catalina; Barton, David N; Chacon, Adriana; Pfaff, Alexander

    2015-01-01

    We estimate the effects on deforestation that have resulted from policy interactions between parks and payments and between park buffers and payments in Costa Rica between 2000 and 2005. We show that the characteristics of the areas where protected and unprotected lands are located differ significantly. Additionally, we find that land characteristics of each of the policies and of the places where they interact also differ significantly. To adequately estimate the effects of the policies and their interactions, we use matching methods. Matching is implemented not only to define adequate control groups, as in previous research, but also to define those groups of locations under the influence of policies that are comparable to each other. We find that it is more effective to locate parks and payments away from each other, rather than in the same location or near each other. The high levels of enforcement inside both parks and lands with payments, and the presence of conservation spillovers that reduce deforestation near parks, significantly reduce the potential impact of combining these two policies.

  12. Evaluating interactions of forest conservation policies on avoided deforestation.

    Directory of Open Access Journals (Sweden)

    Juan Robalino

    Full Text Available We estimate the effects on deforestation that have resulted from policy interactions between parks and payments and between park buffers and payments in Costa Rica between 2000 and 2005. We show that the characteristics of the areas where protected and unprotected lands are located differ significantly. Additionally, we find that land characteristics of each of the policies and of the places where they interact also differ significantly. To adequately estimate the effects of the policies and their interactions, we use matching methods. Matching is implemented not only to define adequate control groups, as in previous research, but also to define those groups of locations under the influence of policies that are comparable to each other. We find that it is more effective to locate parks and payments away from each other, rather than in the same location or near each other. The high levels of enforcement inside both parks and lands with payments, and the presence of conservation spillovers that reduce deforestation near parks, significantly reduce the potential impact of combining these two policies.

  13. Assessment of Social Competence in an Evaluation-Interaction Analogue

    Science.gov (United States)

    Steffen, John J.; Redden, Joan

    1977-01-01

    Discusses a study designed to explore behavior changes in subjects' performances as a function of evaluative feedback and examines the relations between judgements of physical attractiveness and social competence. (MH)

  14. Adverse effects and Drug Interactions Associated with Inhaled Recreational and Medical Marijuana

    Directory of Open Access Journals (Sweden)

    Maisha Kelly Freeman

    2016-06-01

    Full Text Available Objectives: To provide an overview of the addiction potential; adverse effects (e.g., cardiovascular, immune dysfunction, respiratory system, mental health disorders; drug interactions; effects of accidental exposure; crime statistics; and pharmacist’s considerations for the use of inhaled medical marijuana. Methods: A PubMed search was conducted from 1966 to March 2016 to identify articles in which the safety of inhaled medical marijuana was assessed. Key MeSH search terms included medical marijuana with a subheading for adverse effect. Only articles in adult patients were considered. In addition, medical marijuana or cannabis plus one of the following search terms were searched: drug interactions, herb-drug interactions, drug-related side effects and adverse drug reactions, substance-related disorders, addiction, and abuse. A free-text search was also conducted to identify articles not included in the MeSH term search. A bibliographic search was also conducted. Articles were included if they addressed adverse effects of medical marijuana for the treatment of a condition. Meta-analyses, randomized controlled clinical trials, and case reports were included in the review if the primary focus of the article related to the adverse effect profile of inhaled medical marijuana. Medical marijuana efficacy studies were not assessed. In the absence of this information, case reports or reports of inhaled recreational marijuana use was used. Studies were excluded if published in languages other than English. In addition, studies highlighting mechanisms of action, studies of pharmacodynamics or pharmacokinetic effects were excluded, unless these effects were due to drug-drug interactions. Prescription products containing marijuana or derivatives were excluded from evaluation. An Internet search was conducted to locate the most up-to-date information on the laws concerning medical marijuana. Key findings: A PubMed search revealed 58 articles and 28 of

  15. Evaluation of conservatism in analysis of fuel-coolant interaction

    International Nuclear Information System (INIS)

    Reynolds, A.B.; Erdman, C.A.; Garner, P.L.; Haas, P.M.; Allen, C.L.

    Using the ANL parametric model developed by Cho e.a. the following mechanisms and parameters involved in fuel-coolant interaction were examined: coherence of fuel-sodium mixing; two-phase heat transfer; sodium-to-fuel mass ratio; fuel particle size; heat transfer to plenum and core cladding; constraint geometry. Both overpower and loss-of-flow transients were studied. Main attention is given to the maximum mechanical work to be expected. As a general conclusion, it can be stated that more realistic models will result in a reduction of the estimated mechanical work

  16. Evaluating an interactive voice response system for persons with disabilities

    CSIR Research Space (South Africa)

    Greeff, M

    2008-11-01

    Full Text Available -evaluated before the next iteration. During the re-evaluation its current fitness value is compared with its previous fitness value, i.e. its fitness value after the previous iteration. If the two values differ more than a specified value, 2922 978... when the true POF is unknown. The size of the non-dominated solution set can also be used to measure an algorithm’s performance [18]. Ca´mara et al. proposed measures of accuracy, stability and reaction capacity of an algorithm, that are based...

  17. Initial evaluation of an interactive test of sentence gist recognition.

    Science.gov (United States)

    Tye-Murray, N; Witt, S; Castelloe, J

    1996-12-01

    The laser videodisc-based Sentence Gist Recognition (SGR) test consists of sets of topically related sentences that are cued by short film clips. Clients respond to test items by selecting picture illustrations and may interact with the talker by using repair strategies when they do not recognize a test item. The two experiments, involving 40 and 35 adult subjects, respectively, indicated that the SGR may better predict subjective measures of speechreading and listening performance than more traditional audiologic sentence and nonsense syllable tests. Data from cochlear implant users indicated that the SGR accounted for a greater percentage of the variance for selected items of the Communication Profile for the Hearing-Impaired and the Speechreading Questionnaire for Cochlear-Implant Users than two other audiologic tests. As in previous work, subjects were most apt to ask the talker to repeat an utterance that they did not recognize than to ask the talker to restructure it. It is suggested that the SGR may reflect the interactive nature of conversation and provide a simulated real-world listening and/or speechreading task. The principles underlaying this test are consistent with the development of other computer technologies and concepts, such as compact discinteractive and virtual reality.

  18. Evaluating Dialogue Competence in Naturally Occurring Child-Child Interactions

    Science.gov (United States)

    Naerland, Terje

    2011-01-01

    The principal aim of this paper is to contribute to the pursuit of evaluating pragmatic language competence in preschool years by observation-based data. Initially, the relations between age and language development measured as mean length of utterance (MLU) and three dialogue skills are described. The occurrences of "focus on the dialogue…

  19. Experimental evaluation of human-system interaction on alarm design

    International Nuclear Information System (INIS)

    Huang, F.-H.; Lee, Y.-L.; Hwang, S.-L.; Yenn, T.-C.; Yu, Y.-C.; Hsu, C.-C.; Huang, H.-W.

    2007-01-01

    This study evaluates the practicability of automatic reset alarm system in Fourth Nuclear Power Plant (FNPP) of Taiwan. The features of auto-reset alarm system include dynamic prioritization of all alarm signals and fast system reset. Two experiments were conducted to evaluate the effect of automatic/manual reset on operation time, situational awareness (SA), task load index (TLX), and subjective ratings. All participants, including Experts and Novices, took part in the experiment on the alarm system simulator with Load Rejection procedure. The experimental results imply that the auto-reset alarm system may be applied in an advanced control room under Load Rejection procedure, because all participants' operation time were reduced as well as Novice's SA were raised up. Nevertheless, to ensure operating safety in FNPP, the effects of the auto-reset alarm system in other procedures/special situations still need to be tested in the near future

  20. The development of evaluation methodology for advanced interactive communication

    International Nuclear Information System (INIS)

    Okamoto, K.

    2005-01-01

    Face-to-face communication is one of the essential style of communication. Trough face-to-face communication, people exchange much information at a time, both verbal and non-verbal information, which is most effective to learn each other. The authors focused on the face-to-face communication, and developed an evaluation method to quantify the effectiveness of communication. We regard conversation as an exchange of keywords. The effectiveness of conversation is valued by the amount of the keywords, and the achievement of mutual understandings. Through two people's face-to-face communication, the author quantified the shared information by measuring the change of the amount of the participants' knowledge. The participants' knowledge is counted by the words they can give. We measured the change in their shared knowledge (number of the words they gave associated to the theme). And we also quantified the discords in their understandings against their partners by measuring the discords between the knowledge that they think they share and the knowledge that they really share. Through these data, we evaluate the effectiveness of communication and analyzed the trends of mutual understanding. (authors)

  1. Evaluation of the transporter-mediated herb-drug interaction potential of DA-9801, a standardized dioscorea extract for diabetic neuropathy, in human in vitro and rat in vivo.

    Science.gov (United States)

    Song, Im-Sook; Kong, Tae Yeon; Jeong, Hyeon-Uk; Kim, Eun Nam; Kwon, Soon-Sang; Kang, Hee Eun; Choi, Sang-Zin; Son, Miwon; Lee, Hye Suk

    2014-07-17

    Drug transporters play important roles in the absorption, distribution, and elimination of drugs and thereby, modulate drug efficacy and toxicity. With a growing use of poly pharmacy, concurrent administration of herbal extracts that modulate transporter activities with drugs can cause serious adverse reactions. Therefore, prediction and evaluation of drug-drug interaction potential is important in the clinic and in the drug development process. DA-9801, comprising a mixed extract of Dioscoreae rhizoma and Dioscorea nipponica Makino, is a new standardized extract currently being evaluated for diabetic peripheral neuropathy in a phase II clinical study. The inhibitory effects of DA-9801 on the transport functions of organic cation transporter (OCT)1, OCT2, organic anion transporter (OAT)1, OAT3, organic anion transporting polypeptide (OATP)1B1, OATP1B3, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP) were investigated in HEK293 or LLC-PK1 cells. The effects of DA-9801 on the pharmacokinetics of relevant substrate drugs of these transporters were also examined in vivo in rats. DA-9801 inhibited the in vitro transport activities of OCT1, OCT2, OAT3, and OATP1B1, with IC50 values of 106, 174, 48.1, and 273 μg/mL, respectively, while the other transporters were not inhibited by 300 μg/mL DA-9801. To investigate whether this inhibitory effect of DA-9801 on OCT1, OCT2, and OAT3 could change the pharmacokinetics of their substrates in vivo, we measured the pharmacokinetics of cimetidine, a substrate for OCT1, OCT2, and OAT3, and of furosemide, a substrate for OAT1 and OAT3, by co-administration of DA-9801 at a single oral dose of 1,000 mg/kg. Pre-dose of DA-9801 5 min or 2 h prior to cimetidine administration decreased the Cmax of cimetidine in rats. However, DA-9801 did not affect the elimination parameters such as half-life, clearance, or amount excreted in the urine, suggesting that it did not inhibit elimination process of cimetidine, which is

  2. Evaluation of osprey habitat suitability and interaction with contaminant exposure

    Science.gov (United States)

    Toschik, P.C.; Christman, M.C.; Rattner, B.A.; Ottinger, M.A.

    2006-01-01

    Ospreys (Pandion haliaetus) have been the focus of conservation efforts since their dramatic population decline attributed to dichlorodiphenyltrichloroethane and related chemicals in the 1960s. Several recent studies of ospreys nesting in the United States have indicated improved reproduction. However, the density of breeding ospreys varies greatly among locations, with some areas seemingly habitable but not occupied. Because of concerns about pollution in the highly industrialized portions of the Delaware River and Bay, USA, we evaluated contaminant exposure and productivity in ospreys nesting on the Delaware River and Bay in 2002. We characterized habitat in the coastal zone of Delaware, USA, and the area around the river in Pennsylvania, USA, using data we collected as well as extant information provided by state and federal sources. We characterized habitat based on locations of occupied osprey nests in Delaware and Pennsylvania. We evaluated water clarity, water depth, land use and land cover, nest availability, and contaminants in sediment for use in a nest-occupancy model. Our results demonstrated that the presence of occupied nests was associated with water depth, water clarity, distance to an occupied osprey nest, and presence of urban land use, whereas a companion study demonstrated that hatching success was associated with the principal components derived from organochlorine-contaminant concentrations in osprey eggs (total polychlorinated biphenyls, p,p'-dichlorodiphenylethylene, chlordane and metabolites, and heptachlor epoxide). Our study provides guidelines for resource managers and local conservation organizations in management of ospreys and in development of habitat models that are appropriate for other piscivorous and marsh-nesting birds.

  3. Development and Evaluation of an Interactive WebQuest Environment: "Web Macerasi"

    Science.gov (United States)

    Gulbahar, Yasemin; Madran, R. Orcun; Kalelioglu, Filiz

    2010-01-01

    This study was conducted to develop a web-based interactive system, Web Macerasi, for teaching-learning and evaluation purposes, and to find out the possible effects of this system. The study has two stages. In the first stage, a WebQuest site was designed as an interactive system in which various Internet and web technologies were used for…

  4. Studying Interaction in Undergraduate Tutorials: Results from a Small-Scale Evaluation

    Science.gov (United States)

    Shaw, Lorraine; Carey, Phil; Mair, Michael

    2008-01-01

    This article reports on an observation-based evaluation of student-tutor interaction in first-year undergraduate tutorials. Using a single case analysis, the paper looks at how tutors and students built and maintained relationships through two different though interlinked forms of interaction--storytelling and the use of classroom space for…

  5. Evaluation Criteria for Interactive E-Books for Open and Distance Learning

    Science.gov (United States)

    Bozkurt, Aras; Bozkaya, Mujgan

    2015-01-01

    The aim of this mixed method study is to identify evaluation criteria for interactive e-books. To find answers for the research questions of the study, both quantitative and qualitative data were collected through a four-round Delphi study with a panel consisting of 30 experts. After that, a total of 20 interactive e-books were examined with…

  6. Role of cytochrome P450 in drug interactions

    Directory of Open Access Journals (Sweden)

    Bibi Zakia

    2008-10-01

    Full Text Available Abstract Drug-drug interactions have become an important issue in health care. It is now realized that many drug-drug interactions can be explained by alterations in the metabolic enzymes that are present in the liver and other extra-hepatic tissues. Many of the major pharmacokinetic interactions between drugs are due to hepatic cytochrome P450 (P450 or CYP enzymes being affected by previous administration of other drugs. After coadministration, some drugs act as potent enzyme inducers, whereas others are inhibitors. However, reports of enzyme inhibition are very much more common. Understanding these mechanisms of enzyme inhibition or induction is extremely important in order to give appropriate multiple-drug therapies. In future, it may help to identify individuals at greatest risk of drug interactions and adverse events.

  7. Drug interactions between common illicit drugs and prescription therapies.

    Science.gov (United States)

    Lindsey, Wesley T; Stewart, David; Childress, Darrell

    2012-07-01

    The aim was to summarize the clinical literature on interactions between common illicit drugs and prescription therapies. Medline, Iowa Drug Information Service, International Pharmaceutical Abstracts, EBSCO Academic Search Premier, and Google Scholar were searched from date of origin of database to March 2011. Search terms were cocaine, marijuana, cannabis, methamphetamine, amphetamine, ecstasy, N-methyl-3,4-methylenedioxymethamphetamine, methylenedioxymethamphetamine, heroin, gamma-hydroxybutyrate, sodium oxybate, and combined with interactions, drug interactions, and drug-drug interactions. This review focuses on established clinical evidence. All applicable full-text English language articles and abstracts found were evaluated and included in the review as appropriate. The interactions of illicit drugs with prescription therapies have the ability to potentiate or attenuate the effects of both the illicit agent and/or the prescription therapeutic agent, which can lead to toxic effects or a reduction in the prescription agent's therapeutic activity. Most texts and databases focus on theoretical or probable interactions due to the kinetic properties of the drugs and do not fully explore the pharmacodynamic and clinical implications of these interactions. Clinical trials with coadministration of illicit drugs and prescription drugs are discussed along with case reports that demonstrate a potential interaction between agents. The illicit drugs discussed are cocaine, marijuana, amphetamines, methylenedioxymethamphetamine, heroin, and sodium oxybate. Although the use of illicit drugs is widespread, there are little experimental or clinical data regarding the effects of these agents on common prescription therapies. Potential drug interactions between illicit drugs and prescription drugs are described and evaluated on the Drug Interaction Probability Scale by Horn and Hansten.

  8. Questionnaires for eliciting evaluation data from users of interactive question answering

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, Diane; Kantor, Paul B.; Morse, Emile; Scholtz, Jean; Sun, Y.

    2009-01-01

    Evaluating interactive question answering (QA) systems with real users can be challenging because traditional evaluation measures based on the relevance of items returned are difficult to employ since relevance judgments can be unstable in multi-user evaluations. The work reported in this paper evaluates, in distinguishing among a set of interactive QA systems, the effectiveness of three questionnaires: a Cognitive Workload Questionnaire (NASA TLX), and Task and System Questionnaires customized to a specific interactive QA application. These Questionnaires were evaluated with four systems, seven analysts, and eight scenarios during a 2-week workshop. Overall, results demonstrate that all three Questionnaires are effective at distinguishing among systems, with the Task Questionnaire being the most sensitive. Results also provide initial support for the validity and reliability of the Questionnaires.

  9. Combinations of Methods for Collaborative Evaluation of the Usability of Interactive Software Systems

    Directory of Open Access Journals (Sweden)

    Andrés Solano

    2016-01-01

    Full Text Available Usability is a fundamental quality characteristic for the success of an interactive system. It is a concept that includes a set of metrics and methods in order to obtain easy-to-learn and easy-to-use systems. Usability Evaluation Methods, UEM, are quite diverse; their application depends on variables such as costs, time availability, and human resources. A large number of UEM can be employed to assess interactive software systems, but questions arise when deciding which method and/or combination of methods gives more (relevant information. We propose Collaborative Usability Evaluation Methods, CUEM, following the principles defined by the Collaboration Engineering. This paper analyzes a set of CUEM conducted on different interactive software systems. It proposes combinations of CUEM that provide more complete and comprehensive information about the usability of interactive software systems than those evaluation methods conducted independently.

  10. The influence of intention and outcome on evaluations of social interaction.

    Science.gov (United States)

    Wu, Xiaoying; Hua, Rui; Yang, Zhangxiang; Yin, Jun

    2018-01-01

    Reading and making sense of social interactions between individuals is an important part of our daily social lives. Given that actions tend to be interpreted in terms of intent within the observed outcome, we investigated how intent and outcome interactively influence evaluations of social interactions. Through visual animations, intent was operationalized as an agent's (i.e., actor's) act intentionally or unintentionally having an influence on another agent (i.e., affectee). In Experiment 1, the act was helpful and the consequences brought small or great benefits to the affectee. In Experiment 2, the act was harmful and brought small or great losses to the affectee. We found that for both helpful and harmful contexts, social interaction evaluations were influenced by an interaction between the intent and outcome of the act. Specifically, great help/harm (i.e., the great-benefits or great-losses condition) was rated as a stronger social interaction than small help/harm, and the difference was larger in the intentional condition than in the unintentional condition. Furthermore, regardless of the interaction valence, the effect of the intent was larger than the effect of the outcome when evaluating social interaction. This result suggests that observers consider the intent and outcome jointly when evaluating a given social interaction, and the intent has a privileged role in this process. These findings are consistent with the idea that the intent is often deemed to be the cause driving the effect of outcome, and they help us to understand how social interactions are constructed within the action understanding system. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. SecondLife as an Evaluation Platform for Multiagent Systems Featuring Social Interactions

    DEFF Research Database (Denmark)

    Rehm, Matthias; Rosina, Peter

    2008-01-01

    In this paper we propose to use SecondLife as an evaluation environment for multiagent systems that model social group dynamics and social interactions. To this end we developed a control interface for NPCs in SecondLife that allows for running supervised or unsupervised long-term evaluations. Thus...

  12. Automated applications of sandwich-cultured hepatocytes in the evaluation of hepatic drug transport.

    Science.gov (United States)

    Perry, Cassandra H; Smith, William R; St Claire, Robert L; Brouwer, Kenneth R

    2011-04-01

    Predictions of the absorption, distribution, metabolism, excretion, and toxicity of compounds in pharmaceutical development are essential aspects of the drug discovery process. B-CLEAR is an in vitro system that uses sandwich-cultured hepatocytes to evaluate and predict in vivo hepatobiliary disposition (hepatic uptake, biliary excretion, and biliary clearance), transporter-based hepatic drug-drug interactions, and potential drug-induced hepatotoxicity. Automation of predictive technologies is an advantageous and preferred format in drug discovery. In this study, manual and automated studies are investigated and equivalence is demonstrated. In addition, automated applications using model probe substrates and inhibitors to assess the cholestatic potential of drugs and evaluate hepatic drug transport are examined. The successful automation of this technology provides a more reproducible and less labor-intensive approach, reducing potential operator error in complex studies and facilitating technology transfer.

  13. Pharmacovigilance Evaluation of the Association Between DPP-4 Inhibitors and Heart Failure: Stimulated Reporting and Moderation by Drug Interactions.

    Science.gov (United States)

    Fadini, Gian Paolo; Sarangdhar, Mayur; Avogaro, Angelo

    2018-04-01

    In the SAVOR-TIMI trial, the risk of heart failure (HF) was increased by 27% in T2D patients randomized to the dipeptidyl peptidase-4 inhibitor (DPP4i) saxagliptin. Other studies have provided inconsistent results regarding this association. Herein, we performed a pharmacovigilance analysis of the rate of HF associated with DPP4is, focusing on stimulated reporting and moderation by drug-drug interactions. We mined the FDA adverse event (AE) reporting system (FAERS) from 2004q1 to 2017q3, including a total of 9906,642 AE reports. Rates (/1000 reports) of HF within the reports for DPP4is and reports for other antidiabetic drugs were calculated for the period up to 2013q3 (date of publication of the SAVOR-TIMI trial results) and from 2013q4 to 2017q3. Analyses were refined by filtering according to therapeutic area, concomitant diseases and drugs, and competing AEs. The rate of HF among the AE reports filed for DPP4is significantly increased after 2013q3, especially for saxagliptin. When compared to non-insulin non-glitazone antidiabetic drugs, the proportional reporting ratio (PRR) of HF for DPP4is was 0.62 (95% CI 0.56-0.68) up to 2013q3 and 2.12 (95% CI 1.96-2.28) from 2013q4 to 2017q3. This stimulated reporting was consistent in subanalyses based on the presence/absence of cardiac disorders and after controlling for competing AEs. The rate of HF among AE reports for DPP4is was modestly moderated by the concomitant use of metformin (- 15%) and strongly moderated by the concomitant use of SGLT2 inhibitors (- 63%), even after excluding competing AEs. Within the FAERS, the association between HF and DPP4is was biased by stimulated reporting, implying that the publication of the SAVOR-TIMI trial and the subsequent regulatory warnings primed clinicians to report HF events in DPP4i users as drug-related AEs. The rate of HF associated with DPP4is was moderated when they were used in combination with SGLT2 inhibitors.

  14. Evaluation of pedestrian safety at intersections: A theoretical framework based on pedestrian-vehicle interaction patterns.

    Science.gov (United States)

    Ni, Ying; Wang, Menglong; Sun, Jian; Li, Keping

    2016-11-01

    Pedestrians are the most vulnerable road users, and pedestrian safety has become a major research focus in recent years. Regarding the quality and quantity issues with collision data, conflict analysis using surrogate safety measures has become a useful method to study pedestrian safety. However, given the inequality between pedestrians and vehicles in encounters and the multiple interactions between pedestrians and vehicles, it is insufficient to simply use the same indicator(s) or the same way to aggregate indicators for all conditions. In addition, behavioral factors cannot be neglected. To better use information extracted from trajectories for safety evaluation and pay more attention on effects of behavioral factors, this paper develops a more sophisticated framework for pedestrian conflict analysis that takes pedestrian-vehicle interactions into consideration. A concept of three interaction patterns has been proposed for the first time, namely "hard interaction," "no interaction," and "soft-interaction." Interactions have been categorized under one of these patterns by analyzing profiles of speed and conflict indicators during the whole interactive processes. In this paper, a support vector machine (SVM) approach has been adopted to classify severity levels for a dataset including 1144 events extracted from three intersections in Shanghai, China, followed by an analysis of variable importance. The results revealed that different conflict indicators have different contributions to indicating the severity level under various interaction patterns. Therefore, it is recommended either to use specific conflict indicators or to use weighted indicator aggregation for each interaction pattern when evaluating pedestrian safety. The implementation has been carried out at the fourth crosswalk, and the results indicate that the proposed method can achieve a higher accuracy and better robustness than conventional methods. Furthermore, the method is helpful for better

  15. Pharmacokinetics and pharmacodynamics of 3,4-methylenedioxymethamphetamine (MDMA): interindividual differences due to polymorphisms and drug-drug interactions

    NARCIS (Netherlands)

    Rietjens, S.J.; Hondebrink, L.; Westerink, R.H.S.; Meulenbelt, J.

    2012-01-01

    Clinical outcome following 3,4-methylenedioxymethamphetamine (MDMA) intake ranges from mild entactogenic effects to a life-threatening intoxication. Despite ongoing research, the clinically most relevant mechanisms causing acute MDMA-induced adverse effects remain largely unclear. This complicates

  16. Thermodynamic and kinetic approaches for evaluation of monoclonal antibody - Lipoprotein interactions.

    Science.gov (United States)

    Multia, Evgen; Sirén, Heli; Andersson, Karl; Samuelsson, Jörgen; Forssén, Patrik; Fornstedt, Torgny; Öörni, Katariina; Jauhiainen, Matti; Riekkola, Marja-Liisa

    2017-02-01

    Two complementary instrumental techniques were used, and the data generated was processed with advanced numerical tools to investigate the interactions between anti-human apoB-100 monoclonal antibody (anti-apoB-100 Mab) and apoB-100 containing lipoproteins. Partial Filling Affinity Capillary Electrophoresis (PF-ACE) combined with Adsorption Energy Distribution (AED) calculations provided information on the heterogeneity of the interactions without any a priori model assumptions. The AED calculations evidenced a homogenous binding site distribution for the interactions. Quartz Crystal Microbalance (QCM) studies were used to evaluate thermodynamics and kinetics of the Low-Density Lipoprotein (LDL) and anti-apoB-100 Mab interactions. High affinity and selectivity were observed, and the emerging data sets were analysed with so called Interaction Maps. In thermodynamic studies, the interaction between LDL and anti-apoB-100 Mab was found to be predominantly enthalpy driven. Both techniques were also used to study antibody interactions with Intermediate-Density (IDL) and Very Low-Density (VLDL) Lipoproteins. By screening affinity constants for IDL-VLDL sample in a single injection we were able to distinguish affinity constants for both subpopulations using the numerical Interaction Map tool. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. NSAID-antihypertensive drug interactions: Which outpatients are at risk for a rise in systolic blood pressure?

    NARCIS (Netherlands)

    Floor-Schreudering, Annemieke; De Smet, Peter Agm; Buurma, Henk; Kramers, Cornelis; Tromp, P. Chris; Belitser, Svetlana V.; Bouvy, Marcel L.

    2015-01-01

    Background: Management guidelines for drug-drug interactions between non-steroidal anti-inflammatory drugs (NSAIDs) and antihypertensives recommend blood pressure monitoring in hypertensive patients. We measured the short-term effect of initiating NSAIDs on systolic blood pressure (SBP) in users of

  18. NSAID-antihypertensive drug interactions: which outpatients are at risk for a rise in systolic blood pressure?

    NARCIS (Netherlands)

    Floor-Schreudering, A.; Smet, P.A.G.M. de; Buurma, H.; Kramers, C.; Tromp, P.C.; Belitser, S.V.; Bouvy, M.L.

    2015-01-01

    BACKGROUND: Management guidelines for drug-drug interactions between non-steroidal anti-inflammatory drugs (NSAIDs) and antihypertensives recommend blood pressure monitoring in hypertensive patients. We measured the short-term effect of initiating NSAIDs on systolic blood pressure (SBP) in users of

  19. An Evaluation-Driven Design Approach to Develop Learning Environments Based on Full-Body Interaction

    Science.gov (United States)

    Malinverni, Laura; Schaper, Marie-Monique; Pares, Narcís

    2016-01-01

    The development of learning environments based on full-body interaction has become an increasingly important field of research in recent years. However, the design and evaluation strategies currently used present some significant limitations. Two major shortcomings are: the inadequate involvement of children in the design process and a lack of…

  20. Proposing an Evaluation Framework for Interventions: Focusing on Students' Behaviours in Interactive Science Exhibitions

    Science.gov (United States)

    Hauan, Nils Petter; DeWitt, Jennifer; Kolstø, Stein Dankert

    2017-01-01

    Materials designed for self-guided experiences such as worksheets and digital applications are widely used as tools to enable interactive science exhibitions to support students' progress towards conceptual understanding. However, there is a need to find expedient ways to evaluate the quality of educational experiences resulting from the use of…

  1. Evaluating Treatments for Functionally Equivalent Problem Behavior Maintained by Adult Compliance with Mands during Interactive Play

    Science.gov (United States)

    Schmidt, Jonathan D.; Bednar, Mary K.; Willse, Lena V.; Goetzel, Amanda L.; Concepcion, Anthony; Pincus, Shari M.; Hardesty, Samantha L.; Bowman, Lynn G.

    2017-01-01

    A primary goal of behavioral interventions is to reduce dangerous or inappropriate behavior and to generalize treatment effects across various settings. However, there is a lack of research evaluating generalization of treatment effects while individuals with functionally equivalent problem behavior interact with each other. For the current study,…

  2. An Interactive Web-Based Program for Stepfamilies: Development and Evaluation of Efficacy

    Science.gov (United States)

    Gelatt, Vicky A.; Adler-Baeder, Francesca; Seeley, John R.

    2010-01-01

    This study evaluated the efficacy of a family life education program for stepfamilies that is self-administered, interactive, and web-based. The program uses behavior-modeling videos to demonstrate effective couple, parenting, and stepparenting practices. A diverse sample of 300 parents/stepparents of a child aged 11-15 years were randomized into…

  3. Evaluation of Two Methods for Modeling Measurement Errors When Testing Interaction Effects with Observed Composite Scores

    Science.gov (United States)

    Hsiao, Yu-Yu; Kwok, Oi-Man; Lai, Mark H. C.

    2018-01-01

    Path models with observed composites based on multiple items (e.g., mean or sum score of the items) are commonly used to test interaction effects. Under this practice, researchers generally assume that the observed composites are measured without errors. In this study, we reviewed and evaluated two alternative methods within the structural…

  4. Pre-evaluation and interactive editing of B-spline and GERBS curves and surfaces

    Science.gov (United States)

    Laksâ, Arne

    2017-12-01

    Interactive computer based geometry editing is very useful for designers and artists. Our goal has been to develop useful tools for geometry editing in a way that increases the ability for creative design. When we interactively editing geometry, we want to see the change happening gradually and smoothly on the screen. Pre-evaluation is a tool for increasing the speed of the graphics when doing interactive affine operation on control points and control surfaces. It is then possible to add details on surfaces, and change shape in a smooth and continuous way. We use pre-evaluation on basis functions, on blending functions and on local surfaces. Pre-evaluation can be made hierarchi-cally and is thus useful for local refinements. Sampling and plotting of curves, surfaces and volumes can today be handled by the GPU and it is therefore important to have a structured organization and updating system to be able to make interactive editing as smooth and user friendly as possible. In the following, we will show a structure for pre-evaluation and an optimal organisation of the computation and we will show the effect of implementing both of these techniques.

  5. A study of the use of simulated work task situations in interactive information retrieval evaluations

    DEFF Research Database (Denmark)

    Borlund, Pia

    2016-01-01

    Purpose – The purpose of this paper is to report a study of how the test instrument of a simulated work task situation is used in empirical evaluations of interactive information retrieval (IIR) and reported in the research literature. In particular, the author is interested to learn whether....... The paper addresses the need to carefully design and tailor simulated work task situations to suit the test participants in order to obtain the intended authentic and realistic IIR under study. Keywords Interactive information retrieval study, IIR study, Test design, Simulated work task situations, Meta-evaluation...... situations in IIR evaluations. In particular, with respect to the design and creation of realistic simulated work task situations. There is a lack of tailoring of the simulated work task situations to the test participants. Likewise, the requirement to include the test participants’ personal information...

  6. Responsiveness to physicians' requests for information concerning drug interactions: a comparison of brand and generic companies.

    Science.gov (United States)

    Thomas, M; Lexchin, J

    1990-01-01

    Research-based pharmaceutical companies maintain that there are important differences between themselves and their generic competitors. Prominent among them is an alleged greater ability to provide accurate and rapid responses to requests from physicians for information about drug products. This study evaluates pharmaceutical company behavior with regard to these issues. Two drug-drug interactions were identified, along with all of the companies in Canada marketing any of the four drugs involved. Each company received a letter describing symptoms suggestive of an interaction in a patient taking its particular product and the relevant second drug. The companies were asked if they were aware of any evidence of an interaction involving the two drugs. They were also asked to provide references regarding the interaction. Responses were received from all companies contacted except one. There were no significant differences (in the hypothesized direction) between the generic and brand companies with regard to either the accuracy or promptness of the response, or the usefulness of the references cited. On the contrary, generic firms were markedly quicker to respond than were brand manufacturers. The latter were slightly more likely to acknowledge evidence of an adverse drug interaction, and to provide useful references to relevant published research.

  7. INTERACT

    DEFF Research Database (Denmark)

    Jochum, Elizabeth; Borggreen, Gunhild; Murphey, TD

    This paper considers the impact of visual art and performance on robotics and human-computer interaction and outlines a research project that combines puppetry and live performance with robotics. Kinesics—communication through movement—is the foundation of many theatre and performance traditions ...

  8. Evaluation for the design of experience in virtual environments: modeling breakdown of interaction and illusion.

    Science.gov (United States)

    Marsh, T; Wright, P; Smith, S

    2001-04-01

    New and emerging media technologies have the potential to induce a variety of experiences in users. In this paper, it is argued that the inducement of experience presupposes that users are absorbed in the illusion created by these media. Looking to another successful visual medium, film, this paper borrows from the techniques used in "shaping experience" to hold spectators' attention in the illusion of film, and identifies what breaks the illusion/experience for spectators. This paper focuses on one medium, virtual reality (VR), and advocates a transparent or "invisible style" of interaction. We argue that transparency keeps users in the "flow" of their activities and consequently enhances experience in users. Breakdown in activities breaks the experience and subsequently provides opportunities to identify and analyze potential causes of usability problems. Adopting activity theory, we devise a model of interaction with VR--through consciousness and activity--and introduce the concept of breakdown in illusion. From this, a model of effective interaction with VR is devised and the occurrence of breakdown in interaction and illusion is identified along a continuum of engagement. Evaluation guidelines for the design of experience are proposed and applied to usability problems detected in an empirical study of a head-mounted display (HMD) VR system. This study shows that the guidelines are effective in the evaluation of VR. Finally, we look at the potential experiences that may be induced in users and propose a way to evaluate user experience in virtual environments (VEs) and other new and emerging media.

  9. Event Generators for Simulating Heavy Ion Interactions of Interest in Evaluating Risks in Human Spaceflight

    Science.gov (United States)

    Wilson, Thomas L.; Pinsky, Lawrence; Andersen, Victor; Empl, Anton; Lee, Kerry; Smirmov, Georgi; Zapp, Neal; Ferrari, Alfredo; Tsoulou, Katerina; Roesler, Stefan; hide

    2005-01-01

    Simulating the Space Radiation environment with Monte Carlo Codes, such as FLUKA, requires the ability to model the interactions of heavy ions as they penetrate spacecraft and crew member's bodies. Monte-Carlo-type transport codes use total interaction cross sections to determine probabilistically when a particular type of interaction has occurred. Then, at that point, a distinct event generator is employed to determine separately the results of that interaction. The space radiation environment contains a full spectrum of radiation types, including relativistic nuclei, which are the most important component for the evaluation of crew doses. Interactions between incident protons with target nuclei in the spacecraft materials and crew member's bodies are well understood. However, the situation is substantially less comfortable for incident heavier nuclei (heavy ions). We have been engaged in developing several related heavy ion interaction models based on a Quantum Molecular Dynamics-type approach for energies up through about 5 GeV per nucleon (GeV/A) as part of a NASA Consortium that includes a parallel program of cross section measurements to guide and verify this code development.

  10. MATERNAL DEPRESSION AND ATTACHMENT: THE EVALUATION OF MOTHER-CHILD INTERACTIONS DURING FEEDING PRACTICE

    Directory of Open Access Journals (Sweden)

    Alessandra eSantona

    2015-08-01

    Full Text Available Internal working models of attachment (IWM can moderate the effect of maternal depression on mother-child interactions and child development. Clinical depression pre-dating birthgiving has been found to predict incoherent and less sensitive caregiving. Dysfunctional patterns observed, included interactive modes linked to feeding behaviors which may interfere with hunger-satiation biological rhythms and the establishment of children’s autonomy and individuation. Feeding interactions between depressed mothers and their children seem to be characterized by repetitive interactive failures: children refuse food through oppositional behavior or negativity. The aim of this study was to investigate parenting skills in the context of feeding in mothers with major depression from the point of view of attachment theory. This perspective emphasises parents’ emotion, relational and affective history and personal resources. The sample consisted of 60 mother-child dyads. Mothers were divided into two groups: 30 with Major Depression and 30 without disorders. Children’s age ranged between 12 and 36 months The measures employed were the Adult Attachment Interview and the Scale for the Evaluation of Alimentary Interactions between Mothers and Children. Insecure attachment prevailed in mothers with major depression,, with differences on the Subjective Experience and State of Mind Scales. Groups also differed in maternal sensitivity, degrees of interactive

  11. Evaluations of antimony and strontium interaction in an Al–Si–Cu–Zn die cast alloy

    Energy Technology Data Exchange (ETDEWEB)

    Farahany, Saeed, E-mail: saeedfarahany@gmail.com; Idris, Mohd Hasbullah; Ourdjini, Ali

    2014-05-01

    Graphical abstract: - Highlights: • Probable interactions between Sb and Sr in a complex Al–Si alloy were evaluated. • Sequence of addition did not affect thermal and microscopical characteristics. • Threshold ratio for the Sb and Sr interaction is proposed. - Abstract: The interaction between antimony and strontium in an ADC12 die casting alloy is investigated comprehensively by using a computer aided cooling curve thermal analysis coupled with microstructure inspection. The results of the thermal analysis show significant changes in Al–Si eutectic reaction based on different concentrations of Sb and Sr. Sb reduces the efficiency of Sr in modifying the eutectic Si. Based upon the data obtained in this study, the threshold Sr/Sb ratio should exceed about 0.5 in order to obtain fully modified structure. Moreover, a pre-eutectic reaction of Al{sub 2}Si{sub 2}Sr intermetallic was detected for high concentrations of Sr.

  12. A communicational framework for evaluating interaction with IT by analyzing user-reception of electronic texts

    DEFF Research Database (Denmark)

    Wentzer, Helle

    2006-01-01

    Interpreting IT as a medium for continuous communication across time and place of the communicators offers a way of analyzing the effect of IT in concrete practices. The users’ readings determine the actual communication with IT. A poetics of how meaning is translated from one person to another...... through semiotic texts is presented, termed the poetics of the e-text. The poetics of the e-text offers a meta-communicational framework for identifying user constraints in the possibilities of interacting with the system. Identifying communicational problems with ICT-mediated interactions again offer...... grounds for redesigning and re-author the e-text. The poetics of the e-text are subsequently applied as a method of analyzing user-reception and evaluating the interaction with ICT. Examples are given from user-receptions of collaborating with ICT in home care, Denmark....

  13. Protein structure modelling and evaluation based on a 4-distance description of side-chain interactions

    Directory of Open Access Journals (Sweden)

    Inbar Yuval

    2010-07-01

    Full Text Available Abstract Background Accurate evaluation and modelling of residue-residue interactions within and between proteins is a key aspect of computational structure prediction including homology modelling, protein-protein docking, refinement of low-resolution structures, and computational protein design. Results Here we introduce a method for accurate protein structure modelling and evaluation based on a novel 4-distance description of residue-residue interaction geometry. Statistical 4-distance preferences were extracted from high-resolution protein structures and were used as a basis for a knowledge-based potential, called Hunter. We demonstrate that 4-distance description of side chain interactions can be used reliably to discriminate the native structure from a set of decoys. Hunter ranked the native structure as the top one in 217 out of 220 high-resolution decoy sets, in 25 out of 28 "Decoys 'R' Us" decoy sets and in 24 out of 27 high-resolution CASP7/8 decoy sets. The same concept was applied to side chain modelling in protein structures. On a set of very high-resolution protein structures the average RMSD was 1.47 Å for all residues and 0.73 Å for buried residues, which is in the range of attainable accuracy for a model. Finally, we show that Hunter performs as good or better than other top methods in homology modelling based on results from the CASP7 experiment. The supporting web site http://bioinfo.weizmann.ac.il/hunter/ was developed to enable the use of Hunter and for visualization and interactive exploration of 4-distance distributions. Conclusions Our results suggest that Hunter can be used as a tool for evaluation and for accurate modelling of residue-residue interactions in protein structures. The same methodology is applicable to other areas involving high-resolution modelling of biomolecules.

  14. Roles of biomarkers in evaluating interactions among mixtures of lead, cadmium and arsenic

    International Nuclear Information System (INIS)

    Wang Gensheng; Fowler, Bruce A.

    2008-01-01

    Human exposure to environmental chemicals is most correctly characterized as exposure to mixtures of these agents. The metals/metalloids, lead (Pb), cadmium (Cd), and arsenic (As), are among the leading toxic agents detected in the environment. Exposure to these elements, particularly at chronic low dose levels, is still a major public health concern. Concurrent exposure to Pb, Cd, or As may produce additive or synergistic interactions or even new effects that are not seen in single component exposures. Evaluating these interactions on a mechanistic basis is essential for risk assessment and management of metal/metalloid mixtures. This paper will review a number of individual studies that addressed interactions of these metals/metalloids in both experimental and human exposure studies with particular emphasis on biomarkers. In general, co-exposure to metal/metalloid mixtures produced more severe effects at both relatively high dose and low dose levels in a biomarker-specific manner. These effects were found to be mediated by dose, duration of exposure and genetic factors. While traditional endpoints, such as morphological changes and biochemical parameters for target organ toxicity, were effective measures for evaluating the toxicity of high dose metal/metalloid mixtures, biomarkers for oxidative stress, altered heme biosynthesis parameters, and stress proteins showed clear responses in evaluating toxicity of low dose metal/metalloid mixtures. Metallothionein, heat shock proteins, and glutathione are involved in regulating interactive effects of metal/metalloid mixtures at low dose levels. These findings suggest that further studies on interactions of these metal/metalloid mixtures utilizing biomarker endpoints are highly warranted

  15. Evaluation of virtual environment as a form of interactive resuscitation exam

    Science.gov (United States)

    Leszczyński, Piotr; Charuta, Anna; Kołodziejczak, Barbara; Roszak, Magdalena

    2017-10-01

    There is scientific evidence confirming the effectiveness of e-learning within resuscitation, however, there is not enough research on modern examination techniques within the scope. The aim of the pilot research is to compare the exam results in the field of Advanced Life Support in a traditional (paper) and interactive (computer) form as well as to evaluate satisfaction of the participants. A survey was conducted which meant to evaluate satisfaction of exam participants. Statistical analysis of the collected data was conducted at a significance level of α = 0.05 using STATISTICS v. 12. Final results of the traditional exam (67.5% ± 15.8%) differed significantly (p test. Significant differences between the results of a traditional test and the one supported by Computer Based Learning system showed the possibility of achieving a more detailed competence verification in the field of resuscitation thanks to interactive solutions.

  16. In vitro interaction of a novel neutrophil growth factor with human liver microsomal cytochromes P450 and the contribution of UDP-glucuronosyltransferases to its metabolism

    Czech Academy of Sciences Publication Activity Database

    Siller, M.; Anzenbacher, P.; Anzenbacherová, E.; Doležal, Karel; Strnad, Miroslav

    2011-01-01

    Roč. 41, č. 11 (2011), s. 934-944 ISSN 0049-8254 R&D Projects: GA ČR GA301/08/1649 Institutional research plan: CEZ:AV0Z50380511 Keywords : DRUG-DRUG INTERACTION S * SUBSTRATE-SPECIFICITY * R-ROSCOVITINE * GLUCURONIDATION * CELLS Subject RIV: EF - Botanics Impact factor: 1.791, year: 2011

  17. Numerical evaluation of energy barriers and magnetic relaxation in interacting nanostructured magnetic systems

    International Nuclear Information System (INIS)

    Chubykalo-Fesenko, Oksana A.; Chantrell, Roy W.

    2004-01-01

    We discuss a model to quantify long-time thermally induced magnetization reversal in magnetic systems with distributed properties. Two algorithms, based on kinetic and Metropolis Monte Carlo are introduced. While the former requires the constant recalculation of all energy barriers and is useful when the interactions are weak, the latter uses the Metropolis Monte Carlo to estimate the magnetization trajectory and, consequently, only the most probable transition rates are evaluated. The ridge optimization method is used to evaluate the energy barriers in a multidimensional energy landscape. The algorithms are applied to a granular system modeled by means of Voronoi polyhedra and having random in-plane anisotropy

  18. An evaluation of diverse methods of obtaining effective Schroedinger interaction potentials for elastic scattering

    International Nuclear Information System (INIS)

    Amos, K.; Allen, L.J.; Steward, C.; Hodgson, P.E.; Sofianos, S.A.

    1995-01-01

    Direct solution of the Schroedinger equation and inversion methods of analysis of elastic scattering data are considered to evaluate the information that they can provide about the physical interaction between colliding nuclear particles. It was found that both optical model and inversion methods based upon inverse scattering theories are subject to ambiguities. Therefore, it is essential that elastic scattering data analyses are consistent with microscopic calculations of the potential. 25 refs

  19. An evaluation of diverse methods of obtaining effective Schroedinger interaction potentials for elastic scattering

    Energy Technology Data Exchange (ETDEWEB)

    Amos, K.; Allen, L.J.; Steward, C. [Melbourne Univ., Parkville, VIC (Australia). School of Physics; Hodgson, P.E. [Oxford Univ. (United Kingdom). Dept. of Physics; Sofianos, S.A. [University of South Africa (UNISA), Pretoria (South Africa). Dept. of Physics

    1995-10-01

    Direct solution of the Schroedinger equation and inversion methods of analysis of elastic scattering data are considered to evaluate the information that they can provide about the physical interaction between colliding nuclear particles. It was found that both optical model and inversion methods based upon inverse scattering theories are subject to ambiguities. Therefore, it is essential that elastic scattering data analyses are consistent with microscopic calculations of the potential. 25 refs.

  20. The social-devaluation effect: Interactive evaluation deteriorates likeability of objects based on daily relationship

    Directory of Open Access Journals (Sweden)

    Atsunori eAriga

    2015-01-01

    Full Text Available Although previous research has explored the effects of discussion on optimal and collective group outcomes, it is unclear how an individual's preference for an object is modulated by discussion with others. This study investigated the determinants of likeability ratings under two conditions. In Experiment 1, pairs of participants consisting of friends evaluated various photographic images. Under the interactive condition, the participants discussed their impressions of each image for 30 seconds and then independently rated how much they liked it. Under the non-interactive condition, the participants did not interact with each other but instead only thought about their impressions of each image for 30 seconds before rating its likeability. The results indicate that the exchange of impressions between the participants affected the individual likeability ratings of objects. More specifically, the interactive participants generally rated the images as less likeable than did the non-interactive participants (social-devaluation effect. However, in Experiment 2, the effect was eliminated when the pairs consisted of strangers. These findings suggest that shared information modulates individual preferences but only when a daily relationship exists within a group.

  1. Evaluating display fidelity and interaction fidelity in a virtual reality game.

    Science.gov (United States)

    McMahan, Ryan P; Bowman, Doug A; Zielinski, David J; Brady, Rachael B

    2012-04-01

    In recent years, consumers have witnessed a technological revolution that has delivered more-realistic experiences in their own homes through high-definition, stereoscopic televisions and natural, gesture-based video game consoles. Although these experiences are more realistic, offering higher levels of fidelity, it is not clear how the increased display and interaction aspects of fidelity impact the user experience. Since immersive virtual reality (VR) allows us to achieve very high levels of fidelity, we designed and conducted a study that used a six-sided CAVE to evaluate display fidelity and interaction fidelity independently, at extremely high and low levels, for a VR first-person shooter (FPS) game. Our goal was to gain a better understanding of the effects of fidelity on the user in a complex, performance-intensive context. The results of our study indicate that both display and interaction fidelity significantly affect strategy and performance, as well as subjective judgments of presence, engagement, and usability. In particular, performance results were strongly in favor of two conditions: low-display, low-interaction fidelity (representative of traditional FPS games) and high-display, high-interaction fidelity (similar to the real world).

  2. Evaluation of crack interaction effect for in-plane surface cracks using elastic finite element analyses

    International Nuclear Information System (INIS)

    Huh, Nam Su; Choi, Suhn; Park, Keun Bae; Kim, Jong Min; Choi, Jae Boong; Kim, Young Jin

    2008-01-01

    The crack-tip stress fields and fracture mechanics assessment parameters, such as the elastic stress intensity factor and the elastic-plastic J-integral, for a surface crack can be significantly affected by adjacent cracks. Such a crack interaction effect due to multiple cracks can magnify the fracture mechanics assessment parameters. There are many factors to be considered, for instance the relative distance between adjacent cracks, crack shape and loading condition, to quantify a crack interaction effect on the fracture mechanics assessment parameters. Thus, the current guidance on a crack interaction effect (crack combination rule), including ASME Sec. XI, BS7910, British Energy R6 and API RP579, provide different rules for combining multiple surface cracks into a single surface crack. The present paper investigates a crack interaction effect by evaluating the elastic stress intensity factor of adjacent surface cracks in a plate along the crack front through detailed 3-dimensional elastic finite element analyses. The effects of the geometric parameters, the relative distance between cracks and the crack shape, on the stress intensity factor are systematically investigated. As for the loading condition, only axial tension is considered. Based on the elastic finite element results, the acceptability of the crack combination rules provided in the existing guidance was investigated, and the relevant recommendations on a crack interaction for in-plane surface cracks in a plate were discussed

  3. An Interactive Website to Reduce Sexual Risk Behavior: Process Evaluation of TeensTalkHealth.

    Science.gov (United States)

    Brady, Sonya S; Sieving, Renee E; Terveen, Loren G; Rosser, B R Simon; Kodet, Amy J; Rothberg, Vienna D

    2015-09-02

    Different theoretical frameworks support the use of interactive websites to promote sexual health. Although several Web-based interventions have been developed to address sexual risk taking among young people, no evaluated interventions have attempted to foster behavior change through moderated interaction among a virtual network of adolescents (who remain anonymous to one another) and health professionals. The objective was to conduct a summative process evaluation of TeensTalkHealth, an interactive sexual health website designed to promote condom use and other healthy decision making in the context of romantic and sexual relationships. Evaluation data were obtained from 147 adolescents who participated in a feasibility and acceptability study. Video vignettes, teen-friendly articles, and other content served as conversation catalysts between adolescents and health educators on message boards. Adolescents' perceptions that the website encouraged condom use across a variety of relationship situations were very high. Almost 60% (54/92, 59%) of intervention participants completed two-thirds or more of requested tasks across the 4-month intervention. Adolescents reported high levels of comfort, perceived privacy, ease of website access and use, and perceived credibility of health educators. Potential strategies to enhance engagement and completion of intervention tasks during future implementations of TeensTalkHealth are discussed, including tailoring of content, periodic website chats with health educators and anonymous peers, and greater incorporation of features from popular social networking websites. TeensTalkHealth is a feasible, acceptable, and promising approach to complement and enhance existing services for youth.

  4. Interactive contour delineation of organs at risk in radiotherapy: Clinical evaluation on NSCLC patients.

    Science.gov (United States)

    Dolz, J; Kirişli, H A; Fechter, T; Karnitzki, S; Oehlke, O; Nestle, U; Vermandel, M; Massoptier, L

    2016-05-01

    Accurate delineation of organs at risk (OARs) on computed tomography (CT) image is required for radiation treatment planning (RTP). Manual delineation of OARs being time consuming and prone to high interobserver variability, many (semi-) automatic methods have been proposed. However, most of them are specific to a particular OAR. Here, an interactive computer-assisted system able to segment various OARs required for thoracic radiation therapy is introduced. Segmentation information (foreground and background seeds) is interactively added by the user in any of the three main orthogonal views of the CT volume and is subsequently propagated within the whole volume. The proposed method is based on the combination of watershed transformation and graph-cuts algorithm, which is used as a powerful optimization technique to minimize the energy function. The OARs considered for thoracic radiation therapy are the lungs, spinal cord, trachea, proximal bronchus tree, heart, and esophagus. The method was evaluated on multivendor CT datasets of 30 patients. Two radiation oncologists participated in the study and manual delineations from the original RTP were used as ground truth for evaluation. Delineation of the OARs obtained with the minimally interactive approach was approved to be usable for RTP in nearly 90% of the cases, excluding the esophagus, which segmentation was mostly rejected, thus leading to a gain of time ranging from 50% to 80% in RTP. Considering exclusively accepted cases, overall OARs, a Dice similarity coefficient higher than 0.7 and a Hausdorff distance below 10 mm with respect to the ground truth were achieved. In addition, the interobserver analysis did not highlight any statistically significant difference, at the exception of the segmentation of the heart, in terms of Hausdorff distance and volume difference. An interactive, accurate, fast, and easy-to-use computer-assisted system able to segment various OARs required for thoracic radiation therapy has

  5. Learning objects and interactive whiteboards: a evaluation proposal of learning objects for mathematics teaching

    Directory of Open Access Journals (Sweden)

    Silvio Henrique Fiscarelli

    2016-05-01

    Full Text Available The current conditions of the classroom learning tend to be a one-way process based in teacher exposition, this make a negative impact on learning make it a mechanical and not meaningful activity. One possibility to improve the quality of teaching is to innovate methodologies and varying forms of presenting information to students, such as the use of technology in the teaching process. The Interactive Whiteboard (IBW is one of the technologies that are being implemented in Brazilian schools. One of the promising possibilities to add value to the use of LDI in classroom are "learning objects" (LO. However, one problem is that often the LO are not fully suited to the dynamics of IWB, whether functional or pedagogical point of view. The objective of this study is to analyze and propose a set of indicators that evaluate the learning objects for use in conjunction with Interactive Whiteboards. The selection and definition of evaluation indicators was carried from the literature review on the subject and based on LDI experiences of use in Municipal Elementary School. After defining the set of indicators was conducted a evaluation of a sample of 30 OA utilized to teaching mathematics in 3rd grade of elementary school. The results of the evaluation indicate that the proposed indicators are suitable for a pre-analysis of OA and assisting in the process of selection of these.

  6. Evaluating Otto the Auto: Does Engagement in an Interactive Website Improve Young Children's Transportation Safety?

    Science.gov (United States)

    Schwebel, David C; Johnston, Anna; Shen, Jiabin; Li, Peng

    2017-07-19

    Transportation-related injuries are a leading cause of pediatric death, and effective interventions are limited. Otto the Auto is a website offering engaging, interactive activities. We evaluated Otto among a sample of sixty-nine 4- and 5-year-old children, who participated in a randomized parallel group design study. Following baseline evaluation, children engaged with either Otto or a control website for 2 weeks and then were re-evaluated. Children who used Otto failed to show increases in transportation safety knowledge or behavior compared to the control group, although there was a dosage effect whereby children who engaged in the website more with parents gained safer behavior patterns. We conclude Otto may have some efficacy when engaged by children with their parents, but continued efforts to develop and refine engaging, effective, theory-driven strategies to teach children transportation safety, including via internet, should be pursued.

  7. Subjective evaluation of physical and mental workload interactions across different muscle groups.

    Science.gov (United States)

    Mehta, Ranjana K; Agnew, Michael J

    2015-01-01

    Both physical and mental demands, and their interactions, have been shown to increase biomechanical loading and physiological reactivity as well as impair task performance. Because these interactions have shown to be muscle-dependent, the aim of this study was to determine the sensitivity of the NASA Task Load Index (NASA TLX) and Ratings of Perceived Exertion (RPE) to evaluate physical and mental workload during muscle-specific tasks. Twenty-four participants performed upper extremity and low back exertions at three physical workload levels in the absence and presence of a mental stressor. Outcome measures included RPE and NASA TLX (six sub-scales) ratings. The findings indicate that while both RPEs and NASA TLX ratings were sensitive to muscle-specific changes in physical demand, only an additional mental stressor and its interaction with either physical demand or muscle groups influenced the effort sub-scale and overall workload scores of the NASA TLX. While additional investigations in actual work settings are warranted, the NASA TLX shows promise in evaluating perceived workload that is sensitive not only to physical and mental demands but also sensitive in determining workload for tasks that employ different muscle groups.

  8. Evaluating interaction energies of weakly bonded systems using the Buckingham-Hirshfeld method

    Science.gov (United States)

    Krishtal, A.; Van Alsenoy, C.; Geerlings, P.

    2014-05-01

    We present the finalized Buckingham-Hirshfeld method (BHD-DFT) for the evaluation of interaction energies of non-bonded dimers with Density Functional Theory (DFT). In the method, dispersion energies are evaluated from static multipole polarizabilities, obtained on-the-fly from Coupled Perturbed Kohn-Sham calculations and partitioned into diatomic contributions using the iterative Hirshfeld partitioning method. The dispersion energy expression is distributed over four atoms and has therefore a higher delocalized character compared to the standard pairwise expressions. Additionally, full multipolar polarizability tensors are used as opposed to effective polarizabilities, allowing to retain the anisotropic character at no additional computational cost. A density dependent damping function for the BLYP, PBE, BP86, B3LYP, and PBE0 functionals has been implemented, containing two global parameters which were fitted to interaction energies and geometries of a selected number of dimers using a bi-variate RMS fit. The method is benchmarked against the S22 and S66 data sets for equilibrium geometries and the S22x5 and S66x8 data sets for interaction energies around the equilibrium geometry. Best results are achieved using the B3LYP functional with mean average deviation values of 0.30 and 0.24 kcal/mol for the S22 and S66 data sets, respectively. This situates the BHD-DFT method among the best performing dispersion inclusive DFT methods. Effect of counterpoise correction on DFT energies is discussed.

  9. GIS-Based Evaluation of Spatial Interactions by Geographic Disproportionality of Industrial Diversity

    Directory of Open Access Journals (Sweden)

    Jemyung Lee

    2017-11-01

    Full Text Available Diversity of regional industry is regarded as a key factor for regional development, as it has a positive relationship with economic stability, which attracts population. This paper focuses on how the spatial imbalance of industrial diversity contributes to the population change caused by inter-regional migration. This paper introduces a spatial interaction model for the Geographic Information System (GIS-based simulation of the spatial interactions to evaluate the demographic attraction force. The proposed model adopts the notions of gravity, entropy, and virtual work. An industrial classification by profit level is introduced and its diversity is quantified with the entropy of information theory. The introduced model is applied to the cases of 207 regions in South Korea. Spatial interactions are simulated with an optimized model and their resultant forces, the demographic attraction forces, are compared with observed net migration for verification. The results show that the evaluated attraction forces from industrial diversity have a very significant, positive, and moderate relationship with net migration, while other conventional factors of industry, population, economy, and the job market do not. This paper concludes that the geographical quality of industrial diversity has positive and significant effects on population change by migration.

  10. Evaluation of the interaction of surfactants with stratum corneum model membrane from Bothrops jararaca by DSC.

    Science.gov (United States)

    Baby, André Rolim; Lacerda, Aurea Cristina Lemos; Velasco, Maria Valéria Robles; Lopes, Patrícia Santos; Kawano, Yoshio; Kaneko, Telma Mary

    2006-07-06

    The interaction of surfactants sodium dodecyl sulfate (SDS), cetyl trimethyl ammonium chloride (CTAC) and lauryl alcohol ethoxylated (12 mol ethylene oxide) (LAE-12OE) was evaluated on the stratum corneum (SC) of shed snake skins from Bothrops jararaca, used as model membrane, and thermal characterized by differential scanning calorimetry (DSC). Surfactant solutions were employed above of the critical micellar concentration (CMC) with treatment time of 8h. The SDS interaction with the SC model membrane has increased the characteristic transition temperature of 130 degrees C in approximately 10 degrees C for the water loss and keratin denaturation, indicating an augmentation of the water content. Samples treated with CTAC have a decrease of the water loss temperature, while, for the LAE-12OE treated samples, changes on the transition temperature have not been observed.

  11. Evaluating the Effects of Immersive Embodied Interaction on Cognition in Virtual Reality

    Science.gov (United States)

    Parmar, Dhaval

    Virtual reality is on its advent of becoming mainstream household technology, as technologies such as head-mounted displays, trackers, and interaction devices are becoming affordable and easily available. Virtual reality (VR) has immense potential in enhancing the fields of education and training, and its power can be used to spark interest and enthusiasm among learners. It is, therefore, imperative to evaluate the risks and benefits that immersive virtual reality poses to the field of education. Research suggests that learning is an embodied process. Learning depends on grounded aspects of the body including action, perception, and interactions with the environment. This research aims to study if immersive embodiment through the means of virtual reality facilitates embodied cognition. A pedagogical VR solution which takes advantage of embodied cognition can lead to enhanced learning benefits. Towards achieving this goal, this research presents a linear continuum for immersive embodied interaction within virtual reality. This research evaluates the effects of three levels of immersive embodied interactions on cognitive thinking, presence, usability, and satisfaction among users in the fields of science, technology, engineering, and mathematics (STEM) education. Results from the presented experiments show that immersive virtual reality is greatly effective in knowledge acquisition and retention, and highly enhances user satisfaction, interest and enthusiasm. Users experience high levels of presence and are profoundly engaged in the learning activities within the immersive virtual environments. The studies presented in this research evaluate pedagogical VR software to train and motivate students in STEM education, and provide an empirical analysis comparing desktop VR (DVR), immersive VR (IVR), and immersive embodied VR (IEVR) conditions for learning. This research also proposes a fully immersive embodied interaction metaphor (IEIVR) for learning of computational

  12. An Interactive Website to Reduce Sexual Risk Behavior: Process Evaluation of TeensTalkHealth

    Science.gov (United States)

    Sieving, Renee E; Terveen, Loren G; Rosser, BR Simon; Kodet, Amy J; Rothberg, Vienna D

    2015-01-01

    Background Different theoretical frameworks support the use of interactive websites to promote sexual health. Although several Web-based interventions have been developed to address sexual risk taking among young people, no evaluated interventions have attempted to foster behavior change through moderated interaction among a virtual network of adolescents (who remain anonymous to one another) and health professionals. Objective The objective was to conduct a summative process evaluation of TeensTalkHealth, an interactive sexual health website designed to promote condom use and other healthy decision making in the context of romantic and sexual relationships. Methods Evaluation data were obtained from 147 adolescents who participated in a feasibility and acceptability study. Video vignettes, teen-friendly articles, and other content served as conversation catalysts between adolescents and health educators on message boards. Results Adolescents’ perceptions that the website encouraged condom use across a variety of relationship situations were very high. Almost 60% (54/92, 59%) of intervention participants completed two-thirds or more of requested tasks across the 4-month intervention. Adolescents reported high levels of comfort, perceived privacy, ease of website access and use, and perceived credibility of health educators. Potential strategies to enhance engagement and completion of intervention tasks during future implementations of TeensTalkHealth are discussed, including tailoring of content, periodic website chats with health educators and anonymous peers, and greater incorporation of features from popular social networking websites. Conclusions TeensTalkHealth is a feasible, acceptable, and promising approach to complement and enhance existing services for youth. PMID:26336157

  13. On the practice of ignoring center-patient interactions in evaluating hospital performance.

    Science.gov (United States)

    Varewyck, Machteld; Vansteelandt, Stijn; Eriksson, Marie; Goetghebeur, Els

    2016-01-30

    We evaluate the performance of medical centers based on a continuous or binary patient outcome (e.g., 30-day mortality). Common practice adjusts for differences in patient mix through outcome regression models, which include patient-specific baseline covariates (e.g., age and disease stage) besides center effects. Because a large number of centers may need to be evaluated, the typical model postulates that the effect of a center on outcome is constant over patient characteristics. This may be violated, for example, when some centers are specialized in children or geriatric patients. Including interactions between certain patient characteristics and the many fixed center effects in the model increases the risk for overfitting, however, and could imply a loss of power for detecting centers with deviating mortality. Therefore, we assess how the common practice of ignoring such interactions impacts the bias and precision of directly and indirectly standardized risks. The reassuring conclusion is that the common practice of working with the main effects of a center has minor impact on hospital evaluation, unless some centers actually perform substantially better on a specific group of patients and there is strong confounding through the corresponding patient characteristic. The bias is then driven by an interplay of the relative center size, the overlap between covariate distributions, and the magnitude of the interaction effect. Interestingly, the bias on indirectly standardized risks is smaller than on directly standardized risks. We illustrate our findings by simulation and in an analysis of 30-day mortality on Riksstroke. © 2015 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.

  14. An evaluation framework for multimodal interaction determining quality aspects and modality choice

    CERN Document Server

    Wechsung, Ina

    2014-01-01

    This book presents (1) an exhaustive and empirically validated taxonomy of quality aspects of multimodal interaction as well as respective measurement methods, (2) a validated questionnaire specifically tailored to the evaluation of multimodal systems and covering most of the taxonomy‘s quality aspects, (3) insights on how the quality perceptions of multimodal systems relate to the quality perceptions of its individual components, (4) a set of empirically tested factors which influence modality choice, and (5) models regarding the relationship of the perceived quality of a modality and the actual usage of a modality.

  15. [Systematic evaluation of retention behavior of carbohydrates in hydrophilic interaction liquid chromatography].

    Science.gov (United States)

    Fu, Qing; Wang, Jun; Liang, Tu; Xu, Xiaoyong; Jin, Yu

    2013-11-01

    A systematic evaluation of retention behavior of carbohydrates in hydrophilic interaction liquid chromatography (HILIC) was performed. The influences of mobile phase, stationary phase and buffer salt on the retention of carbohydrates were investigated. According to the results, the retention time of carbohydrates decreased as the proportion of acetonitrile in mobile phase decreased. Increased time of carbohydrates was observed as the concentration of buffer salt in mobile phase increased. The retention behavior of carbohydrates was also affected by organic solvent and HILIC stationary phase. Furthermore, an appropriate retention equation was used in HILIC mode. The retention equation lnk = a + blnC(B) + cC(B) could quantitatively describe the retention factors of carbohydrates of plant origin with good accuracy: the relative error of the predicted time to actual time was less than 0.3%. The evaluation results could provide guidance for carbohydrates to optimize the experimental conditions in HILIC method development especially for carbohydrate separation

  16. A life evaluation under creep-fatigue-environment interaction of Ni-base wrought alloys

    International Nuclear Information System (INIS)

    Hattori, Hiroshi; Kitagawa, Masaki; Ohtomo, Akira; Itoh, Mitsuyoshi

    1986-01-01

    In order to determine a failure criteria under cyclic loading and affective environment for HTGR systems, a series of strain controlled low-cycle fatigue tests were carried out at HTGR maximum gas temperatures in air, in vacuum and in HTGR helium environments on two nickel-base wrought alloys, namely Inconel 617 and Hastelloy XR. This paper first describes the creep-fatigue-environment properties of these alloys followed by a proposal of an evaluation method of creep-fatigue-environment interaction based on the experimental data to define the more reasonable design criteria, which is a modification of the linear damage summation rule. Second, the creep-fatigue properties of Hastelloy XR at 900 deg C and the result evaluated by this proposed method are shown. This criterion is successfully applied to the life prediction at 900 deg C. In addition, the creep-fatigue properties of Hastelloy XR-II are discussed. (author)

  17. Design, synthesis, and evaluation of an alpha-helix mimetic library targeting protein-protein interactions.

    Science.gov (United States)

    Shaginian, Alex; Whitby, Landon R; Hong, Sukwon; Hwang, Inkyu; Farooqi, Bilal; Searcey, Mark; Chen, Jiandong; Vogt, Peter K; Boger, Dale L

    2009-04-22

    The design and solution-phase synthesis of an alpha-helix mimetic library as an integral component of a small-molecule library targeting protein-protein interactions are described. The iterative design, synthesis, and evaluation of the candidate alpha-helix mimetic was initiated from a precedented triaryl template and refined by screening the designs for inhibition of MDM2/p53 binding. Upon identifying a chemically and biologically satisfactory design and consistent with the screening capabilities of academic collaborators, the corresponding complete library was assembled as 400 mixtures of 20 compounds (20 x 20 x 20-mix), where the added subunits are designed to mimic all possible permutations of the naturally occurring i, i + 4, i + 7 amino acid side chains of an alpha-helix. The library (8000 compounds) was prepared using a solution-phase synthetic protocol enlisting acid/base liquid-liquid extractions for purification on a scale that insures its long-term availability for screening campaigns. Screening of the library for inhibition of MDM2/p53 binding not only identified the lead alpha-helix mimetic upon which the library was based, but also suggests that a digestion of the initial screening results that accompany the use of such a comprehensive library can provide insights into the nature of the interaction (e.g., an alpha-helix mediated protein-protein interaction) and define the key residues and their characteristics responsible for recognition.

  18. Replication Kits for the papers "Automated Usability Evaluation of Virtual Reality Applications" and "VR Interaction Modalities for the Evaluation of Technical Device Prototypes" submitted to the CHI 2018

    OpenAIRE

    Harms, Patrick; Holderied, Hanna

    2017-01-01

    This replication kit contains all necessary data to reproduce the setup and results of both papers 'Automated Usability Evaluation of Virtual Reality Applications' and 'VR Interaction Modalities for the Evaluation of Technical Device Prototypes' as submitted to the CHI 2018. It includes the Unity Projects that show a coffee machine and a copier scene (sometimes refered to as printer scene, as well, as it is an integrated device) that can be interacted with with the help of the four interactio...

  19. Interactive contour delineation of organs at risk in radiotherapy: Clinical evaluation on NSCLC patients

    International Nuclear Information System (INIS)

    Dolz, J.; Kirişli, H. A.; Massoptier, L.; Fechter, T.; Karnitzki, S.; Oehlke, O.; Nestle, U.; Vermandel, M.

    2016-01-01

    Purpose: Accurate delineation of organs at risk (OARs) on computed tomography (CT) image is required for radiation treatment planning (RTP). Manual delineation of OARs being time consuming and prone to high interobserver variability, many (semi-) automatic methods have been proposed. However, most of them are specific to a particular OAR. Here, an interactive computer-assisted system able to segment various OARs required for thoracic radiation therapy is introduced. Methods: Segmentation information (foreground and background seeds) is interactively added by the user in any of the three main orthogonal views of the CT volume and is subsequently propagated within the whole volume. The proposed method is based on the combination of watershed transformation and graph-cuts algorithm, which is used as a powerful optimization technique to minimize the energy function. The OARs considered for thoracic radiation therapy are the lungs, spinal cord, trachea, proximal bronchus tree, heart, and esophagus. The method was evaluated on multivendor CT datasets of 30 patients. Two radiation oncologists participated in the study and manual delineations from the original RTP were used as ground truth for evaluation. Results: Delineation of the OARs obtained with the minimally interactive approach was approved to be usable for RTP in nearly 90% of the cases, excluding the esophagus, which segmentation was mostly rejected, thus leading to a gain of time ranging from 50% to 80% in RTP. Considering exclusively accepted cases, overall OARs, a Dice similarity coefficient higher than 0.7 and a Hausdorff distance below 10 mm with respect to the ground truth were achieved. In addition, the interobserver analysis did not highlight any statistically significant difference, at the exception of the segmentation of the heart, in terms of Hausdorff distance and volume difference. Conclusions: An interactive, accurate, fast, and easy-to-use computer-assisted system able to segment various OARs

  20. Interactive contour delineation of organs at risk in radiotherapy: Clinical evaluation on NSCLC patients

    Energy Technology Data Exchange (ETDEWEB)

    Dolz, J., E-mail: jose.dolz.upv@gmail.com [AQUILAB, Loos-les-Lille 59120, France and University Lille, Inserm, CHU Lille, U1189–ONCO-THAI–Image Assisted Laser Therapy for Oncology, Lille F-59000 (France); Kirişli, H. A.; Massoptier, L. [AQUILAB, Loos-les-Lille 59120 (France); Fechter, T.; Karnitzki, S.; Oehlke, O.; Nestle, U. [Department of Radiation Oncology, University Medical Center, Freiburg 79106 (Germany); Vermandel, M. [Inserm Onco Thai U1189, Université Lille 2, CHRU Lille, Lille 59037 (France)

    2016-05-15

    Purpose: Accurate delineation of organs at risk (OARs) on computed tomography (CT) image is required for radiation treatment planning (RTP). Manual delineation of OARs being time consuming and prone to high interobserver variability, many (semi-) automatic methods have been proposed. However, most of them are specific to a particular OAR. Here, an interactive computer-assisted system able to segment various OARs required for thoracic radiation therapy is introduced. Methods: Segmentation information (foreground and background seeds) is interactively added by the user in any of the three main orthogonal views of the CT volume and is subsequently propagated within the whole volume. The proposed method is based on the combination of watershed transformation and graph-cuts algorithm, which is used as a powerful optimization technique to minimize the energy function. The OARs considered for thoracic radiation therapy are the lungs, spinal cord, trachea, proximal bronchus tree, heart, and esophagus. The method was evaluated on multivendor CT datasets of 30 patients. Two radiation oncologists participated in the study and manual delineations from the original RTP were used as ground truth for evaluation. Results: Delineation of the OARs obtained with the minimally interactive approach was approved to be usable for RTP in nearly 90% of the cases, excluding the esophagus, which segmentation was mostly rejected, thus leading to a gain of time ranging from 50% to 80% in RTP. Considering exclusively accepted cases, overall OARs, a Dice similarity coefficient higher than 0.7 and a Hausdorff distance below 10 mm with respect to the ground truth were achieved. In addition, the interobserver analysis did not highlight any statistically significant difference, at the exception of the segmentation of the heart, in terms of Hausdorff distance and volume difference. Conclusions: An interactive, accurate, fast, and easy-to-use computer-assisted system able to segment various OARs

  1. A multimedia interactive education system for prostate cancer patients: development and preliminary evaluation.

    Science.gov (United States)

    Diefenbach, Michael A; Butz, Brian P

    2004-01-21

    A cancer diagnosis is highly distressing. Yet, to make informed treatment choices patients have to learn complicated disease and treatment information that is often fraught with medical and statistical terminology. Thus, patients need accurate and easy-to-understand information. To introduce the development and preliminary evaluation through focus groups of a novel highly-interactive multimedia-education software program for patients diagnosed with localized prostate cancer. The prostate interactive education system uses the metaphor of rooms in a virtual health center (ie, reception area, a library, physician offices, group meeting room) to organize information. Text information contained in the library is tailored to a person's information-seeking preference (ie, high versus low information seeker). We conducted a preliminary evaluation through 5 separate focus groups with prostate cancer survivors (N = 18) and their spouses (N = 15). Focus group results point to the timeliness and high acceptability of the software among the target audience. Results also underscore the importance of a guide or tutor who assists in navigating the program and who responds to queries to facilitate information retrieval. Focus groups have established the validity of our approach and point to new directions to further enhance the user interface.

  2. Evaluation of Early Ground Control Station Configurations for Interacting with a UAS Traffic Management (UTM) System

    Science.gov (United States)

    Dao, Arik-Quang V.; Martin, Lynne; Mohlenbrink, Christoph; Bienert, Nancy; Wolte, Cynthia; Gomez, Ashley; Claudatos, Lauren; Mercer, Joey

    2017-01-01

    The purpose of this paper is to report on a human factors evaluation of ground control station design concepts for interacting with an unmanned traffic management system. The data collected for this paper comes from recent field tests for NASA's Unmanned Traffic Management (UTM) project, and covers the following topics; workload, situation awareness, as well as flight crew communication, coordination, and procedures. The goal of this evaluation was to determine if the various software implementations for interacting with the UTM system can be described and classified into design concepts to provide guidance for the development of future UTM interfaces. We begin with a brief description of NASA's UTM project, followed by a description of the test range configuration related to a second development phase. We identified (post hoc) two classes in which the ground control stations could be grouped. This grouping was based on level of display integration. The analysis was exploratory and informal. It was conducted to compare ground stations across those two classes and against the aforementioned topics. Herein, we discuss the results.

  3. Laboratory Evaluation of Interactions in the Degradation of a Polypropylene Geotextile in Marine Environments

    Directory of Open Access Journals (Sweden)

    José Ricardo Carneiro

    2018-01-01

    Full Text Available The long-term behaviour of geosynthetics applied in coastal engineering structures can be adversely affected by many agents. This paper studies the resistance of a nonwoven polypropylene geotextile against some degradation agents present in marine environments and evaluates the existence of interactions between them. For that purpose, the geotextile was exposed to some laboratory degradation tests: immersion tests (in seawater, deionised water, and sodium chloride 35 g·L−1, thermooxidation, and artificial weathering. The geotextile was (1 exposed separately to each degradation test and (2 exposed successively to combinations of two or three degradation tests. The damage caused by the degradation tests was evaluated by monitoring the tensile properties of the geotextile. Based on the changes occurred in tensile strength, reduction factors were determined. The reduction factors obtained directly in the multiple exposures were compared with those obtained by the traditional methodology for the combined effect of the degradation agents. The results, among other findings, showed the existence of relevant interactions between the degradation agents and showed that the reduction factors obtained by the traditional methodology were unable to represent accurately (by underestimating the degradation occurred in the geotextile.

  4. Development and evaluation of an interactive electronic laboratory manual for cooperative learning of medical histology.

    Science.gov (United States)

    Khalil, Mohammed K; Kirkley, Debbie L; Kibble, Jonathan D

    2013-01-01

    This article describes the development of an interactive computer-based laboratory manual, created to facilitate the teaching and learning of medical histology. The overarching goal of developing the manual is to facilitate self-directed group interactivities that actively engage students during laboratory sessions. The design of the manual includes guided instruction for students to navigate virtual slides, exercises for students to monitor learning, and cases to provide clinical relevance. At the end of the laboratory activities, student groups can generate a laboratory report that may be used to provide formative feedback. The instructional value of the manual was evaluated by a questionnaire containing both closed-ended and open-ended items. Closed-ended items using a five-point Likert-scale assessed the format and navigation, instructional contents, group process, and learning process. Open-ended items assessed student's perception on the effectiveness of the manual in facilitating their learning. After implementation for two consecutive years, student evaluation of the manual was highly positive and indicated that it facilitated their learning by reinforcing and clarifying classroom sessions, improved their understanding, facilitated active and cooperative learning, and supported self-monitoring of their learning. Copyright © 2013 American Association of Anatomists.

  5. Evaluation on Impact Interaction between Abutment and Steel Girder Subjected to Nonuniform Seismic Excitation

    Directory of Open Access Journals (Sweden)

    Yue Zheng

    2015-01-01

    Full Text Available This paper aims to evaluate the impact interaction between the abutment and the girder subjected to nonuniform seismic excitation. An impact model based on tests is presented by taking material properties of the backfill of the abutment into consideration. The conditional simulation is performed to investigate the spatial variation of earthquake ground motions. A two-span continuous steel box girder bridge is taken as the example to analyze and assess the pounding interaction between the abutment and the girder. The detailed nonlinear finite element (FE model is established and the steel girder and the reinforced concrete piers are modeled by nonlinear fiber elements. The pounding element of the abutment is simulated by using a trilinear compression gap element. The elastic-perfectly plastic element is used to model the nonlinear rubber bearings. The comparisons of the pounding forces, the shear forces of the nonlinear bearings, the moments of reinforced concrete piers, and the axial pounding stresses of the steel girder are studied. The made observations indicate that the nonuniform excitation for multisupport bridge is imperative in the analysis and evaluation of the pounding effects of the bridges.

  6. A multiplexed microfluidic system for evaluation of dynamics of immune-tumor interactions.

    Science.gov (United States)

    Moore, N; Doty, D; Zielstorff, M; Kariv, I; Moy, L Y; Gimbel, A; Chevillet, J R; Lowry, N; Santos, J; Mott, V; Kratchman, L; Lau, T; Addona, G; Chen, H; Borenstein, J T

    2018-05-25

    Recapitulation of the tumor microenvironment is critical for probing mechanisms involved in cancer, and for evaluating the tumor-killing potential of chemotherapeutic agents, targeted therapies and immunotherapies. Microfluidic devices have emerged as valuable tools for both mechanistic studies and for preclinical evaluation of therapeutic agents, due to their ability to precisely control drug concentrations and gradients of oxygen and other species in a scalable and potentially high throughput manner. Most existing in vitro microfluidic cancer models are comprised of cultured cancer cells embedded in a physiologically relevant matrix, collocated with vascular-like structures. However, the recent emergence of immune checkpoint inhibitors (ICI) as a powerful therapeutic modality against many cancers has created a need for preclinical in vitro models that accommodate interactions between tumors and immune cells, particularly for assessment of unprocessed tumor fragments harvested directly from patient biopsies. Here we report on a microfluidic model, termed EVIDENT (ex vivo immuno-oncology dynamic environment for tumor biopsies), that accommodates up to 12 separate tumor biopsy fragments interacting with flowing tumor-infiltrating lymphocytes (TILs) in a dynamic microenvironment. Flow control is achieved with a single pump in a simple and scalable configuration, and the entire system is constructed using low-sorption materials, addressing two principal concerns with existing microfluidic cancer models. The system sustains tumor fragments for multiple days, and permits real-time, high-resolution imaging of the interaction between autologous TILs and tumor fragments, enabling mapping of TIL-mediated tumor killing and testing of various ICI treatments versus tumor response. Custom image analytic algorithms based on machine learning reported here provide automated and quantitative assessment of experimental results. Initial studies indicate that the system is capable of

  7. Intermolecular interactions in the condensed phase: Evaluation of semi-empirical quantum mechanical methods.

    Science.gov (United States)

    Christensen, Anders S; Kromann, Jimmy C; Jensen, Jan H; Cui, Qiang

    2017-10-28

    To facilitate further development of approximate quantum mechanical methods for condensed phase applications, we present a new benchmark dataset of intermolecular interaction energies in the solution phase for a set of 15 dimers, each containing one charged monomer. The reference interaction energy in solution is computed via a thermodynamic cycle that integrates dimer binding energy in the gas phase at the coupled cluster level and solute-solvent interaction with density functional theory; the estimated uncertainty of such calculated interaction energy is ±1.5 kcal/mol. The dataset is used to benchmark the performance of a set of semi-empirical quantum mechanical (SQM) methods that include DFTB3-D3, DFTB3/CPE-D3, OM2-D3, PM6-D3, PM6-D3H+, and PM7 as well as the HF-3c method. We find that while all tested SQM methods tend to underestimate binding energies in the gas phase with a root-mean-squared error (RMSE) of 2-5 kcal/mol, they overestimate binding energies in the solution phase with an RMSE of 3-4 kcal/mol, with the exception of DFTB3/CPE-D3 and OM2-D3, for which the systematic deviation is less pronounced. In addition, we find that HF-3c systematically overestimates binding energies in both gas and solution phases. As most approximate QM methods are parametrized and evaluated using data measured or calculated in the gas phase, the dataset represents an important first step toward calibrating QM based methods for application in the condensed phase where polarization and exchange repulsion need to be treated in a balanced fashion.

  8. Intermolecular interactions in the condensed phase: Evaluation of semi-empirical quantum mechanical methods

    Science.gov (United States)

    Christensen, Anders S.; Kromann, Jimmy C.; Jensen, Jan H.; Cui, Qiang

    2017-10-01

    To facilitate further development of approximate quantum mechanical methods for condensed phase applications, we present a new benchmark dataset of intermolecular interaction energies in the solution phase for a set of 15 dimers, each containing one charged monomer. The reference interaction energy in solution is computed via a thermodynamic cycle that integrates dimer binding energy in the gas phase at the coupled cluster level and solute-solvent interaction with density functional theory; the estimated uncertainty of such calculated interaction energy is ±1.5 kcal/mol. The dataset is used to benchmark the performance of a set of semi-empirical quantum mechanical (SQM) methods that include DFTB3-D3, DFTB3/CPE-D3, OM2-D3, PM6-D3, PM6-D3H+, and PM7 as well as the HF-3c method. We find that while all tested SQM methods tend to underestimate binding energies in the gas phase with a root-mean-squared error (RMSE) of 2-5 kcal/mol, they overestimate binding energies in the solution phase with an RMSE of 3-4 kcal/mol, with the exception of DFTB3/CPE-D3 and OM2-D3, for which the systematic deviation is less pronounced. In addition, we find that HF-3c systematically overestimates binding energies in both gas and solution phases. As most approximate QM methods are parametrized and evaluated using data measured or calculated in the gas phase, the dataset represents an important first step toward calibrating QM based methods for application in the condensed phase where polarization and exchange repulsion need to be treated in a balanced fashion.

  9. SciSpark: Highly Interactive and Scalable Model Evaluation and Climate Metrics for Scientific Data and Analysis

    Data.gov (United States)

    National Aeronautics and Space Administration — We will construct SciSpark, a scalable system for interactive model evaluation and for the rapid development of climate metrics and analyses. SciSpark directly...

  10. Mechanism of the pharmacokinetic interaction between methotrexate and benzimidazoles: potential role for breast cancer resistance protein in clinical drug-drug interactions

    NARCIS (Netherlands)

    Breedveld, Pauline; Zelcer, Noam; Pluim, Dick; Sönmezer, Ozgür; Tibben, Matthijs M.; Beijnen, Jos H.; Schinkel, Alfred H.; van Tellingen, Olaf; Borst, Piet; Schellens, Jan H. M.

    2004-01-01

    The antifolate drug methotrexate (MTX) is transported by breast cancer resistance protein (BCRP; ABCG2) and multidrug resistance-associated protein1-4 (MRP1-4; ABCC1-4). In cancer patients, coadministration of benzimidazoles and MTX can result in profound MTX-induced toxicity coinciding with an

  11. Evaluation of different delivery modes of an interactive e-learning programme for teaching cultural diversity.

    Science.gov (United States)

    Hawthorne, Kamila; Prout, Hayley; Kinnersley, Paul; Houston, Helen

    2009-01-01

    UK medical schools find it challenging to provide standardised teaching to expanding year intakes. In addition, developing and implementing diversity training can cause difficulties. This paper describes the evaluation of an interactive e-learning programme to raise awareness and understanding of communication difficulties in diversity consultations. The programme was part of an undergraduate portfolio-based community module. Three hundred and two students were assigned to one of three delivery methods--a large group setting, small groups with a facilitator, and as part of distance learning while on community placement. The evaluation included analysis of their coursework marks, a self-completed evaluation questionnaire, and small group discussions. Two hundred and twenty-three students took part in the evaluation. They were able to apply the concepts they learnt to clinical examples from their own experiences. Type of delivery did not affect coursework marks, but students tended to prefer the e-learning as part of a distance learning package. They offered helpful suggestions to improve its complexity and range. The acceptability and utility of this e-learning module both in face to face teaching and remote placement has been demonstrated, and evaluation by the students has provided valuable information for its further development. All medical schools should include some diversity training, and further research should concentrate on the effects of this type of learning on longer term outcomes such as attitude and performance tests. Such tools could reduce demands on staff time in facilitation of small groupwork, and their cost effectiveness could be increased by making them available to other medical schools.

  12. Use of live interactive webcasting for an international postgraduate module in ehealth: case study evaluation.

    Science.gov (United States)

    Jones, Ray B; Maramba, Inocencio; Boulos, Maged N Kamel; Alexander, Tara

    2009-11-13

    Producing "traditional" e-learning can be time consuming, and in a topic such as eHealth, it may have a short shelf-life. Students sometimes report feeling isolated and lacking in motivation. Synchronous methods can play an important part in any blended approach to learning. The aim was to develop, deliver, and evaluate an international postgraduate module in eHealth using live interactive webcasting. We developed a hybrid solution for live interactive webcasting using a scan converter, mixer, and digitizer, and video server to embed a presenter-controlled talking head or copy of the presenter's computer screen (normally a PowerPoint slide) in a student chat room. We recruited 16 students from six countries and ran weekly 2.5-hour live sessions for 10 weeks. The content included the use of computers by patients, patient access to records, different forms of e-learning for patients and professionals, research methods in eHealth, geographic information systems, and telehealth. All sessions were recorded-presentations as video files and the student interaction as text files. Students were sent an email questionnaire of mostly open questions seeking their views of this form of learning. Responses were collated and anonymized by a colleague who was not part of the teaching team. Sessions were generally very interactive, with most students participating actively in breakout or full-class discussions. In a typical 2.5-hour session, students posted about 50 messages each. Two students did not complete all sessions; one withdrew from the pressure of work after session 6, and one from illness after session 7. Fourteen of the 16 responded to the feedback questionnaire. Most students (12/14) found the module useful or very useful, and all would recommend the module to others. All liked the method of delivery, in particular the interactivity, the variety of students, and the "closeness" of the group. Most (11/14) felt "connected" with the other students on the course. Many

  13. A novel apparatus for interocular interaction evaluation in children with and without anisometropic amblyopia.

    Science.gov (United States)

    Lai, Xin Jie Angela; Alexander, Jack; He, Ming Guang; Yang, Zhi Kuan; Suttle, Catherine

    2012-07-01

    Dichoptic visual stimulation may be achieved using shutter goggles and mirror systems. These methods vary in their feasibility for use in children. This study aims to investigate the feasibility of use of a simple trial frame-based system to evaluate interactions in children. Low contrast acuity, contrast sensitivity and alignment sensitivity were measured in the non-dominant eye of 10 normally-sighted children, 14 anisometropic children without amblyopia and 14 anisometropic amblyopic children (aged 5-11 years) using goggles and a trial frame apparatus (TFA). The dominant eye was either fully or partially occluded. The difference in visual functions in the non-dominant eye between the full and partial occlusion conditions was termed the 'interaction index'. Agreement between the TFA and goggles in terms of visual functions and interactions was assessed in anisometropic children with and without amblyopia using the Bland-Altman method and t-test. Training sessions allowed subjects to become accustomed to the systems and tasks. The duration of training, the number of breaks requested by subjects and their willingness to attend further experiments were recorded in 10 subjects from each group and were compared between groups and between systems. Both Bland-Altman and t-test methods indicated acceptable agreement between the TFA and goggles in visual function and interaction measures (p > 0.05), except for contrast sensitivity measured in anisometropic children without amblyopia (p = 0.042). For all subject groups, contrast sensitivity training was significantly longer using goggles than using the TFA (p ≤ 0.001). Significantly more breaks were requested in acuity and contrast sensitivity testing, when goggles were used than when the TFA was used (p amblyopia showed a significantly greater willingness to attend more experiments using the TFA than using goggles (p = 0.025). The TFA may be a useful tool in studies of interactions in amblyopes, particularly in studies

  14. Food-Drug Interactions

    Directory of Open Access Journals (Sweden)

    Arshad Yar Khan

    2011-03-01

    Full Text Available The effect of drug on a person may be different than expected because that drug interacts with another drug the person is taking (drug-drug interaction, food, beverages, dietary supplements the person is consuming (drug-nutrient/food interaction or another disease the person has (drug-disease interaction. A drug interaction is a situation in which a substance affects the activity of a drug, i.e. the effects are increased or decreased, or they produce a new effect that neither produces on its own. These interactions may occur out of accidental misuse or due to lack of knowledge about the active ingredients involved in the relevant substances. Regarding food-drug interactions physicians and pharmacists recognize that some foods and drugs, when taken simultaneously, can alter the body's ability to utilize a particular food or drug, or cause serious side effects. Clinically significant drug interactions, which pose potential harm to the patient, may result from changes in pharmaceutical, pharmacokinetic, or pharmacodynamic properties. Some may be taken advantage of, to the benefit of patients, but more commonly drug interactions result in adverse drug events. Therefore it is advisable for patients to follow the physician and doctors instructions to obtain maximum benefits with least fooddrug interactions. The literature survey was conducted by extracting data from different review and original articles on general or specific drug interactions with food. This review gives information about various interactions between different foods and drugs and will help physicians and pharmacists prescribe drugs cautiously with only suitable food supplement to get maximum benefit for the patient.

  15. No praise, please: Depressive symptoms, reactivity to positive social interaction, and fear of positive evaluation.

    Science.gov (United States)

    Reichenberger, Julia; Wiggert, Nicole; Agroskin, Dmitrij; Wilhelm, Frank H; Blechert, Jens

    2017-03-01

    Depression is characterized by depressed mood and loss of interest or pleasure. Resulting alterations in emotional reactivity have been explained by three different accounts: 'positive attenuation', 'negative potentiation', and 'emotion context insensitivity'. Despite the importance of depression-related emotional alteration in social interactions, research with naturalistic interpersonal stimuli is scarce and underlying mechanisms largely unknown. Hence, the present study examined subjective emotional reactivity to brief negative, positive, and neutral social-evaluative videos as a function of depressive symptoms in an adult sample (N = 84). Fear of positive evaluation (FPE) and fear of negative evaluation (FNE), often conceptualized as cognitive components of social anxiety, were examined as possible mediators. Results revealed that more depression symptoms were related to diminished pleasantness responses to both positive and neutral videos. When considering all three video conditions simultaneously, only responses to positive videos remained significantly related to depression scores, supporting the 'positive attenuation' account. Moreover, FPE was found to uniquely mediate the relationship between depressive symptoms and pleasantness responses to positive videos. Results indicate that emotional reactivity to positive interpersonal stimuli is relevant for theoretical and clinical considerations of depression. This research underlines the importance of FPE not only for understanding social anxiety but also depression. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Evaluating interactive technology for an evolving case study on learning and satisfaction of graduate nursing students.

    Science.gov (United States)

    Vogt, Marjorie A; Schaffner, Barbara H

    2016-07-01

    Nursing education is challenged to prepare students for complex healthcare needs through the integration of teamwork and informatics. Technology has become an important teaching tool in the blended classroom to enhance group based learning experiences. Faculty evaluation of classroom technologies is imperative prior to adoption. Few studies have directly compared various technologies and their impact on student satisfaction and learning. The purpose of this study was to evaluate technology enhanced teaching methods on the learning and satisfaction of graduate students in an advanced pharmacology class using an unfolding case study. After IRB approval, students were randomly assigned to one of three groups: blogging group, wiki group or webinar group. Students completed the evolving case study using the assigned interactive technology. Student names were removed from the case studies. Faculty evaluated the case study using a rubric, while blinded to the assigned technology method used. No significant difference was found on case study grades, the range of grades on the assignment demonstrated little differences between the methods used. Students indicated an overall positive impact related to networking and collaboration on a satisfaction survey. Impact of technology methods needs to be explored in other areas of graduate nursing education. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Ethological Evaluation of the Effects of Social Defeat Stress in Mice: Beyond the Social Interaction Ratio.

    Science.gov (United States)

    Henriques-Alves, Aron M; Queiroz, Claudio M

    2015-01-01

    In rodents, repeated exposure to unavoidable aggression followed by sustained sensory treat can lead to prolonged social aversion. The chronic social defeat stress model explores that phenomenon and it has been used as an animal model for human depression. However, some authors have questioned whether confounding effects may arise as the model also boosts anxiety-related behaviors. Despite its wide acceptance, most studies extract limited information from the behavior of the defeated animal. Often, the normalized occupancy around the social stimulus, the interaction zone, is taken as an index of depression. We hypothesized that this parameter is insufficient to fully characterize the behavioral consequences of this form of stress. Using an ethological approach, we showed that repeated social defeat delayed the expression of social investigation in long (10 min) sessions of social interaction. Also, the incidence of defensive behaviors, including stretched-attend posture and high speed retreats, was significantly higher in defeated mice in comparison to controls. Interestingly, a subpopulation of defeated mice showed recurrent and non-habituating stretched-attend posture and persistent flights during the entire session. Two indexes were created based on defensive behaviors to show that only recurrent flights correlates with sucrose intake. Together, the present study corroborates the idea that this model of social stress can precipitate a myriad of behaviors not readily disentangled. We propose that long sessions (>150 s) and detailed ethological evaluation during social interaction tests are necessary to provide enough information to correctly classify defeated animals in terms of resilience and susceptibility to social defeat stress.

  18. Evaluation of an interactive, case-based review session in teaching medical microbiology

    Science.gov (United States)

    Blewett, Earl L; Kisamore, Jennifer L

    2009-01-01

    Background Oklahoma State University-Center for Health Sciences (OSU-CHS) has replaced its microbiology wet laboratory with a variety of tutorials including a case-based interactive session called Microbial Jeopardy!. The question remains whether the time spent by students and faculty in the interactive case-based tutorial is worthwhile? This study was designed to address this question by analyzing both student performance data and assessing students' perceptions regarding the tutorial. Methods Both quantitative and qualitative data were used in the current study. Part One of the study involved assessing student performance using archival records of seven case-based exam questions used in the 2004, 2005, 2006, and 2007 OSU-CHS Medical Microbiology course. Two sample t-tests for proportions were used to test for significant differences related to tutorial usage. Part Two used both quantitative and qualitative means to assess student's perceptions of the Microbial Jeopardy! session. First, a retrospective survey was administered to students who were enrolled in Medical Microbiology in 2006 or 2007. Second, responses to open-ended items from the 2008 course evaluations were reviewed for comments regarding the Microbial Jeopardy! session. Results Both student performance and student perception data support continued use of the tutorials. Quantitative and qualitative data converge to suggest that students like and learn from the interactive, case-based session. Conclusion The case-based tutorial appears to improve student performance on case-based exam questions. Additionally, students perceived the tutorial as helpful in preparing for exam questions and reviewing the course material. The time commitment for use of the case-based tutorial appears to be justified. PMID:19712473

  19. Evaluation of an interactive, case-based review session in teaching medical microbiology.

    Science.gov (United States)

    Blewett, Earl L; Kisamore, Jennifer L

    2009-08-27

    Oklahoma State University-Center for Health Sciences (OSU-CHS) has replaced its microbiology wet laboratory with a variety of tutorials including a case-based interactive session called Microbial Jeopardy!. The question remains whether the time spent by students and faculty in the interactive case-based tutorial is worthwhile? This study was designed to address this question by analyzing both student performance data and assessing students' perceptions regarding the tutorial. Both quantitative and qualitative data were used in the current study. Part One of the study involved assessing student performance using archival records of seven case-based exam questions used in the 2004, 2005, 2006, and 2007 OSU-CHS Medical Microbiology course. Two sample t-tests for proportions were used to test for significant differences related to tutorial usage. Part Two used both quantitative and qualitative means to assess student's perceptions of the Microbial Jeopardy! session. First, a retrospective survey was administered to students who were enrolled in Medical Microbiology in 2006 or 2007. Second, responses to open-ended items from the 2008 course evaluations were reviewed for comments regarding the Microbial Jeopardy! session. Both student performance and student perception data support continued use of the tutorials. Quantitative and qualitative data converge to suggest that students like and learn from the interactive, case-based session. The case-based tutorial appears to improve student performance on case-based exam questions. Additionally, students perceived the tutorial as helpful in preparing for exam questions and reviewing the course material. The time commitment for use of the case-based tutorial appears to be justified.

  20. Ethological Evaluation of the Effects of Social Defeat Stress in Mice: Beyond the Social Interaction Ratio

    Science.gov (United States)

    Henriques-Alves, Aron M.; Queiroz, Claudio M.

    2016-01-01

    In rodents, repeated exposure to unavoidable aggression followed by sustained sensory treat can lead to prolonged social aversion. The chronic social defeat stress model explores that phenomenon and it has been used as an animal model for human depression. However, some authors have questioned whether confounding effects may arise as the model also boosts anxiety-related behaviors. Despite its wide acceptance, most studies extract limited information from the behavior of the defeated animal. Often, the normalized occupancy around the social stimulus, the interaction zone, is taken as an index of depression. We hypothesized that this parameter is insufficient to fully characterize the behavioral consequences of this form of stress. Using an ethological approach, we showed that repeated social defeat delayed the expression of social investigation in long (10 min) sessions of social interaction. Also, the incidence of defensive behaviors, including stretched-attend posture and high speed retreats, was significantly higher in defeated mice in comparison to controls. Interestingly, a subpopulation of defeated mice showed recurrent and non-habituating stretched-attend posture and persistent flights during the entire session. Two indexes were created based on defensive behaviors to show that only recurrent flights correlates with sucrose intake. Together, the present study corroborates the idea that this model of social stress can precipitate a myriad of behaviors not readily disentangled. We propose that long sessions (>150 s) and detailed ethological evaluation during social interaction tests are necessary to provide enough information to correctly classify defeated animals in terms of resilience and susceptibility to social defeat stress. PMID:26869895

  1. Evaluation of an interactive, case-based review session in teaching medical microbiology

    Directory of Open Access Journals (Sweden)

    Kisamore Jennifer L

    2009-08-01

    Full Text Available Abstract Background Oklahoma State University-Center for Health Sciences (OSU-CHS has replaced its microbiology wet laboratory with a variety of tutorials including a case-based interactive session called Microbial Jeopardy!. The question remains whether the time spent by students and faculty in the interactive case-based tutorial is worthwhile? This study was designed to address this question by analyzing both student performance data and assessing students' perceptions regarding the tutorial. Methods Both quantitative and qualitative data were used in the current study. Part One of the study involved assessing student performance using archival records of seven case-based exam questions used in the 2004, 2005, 2006, and 2007 OSU-CHS Medical Microbiology course. Two sample t-tests for proportions were used to test for significant differences related to tutorial usage. Part Two used both quantitative and qualitative means to assess student's perceptions of the Microbial Jeopardy! session. First, a retrospective survey was administered to students who were enrolled in Medical Microbiology in 2006 or 2007. Second, responses to open-ended items from the 2008 course evaluations were reviewed for comments regarding the Microbial Jeopardy! session. Results Both student performance and student perception data support continued use of the tutorials. Quantitative and qualitative data converge to suggest that students like and learn from the interactive, case-based session. Conclusion The case-based tutorial appears to improve student performance on case-based exam questions. Additionally, students perceived the tutorial as helpful in preparing for exam questions and reviewing the course material. The time commitment for use of the case-based tutorial appears to be justified.

  2. Computational psychotherapy research: scaling up the evaluation of patient-provider interactions.

    Science.gov (United States)

    Imel, Zac E; Steyvers, Mark; Atkins, David C

    2015-03-01

    In psychotherapy, the patient-provider interaction contains the treatment's active ingredients. However, the technology for analyzing the content of this interaction has not fundamentally changed in decades, limiting both the scale and specificity of psychotherapy research. New methods are required to "scale up" to larger evaluation tasks and "drill down" into the raw linguistic data of patient-therapist interactions. In the current article, we demonstrate the utility of statistical text analysis models called topic models for discovering the underlying linguistic structure in psychotherapy. Topic models identify semantic themes (or topics) in a collection of documents (here, transcripts). We used topic models to summarize and visualize 1,553 psychotherapy and drug therapy (i.e., medication management) transcripts. Results showed that topic models identified clinically relevant content, including affective, relational, and intervention related topics. In addition, topic models learned to identify specific types of therapist statements associated with treatment-related codes (e.g., different treatment approaches, patient-therapist discussions about the therapeutic relationship). Visualizations of semantic similarity across sessions indicate that topic models identify content that discriminates between broad classes of therapy (e.g., cognitive-behavioral therapy vs. psychodynamic therapy). Finally, predictive modeling demonstrated that topic model-derived features can classify therapy type with a high degree of accuracy. Computational psychotherapy research has the potential to scale up the study of psychotherapy to thousands of sessions at a time. We conclude by discussing the implications of computational methods such as topic models for the future of psychotherapy research and practice. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  3. Ethological evaluation of the effects of social defeat stress in mice: beyond the social interaction ratio

    Directory of Open Access Journals (Sweden)

    Aron Miranda Henriques-Alves

    2016-02-01

    Full Text Available In rodents, repeated exposure to unavoidable aggression followed by sustained sensory treat can lead to prolonged social aversion. The chronic social defeat stress model explores that phenomenon and it has been used as an animal model for human depression. However, some authors have questioned whether confounding effects may arise as the model also boosts anxiety-related behaviors. Despite its wide acceptance, most studies extract limited information from the behavior of the defeated animal. Often, the normalized occupancy around the social stimulus, the interaction zone, is taken as an index of depression. We hypothesized that this parameter is insufficient to fully characterize the behavioral consequences of this form of stress. Using an ethological approach, we showed that repeated social defeat delayed the expression of social investigation in long (10 min sessions of social interaction. Also, the incidence of defensive behaviors, including stretched-attend posture and high speed retreats, was significantly higher in defeated mice in comparison to controls. Interestingly, a subpopulation of defeated mice showed recurrent and non-habituating stretched-attend posture and persistent flights during the entire session. Two indexes were created based on defensive behaviors to show that only recurrent flights correlates with sucrose intake. Together, the present study corroborates the idea that this model of social stress can precipitate a myriad of behaviors not readily disentangled. We propose that long sessions (> 150 s and detailed ethological evaluation during social interaction tests are necessary to provide enough information to correctly classify defeated animals in terms of resilience and susceptibility to social defeat stress.

  4. Team interaction skills evaluation criteria for nuclear power plant control room operators

    International Nuclear Information System (INIS)

    Montgomery, J.C.; Toquam, J.; Gaddy, C.

    1991-09-01

    Previous research has shown the value of good team interaction skills to group performance, yet little progress has been made on in terms of how such skills can be measured. In this study rating scales developed previously (Montgomery, et al., 1990) were extensively revised and cast into a Behaviorally Anchored Rating Scale (BARS) and a Behavioral Frequency format. Rating data were collected using 13 training instructors at the Diablo Canyon Nuclear Plant, who rated three videotapes of simulator scenario performance during a day-long training session and later evaluated control room crews during requalification training. High levels of interrater agreement on both rating scales were found. However, the factor structure of the ratings was generally inconsistent with that hypothesized. Analysis of training ratings using Cronbach's components of accuracy (Cronbach, 1955) indicated that BARS ratings generally exhibited less error than did the Behavioral Frequency ratings. The results are discussed in terms of both field and research implications

  5. Interaction of core self-evaluations and perceived organizational support on work-to-family enrichment.

    Science.gov (United States)

    McNall, Laurel A; Masuda, Aline D; Shanock, Linda Rhoades; Nicklin, Jessica M

    2011-01-01

    The purpose of this article was to offer an empirical test of J. H. Greenhaus and G. N. Powell's (2006) model of work-family enrichment by examining dispositional (i.e., core self-evaluations; CSEs) and situational (i.e., perceived organizational support; POS) factors associated with work-to-family enrichment (WFE) and whether these variables interact in predicting WFE. In a survey of 220 employed adults, our hierarchical regression analysis revealed that in highly supportive work environments, individuals reported high WFE regardless of CSE. However, when POS was low, individuals high in CSEs reported higher WFE than those low in CSEs, in support of conservation of resources theory (S. E. Hobfoll, 2002). Implications for research and practice are discussed.

  6. Evaluation of genotype x environment interactions in maize hybrids using GGE biplot analysis

    Directory of Open Access Journals (Sweden)

    Fatma Aykut Tonk

    2011-01-01

    Full Text Available Seventeen hybrid maize genotypes were evaluated at four different locations in 2005 and 2006 cropping seasonsunder irrigated conditions in Turkey. The analysis of variance showed that mean squares of environments (E, genotypes (G andGE interactions (GEI were highly significant and accounted for 74, 7 and 19 % of treatment combination sum squares, respectively.To determine the effects of GEI on grain yield, the data were subjected to the GGE biplot analysis. Maize hybrid G16 can be proposedas reliably growing in test locations for high grain yield. Also, only the Yenisehir location could be best representative of overalllocations for deciding about which experimental hybrids can be recommended for grain yield in this study. Consequently, using ofgrain yield per plant instead of grain yield per plot in hybrid maize breeding programs could be preferred by private companies dueto some advantages.

  7. Evaluation of Algorithms for Photon Depth of Interaction Estimation for the TRIMAGE PET Component

    Science.gov (United States)

    Camarlinghi, Niccolò; Belcari, Nicola; Cerello, Piergiorgio; Pennazio, Francesco; Sportelli, Giancarlo; Zaccaro, Emanuele; Del Guerra, Alberto

    2016-02-01

    The TRIMAGE consortium aims to develop a multimodal PET/MR/EEG brain scanner dedicated to the early diagnosis of schizophrenia and other mental health disorders. The TRIMAGE PET component features a full ring made of 18 detectors, each one consisting of twelve 8 ×8 Silicon PhotoMultipliers (SiPMs) tiles coupled to two segmented LYSO crystal matrices with staggered layers. The identification of the pixel where a photon interacted is performed on-line at the front-end level, thus allowing the FPGA board to emit fully digital event packets. This allows to increase the effective bandwidth, but imposes restrictions on the complexity of the algorithms to be implemented. In this work, two algorithms, whose implementation is feasible directly on an FPGA, are presented and evaluated. The first algorithm is driven by physical considerations, while the other consists in a two-class linear Support Vector Machine (SVM). The validation of the algorithm performance is carried out by using simulated data generated with the GAMOS Monte Carlo. The obtained results show that the achieved accuracy in layer identification is above 90% for both the proposed approaches. The feasibility of tagging and rejecting events that underwent multiple interactions within the detector is also discussed.

  8. Application of Differential Colorimetry To Evaluate Anthocyanin-Flavonol-Flavanol Ternary Copigmentation Interactions in Model Solutions.

    Science.gov (United States)

    Gordillo, Belén; Rodríguez-Pulido, Francisco J; González-Miret, M Lourdes; Quijada-Morín, Natalia; Rivas-Gonzalo, Julián C; García-Estévez, Ignacio; Heredia, Francisco J; Escribano-Bailón, M Teresa

    2015-09-09

    The combined effect of anthocyanin-flavanol-flavonol ternary interactions on the colorimetric and chemical stability of malvidin-3-glucoside has been studied. Model solutions with fixed malvidin-3-glucoside/(+)-catechin ratio (MC) and variable quercetin-3-β-d-glucoside concentration (MC+Q) and solutions with fixed malvidin-3-glucoside/quercetin-3-β-d-glucoside ratio (MQ) and variable (+)-catechin concentration (MQ+C) were tested at levels closer to those existing in wines. Color variations during storage were evaluated by differential colorimetry. Changes in the anthocyanin concentration were monitored by HPLC-DAD. CIELAB color-difference formulas were demonstrated to be of practical interest to assess the stronger and more stable interaction of quercetin-3-β-d-glucoside with MC binary mixture than (+)-catechin with MQ mixture. The results imply that MC+Q ternary solutions kept their intensity and bluish tonalities for a longer time in comparison to MQ+C solutions. The stability of malvidin-3-glucoside improves when the concentration of quercetin-3-β-d-glucoside increases in MC+Q mixtures, whereas the addition of (+)-catechin in MQ+C mixtures resulted in an opposite effect.

  9. In vitro evaluation of the interactions between human corneal endothelial cells and extracellular matrix proteins

    International Nuclear Information System (INIS)

    Choi, Jin San; Kim, Eun Young; Kim, Min Jeong; Giegengack, Matthew; Khan, Faraaz A; Soker, Shay; Khang, Gilson

    2013-01-01

    The corneal endothelium is the innermost cell layer of the cornea and rests on Descemet's membrane consisting of various extracellular matrix (ECM) proteins which can directly affect the cellular behaviors such as cell adhesion, proliferation, polarity, morphogenesis and function. The objective of this study was to investigate the interactions between the ECM environment and human corneal endothelial cells (HCECs), with the ultimate goal to improve cell proliferation and function in vitro. To evaluate the interaction of HCECs with ECM proteins, cells were seeded on ECM-coated tissue culture dishes, including collagen type I (COL I), collagen type IV (COL IV), fibronectin (FN), FNC coating mix (FNC) and laminin (LM). Cell adhesion and proliferation of HCECs on each substratum and expression of CEC markers were studied. The results showed that HCECs plated on the COL I, COL IV, FN and FNC-coated plates had enhanced cell adhesion initially; the number for COL I, COL IV, FN and FNC was significantly higher than the control (P < 0.05). In addition, cells grown on ECM protein-coated dishes showed more compact cellular morphology and CEC marker expression compared to cells seeded on uncoated dishes. Collectively, our results suggest that an adequate ECM protein combination can provide a long-term culture environment for HCECs for corneal endothelium transplantation. (paper)

  10. Evaluation of kriging based surrogate models constructed from mesoscale computations of shock interaction with particles

    Energy Technology Data Exchange (ETDEWEB)

    Sen, Oishik, E-mail: oishik-sen@uiowa.edu [Mechanical and Industrial Engineering, The University of Iowa, Iowa City, IA 52242 (United States); Gaul, Nicholas J., E-mail: nicholas-gaul@ramdosolutions.com [RAMDO Solutions, LLC, Iowa City, IA 52240 (United States); Choi, K.K., E-mail: kyung-choi@uiowa.edu [Mechanical and Industrial Engineering, The University of Iowa, Iowa City, IA 52242 (United States); Jacobs, Gustaaf, E-mail: gjacobs@sdsu.edu [Aerospace Engineering, San Diego State University, San Diego, CA 92115 (United States); Udaykumar, H.S., E-mail: hs-kumar@uiowa.edu [Mechanical and Industrial Engineering, The University of Iowa, Iowa City, IA 52242 (United States)

    2017-05-01

    Macro-scale computations of shocked particulate flows require closure laws that model the exchange of momentum/energy between the fluid and particle phases. Closure laws are constructed in this work in the form of surrogate models derived from highly resolved mesoscale computations of shock-particle interactions. The mesoscale computations are performed to calculate the drag force on a cluster of particles for different values of Mach Number and particle volume fraction. Two Kriging-based methods, viz. the Dynamic Kriging Method (DKG) and the Modified Bayesian Kriging Method (MBKG) are evaluated for their ability to construct surrogate models with sparse data; i.e. using the least number of mesoscale simulations. It is shown that if the input data is noise-free, the DKG method converges monotonically; convergence is less robust in the presence of noise. The MBKG method converges monotonically even with noisy input data and is therefore more suitable for surrogate model construction from numerical experiments. This work is the first step towards a full multiscale modeling of interaction of shocked particle laden flows.

  11. Evaluation of potential interactions between forest biomass production and Canadian wildlife. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Coulombe, R.; Lemay, A.B.

    1983-06-01

    Forest management for biomass production can be undertaken in all provinces of Canada. Raw material can be extracted either from sawmills, logged areas, silvicultural treatments or short-rotation intensive culture. All forests are suitable habitats for wildlife. However, some species (e.g. woodland caribou, lynx, marten, owl) are extremely dependant on mature forests. Logging these forests generally contributes to reduction of habitats and thus populations. Management of second growth forests should take into consideration these species by extending rotations so part of the forests will serve the species. Removal of snags and downed logs to increase amount of raw material will contribute to reduced habitats of, for instance, tree-nesting birds. As these aspects have not been intensively studied within the Canadian forest regions, interactions can hardly be specified. Studies are recommended to analyse the overall problems and define measures to prevent detrimental effects. Other species (rare, threatened or endangered) will need specific attention and precaution while managing forests. Some are highly sensitive to noise and human disturbance (e.g. whooping crane, white pelican, peregrine falcon), others are very sensitive to harassment. Increased human presence within managed forests will necessitate more educational programs to prevent detrimental effects. Some species of reptiles, amphibians and fish are so poorly documented that only basic studies of the biology, ecology and distribution will permit to identify and evaluate interactions with these new forestry concepts. 289 refs., 19 figs., 36 tabs.

  12. Evaluation of Tissue Interactions with Mechanical Elements of a Transscleral Drug Delivery Device

    Directory of Open Access Journals (Sweden)

    Jeffrey T. Borenstein

    2012-03-01

    Full Text Available The goal of this work was to evaluate tissue-device interactions due to implantation of a mechanically operated drug delivery system onto the posterior sclera. Two test devices were designed and fabricated to model elements of the drug delivery device—one containing a free-spinning ball bearing and the other encasing two articulating gears. Openings in the base of test devices modeled ports for drug passage from device to sclera. Porous poly(tetrafluoroethylene (PTFE membranes were attached to half of the gear devices to minimize tissue ingrowth through these ports. Test devices were sutured onto rabbit eyes for 10 weeks. Tissue-device interactions were evaluated histologically and mechanically after removal to determine effects on device function and changes in surrounding tissue. Test devices were generally well-tolerated during residence in the animal. All devices encouraged fibrous tissue formation between the sclera and the device, fibrous tissue encapsulation and invasion around the device, and inflammation of the conjunctiva. Gear devices encouraged significantly greater inflammation in all cases and a larger rate of tissue ingrowth. PTFE membranes prevented tissue invasion through the covered drug ports, though tissue migrated in through other smaller openings. The torque required to turn the mechanical elements increased over 1000 times for gear devices, but only on the order of 100 times for membrane-covered gear devices and less than 100 times for ball bearing devices. Maintaining a lower device profile, minimizing microscale motion on the eye surface and covering drug ports with a porous membrane may minimize inflammation, decreasing the risk of damage to surrounding tissues and minimizing disruption of device operation.

  13. Separation and characterization of resins and asphaltenes coming from Castilla crude Evaluation of their molecular interaction

    International Nuclear Information System (INIS)

    Navarro, Lina; Alvarez, Mario; Grosso, Jorge Luis; Navarro, Uriel

    2004-01-01

    The study of resins and asphaltenes, the heaviest fractions of oil, has become an area of interest due to the abundance of heavy crude oils in Colombia and Latin America. We studied the chemical composition of the heavy fractions of Castilla crude oil, evaluated some of its molecular parameters and found evidence of the interaction between the resins extracted from the crude with the asphaltenes of the original crude. With this objective, we carried out at the pilot plant level precipitation of the resin-asphaltene (R-A) aggregate by adding and mixing under controlled conditions, a paraffin solvent, from the Apiay refinery, called Apiasol. By extracting Soxhlet with the same solvent, resin 1 of aggregate R-A was separated. Resin ll defined as the soluble fraction that is part of the maltenes, was separated from the deasphalted crude by open column chromatography, using alumina as support, according to the SAR method (Saturated, Aromatics, Resins). The fractions of resins and the asphaltenes obtained, were characterized by: Nuclear Magnetic Resonance (NMR), FT-lR, DRX, elementary analysis (C, H, N, S), metal content (Ni and V), distribution of molecular weight by GPC, and average molecular weight by VPO. The results obtained show evidence that resin l which is part of the aggregate has less average molecular weight than resin ll which is present in the fraction of maltenes. In addition, some changes were found in the elementary analysis of among the resins. On the one hand, and taking into account the existing theories of molecular interactions among these fractions, it was found that the resins l separated from the R-A aggregate, when added to the crude, they stabilize their asphaltenes. This evaluation was carried out by analyzing the flocculation point of the crude and its mixtures with 1,9% and 3,8% of resin l, when they are titrated with a precipitating agent in an NIR cell that works with high pressure and temperature

  14. Evaluation of the total gamma-ray production cross-sections for nonelastic interaction of fast neutrons with iron nuclei

    International Nuclear Information System (INIS)

    Savin, M.V.; Nefedov, Yu.Ya; Livke, A.V.; Zvenigorodskij, A.G.

    2001-01-01

    Experimental data on the total gamma-ray production cross-sections for inelastic interaction of fast neutrons with iron nuclei were analysed. The total gamma-ray production cross-sections, grouped according to E γ , were evaluated in the neutron energy range 0.5-19 MeV. The statistical spline approximation method was used to evaluate the experimental data. Evaluated data stored in the ENDF, JENDL, BROND, and other libraries on gamma-ray production spectra and cross-sections for inelastic interaction of fast neutrons with iron nuclei, were analysed. (author)

  15. The Blue Dog: evaluation of an interactive software program to teach young children how to interact safely with dogs.

    Science.gov (United States)

    Schwebel, David C; Morrongiello, Barbara A; Davis, Aaron L; Stewart, Julia; Bell, Melissa

    2012-04-01

    Pre-post-randomized design evaluated The Blue Dog, a dog safety software program. 76 children aged 3.5-6 years completed 3 tasks to evaluate dog safety pre- and postintervention: (a) pictures (recognition of safe/risky behavior), (b) dollhouse (recall of safe behavior via simulated dollhouse scenarios), and (c) live dog (actual behavior with unfamiliar live dog). Following preintervention evaluation, children were randomly assigned to dog or fire safety conditions, each involving 3 weeks of home computer software use. Children using Blue Dog had greater change in recognition of risky dog situations than children learning fire safety. No between-group differences emerged in recall (dollhouse) or engagement (live-dog) in risky behavior. Families enjoyed using the software. Blue Dog taught children knowledge about safe engagement with dogs, but did not influence recall or implementation of safe behaviors. Dog bites represent a significant pediatric injury concern and continued development of effective interventions is needed.

  16. The interactive effects of affect and shopping goal on information search and product evaluations.

    Science.gov (United States)

    Chen, Fangyuan; Wyer, Robert S; Shen, Hao

    2015-12-01

    Although shoppers often want to evaluate products to make a purchase decision, they can also shop for enjoyment. In each case, the amount of time they spend on shopping and the number of options they consider can depend on the mood they happen to be in. We predicted that mood can signal whether the goal has been attained and when people should stop processing information. When people are primarily motivated to purchase a particular type of product, positive mood signals that they have done enough. Thus, they consider less information if they are happy than if they are unhappy. When people shop for enjoyment, however, positive mood signals that they are still having fun. Thus, they consider more information when they are happy than when they are not. Four experiments among university students (N = 827) examined these possibilities. Experiment 1 provided initial evidence for the interactive effects of mood and goals on search behavior and product evaluation. Other studies examined the implications of this conceptualization for different domains: (a) the relative impact of brand and attribute information on judgments (Experiment 2), (b) gender differences in shopping behavior (Experiment 3), and (c) the number of options that people review in an actual online shopping website (Experiment 4). (c) 2015 APA, all rights reserved).

  17. Simulations and experimental evaluation of an active orthosis for interaction in virtual environments

    Directory of Open Access Journals (Sweden)

    Tsveov Mihail

    2018-01-01

    Full Text Available In this work, the development of a human arm active orthosis is presented. The orthosis is designed primarily for training and rehabilitation in virtual environments.The orthosis system is intended for embodiment in virtual reality where it is allowing human to perceive forces at different body parts or the weight of lifted objects. In the paper the choice of a mechanical structure is shown equivalent to the structure of the human arm. A mechanical model of the orthosis arm as haptic device is built, where kinematic and dynamic parameters are evaluated. Impedance control scheme is selected as the most suitable for force refection at the hand or arm. An open-loop impedance controller is presented in the paper. Computer experiments are carried out using the dimensions of a real arm orthosis. Computer experiments have been carried out to provide force reflection by VR, according to virtual scenario. The conducted simulations show the range of the forces on the operator hand, orthosis can provide. The results of additional measurements and experimental evaluations of physical quantities in the interaction in a virtual environment are revealed in the paper.

  18. First evaluations of ex-vessel fuel-coolant interaction with MC3D

    International Nuclear Information System (INIS)

    Meignen, R.; Dupas, J.; Chaumont, B.

    2003-01-01

    In the frame of severe accident nuclear safety studies, we evaluate for French PWR's the potential of Steam Explosion in the reactor pit, consecutively to a vessel failure and to the mixing of the corium with the water that might be present. The evaluations are made with MC3D. This thermalhydraulic multiphasic code has firstly been qualified and its main parameters chosen so that a sufficient validation is obtained with regards to reactor situations. The safety study for ex-vessel situations is a step-by-step procedure that leads to a progressive process of hypotheses relaxations. We find that it is important to adequately model the corium ejection from the RPV. The rapid transition of the flow at the breach towards 2-phase dispersed flow leads to an important mixing of corium and water. The vessel pressurization is a very important parameter and strong pressure cases lead to a fine fragmentation and thus a high voiding. The small pressure cases are more dangerous for two reasons: the corium is dispersed in larger drops, and some important interactions (in the premixing sense) are reported

  19. [Validation of interaction databases in psychopharmacotherapy].

    Science.gov (United States)

    Hahn, M; Roll, S C

    2018-03-01

    Drug-drug interaction databases are an important tool to increase drug safety in polypharmacy. There are several drug interaction databases available but it is unclear which one shows the best results and therefore increases safety for the user of the databases and the patients. So far, there has been no validation of German drug interaction databases. Validation of German drug interaction databases regarding the number of hits, mechanisms of drug interaction, references, clinical advice, and severity of the interaction. A total of 36 drug interactions which were published in the last 3-5 years were checked in 5 different databases. Besides the number of hits, it was also documented if the mechanism was correct, clinical advice was given, primary literature was cited, and the severity level of the drug-drug interaction was given. All databases showed weaknesses regarding the hit rate of the tested drug interactions, with a maximum of 67.7% hits. The highest score in this validation was achieved by MediQ with 104 out of 180 points. PsiacOnline achieved 83 points, arznei-telegramm® 58, ifap index® 54 and the ABDA-database 49 points. Based on this validation MediQ seems to be the most suitable databank for the field of psychopharmacotherapy. The best results in this comparison were achieved by MediQ but this database also needs improvement with respect to the hit rate so that the users can rely on the results and therefore increase drug therapy safety.

  20. Heuristics to Evaluate Interactive Systems for Children with Autism Spectrum Disorder (ASD).

    Science.gov (United States)

    Khowaja, Kamran; Salim, Siti Salwah; Asemi, Adeleh

    2015-01-01

    In this paper, we adapted and expanded a set of guidelines, also known as heuristics, to evaluate the usability of software to now be appropriate for software aimed at children with autism spectrum disorder (ASD). We started from the heuristics developed by Nielsen in 1990 and developed a modified set of 15 heuristics. The first 5 heuristics of this set are the same as those of the original Nielsen set, the next 5 heuristics are improved versions of Nielsen's, whereas the last 5 heuristics are new. We present two evaluation studies of our new heuristics. In the first, two groups compared Nielsen's set with the modified set of heuristics, with each group evaluating two interactive systems. The Nielsen's heuristics were assigned to the control group while the experimental group was given the modified set of heuristics, and a statistical analysis was conducted to determine the effectiveness of the modified set, the contribution of 5 new heuristics and the impact of 5 improved heuristics. The results show that the modified set is significantly more effective than the original, and we found a significant difference between the five improved heuristics and their corresponding heuristics in the original set. The five new heuristics are effective in problem identification using the modified set. The second study was conducted using a system which was developed to ascertain if the modified set was effective at identifying usability problems that could be fixed before the release of software. The post-study analysis revealed that the majority of the usability problems identified by the experts were fixed in the updated version of the system.

  1. Research on interactive genetic-geological models to evaluate favourability for undiscovered uranium resources

    International Nuclear Information System (INIS)

    Finch, W.I.; Granger, H.C.; Lupe, R.; McCammon, R.B.

    1980-01-01

    Current methods of evaluating favourability for undiscovered uranium resources are unduly subjective, quite possibly inconsistent and, as a consequence, of questionable reliability. This research is aimed at reducing the subjectivity and increasing the reliability by designing an improved method that depends largely on geological data and their statistical frequency of occurrence. This progress report outlines a genetic approach to modelling the geological factors that controlled uranium mineralization in order to evaluate the favourability for the occurrence of undiscovered uranium deposits of the type modelled. A genetic model is constructed from all the factors that describe the processes, in chronological sequence, that formed uranium deposits thought to have a common origin. The field and laboratory evidence for the processes constitute a geologic-occurrence base that parallels the chronological sequence of events. The genetic model and the geologic-occurrence base are portrayed as two columns of an interactive matrix called the ''genetic-geologic model''. For each column, eight chronological stages are used to describe the overall formation of the uranium deposits. These stages consist of (1) precursor processes; (2) host-rock formation; (3) preparation of host-rock; (4) uranium-source development; (5) transport of uranium; (6) primary uranium deposition; (7) post-deposition modification; and (8) preservation. To apply the genetic-geological model to evaluate favourability, a question is posed that determines the presence or absence of each attribute listed under the geologic-occurrence base. By building a logic circuit of the attributes according to either their essential or non-essential nature, the resultant match between a well-documented control area and the test area may be determined. The degree of match is a measure of favourability for uranium occurrence as hypothesized in the genetic model

  2. Heuristics to Evaluate Interactive Systems for Children with Autism Spectrum Disorder (ASD.

    Directory of Open Access Journals (Sweden)

    Kamran Khowaja

    Full Text Available In this paper, we adapted and expanded a set of guidelines, also known as heuristics, to evaluate the usability of software to now be appropriate for software aimed at children with autism spectrum disorder (ASD. We started from the heuristics developed by Nielsen in 1990 and developed a modified set of 15 heuristics. The first 5 heuristics of this set are the same as those of the original Nielsen set, the next 5 heuristics are improved versions of Nielsen's, whereas the last 5 heuristics are new. We present two evaluation studies of our new heuristics. In the first, two groups compared Nielsen's set with the modified set of heuristics, with each group evaluating two interactive systems. The Nielsen's heuristics were assigned to the control group while the experimental group was given the modified set of heuristics, and a statistical analysis was conducted to determine the effectiveness of the modified set, the contribution of 5 new heuristics and the impact of 5 improved heuristics. The results show that the modified set is significantly more effective than the original, and we found a significant difference between the five improved heuristics and their corresponding heuristics in the original set. The five new heuristics are effective in problem identification using the modified set. The second study was conducted using a system which was developed to ascertain if the modified set was effective at identifying usability problems that could be fixed before the release of software. The post-study analysis revealed that the majority of the usability problems identified by the experts were fixed in the updated version of the system.

  3. A fluvoxamine-caffeine interaction study

    DEFF Research Database (Denmark)

    Jeppesen, U; Loft, S; Poulsen, H E

    1996-01-01

    The selective serotonin reuptake inhibitor fluvoxamine is a very potent inhibitor of the liver enzyme CYP1A2, which is the major P450 catalysing the biotransformation of caffeine. Thus, a pharmacokinetic study was undertaken with the purpose of documenting a drug-drug interaction between fluvoxam......The selective serotonin reuptake inhibitor fluvoxamine is a very potent inhibitor of the liver enzyme CYP1A2, which is the major P450 catalysing the biotransformation of caffeine. Thus, a pharmacokinetic study was undertaken with the purpose of documenting a drug-drug interaction between...... fluvoxamine and caffeine. The study was carried out as a randomized, in vivo, cross-over study including eight healthy volunteers. In Period A of the study, each subject took 200 mg caffeine orally, and in Period B, the subjects took fluvoxamine 50 mg per day for 4 days and 100 mg per day for 8 days. On day 8...... fluvoxamine treatment may lead to caffeine intoxication. Finally, our study provides additional evidence that fluvoxamine can be used to probe CYP1A2 in drug metabolism....

  4. In-site interaction evaluation of Tn density by inhibition/competition assays

    Energy Technology Data Exchange (ETDEWEB)

    Robles, Ana [Radiopharmacy Department, Nuclear Research Center, Faculty of Sciences, University of the Republic, Montevideo (Uruguay)], E-mail: anamar@cin.edu.uy; Medeiros, Andrea [Biochemistry Department, Faculty of Medicine, University of the Republic, Montevideo (Uruguay); Berois, Nora [Laboratory of Glycobiology and Tumor Immunology, Pasteur Institute of Montevideo (Uruguay); Balter, Henia S. [Radiopharmacy Department, Nuclear Research Center, Faculty of Sciences, University of the Republic, Montevideo (Uruguay); Pauwels, Ernest K. [University Medical Center Leiden, Department of Radiology, Leiden (Netherlands); Osinaga, Eduardo [Laboratory of Glycobiology and Tumor Immunology, Pasteur Institute of Montevideo (Uruguay); Department of Immunobiology, Faculty of Medicine, University of the Republic, Montevideo (Uruguay)

    2010-05-15

    The tumor-associated structure N-acetyl-galactosamine-O-Ser/Thr (Tn antigen), which is overexpressed in various tumor cell types, notably of the breast, ovary and colon, is an interesting determinant that is useful for cancer diagnosis and follow-up. The aim of this research was to study different assay strategies in order to determine the most sensitive system for further application in epitope characterization and binding assessment. The tetrameric isolectin obtained from Vicia villosa seeds (VVLB{sub 4}) shows high affinity for the tumor-associated structure. A monoclonal antibody against VVLB{sub 4}, MabVV{sub 34}, was generated, and the interaction between MabVV{sub 34} and VVLB{sub 4} was studied by means of binding and inhibition assays. Several synthetic peptides (10 amino acid sequences) designed from the amino acid sequence of VVLB{sub 4} and obtained from trypsin digestion were tested to determine which amino acids were involved in the interaction between MabVV{sub 34} and VVLB{sub 4}. The further unraveling of this epitope was investigated by inhibition using designed synthetic peptides as well as mixtures mimicking variable density effect. Under the experimental circumstances, MabVV{sub 34} was able to inhibit the binding of VVLB{sub 4} to Tn. Two of the four peptide sequences assayed showed better inhibition properties. Finally, mixtures containing these selected sequences allowed the evaluation of binding and inhibition as a function of Tn density. We conclude that the present study facilitates the further development of a specific Tn marker and may contribute to the development of Tn-like radiolabelled peptides or Tn-specific radiolabelled fragments providing a highly selective tool for cancer diagnosis and treatment. This strategy may contribute to characterize the new generation of radiopharmaceuticals for diagnosis and therapy based on biomolecules like antibodies, fragments or peptides, whose application is directly guided by their specific

  5. Hydroxyurea-Lactose Interaction Study: In Silico and In Vitro Evaluation.

    Science.gov (United States)

    Bachchhao, Kunal B; Patil, R R; Patil, C R; Patil, Dipak D

    2017-11-01

    The Maillard reaction between hydroxyurea (a primary amine-containing drug) and lactose (used as an excipient) was explored. The adduct of these compounds was synthesized by heating hydroxyurea with lactose monohydrate at 60 °C in borate buffer (pH 9.2) for 12 h. Synthesis of the adduct was confirmed using UV-visible spectroscopy and Fourier transform infrared, differential scanning calorimetry, high-pressure liquid chromatography, and liquid chromatography-mass spectrometry studies. An in silico investigation of how the adduct formation affected the interactions of hydroxyurea with its biological target oxyhemoglobin, to which it binds to generate nitric oxide and regulates fetal hemoglobin synthesis, was carried out. The in silico evaluations were complemented by an in vitro assay of the anti-sickling activity. Co-incubation of hydroxyurea with deoxygenated blood samples reduced the percentage of sickled cells from 38% to 12 ± 1.6%, whereas the percentage of sickled cells in samples treated with the adduct was 17 ± 1.2%. This indicated loss of anti-sickling activity in the case of the adduct. This study confirmed that hydroxyurea can participate in a Maillard reaction if lactose is used as a diluent. Although an extended study at environmentally feasible temperatures was not carried out in the present investigation, the partial loss of the anti-sickling activity of hydroxyurea was investigated along with the in silico drug-target interactions. The results indicated that the use of lactose in hydroxyurea formulations needs urgent reconsideration and that lactose must be replaced by other diluents that do not form Maillard adducts.

  6. Evaluation of the pharmacokinetic and pharmacodynamic drug interactions between cilnidipine and valsartan, in healthy volunteers

    Science.gov (United States)

    Lee, Jieon; Lee, Howard; Jang, Kyungho; Lim, Kyoung Soo; Shin, Dongseong; Yu, Kyung-Sang

    2014-01-01

    Purpose Although cilnidipine and valsartan are widely coadministered to patients with hypertension, their drug–drug interaction potential has not been investigated. This study compared the pharmacokinetic (PK), pharmacodynamic (PD), and tolerability profiles of cilnidipine and valsartan, both alone and in combination, in healthy male subjects. Patients and methods Fifty-four subjects, enrolled into an open-label, single-dose, three-treatment, three-period crossover study, randomly received cilnidipine (10 mg), valsartan (160 mg), or both according to one of six sequences. Blood samples were collected at baseline and up to 24 hours after drug administration in each period. Plasma concentrations of cilnidipine and valsartan were determined by liquid chromatography with tandem mass spectrometry. Maximum plasma concentration (Cmax) and area under the concentration-time curve from 0 to the last measurable time (AUClast) were estimated using a noncompartmental method. Tolerability was evaluated by assessing adverse events (AEs), vital signs, electrocardiograms, and clinical laboratory tests. Blood pressure was also measured for PD assessment. Results A total of 51 subjects completed the study. The PK profile of cilnidipine was not significantly affected by coadministered valsartan; the geometric mean ratio and 90% confidence interval (90% CI) of AUClast for cilnidipine with and without valsartan was 1.04 (0.98–1.10). Likewise, cilnidipine did not affect the PK of valsartan; the geometric mean ratio (90% CI) of AUClast for valsartan with and without cilnidipine was 0.94 (0.83–1.07). Coadministration of cilnidipine and valsartan reduced blood pressure in an additive way. No serious AEs were reported, and both cilnidipine and valsartan were well tolerated. Conclusion Coadministered cilnidipine and valsartan do not cause a significant PK or PD interaction, and they are well tolerated. PMID:25336921

  7. Evaluation of algorithms for photon depth of interaction estimation for the TRIMAGE PET component

    Energy Technology Data Exchange (ETDEWEB)

    Camarlinghi, Niccolo; Belcari, Nicola [University of Pisa (Italy); Cerello, Piergiorgio [University of Torino (Italy); Sportelli, Giancarlo [University of Pisa (Italy); Pennazio, Francesco [University of Torino (Italy); Zaccario, Emanuele; Del Guerra, Alberto [University of Pisa (Italy)

    2015-05-18

    The TRIMAGE consortium aims to develop a multimodal PET/MR/EEG brain scanner dedicated to the early diagnosis of schizophrenia and other mental health disorders. The PET component features a full ring made of 18 detectors, each one consisting of twelve 8x8 Silicon PhotoMultipliers (SiPMs) tiles coupled to two segmented LYSO crystal matrices with staggered layers. In each module, the crystals belonging to the bottom layer are coupled one to one to the SiPMs, while each crystal of the top layer is coupled to four crystals of the bottom layer. This configuration allows to increase the crystal thickness while reducing the depth of interaction uncertainty, as photons interacting in different layers are expected to produce different light patterns on the SiPMs. The PET scanner will implement the pixel/layer identification on a front-end FPGA. This will allow increasing the effective bandwidth, setting at the same time restrictions on the complexity of the algorithms to be implemented. In this work two algorithms whose implementation is feasible directly on an FPGA are presented and evaluated. The first algorithm implements a method based on adaptive thresholding, while the other uses a linear Support Vector Machine (SVM) trained to distinguish the light pattern coming from two different layers. The validation of the algorithm performance is carried out by using simulated data generated with the GAMOS Monte Carlo. The obtained results show that the achieved accuracy in layer and pixel identification is above the 90% for both the proposed approaches.

  8. Methods used in evaluating data for the interaction of neutrons with light elements (A < 19)

    International Nuclear Information System (INIS)

    Stewart, L.

    1980-01-01

    In the interaction of neutrons with light nuclei, many anomalies are observed. In particular, the probability for gamma-ray production is generally small over most of the neutron energy range. On the other hand, 6 Li, 3 He, 10 B, and 7 Be have thermal absorption cross sections which range from 940 to 48,000 barns. 10 B is the only isotope that has a positive Q for a 3-body reaction, the (n,t2α). As the neutron energy increases, however, 3- and 4-particle direct breakup and sequential formation cross sections dominate the nonelastic for D, T, 6 Li, 7 Be, 10 B, and 12 C above a few MeV. For higher-mass isotopes, particle emission (protons and α's) are often the preferred mode for deexcitation of levels excited via (n,n') reactions, where energetically possible. Very few of these partial cross sections have been measured with the necessary precision. Problems are particularly inherent in experiments on negative-Q reactions near the 3-body threshold. The many-body problem must be treated as several two-body sequential steps in a theoretical analysis; the emitted particle angular distribution is required as input, but is rarely known. Precise knowledge about individual partial cross sections is often important, especially when neutron multiplication, breeding of fusion fuel, radioactive contamination, depletion or buildup of the target, energy transfer, or time-dependent parameters are required. Specific examples are described for the evaluation of neutron interactions with light elements which employ isotopic spin, inverse reactions, charge-conjugate reactions, and the elastic scattering of charged particles (with Wick's Limit). 18 figures, 1 table

  9. A GOAL QUESTION METRIC (GQM APPROACH FOR EVALUATING INTERACTION DESIGN PATTERNS IN DRAWING GAMES FOR PRESCHOOL CHILDREN

    Directory of Open Access Journals (Sweden)

    Dana Sulistiyo Kusumo

    2017-06-01

    Full Text Available In recent years, there has been an increasing interest to use smart devices’ drawing games for educational benefit. In Indonesia, our government classifies children age four to six years old as preschool children. Not all preschool children can use drawing games easily. Further, drawing games may not fulfill all Indonesia's preschool children’s drawing competencies. This research proposes to use Goal-Question Metric (GQM to investigate and evaluate interaction design patterns of preschool children in order to achieve the drawing competencies for preschool children in two drawing Android-based games: Belajar Menggambar (in English: Learn to Draw and Coret: Belajar Menggambar (in English: Scratch: Learn to Draw. We collected data from nine students of a preschool children education in a user research. The results show that GQM can assist to evaluate interaction design patterns in achieving the drawing competencies. Our approach can also yield interaction design patterns by comparing interaction design patterns in two drawing games used.

  10. Evaluation of an interactive case simulation system in dermatology and venereology for medical students

    Directory of Open Access Journals (Sweden)

    Hindbeck Hans

    2006-08-01

    Full Text Available Abstract Background Most of the many computer resources used in clinical teaching of dermatology and venereology for medical undergraduates are information-oriented and focus mostly on finding a "correct" multiple-choice alternative or free-text answer. We wanted to create an interactive computer program, which facilitates not only factual recall but also clinical reasoning. Methods Through continuous interaction with students, a new computerised interactive case simulation system, NUDOV, was developed. It is based on authentic cases and contains images of real patients, actors and healthcare providers. The student selects a patient and proposes questions for medical history, examines the skin, and suggests investigations, diagnosis, differential diagnoses and further management. Feedback is given by comparing the user's own suggestions with those of a specialist. In addition, a log file of the student's actions is recorded. The program includes a large number of images, video clips and Internet links. It was evaluated with a student questionnaire and by randomising medical students to conventional teaching (n = 85 or conventional teaching plus NUDOV (n = 31 and comparing the results of the two groups in a final written examination. Results The questionnaire showed that 90% of the NUDOV students stated that the program facilitated their learning to a large/very large extent, and 71% reported that extensive working with authentic computerised cases made it easier to understand and learn about diseases and their management. The layout, user-friendliness and feedback concept were judged as good/very good by 87%, 97%, and 100%, respectively. Log files revealed that the students, in general, worked with each case for 60–90 min. However, the intervention group did not score significantly better than the control group in the written examination. Conclusion We created a computerised case simulation program allowing students to manage patients in a non

  11. Importance of Sodium Fuel Interaction in Fast Reactor Safety Evaluation - CEA Point of View

    International Nuclear Information System (INIS)

    Tanguy, P.

    1976-01-01

    The consequences of interactions between molten metal (aluminium-uranium alloy) and water have long been a subject of concern for those in charge of reactor safety, following accidents observed or induced in certain reactors (BORAX, SL1, SPERT 1 D). In such accidents, as in similar cases occurring in traditional industries (aluminium foundries, steel works, paper mills...) the contact between the hot liquid product and the coolant entails rapid vaporization of the latter with effects identical to that of an explosive. Although chemical reactions of water decomposition occur in some cases, the main phenomenon is the conversion of the thermal energy stored in the hot substance into mechanical energy. Despite the fact that a molten oxide fuel differs from an aluminium-uranium alloy, as does sodium from water, the consequences of possible contact between the molten mixed uranium and plutonium oxide and sodium must be carefully studied since such a contact may occur in accident conditions in sodium-cooled fast neutron reactors. The essential purpose of an evaluation of reactor safety in accident conditions is in fact to ensure the containment of dangerous products Consequently, any phenomenon likely to endanger containment barriers must be carefully examined. In conclusion: Whereas an accident within an assembly seems to show little likelihood of creating conditions seriously endangering fuel containment, the gravity of problems associated with an overall accident on the core is worthy of thorough and attentive study. In the case of an overall accident on the core of a fast reactor, the interaction between the molten fuel and the sodium is of consequence at two levels. The first is the retention of mechanical energy which may be considerable. The second is the recovery of fuel fragments in an overall cooled configuration but where local cooling problems may give rise to interaction. A greater effort is required in performing tests and mastering their results to

  12. Evaluation of novel candidate variations and their interactions related to bipolar disorders: Analysis of GWAS data

    Directory of Open Access Journals (Sweden)

    Acikel C

    2016-11-01

    Full Text Available Cengizhan Acikel,1 Yesim Aydin Son,2 Cemil Celik,3 Husamettin Gul4 1Department of Biostatistics, Gulhane Military Medical Academy, 2Department of Health Informatics, Graduate School of Informatics, Middle East Technical University, 3Department of Medical Psychiatry, 4Department of Medical Informatics, Gulhane Military Medical Academy, Ankara, Turkey Background: Multifactor dimensionality reduction (MDR is a nonparametric approach that can be used to detect relevant interactions between single-nucleotide polymorphisms (SNPs. The aim of this study was to build the best genomic model based on SNP associations and to identify candidate polymorphisms that are the underlying molecular basis of the bipolar disorders. Methods: This study was performed on Whole-Genome Association Study of Bipolar Disorder (dbGaP [database of Genotypes and Phenotypes] study accession number: phs000017.v3.p1 data. After preprocessing of the genotyping data, three classification-based data mining methods (ie, random forest, naïve Bayes, and k-nearest neighbor were performed. Additionally, as a nonparametric, model-free approach, the MDR method was used to evaluate the SNP profiles. The validity of these methods was evaluated using true classification rate, recall (sensitivity, precision (positive predictive value, and F-measure. Results: Random forests, naïve Bayes, and k-nearest neighbors identified 16, 13, and ten candidate SNPs, respectively. Surprisingly, the top six SNPs were reported by all three methods. Random forests and k-nearest neighbors were more successful than naïve Bayes, with recall values >0.95. On the other hand, MDR generated a model with comparable predictive performance based on five SNPs. Although different SNP profiles were identified in MDR compared to the classification-based models, all models mapped SNPs to the DOCK10 gene. Conclusion: Three classification-based data mining approaches, random forests, naïve Bayes, and k-nearest neighbors

  13. Evaluation of Lagrangian, Eulerian, and arbitrary Lagrangian-Eulerian methods for fluid-structure interaction problems in HCDA analysis

    International Nuclear Information System (INIS)

    Chang, Y.W.; Chu, H.Y.; Gvildys, J.; Wang, C.Y.

    1979-01-01

    The analysis of fluid-structure interaction involves the calculation of both fluid transient and structure dynamics. In the structural analysis, Lagrangian meshes have been used exclusively, whereas for the fluid transient, Lagrangian, Eulerian, and arbitrary Lagrangian-Eulerian (quasi-Eulerian) meshes have been used. This paper performs an evaluation on these three types of meshes. The emphasis is placed on the applicability of the method in analyzing fluid-structure interaction problems in HCDA analysis

  14. Clinical implications of antiretroviral drug interactions with warfarin: a case-control study.

    Science.gov (United States)

    Esterly, John S; Darin, Kristin M; Gerzenshtein, Lana; Othman, Fidah; Postelnick, Michael J; Scarsi, Kimberly K

    2013-06-01

    Warfarin, a frequently prescribed anticoagulant with a narrow therapeutic index, is susceptible to drug-drug interactions with antiretroviral therapy (ART). This study compared the warfarin maintenance dose (WMD) between patients receiving and not receiving ART and evaluated predictors of warfarin dosage among those on ART. This was a case-control (1:2) study. Cases were HIV-infected patients receiving warfarin and protease inhibitor (PI)- and/or non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART. Controls were randomly selected HIV-uninfected patients receiving warfarin. The WMD was compared between cases and controls and between cases on varying ART regimens. Bivariate comparisons were performed and a linear regression model was developed to identify predictors of WMD. We identified 18 case and 36 control patients eligible for inclusion. Cases were younger than controls (mean age: 45.8 versus 63.1 years, P African American (50.0% versus 22.2%, P=0.04). ART was classified as PI-based (n=9), NNRTI-based (n=7) and PI + NNRTI-based (n=2). The WMD (mean ± SD) differed between cases and controls (8.6  ±  3.4 mg versus 5.1 ± 1.5 mg, P ART regimens (PI: 8.8  ±  4.5 mg; NNRTI: 8.6   ± 1.8 mg; PI + NNRTI: 7.3  ±  3.3 mg; P = 0.86). Race and ritonavir dose were independent predictors of WMD, predicting an increase of 3.9 mg (95% CI: 0.88-6.98, P = 0.02) if a patient was African American or 3.7 mg (95% CI: 0.53-6.89, P = 0.03) if the total daily ritonavir dose was 200 mg. The required WMD was significantly higher in patients receiving ART. Prompt dose titration to achieve a higher WMD with vigilant monitoring may be required due to these drug-drug interactions.

  15. Evaluating Types of Students' Interactions in a Wiki-Based Collaborative Learning Project

    Science.gov (United States)

    Prokofieva, Maria

    2013-01-01

    Wiki technology has been promoted as a collaborative software platform. This study investigates interactions that occur in a wiki-based collaborative learning project. The study draws on interaction literature and investigates the types of interactions with which students are engaged in wiki-based group projects, clusters that reflect online…

  16. Consensus-based evaluation of clinical significance and management of anticancer drug interactions

    NARCIS (Netherlands)

    Jansman, F.G.A.; Reyners, A.K.L.; van Roon, E.N.; Smorenburg, C.H.; Helgason, H.H.; le Comte, M.; Wensveen, B.M.; van den Tweel, A.M.A.; de Blois, M.; Kwee, W.; Kerremans, A.L.; Brouwers, J.R.B.J.

    Background: Anticancer drug interactions can affect the efficacy and toxicity of anticancer treatment and that of the interacting drugs. However, information on the significance, prevention, and management of these interactions is currently lacking. Objective: The purpose of this study was to assess

  17. Social interactions between people with dementia: pilot evaluation of an observational instrument in a nursing home

    NARCIS (Netherlands)

    Mabire, J.B.; Gay, M.C.; Vrignaud, P.; Garitte, C.; Vernooij-Dassen, M.J.F.J.

    2016-01-01

    BACKGROUND: In dementia, cognitive and psychological disorders might interfere with maintaining social interactions. We have little information about the nature of these interactions of people with dementia in nursing homes. The aim of this study is to investigate social interactions between people

  18. Structuring Design and Evaluation of an Interactive Installation Through Swarms of Light Rays with Human-Artifact Model

    DEFF Research Database (Denmark)

    Erkut, Cumhur; Fehr, Jonas

    2016-01-01

    We present the design and evaluation of an interactive installation to be explored by movement and sound under Human-Activity Model. In the installation, movement qualities that are extracted from the motion tracking data excite a dynamical system (a synthetic flock of agents), which responds...... out a questionnaire afterwards. In this paper, we report our preliminary work on the analysis of the tensions of interaction with the installation under the Human-Artifact Model. Our results indicate exploration and discovery as the main motives of the interaction. This is different than utilitarian...

  19. EVALUATING THE TARGET, EFFECT, ACTION INTERACTION (TEA MODEL OF SPINAL MANIPULATION THERAPY ON SACROILIAC JOINT DYSFUNCTION

    Directory of Open Access Journals (Sweden)

    Muhammad Salman Bashir

    2017-08-01

    Full Text Available Background: In physical therapy, usually the effects of treatment on any condition will be evaluated based on the mode of action on the target tissue. Some treatments will have direct and indirect effects. Due to indirect effects, there may be changes in other tissues or systems in and around the target tissue. The interaction between target, effect, and action was studied under TEA model. In sacroiliac joint dysfunction, Muscle Energy Technique (MET and Spinal Manipulation Therapy (SMT were proved as useful treatment approaches but one is targeted on muscles (MET the other targets on joint (SMT. The indirect effects of both the approaches can’t be neglected. This study focused on evaluating indirect effects of SMT. Methods: A pilot study was conducted to see the effect of Spinal Manipulation Therapy on muscles (Transverse Abdominus, Internal Oblique when applied in patients with sacroiliac joint dysfunction. 44 subjects diagnosed with sacroiliac joint dysfunction were recruited in the study. Resting thickness was measured by ultrasound before and after Spinal Manipulation Therapy. SPSS version 17 was used for statistical analysis. Paired t-test compared pre and post test results. Results: After conducting Pilot study revealed that Pre resting thickness of Transverse Abdominus and Internal Oblique is (3.5±0.10 and (5.47± 0.15 Post resting Thickness of TrA (Transverse Abdominus and Internal Oblique (IO is (3.90±0.12 and (7.63±0.80 Results are significant as P-Value 0.000 that is <0.05. Conclusion: Here is concluded that SMT is a useful method to treat muscles through its direct action is on the Sacroiliac joint in Sacroiliac joint dysfunction. So we can use it for treating muscles by applying on joints (Indirect method.

  20. IDRC and BetterEvaluation launch an interactive guide to manage ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2016-10-21

    Oct 21, 2016 ... ... evaluations, this guide is intended for program and project managers. ... used to hire evaluators, and guide the management of the evaluation. ... Strategic Evaluation on Communicating Research for Influence: Part I.

  1. Evaluating interactive computer-based scenarios designed for learning medical technology.

    Science.gov (United States)

    Persson, Johanna; Dalholm, Elisabeth Hornyánszky; Wallergård, Mattias; Johansson, Gerd

    2014-11-01

    The use of medical equipment is growing in healthcare, resulting in an increased need for resources to educate users in how to manage the various devices. Learning the practical operation of a device is one thing, but learning how to work with the device in the actual clinical context is more challenging. This paper presents a computer-based simulation prototype for learning medical technology in the context of critical care. Properties from simulation and computer games have been adopted to create a visualization-based, interactive and contextually bound tool for learning. A participatory design process, including three researchers and three practitioners from a clinic for infectious diseases, was adopted to adjust the form and content of the prototype to the needs of the clinical practice and to create a situated learning experience. An evaluation with 18 practitioners showed that practitioners were positive to this type of tool for learning and that it served as a good platform for eliciting and sharing knowledge. Our conclusion is that this type of tools can be a complement to traditional learning resources to situate the learning in a context without requiring advanced technology or being resource-demanding. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Evaluating the interaction of a tracheobronchial stent in an ovine in-vivo model.

    Science.gov (United States)

    McGrath, Donnacha J; Thiebes, Anja Lena; Cornelissen, Christian G; O'Brien, Barry; Jockenhoevel, Stefan; Bruzzi, Mark; McHugh, Peter E

    2018-04-01

    Tracheobronchial stents are used to restore patency to stenosed airways. However, these devices are associated with many complications such as stent migration, granulation tissue formation, mucous plugging and stent strut fracture. Of these, granulation tissue formation is the complication that most frequently requires costly secondary interventions. In this study a biomechanical lung modelling framework recently developed by the authors to capture the lung in-vivo stress state under physiological loading is employed in conjunction with ovine pre-clinical stenting results and device experimental data to evaluate the effect of stent interaction on granulation tissue formation. Stenting is simulated using a validated model of a prototype covered laser-cut tracheobronchial stent in a semi-specific biomechanical lung model, and physiological loading is performed. Two computational methods are then used to predict possible granulation tissue formation: the standard method which utilises the increase in maximum principal stress change, and a newly proposed method which compares the change in contact pressure over a respiratory cycle. These computational predictions of granulation tissue formation are then compared to pre-clinical stenting observations after a 6-week implantation period. Experimental results of the pre-clinical stent implantation showed signs of granulation tissue formation both proximally and distally, with a greater proximal reaction. The standard method failed to show a correlation with the experimental results. However, the contact change method showed an apparent correlation with granulation tissue formation. These results suggest that this new method could be used as a tool to improve future device designs.

  3. Study on the analytical methods to evaluate the interaction effects of embedded nuclear power plants

    International Nuclear Information System (INIS)

    Fukuzawa, R.; Chiba, O.; Tohdo, M.; Hatori, T.

    1987-01-01

    For the seismic response analyses of nuclear power plants which are more or less embedded into soil medium, it is very important to evaluate the interactive effects on the interface between soil and foundation wall, such as wave propagation to infinity radiated from the side wall. The methods generally used in these analyses can be classified into the two basic procedures. One is the direct procedure in which a structure and soil are medeled together into finite elements or beam elements having the quiet boundary; transmitting boundary, non-reflecting boundary. The other is the substructure procedure in which the computational procedure is divided into two steps. In the first step the behavior of massless foundation due to an external force and seismic motion under the assumption as rigid foundation is analyzed, and the results are represented by impedance functions and foundation input motions. Using the results, the structural response analyses are performed. Taking the substructure procedure for seismic response analyses of embedded nuclear power plants, it is the purpose of this paper to present the features of solutions on impedance functions and foundation input motions obtained by various methods such as 3- or 2-dimensional approach, and their influences on structural responses

  4. Redesign of a computerized clinical reminder for colorectal cancer screening: a human-computer interaction evaluation

    Directory of Open Access Journals (Sweden)

    Saleem Jason J

    2011-11-01

    Full Text Available Abstract Background Based on barriers to the use of computerized clinical decision support (CDS learned in an earlier field study, we prototyped design enhancements to the Veterans Health Administration's (VHA's colorectal cancer (CRC screening clinical reminder to compare against the VHA's current CRC reminder. Methods In a controlled simulation experiment, 12 primary care providers (PCPs used prototypes of the current and redesigned CRC screening reminder in a within-subject comparison. Quantitative measurements were based on a usability survey, workload assessment instrument, and workflow integration survey. We also collected qualitative data on both designs. Results Design enhancements to the VHA's existing CRC screening clinical reminder positively impacted aspects of usability and workflow integration but not workload. The qualitative analysis revealed broad support across participants for the design enhancements with specific suggestions for improving the reminder further. Conclusions This study demonstrates the value of a human-computer interaction evaluation in informing the redesign of information tools to foster uptake, integration into workflow, and use in clinical practice.

  5. On-orbit evaluation of the control system/structural mode interactions on OSO-8

    Science.gov (United States)

    Slafer, L. I.

    1980-01-01

    The Orbiting Solar Observatory-8 experienced severe structural mode/control loop interaction problems during the spacecraft development. Extensive analytical studies, using the hybrid coordinate modeling approach, and comprehensive ground testing were carried out in order to achieve the system's precision pointing performance requirements. A recent series of flight tests were conducted with the spacecraft in which a wide bandwidth, high resolution telemetry system was utilized to evaluate the on-orbit flexible dynamics characteristics of the vehicle along with the control system performance. This paper describes the results of these tests, reviewing the basic design problem, analytical approach taken, ground test philosophy, and on-orbit testing. Data from the tests was used to determine the primary mode frequency, damping, and servo coupling dynamics for the on-orbit condition. Additionally, the test results have verified analytically predicted differences between the on-orbit and ground test environments. The test results have led to a validation of both the analytical modeling and servo design techniques used during the development of the control system, and also verified the approach taken to vehicle and servo ground testing.

  6. Evaluation of physical and chemical properties and their interactions in fat, oil, and grease (FOG) deposits.

    Science.gov (United States)

    Gross, Martin A; Jensen, Jeanette L; Gracz, Hanna S; Dancer, Jens; Keener, Kevin M

    2017-10-15

    Fat, oil and grease (FOG) blockages in sewer systems are a substantial problem in the United States. It has been estimated that over 50% of sewer overflows are a result of FOG blockages. In this work, a thorough laboratory study was undertaken to examine key variables that contribute to FOG deposit formation under controlled conditions. Physical and chemical properties and their interactions were evaluated and conditions that generated deposits that mimicked field FOG deposits were identified. It was found that 96 of the of 128 reaction conditions tested in the laboratory formed FOG deposits with similar physical and chemical characteristics as field FOG deposits. It was also found that FOG deposits can be created through fatty acid crystallization and not just saponification. Furthermore FOG deposits were found to be more complex than previously documented and contain free fatty acids, fatty acid metal salts, triacylglycerol's, diacylglycerol's and, monoacylglycerol's. Lastly it was found that FOG deposits that only contained saturated fatty acids were on average 2.1 times higher yield strength than deposits that contained unsaturated fatty acids. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Evaluation of creep-fatigue/ environment interaction in Ni-base wrought alloys for HTGR application

    International Nuclear Information System (INIS)

    Hattori, Hiroshi; Kitagawa, Masaki; Ohtomo, Akira

    1986-01-01

    High Temperature Gas-cooled Reactor (HTGR) systems should be designed based on the high temperature structural strength design procedures. On the development of design code, the determination of failure criteria under cyclic loading and severe environments is one of the most important items. By using the previous experimental data for Ni-base wrought alloys, Inconel 617 and Hastelloy XR, several evaluation methods for creep-fatigue interaction were examined for their capability to predict their cyclic loading behavior for HTGR application. At first, the strainrange partitioning method, the frequency modified damage function and the linear damage summation rule were discussed. However, these methods were not satisfactory with the above experimental results. Thus, in this paper, a new fracture criterion, which is a modification of the linear damage summation rule, is proposed based on the experimental data. In this criterion, fracture is considered to occur when the sum of the fatigue damage, which is the function of the applied cyclic strain magnitude, and the modified creep damage, which is the function of the applied cyclic stress magnitude (determined as time devided by cyclic creep rupture time reflecting difference of creep damages by tensile creep and compressive creep), reaches a constant value. This criterion was successfully applied to the life prediction of materials at HTGR temperatures. (author)

  8. Electrochemical evaluation of avidin-biotin interaction on self-assembled gold electrodes

    International Nuclear Information System (INIS)

    Ding, S.-J.; Chang, B.-W.; Wu, C.-C.; Lai, M.-F.; Chang, H.-C.

    2005-01-01

    The avidin-biotin interaction on 11-mercaptoundecanoic acid self-assembled gold electrodes was investigated by means of cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The interfacial properties of the modified electrodes were evaluated in the presence of the Fe(China) 6 3-/4- couple redox as a probe. A simple equivalent circuit model with a constant phase element was used to interpret the obtained impedance spectra. The results of cyclic voltammetry showed that the voltammetric behavior of the redox probe was influenced by the electrode surface modification. It is evident that the accumulation of treated substances and the binding of biotin to avidin on the electrode surface resulted in the increasing electron-transfer resistance and the decreasing capacitance. The changes in the electron-transfer resistance on the avidin-modified electrodes were more sensitive than that in the capacitance while detecting biotin over the 2-10 μg/mL concentration. The detection amount can be as low as 20 ng/mL based on the electron-transfer resistance that presented the change of 4.3 kΩ without the use of labels. The development of a rapid, facile, and sensitive method for the quantitation of nanogram quantities of biomolecules utilizing EIS may be achieved

  9. Synthesis of dimeric arylβ-D-galactopyranosides for the evaluation of their interaction with the Erythrina cristagalli lectin

    International Nuclear Information System (INIS)

    Figueiredo, Rute Cunha; Meyer, Nadia Burkowski; Prado, Maria Auxiliadora Fontes; Alves, Ricardo Jose; Rojo, Javier

    2009-01-01

    The synthesis of two new D-galactose-based dimers having a 1,4-butanediamine spacer is reported aiming at the evaluation of their interaction with the Erythrina cristagalli lectin. The title compounds were prepared in four and five steps from 2,3,4,6-tetra-O-acetyl-β-D-galactopyranoside bromide, in 20 % and 15 % overall yield, respectively, using the Doebner modification of the Koenavenagel reaction as the key sep. The lectin-carbohydrate interaction could be evaluated for only one dimer, due to solubility problems. A twofold enhancement of affinity was observed, compared to the corresponding monovalent ligand. (author)

  10. Streamlined analysis technique for the evaluation of pellet clad interaction in PWR reload cores

    International Nuclear Information System (INIS)

    Beard, Ch.; Morita, T.; Brown, J.

    2007-01-01

    For some applications, an analysis is required to explicitly demonstrate that fuel failure due to pellet-clad interaction (PCI) is prevented by the core limits and the protection system for both Condition I (normal operation) operation and for Condition II (events of moderate frequency) events. This analysis needs to address the entire range of normal operation allowed by the Technical Specifications and all Condition II transients. The obvious approach which has been utilized for many years is a simulation of normal operation power maneuvers followed by explicit Condition II transients as a function of key core parameters. This is a sampling approach and has concerns about the overall coverage of the potential space. An alternative approach is the 3D FAC power distribution analysis methodology that was based upon the Westinghouse Relaxed Axial Offset Control Strategy (RAOC) evaluation process. The 3D FAC methodology uses a parametric representation of variables affecting the power distributions, defining a grid mesh over a space of Condition I and Condition II parameters. The operation space is defined by a power range, temperature range, rod position range, axial offset range, core protection limits and representative xenon distributions. Then the 3D FAC evaluation consists of systematically calculating the 3D power distribution and margin to the core and fuel limits for each mesh point of this multi-dimensional space. The PCI margin is obtained by the comparison of the 3D power distributions over the Condition II space and the 3D maximum allowed power, which is dependent on the fuel rod history. The fuel history model utilizes the power history developed in the 3-dimensional nuclear analysis code to define local powers for the specified fuel rods to be analyzed. It tracks the rod history and provides the maximum allowed power for the point. This model is appropriate for base load operation, extended reduced power operation, return to power operation and

  11. Aircraft Abnormal Conditions Detection, Identification, and Evaluation Using Innate and Adaptive Immune Systems Interaction

    Science.gov (United States)

    Al Azzawi, Dia

    Abnormal flight conditions play a major role in aircraft accidents frequently causing loss of control. To ensure aircraft operation safety in all situations, intelligent system monitoring and adaptation must rely on accurately detecting the presence of abnormal conditions as soon as they take place, identifying their root cause(s), estimating their nature and severity, and predicting their impact on the flight envelope. Due to the complexity and multidimensionality of the aircraft system under abnormal conditions, these requirements are extremely difficult to satisfy using existing analytical and/or statistical approaches. Moreover, current methodologies have addressed only isolated classes of abnormal conditions and a reduced number of aircraft dynamic parameters within a limited region of the flight envelope. This research effort aims at developing an integrated and comprehensive framework for the aircraft abnormal conditions detection, identification, and evaluation based on the artificial immune systems paradigm, which has the capability to address the complexity and multidimensionality issues related to aircraft systems. Within the proposed framework, a novel algorithm was developed for the abnormal conditions detection problem and extended to the abnormal conditions identification and evaluation. The algorithm and its extensions were inspired from the functionality of the biological dendritic cells (an important part of the innate immune system) and their interaction with the different components of the adaptive immune system. Immunity-based methodologies for re-assessing the flight envelope at post-failure and predicting the impact of the abnormal conditions on the performance and handling qualities are also proposed and investigated in this study. The generality of the approach makes it applicable to any system. Data for artificial immune system development were collected from flight tests of a supersonic research aircraft within a motion-based flight

  12. Streamlined analysis technique for the evaluation of pellet clad interaction in PWR reload cores

    Energy Technology Data Exchange (ETDEWEB)

    Beard, Ch.; Morita, T.; Brown, J. [Westinghouse Electric Company, LLC, Nuclear Fuel Div., Pittsburgh, PA (United States)

    2007-07-01

    For some applications, an analysis is required to explicitly demonstrate that fuel failure due to pellet-clad interaction (PCI) is prevented by the core limits and the protection system for both Condition I (normal operation) operation and for Condition II (events of moderate frequency) events. This analysis needs to address the entire range of normal operation allowed by the Technical Specifications and all Condition II transients. The obvious approach which has been utilized for many years is a simulation of normal operation power maneuvers followed by explicit Condition II transients as a function of key core parameters. This is a sampling approach and has concerns about the overall coverage of the potential space. An alternative approach is the 3D FAC power distribution analysis methodology that was based upon the Westinghouse Relaxed Axial Offset Control Strategy (RAOC) evaluation process. The 3D FAC methodology uses a parametric representation of variables affecting the power distributions, defining a grid mesh over a space of Condition I and Condition II parameters. The operation space is defined by a power range, temperature range, rod position range, axial offset range, core protection limits and representative xenon distributions. Then the 3D FAC evaluation consists of systematically calculating the 3D power distribution and margin to the core and fuel limits for each mesh point of this multi-dimensional space. The PCI margin is obtained by the comparison of the 3D power distributions over the Condition II space and the 3D maximum allowed power, which is dependent on the fuel rod history. The fuel history model utilizes the power history developed in the 3-dimensional nuclear analysis code to define local powers for the specified fuel rods to be analyzed. It tracks the rod history and provides the maximum allowed power for the point. This model is appropriate for base load operation, extended reduced power operation, return to power operation and

  13. An evaluation of the appropriateness and safety of nurse and midwife prescribing in Ireland.

    LENUS (Irish Health Repository)

    Naughton, Corina

    2012-09-19

    AIM: To evaluate the clinical appropriateness and safety of nurse and midwife prescribing practice. BACKGROUND: The number of countries introducing nurse and midwife prescribing is increasing; however, concerns over patient safety remain. DESIGN: A multi-site documentation evaluation was conducted using purposeful and random sampling. The sample included 142 patients\\' records and 208 medications prescribed by 25 Registered Nurse Prescribers. METHODS: Data were extracted from patient and prescription records between March-May 2009. Two expert reviewers applied the modified Medication Appropriate Index tool (8 criteria) to each drug. The percentage of appropriate or inappropriate responses for each criterion was reported. Reviewer concordance was measured using the Cohen\\'s kappa statistic (inter-rater reliability). RESULTS: Nurse or midwife prescribers from eight hospitals working in seventeen different areas of practice were included. The reviewers judged that 95-96% of medicines prescribed were indicated and effective for the diagnosed condition. Criteria relating to dosage, directions, drug-drugs or disease-condition interaction, and duplication of therapy were judged appropriate in 87-92% of prescriptions. Duration of therapy received the lowest value at 76%. Overall, reviewers indicated that between 69 (reviewer 2)-80% (reviewer 1) of prescribing decisions met all eight criteria. CONCLUSION: The majority of nurse and midwife prescribing decisions were deemed safe and clinically appropriate. However, risk of inappropriate prescribing with the potential for drug errors was detected. Continuing education and evaluation of prescribing practice, especially related to drug and condition interactions, is required to maximize appropriate and safe prescribing.

  14. Comparative evaluation of the drug interaction screening programs MediQ and ID PHARMA CHECK in neurological inpatients.

    Science.gov (United States)

    Zorina, Olesya I; Haueis, Patrick; Semmler, Alexander; Marti, Isabelle; Gonzenbach, Roman R; Guzek, Markus; Kullak-Ublick, Gerd A; Weller, Michael; Russmann, Stefan

    2012-08-01

    The comparative evaluation of clinical decision support software (CDSS) programs regarding their sensitivity and positive predictive value for the identification of clinically relevant drug interactions. In this research, we used a cross-sectional study that identified potential drug interactions using the CDSS MediQ and the ID PHARMA CHECK in 484 neurological inpatients. Interactions were reclassified according to the Zurich Interaction System, a multidimensional classification that incorporates the Operational Classification of Drug Interactions. In 484 patients with 2812 prescriptions, MediQ and ID PHARMA CHECK generated a total of 1759 and 1082 alerts, respectively. MediQ identified 658 unique potentially interacting combinations, 8 classified as "high danger," 164 as "average danger," and 486 as "low danger." ID PHARMA CHECK detected 336 combinations assigned to one or several of 12 risk and management categories. Altogether, both CDSS issued alerts relating to 808 unique potentially interacting combinations. According to the Zurich Interaction System, 6 of these were contraindicated, 25 were provisionally contraindicated, 190 carried a conditional risk, and 587 had a minimal risk of adverse events. The positive predictive value for alerts having at least a conditional risk was 0.24 for MediQ and 0.48 for ID PHARMA CHECK. CDSS showed major differences in the identification and grading of interactions, and many interactions were only identified by one of the two CDSS. For both programs, only a small proportion of all identified interactions appeared clinically relevant, and the selected display of alerts that imply management changes is a key issue in the further development and local setup of such programs. Copyright © 2012 John Wiley & Sons, Ltd.

  15. Evaluation of multiple intelligences in children aged 7 to 11 years through the implementation of an interactive software

    OpenAIRE

    Rebolledo Rodríguez, Rigel A.; Samaniego González, Euclides

    2017-01-01

    This document describes the evaluation project of multiple intelligences in children aged 7 to 11 years through the implementation of an interactive software, developed on Android for tablets, allowing parents, teachers, tutors, psy-chologists or other responsible adult, identifying the different types of intelligences that have children in order to know each other and develop their skills and their future potential. Similarly, research was developed to evaluate the effective-ness of the t...

  16. Measuring the Impact of a Moving Target: Towards a Dynamic Framework for Evaluating Collaborative Adaptive Interactive Technologies

    OpenAIRE

    O?Grady, Laura; Witteman, Holly; Bender, Jacqueline L; Urowitz, Sara; Wiljer, David; Jadad, Alejandro R

    2009-01-01

    Background Website evaluation is a key issue for researchers, organizations, and others responsible for designing, maintaining, endorsing, approving, and/or assessing the use and impact of interventions designed to influence health and health services. Traditionally, these evaluations have included elements such as content credibility, interface usability, and overall design aesthetics. With the emergence of collaborative, adaptive, and interactive ("Web 2.0") technologies such as wikis and o...

  17. Evaluation of documented drug interactions and contraindications associated with herbs and dietary supplements: a systematic literature review.

    Science.gov (United States)

    Tsai, H-H; Lin, H-W; Simon Pickard, A; Tsai, H-Y; Mahady, G B

    2012-11-01

    The use of herbs and dietary supplements (HDS) alone or concomitantly with medications can potentially increase the risk of adverse events experienced by the patients. This review aims to evaluate the documented HDS-drug interactions and contraindications. A structured literature review was conducted on PubMed, EMBASE, Cochrane Library, tertiary literature and Internet. While 85 primary literatures, six books and two web sites were reviewed for a total of 1,491 unique pairs of HDS-drug interactions, 213 HDS entities and 509 medications were involved. HDS products containing St. John's Wort, magnesium, calcium, iron, ginkgo had the greatest number of documented interactions with medications. Warfarin, insulin, aspirin, digoxin, and ticlopidine had the greatest number of reported interactions with HDS. Medications affecting the central nervous system or cardiovascular system had more documented interactions with HDS. Of the 882 HDS-drug interactions being described its mechanism and severity, 42.3% were due to altered pharmacokinetics and 240 were described as major interactions. Of the 152 identified HDS contraindications, the most frequent involved gastrointestinal (16.4%), neurological (14.5%), and renal/genitourinary diseases (12.5%). Flaxseed, echinacea, and yohimbe had the largest number of documented contraindications. Although HDS-drug interactions and contraindications primarily concerned a relatively small subset of commonly used medications and HDS entities, this review provides the summary to identify patients, HDS products, and medications that are more susceptible to HDS-drug interactions and contraindications. The findings would facilitate the health-care professionals to communicate these documented interactions and contraindications to their patients and/or caregivers thereby preventing serious adverse events and improving desired therapeutic outcomes. © 2012 Blackwell Publishing Ltd.

  18. Evaluating Multiple Levels of an Interaction Fidelity Continuum on Performance and Learning in Near-Field Training Simulations.

    Science.gov (United States)

    Bhargava, Ayush; Bertrand, Jeffrey W; Gramopadhye, Anand K; Madathil, Kapil C; Babu, Sabarish V

    2018-04-01

    With costs of head-mounted displays (HMDs) and tracking technology decreasing rapidly, various virtual reality applications are being widely adopted for education and training. Hardware advancements have enabled replication of real-world interactions in virtual environments to a large extent, paving the way for commercial grade applications that provide a safe and risk-free training environment at a fraction of the cost. But this also mandates the need to develop more intrinsic interaction techniques and to empirically evaluate them in a more comprehensive manner. Although there exists a body of previous research that examines the benefits of selected levels of interaction fidelity on performance, few studies have investigated the constituent components of fidelity in a Interaction Fidelity Continuum (IFC) with several system instances and their respective effects on performance and learning in the context of a real-world skills training application. Our work describes a large between-subjects investigation conducted over several years that utilizes bimanual interaction metaphors at six discrete levels of interaction fidelity to teach basic precision metrology concepts in a near-field spatial interaction task in VR. A combined analysis performed on the data compares and contrasts the six different conditions and their overall effects on performance and learning outcomes, eliciting patterns in the results between the discrete application points on the IFC. With respect to some performance variables, results indicate that simpler restrictive interaction metaphors and highest fidelity metaphors perform better than medium fidelity interaction metaphors. In light of these results, a set of general guidelines are created for developers of spatial interaction metaphors in immersive virtual environments for precise fine-motor skills training simulations.

  19. Understanding the Effect of Response Rate and Class Size Interaction on Students Evaluation of Teaching in a Higher Education

    Science.gov (United States)

    Al Kuwaiti, Ahmed; AlQuraan, Mahmoud; Subbarayalu, Arun Vijay

    2016-01-01

    Objective: This study aims to investigate the interaction between response rate and class size and its effects on students' evaluation of instructors and the courses offered at a higher education Institution in Saudi Arabia. Study Design: A retrospective study design was chosen. Methods: One thousand four hundred and forty four different courses…

  20. Designing and Evaluating Tutoring Feedback Strategies for Digital Learning Environments on the Basis of the Interactive Tutoring Feedback Model

    Science.gov (United States)

    Narciss, Susanne

    2013-01-01

    This paper describes the interactive tutoring feedback model (ITF-model; Narciss, 2006; 2008), and how it can be applied to the design and evaluation of feedback strategies for digital learning environments. The ITF-model conceptualizes formative tutoring feedback as a multidimensional instructional activity that aims at contributing to the…

  1. Evaluation of an Interactive Workshop Designed to Teach Practical Welfare Techniques to Beef Cattle Caretakers and Decision Makers

    Science.gov (United States)

    Dewell, Reneé; Hanthorn, Christy; Danielson, Jared; Burzette, Rebecca; Coetzee, Johann; Griffin, D. Dee; Ramirez, Alejandro; Dewell, Grant

    2015-01-01

    The purpose of the project was to evaluate the use of an interactive workshop designed to teach novel practical welfare techniques to beef cattle caretakers and decision makers. Following training, respondents reported being more likely to use or recommend use of local anesthesia for dehorning and castration and were more inclined to use meloxicam…

  2. An Evaluation of the Interactive Query Expansion in an Online Library Catalogue with a Graphical User Interface.

    Science.gov (United States)

    Hancock-Beaulieu, Micheline; And Others

    1995-01-01

    An online library catalog was used to evaluate an interactive query expansion facility based on relevance feedback for the Okapi, probabilistic, term weighting, retrieval system. A graphical user interface allowed searchers to select candidate terms extracted from relevant retrieved items to reformulate queries. Results suggested that the…

  3. CountMeIn: Evaluating Social Presence in a Collaborative Pervasive Mobile Game Using NFC and Touchscreen Interaction

    NARCIS (Netherlands)

    Wolbert, M.; El Ali, A.; Nack, F.

    2014-01-01

    This paper presents the motivation, design and evaluation of CountMeIn, a mobile collaborative pervasive memory game to revive social interactions in public places (e.g. a train station or bus stop). Two versions of CountMeIn were tested; an NFC-based and a touchscreen version. In a 2×1

  4. An Interactive 3D Virtual Anatomy Puzzle for Learning and Simulation - Initial Demonstration and Evaluation.

    Science.gov (United States)

    Messier, Erik; Wilcox, Jascha; Dawson-Elli, Alexander; Diaz, Gabriel; Linte, Cristian A

    2016-01-01

    To inspire young students (grades 6-12) to become medical practitioners and biomedical engineers, it is necessary to expose them to key concepts of the field in a way that is both exciting and informative. Recent advances in medical image acquisition, manipulation, processing, visualization, and display have revolutionized the approach in which the human body and internal anatomy can be seen and studied. It is now possible to collect 3D, 4D, and 5D medical images of patient specific data, and display that data to the end user using consumer level 3D stereoscopic display technology. Despite such advancements, traditional 2D modes of content presentation such as textbooks and slides are still the standard didactic equipment used to teach young students anatomy. More sophisticated methods of display can help to elucidate the complex 3D relationships between structures that are so often missed when viewing only 2D media, and can instill in students an appreciation for the interconnection between medicine and technology. Here we describe the design, implementation, and preliminary evaluation of a 3D virtual anatomy puzzle dedicated to helping users learn the anatomy of various organs and systems by manipulating 3D virtual data. The puzzle currently comprises several components of the human anatomy and can be easily extended to include additional organs and systems. The 3D virtual anatomy puzzle game was implemented and piloted using three display paradigms - a traditional 2D monitor, a 3D TV with active shutter glass, and the DK2 version Oculus Rift, as well as two different user interaction devices - a space mouse and traditional keyboard controls.

  5. Experimental evaluation of the interaction between strength concrete block walls under vertical loads

    Directory of Open Access Journals (Sweden)

    L. O. CASTRO

    Full Text Available Abstract This paper aims to evaluate the interaction between structural masonry walls made of high performance concrete blocks, under vertical loads. Two H-shaped flanged wall series, all full scale and using direct bond, have been analyzed experimentally. In one series, three flanged-walls were built with the central wall (web supported and, in the other one, three specimens were built without any support at the central web. The load was applied on the central wall and vertical displacements were measured by means of displacement transducers located at eighteen points in the wall-assemblages. The results showed that the estimated load values for the flanges were close to those supported by the walls without central support, where 100% of the load transfer to the flanges occur. The average transfer load rate calculated based on the deformation ratio in the upper and lower section of the flanged-walls, with the central web support, were 37.65% and 77.30%, respectively, showing that there is load transfer from the central wall (web toward the flanges, particularly in the lower part of the flanged walls. Thus, there is indication that the distribution of vertical loads may be considered for projects of buildings for service load, such as in the method of isolated walls group. For estimation of the failure load, the method that considers the walls acting independently showed better results, due to the fact that failure started at the top of the central wall, where there is no effect of load distribution from the adjacent walls.

  6. Limbic-Auditory Interactions of Tinnitus: An Evaluation Using Diffusion Tensor Imaging.

    Science.gov (United States)

    Gunbey, H P; Gunbey, E; Aslan, K; Bulut, T; Unal, A; Incesu, L

    2017-06-01

    Tinnitus is defined as an imaginary subjective perception in the absence of an external sound. Convergent evidence proposes that tinnitus perception includes auditory, attentional and emotional components. The aim of this study was to investigate the thalamic, auditory and limbic interactions associated with tinnitus-related distress by Diffusion Tensor Imaging (DTI). A total of 36 tinnitus patients, 20 healthy controls underwent an audiological examination, as well as a magnetic resonance imaging protocol including structural and DTI sequences. All participants completed the Tinnitus Handicap Inventory (THI) and Visual Analog Scales (VAS) related with tinnitus. The fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained for the auditory cortex (AC), inferior colliculus (IC), lateral lemniscus (LL), medial geniculate body (MGB), thalamic reticular nucleus (TRN), amygdala (AMG), hippocampus (HIP), parahippocampus (PHIP) and prefrontal cortex (PFC). In tinnitus patients the FA values of IC, MGB, TRN, AMG, HIP decreased and the ADC values of IC, MGB, TRN, AMG, PHIP increased significantly. The contralateral IC-LL and bilateral MGB FA values correlated negatively with hearing loss. A negative relation was found between the AMG-HIP FA values and THI and VAS scores. Bilateral ADC values of PHIP and PFC significantly correlated with the attention deficiency-VAS scores. In conclusion, this is the first DTI study to investigate the grey matter structures related to tinnitus perception and the significant correlation of FA and ADC with clinical parameters suggests that DTI can provide helpful information for tinnitus. Magnifying the microstructures in DTI can help evaluate the three faces of tinnitus nature: hearing, emotion and attention.

  7. Cytogenetic evaluation and DNA interaction studies of the food colorants amaranth, erythrosine and tartrazine.

    Science.gov (United States)

    Mpountoukas, Panagiotis; Pantazaki, Anastasia; Kostareli, Efterpi; Christodoulou, Pantelitsa; Kareli, Dimitra; Poliliou, Stamatia; Mourelatos, Costas; Lambropoulou, Vasso; Lialiaris, Theodore

    2010-10-01

    Food coloring agents, amaranth, erythrosine and tartrazine have been tested at 0.02-8mM in human peripheral blood cells in vitro, in order to investigate their genotoxic, cytotoxic and cytostatic potential. Amaranth at the highest concentration (8mM) demonstrates high genotoxicity, cytostaticity and cytotoxicity. The frequency of SCEs/cell was increased 1.7 times over the control level. Additionally, erythrosine at 8, 4 and 2mM shows a high cytotoxicity and cytostaticity. Finally, tartrazine seems to be toxic at 8 and 4mM. No signs of genotoxicity were observed. Reversely, tartrazine showed cytotoxicity at 1 and 2mM. Furthermore, spectroscopic titration studies for the interaction of these food additives with DNA showed that these dyes bind to calf thymus DNA and distinct isosbestic points are observed clearly suggesting binding of the dyes to DNA. Additionally DNA electrophoretic mobility experiments showed that these colorants are obviously capable for strong binding to linear dsDNA causing its degradation. PCR amplification of all DNA fragments (which previously were pre-treated with three different concentrations of the colorants, extracted from agarose gel after separation and then purified), seems to be attenuated with a manner dye concentration-dependent reflecting in a delayed electrophoretic mobility due to the possible binding of some molecules of the dyes. Evaluation of the data and curves were obtained after quantitative and qualitative analysis of the lanes of the gel by an analyzer computer program. Our results indicate that these food colorants had a toxic potential to human lymphocytes in vitro and it seems that they bind directly to DNA. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  8. Some fundamental aspects of fault-tree and digraph-matrix relationships for a systems-interaction evaluation procedure

    International Nuclear Information System (INIS)

    Alesso, H.P.

    1982-01-01

    Recent events, such as Three Mile Island-2, Brown's Ferry-3, and Crystal River-3, have demonstrated that complex accidents can occur as a result of dependent (common-cause/mode) failures. These events are now being called Systems Interactions. A procedure for the identification and evaluation of Systems Interactions is being developed by the NRC. Several national laboratories and utilities have contributed preliminary procedures. As a result, there are several important views of the Systems Interaction problem. This report reviews some fundamental mathematical background of both fault-oriented and success-oriented risk analyses in order to bring out the advantages and disadvantages of each. In addition, it outlines several fault-oriented/dependency analysis approaches and several success-oriented/digraph-matrix approaches. The objective is to obtain a broad perspective of present options for solving the Systems Interaction problem

  9. Development and Evaluation of an Interactive Electronic Laboratory Manual for Cooperative Learning of Medical Histology

    Science.gov (United States)

    Khalil, Mohammed K.; Kirkley, Debbie L.; Kibble, Jonathan D.

    2013-01-01

    This article describes the development of an interactive computer-based laboratory manual, created to facilitate the teaching and learning of medical histology. The overarching goal of developing the manual is to facilitate self-directed group interactivities that actively engage students during laboratory sessions. The design of the manual…

  10. Pharmacogenomics of the human ABC transporter ABCG2: from functional evaluation to drug molecular design

    Science.gov (United States)

    Ishikawa, Toshihisa; Tamura, Ai; Saito, Hikaru; Wakabayashi, Kanako; Nakagawa, Hiroshi

    2005-10-01

    In the post-genome-sequencing era, emerging genomic technologies are shifting the paradigm for drug discovery and development. Nevertheless, drug discovery and development still remain high-risk and high-stakes ventures with long and costly timelines. Indeed, the attrition of drug candidates in preclinical and development stages is a major problem in drug design. For at least 30% of the candidates, this attrition is due to poor pharmacokinetics and toxicity. Thus, pharmaceutical companies have begun to seriously re-evaluate their current strategies of drug discovery and development. In that light, we propose that a transport mechanism-based design might help to create new, pharmacokinetically advantageous drugs, and as such should be considered an important component of drug design strategy. Performing enzyme- and/or cell-based drug transporter, interaction tests may greatly facilitate drug development and allow the prediction of drug-drug interactions. We recently developed methods for high-speed functional screening and quantitative structure-activity relationship analysis to study the substrate specificity of ABC transporters and to evaluate the effect of genetic polymorphisms on their function. These methods would provide a practical tool to screen synthetic and natural compounds, and these data can be applied to the molecular design of new drugs. In this review article, we present an overview on the genetic polymorphisms of human ABC transporter ABCG2 and new camptothecin analogues that can circumvent AGCG2-associated multidrug resistance of cancer.

  11. Relevant patient perceptions and experiences for evaluating quality of interaction with physiotherapists during outpatient rehabilitation: a qualitative study.

    Science.gov (United States)

    Del Baño-Aledo, M Elena; Medina-Mirapeix, Francesc; Escolar-Reina, Pilar; Montilla-Herrador, Joaquina; Collins, Sean M

    2014-03-01

    To identify elements of the physiotherapist-patient interaction considered by patients when they evaluate the quality of care in outpatient rehabilitation settings. A qualitative study with nine focus groups, Two researchers conducted the focus groups, and a topic guide with predetermined questions was used. Each group discussion was audiotaped,, transcribed verbatim and analyzed thematically according to a modified grounded theory approach. Three postacute ambulatory centers in Barcelona, Madrid and Seville (Spain). Fifty-seven adults undergoing outpatient rehabilitation for musculoskeletal conditions/injuries. Patients based their evaluations of quality of care on their assessment of physiotherapists' willingness to provide information and education, technical expertise and interpersonal manners (eg. respect, emotional support and sensitivity changes in the patient's status). Both positive and negative aspects of the physiotherapist-patient interaction emerged under all these themes, except for friendly and respectful communication. This study identified which elements of the physiotherapist-patient interaction are considered by patients when evaluating the quality of care in rehabilitation outpatient settings. Further research should work to develop self-report questionnaires about patients' experiences of the physiotherapist-patient interaction in rehabilitation services to provide empirical and quantitative evidence. Copyright © 2013 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

  12. Drug-Target Interaction Prediction through Label Propagation with Linear Neighborhood Information.

    Science.gov (United States)

    Zhang, Wen; Chen, Yanlin; Li, Dingfang

    2017-11-25

    Interactions between drugs and target proteins provide important information for the drug discovery. Currently, experiments identified only a small number of drug-target interactions. Therefore, the development of computational methods for drug-target interaction prediction is an urgent task of theoretical interest and practical significance. In this paper, we propose a label propagation method with linear neighborhood information (LPLNI) for predicting unobserved drug-target interactions. Firstly, we calculate drug-drug linear neighborhood similarity in the feature spaces, by considering how to reconstruct data points from neighbors. Then, we take similarities as the manifold of drugs, and assume the manifold unchanged in the interaction space. At last, we predict unobserved interactions between known drugs and targets by using drug-drug linear neighborhood similarity and known drug-target interactions. The experiments show that LPLNI can utilize only known drug-target interactions to make high-accuracy predictions on four benchmark datasets. Furthermore, we consider incorporating chemical structures into LPLNI models. Experimental results demonstrate that the model with integrated information (LPLNI-II) can produce improved performances, better than other state-of-the-art methods. The known drug-target interactions are an important information source for computational predictions. The usefulness of the proposed method is demonstrated by cross validation and the case study.

  13. Structure and interaction in dense colloidal systems: evaluation of scattering data by the generalized indirect Fourier transformation method

    International Nuclear Information System (INIS)

    Fritz, Gerhard; Glatter, Otto

    2006-01-01

    The generalized indirect Fourier transformation (GIFT) technique is a versatile tool for the evaluation of small angle scattering data. It does not depend on models for the size and shape of the particles and requires model assumptions only for the interaction effects that are typically not as sensitive to the details of the assumptions. We review here the development of the technique from its inception, focusing on the included interaction models for hard, charged and attractive spheres, and lamellae. A considerable number of applications has also been reported ranging from surfactants, emulsions, microemulsions, food science, and ceramics to melts and block-copolymers

  14. A general method, a la Transport, for evaluation of the perturbing effects of solenoidal inserts in storage ring interaction regions

    International Nuclear Information System (INIS)

    Murray, J.J.

    1976-07-01

    It may be expected that solenoid magnets will be used in many storage ring experiments. Typically an insert would consist of a main solenoid at the interaction point with a symmetrical pair of compensating solenoids located somewhere between the main solenoid and the ends of the interaction region. The magnetic fields of such an insert may significantly affect storage ring performance. We suggest here a simple, systematic method for evaluation of the effects, which together with adequate design supervision and field measurements will help to prevent any serious operational problems that might result if significant perturbations went unnoticed. 5 refs

  15. GSFLOW model simulations used to evaluate the impact of irrigated agriculture on surface water - groundwater interaction

    Data.gov (United States)

    Department of the Interior — Watershed-scale coupled surface water (SW) – groundwater (GW) flow modeling was used to examine changes in streamflow and SW – GW interaction resulting from...

  16. Soil-structure interaction effects on the reliability evaluation of reactor containments

    International Nuclear Information System (INIS)

    Pires, J.; Hwang, H.; Reich, M.

    1986-01-01

    The probability-based method for the seismic reliability assessment of nuclear structures, which has been developed at Brookhaven National Laboratory (BNL), is extended to include the effects of soil-structure interaction. A reinforced concrete containment building is analyzed in order to examine soil-structure interaction effects on: (1) structural fragilities; (2) floor response spectra statistics; and (3) correlation coefficients for total acceleration responses at specified structural locations

  17. Cannabidiol exhibits anxiolytic but not antipsychotic property evaluated in the social interaction test.

    Science.gov (United States)

    Almeida, Valéria; Levin, Raquel; Peres, Fernanda Fiel; Niigaki, Suzy T; Calzavara, Mariana B; Zuardi, Antônio W; Hallak, Jaime E; Crippa, José A; Abílio, Vanessa C

    2013-03-05

    Cannabidiol (CBD), a non-psychotomimetic compound of the Cannabis sativa, has been reported to have central therapeutic actions, such as antipsychotic and anxiolytic effects. We have recently reported that Spontaneously Hypertensive Rats (SHRs) present a deficit in social interaction that is ameliorated by atypical antipsychotics. In addition, SHRs present a hyperlocomotion that is reverted by typical and atypical antipsychotics, suggesting that this strain could be useful to study negative symptoms (modeled by a decrease in social interaction) and positive symptoms (modeled by hyperlocomotion) of schizophrenia as well as the effects of potential antipsychotics drugs. At the same time, an increase in social interaction in control animals similar to that induced by benzodiazepines is used to screen potential anxiolytic drugs. The aim of this study was to investigate the effects of CBD on social interaction presented by control animals (Wistar) and SHRs. The lowest dose of CBD (1mg/kg) increased passive and total social interaction of Wistar rats. However, the hyperlocomotion and the deficit in social interaction displayed by SHRs were not altered by any dose of CBD. Our results do not support an antipsychotic property of cannabidiol on symptoms-like behaviors in SHRs but reinforce the anxiolytic profile of this compound in control rats. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Evaluation of the Humanity Research Paradigms based on Analysis of Human – Environment Interaction

    Directory of Open Access Journals (Sweden)

    Reza Sameh

    2015-09-01

    Full Text Available As claimed by many behavioral scientists, designing should be based on the knowledge of interaction between human and environment. Environmental quality is also created in the context in which humans interact with their environment. To achieve such quality, designers should develop appropriate models for explaining this relationship, and this requires an understanding of human nature and the environment. Criticisms on the Modern Movement have shown that architects have often used incomplete and simplistic models in this regard, while most of design ideas are based on the definitions of human and environment and the interaction between them. However, the most important question that is raised is that how understanding of human nature and the environment and their interaction, which depends on foundations of different views, can affect the pursuit of quality in designing? Therefore, the present paper, in addition to introduction and comparison of common paradigms in humanities as the and methodological foundation of human sciences, aims to deal with the relationship of human and the environment from the perspective of objectivist, relativist, and critical paradigms in order to identify the characteristics and differences in their views on the analysis of the quality of this interaction. This is the most important step that paves the way for understanding the qualitative foundations of the environment and human life quality and also the quality of interaction between them.

  19. Evaluation of transporters in drug development: Current status and contemporary issues.

    Science.gov (United States)

    Lee, Sue-Chih; Arya, Vikram; Yang, Xinning; Volpe, Donna A; Zhang, Lei

    2017-07-01

    Transporters govern the access of molecules to cells or their exit from cells, thereby controlling the overall distribution of drugs to their intracellular site of action. Clinically relevant drug-drug interactions mediated by transporters are of increasing interest in drug development. Drug transporters, acting alone or in concert with drug metabolizing enzymes, can play an important role in modulating drug absorption, distribution, metabolism and excretion, thus affecting the pharmacokinetics and/or pharmacodynamics of a drug. The drug interaction guidance documents from regulatory agencies include various decision criteria that may be used to predict the need for in vivo assessment of transporter-mediated drug-drug interactions. Regulatory science research continues to assess the prediction performances of various criteria as well as to examine the strength and limitations of each prediction criterion to foster discussions related to harmonized decision criteria that may be used to facilitate global drug development. This review discusses the role of transporters in drug development with a focus on methodologies in assessing transporter-mediated drug-drug interactions, challenges in both in vitro and in vivo assessments of transporters, and emerging transporter research areas including biomarkers, assessment of tissue concentrations, and effect of diseases on transporters. Published by Elsevier B.V.

  20. Pharmacokinetic interactions between contraceptives and antiepileptic drugs

    DEFF Research Database (Denmark)

    Sabers, A.

    2008-01-01

    The occurrence of bi-directional drug interactions between antiepileptic drugs (AEDs) and combined oral contraceptives (M) pose potential risks of unintended pregnancy and as well as seizure deterioration. It is well established that several of the older AEDs (carbamazepine, phenytoin...... AEDs, which undergoes glucuronidation processes, such as valproate and oxcarbazepine, may be affected by OCs. The magnitude of the drug-drug interactions show in general wide inter-individual variability and the change in the elimination rate is often unpredictable and can be influenced by a number...... of co-variants such as co-medication of other drugs, as well as genetic and environmental factors. It is therefore recommended that change in OC use is assisted by AED monitoring whenever possible. (C) 2007 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved Udgivelsesdato: 2008/3...

  1. DISTANCE LEARNING STUDENTS’ NEED: Evaluating Interactions from Moore’s Theory of Transactional Distance

    Directory of Open Access Journals (Sweden)

    Rusmanizah USTATI

    2013-04-01

    Full Text Available This study draws on the experience from a focus group interviews under the distance learning programme known as Program Pensiswazahan Guru (PPG organized by the Malaysian Ministry of Education in collaboration with local universities and institutes of education. Its purpose is to uncover students’ perception about the platform used by International Islamic University Malaysia (IIUM which is the Learning Management System (LMS. LMS is a vital instructional medium especially for the varsity distant learners. Michael Moore’s Theory of Transactional Distance is used as the guiding framework to gain insights on learning and interactions in this e-learning setting. Teacher-student interactions are analyzed for better understanding of the phenomena under study. The findings indicate that in terms of usability LMS is perceived as a good platform to acquire information on content and to receive feedback from instructors. However, IIUM learners hope for more interactivity where learners can communicate amongst themselves beside engaging with the instructor-learner- content interactions that they currently experience via the system. This study aspires to provide insights on the significance of interactions from distance learners’ perception.

  2. A conceptual framework to evaluate human-wildlife interactions within coupled human and natural systems

    Directory of Open Access Journals (Sweden)

    Anita T. Morzillo

    2014-09-01

    Full Text Available Landscape characteristics affect human-wildlife interactions. However, there is a need to better understand mechanisms that drive those interactions, particularly feedbacks that exist between wildlife-related impacts, human reaction to and behavior as a result of those impacts, and how land use and landscape characteristics may influence those components within coupled human and natural systems. Current conceptual models of human-wildlife interactions often focus on species population size as the independent variable driving those interactions. Such an approach potentially overlooks important feedbacks among and drivers of human-wildlife interactions that result from mere wildlife presence versus absence. We describe an emerging conceptual framework that focuses on wildlife as a driver of human behavior and allows us to better understand linkages between humans, wildlife, and the broader landscape. We also present results of a pilot analysis related to our own ongoing study of urban rodent control behavior to illustrate one application of this framework within a study of urban landscapes.

  3. Evaluation of Drug Interactions and Prescription Errors of Poultry Veterinarians in North of Iran

    Directory of Open Access Journals (Sweden)

    Madadi MS

    2014-03-01

    Full Text Available Drug prescription errors are a common cause of adverse incidents and may lead to adverse outcomes, sometimes in subtle ways, being compounded by circumstances or further errors. Therefore, it is important that veterinarians issue the correct drug at the correct dose. Using two or more prescribed drugs may lead to drug interactions. Some drug interactions are very harmful and may have potential threats to the patient's health that is called antagonism. In a survey study, medication errors of 750 prescriptions, including dosage errors and drug interactions were studied. The results indicated that 20.8% of prescriptions had at least one drug interaction. The most interactions were related to antibiotics (69.1%, Sulfonamides (46.7%, Methenamine (46.7% and Florfenicol (20.2%. Analysis of dosage errors indicated that total drugs consumed by broilers in the summer are more than winter seasons. Based on these results, avoiding medication errors are important in the balanced prescribing of drugs and regular education of veterinary practitioners in a certain interval is needed.

  4. Systematic research review of observational approaches used to evaluate mother-child mealtime interactions during preschool years.

    Science.gov (United States)

    Bergmeier, Heidi; Skouteris, Helen; Hetherington, Marion

    2015-01-01

    The family meal and social interactions during the meal are important events in a child's life. Specifically, mealtime interactions have been linked to child weight status, the development of children's eating patterns, and socialization. Mealtime interactions may be observed and evaluated to provide insights into this important event beyond self-reported measurements. We aimed to identify, review, and examine studies in which mother-child mealtime behaviors were measured through observation. MEDLINE Complete, PsycINFO, and PsycARTICLES were systematically searched by using sensitive search strategies. We included observational studies of mother-child eating and mealtimes and associations between mother-child interactions and preschool child eating or weight status published to March 2014. Thirteen articles were included in our review. All studies but one were cross-sectional, and none of the studies evaluated how mutual dimensions (e.g., parent responsiveness to the child and child responsiveness to the parent) of dyadic interactions between mothers and children influence maternal feeding practices, children's eating, and weight. The parenting style was associated with maternal feeding practices but not directly with children's eating. Parental discouragements to eat and negative statements about food were associated with higher child weight status. Parental encouragement to eat was associated with higher child weight status as well as maternal body mass index. No associations were shown between maternal reports of feeding practices and observed maternal feeding practices. Parents' overarching attitudes and approaches to parenting appear to be associated with their feeding practices or styles. Future studies should implement longitudinal observational methods with the capacity to measure levels of dimensions within bidirectional parent-child interactions and the extent to which these factors influence maternal practices, children's eating, and weight status.

  5. Evaluation of the effect of prepulses on HF laser-target interactions

    International Nuclear Information System (INIS)

    Matzen, M.K.

    1979-06-01

    We have assessed the effect of multinanosecond, low-power-density prepulses on the interaction of multinanosecond, 10 14 W/cm 2 , approx. 3 -μm HF laser pulses with slab targets. The emphasis is on analyzing absorption and x-ray conversion efficiency. A survey of previous experiments gives no evidence that these prepulses will affect the total absorption. However, prepulses have been observed to cause qualitative changes in both the x-ray spectrum and conversion efficiency. Numerical simulations indicate that the laser-target interaction is effectively insensitive to low-power-density prepulses. These studies imply that basic laser-target experiments with multiplexed, HF laser pulses will provide an important characterization of the interaction of long pulse, multi-line, approx. 3 μm radiation with targets. Future wavelength comparison experiments will require prepulse suppression or target isolation

  6. Aging/Systems Interaction Study, Component Residual Lifetime Evaluation and Feasibility of Relicensing. Progress report, FY 1985

    International Nuclear Information System (INIS)

    Close, J.A.; Jacobs, P.T.; Korth, G.E.; Mudlin, J.M.; Server, W.L.; Spaletta, H.W.

    1985-10-01

    This report documents the work performed on four research tasks in Fiscal Year 1985 (FY-1985) which were part of the Aging/Systems Interaction Study, Component Residual Lifetime Evaluation and Feasibility of Relicensing Project. The technical and management/institutional objectives for the project are described, followed by a description of the results of each task. The work on Task 1 involved identifying and prioritizing new research activities for the Nuclear Regulatory Commission (NRC) Nuclear Plant Aging Research (NPAR) Program. A proposed methodology and plan for aging-system interaction studies was developed in Task 2. The description of Task 3 work comprises a summary of nuclear plant life extension activities in the US, the technical basis associated with the residual life of metallic materials and a proposed plan for research on residual life assessment. Task 4 describes the initial evaluation of selected Standard Review Plan (NUREG-0800) sections to investigate the feasibility of relicensing. 14 refs., 13 figs., 20 tabs

  7. Evaluation of bentonite alteration due to interactions with iron. Sensitivity analyses to identify the important factors for the bentonite alteration

    International Nuclear Information System (INIS)

    Sasamoto, Hiroshi; Wilson, James; Sato, Tsutomu

    2013-01-01

    Performance assessment of geological disposal systems for high-level radioactive waste requires a consideration of long-term systems behaviour. It is possible that the alteration of swelling clay present in bentonite buffers might have an impact on buffer functions. In the present study, iron (as a candidate overpack material)-bentonite (I-B) interactions were evaluated as the main buffer alteration scenario. Existing knowledge on alteration of bentonite during I-B interactions was first reviewed, then the evaluation methodology was developed considering modeling techniques previously used overseas. A conceptual model for smectite alteration during I-B interactions was produced. The following reactions and processes were selected: 1) release of Fe 2+ due to overpack corrosion; 2) diffusion of Fe 2+ in compacted bentonite; 3) sorption of Fe 2+ on smectite edge and ion exchange in interlayers; 4) dissolution of primary phases and formation of alteration products. Sensitivity analyses were performed to identify the most important factors for the alteration of bentonite by I-B interactions. (author)

  8. Experimental evaluation of the interaction effect between plastic and creep deformation

    International Nuclear Information System (INIS)

    Ikegami, K.; Niitsu, Y.

    1985-01-01

    An experimental study of plasticity-creep interaction effects is reported. The combined stress tests are performed on thin wall tubular specimens of SUS 304 stainless steel at room temperature and high temperature (600 0 C). The plastic behaviors subsequent to creep pre-strain and creep behaviors subsequent to plastic pre-strain are obtained for loading along straight stress paths with a corner. The inelastic behaviors including both plastic and creep deformations are experimentally investigated. The interaction effects between plastic and creep deformations are quantitatively estimated with the equi-plastic strain surface. (author)

  9. On evaluation of the nuclear interaction effect on muon sticking in μ-catalyzed dt synthesis

    International Nuclear Information System (INIS)

    Khiger, L.Ya.

    1994-01-01

    The effect of nucler interaction on the muon -alpha-particle sticking coefficient is considered on the basis of the previously developed formalism of description of the deuterium and tritium nuclei muon catalysed fusion. The account of Coulomb interaction between the muon and nuclear subsystem in the intermediate state is shown to change substantially this coefficient. The results of numerical calculations of the sticking coefficient are presented, the value of the coefficient turns out to be 3 - 4% higher than that found in the sudden approximation

  10. An interactive FORTRAN program for the evaluation of structure factors and pair distribution functions from neutron diffraction experiments

    International Nuclear Information System (INIS)

    Abel, W.

    1985-02-01

    This report describes an interactive program to evaluate neutron diffraction data using the Graphic System (GS) under MVS (TSO). Different evaluation steps may be directed by a CLIST. The present program is limited to cylindrical sample geometry. From the fully corrected static structure factor the pair correlation function g(r) and the radial density function may be calculated from which the mean coordination number can be obtained by numerical integration over the main peak. Producing a hardcopy output on a mechanical plotter is provided. (orig.) [de

  11. Sound Synthesis and Evaluation of Interactive Footsteps for Virtual Reality Applications

    DEFF Research Database (Denmark)

    Nordahl, Rolf; Serafin, Stefania; Turchet, Luca

    2010-01-01

    A system to synthesize in real-time the sound of footsteps on different materials is presented. The system is based on microphones which allow the user to interact with his own footwear. This solution distinguishes our system from previous efforts that require specific shoes enhanced with sensors...

  12. A systematic evaluation of protein kinase a-a-kinase anchoring protein interaction motifs

    NARCIS (Netherlands)

    Burgers, Pepijn P|info:eu-repo/dai/nl/341566551; van der Heyden, Marcel A G; Kok, Bart; Heck, Albert J R|info:eu-repo/dai/nl/105189332; Scholten, Arjen|info:eu-repo/dai/nl/313939780

    2015-01-01

    Protein kinase A (PKA) in vertebrates is localized to specific locations in the cell via A-kinase anchoring proteins (AKAPs). The regulatory subunits of the four PKA isoforms (RIα, RIβ, RIIα, and RIIβ) each form a homodimer, and their dimerization domain interacts with a small helical region present

  13. A systematic evaluation of protein kinase A-A-kinase anchoring protein interaction motifs

    NARCIS (Netherlands)

    Burgers, Pepijn P; van der Heyden, MAG; Kok, Bart; Heck, Albert J R; Scholten, Arjen

    2015-01-01

    Protein kinase A (PKA) in vertebrates is localized to specific locations in the cell via A-kinase anchoring proteins (AKAPs). The regulatory subunits of the four PKA isoforms (RIα, RIβ, RIIα, and RIIβ) each form a homodimer, and their dimerization domain interacts with a small helical region present

  14. Development and Evaluation of a Chinese Version of the Questionnaire on Teacher Interaction (QTI)

    Science.gov (United States)

    Sun, Xiaojing; Mainhard, Tim; Wubbels, Theo

    2018-01-01

    Teacher-student interpersonal relationships play an important role in education. The Questionnaire on Teacher Interaction (QTI) was designed to measure students' interpersonal perceptions of their teachers. There are two Chinese versions of the QTI for student use, and that inherited the weaknesses of the previous English versions, such as items…

  15. Compilations and evaluations of data on the interaction of electromagnetic radiation with matter

    International Nuclear Information System (INIS)

    Lorenz, A.

    1978-05-01

    The material contained in this report deals with data on the interaction of electromagnetic radiation with matter, listing major compilations of X-ray, photon and gamma-ray cross sections and attentuation coefficients, as well as selected reports featuring data on compton scattering, photoelectric absorption and pair production

  16. Applying the Kirkpatrick Model: Evaluating an "Interaction for Learning Framework" Curriculum Intervention

    Science.gov (United States)

    Paull, Megan; Whitsed, Craig; Girardi, Antonia

    2016-01-01

    Global perspectives and interpersonal and intercultural communication competencies are viewed as a priority within higher education. For management educators, globalisation, student mobility and widening pathways present numerous challenges, but afford opportunities for curriculum innovation. The "Interaction for Learning Framework"…

  17. Evaluating the Quality of Interaction in Asynchronous Discussion Forums in Fully Online Courses

    Science.gov (United States)

    Nandi, Dip; Hamilton, Margaret; Harland, James

    2012-01-01

    Fully online courses are becoming progressively more popular because of their "anytime anywhere" learning flexibility. One of the ways students interact with each other and with the instructors within fully online learning environments is via asynchronous discussion forums. However, student engagement in online discussion forums does not…

  18. A microscopic evaluation of collagen-bilirubin interactions: in vitro surface phenomenon.

    Science.gov (United States)

    Usharani, N; Jayakumar, G C; Rao, J R; Chandrasekaran, B; Nair, B U

    2014-02-01

    This study is carried out to understand the morphology variations of collagen I matrices influenced by bilirubin. The characteristics of bilirubin interaction with collagen ascertained using various techniques like XRD, CLSM, fluorescence, SEM and AFM. These techniques are used to understand the distribution, expression and colocalization patterns of collagen-bilirubin complexes. The present investigation mimic the in vivo mechanisms created during the disorder condition like jaundice. Fluorescence technique elucidates the crucial role played by bilirubin deposition and interaction during collagen organization. Influence of bilirubin during collagen fibrillogenesis and banding patterns are clearly visualize using SEM. As a result, collagen-bilirubin complex provides different reconstructed patterns because of the influence of bilirubin concentration. Selectivity, specificity and spatial organization of collagen-bilirubin are determined through AFM imaging. Consequently, it is observed that the morphology and quantity of the bilirubin binding to collagen varied by the concentrations and the adsorption rate in protein solutions. Microscopic studies of collagen-bilirubin interaction confirms that bilirubin influence the fibrillogenesis and alter the rate of collagen organization depending on the bilirubin concentration. This knowledge helps to develop a novel drug to inhibit the interface point of interaction between collagen and bilirubin. © 2013 The Authors Journal of Microscopy © 2013 Royal Microscopical Society.

  19. Monitoring and evaluating citizen-agency interactions: a framework developed for adaptive management.

    Science.gov (United States)

    Bruce Shindler; Kristin Aldred Cheek; George H. Stankey

    1999-01-01

    As the Forest Service and the Bureau of Land Management turn toward ecosystem and adaptive models of forest stewardship, they are being called on to develop meaningful and lasting relations with citizens. These new management styles require not only improved strategies for public involvement but also methods to examine the interactions between citizens and agencies in...

  20. Evaluating Pharmacokinetic and Pharmacodynamic Interactions with Computational Models in Supporting Cumulative Risk Assessment

    Science.gov (United States)

    Tan, Yu-Mei; Clewell, Harvey; Campbell, Jerry; Andersen, Melvin

    2011-01-01

    Simultaneous or sequential exposure to multiple chemicals may cause interactions in the pharmacokinetics (PK) and/or pharmacodynamics (PD) of the individual chemicals. Such interactions can cause modification of the internal or target dose/response of one chemical in the mixture by other chemical(s), resulting in a change in the toxicity from that predicted from the summation of the effects of the single chemicals using dose additivity. In such cases, conducting quantitative cumulative risk assessment for chemicals present as a mixture is difficult. The uncertainties that arise from PK interactions can be addressed by developing physiologically based pharmacokinetic (PBPK) models to describe the disposition of chemical mixtures. Further, PK models can be developed to describe mechanisms of action and tissue responses. In this article, PBPK/PD modeling efforts conducted to investigate chemical interactions at the PK and PD levels are reviewed to demonstrate the use of this predictive modeling framework in assessing health risks associated with exposures to complex chemical mixtures. PMID:21655141

  1. Design and evaluation of RaPIDO, a platform for rapid prototyping of interactive outdoor games

    NARCIS (Netherlands)

    Soute, I.; Vacaretu, T.; de Wit, J.; Markopoulos, P.

    Outdoor, multi-player games involving social interaction and physical activity are an emerging class of applications particularly interesting for children, for whom the attraction and the health and developmental benefits are clear cut. Implementing and prototyping such games present non-trivial

  2. Colloidal systems with attractive interaction: Evaluation of scattering data using the generalized indirect fourier transformation method

    NARCIS (Netherlands)

    Innerlohinger, J.; Wyss, H.M.; Glatter, O.

    2004-01-01

    Different attractive interacting colloidal systems are characterized by means of static light scattering. As most of these samples are rather concentrated, multiple scattering is suppressed by partial contrast match and the use of very a thin sample cell (13 mum). This is possible with the

  3. THE SIMULATED SOCIAL-INTERACTION TEST - A PSYCHOMETRIC EVALUATION WITH DUTCH SOCIAL PHOBIC PATIENTS

    NARCIS (Netherlands)

    MERSCH, PPA; BREUKERS, P; EMMELKAMP, PMG

    1992-01-01

    The Simulated Social Interaction Test (SSIT) was translated and adjusted for use on a population of Dutch males and females. Seventy-four social phobic patients were assessed with the SSIT, a conversation test, and an interview with an independent observer. Results show that the SSIT is a relatively

  4. Brain Interaction during Cooperation: Evaluating Local Properties of Multiple-Brain Network.

    Science.gov (United States)

    Sciaraffa, Nicolina; Borghini, Gianluca; Aricò, Pietro; Di Flumeri, Gianluca; Colosimo, Alfredo; Bezerianos, Anastasios; Thakor, Nitish V; Babiloni, Fabio

    2017-07-21

    Subjects' interaction is the core of most human activities. This is the reason why a lack of coordination is often the cause of missing goals, more than individual failure. While there are different subjective and objective measures to assess the level of mental effort required by subjects while facing a situation that is getting harder, that is, mental workload, to define an objective measure based on how and if team members are interacting is not so straightforward. In this study, behavioral, subjective and synchronized electroencephalographic data were collected from couples involved in a cooperative task to describe the relationship between task difficulty and team coordination, in the sense of interaction aimed at cooperatively performing the assignment. Multiple-brain connectivity analysis provided information about the whole interacting system. The results showed that averaged local properties of a brain network were affected by task difficulty. In particular, strength changed significantly with task difficulty and clustering coefficients strongly correlated with the workload itself. In particular, a higher workload corresponded to lower clustering values over the central and parietal brain areas. Such results has been interpreted as less efficient organization of the network when the subjects' activities, due to high workload tendencies, were less coordinated.

  5. An Evaluation of Multimodal Interactions with Technology while Learning Science Concepts

    Science.gov (United States)

    Anastopoulou, Stamatina; Sharples, Mike; Baber, Chris

    2011-01-01

    This paper explores the value of employing multiple modalities to facilitate science learning with technology. In particular, it is argued that when multiple modalities are employed, learners construct strong relations between physical movement and visual representations of motion. Body interactions with visual representations, enabled by…

  6. An Evaluation of Independent Learning of the Japanese Hiragana System Using an Interactive CD

    Science.gov (United States)

    Geraghty, Barbara; Quinn, Ann Marcus

    2009-01-01

    As Japanese uses three writing systems (hiragana, katakana, and the ideograms known as kanji), and as materials in the target language include all three, it is a major challenge to learn to read and write quickly. This paper focuses on interactive multi-media methods of teaching Japanese reading which foster learner autonomy. As little has been…

  7. Herb-Drug Interaction between the Traditional Hepatoprotective Formulation and Sorafenib on Hepatotoxicity, Histopathology and Pharmacokinetics in Rats

    Directory of Open Access Journals (Sweden)

    Chin-Tsung Ting

    2017-06-01

    Full Text Available Sorafenib has been used as a standard therapy for advanced hepatocellular carcinoma (HCC. In Asia, patients with HCC are potentially treated with the combination of sorafenib and Chinese herbal medicines to improve the efficiency and reduce the side effects of sorafenib. However, limited information about the herb-drug interactions is available. We hypothesize that the Chinese herbal medicine may exert hepatoprotective effects on the sorafenib-treated group. The aim of this study is to investigate the pharmacokinetic mechanism of drug-drug interactions of sorafenib including interacting with hepatoprotective formulation, Long-Dan-Xie-Gan-Tang formulation (LDXGT and with two cytochrome P450 3A4 (CYP3A4 inhibitors, grapefruit juice and ketoconazole. Liver enzyme levels and histopathology of liver slices were used to evaluate sorafenib-induced hepatotoxicity and the potential hepatoprotective effects of the LDXGT formulation on subjects treated with the combination of sorafenib and the herbal medicine. In this study, a validated HPLC-photodiode array analytical system was developed for the pharmacokinetic study of sorafenib in rats. As the result of the pharmacokinetic data, pretreatment with the LDXGT formulation did not significantly interact with sorafenib compared with sorafenib oral administration alone. Furthermore, grapefruit juice and ketoconazole did not significantly affect sorafenib metabolism. Furthermore, pretreatment with variable, single or repeat doses of the LDXGT formulation did not suppress or exacerbate the sorafenib-induced hepatotoxicity and histopathological alterations. According to these results, the LDXGT formulation is safe, but has no beneficial effects on sorafenib-induced hepatotoxicity. A detailed clinical trial should be performed to further evaluate the efficacy or adverse effects of the LDXGT formulation in combination with sorafenib in humans.

  8. Perceptions of Relationships and Evaluations of Satisfaction: An Exploration of Interaction.

    Science.gov (United States)

    Bruning, Stephen D.; Ledingham, John A.

    2000-01-01

    Examines key public members' perceptions of the personal, professional, and community relationships they have with a bank and relates those perceptions to evaluations of satisfaction. Finds members' perceptions of their personal and professional relationships significantly influence evaluations of overall satisfaction. Discusses implications for…

  9. Using Publicly Available Data to Quantify Plant-Pollinator Interactions and Evaluate Conservation Seeding Mixes in the Northern Great Plains.

    Science.gov (United States)

    Otto, C R V; O'Dell, S; Bryant, R B; Euliss, N H; Bush, R M; Smart, M D

    2017-06-01

    Concern over declining pollinators has led to multiple conservation initiatives for improving forage for bees in agroecosystems. Using data available through the Pollinator Library (npwrc.usgs.gov/pollinator/), we summarize plant-pollinator interaction data collected from 2012-2015 on lands managed by the U.S. Fish and Wildlife Service and private lands enrolled in U.S. Department of Agriculture conservation programs in eastern North Dakota (ND). Furthermore, we demonstrate how plant-pollinator interaction data from the Pollinator Library and seed cost information can be used to evaluate hypothetical seeding mixes for pollinator habitat enhancements. We summarize records of 314 wild bee and 849 honey bee (Apis mellifera L.) interactions detected on 63 different plant species. The wild bee observations consisted of 46 species, 15 genera, and 5 families. Over 54% of all wild bee observations were represented by three genera-Bombus, Lassioglossum, and Melissodes. The most commonly visited forbs by wild bees were Monarda fistulosa, Sonchus arvensis, and Zizia aurea. The most commonly visited forbs by A. mellifera were Cirsium arvense, Melilotus officinalis, and Medicago sativa. Among all interactions, 13% of A. mellifera and 77% of wild bee observations were made on plants native to ND. Our seed mix evaluation shows that mixes may often need to be tailored to meet the unique needs of wild bees and managed honey bees in agricultural landscapes. Our evaluation also demonstrates the importance of incorporating both biologic and economic information when attempting to design cost-effective seeding mixes for supporting pollinators in a critically important part of the United States. Published by Oxford University Press on behalf of Entomological Society of America 2017. This work is written by US Government employees and is in the public domain in the US.

  10. Using publicly available data to quantify plant–pollinator interactions and evaluate conservation seeding mixes in the Northern Great Plains

    Science.gov (United States)

    Otto, Clint R.; O'Dell, Samuel; Bryant, R. B.; Euliss, Ned H. Jr.; Bush, Rachel; Smart, Matthew

    2017-01-01

    Concern over declining pollinators has led to multiple conservation initiatives for improving forage for bees in agroecosystems. Using data available through the Pollinator Library (npwrc.usgs.gov/pollinator/), we summarize plant–pollinator interaction data collected from 2012–2015 on lands managed by the U.S. Fish and Wildlife Service and private lands enrolled in U.S. Department of Agriculture conservation programs in eastern North Dakota (ND). Furthermore, we demonstrate how plant–pollinator interaction data from the Pollinator Library and seed cost information can be used to evaluate hypothetical seeding mixes for pollinator habitat enhancements. We summarize records of 314 wild bee and 849 honey bee (Apis mellifera L.) interactions detected on 63 different plant species. The wild bee observations consisted of 46 species, 15 genera, and 5 families. Over 54% of all wild bee observations were represented by three genera―Bombus, Lassioglossum, and Melissodes. The most commonly visited forbs by wild bees were Monarda fistulosa, Sonchus arvensis, and Zizia aurea. The most commonly visited forbs by A. mellifera were Cirsium arvense, Melilotus officinalis, and Medicago sativa. Among all interactions, 13% of A. mellifera and 77% of wild bee observations were made on plants native to ND. Our seed mix evaluation shows that mixes may often need to be tailored to meet the unique needs of wild bees and managed honey bees in agricultural landscapes. Our evaluation also demonstrates the importance of incorporating both biologic and economic information when attempting to design cost-effective seeding mixes for supporting pollinators in a critically important part of the United States.

  11. Team interaction skills evaluation criteria for nuclear power plant control room operators

    International Nuclear Information System (INIS)

    Montgomery, J.; Gaddy, C.; Toquam, J.

    1991-01-01

    This paper reports on previous research which has shown the value of good team interaction skills to group performance, yet little progress has been made in measuring such skills. Dimensions of team interaction skills developed in an earlier study were extensively revised and cast into a Behaviorally anchored Rating scales (BARS) and a Behavioral Frequency scale format. Rating data were collected using training instructors at a nuclear plant, who rated videotape scenarios of control room performance and later rated control room crews during requalification training. High levels of interrater agreement on both rating scales was, although the hypothesized factor structure did not emerge. Analysis of ratings of the videotapes using Cronbach's components of accuracy indicted that BARS ratings generally exhibited less error than did the Behavioral Frequency ratings. This paper discusses results in terms of both field and research implications

  12. Development and evaluation of an interactive dental video game to teach dentin bonding.

    Science.gov (United States)

    Amer, Rafat S; Denehy, Gerald E; Cobb, Deborah S; Dawson, Deborah V; Cunningham-Ford, Marsha A; Bergeron, Cathia

    2011-06-01

    Written and clinical tests compared the change in clinical knowledge and practical clinical skill of first-year dental students watching a clinical video recording of the three-step etch-and-rinse resin bonding system to those using an interactive dental video game teaching the same procedure. The research design was a randomized controlled trial with eighty first-year dental students enrolled in the preclinical operative dentistry course. Students' change in knowledge was measured through written examination using a pre-test and a post-test, as well as clinical tests in the form of a benchtop shear bond strength test. There was no statistically significant difference between teaching methods in regards to change in either knowledge or clinical skills, with one minor exception relating to the wetness of dentin following etching. Students expressed their preference for an interactive self-paced method of teaching.

  13. Interaction between droplets in a ternary microemulsion evaluated by the relative form factor method

    International Nuclear Information System (INIS)

    Nagao, Michihiro; Seto, Hideki; Yamada, Norifumi L.

    2007-01-01

    This paper describes the concentration dependence of the interaction between water droplets coated by a surfactant monolayer using the contrast variation small-angle neutron scattering technique. In the first part, we explain the idea of how to extract a relatively model free structure factor from the scattering data, which is called the relative form factor method. In the second part, the experimental results for the shape of the droplets (form factor) are described. In the third part the relatively model free structure factor is shown, and finally the concentration dependence of the interaction potential between droplets is discussed. The result indicates the validity of the relative form factor method, and the importance of the estimation of the model free structure factor to discuss the nature of structure formation in microemulsion systems

  14. INTERACTIONS: DESIGN, IMPLEMENTATION AND EVALUATION OF A COMPUTATIONAL TOOL FOR TEACHING INTERMOLECULAR FORCES IN HIGHER EDUCATION

    Directory of Open Access Journals (Sweden)

    Francisco Geraldo Barbosa

    2015-12-01

    Full Text Available Intermolecular forces are a useful concept that can explain the attraction between particulate matter as well as numerous phenomena in our lives such as viscosity, solubility, drug interactions, and dyeing of fibers. However, studies show that students have difficulty understanding this important concept, which has led us to develop a free educational software in English and Portuguese. The software can be used interactively by teachers and students, thus facilitating better understanding. Professors and students, both graduate and undergraduate, were questioned about the software quality and its intuitiveness of use, facility of navigation, and pedagogical application using a Likert scale. The results led to the conclusion that the developed computer application can be characterized as an auxiliary tool to assist teachers in their lectures and students in their learning process of intermolecular forces.

  15. Signalling possible drug-drug interactions in a spontaneous reporting system : delay of withdrawal bleeding during concomitant use of oral contraceptives and itraconazole

    NARCIS (Netherlands)

    Van Puijenbroek, E P; Egberts, A C; Meyboom, R H; Leufkens, H G

    AIMS: In spontaneous adverse drug reaction reporting systems, there is a growing need for methods facilitating the automated detection of signals concerning possible adverse drug reactions. In addition, special attention is needed for the detection of adverse drug reactions resulting from possible

  16. Evaluation of the effect of torsemide on warfarin dosage requirements.

    Science.gov (United States)

    Lai, Sophia; Momper, Jeremiah D; Yam, Felix K

    2017-08-01

    Background According to drug interaction databases, torsemide may potentiate the effects of warfarin. Evidence for this drug-drug interaction, however, is conflicting and the clinical significance is unknown. Objective The aim of this study is to evaluate the impact of torsemide initiation on warfarin dosage requirements. Setting This study was conducted at the Veterans Affairs Healthcare System in San Diego, California. Method A retrospective cohort study was conducted using Veterans Affairs data from patients who were converted from bumetanide to torsemide between March 2014 and July 2014. Patients were also prescribed and taking warfarin during the observation period. Warfarin dosage requirements were evaluated to determine if any changes occurred within the first 3 months of starting torsemide. Main outcome measure The primary outcome was the average weekly warfarin dose before and after torsemide initiation. Results Eighteen patients met study inclusion criteria. The weekly warfarin dose before and after initiation of torsemide was not significantly different (34 ± 15 and 34 ± 13 mg, p > 0.05). Of those eighteen patients, only two experienced elevations in INR that required a decrease in warfarin dosage after torsemide initiation. Between those two patients, dosage reductions ranged from 5.3 to 18%. Conclusion These results indicated that most patients did not require any warfarin dosage adjustments after torsemide was initiated. The potential for interaction, however, still exists. While empiric warfarin dosage adjustments are not recommended when initiating torsemide, increased monitoring is warranted to minimize the risk of adverse effects.

  17. Evaluating Educational Technologies: Interactive White Boards and Tablet Computers in the EFL Classroom

    OpenAIRE

    NFOR, Samuel

    2018-01-01

    One of the objectives outlined in "Trends and Development in Education, Science and Technology Policies": MEXT 2011 by the Ministry of Education, Culture, Sports, Science and Technology of Japan is for all elementary and junior high students to use electronic versions of printed textbooks in the coming years. Students will use digital textbooks on tablet personal computers in classrooms with interactive whiteboards (IWB). This paper considers IWB and tablet computers (tablets) technologies fo...

  18. Evaluation of R-curves in ceramic materials based on bridging interactions

    International Nuclear Information System (INIS)

    Fett, T.; Munz, D.

    1991-10-01

    In coarse-grained alumina the crack growth resistance increases with increasing crack extension due to crack-border interactions. The crack shielding stress intensity factor can be calculated from the relation between the bridging stresses and the crack opening displacement. The parameters of this relation can be obtained from experimental results on stable or subcritical crack extension. Finally the effected of the R-curve on the behaviour of components with small cracks is discussed. (orig.) [de

  19. Evaluation of Pseudo-Haptic Interactions with Soft Objects in Virtual Environments.

    Directory of Open Access Journals (Sweden)

    Min Li

    Full Text Available This paper proposes a pseudo-haptic feedback method conveying simulated soft surface stiffness information through a visual interface. The method exploits a combination of two feedback techniques, namely visual feedback of soft surface deformation and control of the indenter avatar speed, to convey stiffness information of a simulated surface of a soft object in virtual environments. The proposed method was effective in distinguishing different sizes of virtual hard nodules integrated into the simulated soft bodies. To further improve the interactive experience, the approach was extended creating a multi-point pseudo-haptic feedback system. A comparison with regards to (a nodule detection sensitivity and (b elapsed time as performance indicators in hard nodule detection experiments to a tablet computer incorporating vibration feedback was conducted. The multi-point pseudo-haptic interaction is shown to be more time-efficient than the single-point pseudo-haptic interaction. It is noted that multi-point pseudo-haptic feedback performs similarly well when compared to a vibration-based feedback method based on both performance measures elapsed time and nodule detection sensitivity. This proves that the proposed method can be used to convey detailed haptic information for virtual environmental tasks, even subtle ones, using either a computer mouse or a pressure sensitive device as an input device. This pseudo-haptic feedback method provides an opportunity for low-cost simulation of objects with soft surfaces and hard inclusions, as, for example, occurring in ever more realistic video games with increasing emphasis on interaction with the physical environment and minimally invasive surgery in the form of soft tissue organs with embedded cancer nodules. Hence, the method can be used in many low-budget applications where haptic sensation is required, such as surgeon training or video games, either using desktop computers or portable devices, showing

  20. Towards a Context Oriented Approach to Ethical Evaluation of Interactive Technologies

    DEFF Research Database (Denmark)

    Gram-Hansen, Sandra Burri; Schärfe, Henrik; Dinesen, Jens Vilhelm

    2011-01-01

    This paper explores and develops the notion of applying the ethical perspective of Danish philosopher and theologian K.E. Løgstrup, when designing and developing interactive technologies. The ethical reflections presented in this paper are currently considered in the development of Persuasive...... Learning Designs within the EU funded PLOT project, thus enabling this paper to support the argumentation with a practical example of integrating ethical considerations into the different stages of a design process....

  1. Evaluate the interactive and reusable service in adaptive on demand applications

    OpenAIRE

    Hwang , Chyi-Wen

    2007-01-01

    In this paper, the researcher based on the open platforms and tools for personalized learning idea, with the “ Interactive & reusable” function in UI design model, directly dealing with Knowledge on demand (KOD) service from the aspect-oriented and object-oriented issue. Moreover, to propose the KOD combine with VOD (Video on Demand); AOD (Audio on Demand); COD (Course on Demand) and IOD (Information on Demand in Global index searching) in diversity of hypermedia metadata.

  2. Evaluation of a Tool for Producing and Presenting Interactive Videodisc Job Aids

    Science.gov (United States)

    1994-03-01

    effective as traditional classroom presentations ( Whittington , 1987). However, most television presentations do not allow the student to interact with...presentation of the visual material. He indicated that he had come to rely on viewing the motion video and felt deprived when it was not provided. Subject 2...media in instruction (NPRDC-TR-93-4). San Diego, CA: Navy Personnel Research and Development Center. (AD-A264 228) Whittington , N. (1987). Is

  3. Evaluation of Binocular Eye Trackers and Algorithms for 3D Gaze Interaction in Virtual Reality Environments

    OpenAIRE

    Thies Pfeiffer; Ipke Wachsmuth; Marc E. Latoschik

    2009-01-01

    Tracking user's visual attention is a fundamental aspect in novel human-computer interaction paradigms found in Virtual Reality. For example, multimodal interfaces or dialogue-based communications with virtual and real agents greatly benefit from the analysis of the user's visual attention as a vital source for deictic references or turn-taking signals. Current approaches to determine visual attention rely primarily on monocular eye trackers. Hence they are restricted to the interpretation of...

  4. Evaluation of the Coulomb logarithm using cutoff and screened Coulomb interaction potentials

    International Nuclear Information System (INIS)

    Ordonez, C.A.; Molina, M.I.

    1994-01-01

    The Coulomb logarithm is a fundamental plasma parameter which is commonly derived within the framework of the binary collision approximation. The conventional formula for the Coulomb logarithm, λ=ln Λ, takes into account a pure Coulomb interaction potential for binary collisions and is not accurate at small values (λ D in place of λ D (the Debye length) in the conventional formula for the Coulomb logarithm

  5. NNAlign: a platform to construct and evaluate artificial neural network models of receptor-ligand interactions

    DEFF Research Database (Denmark)

    Nielsen, Morten; Andreatta, Massimo

    2017-01-01

    Peptides are extensively used to characterize functional or (linear) structural aspects of receptor-ligand interactions in biological systems, e.g. SH2, SH3, PDZ peptide-recognition domains, the MHC membrane receptors and enzymes such as kinases and phosphatases. NNAlign is a method for the ident...... with insertions and deletions, encoding of receptor pseudo-sequences, and custom alphabets for the training sequences. The server is available at http://www.cbs.dtu.dk/services/NNAlign-2.0....

  6. Threshold and channel interaction in cochlear implant users: evaluation of the tripolar electrode configuration.

    Science.gov (United States)

    Bierer, Julie Arenberg

    2007-03-01

    The efficacy of cochlear implants is limited by spatial and temporal interactions among channels. This study explores the spatially restricted tripolar electrode configuration and compares it to bipolar and monopolar stimulation. Measures of threshold and channel interaction were obtained from nine subjects implanted with the Clarion HiFocus-I electrode array. Stimuli were biphasic pulses delivered at 1020 pulses/s. Threshold increased from monopolar to bipolar to tripolar stimulation and was most variable across channels with the tripolar configuration. Channel interaction, quantified by the shift in threshold between single- and two-channel stimulation, occurred for all three configurations but was largest for the monopolar and simultaneous conditions. The threshold shifts with simultaneous tripolar stimulation were slightly smaller than with bipolar and were not as strongly affected by the timing of the two channel stimulation as was monopolar. The subjects' performances on clinical speech tests were correlated with channel-to-channel variability in tripolar threshold, such that greater variability was related to poorer performance. The data suggest that tripolar channels with high thresholds may reveal cochlear regions of low neuron survival or poor electrode placement.

  7. Evaluating Remapped Physical Reach for Hand Interactions with Passive Haptics in Virtual Reality.

    Science.gov (United States)

    Han, Dustin T; Suhail, Mohamed; Ragan, Eric D

    2018-04-01

    Virtual reality often uses motion tracking to incorporate physical hand movements into interaction techniques for selection and manipulation of virtual objects. To increase realism and allow direct hand interaction, real-world physical objects can be aligned with virtual objects to provide tactile feedback and physical grasping. However, unless a physical space is custom configured to match a specific virtual reality experience, the ability to perfectly match the physical and virtual objects is limited. Our research addresses this challenge by studying methods that allow one physical object to be mapped to multiple virtual objects that can exist at different virtual locations in an egocentric reference frame. We study two such techniques: one that introduces a static translational offset between the virtual and physical hand before a reaching action, and one that dynamically interpolates the position of the virtual hand during a reaching motion. We conducted two experiments to assess how the two methods affect reaching effectiveness, comfort, and ability to adapt to the remapping techniques when reaching for objects with different types of mismatches between physical and virtual locations. We also present a case study to demonstrate how the hand remapping techniques could be used in an immersive game application to support realistic hand interaction while optimizing usability. Overall, the translational technique performed better than the interpolated reach technique and was more robust for situations with larger mismatches between virtual and physical objects.

  8. Evaluating web-based static, animated and interactive maps for injury prevention

    Directory of Open Access Journals (Sweden)

    Jonathan Cinnamon

    2009-11-01

    Full Text Available Public health planning can benefit from visual exploration and analysis of geospatial data. Maps and geovisualization tools must be developed with the user-group in mind. User-needs assessment and usability testing are crucial elements in the iterative process of map design and implementation. This study presents the results of a usability test of static, animated and interactive maps of injury rates and socio-demographic determinants of injury by a sample of potential end-users in Toronto, Canada. The results of the user-testing suggest that different map types are useful for different purposes and for satisfying the varying skill level of the individual user. The static maps were deemed to be easy to use and versatile, while the animated maps could be made more useful if animation controls were provided. The split-screen concept of the interactive maps was highlighted as particularly effective for map comparison. Overall, interactive maps were identified as the preferred map type for comparing patterns of injury and related socio-demographic risk factors. Information collected from the user-tests is being used to expand and refine the injury web maps for Toronto, and could inform other public health-related geo-visualization projects.

  9. Supramolecular interactions between triphenylphosphine oxide and benzamide evaluated by positron annihilation lifetime spectroscopy

    Science.gov (United States)

    Oliveira, F. C.; Denadai, A. M. L.; Fulgêncio, F.; Oliveira, A. M.; Andrade, A. C. A.; Melo, A. C. A.; Yoshida, M. I.; Windmöller, D.; Magalhães, W. F.

    2017-04-01

    In the present work, intermolecular interactions between triphenylphosphine oxide (TPPO) and benzamide (BZM) has been studied in solid state by Positron Annihilation Lifetime Spectroscopy (PALS) and supported by several analytical techniques (in solid state and in solution) and by computational modeling (in gaseous phase). Isothermal Titration Calorimetry (ITC) in ethyl acetate solvent showed that complexation is a stepwise process, with 2:1 and 1:1 TPPO/BZM stoichiometries, both driven by entropy. HPLC analysis of isolated single crystal confirmed the existence of a 2:1 TPPO/BZM crystalline complex in solid state. The results of thermal analysis (TGA, DTA and DSC) and FTIR spectroscopy showed that the interactions in the complexes are relatively weaker than those found in pure precursors. Finally, PALS showed higher positronium formation probability (I3) at [TPPO0.62·BZM0.38] and [TPPO0.25·BZM0.75] molar fractions, corroborating the existence of two stoichiometries for the TPPO/BZM system and suggesting greater electronic availability of n- and π-electrons in heterosynton complexes, as resulting of interactions, bring forward new evidences of the participation of electronic excited states on the positronium formation mechanism.

  10. Seismic Performance Evaluation of Concrete Gravity Dams with Penetrated Cracks Considering Fluid–Structure Interaction

    Directory of Open Access Journals (Sweden)

    A. Behshad

    2018-02-01

    Full Text Available In this paper, a comprehensive study on the seismic behavior of fractured concrete gravity dams during ground shakings is carried out considering dam–reservoir interaction effects. To gain the seismic behavior of the whole system, finite and boundary elements are employed to model the liquid region and the cracked structure, respectively. Formulation and different computational aspects of the suggested staggered hybrid approach are thoroughly argued. A computer code was developed in order to discuss the presented hybrid BE–DE technique and comparisons are made between the obtained results and those reported in the literature. To gain this goal, several problems of seismic excitations in frequency- and time-domains are presented employing the proposed approach, showing that the present results agree well with the results from other numerical procedures. The cracked Koyna Dam is scrutinized, considering the dynamic interaction between dam and reservoir with focus on the nonlinear behavior due to its top profile crack. The developed numerical model is rigorously validated by extensive comparisons with available results in the literature in which the dam–reservoir interaction were simplified by added masses. It can be concluded that there is significant disparity between the overturning and sliding response schemes of the nonlinear analysis and those of added mass technique.

  11. Fundamental evaluation of the interaction between RAS/RAP and virgin asphalt binders.

    Science.gov (United States)

    2017-08-01

    A comprehensive laboratory testing program was conducted in this research project to examine the blending between reclaimed asphalt pavement (RAP)/recycled asphalt shingles (RAS) and virgin asphalt binders and to evaluate the factors that may affect ...

  12. An evaluation of touchscreen versus keyboard/mouse interaction for large screen process control displays.

    Science.gov (United States)

    Noah, Benjamin; Li, Jingwen; Rothrock, Ling

    2017-10-01

    The objectives of this study were to test the effect of interaction device on performance in a process control task (managing a tank farm). The study compared the following two conditions: a) 4K-resolution 55" screen with a 21" touchscreen versus b) 4K-resolution 55″ screen with keyboard/mouse. The touchscreen acted both as an interaction device for data entry and navigation and as an additional source of information. A within-subject experiment was conducted among 20 college engineering students. A primary task of preventing tanks from overfilling as well as a secondary task of manual logging with situation awareness questions were designed for the study. Primary Task performance (including tank level at discharge, number of tank discharged and performance score), Secondary Task Performance (including Tank log count, performance score), system interaction times, subjective workload, situation awareness questionnaire, user experience survey regarding usability and condition comparison were used as the measures. Parametric data resulted in two metrics statistically different means between the two conditions: The 4K-keyboard condition resulted in faster Detection + Navigation time compared to the 4K-touchscreen condition, by about 2 s, while participants within the 4K-touchscreen condition were about 2 s faster in data entry than in the 4K-keyboard condition. No significant results were found for: performance on the secondary task, situation awareness, and workload. Additionally, no clear significant differences were found in the non-parametric data analysis. However, participants showed a slight preference for the 4K-touchscreen condition compared to the 4K-keyboard condition in subjective responses in comparing the conditions. Introducing the touchscreen as an additional/alternative input device showed to have an effect in interaction times, which suggests that proper design considerations need to be made. While having values shown on the interaction device

  13. Perturbative evaluation of the zero-point function for self-interacting scalar field on a manifold with boundary

    International Nuclear Information System (INIS)

    Tsoupros, George

    2002-01-01

    The character of quantum corrections to the gravitational action of a conformally invariant field theory for a self-interacting scalar field on a manifold with boundary is considered at third loop-order in the perturbative expansion of the zero-point function. Diagramatic evaluations and higher loop-order renormalization can be best accomplished on a Riemannian manifold of positive constant curvature accommodating a boundary of constant extrinsic curvature. The associated spherical formulation for diagramatic evaluations reveals a non-trivial effect which the topology of the manifold has on the vacuum processes and which ultimately dissociates the dynamical behaviour of the quantized field from its behaviour in the absence of a boundary. The first surface divergence is evaluated and the necessity for simultaneous renormalization of volume and surface divergences is shown

  14. Evaluation of New Chemical Entities as Substrates of Liver Transporters in the Pharmaceutical Industry: Response to Regulatory Requirements and Future Steps.

    Science.gov (United States)

    Okudaira, Noriko

    2017-09-01

    This article discusses the evaluation of drug candidates as hepatic transporter substrates. Recently, research on the applications of hepatic transporters in the pharmaceutical industry has improved to meet the requirements of the regulatory guidelines for the evaluation of drug interactions. To identify the risk of transporter-mediated drug-drug interactions at an early stage of drug development, we used a strategy of reviewing the in vivo animal pharmacokinetics and tissue distribution data obtained in the discovery stage together with the in vitro data obtained for regulatory submission. In the context of nonclinical evaluation of new chemical entities as medicines, we believe that transporter studies are emerging as a key strategy to predict their pharmacological and toxicological effects. In combination with the recent progress in systems approaches, the estimation of effective concentrations in the target tissues, by using mathematical models to describe the transporter-mediated distribution and elimination, has enabled us to identify promising compounds for clinical development at the discovery stage. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  15. Evaluation of Restoration and Flow Interactions on River Structure and Function: Channel Widening of the Thur River, Switzerland

    Directory of Open Access Journals (Sweden)

    Eduardo J. Martín

    2018-04-01

    Full Text Available Removal of lateral constraints to restore rivers has become increasingly common in river resource management, but little is known how the interaction of de-channelization with flow influences ecosystem structure and function. We evaluated the ecosystem effects of river widening to improve sediment relations in the Thur River, Switzerland, 12 years after implementation. We tested if restored and non-restored reaches differed in water physico-chemistry, hyporheic function, primary production, and macroinvertebrate density and composition in relation to the flow regime. Our results showed that (i spatio-temporal variation in sediment respiration and macroinvertebrate taxonomic richness were driven by interactions between restoration and flow; (ii riverbed conditions including substrate size, organic matter content, and groundwater–surface water exchange changed due to restoration, but (iii physico-chemistry, hydraulic conditions, and primary production were not altered by restoration. Importantly, our study revealed that abiotic conditions, except channel morphology, changed only marginally, whereas other ecosystem attributes responded markedly to changes in flow-restoration interactions. These results highlight integrating a more holistic ecosystem perspective in the design and monitoring of restoration projects such as river widening in resource management, preferably in relation to flow-sediment regimes and interactions with the biotic components of the ecosystem.

  16. Cation-π interactions: computational analyses of the aromatic box motif and the fluorination strategy for experimental evaluation.

    Science.gov (United States)

    Davis, Matthew R; Dougherty, Dennis A

    2015-11-21

    Cation-π interactions are common in biological systems, and many structural studies have revealed the aromatic box as a common motif. With the aim of understanding the nature of the aromatic box, several computational methods were evaluated for their ability to reproduce experimental cation-π binding energies. We find the DFT method M06 with the 6-31G(d,p) basis set performs best of several methods tested. The binding of benzene to a number of different cations (sodium, potassium, ammonium, tetramethylammonium, and guanidinium) was studied. In addition, the binding of the organic cations NH4(+) and NMe4(+) to ab initio generated aromatic boxes as well as examples of aromatic boxes from protein crystal structures were investigated. These data, along with a study of the distance dependence of the cation-π interaction, indicate that multiple aromatic residues can meaningfully contribute to cation binding, even with displacements of more than an angstrom from the optimal cation-π interaction. Progressive fluorination of benzene and indole was studied as well, and binding energies obtained were used to reaffirm the validity of the "fluorination strategy" to study cation-π interactions in vivo.

  17. Evaluation of Big Data and Innovation Interaction in Increase Supply Chain Competencies

    Directory of Open Access Journals (Sweden)

    Zumrut Ecevit Sati

    2017-12-01

    Full Text Available In business today, it means a great deal to uncover meaningful relationships, patterns and trends from the huge stacks of data that are often now available. The explosion in data diversity and volume coming from enterprise content and application data, data from social media, sensor data and also data including streams from third parties is significantly changing the ways and methods of interaction for both companies and their customers. This pressure is felt considerably more in the management of innovation through trying to develop the capability to integrate the supply chain to match the correct methods with the right information. This situation has directed companies into using “big data” in managing both their structured and unstructured data. Big data, which is information, held on a vast scale, can reveal significant potential in its transparency and convenience. To bring about a balanced approach to the use of internal and external information, supporting improved capabilities to better predict future competence, and provide that all important “big picture” through business analytics can improve the vision of businesses through the provision of more in-depth information about how to best access their customers. Improved communication and information links between partners of the supply chain may create major sources of information by bringing together both internal and external resources for customers, partners, stakeholders and suppliers in managing innovation. In this study, it is aimed to provide an extensive literature review on the interaction of innovation and big data in order to increase supply chain competencies and to study the problem, obstacles and driving forces for such interactions, and to consider projections for the future through the application of technology-based methods.

  18. Evaluation by Expert Dancers of a Robot That Performs Partnered Stepping via Haptic Interaction.

    Directory of Open Access Journals (Sweden)

    Tiffany L Chen

    Full Text Available Our long-term goal is to enable a robot to engage in partner dance for use in rehabilitation therapy, assessment, diagnosis, and scientific investigations of two-person whole-body motor coordination. Partner dance has been shown to improve balance and gait in people with Parkinson's disease and in older adults, which motivates our work. During partner dance, dance couples rely heavily on haptic interaction to convey motor intent such as speed and direction. In this paper, we investigate the potential for a wheeled mobile robot with a human-like upper-body to perform partnered stepping with people based on the forces applied to its end effectors. Blindfolded expert dancers (N=10 performed a forward/backward walking step to a recorded drum beat while holding the robot's end effectors. We varied the admittance gain of the robot's mobile base controller and the stiffness of the robot's arms. The robot followed the participants with low lag (M=224, SD=194 ms across all trials. High admittance gain and high arm stiffness conditions resulted in significantly improved performance with respect to subjective and objective measures. Biomechanical measures such as the human hand to human sternum distance, center-of-mass of leader to center-of-mass of follower (CoM-CoM distance, and interaction forces correlated with the expert dancers' subjective ratings of their interactions with the robot, which were internally consistent (Cronbach's α=0.92. In response to a final questionnaire, 1/10 expert dancers strongly agreed, 5/10 agreed, and 1/10 disagreed with the statement "The robot was a good follower." 2/10 strongly agreed, 3/10 agreed, and 2/10 disagreed with the statement "The robot was fun to dance with." The remaining participants were neutral with respect to these two questions.

  19. Evaluation by Expert Dancers of a Robot That Performs Partnered Stepping via Haptic Interaction

    Science.gov (United States)

    Chen, Tiffany L.; Bhattacharjee, Tapomayukh; McKay, J. Lucas; Borinski, Jacquelyn E.; Hackney, Madeleine E.; Ting, Lena H.; Kemp, Charles C.

    2015-01-01

    Our long-term goal is to enable a robot to engage in partner dance for use in rehabilitation therapy, assessment, diagnosis, and scientific investigations of two-person whole-body motor coordination. Partner dance has been shown to improve balance and gait in people with Parkinson's disease and in older adults, which motivates our work. During partner dance, dance couples rely heavily on haptic interaction to convey motor intent such as speed and direction. In this paper, we investigate the potential for a wheeled mobile robot with a human-like upper-body to perform partnered stepping with people based on the forces applied to its end effectors. Blindfolded expert dancers (N=10) performed a forward/backward walking step to a recorded drum beat while holding the robot's end effectors. We varied the admittance gain of the robot's mobile base controller and the stiffness of the robot's arms. The robot followed the participants with low lag (M=224, SD=194 ms) across all trials. High admittance gain and high arm stiffness conditions resulted in significantly improved performance with respect to subjective and objective measures. Biomechanical measures such as the human hand to human sternum distance, center-of-mass of leader to center-of-mass of follower (CoM-CoM) distance, and interaction forces correlated with the expert dancers' subjective ratings of their interactions with the robot, which were internally consistent (Cronbach's α=0.92). In response to a final questionnaire, 1/10 expert dancers strongly agreed, 5/10 agreed, and 1/10 disagreed with the statement "The robot was a good follower." 2/10 strongly agreed, 3/10 agreed, and 2/10 disagreed with the statement "The robot was fun to dance with." The remaining participants were neutral with respect to these two questions. PMID:25993099

  20. Evaluation of salivary flow and drug interactions in patients with a diagnosis of diabetes mellitus.

    Science.gov (United States)

    Noboru Kuroiwa, D; Ruiz Da Cunha Melo, M A; Balducci, I; Bortolin Lodi, K; Ghislaine Oliveira Alves, M; Dias Almeida, J

    2014-01-01

    Diabetes mellitus (DM) is one of the most common chronic diseases responsible for substantial loss on the quality of life in elderly. Oral manifestations in these patients include xerostomia and alterations in salivary flow and salivary pH. The aim of this study was to analyze the relationship between salivary flow, pH and medication. The sample consisted of 53 subjects aged 60 years and older, including 30 patients with a diagnosis of type 2 DM and 23 controls. Salivary flow was 1.066±0.814 mL/min in the control group and 0.955±0.606 mL/min in the DM group, with no significant difference between groups (P=0.588). There was a significant difference (P=0.045) in mean salivary pH (DM: 5.267±0.828; control: 5.783±0.951). Only 32.07% of the patients reported to remove their denture while sleeping. Three of 53 subjects using medications presented severe drug interactions. In summary, dentists must be able to make the diagnosis, to recognize all factors related to salivary alterations in DM, and to prescribe adequate treatment related to oral condition. Patients with DM presented salivary pH below normal reference values. It is important to advice patients to remove their denture while sleeping in order to prevent traumatic irritations and infections with Candida albicans. Potentially harmful cases of drug interactions have to be observed in elderly patient. Further studies focusing on the nature of drug interactions as the cause of adverse events such as xerostomia and increased salivary pH are needed.

  1. Evaluating the Cognitive Aspects of User Interaction with 2D Visual Tagging Systems

    Directory of Open Access Journals (Sweden)

    Samuel Olugbenga King

    2008-04-01

    Full Text Available There has been significant interest in thedevelopment and deployment of visual taggingapplications in recent times. But user perceptions aboutthe purpose and function of visual tagging systems havenot received much attention. This paper presents a userexperience study that investigates the cognitive modelsthat novice users have about interacting with visualtagging applications. The results of the study show thatalthough most users are unfamiliar with visual taggingtechnologies, they could accurately predict the purposeand mode of retrieval of data stored in visual tags. Thestudy concludes with suggestions on how to improve therecognition, ease of recall and design of visual tags.

  2. Recursive evaluation of interaction forces of unbounded soil in time domain

    International Nuclear Information System (INIS)

    Motosaka, M.

    1987-01-01

    Recursive formulations have hardly been used in the analysis of soil-structure interaction. A notable exception is described in Verbic 1973, which corresponds to the impulse-invariant way discussed in Section 2. Section 3 describes another possibility to derive a recursive relation based on a segment approach using z-transforms. An illustrative example is examined in Section 4, and in Section 5 the number of operations is addressed. This compact paper is based on Wolf and Motosaka 1988. (orig./HP)

  3. Electron trajectory evaluation in laser-plasma interaction for effective output beam

    Science.gov (United States)

    Zobdeh, P.; Sadighi-Bonabi, R.; Afarideh, H.

    2010-06-01

    Using the ellipsoidal cavity model, the quasi-monoenergetic electron output beam in laser-plasma interaction is described. By the cavity regime the quality of electron beam is improved in comparison with those generated from other methods such as periodic plasma wave field, spheroidal cavity regime and plasma channel guided acceleration. Trajectory of electron motion is described as hyperbolic, parabolic or elliptic paths. We find that the self-generated electron bunch has a smaller energy width and more effective gain in energy spectrum. Initial condition for the ellipsoidal cavity is determined by laser-plasma parameters. The electron trajectory is influenced by its position, energy and cavity electrostatic potential.

  4. Evaluation of the Stillinger-Weber classical interaction potential for tetragonal semiconductors in nonideal atomic configurations

    International Nuclear Information System (INIS)

    Dodson, B.W.

    1986-01-01

    A classical potential incorporating two- and three-body interaction terms has recently been introduced by Stillinger and Weber (SW) for simulation of the liquefaction transition of silicon. The equilibrium mechanical properties of this potential are determined and found to agree well with experimental values. The potential also seems to be adequate for problems involving computation of defect energies, such as the stability of strained-layer superlattice interfaces. However, inadequate treatment of configurations with low coordination number makes modeling of the epitaxial growth of (111) silicon impossible. Simple modifications of the SW potential form do allow for (111) epitaxial growth, but the earliest stages of growth then become unphysical

  5. FENDL/E-2.0. Evaluated nuclear data library of neutron-nucleus interaction cross sections and photon production cross sections and photon-atom interaction cross sections for fusion applications. Version 1, March 1997. Summary documentation

    International Nuclear Information System (INIS)

    Pashchenko, A.B.; Wienke, H.

    1998-01-01

    This document presents the description of a physical tape containing the basic evaluated nuclear data library of neutron-nucleus interaction cross sections, photon production cross sections and photon-atom interaction cross sections for fusion applications. It is part of the evaluated nuclear data library for fusion applications FENDL-2. The data are available cost-free from the Nuclear Data Section upon request. The data can also be retrieved by the user via online access through international computer networks. (author)

  6. Seismic evaluation of a cooling water reservoir facility including fluid-structure and soil-structure interaction effects

    International Nuclear Information System (INIS)

    Kabir, A.F.; Maryak, M.E.

    1991-01-01

    Seismic analyses and structural evaluations were performed for a cooling water reservoir of a nuclear reactor facility. The horizontal input seismic motion was the NRC Reg. guide 1.60 spectrum shape anchored at 0.20g zero period acceleration. Vertical input was taken as two-thirds of the horizontal input. Soil structure interaction and hydrodynamic effects were addressed in the seismic analyses. Uncertainties in the soil properties were accounted for by considering three soil profiles. Two 2-dimensional SSI models and a 3-dimensional static model. Representing different areas of the reservoir structures were developed and analyzed to obtain seismic forces and moments, and accelerations at various locations. The results included in this paper indicated that both hydrodynamic and soil-structure interaction effects are significant contributors to the seismic responses of the water-retaining walls of the reservoir

  7. Training of goal directed arm movements with motion interactive video games in children with cerebral palsy - a kinematic evaluation.

    Science.gov (United States)

    Sandlund, Marlene; Domellöf, Erik; Grip, Helena; Rönnqvist, Louise; Häger, Charlotte K

    2014-10-01

    The main aim of this study was to evaluate the quality of goal-directed arm movements in 15 children with cerebral palsy (CP) following four weeks of home-based training with motion interactive video games. A further aim was to investigate the applicability and characteristics of kinematic parameters in a virtual context in comparison to a physical context. Kinematics and kinetics were captured while the children performed arm movements directed towards both virtual and physical targets. The children's movement precision improved, their centre of pressure paths decreased, as did the variability in maximal shoulder angles when reaching for virtual objects. Transfer to a situation with physical targets was mainly indicated by increased movement smoothness. Training with motion interactive games seems to improve arm motor control in children with CP. The results highlight the importance of considering both the context and the task itself when investigating kinematic parameters.

  8. Evaluating the Effects of Interactivity in a Post-Editing Workbench

    DEFF Research Database (Denmark)

    Underwood, Nancy; Mesa-Lao, Bartolomé; Martinez, Mercedes Garcia

    2014-01-01

    This paper describes the field trial and subsequent evaluation of a post-editing workbench which is currently under development in the EU-funded CasMaCat project. Based on user evaluations of the initial prototype of the workbench, this second prototype of the workbench includes a number of inter...... on productivity, quality, user satisfaction and cognitive load as reflected in the post-editors’ gaze activity. These quantitative results are combined with the qualitative results derived from user questionnaires and interviews conducted with all the participants....

  9. Design, development, and evaluation of an interactive simulator for engineering ethics education (SEEE).

    Science.gov (United States)

    Chung, Christopher A; Alfred, Michael

    2009-06-01

    Societal pressures, accreditation organizations, and licensing agencies are emphasizing the importance of ethics in the engineering curriculum. Traditionally, this subject has been taught using dogma, heuristics, and case study approaches. Most recently a number of organizations have sought to increase the utility of these approaches by utilizing the Internet. Resources from these organizations include on-line courses and tests, videos, and DVDs. While these individual approaches provide a foundation on which to base engineering ethics, they may be limited in developing a student's ability to identify, analyze, and respond to engineering ethics situations outside of the classroom environment. More effective approaches utilize a combination of these types of approaches. This paper describes the design and development of an internet based interactive Simulator for Engineering Ethics Education. The simulator places students in first person perspective scenarios involving different types of ethical situations. Students must gather data, assess the situation, and make decisions. This requires students to develop their own ability to identify and respond to ethical engineering situations. A limited comparison between the internet based interactive simulator and conventional internet web based instruction indicates a statistically significant improvement of 32% in instructional effectiveness. The simulator is currently being used at the University of Houston to help fulfill ABET requirements.

  10. Team interaction skills evaluation criteria for nuclear power plant control room operators

    International Nuclear Information System (INIS)

    Montgomery, J.C.; Hauth, J.T.

    1991-01-01

    Team interaction skills are an essential aspect of safe nuclear power plant control room operations. Previous research has shown that, when a group works together, rather than as individuals, more effective operations are possible. However, little research has addressed how such team interaction skills can be measured. In this study rating scales were developed specifically for such a measurement purpose. Dimensions of team skill performance were identified from previous research and experience in the area, incorporating the input of Pacific Northwest Laboratory (PNL) contract operator licensing examiners. Rating scales were developed on the basis of these dimensions, incorporating a modified Behaviorally Anchored Rating Scale (BARS) as well as Behavioral Frequency formats. After a pilot-testing/revision process, rating data were collected using 11 control room crews responding to simulator scenarios at a boiling water and a pressurized water reactor. Statistical analyses of the resulting data revealed moderate inter-rater reliability using the Behavioral Frequency scales, relatively low inter-rater reliability using the BARS, and moderate support for convergent and discriminant validity of the scales. It was concluded that the scales show promise psychometrically and in terms of user acceptability, but that additional scale revision is needed before field implementation. Recommendations for scale revision and directions for future research were presented

  11. Can social support work virtually? Evaluation of rheumatoid arthritis patients' experiences with an interactive online tool.

    Science.gov (United States)

    Kostova, Zlatina; Caiata-Zufferey, Maria; Schulz, Peter J

    2015-01-01

    There is strong empirical evidence that the support that chronic patients receive from their environment is fundamental for the way they cope with physical and psychological suffering. Nevertheless, in the case of rheumatoid arthritis (RA), providing the appropriate social support is still a challenge, and such support has often proven to be elusive and unreliable in helping patients to manage the disease. To explore whether and how social support for RA patients can be provided online, and to assess the conditions under which such support is effective. An online support tool was designed to provide patients with both tailored information and opportunities to interact online with health professionals and fellow sufferers. The general purpose was to identify where the support provided did - or did not - help patients, and to judge whether the determinants of success lay more within patients - their engagement and willingness to participate - or within the design of the website itself. The present study reports qualitative interviews with 19 users of the tool. A more specific purpose was to elaborate qualitatively on results from a quantitative survey of users, which indicated that any positive impact was confined to practical matters of pain management rather than extending to more fundamental psychological outcomes such as acceptance. Overall, online learning and interaction can do much to help patients with the everyday stresses of their disease; however, its potential for more durable positive impact depends on various individual characteristics such as personality traits, existing social networks, and the severity and longevity of the disease.

  12. Evaluation of two novel leptospiral proteins for their interaction with human host components.

    Science.gov (United States)

    Silva, Lucas P; Fernandes, Luis G V; Vieira, Monica L; de Souza, Gisele O; Heinemann, Marcos B; Vasconcellos, Silvio A; Romero, Eliete C; Nascimento, Ana L T O

    2016-07-01

    Pathogenic species of the genus Leptospira are the etiological agents of leptospirosis, the most widespread zoonosis. Mechanisms involved in leptospiral pathogenesis are not well understood. By data mining the genome sequences of Leptospira interrogans we have identified two proteins predicted to be surface exposed, LIC10821 and LIC10064. Immunofluorescence and proteinase K assays confirmed that the proteins are exposed. Reactivity of the recombinant proteins with human sera has shown that rLIC10821, but not rLIC10064, is recognized by antibodies in confirmed leptospirosis serum samples, suggesting its expression during infection. The rLIC10821 was able to bind laminin, in a dose-dependent fashion, and was called Lsa37 (leptospiral surface adhesin of 37 kDa). Studies with human plasma components demonstrated that rLIC10821 interacts with plasminogen (PLG) and fibrinogen (Fg). The binding of Lsa37 with PLG generates plasmin when PLG activator was added. Fibrin clotting reduction was observed in a thrombin-catalyzed reaction, when Fg was incubated with Lsa37, suggesting that this protein may interfere in the coagulation cascade during the disease. Although LIC10064 protein is more abundant than the corresponding Lsa37, binding activity with all the components tested was not detected. Thus, Lsa37 is a novel versatile adhesin that may mediate Leptospira-host interactions. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Pharmacokinetic evaluation of the interaction between oral kaempferol and ethanol in rats.

    Science.gov (United States)

    Zhou, Zhaoxiang; Wang, Meng; Guo, Zengjun; Zhang, Xiaoying

    2016-12-01

    This study was aimed at investigating the effect of ethanol on oral bioavailability of kaempferol in rats, namely, at disclosing their possible interaction. Kaempferol (100 or 250 mg kg-1 bm) was administered to the rats by oral gavage with or without ethanol (600 mg kg-1 bm) co-administration. Intravenous administration (10 and 25 mg kg-1 bm) of kaempferol was used to determine the bioavailability. The concentration of kaempferol in plasma was estimated by ultra high performance liquid chromatography. During coadministration, a significant increase of the area under the plasma concentration-time curve as well as the peak concentration were observed, along with a dramatic decrease in total body clearance. Consequently, the bioavailability of kaempferol in oral control groups was 3.1 % (100 mg kg-1 bm) and 2.1 % (250 mg kg-1 bm). The first was increased by 4.3 % and the other by 2.8 % during ethanol co-administration. Increased permeability of cell membrane and ethanolkaempferol interactions on CYP450 enzymes may enhance the oral bioavailability of kaempferol in rats.

  14. A discussion of techniques used in defining the Interactive Measurement Evaluation and Control System at Rocky Flats

    International Nuclear Information System (INIS)

    Greer, B.K.; Hunt, V.; Schweitzer, M.F.

    1983-01-01

    This paper describes both the general methodology used to study the current needs for a measurement control and evaluation system at Rocky Flats Plant and the recommendations for implementation into the Interactive Measurement Evaluation and Control System (IMECS). The study resulted in a clear assessment of the current system and recommendations for the system which will be its replacement. To arrive at the recommendations, the authors used a formal analysis approach that is based on an in-depth study of the measurement evaluation and control problems and user needs. The problems and needs were defined by interviews with present and potential users of this kind of system throughout the nuclear industry. Some of the recommendations are to provide: timely sample measurement feedback; representative measurement error estimates; a history data base of sample measurements To meet the user needs, the new system will: be interactive with user selection menus; use standards which cover the range of application; facilitate historical analysis of sample data and bookkeeping. The implementation of this program is projected to be more cost effective than the current program. Also included are the authors' recommendations to those involved in the design of a system of similar large magnitude

  15. WIPP [Waste Isolation Pilot Plant] panel entryway seal: Numerical simulation of seal composite interaction for preliminary design evaluation

    International Nuclear Information System (INIS)

    Argueello, J.G.

    1988-04-01

    This report presents the results of a series of structural analyses performed to evaluate the structural interaction of the components of a potential two-component panel entryway seal configuration with each other and with the rock salt formation at the repository horizon of the Waste Isolation Pilot Plant. A two-dimensional axisymmetric geomechanical model is used to numerically simulate the interaction of the components of a 30.48 m (100 ft) long seal, consisting of concrete end caps and a crushed salt core, with each other and with the surrounding formation. Issues addressed in this report pertain to the consolidation of the crushed salt in terms of how much of the seal core reaches effective consolidation in the presence of the stiff concrete end caps since these could conceivably cause bridging (retardation of closure around the core) to occur. In addition, the stress field in the end caps is evaluated to determine if the concrete component maintains its integrity. The stresses induced in the surrounding formation are also evaluated to determine if the presence of the concrete component in the seal system results in a ''tightening'' of the formation around the seal. 20 refs., 43 figs., 2 tabs

  16. [Evaluate drug interaction of multi-components in Morus alba leaves based on α-glucosidase inhibitory activity].

    Science.gov (United States)

    Ji, Tao; Su, Shu-Lan; Guo, Sheng; Qian, Da-Wei; Ouyang, Zhen; Duan, Jin-Ao

    2016-06-01

    Column chromatography was used for enrichment and separation of flavonoids, alkaloids and polysaccharides from the extracts of Morus alba leaves; glucose oxidase method was used with sucrose as the substrate to evaluate the multi-components of M. alba leaves in α-glucosidase inhibitory models; isobole method, Chou-Talalay combination index analysis and isobolographic analysis were used to evaluate the interaction effects and dose-effect characteristics of two components, providing scientific basis for revealing the hpyerglycemic mechanism of M. alba leaves. The components analysis showed that flavonoid content was 5.3%; organic phenolic acids content was 10.8%; DNJ content was 39.4%; and polysaccharide content was 18.9%. Activity evaluation results demonstrated that flavonoids, alkaloids and polysaccharides of M. alba leaves had significant inhibitory effects on α-glucosidase, and the inhibitory rate was increased with the increasing concentration. Alkaloids showed most significant inhibitory effects among these three components. Both compatibility of alkaloids and flavonoids, and the compatibility of alkaloids and polysaccharides demonstrated synergistic effects, but the compatibility of flavonoids and polysaccharides showed no obvious synergistic effects. The results have confirmed the interaction of multi-components from M. alba leaves to regulate blood sugar, and provided scientific basis for revealing hpyerglycemic effectiveness and mechanism of the multi-components from M. alba leaves. Copyright© by the Chinese Pharmaceutical Association.

  17. Use of Interactive Electronic Audience Response Tools (Clickers) to Evaluate Knowledge Gained in Extension Programming

    Science.gov (United States)

    Gunn, Patrick; Loy, Dan

    2015-01-01

    Effectively measuring short-term impact, particularly a change in knowledge resulting from Extension programming, can prove to be challenging. Clicker-based technology, when used properly, is one alternative that may allow educators to better evaluate this aspect of the logic model. While the potential interface between clicker technology and…

  18. Organizational Compliance : An agent-based model for designing and evaluating organizational interactions

    NARCIS (Netherlands)

    Jiang, J.

    2015-01-01

    The motivation of this research comes from the need of devising and evaluating solutions to achieving organizational compliance, which is an important factor in ensuring the success of business operations and the safety of business environments. Using normative multi-agent systems as the basis of

  19. Evaluation of unimodal and multimodal communication cues for attracting attention in human–robot interaction

    NARCIS (Netherlands)

    Torta, E.; van Heumen, J.; Piunti, F.; Romeo, L.; Cuijpers, R.H.

    2015-01-01

    One of the most common tasks of a robot companion in the home is communication. In order to initiate an information exchange with its human partner, the robot needs to attract the attention of the human. This paper presents results of two user studies ( N=12 ) to evaluate the effectiveness of

  20. Evaluation of an Online Three-Dimensional Interactive Resource for Undergraduate Neuroanatomy Education

    Science.gov (United States)

    Allen, Lauren K.; Eagleson, Roy; de Ribaupierre, Sandrine

    2016-01-01

    Neuroanatomy is one of the most challenging subjects in anatomy, and novice students often experience difficulty grasping the complex three-dimensional (3D) spatial relationships. This study evaluated a 3D neuroanatomy e-learning module, as well as the relationship between spatial abilities and students' knowledge in neuroanatomy. The study's…

  1. Evaluation of possible interaction among drugs contemplated for use during manned space flights

    Science.gov (United States)

    1973-01-01

    Possible interactions among drugs contemplated for use during manned spaceflights have been studied in several animal species. The following seven drugs were investigated: nitrofurantoin, chloral hydrate, hexobarbital, phenobarbital, flurazepam, diphenoxylate, and phenazopyridine. Particular combinations included: chloral hydrate, hexabarbital or flurazepam with nitrofurantoin; phenobarbital or flurazepam with phenazopyridine; and diphenoxylate with two does formulations of nitrofurantoin. Studies were carried out in several species to determine whether induction of liver microsomal enzymes would increase the tendency of phenazopyridine to produce methemoglobin in vivo. Animals were premedicated with phenobarbital, a known inducer of azoreductase, and in a separate experiment with flurazepam, before administration of phenazopyridine. Methemoglobin production was determined in each animal after receiving phenazopyridine. No evidence was found for increased production of methemoglobin in the rat, dog, or rabbit that could be attributed to increased amounts of microsomal enzymes.

  2. Less is more: development and evaluation of an interactive e-atlas to support anatomy learning.

    Science.gov (United States)

    Guy, Richard; Pisani, Heather R; Rich, Peter; Leahy, Cathy; Mandarano, Giovanni; Molyneux, Tom

    2015-01-01

    An Interactive electronic Atlas (IeA) was developed to assist first-year nursing students with interpretation of laboratory-based prosected cadaveric material. It was designed, using pedagogically sound principles, as a student-centered resource accessible to students from a wide range of learning backgrounds. It consisted of a highly simplified interactive interface limited to essential anatomical structures and was intended for use in a blended learning situation. The IeA's nine modules mirrored the body systems covered in a Nursing Biosciences course, with each module comprising a maximum of 10 pages using the same template: an image displaying a cadaveric specimen and, in most cases, a corresponding anatomical model with navigation panes (menus) on one side. Cursor movement over the image or clicking the menu highlighted the structure with a transparent overlay and revealed a succinct functional description. The atlas was complemented by a multiple-choice database of nearly 1,000 questions using IeA images. Students' perceptions of usability and utility were measured by survey (n = 115; 57% of the class) revealing mean access of 2.3 times per week during the 12-week semester and a median time of three hours of use. Ratings for usability and utility were high, with means ranging between 4.24 and 4.54 (five-point Likert scale; 5 = strongly agree). Written responses told a similar story for both usability and utility. The role of providing basic computer-assisted learning support for a large first-year class is discussed in the context of current research into student-centered resources and blended learning in human anatomy. © 2014 American Association of Anatomists.

  3. Statins and daptomycin: safety assessment of concurrent use and evaluation of drug interaction liability.

    Science.gov (United States)

    Golightly, Larry K; Barber, Gerard R; Barron, Michelle A; Page, Robert L

    2013-01-01

    Acute muscle injury and potentially fatal rhabdomyolysis may occur with use of statins and certain interacting medications. This investigation assessed risk for myopathy in patients receiving treatment with a statin in combination with daptomycin, a medication also associated with muscle injury. Patients hospitalized from July 1, 2005, through June 30, 2010, who received simvastatin or rosuvastatin concurrently with daptomycin were identified and their medical records were examined. Patients were judged to have treatment-related muscle injury if their records contained evidence of myalgia with or without weakness and secondarily impaired mobility together with elevated creatine kinase (CK) levels. These assessments were compared with similar data from hospitalized patients who received a statin alone. A total of 52 patients received 66 courses of concurrent treatment with simvastatin or rosuvastatin and daptomycin. Of these, no patient (0%) met evidentiary requirements for diagnosis of myopathy or related complications. No patient (0%) developed muscle pain or discomfort and none developed markedly elevated CK levels. The incidence of asymptomatic elevations of CK in these simvastatin or rosuvastatin plus daptomycin recipients (9%) was statistically indistinguishable from the incidence of CK elevations found in a cohort of 105 inpatients who received simvastatin or rosuvastatin alone (21%; p=0.135). In patients receiving treatment with simvastatin or rosuvastatin and daptomycin, no symptoms or objective evidence of muscle injury attributable to a drug interaction were identified. These findings are consistent with data indicating that the myopathic effects of statins and daptomycin are incited by disparate and perhaps unique pharmacological mechanisms. Risk of muscle injury therefore appears to be no greater when a statin is administered with daptomycin than when either medication is used alone.

  4. In vitro, in vivo, and clinical studies of tedizolid to assess the potential for peripheral or central monoamine oxidase interactions.

    Science.gov (United States)

    Flanagan, S; Bartizal, K; Minassian, S L; Fang, E; Prokocimer, P

    2013-07-01

    Tedizolid phosphate is a novel oxazolidinone prodrug whose active moiety, tedizolid, has improved potency against Gram-positive pathogens and pharmacokinetics, allowing once-daily administration. Given linezolid warnings for drug-drug and drug-food interactions mediated by monoamine oxidase (MAO) inhibition, including sporadic serotonergic toxicity, these studies evaluated tedizolid for potential MAO interactions. In vitro, tedizolid and linezolid were reversible inhibitors of human MAO-A and MAO-B; the 50% inhibitory concentration (IC50) for tedizolid was 8.7 μM for MAO-A and 5.7 μM for MAO-B and 46.0 and 2.1 μM, respectively, with linezolid. Tedizolid phosphate was negative in the mouse head twitch model of serotonergic activity. Two randomized placebo-controlled crossover clinical studies assessed the potential of 200 mg/day tedizolid phosphate (at steady state) to enhance pressor responses to coadministered oral tyramine or pseudoephedrine. Sensitivity to tyramine was determined by comparing the concentration of tyramine required to elicit a ≥ 30-mmHg increase in systolic blood pressure (TYR30) when administered with placebo versus tedizolid phosphate. The geometric mean tyramine sensitivity ratio (placebo TYR30/tedizolid phosphate TYR30) was 1.33; a ratio of ≥ 2 is considered clinically relevant. In the pseudoephedrine study, mean maximum systolic blood pressure was not significantly different when pseudoephedrine was coadministered with tedizolid phosphate versus placebo. In summary, tedizolid is a weak, reversible inhibitor of MAO-A and MAO-B in vitro. Provocative testing in humans and animal models failed to uncover significant signals that would suggest potential for hypertensive or serotonergic adverse consequences at the therapeutic dose of tedizolid phosphate. Clinical studies are registered at www.clinicaltrials.gov as NCT01539473 (tyramine interaction study conducted at Covance Clinical Research Center, Evansville, IN) and NCT01577459

  5. Linear Interaction Energy Based Prediction of Cytochrome P450 1A2 Binding Affinities with Reliability Estimation.

    Directory of Open Access Journals (Sweden)

    Luigi Capoferri

    Full Text Available Prediction of human Cytochrome P450 (CYP binding affinities of small ligands, i.e., substrates and inhibitors, represents an important task for predicting drug-drug interactions. A quantitative assessment of the ligand binding affinity towards different CYPs can provide an estimate of inhibitory activity or an indication of isoforms prone to interact with the substrate of inhibitors. However, the accuracy of global quantitative models for CYP substrate binding or inhibition based on traditional molecular descriptors can be limited, because of the lack of information on the structure and flexibility of the catalytic site of CYPs. Here we describe the application of a method that combines protein-ligand docking, Molecular Dynamics (MD simulations and Linear Interaction Energy (LIE theory, to allow for quantitative CYP affinity prediction. Using this combined approach, a LIE model for human CYP 1A2 was developed and evaluated, based on a structurally diverse dataset for which the estimated experimental uncertainty was 3.3 kJ mol-1. For the computed CYP 1A2 binding affinities, the model showed a root mean square error (RMSE of 4.1 kJ mol-1 and a standard error in prediction (SDEP in cross-validation of 4.3 kJ mol-1. A novel approach that includes information on both structural ligand description and protein-ligand interaction was developed for estimating the reliability of predictions, and was able to identify compounds from an external test set with a SDEP for the predicted affinities of 4.6 kJ mol-1 (corresponding to 0.8 pKi units.

  6. Interactive Block Games for Assessing Children's Cognitive Skills: Design and Preliminary Evaluation

    Directory of Open Access Journals (Sweden)

    Kiju Lee

    2018-05-01

    Full Text Available Background: This paper presents design and results from preliminary evaluation of Tangible Geometric Games (TAG-Games for cognitive assessment in young children. The TAG-Games technology employs a set of sensor-integrated cube blocks, called SIG-Blocks, and graphical user interfaces for test administration and real-time performance monitoring. TAG-Games were administered to children from 4 to 8 years of age for evaluating preliminary efficacy of this new technology-based approach.Methods: Five different sets of SIG-Blocks comprised of geometric shapes, segmented human faces, segmented animal faces, emoticons, and colors, were used for three types of TAG-Games, including Assembly, Shape Matching, and Sequence Memory. Computational task difficulty measures were defined for each game and used to generate items with varying difficulty. For preliminary evaluation, TAG-Games were tested on 40 children. To explore the clinical utility of the information assessed by TAG-Games, three subtests of the age-appropriate Wechsler tests (i.e., Block Design, Matrix Reasoning, and Picture Concept were also administered.Results: Internal consistency of TAG-Games was evaluated by the split-half reliability test. Weak to moderate correlations between Assembly and Block Design, Shape Matching and Matrix Reasoning, and Sequence Memory and Picture Concept were found. The computational measure of task complexity for each TAG-Game showed a significant correlation with participants' performance. In addition, age-correlations on TAG-Game scores were found, implying its potential use for assessing children's cognitive skills autonomously.

  7. High-throughput evaluation of interactions between biomaterials, proteins and cells using patterned superhydrophobic substrates

    OpenAIRE

    Neto, Ana I.; Custódio, Catarina A.; Wenlong Song; Mano, J. F.

    2011-01-01

    We propose a new low cost platform for high-throughput analysis that permits screening the biological performance of independent combinations of biomaterials, cells and culture media. Patterned superhydrophobic flat substrates with controlled wettable spots are used to produce microarray chips for accelerated multiplexing evaluation. This work was partially supported by Fundação para a Ciência e Tecnologia (FCT) under project PTDC/FIS/68517/2006.

  8. Evaluation of tritium production cross-section for neutron-interaction with 7Li

    International Nuclear Information System (INIS)

    Yu Baosheng; Cai Dunjiu

    1987-01-01

    The 7 Li(n, n't) α reaction cross-section has been evaluated and recommended. These experimental data were selected up to the end of 1986, in which main microscopic nuclear data and benchmark measurements were included. These data are retrieved from EXFOR master files of International Atomic Energy Agency, and new information is added in which IAE (the Chinese Institute of Atomic Energy) experimental results is considered

  9. Preparation of modified clay with benzethonium or cetylpyridinium chloride and evaluation of their interactions with PVC

    International Nuclear Information System (INIS)

    Resende, Daniel K.; Dornelas, Camila B.; Moreira, Leonardo A.; Gomes, Ailton S.; Tavares, Maria I.B.; Cabral, Lucio M.; Simeoni, Luiz A.

    2009-01-01

    The objective of this work was the preparation of modified clays with benzethonium or cetylpyridinium to obtain organophilic silicates with good stability and evaluate the possible use of them for the preparation of nanocomposites of poly(vinyl chloride) (PVC). The reactions of modification of clays and the PVC were prepared by solution intercalation. The new clays were evaluated by X-ray diffraction (XRD) and Low field nuclear magnetic resonance (NMR). The reactions of clays with PVC were assessed by Low-field NMR, through the determination of proton spin lattice relaxation time. The stability of new organophilic clays and their reactions with PVC were evaluated by thermogravimetric analysis (TGA). High stability was observed for organophilic clays prepared. The degradation of PVC materials obtained with the organophilic clay began at temperatures above 200 deg C. If it is considered that the temperatures normally used in the processing of PVC are between 140 deg C to 180 deg C, the observed results may indicate the possibility of the use of clays for preparation of nanomaterials with PVC. (author)

  10. A novel interaction fingerprint derived from per atom score contributions: exhaustive evaluation of interaction fingerprint performance in docking based virtual screening.

    Science.gov (United States)

    Jasper, Julia B; Humbeck, Lina; Brinkjost, Tobias; Koch, Oliver

    2018-03-16

    Protein ligand interaction fingerprints are a powerful approach for the analysis and assessment of docking poses to improve docking performance in virtual screening. In this study, a novel interaction fingerprint approach (PADIF, protein per atom score contributions derived interaction fingerprint) is presented which was specifically designed for utilising the GOLD scoring functions' atom contributions together with a specific scoring scheme. This allows the incorporation of known protein-ligand complex structures for a target-specific scoring. Unlike many other methods, this approach uses weighting factors reflecting the relative frequency of a specific interaction in the references and penalizes destabilizing interactions. In addition, and for the first time, an exhaustive validation study was performed that assesses the performance of PADIF and two other interaction fingerprints in virtual screening. Here, PADIF shows superior results, and some rules of thumb for a successful use of interaction fingerprints could be identified.

  11. Patient-centred communication intervention study to evaluate nurse-patient interactions in complex continuing care

    Science.gov (United States)

    2012-01-01

    Background Communication impairment is a frequent consequence of stroke. Patients who cannot articulate their needs respond with frustration and agitation, resulting in poor optimization of post-stroke functions. A key component of patient-centred care is the ability of staff to communicate in a way that allows them to understand the patient’s needs. We developed a patient-centred communication intervention targeting registered and unregulated nursing staff caring for complex continuing care patients with communication impairments post stroke. Research objectives include 1) examining the effects of the intervention on patients’ quality of life, depression, satisfaction with care, and agitation; and (2) examining the extent to which the intervention improves staff’s attitudes and knowledge in caring for patients with communication impairments. The intervention builds on a previous pilot study. Methods/design A quasi-experimental repeated measures non-equivalent control group design in a complex continuing care facility is being used. Patients with a communication impairment post-stroke admitted to the facility are eligible to participate. All staff nurses are eligible. Baseline data are collected from staff and patients. Follow-up will occur at 1 and 3 months post-intervention. Subject recruitment and data collection from 60 patients and 30 staff will take approximately 36 months. The Patient-Centred Communication Intervention consists of three components: (1) development of an individualized patient communication care plan; (2) a one-day workshop focused on communication and behavioural management strategies for nursing staff; and (3) a staff support system. The intervention takes comprehensive patient assessments into account to inform the development of communication and behavioural strategies specifically tailored to each patient. Discussion The Patient-Centred Communication Intervention will provide staff with strategies to facilitate interactions with

  12. Patient-centred communication intervention study to evaluate nurse-patient interactions in complex continuing care

    Directory of Open Access Journals (Sweden)

    McGilton Katherine S

    2012-10-01

    facilitate interactions with patients and to minimize agitation associated with considerable stress. The improvement of these interactions will lead to a reduction of agitation, which has the additional significance of increasing patients’ well-being, quality of life, and satisfaction with care. Trial registration ClinicalTrials.gov Identifier NCT01654029

  13. Evaluation of an interactive web-based nursing course with streaming videos for medication administration skills.

    Science.gov (United States)

    Sowan, Azizeh K; Idhail, Jamila Abu

    2014-08-01

    Nursing students should exhibit competence in nursing skills in order to provide safe and quality patient care. This study describes the design and students' response to an interactive web-based course using streaming video technology tailored to students' needs and the course objectives of the fundamentals of nursing skills clinical course. A mixed-methodology design was used to describe the experience of 102 first-year undergraduate nursing students at a school of nursing in Jordan who were enrolled in the course. A virtual course with streaming videos was designed to demonstrate medication administration fundamental skills. The videos recorded the ideal lab demonstration of the skills, and real-world practice performed by registered nurses for patients in a hospital setting. After course completion, students completed a 30-item satisfaction questionnaire, 8 self-efficacy scales, and a 4-item scale solicited their preferences of using the virtual course as a substitute or a replacement of the lab demonstration. Students' grades in the skill examination of the procedures were measured. Relationships between the main variables and predictors of satisfaction and self-efficacy were examined. Students were satisfied with the virtual course (3.9 ± 0.56, out of a 5-point scale) with a high-perceived overall self-efficacy (4.38 ± 0.42, out of a 5-point scale). Data showed a significant correlation between student satisfaction, self-efficacy and achievement in the virtual course (r = 0.45-0.49, p students accessed the course from home and some faced technical difficulties. Significant predictors of satisfaction were ease of access the course and gender (B = 0.35, 0.25, CI = 0.12-0.57, 0.02-0.48 respectively). The mean achievement score of students in the virtual class (7.5 ± 0.34) was significantly higher than that of a previous comparable cohort who was taught in the traditional method (6.0 ± 0.23) (p students believed that the virtual course is a sufficient

  14. Uranium mobility in mine areas: evaluation of the water-rock interaction

    Energy Technology Data Exchange (ETDEWEB)

    Zuddas, P. [UFR Sciences de la Terre. PEPS. Universite Claude Bernard. Lyon (France); Rocha Scislewski, A.; Faivre, D.; Lopez, O. [Institut de Physique du Globe de Paris (France)

    2005-07-01

    Full text of publication follows: Toxicity and natural radioactivity of uranium are among the main environmental concerns for exploitation and processing of uranium ore. Weathering processes and potential contamination paths of these areas have to be identified to preserve the water resources. In this work, leaching experiments were carried out in flow-through reactors. Approximately 750 g of crushed rock of selected grain size between 0.35 and 0.80 mm were introduced into a Pyrex column. Distilled and deionized water, saturated with 5% CO{sub 2}/95% air mixture, was introduced through a glass inlet fitted at the base of the column. Input solution pH was constantly equal to 4.2 while the low flow rate was obtained from a peristaltic pump. The output solution was sampled periodically for about 1 year. Three different rock samples were used: an untreated granite rock with high levels of uranium minerals, a rock with low uranium content and a rock rejected after the lixiviation process for uranium industrial extraction. For untreated rocks pH and silica decrease by 1-2 orders of magnitude while sodium decreases by 2-3 orders of magnitude. This indicates the strong albitite dissolution. Total dissolved uranium has a rather constant level indicating the constant dissolution rate of the uranium mineral assemblage. Thermodynamic modelling of the interacting output solutions indicates that 80% of the dissolved uranium content is under the form of two main carbonate complexes (i.e. UO{sub 2}(CO{sub 3}){sub 2}{sup 2-} and UO{sub 2}(CO{sub 3}){sub 3}{sup 4-}), while solutions are saturated on chalcedony, kaolinite and calcium clay minerals. Solutions are under saturated with respect to uraninite and low-temperature albite. In experiments where material was treated with sulphuric acid in the plant, pH is constantly equal to 4 indicating the lack of rock buffering properties. Na, Ca, and SO{sub 4} decrease by several orders of magnitude (from some initial mmol/kg) reaching

  15. Evaluating public education messages aimed at monitoring and responding to social interactive technology on smartphones among young drivers.

    Science.gov (United States)

    Gauld, Cassandra S; Lewis, Ioni; White, Katherine M; Fleiter, Judy J; Watson, Barry

    2017-07-01

    Young drivers are more likely than any other age group to access social interactive technology (e.g., Facebook, E-mail) on a smartphone while driving. The current study formed part of a larger investigation and was guided by The Step Approach to Message Design and Testing (SatMDT) to evaluate the relative effectiveness of three different public education messages aimed at reducing smartphone use among young drivers. The messages were each adapted to the specific behaviours of monitoring/reading and responding to social interactive technology on smartphones. Participants (n=288; 199F, 89M) were drivers aged 17-25 years who resided in the Australian state of Queensland. Message acceptance (i.e., intention and effectiveness) and message rejection were both assessed using a self-report survey. Multivariate analyses found that, overall, the messages targeting monitoring/reading behaviour were considered more effective than those targeting responding behaviour. The message that challenged the underlying motivation that believing you are a good driver makes it easier to monitor/read social interactive technology while driving was considered particularly effective by young male drivers. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Evaluating the Intraspecific Interactions of Indian Rosewood (Dalbergia sissoo Roxb. Trees in Indian Rosewood Reserveof Khuzestan Province

    Directory of Open Access Journals (Sweden)

    Y. Erfanifard

    2016-05-01

    Full Text Available Positive and negative (facilitative and competitive interactions of plants are important issues in autecology and can be evaluated by the spatial pattern analysis in plant ecosystems. This study investigates the intraspecific interactions of Indian rosewood (Dalbergia sissoo Roxb. trees in Indian rosewood Reserve of Khuzestan province. Three 150 m × 200 m plots were selected and the spatial locations of all Indian rosewoods (239 trees were specified. Structurally different summary statistics (nearest neighbour distribution function D(r, K2-index K2(r, pair correlation function g(r, and O-ring O(r were also implemented to analyze the spatial pattern of the trees. The distribution of Indian rosewood trees significantly followed inhomogeneous Poisson process (α=0.05. The results of D(r and K2(r showed that the maximum distance to nearest tree was 12 m and density was decreased to this scale. The results of g(r and O(r also revealed the significant aggregation of Indian rosewood trees at scales of 1.5 to 4 m (α=0.05. In general, it was concluded that Indian rosewood trees had positive intraspecific interactions in Indian rosewood Reserve of Khuzestan province and their aggregation showed their facilitative effects on one another.

  17. Tacrolimus interaction with nafcillin resulting in significant decreases in tacrolimus concentrations: A case report.

    Science.gov (United States)

    Wungwattana, Minkey; Savic, Marizela

    2017-04-01

    Tacrolimus (TAC) is subject to many drug interactions as a result of its metabolism primarily via CYP450 isoenzyme 3A4. Numerous case reports of TAC and CYP3A4 inducers and inhibitors have been described including antimicrobials, calcium channel antagonists, and antiepileptic drugs. We present the case of a 13-year-old patient with cystic fibrosis and a history of liver transplantation, where subtherapeutic TAC concentrations were suspected to be a result of concomitant TAC and nafcillin (NAF) therapy. The observed drug interaction occurred on two separate hospital admissions, during both of which the patient exhibited therapeutic TAC concentrations prior to exposure to NAF, a CYP3A4 inducer. Upon discontinuation of NAF, TAC concentrations recovered in both instances. This case represents a drug-drug interaction between TAC and NAF that has not previously been reported to our knowledge. Despite the lack of existing reports of interaction between these two agents, this case highlights the importance of therapeutic drug monitoring and assessing for any potential drug-drug or drug-food interactions in patients receiving TAC therapy. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Evaluation of a treatment manual and workshops for disseminating, parent-child interaction therapy.

    Science.gov (United States)

    Herschell, Amy D; McNeil, Cheryl B; Urquiza, Anthony J; McGrath, Jean M; Zebell, Nancy M; Timmer, Susan G; Porter, Alissa

    2009-01-01

    This study's main purposes were to: (a) evaluate a treatment manual as a dissemination strategy, (b) compare two workshop formats for evidence-based treatment (EBT) training, and (c) provide preliminary data on therapist characteristics potentially associated with successful EBT adoption. Forty-two community-based clinicians were assigned to one of two training groups (didactic or experiential). Behavior observation and self-report data were collected at four time points. Results suggest that reading a treatment manual is useful, but not sufficient. Experiential and didactic training were equally effective in increasing knowledge, skill, and satisfaction; however, after a 2-day training, few participants demonstrated mastery of skills.

  19. Evaluation of the exchange interaction and crystal fields in a prototype Dy2 SMM

    Science.gov (United States)

    Zhang, Qing; Sarachik, Myriam; Baker, Michael; Chen, Yizhang; Kent, Andrew; Pineda, Eufemio; McInnes, Eric

    In order to gain an understanding of the INS and magnetization data obtained for Dy2, the simplest member of a newly synthesized family of dysprosium-based molecular magnets, we report on calculations of the magnetic behavior of a Dy2 cluster with the formula [hqH2][Dy2(hq)4(NO3)3].MeOH. The molecular complex contains one high symmetry Dy(III) ion and one low symmetry Dy(III) ion. Our calculations suggest that exchange coupling between the two ions controls the behavior of the magnetization at low temperature, while the crystal field of the low symmetry Dy(III) ion controls the behavior at higher temperature. A point charge electrostatic model, based on crystallographic coordinates, provides a starting point for the determination of the crystal field. Parameters in these calculations are adjusted to provide best fits to inelastic neutron scattering data (INS) and low temperature magnetometry: the INS measurements access crystal field energies and low temperature magnetization probes the Dy-Dy exchange interaction. Work supported by ARO W911NF-13-1-1025 (CCNY) and NSF-DMR-1309202 (NYU).

  20. mCLEV-R: Design and Evaluation of an Interactive and Collaborative M-Learning Application

    Directory of Open Access Journals (Sweden)

    Teresa Monahan

    2007-06-01

    Full Text Available Continuous enhancements in computer technology and the current widespread computer literacy among the public have resulted in a new generation of students that expect increasingly more from their e-learning experiences. To keep up with such expectations, e-learning systems have gone through a radical change from the initial text-based environments to more stimulating multimedia systems. E-learning functionalities are now also being extended to mobile platforms in order to be more available and convenient for users. Many mobile learning applications have now been developed and they too are becoming more advanced. However, providing truly collaborative and interactive mobile learning tools still remains a challenge. In this paper, we present a desktop e-learning system called CLEV-R and in particular a component of the system that we have developed for mobile devices. This mobile component explores the possibility of providing collaboration tools for mobile learners while also presenting the learning experience through an engaging 3D environment.