scholarly journals Observational Study of the Clinical Efficacy of Voriconazole and Its Relationship to Plasma Concentrations in Patients

2011 ◽  
Vol 55 (10) ◽  
pp. 4782-4788 ◽  
Author(s):  
Peter F. Troke ◽  
Hans P. Hockey ◽  
William W. Hope
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Clinical Response ◽  
Response Rate ◽  
Fungal Infections ◽  
Lower Probability ◽  
Therapeutic Drug ◽  
The Impact ◽  
The Relationship ◽  
Probability Of Response

ABSTRACTVoriconazole is approved for treating invasive fungal infections. We examined voriconazole exposure-response relationships for patients from nine published clinical trials. The relationship between the mean voriconazole plasma concentration (Cavg) and clinical response and between the freeCavg/MIC ratio versus the clinical response were explored using logistic regression. The impact of covariates on response was also assessed. Monte Carlo simulation was used to estimate the relationship between the trough concentration/MIC ratio and the probability of response. The covariates individually related to response were as follows: study (P< 0.001), therapy (primary/salvage,P< 0.001), primary diagnosis (P< 0.001), race (P= 0.004), baseline bilirubin (P< 0.001), baseline alkaline phosphatase (P= 0.014), and pathogen (yeast/mold,P< 0.001). TheCavgfor 72% of the patients was 0.5 to 5.0 μg/ml, with the maximum response rate (74%) at 3.0 to 4.0 μg/ml. TheCavgshowed a nonlinear relationship to response (P< 0.003), with a lower probability at the extremes. For patients withCavg< 0.5 μg/ml, the response rate was 57%. The lowest response rate (56%) was seen with aCavg≥ 5.0 μg/ml (18% of patients) and was associated with significantly lower mold infection responses compared to yeasts (P< 0.001) but not with voriconazole toxicity. Higher freeCavg/MIC ratios were associated with a progressively higher probability of response. Monte Carlo simulation suggested that a trough/MIC ratio of 2 to 5 is associated with a near-maximal probability of response. The probability of response is lower at the extremes ofCavg. Patients with higher freeCavg/MIC ratios have a higher probability of clinical response. A trough/MIC ratio of 2 to 5 can be used as a target for therapeutic drug monitoring.

scholarly journals Population Pharmacokinetics of Voriconazole in Adults

2011 ◽  
Vol 56 (1) ◽  
pp. 526-531 ◽  
Author(s):  
William W. Hope
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Healthy Volunteers ◽  
Clinical Response ◽  
Population Pharmacokinetics ◽  
Drug Exposure ◽  
Fungal Infections ◽  
Parameter Estimates ◽  
Pharmacokinetic Studies ◽  
Pharmacokinetic Data

ABSTRACTVoriconazole is a first-line agent for the treatment of invasive fungal infections. The pharmacology of voriconazole is characterized by extensive interindividual variability and nonlinear pharmacokinetics. The population pharmacokinetics of voriconazole in 64 adults is described. The patient population consisted of 21 healthy volunteers, who received a range of intravenous (i.v.) and oral voriconazole regimens, and 43 patients with proven or probable invasive aspergillosis, who received the currently licensed dosage. Voriconazole concentrations were measured using high-performance liquid chromatography (HPLC). The pharmacokinetic data were modeled using a nonparametric methodology and with a nonlinear pharmacokinetic structural model. The extent and consequences of pharmacokinetic variability were explored using Monte Carlo simulation. The relationship between drug exposure and clinical response was explored using logistic regression. Optimal sampling times were identified using D-optimal design. The fit of the nonlinear model was acceptable. Data from the healthy volunteers provided robust estimates forKmand the maximum rate of enzyme activity (Vmax). The Bayesian parameter estimates were more variable and statistically different in patients than in volunteers. There was a linear relationship between the trough concentration and area under the concentration-time curve (AUC0-12). There was no relationship between the AUC0-12and clinical response. The original parameter values were readily recapitulated using Monte Carlo simulation. Initial i.v. dosing resulted in higher AUC0-12and trough concentrations compared with oral dosing. Sample collection times of 1, 2, 3, 4, 8, and 12 h after an i.v. infusion are maximally informative times for future pharmacokinetic studies.

scholarly journals UNCERTAINTY OF BATHYMETRY MODELS AND EFFECT ON TSUNAMI MODELS

2020 ◽  
pp. 22
Author(s):  
Ignacio Sepulveda ◽  
Jennifer S. Haase ◽  
Philip L.-F. Liu ◽  
Mircea Grigoriu ◽  
Brook Tozer ◽  
...  
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Random Field ◽  
Field Model ◽  
Tsunami Hazard ◽  
Response Uncertainty ◽  
Random Field Model ◽  
Three Stages ◽  
Hazard Assessments ◽  
The Impact

We describe the uncertainties of altimetry-predicted bathymetry models and then quantify the impact of this uncertainty in tsunami hazard assessments. The study consists of three stages. First, we study the statistics of errors of altimetry-predicted bathymetry models. Second, we employ these statistics to propose a random field model for errors anywhere. Third, we use bathymetry samples to conduct a Monte Carlo simulation and describe the tsunami response uncertainty. We found that bathymetry uncertainties have a greater impact in shallow areas. We also noted that tsunami leading waves are less affected by uncertainties.Recorded Presentation from the vICCE (YouTube Link): https://youtu.be/zzL_XWWAQ7o

scholarly journals Changes in the Portfolio Management and Construction under the Pandemic Era

2021 ◽  
Vol 275 ◽  
pp. 01005
Author(s):  
Ruipeng Tan
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Stock Returns ◽  
Financial Market ◽  
Portfolio Management ◽  
Portfolio Construction ◽  
Sample Data ◽  
Before And After ◽  
Reduce Risk ◽  
The Impact

This paper focuses on comparing portfolio management and construction before and after the coronavirus. First, this paper presents the importance of building up portfolios for investors to diversify their risks. Theories on portfolio management are discussed in this section to show how they have been developed to help on investing and reduce risk. Then, the paper moves on to show the impact of the pandemic on the financial market and portfolio management. Sample data on tech stock returns are collected to perform a Monte Carlo simulation on portfolio construction to find out the efficient portfolio before and after the COVID-19 outbreak. The efficient portfolio is build based on the Markowitz theory to find the combination. Comparisons between these portfolio constructions are made to find out the changes in portfolio management and construction under the pandemic era. In conclusion, this paper presents how pandemic has changed and impacted the investments and lists recommendations on future portfolio management and construction.

scholarly journals Social-network-based water supply network sectorization methodology using monte carlo simulation to predict economical and operational benefits

2017 ◽  
Vol 26 ◽  
pp. 44-53
Author(s):  
Enrique Campbell ◽  
Amilkar Illaya-Ayza ◽  
Joaquín Izquierdo ◽  
Rafael Pérez-García ◽  
Idel Montalvo
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Water Supply ◽  
Optimization Method ◽  
Supply Network ◽  
Water Supply Network ◽  
Water Supply Management ◽  
Net Profit ◽  
Short Run ◽  
The Impact

Water Supply Network (WSN) sectorization is a broadly known technique aimed at enhancing water supply management. In general, existing methodologies for sectorization of WSNs are limited to assessment of the impact of its implementation over reduction of background leakage, underestimating increased capacity to detect new leakage events and undermining appropriate investment substantiation. In this work, we raise this issue and put in place a methodology to optimize sectors' design. To this end, we carry out a novel combination of the Short Run Economic Leakage Level concept (SRELL- corresponding to leakage level that can occur in a WSN in a certain period of time and whose reparation would be more costly than the benefits that can be obtained). With a non-deterministic optimization method based on Genetic Algorithms (GAs) in combination with Monte Carlo simulation. As an example of application, methodology is implemented over a 246 km pipe-long WSN, reporting 72 397 $/year as net profit.

Benchmarking Fuel Economy of Connected and Automated Vehicles in Real World Driving Conditions via Monte Carlo Simulation

2020 ◽  
Author(s):  
Shreshta Rajakumar Deshpande ◽  
Shobhit Gupta ◽  
Dennis Kibalama ◽  
Nicola Pivaro ◽  
Marcello Canova
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Fuel Economy ◽  
Real World ◽  
Human Subjects ◽  
Driver Model ◽  
Traffic Information ◽  
Vehicle Speed ◽  
Instrumented Vehicle ◽  
The Impact

Abstract Connectivity and automation have accelerated the development of algorithms that use route and real-time traffic information for improving energy efficiency. The evaluation of such benefits, however, requires establishing a reliable baseline that is representative of a real-world driving environment. In this context, virtual driver models are generally adopted to predict the vehicle speed based on route data and presence of lead vehicles, in a way that mimics the response of human drivers. This paper proposes an Enhanced Driver Model (EDM) that forecasts the human response when driving in urban conditions, considering the effects of Signal Phasing and Timing (SPaT) by introducing the concept of Line-of-Sight (LoS). The model was validated against data collected on an instrumented vehicle driven on public roads by different human subjects. Using this model, a Monte Carlo simulation is conducted to determine the statistical distribution of fuel consumption and travel time on a given route, varying driver behavior (aggressiveness), traffic conditions and SPaT. This allows one to quantify the impact of uncertainties associated to real-world driving in fuel economy estimates.

scholarly journals Evaluating network importance measures based on the construction spectrum

2019 ◽  
Vol 11 (3) ◽  
pp. 168781401983083
Author(s):  
Yongjun Du ◽  
Zhenggeng Ye ◽  
Pan Zhang ◽  
Yaqi Guo ◽  
Zhiqiang Cai
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Network Structure ◽  
Network Reliability ◽  
Equal Probability ◽  
Numerical Example ◽  
Estimate Reliability ◽  
The Impact

The construction spectrum is a useful tool to investigate the network reliability, which only depends on network structure and is called structure invariant. Importance measures are efficient tools to quantify and rank the impact of edges within a network. This study considers the K-terminal network with n edges and assumes that edges fail with an equal probability. The article focuses on investigating the importance measures of individual edge for the K-terminal network, including reliability achievement worth and reliability reduction worth, via the construction spectrum–based method. Generally, we establish the equations for reliability achievement worth and reliability reduction worth using the construction spectrum and determine the conditions under which the importance rankings generated by reliability achievement worth and reliability reduction worth only depend on the network structure through the construction spectrum. Similar results are obtained with reliability achievement worth and reliability reduction worth for pair of edges. A construction spectrum–based Monte-Carlo simulation is used to estimate reliability achievement worth and reliability reduction worth. Finally, a numerical example is presented to illustrate the application of these measures.

scholarly journals Practical Risk Assessment of Ground Vibrations Resulting from Blasting, Using Gene Expression Programming and Monte Carlo Simulation Techniques

2020 ◽  
Vol 10 (2) ◽  
pp. 472 ◽  
Author(s):  
Amir Mahdiyar ◽  
Danial Jahed Armaghani ◽  
Mohammadreza Koopialipoor ◽  
Ahmadreza Hedayat ◽  
Arham Abdullah ◽  
...  
Keyword(s):  
Gene Expression ◽  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Gene Expression Programming ◽  
Sensitivity Analyses ◽  
Accurate Estimation ◽  
Blasting Operation ◽  
Simulation Techniques ◽  
Input Variables ◽  
The Impact

Peak particle velocity (PPV) is a critical parameter for the evaluation of the impact of blasting operations on nearby structures and buildings. Accurate estimation of the amount of PPV resulting from a blasting operation and its comparison with the allowable ranges is an integral part of blasting design. In this study, four quarry sites in Malaysia were considered, and the PPV was simulated using gene expression programming (GEP) and Monte Carlo simulation techniques. Data from 149 blasting operations were gathered, and as a result of this study, a PPV predictive model was developed using GEP to be used in the simulation. In order to ensure that all of the combinations of input variables were considered, 10,000 iterations were performed, considering the correlations among the input variables. The simulation results demonstrate that the minimum and maximum PPV amounts were 1.13 mm/s and 34.58 mm/s, respectively. Two types of sensitivity analyses were performed to determine the sensitivity of the PPV results based on the effective variables. In addition, this study proposes a method specific to the four case studies, and presents an approach which could be readily applied to similar applications with different conditions.

Spiegel Online

2017 ◽  
pp. 1-11
Author(s):  
Karl Schmedders ◽  
Armin Rott
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Web Site ◽  
Business Plan ◽  
Decision Makers ◽  
Bottom Line ◽  
Art Objects ◽  
Input Parameters ◽  
High Level ◽  
The Impact

Spiegel Online (www.spiegel.de) is the leading news Web site in Germany. The site was first designed to accompany Der Spiegel, one of Europe's largest and Germany's most influential weekly magazine, which has a weekly circulation of around one million. The site's content is produced by a team of more than fifty journalists writing in several categories: politics, business, networld, panorama, arts and entertainment, science, university, school, sports, travel, weather, and automobiles. The original content is complemented by articles purchased from news agencies and selected articles from the print edition. Spiegel-Verlag is a major contributor to the Hamburg Media School, which offers professional master's degree programs in Media Management (MBA), film, and journalism. In their second year, MBA students typically engage in consulting projects with major media companies. In a recent assignment, Spiegel Online posed two questions to the MBA team: are there any chances for an economically successful entry into the market for interactive classifieds? And if so, what should the business model look like in detail? A student team analyzed markets for classified ads and found one market segment that appeared to be particularly promising: the market for art objects. During the development of a business plan for a new venture in this market it became apparent that there is much uncertainty about the key input parameters to the business plan. As a result, it is very difficult to assess the viability of the business idea. How can the team properly account for the uncertain input parameters? What is the impact of this uncertainty on the bottom line? Will a Web site for art objects earn or lose money? How can the team communicate this uncertainty to a group of high-level decision makers who want a simple “go or no-go” recommendation?The objective is to make students aware of the applicability of Monte Carlo simulation to the analysis of complex business plans. Students should learn how to explicitly account for uncertain inputs in a business plan, how to assess the impact of uncertainty on the bottom line via Monte Carlo simulation, and how to communicate the results of their analysis to high-level decision makers.

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