Calculation of Franck-Condon factors including anharmonicity: simulation of the C2 H4+ X̃2B 3u←C2 H4X̃1 Ag band in the photoelectron spectrum of ethylene

Our new simple method for calculating accurate Franck-Condon factors including nondiagonal (i.e., mode-mode) anharmonic coupling is used to simulate the C2H4+X2B 3u←C2H4X̃1 Ag band in the photoelectron spectrum. An improved vibrational basis set truncation algorithm, which permits very efficient computations, is employed. Because the torsional mode is highly anharmonic it is separated from the other modes and treated exactly. All other modes are treated through the second-order perturbation theory. The perturbation-theory corrections are significant and lead to a good agreement with experiment, although the separability assumption for torsion causes the C2 D4 results to be not as good as those for C2 H4. A variational formulation to overcome this circumstance, and deal with large anharmonicities in general, is suggested

Improved earthquake response via simulation and integrated space- and ground-based technologies: the TREMOR proposal

Earthquakes occurring around the world each year cause thousands ofdeaths, millions of dollars in damage to infrastructure, and incalculablehuman suffering. In recent years, satellite technology has been asignificant boon to response efforts following an earthquake and itsafter-effects by providing mobile communications between response teamsand remote sensing of damaged areas to disaster management organizations.In 2007, an international team of students and professionals assembledduring theInternational Space University’s Summer Session Program in Beijing, Chinato examine how satellite and ground-based technology could be betterintegrated to provide an optimised response in the event of an earthquake.The resulting Technology Resources for Earthquake MOnitoring and Response(TREMOR) proposal describes an integrative prototype response system thatwill implement mobile satellite communication hubs providing telephone anddata links between response teams, onsite telemedicine consultation foremergency first-responders, and satellite navigation systems that willlocate and track emergency vehicles and guide search-and-rescue crews. Aprototype earthquake simulation system is also proposed, integratinghistorical data, earthquake precursor data, and local geomatics andinfrastructure information to predict the damage that could occur in theevent of an earthquake. The backbone of these proposals is a comprehensiveeducation and training program to help individuals, communities andgovernments prepare in advance. The TREMOR team recommends thecoordination of these efforts through a centralised, non-governmentalorganization.

Orthotropic active strain models for the numerical simulation of cardiac biomechanics

An active strain formulation for orthotropic constitutive laws arising in cardiac mechanics modeling is introduced and studied. The passive mechanical properties of the tissue are described by the Holzapfel-Ogden relation. In the active strain formulation, the Euler-Lagrange equations for minimizing the total energy are written in terms of active and passive deformation factors, where the active part is assumed to depend, at the cell level, on the electrodynamics and on the specific orientation of the cardiac cells. The well-posedness of the linear system derived from a generic Newton iteration of the original problem is analyzed and different mechanical activation functions are considered. In addition, the active strain formulation is compared with the classical active stress formulation from both numerical and modeling perspectives. Taylor-Hood and MINI finite elements are employed to discretize the mechanical problem. The results of several numerical experiments show that the proposed formulation is mathematically consistent and is able to represent the main key features of the phenomenon, while allowing savings in computational costs.

Simulation methods with extended stability for stiff biochemical kinetics

Background: With increasing computer power, simulating the dynamics of complex systems in chemistry and biology is becoming increasingly routine. The modelling of individual reactions in (bio)chemical systems involves a large number of random events that can be simulated by the stochastic simulation algorithm (SSA). The key quantity is the step size, or waiting time, τ, whose value inversely depends on the size of the propensities of the different channel reactions and which needs to be re-evaluated after every firing event. Such a discrete event simulation may be extremely expensive, in particular for stiff systems where τ can be very short due to the fast kinetics of some of the channel reactions. Several alternative methods have been put forward to increase the integration step size. The so-called τ-leap approach takes a larger step size by allowing all the reactions to fire, from a Poisson or Binomial distribution, within that step. Although the expected value for the different species in the reactive system is maintained with respect to more precise methods, the variance at steady state can suffer from large errors as τ grows. Results: In this paper we extend Poisson τ-leap methods to a general class of Runge-Kutta (RK) τ-leap methods. We show that with the proper selection of the coefficients, the variance of the extended τ-leap can be well-behaved, leading to significantly larger step sizes.Conclusions: The benefit of adapting the extended method to the use of RK frameworks is clear in terms of speed of calculation, as the number of evaluations of the Poisson distribution is still one set per time step, as in the original τ-leap method. The approach paves the way to explore new multiscale methods to simulate (bio)chemical systems.

Jambes lourdes, insuffisance veineuse des membres inférieurs et hormonothérapie substitutive [Heavy legs, venous insufficiency of the legs and hormone substitution therapy]

The effects of estrogens and gestagens on veins and circulation have been studied since prescription of these hormones as oral contraception and description of related thromboembolic events. The identification of different receptors and the description of these receptors in venous walls have helped to understand some hormonal effects. However, the actual knowledge remains insufficient to explain the complexity of the actions of hormones on venous function. The distribution, the density and the receptor types vary with age, gender, hormonal status and vascular bed. Gestagens mainly reduce the tone of venous walls, whereas estrogens have various effects. Between 25% and 50% of European adults and even 80% or more in some risk groups complain about heavy legs, with or without chronic venous insufficiency. The number of women to whom hormonal substitution is or could be prescribed increases along with aging of populations and the better understanding of potential benefits. The need for a better understanding of vascular effects of sexual hormones is growing, since the incidence of chronic venous insufficiency of the legs increases with age. The life prognosis will not be affected by a deterioration of a chronic venous insufficiency. In contrast, the quality of life, morbidity and the cost of treatment will be expected to change. In addition, thromboembolic events have to be considered, as has been shown in recent studies. These findings outline the need for further studies on the relation between hormones and venous function and for some caution when prescribing hormonal substitution.

Guidelines for the Conversion of Urban Four-Lane Undivided Roadways to Three-Lane Two-Way Left-turn Lane Facilities, April 2001

Four-lane undivided roadways in urban areas can experience a degradation of service and/or safety as traffic volumes increase. In fact, the existence of turning vehicles on this type of roadway has a dramatic effect on both of these factors. The solution identified for these problems is typically the addition of a raised median or two-way left-turn lane (TWLTL). The mobility and safety benefits of these actions have been proven and are discussed in the “Past Research” chapter of this report along with some general cross section selection guidelines. The cost and right-of-way impacts of these actions are widely accepted. These guidelines focus on the evaluation and analysis of an alternative to the typical four-lane undivided cross section improvement approach described above. It has been found that the conversion of a four-lane undivided cross section to three lanes (i.e., one lane in each direction and a TWLTL) can improve safety and maintain an acceptable level of service. These guidelines summarize the results of past research in this area (which is almost nonexistent) and qualitative/quantitative before-and-after safety and operational impacts of case study conversions located throughout the United States and Iowa. Past research confirms that this type of conversion is acceptable or feasible in some situations but for the most part fails to specifically identify those situations. In general, the reviewed case study conversions resulted in a reduction of average or 85th percentile speeds (typically less than five miles per hour) and a relatively dramatic reduction in excessive speeding (a 60 to 70 percent reduction in the number of vehicles traveling five miles per hour faster than the posted speed limit was measured in two cases) and total crashes (reductions between 17 to 62 percent were measured). The 13 roadway conversions considered had average daily traffic volumes of 8,400 to 14,000 vehicles per day (vpd) in Iowa and 9,200 to 24,000 vehicles per day elsewhere. In addition to past research and case study results, a simulation sensitivity analysis was completed to investigate and/or confirm the operational impacts of a four-lane undivided to three-lane conversion. First, the advantages and disadvantages of different corridor simulation packages were identified for this type of analysis. Then, the CORridor SIMulation (CORSIM) software was used x to investigate and evaluate several characteristics related to the operational feasibility of a four-lane undivided to three-lane conversion. Simulated speed and level of service results for both cross sections were documented for different total peak-hour traffic, access densities, and access-point left-turn volumes (for a case study corridor defined by the researchers). These analyses assisted with the identification of the considerations for the operational feasibility determination of a four -lane to three-lane conversion. The results of the simulation analyses primarily confirmed the case study impacts. The CORSIM results indicated only a slight decrease in average arterial speed for through vehicles can be expected for a large range of peak-hour volumes, access densities, and access-point left-turn volumes (given the assumptions and design of the corridor case study evaluated). Typically, the reduction in the simulated average arterial speed (which includes both segment and signal delay) was between zero and four miles per hour when a roadway was converted from a four-lane undivided to a three-lane cross section. The simulated arterial level of service for a converted roadway, however, showed a decrease when the bi-directional peak-hour volume was about 1,750 vehicles per hour (or 17,500 vehicles per day if 10 percent of the daily volume is assumed to occur in the peak hour). Past research by others, however, indicates that 12,000 vehicles per day may be the operational capacity (i.e., level of service E) of a three-lane roadway due to vehicle platooning. The simulation results, along with past research and case study results, appear to support following volume-related feasibility suggestions for four-lane undivided to three-lane cross section conversions. It is recommended that a four-lane undivided to three-lane conversion be considered as a feasible (with respect to volume only) option when bi-directional peak-hour volumes are less than 1,500 vehicles per hour, but that some caution begin to be exercised when the roadway has a bi-directional peak-hour volume between 1,500 and 1,750 vehicles per hour. At and above 1,750 vehicles per hour, the simulation indicated a reduction in arterial level of service. Therefore, at least in Iowa, the feasibility of a four-lane undivided to three-lane conversion should be questioned and/or considered much more closely when a roadway has (or is expected to have) a peak-hour volume of more than 1,750 vehicles. Assuming that 10 percent of the daily traffic occurs during the peak-hour, these volume recommendations would correspond to 15,000 and 17,500 vehicles per day, respectively. These suggestions, however, are based on the results from one idealized case xi study corridor analysis. Individual operational analysis and/or simulations should be completed in detail once a four-lane undivided to three-lane cross section conversion is considered feasible (based on the general suggestions above) for a particular corridor. All of the simulations completed as part of this project also incorporated the optimization of signal timing to minimize vehicle delay along the corridor. A number of determination feasibility factors were identified from a review of the past research, before-and-after case study results, and the simulation sensitivity analysis. The existing and expected (i.e., design period) statuses of these factors are described and should be considered. The characteristics of these factors should be compared to each other, the impacts of other potentially feasible cross section improvements, and the goals/objectives of the community. The factors discussed in these guidelines include • roadway function and environment • overall traffic volume and level of service • turning volumes and patterns • frequent-stop and slow-moving vehicles • weaving, speed, and queues • crash type and patterns • pedestrian and bike activity • right-of-way availability, cost, and acquisition impacts • general characteristics, including - parallel roadways - offset minor street intersections - parallel parking - corner radii - at-grade railroad crossings xii The characteristics of these factors are documented in these guidelines, and their relationship to four-lane undivided to three-lane cross section conversion feasibility identified. This information is summarized along with some evaluative questions in this executive summary and Appendix C. In summary, the results of past research, numerous case studies, and the simulation analyses done as part of this project support the conclusion that in certain circumstances a four-lane undivided to three-lane conversion can be a feasible alternative for the mitigation of operational and/or safety concerns. This feasibility, however, must be determined by an evaluation of the factors identified in these guidelines (along with any others that may be relevant for a individual corridor). The expected benefits, costs, and overall impacts of a four-lane undivided to three-lane conversion should then be compared to the impacts of other feasible alternatives (e.g., adding a raised median) at a particular location.

Population PK-guided simulation study in children exposed to drugs in human milk

Risks of significant infant drug exposure through human milk arepoorly defined due to lack of large-scale PK data. We propose to useBayesian approach based on population PK (popPK)-guided modelingand simulation for risk prediction. As a proof-of-principle study, weexploited fluoxetine milk concentration data from 25 women. popPKparameters including milk-to-plasma ratio (MP ratio) were estimatedfrom the best model. The dose of fluoxetine the breastfed infant wouldreceive through mother's milk, and infant plasma concentrations wereestimated from 1000 simulated mother-infant pairs, using randomassignment of feeding times and milk volume. A conservative estimateof CYP2D6 activity of 20% of the allometrically-adjusted adult valuewas assumed. Derived model parameters, including MP ratio were consistentwith those reported in the literature. Visual predictive check andother model diagnostics showed no signs of model misspecifications.The model simulation predicted that infant exposure levels to fluoxetinevia mother's milk were below 10% of weight-adjusted maternal therapeuticdoses in >99% of simulated infants. Predicted median ratio ofinfant-mother serum levels at steady state was 0.093 (range 0.033-0.31),consistent with literature reported values (mean=0.07; range 0-0.59).Predicted incidence of relatively high infant-mother ratio (>0.2) ofsteady-state serum fluoxetine concentrations was <1.3%. Overall, ourpredictions are consistent with clinical observations. Our approach maybe valid for other drugs, allowing in silico prediction of infant drugexposure risks through human milk. We will discuss application of thisapproach to another drug used in lactating women.

Prediction of infant drug exposure through breastfeeding: population PK modeling and simulation of fluoxetine

BACKGROUND: Risks of significant infant drug exposurethrough breastmilk are poorly defined for many drugs, and largescalepopulation data are lacking. We used population pharmacokinetics(PK) modeling to predict fluoxetine exposure levels ofinfants via mother's milk in a simulated population of 1000 motherinfantpairs.METHODS: Using our original data on fluoxetine PK of 25breastfeeding women, a population PK model was developed withNONMEM and parameters, including milk concentrations, wereestimated. An exponential distribution model was used to account forindividual variation. Simulation random and distribution-constrainedassignment of doses, dosing time, feeding intervals and milk volumewas conducted to generate 1000 mother-infant pairs with characteristicssuch as the steady-state serum concentrations (Css) and infantdose relative to the maternal weight-adjusted dose (relative infantdose: RID). Full bioavailability and a conservative point estimate of1-month-old infant CYP2D6 activity to be 20% of the adult value(adjusted by weigth) according to a recent study, were assumed forinfant Css calculations.RESULTS: A linear 2-compartment model was selected as thebest model. Derived parameters, including milk-to-plasma ratios(mean: 0.66; SD: 0.34; range, 0 - 1.1) were consistent with the valuesreported in the literature. The estimated RID was below 10% in >95%of infants. The model predicted median infant-mother Css ratio was0.096 (range 0.035 - 0.25); literature reported mean was 0.07 (range0-0.59). Moreover, the predicted incidence of infant-mother Css ratioof >0.2 was less than 1%.CONCLUSION: Our in silico model prediction is consistent withclinical observations, suggesting that substantial systemic fluoxetineexposure in infants through human milk is rare, but further analysisshould include active metabolites. Our approach may be valid forother drugs. [supported by CIHR and Swiss National Science Foundation(SNSF)]

Motor Vehicle Accident Fatalities for the Week Ending, February 24, 2006

Record of the Fatalities for Motor Vehicle Accidents in Iowa per week.

Motor Vehicle Accident Fatalities for the Week Ending, February 3, 2006

Record of the Fatalities for Motor Vehicle Accidents in Iowa per week.

Motor Vehicle Accident Fatalities for the Week Ending, March 3, 2006

Record of the Fatalities for Motor Vehicle Accidents in Iowa per week.

Motor Vehicle Accident Fatalities for the Week Ending, March 17, 2006

Record of the Fatalities for Motor Vehicle Accidents in Iowa per week.

Motor Vehicle Accident Fatalities for the Week Ending, March 31, 2006

Record of the Fatalities for Motor Vehicle Accidents in Iowa per week.

Motor Vehicle Accident Fatalities for the Week Ending, February 10, 2006

Record of the Fatalities for Motor Vehicle Accidents in Iowa per week.