Statistics of depth probed by cw measurement of photons in a turbid medium

Photon migration in a turbid medium has been modeled in many different ways. The motivation for such modeling is based on technology that can be used to probe potentially diagnostic optical properties of biological tissue. Surprisingly, one of the more effective models is also one of the simplest. It is based on statistical properties of a nearest-neighbor lattice random walk. Here we develop a theory allowing one to calculate the number of visits by a photon to a given depth, if it is eventually detected at an absorbing surface. This mimics cw measurements made on biological tissue and is directed towards characterizing the depth reached by photons injected at the surface. Our development of the theory uses formalism based on the theory of a continuous-time random walk (CTRW). Formally exact results are given in the Fourier-Laplace domain, which, in turn, are used to generate approximations for parameters of physical interest.

Quantum relaxation in random magnets

We present a comprehensive study of the low-temperature magnetic relaxation in random magnets. The first part of the paper contains theoretical analysis of the expected features of the relaxation, based upon current theories of quantum tunneling of magnetization. Models of tunneling, dissipation, the crossover from the thermal to the quantum regime, and the effect of barrier distribution on the relaxation rate are discussed. It is argued that relaxation-type experiments are ideally suited for the observation of magnetic tunneling, since they automatically provide the condition of very low barriers. The second part of the paper contains experimental results on transition-metal¿rare-earth amorphous magnets. Structural and magnetic characterization of materials is presented. The temperature and field dependence of the magnetic relaxation is studied. Our key observation is a nonthermal character of the relaxation below a few kelvin. The observed features are in agreement with theoretical suggestions on quantum tunneling of magnetization.

Quantum tunneling of vortices in the Tl2CaBa2Cu2O8 superconductor

Magnetic-relaxation measurements of a Tl-based high-Tc superconductor show temperature-independent flux creep below 6 K. The effect is analyzed in terms of the overdamped quantum diffusion of two-dimensional vortices. Good agreement between theory and experiment is found.

A bio-inspired agent-based programming environment for pervasive platforms

Abstract in English : Ubiquitous Computing is the emerging trend in computing systems. Based on this observation this thesis proposes an analysis of the hardware and environmental constraints that rule pervasive platforms. These constraints have a strong impact on the programming of such platforms. Therefore solutions are proposed to facilitate this programming both at the platform and node levels. The first contribution presented in this document proposes a combination of agentoriented programming with the principles of bio-inspiration (Phylogenesys, Ontogenesys and Epigenesys) to program pervasive platforms such as the PERvasive computing framework for modeling comPLEX virtually Unbounded Systems platform. The second contribution proposes a method to program efficiently parallelizable applications on each computing node of this platform. Résumé en Français : Basée sur le constat que les calculs ubiquitaires vont devenir le paradigme de programmation dans les années à venir, cette thèse propose une analyse des contraintes matérielles et environnementale auxquelles sont soumises les plateformes pervasives. Ces contraintes ayant un impact fort sur la programmation des plateformes. Des solutions sont donc proposées pour faciliter cette programmation tant au niveau de l'ensemble des noeuds qu'au niveau de chacun des noeuds de la plateforme. La première contribution présentée dans ce document propose d'utiliser une alliance de programmation orientée agent avec les grands principes de la bio-inspiration (Phylogénèse, Ontogénèse et Épigénèse). Ceci pour répondres aux contraintes de programmation de plateformes pervasives comme la plateforme PERvasive computing framework for modeling comPLEX virtually Unbounded Systems . La seconde contribution propose quant à elle une méthode permettant de programmer efficacement des applications parallélisable sur chaque noeud de calcul de la plateforme

Benchmarking therapeutic drug monitoring software: A systematic evaluation of available computer tools

Objectives: Therapeutic drug monitoring (TDM) aims at optimizing treatment by individualizing dosage regimen based on blood concentrations measurement. Maintaining concentrations within a target range requires pharmacokinetic (PK) and clinical capabilities. Bayesian calculation represents a gold standard in TDM approach but requires computing assistance. The aim of this benchmarking was to assess and compare computer tools designed to support TDM clinical activities.¦Methods: Literature and Internet were searched to identify software. Each program was scored against a standardized grid covering pharmacokinetic relevance, user-friendliness, computing aspects, interfacing, and storage. A weighting factor was applied to each criterion of the grid to consider its relative importance. To assess the robustness of the software, six representative clinical vignettes were also processed through all of them.¦Results: 12 software tools were identified, tested and ranked. It represents a comprehensive review of the available software characteristics. Numbers of drugs handled vary from 2 to more than 180, and integration of different population types is available for some programs. Nevertheless, 8 programs offer the ability to add new drug models based on population PK data. 10 computer tools incorporate Bayesian computation to predict dosage regimen (individual parameters are calculated based on population PK models). All of them are able to compute Bayesian a posteriori dosage adaptation based on a blood concentration while 9 are also able to suggest a priori dosage regimen, only based on individual patient covariates. Among those applying Bayesian analysis, MM-USC*PACK uses a non-parametric approach. The top 2 programs emerging from this benchmark are MwPharm and TCIWorks. Others programs evaluated have also a good potential but are less sophisticated or less user-friendly.¦Conclusions: Whereas 2 software packages are ranked at the top of the list, such complex tools would possibly not fit all institutions, and each program must be regarded with respect to individual needs of hospitals or clinicians. Programs should be easy and fast for routine activities, including for non-experienced users. Although interest in TDM tools is growing and efforts were put into it in the last years, there is still room for improvement, especially in terms of institutional information system interfacing, user-friendliness, capability of data storage and automated report generation.

Relaxivity of Gd-based contrast agents on X nuclei with long intrinsic relaxation times in aqueous solutions.

The relaxivity of commercially available gadolinium (Gd)-based contrast agents was studied for X-nuclei resonances with long intrinsic relaxation times ranging from 6 s to several hundred seconds. Omniscan in pure 13C formic acid had a relaxivity of 2.9 mM(-1) s(-1), whereas its relaxivity on glutamate C1 and C5 in aqueous solution was approximately 0.5 mM(-1) s(-1). Both relaxivities allow the preparation of solutions with a predetermined short T1 and suggest that in vitro substantial sensitivity gains in their measurement can be achieved. 6Li has a long intrinsic relaxation time, on the order of several minutes, which was strongly affected by the contrast agents. Relaxivity ranged from approximately 0.1 mM(-1) s(-1) for Omniscan to 0.3 for Magnevist, whereas the relaxivity of Gd-DOTP was at 11 mM(-1) s(-1), which is two orders of magnitude higher. Overall, these experiments suggest that the presence of 0.1- to 10-microM contrast agents should be detectable, provided sufficient sensitivity is available, such as that afforded by hyperpolarization, recently introduced to in vivo imaging.

Measurement of multi-segment foot joint angles during gait using a wearable system.

Usually the measurement of multi-segment foot and ankle complex kinematics is done with stationary motion capture devices which are limited to use in a gait laboratory. This study aimed to propose and validate a wearable system to measure the foot and ankle complex joint angles during gait in daily conditions, and then to investigate its suitability for clinical evaluations. The foot and ankle complex consisted of four segments (shank, hindfoot, forefoot, and toes), with an inertial measurement unit (3D gyroscopes and 3D accelerometers) attached to each segment. The angles between the four segments were calculated in the sagittal, coronal, and transverse planes using a new algorithm combining strap-down integration and detection of low-acceleration instants. To validate the joint angles measured by the wearable system, three subjects walked on a treadmill for five minutes at three different speeds. A camera-based stationary system that used a cluster of markers on each segment was used as a reference. To test the suitability of the system for clinical evaluation, the joint angle ranges were compared between a group of 10 healthy subjects and a group of 12 patients with ankle osteoarthritis, during two 50-m walking trials where the wearable system was attached to each subject. On average, over all joints and walking speeds, the RMS differences and correlation coefficients between the angular curves obtained using the wearable system and the stationary system were 1 deg and 0.93, respectively. Moreover, this system was able to detect significant alteration of foot and ankle function between the group of patients with ankle osteoarthritis and the group of healthy subjects. In conclusion, this wearable system was accurate and suitable for clinical evaluation when used to measure the multi-segment foot and ankle complex kinematics during long-distance walks in daily life conditions.

An active contour-based atlas registration model applied to automatic subthalamic nucleus targeting on MRI: method and validation.

This paper presents a new non parametric atlas registration framework, derived from the optical flow model and the active contour theory, applied to automatic subthalamic nucleus (STN) targeting in deep brain stimulation (DBS) surgery. In a previous work, we demonstrated that the STN position can be predicted based on the position of surrounding visible structures, namely the lateral and third ventricles. A STN targeting process can thus be obtained by registering these structures of interest between a brain atlas and the patient image. Here we aim to improve the results of the state of the art targeting methods and at the same time to reduce the computational time. Our simultaneous segmentation and registration model shows mean STN localization errors statistically similar to the most performing registration algorithms tested so far and to the targeting expert's variability. Moreover, the computational time of our registration method is much lower, which is a worthwhile improvement from a clinical point of view.

Active Contour-Based Segmentation of Head and Neck with Adaptive Atlas Selection

This paper presents automated segmentation of structuresin the Head and Neck (H\&N) region, using an activecontour-based joint registration and segmentation model.A new atlas selection strategy is also used. Segmentationis performed based on the dense deformation fieldcomputed from the registration of selected structures inthe atlas image that have distinct boundaries, onto thepatient's image. This approach results in robustsegmentation of the structures of interest, even in thepresence of tumors, or anatomical differences between theatlas and the patient image. For each patient, an atlasimage is selected from the available atlas-database,based on the similarity metric value, computed afterperforming an affine registration between each image inthe atlas-database and the patient's image. Unlike manyof the previous approaches in the literature, thesimilarity metric is not computed over the entire imageregion; rather, it is computed only in the regions ofsoft tissue structures to be segmented. Qualitative andquantitative evaluation of the results is presented.

LiveCount Assay: concomitant measurement of cytolytic activity and phenotypic characterisation of CD8(+) T-cells by flow cytometry.

Tumour immunologists strive to develop efficient tumour vaccination and adoptive transfer therapies that enlarge the pool of tumour-specific and -reactive effector T-cells in vivo. To assess the efficiency of the various strategies, ex vivo assays are needed for the longitudinal monitoring of the patient's specific immune responses providing both quantitative and qualitative data. In particular, since tumour cell cytolysis is the end goal of tumour immunotherapy, routine immune monitoring protocols need to include a read-out for the cytolytic efficiency of Ag-specific cells. We propose to combine current immune monitoring techniques in a highly sensitive and reproducible multi-parametric flow cytometry based cytotoxicity assay that has been optimised to require low numbers of Ag-specific T-cells. The possibility of re-analysing those T-cells that have undergone lytic activity is illustrated by the concomitant detection of CD107a upregulation on the surface of degranulated T-cells. To date, the LiveCount Assay provides the only possibility of assessing the ex vivo cytolytic activity of low-frequency Ag-specific cytotoxic T-lymphocytes from patient material.

The vitamin D receptor gene bAt (CCA) haplotype impairs the response to pegylated-interferon/ribavirin-based therapy in chronic hepatitis C patients.

BACKGROUND: Chronic hepatitis C infection is a major cause of end-stage liver disease. Therapy outcome is influenced by 25-OH vitamin D deficiency. To further address this observation, our study investigates the impact of the vitamin D receptor (NR1I1) haplotype and combined effects of plasma vitamin D levels in a well-described cohort of hepatitis C patients. METHODS: A total of 155 chronic hepatitis C patients were recruited from the Swiss Hepatitis C Cohort Study for NR1I1 genotyping and plasma 25-OH vitamin D level measurement. NR1I1 genotype data and combined effects of plasma 25-OH vitamin D level were analysed regarding therapy response (sustained virological response). RESULTS: A strong association was observed between therapy non-response and the NR1I1 CCA (bAt) haplotype consisting of rs1544410 (BsmI) C, rs7975232 (ApaI) C and rs731236 (TaqI) A alleles. Of the HCV patients carrying the CCA haplotype, 50.3% were non-responders (odds ratio [OR] 1.69, 95% CI 1.07, 2.67; P=0.028). A similar association was observed for the combinational CCCCAA genotype (OR 2.94, 95% CI 1.36, 6.37; P=0.007). The combinational CCCCAA genotype was confirmed as an independent risk factor for non-response in multivariate analysis (OR 2.50, 95% CI 1.07, 5.87; P=0.034). Analysing combined effects, a significant impact of low 25-OH vitamin D levels on sustained virological response were only seen in patients with the unfavourable NR1I1 CCA (bAt) haplotype (OR for non-SVR 3.55; 95% CI 1.005, 12.57; P=0.049). CONCLUSIONS: NR1I1 vitamin D receptor polymorphisms influence response to pegylated-interferon/ribavirin-based therapy in chronic hepatitis C and exert an additive genetic predisposition to previously described low 25-OH vitamin D serum levels.

Quantifying Uncertainty in Real Time Performance Measurement for Highway Winter Maintenance Operations – Phase 2, RB03-013, 2014

Winter weather in Iowa is often unpredictable and can have an adverse impact on traffic flow. The Iowa Department of Transportation (Iowa DOT) attempts to lessen the impact of winter weather events on traffic speeds with various proactive maintenance operations. In order to assess the performance of these maintenance operations, it would be beneficial to develop a model for expected speed reduction based on weather variables and normal maintenance schedules. Such a model would allow the Iowa DOT to identify situations in which speed reductions were much greater than or less than would be expected for a given set of storm conditions, and make modifications to improve efficiency and effectiveness. The objective of this work was to predict speed changes relative to baseline speed under normal conditions, based on nominal maintenance schedules and winter weather covariates (snow type, temperature, and wind speed), as measured by roadside weather stations. This allows for an assessment of the impact of winter weather covariates on traffic speed changes, and estimation of the effect of regular maintenance passes. The researchers chose events from Adair County, Iowa and fit a linear model incorporating the covariates mentioned previously. A Bayesian analysis was conducted to estimate the values of the parameters of this model. Specifically, the analysis produces a distribution for the parameter value that represents the impact of maintenance on traffic speeds. The effect of maintenance is not a constant, but rather a value that the researchers have some uncertainty about and this distribution represents what they know about the effects of maintenance. Similarly, examinations of the distributions for the effects of winter weather covariates are possible. Plots of observed and expected traffic speed changes allow a visual assessment of the model fit. Future work involves expanding this model to incorporate many events at multiple locations. This would allow for assessment of the impact of winter weather maintenance across various situations, and eventually identify locations and times in which maintenance could be improved.

Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours.

AIM: Total imatinib concentrations are currently measured for the therapeutic drug monitoring of imatinib, whereas only free drug equilibrates with cells for pharmacological action. Due to technical and cost limitations, routine measurement of free concentrations is generally not performed. In this study, free and total imatinib concentrations were measured to establish a model allowing the confident prediction of imatinib free concentrations based on total concentrations and plasma proteins measurements. METHODS: One hundred and fifty total and free plasma concentrations of imatinib were measured in 49 patients with gastrointestinal stromal tumours. A population pharmacokinetic model was built up to characterize mean total and free concentrations with inter-patient and intrapatient variability, while taking into account α1 -acid glycoprotein (AGP) and human serum albumin (HSA) concentrations, in addition to other demographic and environmental covariates. RESULTS: A one compartment model with first order absorption was used to characterize total and free imatinib concentrations. Only AGP influenced imatinib total clearance. Imatinib free concentrations were best predicted using a non-linear binding model to AGP, with a dissociation constant Kd of 319 ng ml(-1) , assuming a 1:1 molar binding ratio. The addition of HSA in the equation did not improve the prediction of imatinib unbound concentrations. CONCLUSION: Although free concentration monitoring is probably more appropriate than total concentrations, it requires an additional ultrafiltration step and sensitive analytical technology, not always available in clinical laboratories. The model proposed might represent a convenient approach to estimate imatinib free concentrations. However, therapeutic ranges for free imatinib concentrations remain to be established before it enters into routine practice.

Role of structural saturation and geometry in the luminescence of silicon-based nanostructured materials

The structural saturation and stability, the energy gap, and the density of states of a series of small, silicon-based clusters have been studied by means of the PM3 and some ab initio (HF/6-31G* and 6-311++G**, CIS/6-31G* and MP2/6-31G*) calculations. It is shown that in order to maintain a stable nanometric and tetrahedral silicon crystallite and remove the gap states, the saturation atom or species such as H, F, Cl, OH, O, or N is necessary, and that both the cluster size and the surface species affect the energetic distribution of the density of states. This research suggests that the visible luminescence in the silicon-based nanostructured material essentially arises from the nanometric and crystalline silicon domains but is affected and protected by the surface species, and we have thus linked most of the proposed mechanisms of luminescence for the porous silicon, e.g., the quantum confinement effect due to the cluster size and the effect of Si-based surface complexes.

Strength Development of Concrete Based on Maturity and Pulse Velocity, MLR-95-03, 1995

The effect of curing temperature, in the range of 4.4 to 22.8 degrees C (40 to 73 degrees F), on strength development was studied based on the maturity and pulse velocity measurements in this report. The strength-maturity relationships for various mixes using a Type I cement and using a Type IP cement, respectively, were experimentally developed. The similar curves for early age strength development of both the patching concrete, using a Type I cement with the addition of calcium chloride, and the fast track concrete, using a Type III cement and fly ash, have also been proposed. For the temperature ranges studied, the strength development of concrete can be determined using a pulse velocity measurement, but only for early ages up to 24 hours. These obtained relationships can be used to determine when a pavement can be opened to traffic. The amount of fly ash substitution, up to 30%, did not have a significant influence on the strength-maturity relationship.