[Archives de la Parole]. , [Parable of the prodigal son] : Récit en hindoustani / [Sir George Grierson], éd. ; Linguistic survey of India ; [Baqir Ali], voix

[Traditions. Asie. Inde. Province de Delhi]

Personalized modeling for drug concentration prediction using Support Vector Machine

Building a personalized model to describe the drug concentration inside the human body for each patient is highly important to the clinical practice and demanding to the modeling tools. Instead of using traditional explicit methods, in this paper we propose a machine learning approach to describe the relation between the drug concentration and patients' features. Machine learning has been largely applied to analyze data in various domains, but it is still new to personalized medicine, especially dose individualization. We focus mainly on the prediction of the drug concentrations as well as the analysis of different features' influence. Models are built based on Support Vector Machine and the prediction results are compared with the traditional analytical models.

[Archives de la Parole]. , Récit [An unlucky face] : hindi / [Sir George Grierson], éd. ; Linguistic survey of India ; [Dhanibux Sanwankhan], voix

[Traditions. Asie. Inde. Pakistan. Province du Sind. Haidarābād]

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)]

The challenge of modeling nuclear receptor regulatory networks in mammalian cells.

Nuclear receptors are a major component of signal transduction in animals. They mediate the regulatory activities of many hormones, nutrients and metabolites on the homeostasis and physiology of cells and tissues. It is of high interest to model the corresponding regulatory networks. While molecular and cell biology studies of individual promoters have provided important mechanistic insight, a more complex picture is emerging from genome-wide studies. The regulatory circuitry of nuclear receptor regulated gene expression networks, and their response to cellular signaling, appear highly dynamic, and involve long as well as short range chromatin interactions. We review how progress in understanding the kinetics and regulation of cofactor recruitment, and the development of new genomic methods, provide opportunities but also a major challenge for modeling nuclear receptor mediated regulatory networks.

Aerodynamic drag modeling of alpine skiers performing giant slalom turns.

PURPOSE: Aerodynamic drag plays an important role in performance for athletes practicing sports that involve high-velocity motions. In giant slalom, the skier is continuously changing his/her body posture, and this affects the energy dissipated in aerodynamic drag. It is therefore important to quantify this energy to understand the dynamic behavior of the skier. The aims of this study were to model the aerodynamic drag of alpine skiers in giant slalom simulated conditions and to apply these models in a field experiment to estimate energy dissipated through aerodynamic drag. METHODS: The aerodynamic characteristics of 15 recreational male and female skiers were measured in a wind tunnel while holding nine different skiing-specific postures. The drag and the frontal area were recorded simultaneously for each posture. Four generalized and two individualized models of the drag coefficient were built, using different sets of parameters. These models were subsequently applied in a field study designed to compare the aerodynamic energy losses between a dynamic and a compact skiing technique. RESULTS: The generalized models estimated aerodynamic drag with an accuracy of between 11.00% and 14.28%, and the individualized models estimated aerodynamic drag with an accuracy between 4.52% and 5.30%. The individualized model used for the field study showed that using a dynamic technique led to 10% more aerodynamic drag energy loss than using a compact technique. DISCUSSION: The individualized models were capable of discriminating different techniques performed by advanced skiers and seemed more accurate than the generalized models. The models presented here offer a simple yet accurate method to estimate the aerodynamic drag acting upon alpine skiers while rapidly moving through the range of positions typical to turning technique.

[Archives de la Parole]. , Chanson fantaisiste en mēwātī / [Sir George Grierson], éd. ; Linguistic survey of India ; [Hassaina], voix ; accompagnement instrumental (harmonium indien et tabla)

[Traditions. Asie. Inde. Province de Delhi. Delhi]

[Archives de la Parole]. , Fortune favours the brave : in Bhojpuri of Shahabad (récit, fable) / [Sir George Grierson], éd. ; Linguistic survey of India ; [Hari Sankar Nath], voix

[Traditions. Asie. Inde. Bihar]

[Archives de la Parole]. , The covetous Brahmin [and his reward] : in Oriya - Récit - Indo-Aryen - Ling[uistic] Survey of India / [Sir George Grierson], éd. ; Linguistic survey of India ; [Bepin Chandra Patra], voix

[Traditions. Asie. Inde. Orissa]

[Archives de la Parole]. , Special text in santali / [Sir George Grierson], éd. ; Linguistic survey of India ; Voix parlée, homme

[Traditions. Asie. Inde. Chotā Nāgpur]

[Archives de la Parole]. , A kahani : in Mundari / [Sir George Grierson], éd. ; Linguistic survey of India ; Voix parlée, homme

[Traditions. Asie. Inde. Chotā Nāgpur]

[Archives de la Parole]. , Special text in mundari / [Sir George Grierson], éd. ; Linguistic survey of India ; Voix parlée, homme

[Traditions. Asie. Inde. Chotā Nāgpur]

[Archives de la Parole]. , The Monkey and the Cats : in Bhojpuri of Shahabad / [Sir George Grierson], éd. ; Linguistic survey of India ; [Radha Mohan Prasad Srivastava], voix

[Traditions. Asie. Inde. Bihar]

[Archives de la Parole]. , Parable of the prodigal son : in Nagpuria Bhojpuri / [Sir George Grierson], éd. ; Linguistic survey of India ; [Shiva Sahay Lal], voix

[Traditions. Asie. Inde. Bihar]