Introducing mathematical modelling of kinetics into the therapeutic decision

Background Evolution of metastatic melanoma (MM) under B-RAF inhibitors (BRAFi) is unpredictable, but anticipation is crucial for therapeutic decision. Kinetics changes in metastatic growth are driven by molecular and immune events, and thus we hypothesized that they convey relevant information for decision making. Patients and methods We used a retrospective cohort of 37 MM patients treated by BRAFi only with at least 2 close CT-scans available before BRAFi, as a model to study kinetics of metastatic growth before, under and after BRAFi. All metastases (mets) were individually measured at each CT- scan. From these measurements, different measures of growth kinetics of each met and total tumor volume were computed at different time points. A historical cohort permitted to build a reference model for the expected spontaneous disease kinetics without BRAFi. All variables were included in Cox and multistate regression models for survival, to select best candidates for predicting overall survival. Results Before starting BRAFi, fast kinetics and moreover a wide range of kinetics (fast and slow growing mets in a same patient) were pejorative markers. At the first assessment after BRAFi introduction, high heterogeneity of kinetics predicted short survival, and added independent information over RECIST progression in multivariate analysis. Metastatic growth rates after BRAFi discontinuation was usually not faster than before BRAFi introduction, but they were often more heterogeneous than before. Conclusions Monitoring kinetics of different mets before and under BRAFi by repeated CT-scan provides information for predictive mathematical modelling. Disease kinetics deserves more interes

Effect of skilled and unskilled training on nerve regeneration and functional recovery

The most disabling aspect of human peripheral nerve injuries, the majority of which affect the upper limbs, is the loss of skilled hand movements. Activity-induced morphological and electrophysiological remodeling of the neuromuscular junction has been shown to influence nerve repair and functional recovery. In the current study, we determined the effects of two different treatments on the functional and morphological recovery after median and ulnar nerve injury. Adult Wistar male rats weighing 280 to 330 g at the time of surgery (N = 8-10 animals/group) were submitted to nerve crush and 1 week later began a 3-week course of motor rehabilitation involving either “skilled” (reaching for small food pellets) or “unskilled” (walking on a motorized treadmill) training. During this period, functional recovery was monitored weekly using staircase and cylinder tests. Histological and morphometric nerve analyses were used to assess nerve regeneration at the end of treatment. The functional evaluation demonstrated benefits of both tasks, but found no difference between them (P > 0.05). The unskilled training, however, induced a greater degree of nerve regeneration as evidenced by histological measurement (P < 0.05). These data provide evidence that both of the forelimb training tasks used in this study can accelerate functional recovery following brachial plexus injury

Electromyographic signs of neuromuscular fatigue are concomitant with further increase in ventilation during static handgrip

We questioned if a non-linear increase in ventilation defining a ventilatory threshold (VTh) accompanied the electromyographic (EMG) signs of neuromuscular fatigue. Indeed, the intramuscular accumulation of metabolites may activate the afferent nervous pathways responsible for both the ‘muscle wisdom’ phenomenon and the respiratory centre activation. During inframaximal (50%) handgrip sustained until exhaustion, minute ventilation (VE), VE/Vo2 and VE/Vco2 ratios were measured simultaneously with surface EMG of the ‘flexor digitorum’ muscle. VTh was defined as a non-linear VE increase and/or an abrupt VE/Vo2 increase without any concomitant increase in the VE/Vco2 ratio. Handgrip was repeated during complete arterial blood flow interruption in order to suppress any venous return from the exercising forearm. In both control and blood flow interruption conditions, an abrupt increase in the VE/Vo2 ratio was measured in the majority of trials (13 of 15 and 14 of 15, respectively) and the EMG signs of neuromuscular fatigue (a decline in median frequency and/or a non-linear increase in low-frequency EMG energies, EL) were concomitant with the VTh determination. Thus, VTh occurs during sustained static contraction and is concomitant with EMG signs of neuromuscular fatigue. Neurogenic factors seem to be responsible for the two responses which persist despite the absence of any release of metabolites in the circulation

Personal laws of Bangladesh : a gender study in light of the equality-approach of the constitution

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Bayesian Network classifiers inferring workload from physiological features: compared performance

IEEE Intelligent Vehicles Symposium (IV), Alcala de Henares, SPAIN, JUN 03-07, 2012International audienceThis paper presents an approach based on Bayesian Networks to estimate the workload of operators. The models take as inputs the entropy of different number of physiological features, as well as a cognitive feature (reaction time to a secondary task). They output the workload variation of subjects involved in successive tasks demanding different levels of cognitive resources. The performances of the classifiers are discussed in term of two criteria to be jointly optimized: the diversity, i.e. the ability of the model to perform on different subjects, and the accuracy, i.e., how close from the (subjectively estimated) workload level the model prediction is