BACKGROUND- Motor vehicle crashes pose a serious public health problem. Many serious crashes are due to faulty driving by unfit operators, including several categories of neurological patients. Unfortunately, there seems to be little agreement among health professionals, driving experts, and state government on how to advise these individuals. REVIEW SUMMARY- This article reviews the question of driving in neurological patients. Decisions on driver fitness should be based on empirical observations of performance and not on criteria of age or medical diagnosis, which alone are unreliable predictors. Relevant data can be collected either on a road test or off-road, using different probes of vision and cognition, in the setting of a Department of Motor Vehicles office or medical clinic. The use of a driving simulator is also feasible. The predictive value of these performance assessments is a topic of active research. CONCLUSION- Understanding how performance data from off-road and on-road observations correlate with real-life crash risk is a key step toward developing safe, fair, and accurate means of predicting driver fitness. One potential benefit is the prevention of injury, and another is the preservation of mobility and independence of individuals whose licenses are being unduly revoked because of old age or illness.

Indiana University-Purdue University Indianapolis (IUPUI) / Self-driving is simply the capacity of a vehicle to drive itself without human intervention. To accomplish this, the vehicle utilizes mechanical and electronic parts, sensors, actuators and an AI computer. The on-board PC runs advanced programming, which permits the vehicle to see and comprehend its current circumstance dependent on sensor input, limit itself in that climate and plan the ideal course from point A to point B. Independent driving is not an easy task, and to create self-sufficient driving arrangements is an exceptionally significant ability in the present programming designing field. ROS is a robust and versatile communication middle ware (framework) tailored and widely used for robotics applications. This thesis work intends to show how ROS could be used to create independent driving programming by investigating self-governing driving issues, looking at existing arrangements and building up a model vehicle utilizing ROS. The main focus of this thesis is to develop and implement a one-tenth scale of an autonomous RACECAR equipped with Jetson Nano board as the on-board computer, PCA9685 as PWM driver, sensors, and a ROS based software architecture. Finally, by following the methods presented in this thesis, it is conceivable to build an autonomous RACECAR that runs on ROS. By following the means portrayed in this theory of work, it is conceivable to build up a self-governing vehicle.

The state-of-the-art traffic simulation packages model traffic on a microscopic level. This includes the use of several sets of models that dictate how traffic moves within a transportation network. These models include car-following, gap acceptance, lane-changing and route choice models. The aim of this thesis is to improve the treatment of vehicle dynamics in traffic simulation and, as a result, special attention was paid to car-following models. These models were highlighted because they are largely responsible for capturing a vehicle’s motion and its relevant dynamics in traffic simulation. In order to improve the treatment of vehicle dynamics in traffic simulation, a Dynamic-Interactive-Vehicle (DIV) model was developed. This vehicle model is calibrated with the use of essential vehicle performance specifications that are responsible for the movement of a vehicle in a transportation network. After the calibration process the model is able to accept three inputs from a driver – gas pedal, brake pedal and steering wheel positions. The model then outputs the corresponding longitudinal and latitudinal values which represent the movement of a vehicle along a roadway. The vehicle model will also account for most of the dominant external forces that affect an automobile’s performance along a roadway. This thesis will validate the proposed model by comparing its output from a few performance tests with the performance test results of three passenger cars. The DIV model was validated by comparing the acceleration, braking and steering performance test results of three passenger cars with the output from the DIV model upon performing similar tests. It was found that the DIV model was successful at replicating the two-dimensional vehicle motion.

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Jakub Draský Supervisor: prof. PharmDr. Petr Pávek, Ph.D. Title of diploma thesis: Pharmacological influence of nuclear receptors in diabetes mellitus therapy Nuclear receptors belong to the superfamily of transcription factors, their main functions include regulating the expression of target genes. In my work I focused mainly on the group of orphan receptors, namely the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR). A common feature of these receptors is their activation by a specific ligand. Both CAR and PXR have an essential function as biological sensors of hydrophobic xenobiotics when they induce enzymes I and II. phase of metabolism. They are also essential in the regulation of gluconeogenesis, insulin response, adipogenesis, cholesterol homeostasis, fatty acids, triglycerides and glycogen. The aim of this experimental work was to introduce a luciferase reporter assay method for two DNA constructs containing the promoter region of the PEPCK and CYP7A1 genes. We used the known agonist rifampicin and the antagonist SPA70 to activate/deactivate PXR. We used CITCO as a CAR receptor agonist. We first verified the functionality of the luciferase reporter gene assay...

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Though comparisons of simulation models have been conducted, few investigations have examined in detail the logical differences between models. If the output measures of effectiveness are to be interpreted correctly, it is important that the analyst understand some of the underlying logic and assumptions upon which the results are based. An understanding of model logic and its inherent effect on the results will aid the transportation analyst in the application and calibration of a simulation model. In this thesis, the car-following behavior of the CORSIM and INTEGRATION simulation models are examined in significant detail, and its impact on output results explained. In addition, the thesis presents a calibration procedure for the CORSIM sub-model, FRESIM. Currently, FRESIM is calibrated by ad hoc trial-and-error, or by utilizing empirically developed cross-referencing tables. The literature reveals that the relationship between the microscopic input parameters of the CORSIM model, and the macroscopic parameters of capacity is not understood. The thesis addresses this concern. Finally, the thesis compares the INTEGRATION and CORSIM models in freeway and urban environments. The comparison is unique in that the simulated networks were configured such that differences in results could be identified, isolated, and explained. Additionally, the simplified nature of the test networks allowed for the formulation of analytical solutions. The thesis begins by relating steady-state car-following behavior to macroscopic traffic stream models. This is done so that a calibration procedure for the FRESIM (Pipes) car-following model could be developed. The proposed calibration procedure offers an avenue to calibrate microscopic car-following behavior using macroscopic field measurements that can be easily obtained from loop detectors. The calibration procedure, while it does not overcome the inherent shortcomings of the Pipes model, does provide an opportunity to better calibrate the network FRESIM car-following sensitivity factor to existing roadway conditions. The thesis then reports an observed inconsistency in the link-specific car-following sensitivity factor of the FRESIM model. Because calibration of a network on a link-specific basis is key to an accurate network representation, a correction factor was developed that should be applied to the analytically calculated link-specific car-following sensitivity factor. The application of the correction factor resulted in observed saturation flow rates that were within 5% of the desired saturation flow rates. The thesis concludes with a comparison of the CORSIM and INTEGRATION models for transient conditions. As a result of the various intricacies and subtleties that are involved in transient behavior, the comparisons were conducted by running the models on simple networks where analytical solutions to the problem could be formulated. In urban environments, it was observed that the models are consistent in estimates of delay and travel time, and inconsistent in estimates of vehicle stops, stopped delay, fuel consumption, and emissions. Specifically, it was observed that the NETSIM model underestimates the number of vehicle stops in comparison with INTEGRATION and the analytical formulation. It was also observed that the NETSIM vehicles speed and acceleration profiles are characterized by abrupt accelerations and decelerations. These abrupt movements significantly impact stopped time delay and vehicle emissions estimates. Inconsistencies in emissions estimates can also be attributed to differences in the embedded rate tables of each model. In freeway environments for under-saturated conditions, INTEGRATION returned higher values of travel time and delay, and lower values of average speed than the FRESIM model. These results are consistent with the analytical solution, and can be attributed to the speed-flow relationship of each model. In saturated conditions, when the capacity of the bottleneck is equal to the demand volume, the emergent vehicle behavior of the FRESIM model was observed to be inconsistent with the analytical solution. The FRESIM vehicles were observed to dramatically decelerate upon entering a lower-capacity link. This deceleration behavior led to higher travel time and delay time estimates in FRESIM than in INTEGRATION. In over-saturated conditions, longer queue lengths were observed in FRESIM than in INTEGRATION, resulting in slightly higher travel and delay estimates in the FRESIM model. The reason for the discrepancy in queue lengths is unclear, as the network jam density in each model was equivalent. / Master of Science

Due to technological developments and raising environmental concerns, vehicle industry is ina transformation process. Current dominant design in the industry is the internal combustionengine vehicle but there are already different alternative vehicles like electric vehicles (EV),hybrids, and vehicles running on ethanol or hydrogen. These alternatives started to expandand they are competing to have a strong position in the market. The question is whichtechnology (EV, hybrid, ethanol) will have an important position in the future. This studyfocuses on the progress of electric vehicles towards being the dominant design in the vehicleindustry and aims to give advices and suggestions to electric car manufacturers what theyshould develop and concentrate on in the future. To achieve this aim, interviews with Renaultand Stockholm Municipality is conducted and analyzed in detail. Many manufacturers areinterested in EV technology and started to invest in the technology to have a strong position inthe future. Although EVs are ready to expand, there are still some obstacles in their way.Some of these problems can be solved in a short term, while others, mostly technology relatedimprovements still require time.

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INTRODUCTION: Multiple Myeloma (MM) is a plasma cell malignancy that causes improper production of immunoglobulins and elevated levels of monoclonal protein. Resulting morbidity is a conglomeration of symptoms due to organ failure, lytic bone disease, and hematological insufficiencies. The American Cancer Society estimates more than 35,000 patients will be diagnosed with multiple myeloma in the United States in 2023. Current therapeutic regimen hinge on the idea of myeloma as a chronic disease that cannot be entirely cured and toxic chemotherapies with long-term treatment cycles are the standard of care. The need for a one-time therapy that is both safe and efficacious and with potentially curative action has led to the development of anti-BCMA CAR T-cell infusions. The overwhelming success of this novel therapy in MM has been demonstrated in clinical trials, but the need for data surrounding the long-term toxicities post-CAR T-cell treatment in a real-world population of MM patients still exists. Common expected adverse events that have been identified in clinical trials include cytokine release syndrome, neurotoxic events, hematological toxicities, and infections associated with immunosuppression. This study was formed to elucidate the long-term adverse events associated with anti-BCMA CAR T-cell therapy in a real-world patient population. METHODS: A total of 54 patients who received a CAR T-cell infusion for their relapsed and refractory multiple myeloma were studied in a retrospective analysis at Dana-Farber Cancer Institute. Data were collected prior, during, and after infusion to gauge treatment performance and toxic side effects. Analyses of collected data, including complete blood counts, serum protein electrophoresis, fluorescence in-situ hybridization (FISH) data from bone marrow biopsy, and imaging were performed. RESULTS: Patients were followed for a mean average of 165 days (range 29-462) post-infusion. Patients either received CiltaCel (n = 7) or IdeCel (n = 47). Grade 3 or greater cytopenia occurred in 48% of patients at some point following infusion and the median time to first onset was 30 days (10-189). Forty-six patients (85%) achieved a partial response or better as their best response to therapy. During inpatient infusion, 76% of patients experienced grade 1 or 2 cytokine release syndrome (CRS) and 8% experienced grade 1 or 2 immune effector cell-associated neurotoxicity syndrome (ICANS). A total of 12 patients (22%) developed infections after infusion with respiratory infections being the most frequent (17%). Nine patients were also evaluated on a closer scale for their experience with prolonged cytopenia, but no significant commonalities were found. DISCUSSION: The analysis of this study found this patient population to have a considerably less frequent incidence of high grade cytopenia as compared to clinical trial data. However, 92% of patients developed grade 1-3 anemia and 77% developed any grade thrombocytopenia, both figures are greater than those presented in the KarMMa-2 clinical trial study for ide-cel. Patients who developed severe cytopenia were able to recover absolute neutrophil counts (ANC) over the course of their follow-up appointments which is an important aspect in the prevention and avoidance of serious infection. This same recovery was not observed in platelet or hemoglobin counts. Additionally, 15 patients were reported to still have high-grade cytopenia at 30—60-days post infusion, but this number drops to only 5 patients for the 60—90-day timeframe, this steep drop is indicative of an early onset of severe cytopenia that may not carry on as the patient progresses further from their infusion date. Compared to the KarMMa-2 study which reported an infection incidence of 69%, observations from this current study suggest this real-world patient population remained healthier after infusion in terms of infection with only 23% of patients developing post-infusion infection. Instances of CRS and ICANS were comparable to data evaluated in clinical trials. Finally, treatment responses did not significantly differ between the population of patients who developed grade 3 or greater cytopenia and those patients who did not. More data is required to determine the risk-benefit profile of early intervention with CAR T-cell therapy as directly compared to the current standard of care. This study is an encouraging insight into the performance of real-world RRMM patients that should assure patients and clinicians of the safety and uncompromising efficacy of anti-BCMA therapy as a treatment option for multiple myeloma.

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