Design and implementation of a teleoperator’s workstation

Treball desenvolupat en el marc del programa "European Project Semester".The project aims to implement a way for a teleoperator to control an existing self-driving car if the autonomous driving algorithms fail to respond to the encountered situation. The project will rely on the existing code developed by the MechLab Team at the HTW in Dresden, who have converted a BMW i3 into a self-driving car using surround and proximity sensors and a homemade software that controls the vehicle's speed and steering. The car is also able to detect pedestrians and other obstacles thanks to a deep learning algorithm dedicated to this part. Teleoperation systems pose many challenges, such as providing the teleoperator with the same level of situational awareness as a driver in the car. The driver needs to focus more on the surroundings, and therefore teleoperated drivers will have to rest more often and take more breaks. To address this challenge, the teleoperation system will use high information density sensors, including LiDAR, radar, and ultrasonic sensors, to provide the driver with an overlay of detected obstacles and the predicted path, enhancing reality to compensate for latency in communication by taking some workload off the operator. Another big challenge is to switch between the autonomous and teleoperated driving modes, as there are different problems that can appear. Most noticeably, during the time it takes for the operator to get aware of the situation and respond to the call, the car must be able to safely stop and wait for instructions from the operator. The failure to do so could result in dangerous or even deadly situations for the autonomous vehicle’s occupants as well as for the other road users, who do not need to wait for the communication to be established. One of the last great challenges is allow stable and fast communication between the car and the teleoperator. This can be achieved by narrowing the data transmitted for example by reducing video quality in predefined cases, or by ensuring redundancy in the communication media. Nevertheless, a complete loss of communication is not impossible, so a protocol needs to be defined in order to safely halt the vehicle while waiting on the reconnection of the transmission. To fulfil this project, our team will use MATLAB and Simulink in combination with different toolboxes from the MathWorks company. We will try to develop a human-machine interface for the teleoperator, implement a way for the operator to take over control of the vehicle, build scenarios to test and simulate our different programs and much more. All of this is done in order to build safer and more reliable autonomous vehicles for the future.Incomin

Identification of genes associated with dissociation of cognitive performance and neuropathological burden: Multistep analysis of genetic, epigenetic, and transcriptional data

Introduction: The molecular underpinnings of the dissociation of cognitive performance and neuropathological burden are poorly understood, and there are currently no known genetic or epigenetic determinants of the dissociation. Methods and findings: “Residual cognition” was quantified by regressing out the effects of cerebral pathologies and demographic characteristics on global cognitive performance proximate to death. To identify genes influencing residual cognition, we leveraged neuropathological, genetic, epigenetic, and transcriptional data available for deceased participants of the Religious Orders Study (n = 492) and the Rush Memory and Aging Project (n = 487). Given that our sample size was underpowered to detect genome-wide significance, we applied a multistep approach to identify genes influencing residual cognition, based on our prior observation that independent genetic and epigenetic risk factors can converge on the same locus. In the first step (n = 979), we performed a genome-wide association study with a predefined suggestive p < 10−5, and nine independent loci met this threshold in eight distinct chromosomal regions. Three of the six genes within 100 kb of the lead SNP are expressed in the dorsolateral prefrontal cortex (DLPFC): UNC5C, ENC1, and TMEM106B. In the second step, in the subset of participants with DLPFC DNA methylation data (n = 648), we found that residual cognition was related to differential DNA methylation of UNC5C and ENC1 (false discovery rate < 0.05). In the third step, in the subset of participants with DLPFC RNA sequencing data (n = 469), brain transcription levels of UNC5C and ENC1 were evaluated for their association with residual cognition: RNA levels of both UNC5C (estimated effect = −0.40, 95% CI −0.69 to −0.10, p = 0.0089) and ENC1 (estimated effect = 0.0064, 95% CI 0.0033 to 0.0096, p = 5.7 × 10−5) were associated with residual cognition. In secondary analyses, we explored the mechanism of these associations and found that ENC1 may be related to the previously documented effect of depression on cognitive decline, while UNC5C may alter the composition of presynaptic terminals. Of note, the TMEM106B allele identified in the first step as being associated with better residual cognition is in strong linkage disequilibrium with rs1990622A (r2 = 0.66), a previously identified protective allele for TDP-43 proteinopathy. Limitations include the small sample size for the genetic analysis, which was underpowered to detect genome-wide significance, the evaluation being limited to a single cortical region for epigenetic and transcriptomic data, and the use of categorical measures for certain non-amyloid-plaque, non-neurofibrillary-tangle neuropathologies. Conclusions: Through a multistep analysis of cognitive, neuropathological, genomic, epigenomic, and transcriptomic data, we identified ENC1 and UNC5C as genes with convergent genetic, epigenetic, and transcriptomic evidence supporting a potential role in the dissociation of cognition and neuropathology in an aging population, and we expanded our understanding of the TMEM106B haplotype that is protective against TDP-43 proteinopathy

Component Processes of Decision Making in a Community Sample of Precariously Housed Persons: Associations With Learning and Memory, and Health-Risk Behaviors

The Iowa Gambling Task (IGT) is a widely used measure of decision making, but its value in signifying behaviors associated with adverse, “real-world” consequences has not been consistently demonstrated in persons who are precariously housed or homeless. Studies evaluating the ecological validity of the IGT have primarily relied on traditional IGT scores. However, computational modeling derives underlying component processes of the IGT, which capture specific facets of decision making that may be more closely related to engagement in behaviors associated with negative consequences. This study employed the Prospect Valence Learning (PVL) model to decompose IGT performance into component processes in 294 precariously housed community residents with substance use disorders. Results revealed a predominant focus on gains and a lack of sensitivity to losses in these vulnerable community residents. Hypothesized associations were not detected between component processes and self-reported health-risk behaviors. These findings provide insight into the processes underlying decision making in a vulnerable substance-using population and highlight the challenge of linking specific decision making processes to “real-world” behaviors

Detection of cannabinoid receptor type 2 in native cells and zebrafish with a highly potent, cell-permeable fluorescent probe.

Despite its essential role in the (patho)physiology of several diseases, CB2R tissue expression profiles and signaling mechanisms are not yet fully understood. We report the development of a highly potent, fluorescent CB2R agonist probe employing structure-based reverse design. It commences with a highly potent, preclinically validated ligand, which is conjugated to a silicon-rhodamine fluorophore, enabling cell permeability. The probe is the first to preserve interspecies affinity and selectivity for both mouse and human CB2R. Extensive cross-validation (FACS, TR-FRET and confocal microscopy) set the stage for CB2R detection in endogenously expressing living cells along with zebrafish larvae. Together, these findings will benefit clinical translatability of CB2R based drugs

Mourning and melancholia revisited: correspondences between principles of Freudian metapsychology and empirical findings in neuropsychiatry

Freud began his career as a neurologist studying the anatomy and physiology of the nervous system, but it was his later work in psychology that would secure his place in history. This paper draws attention to consistencies between physiological processes identified by modern clinical research and psychological processes described by Freud, with a special emphasis on his famous paper on depression entitled 'Mourning and melancholia'. Inspired by neuroimaging findings in depression and deep brain stimulation for treatment resistant depression, some preliminary physiological correlates are proposed for a number of key psychoanalytic processes. Specifically, activation of the subgenual cingulate is discussed in relation to repression and the default mode network is discussed in relation to the ego. If these correlates are found to be reliable, this may have implications for the manner in which psychoanalysis is viewed by the wider psychological and psychiatric communities

Clozapine-Induced Cardiovascular Side Effects and Autonomic Dysfunction: A Systematic Review

Background: Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia and has minimal risk for extrapyramidal symptoms. Therapeutic benefits, however, are accompanied by a myriad of cardiometabolic side-effects. The specific reasons for clozapine's high propensity to cause adverse cardiometabolic events remain unknown, but it is believed that autonomic dysfunction may play a role in many of these.Objective: This systematic review summarizes the literature on autonomic dysfunction and related cardiovascular side effects associated with clozapine treatment.Method: A search of the EMBASE, MEDLINE, and EBM Cochrane databases was conducted using the search terms antipsychotic agents, antipsychotic drug*, antipsychotic*, schizophrenia, schizophren*, psychos*, psychotic*, mental ill*, mental disorder*, neuroleptic*, cardiovascular*, cardiovascular diseases, clozapine*, clozaril*, autonomic*, sympathetic*, catecholamine*, norepinephrine, noradrenaline, epinephrine, adrenaline.Results: The search yielded 37 studies that were reviewed, of which only 16 studies have used interventions to manage cardiovascular side effects. Side effects reported in the studies include myocarditis, orthostatic hypotension and tachycardia. These were attributed to sympathetic hyperactivity, decreased vagal contribution, blockade of cholinergic and adrenergic receptors, reduced heart rate variability and elevated catecholamines with clozapine use. Autonomic neuropathy was identified by monitoring blood pressure and heart rate changes in response to stimuli and by spectral analysis of heart rate variability. Metoprolol, lorazepam, atenolol, propranolol, amlodipine, vasopressin and norepinephrine infusion were used to treat tachycardia and fluctuations in blood pressure, yet results were limited to case reports.Conclusion: The results indicate there is a lack of clinical studies investigating autonomic dysfunction and a limited use of interventions to manage cardiovascular side effects associated with clozapine. As there is often no alternative treatment for refractory schizophrenia, the current review highlights the need for better designed studies, use of autonomic tests for prevention of cardiovascular disease and development of novel interventions for clozapine-induced side effects