Tolerance to the pain-relieving effects of cannabinoids limits the therapeutic potential of these drugs in patients with chronic pain. Recent preclinical research with rodents and clinical studies in ...humans has suggested important differences between males and females in the development of tolerance to cannabinoids. Our previous work found that male mice expressing a desensitization resistant form (S426A/S430A) of the type 1 cannabinoid receptor (CB
R) show delayed tolerance and increased sensitivity to the antinociceptive effects of delta-9-tetrahydrocannabinol (∆
-THC). Sex differences in tolerance have been reported in rodent models with females acquiring tolerance to ∆
-THC faster than males. However, it remains unknown whether the S426A/S430A mutation alters analgesic tolerance to ∆
-THC in mice with chemotherapy-evoked chronic neuropathic pain, and also whether this tolerance might be different between males and females. Male and female S426A/S430A mutant and wild-type littermates were made neuropathic using four once-weekly injections of 5 mg/kg cisplatin and subsequently assessed for tolerance to the anti-allodynic effects of 6 and/or 10 mg/kg ∆
-THC. Females acquired tolerance to the anti-allodynic effects of both 6 and 10 mg/kg ∆
-THC faster than males. In contrast, the S426A/S430A mutation did not alter tolerance to ∆
-THC in either male or female mice. The anti-allodynic effects of ∆
-THC were blocked following pretreatment with the CB
R antagonist, rimonabant, and partially blocked following pretreatment with the CB
R inverse agonist, SR144528. Our results show that disruption of the GRK/β-arrestin-2 pathway of desensitization did not affect sensitivity and/or tolerance to ∆
-THC in a chronic pain model of neuropathy.
Studies and field implementations demonstrate that variable speed limit (VSL) systems help freeway traffic congestion mitigations. This study presents a cycle-based variable speed limit (CVSL) ...strategy that could variate speed limits in the upstream segment of freeway merging areas. CVSL reduces speed limits in a fraction of a cycle. This variation creates artificial gaps on freeway mainlines, which in turn increases merging opportunities for incoming on-ramp vehicles. CVSL retains VSL's benefit in reducing delays while overcoming its shortcoming of no significant throughput increase. The authors establish analytical CVSL delay models, including freeway mainline and ramp delays with CVSL speed as a decision variable, and propose a robotic solution method to minimise the delays. The delay model and solutions are implemented and independently evaluated in microscopic traffic simulation. Particularly, the CVSL system is implemented and interfaced with the transportation flow open-source microscopic model (ETFOMM). Detector information from ETFOMM is fed into the delay model, and the optimised speed limit is fed back to ETFOMM. Two performance measures, total travel delay and throughput, are used to evaluate the CVSL system. Their simulation evaluation indicated up to 16% delay reduction and 6% throughput increase. This CVSL strategy is ready for field evaluation.
High-granularity vehicle trajectory data can help researchers develop traffic simulation models, understand traffic flow characteristics, and thus propose insightful strategies for road traffic ...management. This paper proposes a novel vehicle trajectory extraction method that can extract high-granularity vehicle trajectories from aerial videos. The proposed method includes video calibration, vehicle detection and tracking, lane marking identification, and vehicle motion characteristics calculation. In particular, the authors propose a Monte-Carlo-based lane marking identification approach to identify each vehicle's lane. This is a challenging problem for vehicle trajectory extraction, especially when the aerial videos are taken from a high altitude. The authors applied the proposed method to extract vehicle trajectories from several high-resolution aerial videos recorded from helicopters. The extracted dataset is named by the High-Granularity Highway Simulation (HIGH-SIM) vehicle trajectory dataset. To demonstrate the effectiveness of the proposed method and understand the quality of the HIGH-SIM dataset, we compared the HIGH-SIM dataset with a well-known dataset, the NGSIM US-101 dataset, regarding the accuracy and consistency aspects. The comparison results showed that the HIGH-SIM dataset has more reasonable speed and acceleration distributions than the NGSIM US-101 dataset. Also, the internal and platoon consistencies of the HIGH-SIM dataset give lower errors compared to the NGSIM US-101 dataset. To benefit future research, the authors have published the HIGH-SIM dataset online for public use.
•Collect high-resolution traffic flow videos from a helicopter.•Propose a deep learning-based vehicle trajectory extraction method to extract vehicle trajectories from aerial videos.•Propose a Monte-Carlo-based lane marking identification approach to identify each vehicle's lane.•The extracted long-coverage trajectory dataset has been published online for public use.
•We compare heuristic methods in their efficiency of optimizing traffic signal timing.•All methods had equal improvement versus time, but some avoid premature convergence.•Simulated annealing and ...genetic algorithm did not converge if used with good parameters.•Tabu searching was not helpful, and hill-climbing always converged prematurely.•Early convergence reduced benefits by 22–33%, so parameters should be chosen carefully.
Simulation-based optimization of traffic signal timing has become pervasive and popular, in the field of traffic engineering. When the underlying simulation model is well-trusted and/or well-calibrated, it is only natural that typical engineers would want their signal timing optimized using the judgment of that same model. As such, it becomes important that the heuristic search methods typically used by these optimizations are capable of locating global optimum solutions, for a wide range of signal systems. However off-line and real-time solutions alike offer just a subset of the available search methods. The result is that many optimizations are likely converging prematurely on mediocre solutions. In response, this paper compares several search methods from the literature, in terms of both optimality (i.e., solution quality) and computer run times. Simulated annealing and genetic algorithm methods were equally effective in achieving near-global optimum solutions. Two selection methods (roulette wheel and tournament), commonly used within genetic algorithms, exhibited similar effectiveness. Tabu searching did not provide significant benefits. Trajectories of optimality versus run time (OVERT) were similar for each method, except some methods aborted early along the same trajectory. Hill-climbing searches always aborted early, even with a large number of step-sizes. Other methods only aborted early when applied with ineffective parameter settings (e.g. mutation rate, annealing schedule). These findings imply (1) today’s products encourage a sub-optimal “one size fits all” approach, (2) heuristic search methods and parameters should be carefully selected based on the system being optimized, (3) weaker searches abort early along the OVERT curve, and (4) improper choice of methods and/or parameters can reduce optimization benefits by 22–33%.
The head impulse-nystagmus-test of skew (+ hearing) or HINTS+ exam is a well-established clinical bedside test used in evaluating whether patients with the acute vestibular syndrome have features ...concerning for a central etiology (e.g., stroke). There are other components of the ocular motor exam that are helpful in the acute setting, including smooth pursuit and saccades. We discuss the anatomy and physiology of the saccade and smooth pursuit pathways from the cortex to the infratentorial region in the context of anterior and posterior circulation strokes in general but with a particular emphasis on distinct vestibular stroke syndromes. For each stroke localization, we review the vascular supply and the expected findings on the HINTS+ exam and correlate this with the expected findings on the smooth pursuit and saccade exams to aid in bedside diagnosis.
Simultaneous Perturbation Stochastic Approximation (SPSA) has gained favor as an efficient optimization method for calibrating computationally intensive, "black box" traffic flow simulations. Few ...recent studies have investigated the efficiency of SPSA for traffic signal timing optimization. It is important for this to be investigated, because significant room for improvement exists in the area of signal optimization. Some signal timing methods and products perform optimization very quickly, but deliver mediocre solutions. Other methods and products deliver high-quality solutions, but at a very slow rate. When using commercialized desktop signal timing products, engineers are often forced to choose between speed and solution quality. Real-time adaptive control products, which must optimize timings within seconds on a cycle-by-cycle basis, have limited time to reach a high-quality solution. The existing literature indicates that SPSA provides the potential for upgrading both off-line and on-line solutions alike, by delivering high-quality solutions within seconds. This article describes an extensive set of optimization tests involving SPSA and genetic algorithms (GAs). The final results suggest that GA was slightly more efficient than SPSA. Moreover, the results suggest today's signal timing solutions could be improved significantly by incorporating GA, SPSA, and "playbooks" of preoptimized starting points. However, it may take another 5-10 years before our computers become fast enough to simultaneously optimize coordination settings (i.e., cycle length, phasing sequence, and offsets) at numerous intersections, using the most powerful heuristic methods, at speeds that are compatible with real-time adaptive solutions.
We previously reported decreased mortality following implementation of a community-acquired pneumonia guideline derived from specialty society recommendations. However, patients with respiratory ...failure and sepsis from pneumonia were not included, adjustment for comorbidities was limited, and no guideline compliance data were available. We also questioned whether decreased mortality continued after 1997.
We utilized Utah data from the Centers for Medicare and Medicaid from 1993 to 2003 to determine if pneumonia guideline implementation was associated with 30-day all-cause mortality, length of hospital stay, and readmission rate. We adjusted outcomes by age, gender, Deyo comorbidity score, prior hospitalizations, and race. Guideline compliance was measured by initial default guideline antibiotic administration. We included patients ≥ 66 years old with primary International Classification of Diseases, Ninth Revision, Clinical Modification codes 480.0–483.9, 485.0–486.9, 487.0, 507.0 or 518.81, and 038.x with secondary code pneumonia. We excluded patients with prior hospitalization within 10 days, patients with HIV infection or transplant recipients, and patients not treated by physicians closely affiliated with study hospitals.
Mean (± SD) age of 17,728 pneumonia patients admitted to the hospital was 72.3 ± 12.0 years, 55.2% were female, and 96.0% were white. Within Intermountain Healthcare hospitals, a 1-SD increase (10%) in guideline compliance (range, 61 to 100%) was associated with mortality odds ratio (OR) of 0.92 (95% confidence intervalCI, 0.87 to 0.98; p = 0.007). Mortality OR at 16 Intermountain Healthcare hospitals was 0.89 (95% CI, 0.82 to 0.97; p = 0.007) compared with 19 other Utah hospitals. This mortality difference corresponds to approximately 20 lives saved yearly. The readmission rate was also lower.
Improved clinical outcomes were associated with pneumonia guideline utilization.
ObjectiveThe purpose of this study was to assess the risk of hemorrhagic complications in thrombocytopenic patients after Ommaya reservoir placement.MethodsBetween 2009 and 2017, 192 patients were ...identified on the National Neoplastic Meningitis Registry and had undergone Ommaya reservoir placement for intrathecal chemotherapy. A retrospective chart review was performed to collect the preoperative and postoperative platelet levels, whether or not the patient received any transfusion of platelets, neurological exams, and whether a postoperative head CT was obtained. Using generally accepted recommendations, a platelet level less than 100,000/μL was considered clinically significant and used as our threshold for thrombocytopenia.ResultsSeven patients (3.6%) were identified as thrombocytopenic in our patient population with platelet counts ranging from 54,000 to 99,000/μL. Primary diagnoses for the seven patients included leukemia, prostate cancer, primary brain cancer (four patients), and lung cancer (non-small-cell lung carcinoma). One patient received platelet transfusions preoperatively. Three patients had a routine head CT obtained postoperatively with no abnormal findings noted. There were no changes in the neurological exam noted in all of the patients included in this study. No clinically significant hemorrhages were identified in our patients.ConclusionsFrom our single institutional experience, we found that thrombocytopenia is fairly uncommon, found in only 3.6% of our patients undergoing placement of Ommaya reservoirs. We did not encounter any increased risks of postoperative hemorrhage in studied thrombocytopenic patients.
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