PKR as a conserved neuroinflammatory mediator under viral, bacterial, & metabolic challenge: A role in Parkinsonian pathogenesis?

Neuroinflammation has emerged as a pathological component of neurodegenerative disease onset and progression, including Parkinson’s disease. Given the current absence of disease-modifying therapies for this progressive disorder, approaches have now begun to explore the inflammatory burden that detrimental host factors place on the brain and how they can drive disease development. Our lab has identified the novel expression of the double-stranded RNA-dependent protein kinase (PKR) within the rodent brain following i) metabolic inflammation (diet-induced obesity), ii) viral infection (non-neurotropic influenza), and iii) bacterial sepsis (lipopolysaccharide). PKR stereotypically functions as an antiviral kinase, but has been implicated as a signal transduction element in response to a number of cell stresses. This biological target has been proposed to be upstream of inflammatory signaling cascades that contribute to, and aggravate, Parkinsonian pathology. By studying CNS PKR expression in three host conditions known to perturb CNS homeostasis through pro-inflammatory insult of the brain, our lab has characterized the cellular and molecular level expression of PKR in animal models and attempted to determine this signal’s possible role in Parkinson’s disease pathogenesis. Our results suggest that PKR serves as a cell stress signal that may precede neurodegeneration and functions to promote apoptosis and inflammation. Studying PKR’s expression across a broad variety of host states may lead to the development of meaningful anti-inflammatory therapeutics that may be used against Parkinson’s disease and related conditions

SOCRATES: Text-based Human Search and Approach using a Robot Dog

In this paper, we propose a SOCratic model for Robots Approaching humans based on TExt System (SOCRATES) focusing on the human search and approach based on free-form textual description; the robot first searches for the target user, then the robot proceeds to approach in a human-friendly manner. In particular, textual descriptions are composed of appearance (e.g., wearing white shirts with black hair) and location clues (e.g., is a student who works with robots). We initially present a Human Search Socratic Model that connects large pre-trained models in the language domain to solve the downstream task, which is searching for the target person based on textual descriptions. Then, we propose a hybrid learning-based framework for generating target-cordial robotic motion to approach a person, consisting of a learning-from-demonstration module and a knowledge distillation module. We validate the proposed searching module via simulation using a virtual mobile robot as well as through real-world experiments involving participants and the Boston Dynamics Spot robot. Furthermore, we analyze the properties of the proposed approaching framework with human participants based on the Robotic Social Attributes Scale (RoSAS)Comment: Project page: https://socratesrobotdog.github.io

The impact of wastewater characteristics, algal species selection and immobilisation on simultaneous nitrogen and phosphorus removal

Nutrient removal from wastewater reduces the environmental impact of its discharge and provides opportunity for water reclamation. Algae can accomplish simultaneous nitrogen and phosphorus removal while also adding value to the wastewater treatment process through resource recovery. The application of algae to wastewater treatment has been limited by a low rate of nutrient removal and difficulty in recovering the algal biomass. Immobilising the algal cells can aid in overcoming both these issues and so improve the feasibility of algal wastewater treatment. Trends for nutrient removal by algal systems over different wastewater characteristics and physical conditions are reviewed. The impact that the selection of algal species and immobilisation has on simultaneous nutrient removal as well as the interdependence of nitrogen and phosphorus are established. Understanding these behaviours will allow the performance of algal wastewater treatment systems to be predicted, assist in their optimisation, and help to identify directions for future research

Regulators, Pivotal Clinical Trials, and Drug Regulation in the Age of COVID-19

Medicine regulators rely on pivotal clinical trials to make decisions about approving a new drug, but little is known about how they judge whether pivotal trials justify the approval of new drugs. We explore this issue by looking at the positions of 3 major regulators: the European Medicines Agency, Food and Drug Administration, and Health Canada. Here we report their views and the implications of those views for the approval process. On various points, the 3 regulators are ambiguous, consistent, and demonstrate flexibility. The range of views may well reflect different regulatory cultures. Although clinical trial information from pivotal trials is becoming more available, regulators are still reluctant to provide detailed information about how that information is interpreted. As medicines and vaccines come up for approval for treatment of COVID-19, transparency in how pivotal trials are interpreted will be critical in determining how these treatments should be used

Regulators, Pivotal Clinical Trials, and Drug Regulation in the Age of COVID-19

Medicine regulators rely on pivotal clinical trials to make decisions about approving a new drug, but little is known about how they judge whether pivotal trials justify the approval of new drugs. We explore this issue by looking at the positions of 3 major regulators: the European Medicines Agency, Food and Drug Administration, and Health Canada. Here we report their views and the implications of those views for the approval process. On various points, the 3 regulators are ambiguous, consistent, and demonstrate flexibility. The range of views may well reflect different regulatory cultures. Although clinical trial information from pivotal trials is becoming more available, regulators are still reluctant to provide detailed information about how that information is interpreted. As medicines and vaccines come up for approval for treatment of COVID-19, transparency in how pivotal trials are interpreted will be critical in determining how these treatments should be used

Evaluation of uncomplicated acute respiratory tract infection management in veterans: A national utilization review.

BackgroundAntibiotics are overprescribed for acute respiratory tract infections (ARIs). Guidelines provide criteria to determine which patients should receive antibiotics. We assessed congruence between documentation of ARI diagnostic and treatment practices with guideline recommendations, treatment appropriateness, and outcomes.MethodsA multicenter quality improvement evaluation was conducted in 28 Veterans Affairs facilities. We included visits for pharyngitis, rhinosinusitis, bronchitis, and upper respiratory tract infections (URI-NOS) that occurred during the 2015-2016 winter season. A manual record review identified complicated cases, which were excluded. Data were extracted for visits meeting criteria, followed by analysis of practice patterns, guideline congruence, and outcomes.ResultsOf 5,740 visits, 4,305 met our inclusion criteria: pharyngitis (n = 558), rhinosinusitis (n = 715), bronchitis (n = 1,155), URI-NOS (n = 1,475), or mixed diagnoses (>1 ARI diagnosis) (n = 402). Antibiotics were prescribed in 68% of visits: pharyngitis (69%), rhinosinusitis (89%), bronchitis (86%), URI-NOS (37%), and mixed diagnosis (86%). Streptococcal diagnostic testing was performed in 33% of pharyngitis visits; group A Streptococcus was identified in 3% of visits. Streptococcal tests were ordered less frequently for patients who received antibiotics (28%) than those who did not receive antibiotics 44%; P < .01). Although 68% of visits for rhinosinusitis had documentation of symptoms, only 32% met diagnostic criteria for antibiotics. Overall, 39% of patients with uncomplicated ARIs received appropriate antibiotic management. The proportion of 30-day return visits for ARI care was similar for appropriate (11%) or inappropriate (10%) antibiotic management (P = .22).ConclusionsAntibiotics were prescribed in most uncomplicated ARI visits, indicating substantial overuse. Practice was frequently discordant with guideline diagnostic and treatment recommendations