Gain Scheduling for the Orion Launch Abort Vehicle Controller

One of NASAs challenges for the Orion vehicle is the control system design for the Launch Abort Vehicle (LAV), which is required to abort safely at any time during the atmospheric ascent portion of ight. The focus of this paper is the gain design and scheduling process for a controller that covers the wide range of vehicle configurations and flight conditions experienced during the full envelope of potential abort trajectories from the pad to exo-atmospheric flight. Several factors are taken into account in the automation process for tuning the gains including the abort effectors, the environmental changes and the autopilot modes. Gain scheduling is accomplished using a linear quadratic regulator (LQR) approach for the decoupled, simplified linear model throughout the operational envelope in time, altitude and Mach number. The derived gains are then implemented into the full linear model for controller requirement validation. Finally, the gains are tested and evaluated in a non-linear simulation using the vehicles ight software to ensure performance requirements are met. An overview of the LAV controller design and a description of the linear plant models are presented. Examples of the most significant challenges with the automation of the gain tuning process are then discussed. In conclusion, the paper will consider the lessons learned through out the process, especially in regards to automation, and examine the usefulness of the gain scheduling tool and process developed as applicable to non-Orion vehicles

Innovations from the Margins: Creating Inclusive and Equitable Academic-Community Research Collaborations

How does one build a Request for Proposals (RFP) process that allows for bottom-up participation while simultaneously being pragmatic and adept enough to manoeuvre the complexities of a multi-stakeholder environment defined by differing interests, objectives, mandates, and power dynamics? This article showcases the findings from participatory work with stakeholder groups working in the area of food security in Southern Ontario’s Halton Region. It demonstrates a process designed with the specific intent of increasing the engagement of beneficiaries and service providers in the RFP process. Finally, the article seeks to shed additional light on theory and practice of “participatory approaches” in the context of philanthropy. It is important to be realistic in not reifying participation itself in this context. In both theory and practice, this means adopting lenses and models that openly consider the complex realities, political obstacles, and trade-offs that occur when negotiating participation in this environment

Innovations from the Margins: The Community Ideas Factory community collaboration

This paper explores the importance of building more inclusive, equitable, and mutually-beneficial partnerships in academic-community research collaborations for social innovation. The Community Ideas Factory is a research project that examines food security, affordable housing, employment equity and wrap-around services in the Region of Halton in Ontario, Canada. The project is a unique and dynamic collaboration between researchers from Sheridan College and the Oakville Community Foundation. In recognizing the limitations of traditional, paternalistic, subjective academic-community research collaborations this paper discusses how Participatory Rural Appraisal tools and other community-based problem-solving activities can be used to help communities define and prioritize their own problems, identify resources, and develop practical solutions to the problems they experience. We seek to demonstrate the potential of a new role for the ‘researcher’; one in which she/he assumes a more active and dynamic, yet facilitative, role in community project-building. Drawing examples from our research into food security this examination aims to provide insights, directions, and considerations for scholars, community stakeholders, and granting agencies alike who share an interest in the prospects and possibilities of academic-community collaborations for social innovation research

Community Ideas Factory

The Community Ideas Factory is a community-college partnership exploring social innovations within the charitable sector of the Halton Region. It is a collaborative research project between Sheridan College and the Oakville Community Foundation. The goal of the project is to change the philanthropic granting process in Oakville so that it is more bottom-up, participatory, and evidenced-based. The principle community partner on the project is The Foundation (OCF). A community organization tasked with managing and disbursing donor contributions for philanthropic projects in the Town of Oakville. The Community Ideas Factory is made possible by the College-Community Social Innovation Fund of the Social Sciences and Humanities Research Council of Canada (SSHRC)

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

An oral non-covalent non-peptidic inhibitor of SARS-CoV-2 Mpro ameliorates viral replication and pathogenesis in vivo

Safe, effective, and low-cost oral antiviral therapies are needed to treat those at high risk for developing severe COVID-19. To that end, we performed a high-throughput screen to identify non-peptidic, non-covalent inhibitors of the SARS-CoV-2 main protease (Mpro), an essential enzyme in viral replication. NZ-804 was developed from a screening hit through iterative rounds of structure-guided medicinal chemistry. NZ-804 potently inhibits SARS-CoV-2 Mpro (0.009 μM IC50) as well as SARS-CoV-2 replication in human lung cell lines (0.008 μM EC50) and primary human airway epithelial cell cultures. Antiviral activity is maintained against distantly related sarbecoviruses and endemic human CoV OC43. In SARS-CoV-2 mouse and hamster disease models, NZ-804 therapy given once or twice daily significantly diminished SARS-CoV-2 replication and pathogenesis. NZ-804 synthesis is low cost and uncomplicated, simplifying global production and access. These data support the exploration of NZ-804 as a therapy for COVID-19 and future emerging sarbecovirus infections

Rates and Predictors of Treatment Failure in Staphylococcus aureus Prosthetic Joint Infections According to Different Management Strategies: A Multinational Cohort Study—The ARTHR-IS Study Group

Introduction: Guidelines have improved the management of prosthetic joint infections (PJI). However, it is necessary to reassess the incidence and risk factors for treatment failure (TF) of Staphylococcus aureus PJI (SA-PJI) including functional loss, which has so far been neglected as an outcome. Methods: A retrospective cohort study of SA-PJI was performed in 19 European hospitals between 2014 and 2016. The outcome variable was TF, including related mortality, clinical failure and functional loss both after the initial surgical procedure and after all procedures at 18 months. Predictors of TF were identified by logistic regression. Landmark analysis was used to avoid immortal time bias with rifampicin when debridement, antibiotics and implant retention (DAIR) was performed. Results: One hundred twenty cases of SA-PJI were included. TF rates after the first and all surgical procedures performed were 32.8% and 24.2%, respectively. After all procedures, functional loss was 6.0% for DAIR and 17.2% for prosthesis removal. Variables independently associated with TF for the first procedure were Charlson >= 2, haemoglobin 30 kg/m(2) and delay of DAIR, while rifampicin use was protective. For all procedures, the variables associated with TF were haemoglobin < 10 g/dL, hip fracture and additional joint surgery not related to persistent infection. Conclusions: TF remains common in SA-PJI. Functional loss accounted for a substantial proportion of treatment failures, particularly after prosthesis removal. Use of rifampicin after DAIR was associated with a protective effect. Among the risk factors identified, anaemia and obesity have not frequently been reported in previous studies. [GRAPHICS]

Systematic in vitro evolution in Plasmodium falciparum reveals key determinants of drug resistance

Surveillance of drug resistance and the discovery of novel targets-key objectives in the fight against malaria-rely on identifying resistance-conferring mutations in Plasmodium parasites. Current approaches, while successful, require laborious experimentation or large sample sizes. To elucidate shared determinants of antimalarial resistance that can empower in silico inference, we examined the genomes of 724 Plasmodium falciparum clones, each selected in vitro for resistance to one of 118 compounds. We identified 1448 variants in 128 recurrently mutated genes, including drivers of antimalarial multidrug resistance. In contrast to naturally occurring variants, those selected in vitro are more likely to be missense or frameshift, involve bulky substitutions, and occur in conserved, ordered protein domains. Collectively, our dataset reveals mutation features that predict drug resistance in eukaryotic pathogens.</p

Process evaluation of the Getting it Right study and acceptability and feasibility of screening for depression with the aPHQ-9

The Getting it Right study determined the validity, sensitivity, specificity and acceptability of the culturally adapted 9-item Patient Health Questionnaire (aPHQ-9) as a screening tool for depression in Aboriginal and Torres Strait Islander (hereafter referred to as Indigenous) people. In this process evaluation we aimed to explore staff perceptions about whether Getting it Right was conducted per protocol, and if the aPHQ-9 was considered an acceptable and feasible screening tool for depression in primary healthcare. This process evaluation will provide information for clinicians and policy makers about the experiences of staff and patients with Getting it Right and what they thought about using the aPHQ-9. Process evaluation using grounded theory approaches. Semi-structured interviews with primary healthcare staff from services participating in Getting it Right were triangulated with feedback (free-text and elicited) from participants collected during the validation study and field notes. Data were thematically analysed according to the Getting it Right study protocol to identify the acceptability and feasibility of the aPHQ-9. Primary healthcare staff (n = 36) and community members (n = 4) from nine of the ten participating Getting it Right services and Indigenous participants (n = 500) from the ten services that took part. Most staff reported that the research was conducted according to the study protocol. Staff from two services reported sometimes recruiting opportunistically (rather than recruiting consecutive patients attending the service as outlined in the main study protocol), when they spoke to patients who they knew from previous interactions, because they perceived their previous relationship may increase the likelihood of patients participating. All Getting it Right participants responded to at least six of the seven feedback questions and 20% provided free-text feedback. Most staff said they would use the aPHQ-9 and most participants said that the questions were easy to understand (87%), the response categories made sense (89%) and that they felt comfortable answering the questions (91%). Getting it Right was predominantly conducted according to the study protocol. The aPHQ-9, the first culturally adapted, nationally validated, freely available depression screening tool for use by Indigenous people, appears to be acceptable and feasible to use. Australian New Zealand Clinical Trial Registry ANZCTR12614000705684 , 03/07/2014