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- Algurén, Beatrix, 1977, et al.
(författare)
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Development of an international standard set of patient-centred outcome measures for overall paediatric health: a consensus process
- 2021
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Ingår i: Archives of Disease in Childhood. - : BMJ. - 0003-9888 .- 1468-2044. ; 106:9, s. 868-876
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Tidskriftsartikel (refereegranskat)abstract
- Objective To develop an Overall Pediatric Health Standard Set (OPH-SS) of outcome measures that captures what matters to young people and their families and recognising the biopsychosocial aspects of health for all children and adolescents regardless of health condition. Design A modified Delphi process. Setting The International Consortium for Health Outcomes Measurement convened an international Working Group (WG) comprised of 23 international experts from 12 countries in the field of paediatrics, family medicine, psychometrics as well as patient advisors. The WG participated in 11 video-conferences, through a modified Delphi process and 9 surveys between March 2018 and January 2020 consensus was reached on a final recommended health outcome standard set. By a literature review conducted in March 2018, 1136 articles were screened for clinician and patient-reported or proxy-reported outcomes. Further, 4315 clinical trials and 12 paediatric health surveys were scanned. Between November 2019 and January 2020, the final standard set was endorsed by a patient validation (n=270) and a health professional (n=51) survey. Results From a total of 63 identified outcomes, consensus was formed on a standard set of outcome measures that comprises 10 patient-reported outcomes, 5 clinician-reported measures, and 6 case-mix variables. The four developmental age-specific packages (ie, 0–5, 6–12, 13–17, 18–24 years) include either five or six measures with an average time for completion of 20min. Conclusions The OPH-SS is a starting point to drive value-based paediatric healthcare delivery from a global perspective for enhancing child and adolescent physical health and psychosocial well-being.
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| 2. |
- Salt Ducajú, Julián M., et al.
(författare)
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Autonomous ground vehicle lane-keeping LPV model-based control : Dual-rate state estimation and comparison of different real-time control strategies
- 2021
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Ingår i: Sensors. - : MDPI AG. - 1424-8220. ; 21:4
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Tidskriftsartikel (refereegranskat)abstract
- In this contribution, we suggest two proposals to achieve fast, real-time lane-keeping control for Autonomous Ground Vehicles (AGVs). The goal of lane-keeping is to orient and keep the vehicle within a given reference path using the front wheel steering angle as the control action for a specific longitudinal velocity. While nonlinear models can describe the lateral dynamics of the vehicle in an accurate manner, they might lead to difficulties when computing some control laws such as Model Predictive Control (MPC) in real time. Therefore, our first proposal is to use a Linear Parameter Varying (LPV) model to describe the AGV’s lateral dynamics, as a trade-off between computational complexity and model accuracy. Additionally, AGV sensors typically work at different measurement acquisition frequencies so that Kalman Filters (KFs) are usually needed for sensor fusion. Our second proposal is to use a Dual-Rate Extended Kalman Filter (DREFKF) to alleviate the cost of updating the internal state of the filter. To check the validity of our proposals, an LPV model-based control strategy is compared in simulations over a circuit path to another reduced computational complexity control strategy, the Inverse Kinematic Bicycle model (IKIBI), in the presence of process and measurement Gaussian noise. The LPV-MPC controller is shown to provide a more accurate lane-keeping behavior than an IKIBI control strategy. Finally, it is seen that Dual-Rate Extended Kalman Filters (DREKFs) constitute an interesting tool for providing fast vehicle state estimation in an AGV lane-keeping application.
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| 3. |
- Ahwazi, Danial, et al.
(författare)
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Investigation of the specificity and mechanism of action of the ULK1/AMPK inhibitor SBI-0206965
- 2021
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Ingår i: Biochemical Journal. - 0264-6021. ; 478:15, s. 2977-2997
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Tidskriftsartikel (refereegranskat)abstract
- SBI-0206965, originally identified as an inhibitor of the autophagy initiator kinase ULK1, has recently been reported as a more potent and selective AMP-activated protein kinase (AMPK) inhibitor relative to the widely used, but promiscuous inhibitor Compound C/ Dorsomorphin. Here, we studied the effects of SBI-0206965 on AMPK signalling and metabolic readouts in multiple cell types, including hepatocytes, skeletal muscle cells and adipocytes. We observed SBI-0206965 dose dependently attenuated AMPK activator (991)-stimulated ACC phosphorylation and inhibition of lipogenesis in hepatocytes. SBI-0206965 (≥25 μM) modestly inhibited AMPK signalling in C2C12 myotubes, but also inhibited insulin signalling, insulin-mediated/AMPK-independent glucose uptake, and AICA-riboside uptake. We performed an extended screen of SBI-0206965 against a panel of 140 human protein kinases in vitro, which showed SBI-0206965 inhibits several kinases, including members of AMPK-related kinases (NUAK1, MARK3/4), equally or more potently than AMPK or ULK1. This screen, together with molecular modelling, revealed that most SBI-0206965-sensitive kinases contain a large gatekeeper residue with a preference for methionine at this position. We observed that mutation of the gatekeeper methionine to a smaller side chain amino acid (threonine) rendered AMPK and ULK1 resistant to SBI-0206965 inhibition. These results demonstrate that although SBI-0206965 has utility for delineating AMPK or ULK1 signalling and cellular functions, the compound potently inhibits several other kinases and critical cellular functions such as glucose and nucleoside uptake. Our study demonstrates a role for the gatekeeper residue as a determinant of the inhibitor sensitivity and inhibitor-resistant mutant forms could be exploited as potential controls to probe specific cellular effects of SBI-0206965.
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