Temporal aiming.
Ontology highlight
ABSTRACT:
SUBMITTER: Pacheco-Pena V
PROVIDER: S-EPMC7371637 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The spatial and temporal aspects of movement variability have typically been studied separately. As a result the relationship between spatial and temporal variabilities remains largely unknown. In two experiments we examined the evolution and covariation of spatial and temporal variabilities over variations in the duration of reciprocal aiming movements. Experiments differed in settings: In Experiment 1 participants moved unperturbed whereas in Experiment 2 they were confronted with an elastic force field. Different movement durations-for a constant inter-target distance-were either evoked by imposing spatial accuracy constraints while requiring participants to move as fast as possible, or prescribed by means of an auditory metronome while requiring participants to maximize spatial accuracy. Analyses focused on absolute and relative variabilities, respectively captured by the standard deviation (SD) and the coefficient of variation (CV = SD/mean). Spatial variability (both SDspace and CVspace) decreased with movement duration, while temporal variability (both SDtime and CVtime) increased with movement duration. We found strong negative correlations between spatial and temporal variabilities over variations in movement duration, whether the variability examined was absolute or relative. These findings observed at the level of the full movement contrasted with the findings observed at the level of the separate acceleration and deceleration phases of movement. During the separate acceleration and deceleration phases both spatial and temporal variabilities (SD and CV) were found to increase with their respective durations, leading to positive correlations between them. Moreover, variability was generally larger at the level of the constituent movement phases than at the level of the full movement. The general pattern of results was robust, as it emerged in both tasks in each of the two experiments. We conclude that feedback mechanisms operating to maximize task performance are subjected to a form of competition between spatial and temporal variabilities.
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Project description:The lawful continuous linear relation between movement time and task difficulty (i.e., index of difficulty; ID) in a goal-directed rapid aiming task (Fitts' law) has been recently challenged in reciprocal performance. Specifically, a discontinuity was observed at critical ID and was attributed to a transition between two distinct dynamic regimes that occurs with increasing difficulty. In the present paper, we show that such a discontinuity is also present in discrete aiming when ID is manipulated via target width (experiment 1) but not via target distance (experiment 2). Fitts' law's discontinuity appears, therefore, to be a suitable indicator of the underlying functional adaptations of the neuro-muscular-skeletal system to task properties/requirements, independently of reciprocal or discrete nature of the task. These findings open new perspectives to the study of dynamic regimes involved in discrete aiming and sensori-motor mechanisms underlying the speed-accuracy trade-off.
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Project description:Body area networks (BANs), cloud computing, and machine learning are platforms that can potentially enable advanced healthcare outside the hospital. By applying distributed sensors and drug delivery devices on/in our body and connecting to such communication and decision-making technology, a system for remote diagnostics and therapy is achieved with additional autoregulation capabilities. Challenges with such autarchic on-body healthcare schemes relate to integrity and safety, and interfacing and transduction of electronic signals into biochemical signals, and vice versa. Here, we report a BAN, comprising flexible on-body organic bioelectronic sensors and actuators utilizing two parallel pathways for communication and decision-making. Data, recorded from strain sensors detecting body motion, are both securely transferred to the cloud for machine learning and improved decision-making, and sent through the body using a secure body-coupled communication protocol to auto-actuate delivery of neurotransmitters, all within seconds. We conclude that both highly stable and accurate sensing-from multiple sensors-are needed to enable robust decision making and limit the frequency of retraining. The holistic platform resembles the self-regulatory properties of the nervous system, i.e., the ability to sense, communicate, decide, and react accordingly, thus operating as a digital nervous system.
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Project description:Knowledge of the three-dimensional structure of therapeutically relevant targets has informed drug discovery since the first protein structures were determined using X-ray crystallography in the 1950s and 1960s. In this editorial we provide a brief overview of the powerful impact of structure-based drug design (SBDD), which has its roots in computational and structural biology, with major contributions from both academia and industry. We describe advances in the application of SBDD for integral membrane protein targets that have traditionally proved very challenging. We emphasize the major progress made in fragment-based approaches for which success has been exemplified by over 30 clinical drug candidates and importantly three FDA-approved drugs in oncology. We summarize the articles in this issue that provide an excellent snapshot of the current state of the field of SBDD and fragment-based drug design and which offer key insights into exciting new developments, such as the X-ray free-electron laser technology, cryo-electron microscopy, open science approaches and targeted protein degradation. We stress the value of SBDD in the design of high-quality chemical tools that are used to interrogate biology and disease pathology, and to inform target validation. We emphasize the need to maintain the scientific rigour that has been traditionally associated with structural biology and extend this to other methods used in drug discovery. This is particularly important because the quality and robustness of any form of contributory data determines its usefulness in accelerating drug design, and therefore ultimately in providing patient benefit.
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Project description:Animal and human literature supports spatial-motor "Aiming" bias, a frontal-subcortical syndrome, as a core deficit in spatial neglect. However, spatial neglect treatment studies rarely assess Aiming errors. Two knowledge gaps result: spatial neglect rehabilitation studies fail to capture the impact on motor-exploratory aspects of functional disability. Also, across spatial neglect treatment studies, discrepant treatment effects may also result from sampling different proportions of patients with Aiming bias. We review behavioural evidence for Aiming spatial neglect, and demonstrate the importance of measuring and targeting Aiming bias for treatment, by reviewing literature on Aiming spatial neglect and prism adaptation treatment, and presenting new preliminary data on bromocriptine treatment. Finally, we review neuroanatomical and network disruption that may give rise to Aiming spatial neglect. Because Aiming spatial neglect predicts prism adaptation treatment response, assessment may broaden the ability of rehabilitation research to capture functionally-relevant disability. Frontal brain lesions predict both the presence of Aiming spatial neglect, and a robust response to some spatial neglect interventions. Research is needed that co-stratifies spatial neglect patients by lesion location and Aiming spatial neglect, to personalize spatial neglect rehabilitation and perhaps even open a path to spatial retraining as a means of promoting better mobility after stroke.
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Project description:BACKGROUND:Locoregionally advanced, recurrent, and metastatic squamous cell carcinomas of the head and neck (SCCHN) remain difficult to treat disease entities, in which systemic treatment often forms an integral part of their management. Immunotherapy is based on functional restoration of the host immune system, helping to counteract various tumour evasion strategies. Broadly, immunotherapeutic approaches encompass tumour-specific antibodies, cancer vaccines, cytokines, adoptive T-cell transfer, and immune-modulating agents. Until 2015, the epidermal growth factor receptor inhibitor cetuximab, a tumour-specific antibody, represented the only Food and Drug Administration (FDA)-approved targeted therapy for SCCHN. Subsequently, in 2016, the results from two prospective trials employing the immune-modulating antibodies nivolumab and pembrolizumab heralded a new era of anticancer treatment. DISCUSSION:Nivolumab and pembrolizumab are monoclonal antibodies against programmed cell death protein-1 (PD-1), an 'immune checkpoint' receptor. Found on the surface of T-cells, PD-1 negatively regulates their activation and can thus be exploited during carcinogenesis. The second-line phase III trial CheckMate-141 randomly assigned 361 patients with recurrent and/or metastatic SCCHN in a 2:1 ratio to receive either single-agent nivolumab (3 mg/kg intravenously every 2 weeks) or standard monotherapy (methotrexate, docetaxel, or cetuximab). Nivolumab improved the objective response rate (13% versus 6%) and median overall survival (OS; 7.5 versus 5.1 months, p?=?0.01) without increasing toxicity. Exploratory biomarker analyses indicated that patients treated with nivolumab had longer OS than those given standard therapy, regardless of tumour PD-1 ligand (PD-L1) expression or p16 status. In the non-randomised, multicohort phase Ib study KEYNOTE-012, treatment with pembrolizumab achieved comparable results. Importantly, most of the responding patients had a long-lasting response. CONCLUSION:Based on recent results, nivolumab and pembrolizumab have been approved by the FDA as new standard-of-care options for the second-line treatment of recurrent and/or metastatic SCCHN. Generally well tolerated, these novel drugs demonstrated modest response rates, with tumour regressions usually being durable, even in platinum-resistant/refractory cases. The next step will be to extend the observed benefit to first-line treatment, currently dominated by the EXTREME regimen (platinum/5-fluorouracil/cetuximab), and to the locoregionally advanced setting, where concurrent chemoradiation with cisplatin is standard. Regimens combining immunotherapy with other modalities will probably further improve outcomes.
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Project description:Continuous dopaminergic stimulation in Parkinson's disease (PD) has several advantages over pulsatile, non-continuous, stimulation. These therapies currently consist of pump-based and transcutaneous therapies and are based on a more constant delivery of the dopaminergic drug resulting in continuous dopaminergic stimulation and a more stable treatment effect. Several clinical and experimental observations have shown that continuous stimulation of dopaminergic receptors induces fewer complications, such as dyskinesia, compared to pulsatile stimulation. Currently available non-oral pharmacological continuous therapies in PD include the transdermal Rotigotine (RTG) patch, infusion therapies with Apomorphine and Intrajejunal Levodopa (IJLI) and the Rivastigmine patch. Here we aim to provide a concise review of these current therapies and discuss ongoing and future developments of continuous non-oral pharmacological dopaminergic therapies in PD.
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Project description:IntroductionTransforming a health system into a learning one is increasingly recognized as necessary to support the implementation of a national strategic direction on quality with a focus on frontline experience. The approach to a learning system that bridges the gap between practice and policy requires active exploration.MethodsThis scoping review adapted the methodological framework for scoping studies from Arksey and O'Malley. The central research question focused on common themes for learning to improve the quality of health services at all levels of the national health system, from government policy to point-of-care delivery.ResultsA total of 3507 records were screened, resulting in 101 articles on strategic learning across the health system: health professional level (19%), health organizational level (15%), subnational/national level (26%), multiple levels (35%), and global level (6%). Thirty-five of these articles focused on learning systems at multiple levels of the health system. A national learning system requires attention at the organizational, subnational, and national levels guided by the needs of patients, families, and the community. The compass of the national learning system is centred on four cross-cutting themes across the health system: alignment of priorities, systemwide collaboration, transparency and accountability, and knowledge sharing of real-world evidence generated at the point of care.ConclusionThis paper proposes an approach for building a national learning system to improve the quality of health services. Future research is needed to validate the application of these guiding principles and make improvements based on the findings.
| S-EPMC8287697 | biostudies-literature