Action Observation Research Articles

Bactericide polymers obtained from nitrofuran and chitosan derivatives

Background: In this study, the synthesis and characterization of chitosan polymeric materials grafted with nitrofuran derivatives – furaceline and isofural in terms of antibacterial properties and prolongation of their action were performed. Material and methods: Synthesis of chitosan analog polymers with maleic anhydride was performed, followed by grafting of nitrofuran derivatives using ethyl chloroformate. The chemical composition of the obtained polymers was confirmed by FT-IR spectroscopy. Antibacterial study has been performed on a wide range of Gram-positive and Gram-negative microorganisms. Results: Chitosan derivatives with a content of 30 mol% of maleic anhydride were obtained. To the analogous polymer ”chitosan maleinized” the medicinal products isofural or furaciline with the help of the ethyl chloroformate were functionalized. By comparative analysis of the IR spectra of the final products with the IR spectra of maleinized chitosan and furacilin or isofuran was demonstrated the individual structure of the polymeric preparations “maleinized chitosan grafted with furacilin“ / “maleinized chitosan grafted with isofural”. The antibacterial substances, isofural and furaciline, among nitrofurans, being grafted with chitosan maleinized, keep their bactericidal activity in the limits of 75-300 μg/mL. The polymeric materials from chitosan maleate grafted with isofural or furacillin in a ratio of 70:30 have a prolonged antibacterial action (observation period 72 hours). Conclusions: It has been found that isofural and furacilin, among nitrofurans, being grafted on chitosan polymeric material, retain their bactericidal activity and possess prolonged antibacterial action.

Transdiagnostic investigation into the relationship between mirror neuron system activity, echo-phenomena, and theory of mind in major psychoses.

The association between social cognition and putative mirror neuron system (MNS)-activity in major psychoses might be contingent upon frontal dysregulation. We used a transdiagnostic ecological approach to enrich a specific behavioral phenotype (echophenomena or hyper-imitative states) across clinical diagnoses (mania and schizophrenia) to compare behavioral and physiological markers of social cognition and frontal disinhibition. We examined 114 participants with schizophrenia (N=53) and mania (N=61) for the presence and severity of echo-phenomena (echopraxia, incidental, and induced echolalia) using an ecological paradigm to simulate real-life social communication. Symptom severity, frontal release reflexes, and theory of mind performance were also assessed. In a proportion of these participants with (N=20) and without (N=20) echo-phenomena, we compared motor resonance (motor evoked potential facilitation during action observation compared to static image viewing) and cortical silent period (CSP) as putative markers of MNS-activity and frontal disinhibition, respectively, using Transcranial Magnetic Stimulation. While the prevalence of echo-phenomena was similar between mania and schizophrenia, incidental echolalia was more severe in mania. Participants with echo-phenomena (compared to those without) had significantly greater motor resonance with singlepulse (not with paired-pulse) stimuli, poorer theory of mind scores, higher frontal release reflexes but similar CSP, and greater symptom severity. None of these parameters significantly differed between participants with mania and schizophrenia. We observed relatively better phenotypic and neurophysiological characterization of major psychoses by categorizing participants based on the presence of echophenomena than clinical diagnoses. Higher putative MNS-activity was associated with poorer theory of mind in a hyper-imitative behavioral state.

Effectiveness of a Telecare Physical Therapy Program in Improving Functionality in Children and Adolescents with Cerebral Palsy: A Cases Study.

Cerebral palsy (CP) is the most common physical disability in childhood and results in motor impairment that is often associated with other disorders. The aim of this study was to assess whether a telecare intervention consisting of Action Observation Therapy with a family-center approach produces improvements in functionality in children and adolescents with CP. Seven girls with CP ages between 6 and 17 participated in this case series study that lasted 12 weeks: 6 weeks of telecare program with a total of six sessions; and a follow-up period of 6 weeks. The outcome variables were Gross Motor Function (Spanish version of the Gross Motor Function Measure), balance (Spanish version of the Pediatric Balance Scale), walking endurance (6-min walk test) and walking speed (10-m walk test). The variables were measured before starting the study, after 6 weeks of intervention and after the 6-week follow-up period. Results showed statistically significant improvements in gross motor function (p = 0.02) after the intervention. After the follow-up period, gross motor function remained statistically significant (p = 0.02), as well as balance (p = 0.04) and walking endurance (p = 0.02). These results show that a telecare program has been beneficial in improving functionality with enhancements in gross motor function, balance and endurance in children and adolescents with CP that will facilitate participation.

The Role of Mirror Neuron System (MNS) in Autism Spectrum Disorders (ASD)

The Mirror Neuron System (MNS) is a group of specialized neurons that discharge when an individual performs an action or observes another individual performing the same activity. This system is divided into two principal hubs; the premotor area in the frontal lobe and inferior parietal lobule(IPL). Mirror neurons play an essential role fundamentally in human social interaction, such as action observation, imitation, understanding the emotions of others, and a myriad of other sophisticated human behavior and thought processes as well as the theory of mind. Since people with Autism Spectrum Disorders (ASD) have disorders and defects in communication, social interaction, the theory of mind, etc . So it can be suggested that defects in the mirror neuron system (MNS) may be linked to disorders like ASD and also play an essential role in this phenomenon. In this review, we discuss this connection.

Simultaneous multimodal fNIRS-EEG recordings reveal new insights in neural activity during motor execution, observation, and imagery

Motor execution, observation, and imagery are important skills used in motor learning and rehabilitation. The neural mechanisms underlying these cognitive-motor processes are still poorly understood. We used a simultaneous recording of functional near-infrared spectroscopy (fNIRS) and electroencephalogram (EEG) to elucidate the differences in neural activity across three conditions requiring these processes. Additionally, we used a new method called structured sparse multiset Canonical Correlation Analysis (ssmCCA) to fuse the fNIRS and EEG data and determine the brain regions of neural activity consistently detected by both modalities. Unimodal analyses revealed differentiated activation between conditions; however, the activated regions did not fully overlap across the two modalities (fNIRS: left angular gyrus, right supramarginal gyrus, as well as right superior and inferior parietal lobes; EEG: bilateral central, right frontal, and parietal). These discrepancies might be because fNIRS and EEG detect different signals. Using fused fNIRS-EEG data, we consistently found activation over the left inferior parietal lobe, superior marginal gyrus, and post-central gyrus during all three conditions, suggesting that our multimodal approach identifies a shared neural region associated with the Action Observation Network (AON). This study highlights the strengths of using the multimodal fNIRS-EEG fusion technique for studying AON. Neural researchers should consider using the multimodal approach to validate their findings.

Action Observation Training to Improve Upper Limb Function in Infants with Unilateral Brain Lesion – a Feasibility Study

ABSTRACT In this study, the feasibility of Action Observation Training (AOT) in combination with sensor-based measurements in infants at high risk of Unilateral Spastic Cerebral Palsy (UCP) were evaluated. Over a four-week period, eight infants at high risk of UCP performed AOT at home while wearing sensors with assistance of caregivers. Sensor data were compared to clinical assessments of upper limb function, the Hand Assessment for Infants (HAI) and the Mini-Assisting Hand Assessment (Mini-AHA). AOT training time and acceptance by the caregivers were considered as indicators for feasibility. The excellent training adherence and positive feedback of the caregivers showed that the AOT was feasible in this patient group and setting. Sensor measurements were accepted and displayed significant correlations with hand function. These preliminary results indicate the potential of wearable sensors to record upper limb function over the course of AOT for infants at high risk of UCP. Thus, AOT in combination with sensor measurements are proposed as a feasible training tool to complement usual care.

My view on your actions: Dynamic changes in viewpoint-dependent auditory ERP attenuation during action observation.

It has been suggested that during action observation, a sensory representation of the observed action is mapped onto one's own motor system. However, it is largely unexplored what this may imply for the early processing of the action's sensory consequences, whether the observational viewpoint exerts influence on this and how such a modulatory effect might change over time. We tested whether the event-related potential of auditory effects of actions observed from a first- versus third-person perspective show amplitude reductions compared with externally generated sounds, as revealed for self-generated sounds. Multilevel modeling on trial-level data showed distinct dynamic patterns for the two viewpoints on reductions of the N1, P2, and N2 components. For both viewpoints, an N1 reduction for sounds generated by observed actions versus externally generated sounds was observed. However, only during first-person observation, we found a temporal dynamic within experimental runs (i.e., the N1 reduction only emerged with increasing trial number), indicating time-variant, viewpoint-dependent processes involved in sensorimotor prediction during action observation. For the P2, only a viewpoint-independent reduction was found for sounds elicited by observed actions, which disappeared in the second half of the experiment. The opposite pattern was found in an exploratory analysis concerning the N2, revealing a reduction that increased in the second half of the experiment, and, moreover, a temporal dynamic within experimental runs for the first-person perspective, possibly reflecting an agency-related process. Overall, these results suggested that the processing of auditory outcomes of observed actions is dynamically modulated by the viewpoint over time.

“Left and right prefrontal routes to action comprehension”

Successful action comprehension requires the integration of motor information and semantic cues about objects in context. Previous evidence suggests that while motor features are dorsally encoded in the fronto-parietal action observation network (AON); semantic features are ventrally processed in temporal structures. Importantly, these dorsal and ventral routes seem to be preferentially tuned to low (LSF) and high (HSF) spatial frequencies, respectively. Recently, we proposed a model of action comprehension where we hypothesized an additional route to action understanding whereby coarse LSF information about objects in context is projected to the dorsal AON via the prefrontal cortex (PFC), providing a prediction signal of the most likely intention afforded by them. Yet, this model awaits for experimental testing. To this end, we used a perturb-and-measure continuous theta burst stimulation (cTBS) approach, selectively disrupting neural activity in the left and right PFC and then evaluating the participant's ability to recognize filtered action stimuli containing only HSF or LSF. We find that stimulation over PFC triggered different spatial-frequency modulations depending on lateralization: left-cTBS and right-cTBS led to poorer performance on HSF and LSF action stimuli, respectively. Our findings suggest that left and right PFC exploit distinct spatial frequencies to support action comprehension, providing evidence for multiple routes to social perception in humans.

Task-Based and Resting-State Cortical Functional Differences After Spinal Cord Injury: A Pilot Functional Near-Infrared Spectroscopy Study.

Brain reorganization following spinal cord injury (SCI) has been well-established using animal and human studies. Yet, much is unknown regarding functional recovery and adverse secondary outcomes after SCI. Functional near-infrared spectroscopy (fNIRS) is a neuroimaging technique that offers methodological flexibility in a real-world setting. We used fNIRS to examine the cortical functional differences between 12 males with thoracolumbar SCI (46.41 ± 11.09 years of age) and 12 healthy males (47.61 ± 11.94 years of age) during resting state and task conditions-bilateral finger tapping (FT), mental imagery of bilateral FT with action observation (FTI+AO), and bilateral ankle tapping (AT). We found an overall decrease in hemodynamic response of the SCI group during all three task conditions. Task modulated functional connectivity (FC) computed using beta series correlation technique was compared using independent sample t-tests at α = 0.05. Connectivity between the right mediolateral sensorimotor network (SMN) and the right medial SMN was reduced during the FT task in SCI. A mixed analysis of variance revealed that the FC within the right mediolateral SMN was reduced during FT but preserved during FTI+AO (i.e., comparable to controls) in the SCI group. Lower FC of these regions was associated with longer injury durations. Additionally, we found a general decrease in resting state FC of the SCI group, specifically in the Slow-3 frequency range (0.073 to 0.1 Hz). These results, though preliminary, are consistent with past studies and highlight the potential of fNIRS in SCI and rehabilitative research.

Methodological strategies for the generation of conceptual models in nursing

Introduction: among the elements that make up the disciplinary knowledge of nursing are the conceptual models, which guide the work, so it is necessary to know the methodological strategies used for their construction. Objective: to analyze in the available state of the art the methodological strategies used for the generation of conceptual models in nursing. Methods: an integrative review was carried out according to the "Integra" methodology, consulting the WoS, SCOPUS, CINAHL and Dialnet databases, which were complemented with a manual search. After applying filters, inclusion and exclusion criteria, the final sample consisted of 27 manuscripts. Results: the identified manuscripts fluctuated between 1968 and 2021, distinguishing a predominance in the inductive approach, the authors used elements that represent a specific reality for the construction of conceptual models of nursing, through empirical evidence through ethnographies, narrative studies, grounded theory and action research, practice experiences, observations, interviews, reflection, literature review and consensus of the researchers. Conclusions: three methodological approaches were identified for the generation of conceptual models in nursing, the inductive, deductive, and finally the mixed approach, the latter triangulating the first two, being able to enhance the strengths of each approach and diminishing its weaknesses

Enhancing upper-limb neurorehabilitation in chronic stroke survivors using combined action observation and motor imagery therapy.

For people who have had a stroke, recovering upper-limb function is a barrier to independence. When movement is difficult, mental practice can be used to complement physical therapy. In this within-participants study we investigated the effects of combined action observation and motor imagery (AO + MI) therapy on upper-limb recovery in chronic stroke survivors. A Graeco-Latin Square design was used to counterbalance four mental practice conditions (AO + MI, AO, MI, Control) across four cup-stacking tasks of increasing complexity. Once a week, for five consecutive weeks, participants (n = 10) performed 16 mental practice trials under each condition. Each trial displayed a 1st person perspective of a cup-stacking task performed by an experienced model. For AO, participants watched each video and responded to an occasional color cue. For MI, participants imagined the effort and sensation of performing the action; cued by a series of still-images. For combined AO + MI, participants observed a video of the action while they simultaneously imagined performing the same action in real-time. At three time points (baseline; post-test; two-week retention test) participants physically executed the three mentally practiced cup-stacking tasks, plus a fourth unpractised sequence (Control), as quickly and accurately as possible. Mean movement execution times were significantly reduced overall in the post-test and the retention test compared to baseline. At retention, movement execution times were significantly shorter for combined AO + MI compared to both MI and the Control. Individual participants reported clinically important changes in quality of life (Stroke Impact Scale) and positive qualitative experiences of AO + MI (social validation). These results indicate that when physical practice is unsuitable, combined AO + MI therapy could offer an effective adjunct for neurorehabilitation in chronic stroke survivors.

Movement Representation Strategies as a Tool for Educational Innovation in Physiotherapy Students: A Randomized Single-Blind Controlled-Pilot Trial.

Physiotherapy has a strictly theoretical body of knowledge, but for the most part, the physiotherapist's learning is practical. The practical part is fundamental to acquire clinical skills that the physiotherapist will later use in professional practice. The main aim of this study was to assess the effectiveness of movement representation strategies (MRS) in the improvement of manual skills of physiotherapy students as an educational innovation strategy. We randomly assigned 30 participants to an action observation practice (AOP), motor imagery practice (MIP), or sham observation (SO) group. A high velocity, low amplitude lumbar manipulation technique that is widely used in clinical physiotherapy practice was taught in one session. The primary outcomes were required time and test score. The secondary outcomes were perceived mental fatigue and perceived difficulty for learning. The outcomes were assessed preintervention and immediately after the intervention (postintervention). The main results showed that both AOP and MIP improved the total time required and the test score, as well as entailed less perceived difficulty for learning. However, both strategies showed a higher level of mental fatigue after the intervention, which was higher in the MIP group. Based on the results obtained, it seems that the application of MRS promotes greater learning of manual motor tasks in physiotherapy students and could be used as educational innovation strategies.

The effect of action observation combined with high-definition transcranial direct current stimulation on motor performance in healthy adults: A randomized controlled trial.

Action observation (AO) can improve motor performance in humans, probably via the human mirror neuron system. In addition, there is some evidence that transcranial direct current stimulation (tDCS) can improve motor performance. However, it is yet to be determined whether AO combined with tDCS has an enhanced effect on motor performance. We investigated the effect of AO combined with high-definition tDCS (HD-tDCS) targeting the inferior parietal lobe (IPL) and inferior frontal gyrus (IFG), the main aggregates of the human mirror neuron system, on motor performance in healthy adults and compared the immediate vs. 24-h retention test effects (anodal electrodes were placed over these regions of interest). Sixty participants were randomly divided into three groups that received one of the following single-session interventions: (1) observation of a video clip that presented reaching movement sequences toward five lighted units + active HD-tDCS stimulation (AO + active HD-tDCS group); (2) observation of a video clip that presented the same reaching movement sequences + sham HD-tDCS stimulation (AO + sham HD-tDCS group); and (3) observation of a video clip that presented neutral movie while receiving sham stimulation (NM + sham HD-tDCS group). Subjects' reaching performance was tested before and immediately after each intervention and following 24 h. Subjects performed reaching movements toward units that were activated in the same order as the observed sequence during pretest, posttest, and retest. Occasionally, the sequence order was changed by beginning the sequence unexpectedly with a different activated unit. Outcome measures included mean Reaching Time and difference between the Reaching Time of the unexpected and expected reaching movements (Delta). In the posttest and retest, Reaching Time and Delta improved in the AO + sham HD-tDCS group compared to the NM + HD-sham tDCS group. In addition, at posttest, Delta improved in the AO + active HD-tDCS group compared to the NM + sham HD-tDCS group. It appears that combining a montage of active HD-tDCS, which targets the IPL and IFG, with AO interferes with the positive effects of AO alone on the performance of reaching movement sequences.

Effects of integrated action and sensory observation therapy based on mirror neuron and embodied cognition theory on upper limb sensorimotor function in chronic stroke: a study protocol for a randomised controlled trial

IntroductionThis study protocol aims to explore the effectiveness and neural mechanism of the integration of action observation therapy (AOT) and sensory observation therapy (SOT) for post-stroke patients on upper limb...

The Effects of Sleep, Posterior Interference and Type of Exercise (Physical and Combine it With Observation of Action) on Consolidate Processing Consolidate Beginner Children's Motor Memory in Volleyball

Background and Aims Memory consolidation is a set of processes that converts memory from an unstable state to a stable one. Various factors affect the consolidation of memory, including sleep and the type of exercise have an effect on consolidation. Given that little research on consolidation has used a motor task for the age group of children, the aim of thise study was to investigate the effect of sleep, type of exercise (Physical and Combine it whit observation of action) and posterior interference on consolidation processing based on stability and promotion of motor memory. Methods This research was a semi-experimental study with an pretest- posttest design. The statistical population included girls aged 10 to 12 years who had registered in volleyball in clubs in east Tehran in 2018. The sample included 62 novice girls in volleyball who were selected by available sampling method according to the inclusion and exclusion criteria. The experiments were divided into combined observation and physical exercise groups. The tools used in this study were, Landgrafe and Abetz child health questionnaire (1996), owens children's sleep habits questionnaire (2000), Aahperd Volleyball Serving Test (1969). Data were analyzed using combined factor analysis of variance with repeated measures and Benfferroni post hoc test. Results The results of the analysis of variance-covariance with repeated measures showed that a night's sleep has a positive effect on stabilizing processing based on stability and promoting motor memory in children (F=15.40, P=0.001), but the type of exercise (F=0.18, P=0.67), (Physically or observational) and type of posterior interference (performing or observing the action) (F=0.48, P=0.489) have no significant effect on consolidation processing. Comparison of averages showed that physical practice is more stable and promotion motor memory than observation. Conclusion Coaches and educators are recommended in addition to physical exercise, children can use observational exercise to process memory consolidation

PENINGKATAN KEMAMPUAN MENGENAL KONSEP BILANGAN DENGAN MENGGUNAKAN MEDIA APRON PADA ANAK USIA DINI KELOMPOK B TKIT NUSANTARA BANTEN

Knowing the concept of numbers is very important, because it is indirectly related to human daily life. In the introduction of the concept of numbers in group B it is still relatively lacking, which is marked by the lack of children's ability to say numbers in sequence, connecting number symbols with the number of objects. If learning the concept of numbers is given according to the child's abilities, then the child will have more control over the ability to recognize the concept of numbers. In learning to recognize the concept of numbers, it requires media that is attractive to children, one of which is the counting apron media. This study aims to improve the ability to recognize the concept of numbers in early childhood through the media of calculating aprons. This research method is classroom action research which refers to the Kemmis and Mc. Taggart includes four stages, namely (1) planning (2) action (3) observation (4) reflection. This research consists of 1 cycle, with 2 meetings. The data analysis technique used in this research is qualitative and quantitative data analysis. Data collection techniques using observation instruments, interviews, documentation, field notes and discussions. The results of this study stated that there was an increase in children's gross motor skills through traditional games, as evidenced by the average score of children's initial gross motor skills of 63.61% and the first cycle of 79.33%. The research findings that traditional games of cat and mouse can improve gross motor skills of TKIT Nusantara Banten children.

PENINGKATAN KETERAMPILAN MOTORIK KASAR MELALUI PERMAINAN TRADISIONAL KUCING DAN TIKUS

The purpose of this research is to improve of gross motor skills of children through the traditional game of cats and mice at TK B Cifor Ceria Kota Depok 2017. The subject of research were 10 children. This research method was based on the research action class of Kemmis and Mc Taggart model included of four steps: (1) planning (2) action (3) observation and evaluation (4) reflection. The study consisted of one cycle, with two times meetings. Data analysis technique were used qualitative and quantitative data. The data were collected used observation instruments, interview non structur and documentation. Results of this research are showed an increased in gross motor skills of children through traditional games, evidenced by the average score of early motor skills crude children 63.61% and cycle I 79.33%. Research findings that the traditional game of cats and mice could increase children gross motor skill in TK B Cifor Ceria

Neural responses to biological motion distinguish autistic and schizotypal traits.

Difficulties in social interactions characterize both autism and schizophrenia and are correlated in the neurotypical population. It is unknown whether this represents a shared etiology or superficial phenotypic overlap. Both conditions exhibit atypical neural activity in response to the perception of social stimuli and decreased neural synchronization between individuals. This study investigated if neural activity and neural synchronization associated with biological motion perception are differentially associated with autistic and schizotypal traits in the neurotypical population. Participants viewed naturalistic social interactions while hemodynamic brain activity was measured with fMRI, which was modeled against a continuous measure of the extent of biological motion. General linear model analysis revealed that biological motion perception was associated with neural activity across the action observation network. However, intersubject phase synchronization analysis revealed neural activity to be synchronized between individuals in occipital and parietal areas but desynchronized in temporal and frontal regions. Autistic traits were associated with decreased neural activity (precuneus and middle cingulate gyrus), and schizotypal traits were associated with decreased neural synchronization (middle and inferior frontal gyri). Biological motion perception elicits divergent patterns of neural activity and synchronization, which dissociate autistic and schizotypal traits in the general population, suggesting that they originate from different neural mechanisms.

Early sleep after action observation and motor imagery training boosts improvements in manual dexterity

The systematic observation and imagination of actions promotes acquisition of motor skills. Furthermore, studies demonstrated that early sleep after practice enhances motor learning through an offline stabilization process. Here, we investigated behavioral effects and neurodynamical correlates of early sleep after action observation and motor imagery training (AO + MI-training) on motor learning in terms of manual dexterity. Forty-five healthy participants were randomized into three groups receiving a 3 week intervention consisting of AO + MI-training immediately before sleeping or AO + MI-training at least 12 h before sleeping or a control stimulation. AO + MI-training implied the observation and motor imagery of transitive manual dexterity tasks, whereas the control stimulation consisted of landscape video-clips observation. Manual dexterity was assessed using functional tests, kinematic and neurophysiological outcomes before and after the training and at 1-month follow-up. AO + MI-training improved manual dexterity, but subjects performing AO + MI-training followed by early sleep had significantly larger improvements than those undergoing the same training at least 12 h before sleeping. Behavioral findings were supported by neurodynamical correlates during motor performance and additional sleep-dependent benefits were also detected at 1 month follow-up. These findings introduce a new approach to enhance the acquisition of new motor skills or facilitate recovery in patients with motor impairments.

Development and feasibility testing of action observation training videos in acute stroke survivors: Preliminary findings.

Background: Action observation training (AOT) is used for lower limb (LL) stroke rehabilitation in subacute and chronic stages, but concise information regarding the types of activities to be used and the feasibility of administration in the acute stroke population is unknown. The aim of this study was to develop and validate videos of appropriate activities for LL AOT and test administrative feasibility in acute stroke. Method: A video inventory of LL activities was created after a literature survey and expert scrutiny. Five stroke rehabilitation experts validated the videos per domains of relevance, comprehension, clarity, camera position and brightness. LL AOT was then tested on ten individuals with acute stroke for uncovering barriers for clinical use in a feasibility study. Participants watched the activities and attempted imitation of the same. Determination of administrative feasibility was undertaken via participant interviews. Results: Suitable LL activities for stroke rehabilitation were identified. Content validation of videos led to improvements in selected activities and video quality. Expert scrutiny led to further video processing to include different perspectives of view and speeds of projected movements. Barriers identified included inability to imitate actions shown in videos and increased distractibility for some participants. Conclusion: A video catalogue of LL activities was developed and validated. AOT was deemed safe and feasible for acute stroke rehabilitation and may be used in future research and clinical practice.