Effectiveness of a Novel Video Game Platform in the Treatment of Pediatric Amblyopia.

PURPOSE: To test the non-inferiority of a novel game platform for the treatment of pediatric amblyopia compared to standard eye patching. METHODS: Forty participants (ages 4 to 18 years) across seven optometric clinics in the United States diagnosed as having amblyopia associated with anisometropia were randomly assigned to either 12 weeks of eye patching therapy (n = 19) or Barron Vision (Barron Associates, Inc) video game treatment (n = 21). Participants in the eye patching group with best corrected visual acuity (BCVA) worse than 20/200 in their amblyopic eye were prescribed 6 hours of patching daily, whereas those whose BCVA was 20/200 (1.00 logarithm of the minimum angle of resolution [logMAR]) or better were instructed to patch for 2 hours daily. Participants in the video game group, irrespective of the severity of their amblyopia, were instructed to play four different 5-minute mini-games five times a week for a total of 20 minutes a day. RESULTS: A mixed linear modeling analysis of before and after BCVA differences after 12 weeks showed the non-inferiority of video game treatment to eye patching using a 0.10 logMAR threshold while adjusting for the participant's age, sex, and baseline BCVA. CONCLUSIONS: The results of the study suggest that a 12-week home-based video game vision therapy intervention can provide equivalent treatment outcomes to eye patching for amblyopia in children ages 5 to 18 years. Video game-based vision therapy may be a more acceptable and time-efficient alternative to existing approaches. By incorporating elements of perceptual learning, approaches such as Barron Vision video game treatment may have additional long-term therapeutic benefits and may improve treatment compliance. [J Pediatr Ophthalmol Strabismus. 2024;61(1):20-29.].

Concurrent Validity of Measures of Upper Extremity Function Derived from Videogame-Based Motion Capture for Children with Hemiplegia.

Objective: Pediatric hemiplegia is associated with wide-ranging deficits in arm and hand motor function, neg-atively impacting participation in daily occupations and quality of life. This study investigated whether performance measures generated during therapy videogame play by children with hemiplegia can be valid indicators of upper extremity motor function. Materials and Methods: Ten children with hemiplegia used a custom therapy game system alternatively using their affected and non-affected hand to provide motion capture data that spans a wide range of motor function status. The children also completed a series of standardized outcome measure assessments with each hand, including the Quality of Upper Extremity Skills Test, the Jebsen Taylor Hand Function Test, and the Wolf Motor Function Test. Results: Statistical analysis using the nonparametric Spearman rank correlation revealed high and significant correlation between videogame-derived motion capture measures, characterizing the speed and smoothness of movements, and the standardized outcome measure assessments. Conclusion: The results suggest that a low-cost motion capture system can be used to monitor a child's motor function status and progress during a therapy program.

Telehealth-Guided Virtual Reality for Recovery of Upper Extremity Function Following Stroke.

This rater-blinded, randomized control trial (RCT) investigated the effectiveness of a Glove Rehabilitation Application for Stroke Patients (GRASP) virtual reality home exercise program (HEP) for upper extremity (UE) motor recovery following stroke. The GRASP system facilitates the use of the affected UE in simulated instrumental activities of daily living (IADLs). Participants were asked to use the system at home in asynchronous telehealth sessions 4 times per week over 8 weeks. A non-blinded occupational therapist (OT) provided synchronous telehealth visits biweekly. Analysis comparing pre- and post-assessment results for the Fugl-Meyer UE assessment (FMUE) shows a clinically important and statistically significant between-group difference for participants completing the GRASP HEP protocol compared with usual and customary care controls. Statistically significant and clinically important differences were also found in Motor Activity Log (MAL) scores. This evidence provides support for the effectiveness of home-based, IADL-focused, virtual reality therapy with telehealth support.

Upper Extremity Function Assessment Using a Glove Orthosis and Virtual Reality System.

Hand motor control deficits following stroke can diminish the ability of patients to participate in daily activities. This study investigated the criterion validity of upper extremity (UE) performance measures automatically derived from sensor data during manual practice of simulated instrumental activities of daily living (IADLs) within a virtual environment. A commercial glove orthosis was specially instrumented with motion tracking sensors to enable patients to interact, through functional UE movements, with a computer-generated virtual world using the SaeboVR software system. Fifteen stroke patients completed four virtual IADL practice sessions, as well as a battery of gold-standard assessments of UE motor and hand function. Statistical analysis using the nonparametric Spearman rank correlation reveals high and significant correlation between virtual world-derived measures and the gold-standard assessments. The results provide evidence that performance measures generated during manual interactions with a virtual environment can provide a valid indicator of UE motor status.

Longitudinal qualitative evaluation of pharmacist integration into the urgent care setting.

PURPOSE: To describe the most effective model for managing, educating, and training pharmacist advanced clinical practitioners (ACPs) in the urgent care center (UCC) setting, role evolution and how to measure their effectiveness. PARTICIPANTS AND METHODS: Ethical approval was obtained to perform a qualitative longitudinal cohort study in three sites, with three pharmacists in each trained as ACPs from 2016 to 2017. ACP role, location, management, mentorship, and supervision were locally determined. ACPs attended focus groups (FGs) at 1 and 3 months (sites 1-3), 6 and 12 months (site 1 only), and the UCC staff were interviewed once with a topic guide regarding training, integration, role, and impact. Verbatim transcriptions were analyzed thematically. RESULTS: Eight ACP FGs and 24 stakeholder interviews produced major themes of communication, management, education and training, role, and outcomes. Effective education, training, and integration required communication of role to address concerns regarding salary differentials, supportive management structure, and multi-professional learning. ACPs reported that the model of workplace training, experiential learning, and university-based education was appropriate. Training was better located in the minor injuries and general practitioner areas. Recommended measures of effectiveness included patient satisfaction and workload transfer. CONCLUSION: The education and training model was appropriate. Communication and management require careful consideration to ensure effective integration and role development. Pharmacists were better located initially in the minor illness rather than major trauma areas. Quality of patient experience resulting from the new role was important in addition to reassurance that the role represented a positive contribution to workload.

Virtual Activities of Daily Living for Recovery of Upper Extremity Motor Function.

A study was conducted to investigate the effectiveness of virtual activities of daily living (ADL) practice using the SaeboVR software system for the recovery of upper extremity (UE) motor function following stroke. The system employs Kinect sensor-based tracking to translate human UE motion into the anatomical pose of the arm of the patient's avatar within a virtual environment, creating a virtual presence within a simulated task space. Patients gain mastery of 12 different integrated activities while traversing a metaphorical "road to recovery" that includes thematically linked levels and therapist-selected difficulty settings. Clinical trials were conducted under the study named Virtual Occupational Therapy Application. A total of 15 chronic phase stroke survivors completed a protocol involving three sessions per week over eight weeks, during which they engaged in repetitive task practice through performance of the virtual ADLs. Results show a clinically important improvement and statistically significant difference in Fugl-Meyer UE assessment scores in the study population of chronic stroke survivors over the eight-week interventional period compared with a non-interventional control period of equivalent duration. Statistically significant and clinically important improvements are also found in the wolf motor function test scores. These results provide new evidence for the use of virtual ADL practice as a tool for UE therapy for stroke patients. Limitations of the study include non-blinded assessments and the possibility of selection and/or attrition bias.

Unipolar distributions of junctional Myosin II identify cell stripe boundaries that drive cell intercalation throughout Drosophila axis extension.

Convergence and extension movements elongate tissues during development. Drosophila germ-band extension (GBE) is one example, which requires active cell rearrangements driven by Myosin II planar polarisation. Here, we develop novel computational methods to analyse the spatiotemporal dynamics of Myosin II during GBE, at the scale of the tissue. We show that initial Myosin II bipolar cell polarization gives way to unipolar enrichment at parasegmental boundaries and two further boundaries within each parasegment, concomitant with a doubling of cell number as the tissue elongates. These boundaries are the primary sites of cell intercalation, behaving as mechanical barriers and providing a mechanism for how cells remain ordered during GBE. Enrichment at parasegment boundaries during GBE is independent of Wingless signaling, suggesting pair-rule gene control. Our results are consistent with recent work showing that a combinatorial code of Toll-like receptors downstream of pair-rule genes contributes to Myosin II polarization via local cell-cell interactions. We propose an updated cell-cell interaction model for Myosin II polarization that we tested in a vertex-based simulation.

Mechanical Coupling between Endoderm Invagination and Axis Extension in Drosophila.

How genetic programs generate cell-intrinsic forces to shape embryos is actively studied, but less so how tissue-scale physical forces impact morphogenesis. Here we address the role of the latter during axis extension, using Drosophila germband extension (GBE) as a model. We found previously that cells elongate in the anteroposterior (AP) axis in the extending germband, suggesting that an extrinsic tensile force contributed to body axis extension. Here we further characterized the AP cell elongation patterns during GBE, by tracking cells and quantifying their apical cell deformation over time. AP cell elongation forms a gradient culminating at the posterior of the embryo, consistent with an AP-oriented tensile force propagating from there. To identify the morphogenetic movements that could be the source of this extrinsic force, we mapped gastrulation movements temporally using light sheet microscopy to image whole Drosophila embryos. We found that both mesoderm and endoderm invaginations are synchronous with the onset of GBE. The AP cell elongation gradient remains when mesoderm invagination is blocked but is abolished in the absence of endoderm invagination. This suggested that endoderm invagination is the source of the tensile force. We next looked for evidence of this force in a simplified system without polarized cell intercalation, in acellular embryos. Using Particle Image Velocimetry, we identify posteriorwards Myosin II flows towards the presumptive posterior endoderm, which still undergoes apical constriction in acellular embryos as in wildtype. We probed this posterior region using laser ablation and showed that tension is increased in the AP orientation, compared to dorsoventral orientation or to either orientations more anteriorly in the embryo. We propose that apical constriction leading to endoderm invagination is the source of the extrinsic force contributing to germband extension. This highlights the importance of physical interactions between tissues during morphogenesis.

Designing Haptic Assistive Technology for Individuals Who Are Blind or Visually Impaired.

This paper considers issues relevant for the design and use of haptic technology for assistive devices for individuals who are blind or visually impaired in some of the major areas of importance: Braille reading, tactile graphics, orientation and mobility. We show that there is a wealth of behavioral research that is highly applicable to assistive technology design. In a few cases, conclusions from behavioral experiments have been directly applied to design with positive results. Differences in brain organization and performance capabilities between individuals who are "early blind" and "late blind" from using the same tactile/haptic accommodations, such as the use of Braille, suggest the importance of training and assessing these groups individually. Practical restrictions on device design, such as performance limitations of the technology and cost, raise questions as to which aspects of these restrictions are truly important to overcome to achieve high performance. In general, this raises the question of what it means to provide functional equivalence as opposed to sensory equivalence.

Assessing upper extremity motor function in practice of virtual activities of daily living.

A study was conducted to investigate the criterion validity of measures of upper extremity (UE) motor function derived during practice of virtual activities of daily living (ADLs). Fourteen hemiparetic stroke patients employed a Virtual Occupational Therapy Assistant (VOTA), consisting of a high-fidelity virtual world and a Kinect™ sensor, in four sessions of approximately one hour in duration. An unscented Kalman Filter-based human motion tracking algorithm estimated UE joint kinematics in real-time during performance of virtual ADL activities, enabling both animation of the user's avatar and automated generation of metrics related to speed and smoothness of motion. These metrics, aggregated over discrete sub-task elements during performance of virtual ADLs, were compared to scores from an established assessment of UE motor performance, the Wolf Motor Function Test (WMFT). Spearman's rank correlation analysis indicates a moderate correlation between VOTA-derived metrics and the time-based WMFT assessments, supporting the criterion validity of VOTA measures as a means of tracking patient progress during an UE rehabilitation program that includes practice of virtual ADLs.

A dynamic microtubule cytoskeleton directs medial actomyosin function during tube formation.

The cytoskeleton is a major determinant of cell-shape changes that drive the formation of complex tissues during development. Important roles for actomyosin during tissue morphogenesis have been identified, but the role of the microtubule cytoskeleton is less clear. Here, we show that during tubulogenesis of the salivary glands in the fly embryo, the microtubule cytoskeleton undergoes major rearrangements, including a 90° change in alignment relative to the apicobasal axis, loss of centrosomal attachment, and apical stabilization. Disruption of the microtubule cytoskeleton leads to failure of apical constriction in placodal cells fated to invaginate. We show that this failure is due to loss of an apical medial actomyosin network whose pulsatile behavior in wild-type embryos drives the apical constriction of the cells. The medial actomyosin network interacts with the minus ends of acentrosomal microtubule bundles through the cytolinker protein Shot, and disruption of Shot also impairs apical constriction.

Contractile and mechanical properties of epithelia with perturbed actomyosin dynamics.

Mechanics has an important role during morphogenesis, both in the generation of forces driving cell shape changes and in determining the effective material properties of cells and tissues. Drosophila dorsal closure has emerged as a reference model system for investigating the interplay between tissue mechanics and cellular activity. During dorsal closure, the amnioserosa generates one of the major forces that drive closure through the apical contraction of its constituent cells. We combined quantitation of live data, genetic and mechanical perturbation and cell biology, to investigate how mechanical properties and contraction rate emerge from cytoskeletal activity. We found that a decrease in Myosin phosphorylation induces a fluidization of amnioserosa cells which become more compliant. Conversely, an increase in Myosin phosphorylation and an increase in actin linear polymerization induce a solidification of cells. Contrary to expectation, these two perturbations have an opposite effect on the strain rate of cells during DC. While an increase in actin polymerization increases the contraction rate of amnioserosa cells, an increase in Myosin phosphorylation gives rise to cells that contract very slowly. The quantification of how the perturbation induced by laser ablation decays throughout the tissue revealed that the tissue in these two mutant backgrounds reacts very differently. We suggest that the differences in the strain rate of cells in situations where Myosin activity or actin polymerization is increased arise from changes in how the contractile forces are transmitted and coordinated across the tissue through ECadherin-mediated adhesion. Altogether, our results show that there is an optimal level of Myosin activity to generate efficient contraction and suggest that the architecture of the actin cytoskeleton and the dynamics of adhesion complexes are important parameters for the emergence of coordinated activity throughout the tissue.

Properties of Rasch residual fit statistics.

This paper examines the residual-based fit statistics commonly used in Rasch measurement. In particular, the paper analytically examines some of the theoretical properties of the residual-based fit statistics with a view to establishing the inferences that can be made using these fit statistics. More specifically, the relationships between the distributional properties of the fit statistics and sample size are discussed; some research that erroneously concludes that residual-based fit statistics are unstable is reviewed; and finally, it is analytically illustrated that, for dichotomous items, residual-based fit statistics provide a measure of the relative slope of empirical item characteristic curves. With a clear understanding of the theoretical properties of the fit statistics, the use and limitations of these statistics can be placed in the right light.

Dynamic regulation of growing domains for elongating and branching morphogenesis in plants.

With their continuous growth, understanding how plant shapes form is fundamentally linked to understanding how growth rates are controlled across different regions of the plant. Much of a plant's architecture is generated in shoots and roots, where fast growth in tips contrasts with slow growth in supporting stalks. Shapes can be determined by where the boundaries between fast- and slow-growing regions are positioned, determining whether tips elongate, branch, or cease to grow. Across plants, there is a diversity in the cell wall chemistry through which growth operates. However, prototypical morphologies, such as tip growth and branching, suggest there are common dynamic constraints in localizing chemical growth catalysts. We have used Turing-type reaction-diffusion mechanisms to model this spatial localization and the resulting growth trajectories, characterizing the chemistry-growth feedback necessary for maintaining tip growth and for inducing branching. The mechanism defining the boundaries between fast- and slow-growing regions not only affects tip shape, it must be able to form new boundaries when the pattern-forming dynamics break symmetry, for instance in the branching of a tip. In previous work, we used an arbitrary concentration threshold to switch between two dynamic regimes of the growth catalyst in order to define growth boundaries. Here, we present a chemical dynamic basis for this threshold, in which feedback between two pattern-forming mechanisms controls the extent of the regions in which fast growth occurs. This provides a general self-contained mechanism for growth control in plant morphogenesis (not relying on external cues) which can account for both simple tip extension and symmetry-breaking branching phenomena.

Measuring the multi-scale integration of mechanical forces during morphogenesis.

The elaborate changes in morphology of an organism during development are the result of mechanical contributions that are a mixture of those generated locally and those that influence from a distance. We would like to know how chemical and mechanical information is transmitted and transduced, how work is done to achieve robust morphogenesis and why it sometimes fails. We introduce a scheme for separating the influence of two classes of forces. Active intrinsic forces integrate up levels of scale to shape tissues. Counter-currently, extrinsic forces exert influence from higher levels downwards and feed back directly and indirectly upon the intrinsic behaviours. We identify the measurable signatures of different kinds of forces and identify the frontiers where work is most needed.

Cytoskeletal dynamics and supracellular organisation of cell shape fluctuations during dorsal closure.

Fluctuations in the shape of amnioserosa (AS) cells during Drosophila dorsal closure (DC) provide an ideal system with which to understand contractile epithelia, both in terms of the cellular mechanisms and how tissue behaviour emerges from the activity of individual cells. Using quantitative image analysis we show that apical shape fluctuations are driven by the medial cytoskeleton, with periodic foci of contractile myosin and actin travelling across cell apices. Shape changes were mostly anisotropic and neighbouring cells were often, but transiently, organised into strings with parallel deformations. During the early stages of DC, shape fluctuations with long cycle lengths produced no net tissue contraction. Cycle lengths shortened with the onset of net tissue contraction, followed by a damping of fluctuation amplitude. Eventually, fluctuations became undetectable as AS cells contracted rapidly. These transitions were accompanied by an increase in apical myosin, both at cell-cell junctions and medially, the latter ultimately forming a coherent, but still dynamic, sheet across cells. Mutants with increased myosin activity or actin polymerisation exhibited precocious cell contraction through changes in the subcellular localisation of myosin. thick veins mutant embryos, which exhibited defects in the actin cable at the leading edge, showed similar timings of fluctuation damping to the wild type, suggesting that damping is an autonomous property of the AS. Our results suggest that cell shape fluctuations are a property of cells with low and increasing levels of apical myosin, and that medial and junctional myosin populations combine to contract AS cell apices and drive DC.

Cell shape changes indicate a role for extrinsic tensile forces in Drosophila germ-band extension.

Drosophila germ-band extension (GBE) is an example of the convergence and extension movements that elongate and narrow embryonic tissues. To understand the collective cell behaviours underlying tissue morphogenesis, we have continuously quantified cell intercalation and cell shape change during GBE. We show that the fast, early phase of GBE depends on cell shape change in addition to cell intercalation. In antero-posterior patterning mutants such as those for the gap gene Krüppel, defective polarized cell intercalation is compensated for by an increase in antero-posterior cell elongation, such that the initial rate of extension remains the same. Spatio-temporal patterns of cell behaviours indicate that an antero-posterior tensile force deforms the germ band, causing the cells to change shape passively. The rate of antero-posterior cell elongation is reduced in twist mutant embryos, which lack mesoderm. We propose that cell shape change contributing to germ-band extension is a passive response to mechanical forces caused by the invaginating mesoderm.

Active cell movements coupled to positional induction are involved in lineage segregation in the mouse blastocyst.

In the mouse blastocyst, some cells of the inner cell mass (ICM) develop into primitive endoderm (PE) at the surface, while deeper cells form the epiblast. It remained unclear whether the position of cells determines their fate, such that gene expression is adjusted to cell position, or if cells are pre-specified at random positions and then sort. We have tracked and characterised dynamics of all ICM cells from the early to late blastocyst stage. Time-lapse microscopy in H2B-EGFP embryos shows that a large proportion of ICM cells change position between the surface and deeper compartments. Most of this cell movement depends on actin and is associated with cell protrusions. We also find that while most cells are precursors for only one lineage, some give rise to both, indicating that lineage segregation is not complete in the early ICM. Finally, changing the expression levels of the PE marker Gata6 reveals that it is required in surface cells but not sufficient for the re-positioning of deeper cells. We provide evidence that Wnt9A, known to be expressed in the surface ICM, facilitates re-positioning of Gata6-expressing cells. Combining these experimental results with computer modelling suggests that PE formation involves both cell sorting movements and position-dependent induction.

Tissue tectonics: morphogenetic strain rates, cell shape change and intercalation.

The dynamic reshaping of tissues during morphogenesis results from a combination of individual cell behaviors and collective cell rearrangements. However, a comprehensive framework to unambiguously measure and link cell behavior to tissue morphogenesis is lacking. Here we introduce such a kinematic framework, bridging cell and tissue behaviors at an intermediate, mesoscopic, level of cell clusters or domains. By measuring domain deformation in terms of the relative motion of cell positions and the evolution of their shapes, we characterized the basic invariant quantities that measure fundamental classes of cell behavior, namely tensorial rates of cell shape change and cell intercalation. In doing so we introduce an explicit definition of cell intercalation as a continuous process. We mapped strain rates spatiotemporally in three models of tissue morphogenesis, gaining insight into morphogenetic mechanisms. Our quantitative approach has broad relevance for the precise characterization and comparison of morphogenetic phenotypes.