Adherence to the two-thirds power law and kinematic differences in children with autism during ellipse drawing and tracing activities on smart-tablet

Autistic individuals often demonstrate atypical motor control of purposeful action1, especially in the area of fine motor skills. • Studies assessing writing and drawing reveal larger peak velocities and greater sizing variability in autistic participants.2 • During swiping gestures on a tablet, those with autism show atypical kinematics compared to typically-developing (TD) controls.3 • The emergence of these atypical kinematic features require further investigation. • One method used to characterize motor control is the two-thirds power law (⅔ PL), a law of motion involving a covariation between the velocity and curvature, in which velocity decreases in more curved parts and increases in less curved parts of movement, as specified by the equation: • Tangential Velocity = K * Radius of Curvature1/3 • The ⅔ PL governs many types of human movement, including of the arm4, foot5 and eyes.6 • It is present in early in development7 and the velocity-curvature coupling appears to progress with age.8 • The goal of this study is to assess adherence to the ⅔ PL and kinematic features during drawing movements in autistic and TD children ages 4 through 8. • The law has yet to be studied in autism. • It may offer insight into atypical motor development and provide a better metric by which to assess motor kinematics

Motor control adherence to the two-thirds power law differs in autistic development

Purpose: Autistic individuals often exhibit motor atypicalities, which may relate to difficulties in social communication. This study utilized a smart tablet activity to computationally characterize motor control by testing adherence to the two-thirds power law (2/3 PL), which captures a systematic covariation between velocity and curvature in motor execution and governs many forms of human movement. Methods: Children aged 4-8 years old participated in this study, including 24 autistic children and 33 typically developing children. Participants drew and traced ellipses on an iPad. We extracted data from finger movements on the screen, and computed adherence to the 2/3 PL and other kinematic metrics. Measures of cognitive and motor functioning were also collected. Results: In comparison to the typically developing group, the autistic group demonstrated greater velocity modulation between curved and straight sections of movement, increased levels of acceleration and jerk, and greater intra- and inter-individual variability across several kinematic variables. Further, significant motor control development was observed in typically developing children, but not in those with autism. Conclusion: This study is the first to examine motor control adherence to the 2/3 PL in autistic children, revealing overall diminished motor control. Less smooth, more varied movement and an indication of developmental stasis in autistic children were observed. This study offers a novel tool for computational characterization of the autism motor signature in children’s development, demonstrating how smart tablet technology enables accessible assessment of children’s motor performance in an objective, quantifiable and scalable manner

Some classifications of biharmonic hypersurfaces with constant scalar curvature

We give some classifications of biharmonic hypersurfaces with constant scalar curvature. These include biharmonic Einstein hypersurfaces in space forms, compact biharmonic hypersurfaces with constant scalar curvature in a sphere, and some complete biharmonic hypersurfaces of constant scalar curvature in space forms and in a non-positively curved Einstein space. Our results provide additional cases (Theorem 2.3 and Proposition 2.8) that supports the conjecture that a biharmonic submanifold in a sphere has constant mean curvature, and two more cases that support Chen's conjecture on biharmonic hypersurfaces (Corollaries 2.2,2.7).Comment: 11 page

The distribution and host range of the banana Fusarium wilt fungus, Fusarium oxysporum f. sp. cubense, in Asia

Fusarium oxysporum formae specialis cubense (Foc) is a soil-borne fungus that causes Fusarium wilt, which is considered to be the most destructive disease of bananas. The fungus is believed to have evolved with its host in the Indo-Malayan region, and from there it was spread to other banana-growing areas with infected planting material. The diversity and distribution of Foc in Asia was investigated. A total of 594 F. oxysporum isolates collected in ten Asian countries were identified by vegetative compatibility groups (VCGs) analysis. To simplify the identification process, the isolates were first divided into DNA lineages using PCR-RFLP analysis. Six lineages and 14 VCGs, representing three Foc races, were identified in this study. The VCG complex 0124/5 was most common in the Indian subcontinent, Vietnam and Cambodia; whereas the VCG complex 01213/16 dominated in the rest of Asia. Sixty-nine F. oxysporum isolates in this study did not match any of the known VCG tester strains. In this study, Foc VCG diversity in Bangladesh, Cambodia and Sri Lanka was determined for the first time and VCGs 01221 and 01222 were first reported from Cambodia and Vietnam. New associations of Foc VCGs and banana cultivars were recorded in all the countries where the fungus was collected. Information obtained in this study could help Asian countries to develop and implement regulatory measures to prevent the incursion of Foc into areas where it does not yet occur. It could also facilitate the deployment of disease resistant banana varieties in infested areas.S1 Table. Morphological identity, PCR-RFLP clade and lineage identity, vegetative compatibility group, host and host subgroup, location and origin of Fusariumisolates collected in Asia.S2 Table. Vegetative compatibility tester strains used to characterize compatibility to Asian Fusariumoxysporumf. sp. cubense isolates.http://www.plosone.orgam2018Forestry and Agricultural Biotechnology Institute (FABI)Microbiology and Plant Patholog

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir

Perception and Execution of Biological Motion Adhering to the Two-thirds Power Law: A Comparison Between Autism Spectrum and Typical Development

Individuals with autism spectrum development (ASD) often demonstrate atypical perception and production of biological motion (BM), a term for the movement patterns of animate beings. Given the importance of visual perceptual and motor skills for social interaction and communication, a fundamental concern for those with ASD, further investigation into these domains, their potential association and their underlying role in ASD is critical. This project aimed to examine performance in both domains using a common metric, the two-thirds power law (2/3 PL), a law of motion that characterizes many forms of human movement. Using a preferential looking paradigm, this study examined attentional patterns toward motion adhering to this law, as well as more traditional BM stimuli with temporal or spatial manipulations. The study also employed a novel task to assess adherence to the law and other kinematics during drawing movements on an iPad tablet. Measures of cognitive, motor and social functioning were collected to explore whether task-specific performance related to atypical functioning in these areas. While the study did not detect a significant relationship between domains with respect to the law, the tasks did reveal a number of atypicalities in perceptual and motor performance in autism, as well as some associations with broader social functioning. Limitations and future directions of this research are also discussed

Perception and Execution of Biological Motion Adhering to the Two-thirds Power Law: A Comparison Between Autism Spectrum and Typical Development

Individuals with autism spectrum development (ASD) often demonstrate atypical perception and production of biological motion (BM), a term for the movement patterns of animate beings. Given the importance of visual perceptual and motor skills for social interaction and communication, a fundamental concern for those with ASD, further investigation into these domains, their potential association and their underlying role in ASD is critical. This project aimed to examine performance in both domains using a common metric, the two-thirds power law (2/3 PL), a law of motion that characterizes many forms of human movement. Using a preferential looking paradigm, this study examined attentional patterns toward motion adhering to this law, as well as more traditional BM stimuli with temporal or spatial manipulations. The study also employed a novel task to assess adherence to the law and other kinematics during drawing movements on an iPad tablet. Measures of cognitive, motor and social functioning were collected to explore whether task-specific performance related to atypical functioning in these areas. While the study did not detect a significant relationship between domains with respect to the law, the tasks did reveal a number of atypicalities in perceptual and motor performance in autism, as well as some associations with broader social functioning. Limitations and future directions of this research are also discussed