Interventions to Promote the Development of Motor Performance Skills in Primary School Aged Children with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis of Controlled Trials

Background: The development of proficiency in motor performance skills (MPS) builds the foundation for the complex movement skills required to participate in a range of sports and physical activities throughout the lifespan. Objective: To assess the efficacy of different intervention approaches on developing MPS proficiency in children with autism spectrum disorder (ASD) and examine the intervention factors that influence change. Method: Searches were completed in three databases (PubMed/MEDLINE, Scopus, Web of Science) up to March 2022. Only randomised controlled trials (RCTs) or controlled trials (CTs), that evaluated the effectiveness of interventions on overall MPS proficiency or specific MPS such as balance, running speed and agility, bilateral coordination, jumping, ball skills and push-ups in children (4–13 years old) were included. The DerSimonian and Laird random-effects model was used to compute the meta-analyses. The effect sizes were reported as Hedges’ g. Using a random-effects model, potential sources of heterogeneity were identified, including subgroup analyses (type of intervention), and single training factor analysis (total number of weeks, session frequency, total intervention time, total number of training sessions). In addition, a multivariate meta-regression calculation was performed for balance. The GRADE framework was applied to assess certainty of evidence. Results: Seventeen interventions (13 RCTs and 4 CTs) revealed significant differences among groups favouring the intervention group with moderate to very large effects. Significant (p 0.05) small-to-large effects of interventions were evident on overall motor performance skills (ES = 2.43), ball skills (ES = 2.95), jumping (ES = 1.89), bilateral coordination (ES = 2.21), push-ups (ES = 1.92), balance (ES = 1.56), running speed and agility (ES = 1.31). Multivariate meta-regression for balance revealed that total sessions, total intervention time and session frequency predicted (p = 0.009, p0.001, p = 0.036, respectively) the effects of interventions on change in balance performance. Conclusion: Structured interventions that explicitly teach traditional FMS or promote the development and learning of movement skills specifically associated with a type of physical activity or sport, effectively improve MPS in children with ASD. Education settings should implement ‘planned’ movement experiences or interventions as a strategy to promote MPS proficiency in children with ASD

Phenylbutazone concentrations in synovial fluid following administration via intravenous regional limb perfusion in the forelimbs of six adult horses

BackgroundPain management is critical to equine welfare with non-steroidal anti-inflammatory drugs (NSAID) commonly used in horses. However, systemic NSAID use is limited by harmful gastrointestinal and renal side effects. Intravenous regional limb perfusion (IVRLP) is a technique used in horses that produces high, local antibiotic concentrations while limiting systemic circulation. NSAID-IVRLP would be a novel method of local pain management while limiting systemic NSAID side effects. To date, NSAID-IVRLP administration has not been reported in horses. This study aimed to identify the pharmacokinetics and local complications associated with using the NSAID phenylbutazone (PBZ) for IVRLP in six standing adult horses.MethodsPBZ-IVRLP, at a dose of 2.2 mg/kg PBZ, was performed in a randomly assigned forelimb cephalic vein in 6 standing, healthy adult horses. A placebo-IVRLP was performed in the contralateral forelimb for comparison. Systemic serum and radiocarpal joint synovial fluid PBZ concentrations were identified at various timepoints (before IVRLP T-0 h, just after tourniquet removal T-0.5, 1.5, 3, 5, 12, 16, and 24 h post IVRLP) for non-compartmental pharmacokinetic analysis and concentration over time curves. Local complications associated with PBZ-IVRP were evaluated for up to 7 days following PBZ-IVRLP using physical and ultrasonographic assessment. On day 7 horses were humanely euthanized with histology performed on both forelimbs at PBZ-IVRLP and placebo-IVRLP administration sites.ResultsNon-compartmental pharmacokinetics for PBZ, and its major metabolite oxyphenbutazone (OBZ), were determined for serum and synovial fluid. Synovial PBZ concentrations (mean ± SD; 1.9 ± 2.1 μg/mL) were significantly lower (p = 0.03; CI,0.46–7.36) than serum PBZ concentrations (5.8 ± 5.1 μg/mL) at any time point. Physical and ultrasonographic measurements were not significantly different between PBZ- and placebo-IVRLP forelimbs. The most common histologic findings included focal deep dermal/subcutaneous hemorrhage and edema. Two horses showed perivasculitis and one horse showed a resolving thrombus in the cephalic vein of the PBZ-IVRLP limb. This horse also had severe perivasculitis and fibrinosuppurative dermatitis/panniculitis in the placebo-IVRLP limb.ConclusionPBZ-IVRLP pharmacokinetics at a 2.2 mg/kg dose showed no benefit compared to systemic PBZ administration in standing adult horses. Local complications associated with PBZ-IVRLP were similar to placebo-IVRLP on physical and ultrasonographic evaluation

Development and Implementation of a High Throughput Screen for the Human Sperm-Specific Isoform of Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDHS)

Glycolytic isozymes that are restricted to the male germline are potential targets for the development of reversible, non-hormonal male contraceptives. GAPDHS, the sperm-specific isoform of glyceraldehyde-3-phosphate dehydrogenase, is an essential enzyme for glycolysis making it an attractive target for rational drug design. Toward this goal, we have optimized and validated a high-throughput spectrophotometric assay for GAPDHS in 384-well format. The assay was stable over time and tolerant to DMSO. Whole plate validation experiments yielded Z’ values >0.8 indicating a robust assay for HTS. Two compounds were identified and confirmed from a test screen of the Prestwick collection. This assay was used to screen a diverse chemical library and identified fourteen small molecules that modulated the activity of recombinant purified GAPDHS with confirmed IC50 values ranging from 1.8 to 42 µM. These compounds may provide useful scaffolds as molecular tools to probe the role of GAPDHS in sperm motility and long term to develop potent and selective GAPDHS inhibitors leading to novel contraceptive agents

Mechanical Properties of Molybdenum Disulfide and the Effect of Doping: An in Situ TEM Study

Direct observations on nanopillars composed of molybdenum disulfide (MoS₂) and chromium-doped MoS₂ and their response to compressive stress have been made. Time-resolved transmission electron microscopy (TEM) during compression of the submicrometer diameter pillars of MoS₂- and Cr-doped MoS₂ (Cr: 0, 10, and 50 at %) allow the deformation process of the material to be observed and can be directly correlated with mechanical response to applied load. The addition of chromium to the MoS₂ changed the failure mode from plastic deformation to catastrophic brittle fracture, an effect that was more pronounced as chromium content increased

A Response to the Draft National Mitigation Plan. Teagasc submission to the Department of Communications, Climate Action & theEnvironment

Teagasc SubmissionThis submission details the mitigation potential of agriculture to shortly be published as an update to the Marginal Abatement Cost Curve (MACC) for Agriculture and and describes how the MACC mitigation strategies relate to the measures in the National Mitigation Plan

OpenFermion: The Electronic Structure Package for Quantum Computers

Quantum simulation of chemistry and materials is predicted to be an important application for both near-term and fault-tolerant quantum devices. However, at present, developing and studying algorithms for these problems can be difficult due to the prohibitive amount of domain knowledge required in both the area of chemistry and quantum algorithms. To help bridge this gap and open the field to more researchers, we have developed the OpenFermion software package (www.openfermion.org). OpenFermion is an open-source software library written largely in Python under an Apache 2.0 license, aimed at enabling the simulation of fermionic models and quantum chemistry problems on quantum hardware. Beginning with an interface to common electronic structure packages, it simplifies the translation between a molecular specification and a quantum circuit for solving or studying the electronic structure problem on a quantum computer, minimizing the amount of domain expertise required to enter the field. The package is designed to be extensible and robust, maintaining high software standards in documentation and testing. This release paper outlines the key motivations behind design choices in OpenFermion and discusses some basic OpenFermion functionality which we believe will aid the community in the development of better quantum algorithms and tools for this exciting area of research.Comment: 22 page

Recombinant human sperm-specific glyceraldehyde-3-phosphate dehydrogenase (GAPDHS) is expressed at high yield as an active homotetramer in baculovirus-infected insect cells

The sperm-specific glyceraldehyde-3-phosphate dehydrogenase (GAPDHS) isoform is a promising contraceptive target because it is specific to male germ cells, essential for sperm motility and male fertility, and well suited to pharmacological inhibition. However, GAPDHS is difficult to isolate from native sources and recombinant expression frequently results in high production of insoluble enzyme. We chose to use the Bac-to-Bac baculovirus-insect cell system to express a His-tagged form of human GAPDHS (Hu his-GAPDHS) lacking the proline-rich N-terminal sequence. This recombinant Hu his-GAPDHS was successfully produced in Spodoptera frugiperda 9 (Sf9) cells by infection with recombinant virus as a soluble, enzymatically active form in high yield, >35mg/L culture. Biochemical characterization of the purified enzyme by mass spectrometry and size exclusion chromatography confirmed the presence of the tetrameric form. Further characterization by peptide ion matching mass spectrometry and Edman sequencing showed that unlike the mixed tetramer forms produced in bacterial expression systems, human his-GAPDHS expressed in baculovirus-infected insect cells is homotetrameric. The ability to express and purify active human GAPDHS as homotetramers in high amounts will greatly aid in drug discovery efforts targeting this enzyme for discovery of novel contraceptives and three compounds were identified as inhibitors of Hu his-GAPDHS from a pilot screen of 1120 FDA-approved compounds

Effect of Layer-Stacking on the Electronic Structure of Graphene Nanoribbons

The evolution of electronic structure of graphene nanoribbons (GNRs) as a function of the number of layers stacked together is investigated using \textit{ab initio} density functional theory (DFT) including interlayer van der Waals interactions. Multilayer armchair GNRs (AGNRs), similar to single-layer AGNRs, exhibit three classes of band gaps depending on their width. In zigzag GNRs (ZGNRs), the geometry relaxation resulting from interlayer interactions plays a crucial role in determining the magnetic polarization and the band structure. The antiferromagnetic (AF) interlayer coupling is more stable compared to the ferromagnetic (FM) interlayer coupling. ZGNRs with the AF in-layer and AF interlayer coupling have a finite band gap while ZGNRs with the FM in-layer and AF interlayer coupling do not have a band gap. The ground state of the bi-layer ZGNR is non-magnetic with a small but finite band gap. The magnetic ordering is less stable in multilayer ZGNRs compared to single-layer ZGNRs. The quasipartcle GW corrections are smaller for bilayer GNRs compared to single-layer GNRs because of the reduced Coulomb effects in bilayer GNRs compared to single-layer GNRs.Comment: 10 pages, 5 figure

Development of a core outcome set for orthodontic trials using a mixed-methods approach: Protocol for a multicentre study

© 2017 The Author(s). Background: Orthodontic treatment is commonly undertaken in young people, with over 40% of children in the UK needing treatment and currently one third having treatment, at a cost to the National Health Service in England and Wales of £273 million each year. Most current research about orthodontic care does not consider what patients truly feel about, or want, from treatment, and a diverse range of outcomes is being used with little consistency between studies. This study aims to address these problems, using established methodology to develop a core outcome set for use in future clinical trials of orthodontic interventions in children and young people. Methods/design: This is a mixed-methods study incorporating four distinct stages. The first stage will include a scoping review of the scientific literature to identify primary and secondary outcome measures that have been used in previous orthodontic clinical trials. The second stage will involve qualitative interviews and focus groups with orthodontic patients aged 10 to 16 years to determine what outcomes are important to them. The outcomes elicited from these two stages will inform the third stage of the study in which a long-list of outcomes will be ranked in terms of importance using electronic Delphi surveys involving clinicians and patients. The final stage of the study will involve face-to-face consensus meetings with all stakeholders to discuss and agree on the outcome measures that should be included in the final core outcome set. Discussion: This research will help to inform patients, parents, clinicians and commissioners about outcomes that are important to young people undergoing orthodontic treatment. Adoption of the core outcome set in future clinical trials of orthodontic treatment will make it easier for results to be compared, contrasted and combined. This should translate into improved decision-making by all stakeholders involved. Trial registration: The project has been registered on the Core Outcome Measures in Effectiveness Trials (COMET) website, January 2016