A systematic review of high quality randomized controlled trials investigating motor skill programmes for children with developmental coordination disorder.

To identify effective motor training interventions for children with developmental coordination disorder from research graded as high quality (using objective criteria) for the purpose of informing evidence-based clinical practice.We followed the guidance for conducting systematic reviews issued by the Centre for Reviews and Dissemination. Six OvidSP electronic databases (AMED, All EBM reviews (including Cochrane), Embase, Ovid MEDLINE, PsychARTICLES Full Text, PsycINFO) were searched systematically. We aimed to retain only randomized control trials and systematic reviews of randomized control trials, defined as the highest level of evidence by the Oxford Centre for Evidence-Based Medicine. We searched reference lists of retained articles to identify further appropriate articles.Two reviewers critically appraised and categorized articles by effect size (including confidence intervals), inclusion of power calculations and quality using the Physiotherapy Evidence Database (PEDro) scale. Only studies scoring seven or more on the PEDro scale (classed by the PEDro as high reliability) were retained.No systematic reviews met our criteria for inclusion from 846 articles yielded by the systematic search. Nine randomized control trials investigating 15 interventions to improve motor skills met our inclusion criteria for 'high quality'. Nevertheless, not all included studies were adequately powered for determining an effect.Large effect sizes associated with 95 % confidence intervals suggest that 'Neuromotor Task Training', 'Task-oriented Motor Training' and 'Motor Imagery + Task Practice Training' are the most effective reported interventions for improving motor skills in children with developmental coordination disorder

OXA-66 structure and oligomerisation of OXAAb enzymes

The OXA β-lactamases are responsible for hydrolysing β-lactam antibiotics and contribute to the multidrug-resistant phenotype of several major human pathogens. The OXAAb enzymes are intrinsic to Acinetobacter baumannii and can confer resistance to carbapenem antibiotics. Here we determined the structure of the most prevalent OXAAb enzyme, OXA-66. The structure of OXA-66 was solved at a resolution of 2.1 Å and found to be very similar to the structure of OXA-51, the only other OXAAb enzyme that has had its structure solved. Our data contained one molecule per asymmetric unit, and analysis of positions responsible for dimer formation in other OXA enzymes suggest that OXA-66 likely exists as a monomer

Structural and mechanistic analysis of ATPase inhibitors targeting mycobacterial DNA gyrase

Objectives To evaluate the efficacy of two novel compounds against mycobacteria and determine the molecular basis of their action on DNA gyrase using structural and mechanistic approaches. Methods Redx03863 and Redx04739 were tested in antibacterial assays, and also against their target, DNA gyrase, using DNA supercoiling and ATPase assays. X-ray crystallography was used to determine the structure of the gyrase B protein ATPase sub-domain from Mycobacterium smegmatis complexed with the aminocoumarin drug novobiocin, and structures of the same domain from Mycobacterium thermoresistibile complexed with novobiocin, and also with Redx03863. Results Both compounds, Redx03863 and Redx04739, were active against selected Gram-positive and Gram-negative species, with Redx03863 being the more potent, and Redx04739 showing selectivity against M. smegmatis. Both compounds were potent inhibitors of the supercoiling and ATPase reactions of DNA gyrase, but did not appreciably affect the ATP-independent relaxation reaction. The structure of Redx03863 bound to the gyrase B protein ATPase sub-domain from M. thermoresistibile shows that it binds at a site adjacent to the ATP- and novobiocin-binding sites. We found that most of the mutations that we made in the Redx03863-binding pocket, based on the structure, rendered gyrase inactive. Conclusions Redx03863 and Redx04739 inhibit gyrase by preventing the binding of ATP. The fact that the Redx03863-binding pocket is distinct from that of novobiocin, coupled with the lack of activity of resistant mutants, suggests that such compounds could have potential to be further exploited as antibiotics

Exploring the 5-Substituted 2-Aminobenzothiazole-Based DNA Gyrase B Inhibitors Active against ESKAPE Pathogens

We present a new series of 2-aminobenzothiazole-basedDNA gyraseB inhibitors with promising activity against ESKAPE bacterial pathogens.Based on the binding information extracted from the cocrystal structureof DNA gyrase B inhibitor A, in complex with Escherichia coli GyrB24, we expanded the chemicalspace of the benzothiazole-based series to the C5 position of thebenzothiazole ring. In particular, compound E showedlow nanomolar inhibition of DNA gyrase (IC50 < 10 nM)and broad-spectrum antibacterial activity against pathogens belongingto the ESKAPE group, with the minimum inhibitory concentration <0.03 & mu;g/mL for most Gram-positive strains and 4-16 & mu;g/mLagainst Gram-negative E. coli, Acinetobacter baumannii, Pseudomonasaeruginosa, and Klebsiella pneumoniae. To understand the binding mode of the synthesized inhibitors, acombination of docking calculations, molecular dynamics (MD) simulations,and MD-derived structure-based pharmacophore modeling was performed.The computational analysis has revealed that the substitution at positionC5 can be used to modify the physicochemical properties and antibacterialspectrum and enhance the inhibitory potency of the compounds. Additionally,a discussion of challenges associated with the synthesis of 5-substituted2-aminobenzothiazoles is presented

Analysis of Photon Detection Efficiency and Dynamic Range in SPAD based Visible Light Receivers

We investigate the photon detection efficiency (PDE) and the dynamic range for digital silicon photomultipliers (dSiPMs) over a selection of design parameters: dSiPM unit cell dead time, PDE, unit cell area and fill factor, number of cells, and total dSiPM active area. Two receiver scaling scenarios are con-sidered: varying the number of cells for 1) a fixed unit cell area or 2) a fixed total dSiPM area. Theoretical and simulated results are confirmed with experimental data from a selection of dSiPMs realised on a test chip in130-nm CMOS process

Parents' Online Portrayals of Pediatric Treatment and Research Options

Parents of seriously ill children face difficult decisions when standard therapies are limited or ineffective. In their search for information, they may turn to websites created by other parents facing similar experiences. We conducted a qualitative content analysis of 21 websites created by families with children affected by cancer or genetic disease, two serious conditions with a range of treatment and clinical trial options. Our research questions address how parent authors portray serious pediatric illness, available options, parties to decision making, and sources of influence. In addition, we examine what these sites reveal about family vulnerability to various risks, particularly the risk of misunderstanding the distinction between standard treatment and research and the risk of overestimating the likely benefits of research participation, as well as whether vulnerability varies by type of condition. Our results demonstrate typically favorable views on research, but with inadequate distinctions between research and treatment and a complex set of trade-offs in consideration of research risks and potential benefits. While portraits of vulnerability emerge for both parents and children, so do portraits of strength and resilience. As a result, parents describe frustration with both under- and over-protection from research participation. Our discussion of these findings clarifies the potential for parent-authored websites to inform and influence families considering research and treatment options for their seriously ill children