Evaluating the effectiveness of home exercise programmes using an online exercise prescription tool in children with cerebral palsy: protocol for a randomised controlled trial.

Introduction: Children with cerebral palsy (CP) and other neurodevelopmental disabilities often receive a home programme of exercises to assist in reaching their therapy goals. Adherence to exercise programmes is necessary to attain the level of practice required to achieve goals; however, adherence can be difficult to accomplish. In this paper, we describe the protocol for a randomised controlled trial to evaluate the effectiveness of delivering a home exercise programme to school-age children with disabilities using Physitrack, an online exercise prescription tool with a website or app interface. Methods and analysis: Participants aged 6–17 years, with CP or other neurodevelopmental disabilities, receiving community physiotherapy services in Western Australia, will be recruited. Participants will be stratified by age and functional mobility and randomised to either the intervention group, who will complete an 8-week home exercise programme using Physitrack, or the control group, who will complete an 8-week exercise programme without Physitrack. Researcher blinding to group allocation, and participant blinding to outcome, will be maintained. The primary outcome measures are adherence to the home exercise programme with weekly collection of home exercise logs; achievement of individualised goals by phone interview before and after intervention; and correctness of exercise performance by collection and analysis of videos of participants performing home exercises. Secondary outcome measures include enjoyment of physical activity, confidence to complete exercise programme, preferred method of delivery of programme and usability of Physitrack. A sample size of 58 participants will be necessary to see an effect on home programme adherence. Data will be analysed using the intention-to-treat principle. Ethics and dissemination: Ethical approval was obtained from Curtin University Human Research Ethics Committee in July 2016 (10391). Outcomes will be disseminated through publication in peer-reviewed journals and presentations at scientific conferences. Trial registration number: ACTRN12616000743460; Pre-results

pH-responsive nanocomposite fibres allowing MRI monitoring of drug release

Magnetic resonance imaging (MRI) is one of the most widely-used non-invasive clinical imaging tools, producing detailed anatomical images whilst avoiding side effects such as trauma or X-ray radiation exposure. In this article, a new approach to non-invasive monitoring of drug release from a drug delivery vehicle via MRI was developed, using pH-responsive Eudragit L100 and S100 fibres encapsulating superparamagnetic iron oxide nanoparticles (SPIONs) and carmofur (a drug used in the treatment of colon cancer). Fibres were prepared by electrospinning, and found to be smooth and cylindrical with diameters of 645 ± 225 nm for L100 and 454 ± 133 nm for S100. The fibres exhibited pH responsive dissolution behaviour. Around the physiological pH range, clear pH-responsive proton relaxation rate changes due to matrix swelling/dissolution can be observed: r2 values of L100 fibres increase from 29.3 ± 8.3 to 69.8 ± 2.5 mM-1s-1 over 3 h immersion in a pH 7.4 medium, and from 13.5 ± 2.0 mM-1 s-1 to 42.1 ± 3.0 mM-1 s-1 at pH 6.5. The r2 values of S100 fibres grow from 30.4 ± 4.4 to 64.7 ± 1.0 mM-1 s-1 at pH 7.4, but at pH 6.5, where the S100 fibres are not soluble, r2 remains very low ( 0.94) between the two. Mathematical equations were developed to predict carmofur release in vitro, with very similar experimental and predicted release profiles obtained. Therefore, the formulations developed herein have the potential to be used for non-invasive monitoring of drug release in vivo, and could ultimately result in dramatic reductions to off-target side effects from interventions such as chemotherapy

SiO₂-coated layered gadolinium hydroxides for simultaneous drug delivery and magnetic resonance imaging

Layered gadolinium hydroxides (LGdH) have significant potential in simultaneous drug delivery and magnetic resonance imaging (MRI). In this work, we synthesized LGdH nanocomposites surface functionalised with SiO₂ nanodots (LGdH@SiO₂). We find these to have good dispersibility in cell culture medium, and a reduced tendency to aggregate compared to their uncoated analogue. Under the optimal reaction conditions, SiO₂ nanodots were evenly spread across the surface of the LGdH particles. We further intercalated ibuprofen (Ibu) and 5-fluorouracil (5FU) into LGdH@SiO₂, and explored the use of the resultant composites for drug delivery in vitro. While the SiO₂ coating could effectively reduce aggregation of the Ibu intercalate prepared by ion exchange from the parent LGdH, it was noted to increase aggregation in the case of the 5FU-loaded systems produced by coprecipitation. With a SiO₂ coating, 5FU release from the composite was almost zero-order at pH 7.4. The LGdH-5FU@SiO₂ composites can effectively inhibit the growth of A549 cells (a human adenocarcinoma cell line). In contrast, the Ibu-loaded materials are highly biocompatible. After SiO₂ modification, LGdH-5FU@SiO₂ retains the same proton relaxivity properties as LGdH-5FU, while LGdH-Ibu@SiO₂ ecomes suitable for use as a negative contrast agent in MRI. Overall, we find the LGdH@SiO₂ nanocomposites are promising materials for theranostic applications

Influence of solvent in crystal engineering : a significant change to the order–disorder transition in ferrocene

We present the structure of a novel solvate adduct formed by dissolving ferrocene, FeCp2, in hexafluorobenzene, C6F6. This adduct demonstrates the remarkably strong interactions between the five-membered aromatic rings of FeCp2 and the six-membered aromatic ring of C6F6. These molecular interactions are sufficiently strong and anisotropic to change the temperature of the order–disorder transition of the ferrocene molecule from below ca. 164 K to RT. No solvate adduct could be formed between benzene and FeCp2. These observations will be of particular relevance to the crystal engineering community, whose goal is the design of solids with bespoke properties

Effect of sedimentary heterogeneities in the sealing formation on predictive analysis of geological CO₂ storage

Numerical models of geologic carbon sequestration (GCS) in saline aquifers use multiphase fluid flow-characteristic curves (relative permeability and capillary pressure) to represent the interactions of the non-wetting CO2 and the wetting brine. Relative permeability data for many sedimentary formations is very scarce, resulting in the utilisation of mathematical correlations to generate the fluid flow characteristics in these formations. The flow models are essential for the prediction of CO2 storage capacity and trapping mechanisms in the geological media. The observation of pressure dissipation across the storage and sealing formations is relevant for storage capacity and geomechanical analysis during CO2 injection. This paper evaluates the relevance of representing relative permeability variations in the sealing formation when modelling geological CO2 sequestration processes. Here we concentrate on gradational changes in the lower part of the caprock, particularly how they affect pressure evolution within the entire sealing formation when duly represented by relative permeability functions. The results demonstrate the importance of accounting for pore size variations in the mathematical model adopted to generate the characteristic curves for GCS analysis. Gradational changes at the base of the caprock influence the magnitude of pressure that propagates vertically into the caprock from the aquifer, especially at the critical zone (i.e. the region overlying the CO2 plume accumulating at the reservoir-seal interface). A higher degree of overpressure and CO2 storage capacity was observed at the base of caprocks that showed gradation. These results illustrate the need to obtain reliable relative permeability functions for GCS, beyond just permeability and porosity data. The study provides a formative principle for geomechanical simulations that study the possibility of pressure-induced caprock failure during CO2 sequestration

The supernova rate and delay time distribution in the Magellanic Clouds

We use the supernova remnants (SNRs) in the Magellanic Clouds (MCs) as a supernova (SN) survey, "conducted" over tens of kyr, from which we derive the current SN rate, and the SN delay time distribution (DTD), i.e., the SN rate vs. time that would follow a hypothetical brief burst of a star formation. In Badenes, Maoz, & Draine (2010) we have compiled a list of 77 SNRs in the MCS, and argued it is a fairly complete record of the SNRs in the Sedov phase of their expansions. We recover the DTD by comparing the numbers of SNRs observed in small individual "cells" in these galaxies to the star-formation histories of each cell, as calculated from resolved stellar populations by Harris & Zaritsky. The visibility times of SNRs are the Sedov-phase lifetimes, which depend on the local ambient densities. The local densities are estimated from HI emission, from an inverse Schmidt law based on either Halpha flux or on the resolved star-formation rate, and from combinations of these tracers. In the DTD, we detect "prompt" type-Ia SNe (that explode within 330 Myr of star formation) at >99% confidence level (c.l.). The best fit for the number of prompt SNe-Ia per stellar mass formed is (2.7-11.0) x 10^{-3} /Msun, depending on the density tracer used. The 95% c.l. range for a "delayed" SN Ia component (from 330 Myr to a Hubble time) is < 1.6 x 10^{-13} SN/yr/Msun, consistent with rate measurements in old populations. The current total (core-collapse+Ia) SN rate in the MCs is 2.5-4.6 SNe per millenium (68% c.l.+systematics), or 1.7-3.1 SNuM [SNe/100 yr/10^{10}Msun], in agreement with the historical record and with rates measured in other dwarf irregulars. Conversely, assuming the SNRs are in free expansion, rather than in their Sedov phase, would impose on the SNRs a maximum age of 6 kyr, and would imply a MC SN rate per unit mass that is 5 times higher than in any type of galaxy.Comment: MNRAS, in pres

Engineering an improved light-induced dimer (iLID) for controlling the localization and activity of signaling proteins

Photoactivatable proteins are powerful tools for studying biological processes. Light-induced dimers are especially useful because they can be turned on and off with high spatial and temporal resolution in living systems, allowing for control of protein localization and activity. Here, we develop and apply methods for identifying mutations that improve the effectiveness of a light-induced dimer. The engineered switch is modular, can be used in most organisms, has more than 50-fold change in binding affinity upon light stimulation, and can be used to initiate signaling pathways in a specific region of a cell

Validation of a stochastic digital packing algorithm for porosity prediction in fluvial gravel deposits

Porosity as one of the key properties of sediment mixtures is poorly understood. Most of the existing porosity predictors based upon grain size characteristics have been unable to produce satisfying results for fluvial sediment porosity, due to the lack of consideration of other porosity-controlling factors like grain shape and depositional condition. Considering this, a stochastic digital packing algorithm was applied in this work, which provides an innovative way to pack particles of arbitrary shapes and sizes based on digitization of both particles and packing space. The purpose was to test the applicability of this packing algorithm in predicting fluvial sediment porosity by comparing its predictions with outcomes obtained from laboratory measurements. Laboratory samples examined were two natural fluvial sediments from the Rhine River and Kall River (Germany), and commercial glass beads (spheres). All samples were artificially combined into seven grain size distributions: four unimodal distributions and three bimodal distributions. Our study demonstrates that apart from grain size, grain shape also has a clear impact on porosity. The stochastic digital packing algorithm successfully reproduced the measured variations in porosity for the three different particle sources. However, the packing algorithm systematically overpredicted the porosity measured in random dense packing conditions, mainly because the random motion of particles during settling introduced unwanted kinematic sorting and shape effects. The results suggest that the packing algorithm produces loose packing structures, and is useful for trend analysis of packing porosity

The role of tides in beach cusp development

Author Posting. © American Geophysical Union, 2004. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 109 (2004): C04011, doi:10.1029/2003JC002154.Field measurements of morphology and swash flow during three episodes of beach cusp development indicate that tides modulate the height and cross-shore position of beach cusps. During rising tide, beach cusp height decreases as embayments accrete more than horns and the cross-shore extent of beach cusps decreases. During falling tide, beach cusp height increases as embayments erode more than horns and cross-shore extent increases. A numerical model for beach cusp formation based on self-organization, extended to include the effects of morphological smoothing seaward of the swash front and infiltration into the beach, reproduces the observed spacing, position, and tidal modulation. During rising tide, water particles simulating swash infiltrate, preferentially in embayments, causing enhanced deposition. During falling tide, exfiltration of water particles combined with diversion of swash from horns causes enhanced erosion in embayments. Smoothing of beach morphology in the swash zone seaward of the swash front and in the shallow surf zone accounts for most of the observed tidal modulation, even in the absence of infiltration and exfiltration. Despite the qualitative, and in some cases quantitative, agreement of the model and measurements, the model fails to reproduce observed large deviations of horn orientation from shore normal, some aspects of beach cusp shape, and deviations from the basic tidal modulation, possibly because of the simplified parameterization of cross-shore sediment transport and the neglect of the effects of sea surface gradients on flow.Field experiments supported by an Office of Naval Research (ONR) Young Investigator Award (N00014-92-J-1446) and ONR, Coastal Dynamics. Data analysis and numerical simulations supported by an ONR Young Investigator Award and a Navy/ONR Scholar Award (N00014-97-1-0154). Manuscript preparation supported by a Navy/ONR Scholar Award, ONR Coastal Geosciences, the Army Research Office, and the National Ocean Partnership Program. GC also supported by the (New Zealand) Foundation for Research, Science and Technology (contract CO1X0218)