Synthesis, characterization and modelling of zinc and silicate co-substituted hydroxyapatite.

Experimental chemistry and atomic modelling studies were performed here to investigate a novel ionic co-substitution in hydroxyapatite (HA). Zinc, silicate co-substituted HA (ZnSiHA) remained phase pure after heating to 1100 °C with Zn and Si amounts of 0.6 wt% and 1.2 wt%, respectively. Unique lattice expansions in ZnSiHA, silicate Fourier transform infrared peaks and changes to the hydroxyl IR stretching region suggested Zn and silicate co-substitution in ZnSiHA. Zn and silicate insertion into HA was modelled using density functional theory (DFT). Different scenarios were considered where Zn substituted for different calcium sites or at a 2b site along the c-axis, which was suspected in singly substituted ZnHA. The most energetically favourable site in ZnSiHA was Zn positioned at a previously unreported interstitial site just off the c-axis near a silicate tetrahedron sitting on a phosphate site. A combination of experimental chemistry and DFT modelling provided insight into these complex co-substituted calcium phosphates that could find biomedical application as a synthetic bone mineral substitute.This work was supported by a NSFGRFP grant (DGE-1042796) (RJF) and a Cambridge International Scholarship (RJF). The modelling work was performed using the Darwin Supercomputer of the University of Cambridge High Performance Computing Service (http://www.hpc.cam.ac.uk/), provided by Dell Inc. using Strategic Research Infrastructure Funding from the Higher Education Funding Council for England and funding from the Science and Technology Facilities Council. HC would like to thank the UK Medical Research Council (Grant number U105960399) for their support.This is the final version of the article. It first appeared from Royal Society Publishing via http://dx.doi.org/10.1098/rsif.2015.019

Searching for Clusters with SUMSS

Statistical overdensities of radiosources in the Sydney University Molonglo Sky Survey (SUMSS) are used as signposts to identify high-redshift clusters of galaxies. These potential clusters have been observed at 20 and 13 cm at the Australia Telescope Compact Array (ATCA) to obtain better positional accuracy for the sources. A subsample have been imaged in V, R and I at the 2.3-m telescope at Siding Spring and in J and K at the Anglo Australian Telescope (AAT) and the New Technology Telescope (NTT) at La Silla, Chile. The colours obtained from these observations will be used to estimate redshifts for the potential cluster members.Comment: LaTeX, 5 pages, 4 figures Elsevier Science format. To appear in "Radio galaxies: past, present & future". eds. M. Jarvis et al., Leiden, Nov 200

Effect of classroom-based physical activity interventions on academic and physical activity outcomes: a systematic review and meta-analysis

BACKGROUND: Physical activity is associated with many physical and mental health benefits, however many children do not meet the national physical activity guidelines. While schools provide an ideal setting to promote children\u27s physical activity, adding physical activity to the school day can be difficult given time constraints often imposed by competing key learning areas. Classroom-based physical activity may provide an opportunity to increase school-based physical activity while concurrently improving academic-related outcomes. The primary aim of this systematic review and meta-analysis was to evaluate the impact of classroom-based physical activity interventions on academic-related outcomes. A secondary aim was to evaluate the impact of these lessons on physical activity levels over the study duration. METHODS: A systematic search of electronic databases (PubMed, ERIC, SPORTDiscus, PsycINFO) was performed in January 2016 and updated in January 2017. Studies that investigated the association between classroom-based physical activity interventions and academic-related outcomes in primary (elementary) school-aged children were included. Meta-analyses were conducted in Review Manager, with effect sizes calculated separately for each outcome assessed. RESULTS: Thirty-nine articles met the inclusion criteria for the review, and 16 provided sufficient data and appropriate design for inclusion in the meta-analyses. Studies investigated a range of academic-related outcomes including classroom behaviour (e.g. on-task behaviour), cognitive functions (e.g. executive function), and academic achievement (e.g. standardised test scores). Results of the meta-analyses showed classroom-based physical activity had a positive effect on improving on-task and reducing off-task classroom behaviour (standardised mean difference = 0.60 (95% CI: 0.20,1.00)), and led to improvements in academic achievement when a progress monitoring tool was used (standardised mean difference = 1.03 (95% CI: 0.22,1.84)). However, no effect was found for cognitive functions (standardised mean difference = 0.33 (95% CI: -0.11,0.77)) or physical activity (standardised mean difference = 0.40 (95% CI: -1.15,0.95)). CONCLUSIONS: Results suggest classroom-based physical activity may have a positive impact on academic-related outcomes. However, it is not possible to draw definitive conclusions due to the level of heterogeneity in intervention components and academic-related outcomes assessed. Future studies should consider the intervention period when selecting academic-related outcome measures, and use an objective measure of physical activity to determine intervention fidelity and effects on overall physical activity levels

Effect of audibility on spatial release from speech-on-speech masking

This study investigated to what extent spatial release from masking (SRM) deficits in hearing-impaired adults may be related to reduced audibility of the test stimuli. Sixteen adults with sensorineural hearing loss and 28 adults with normal hearing were assessed on the Listening in Spatialized Noise–Sentences test, which measures SRM using a symmetric speech-on-speech masking task. Stimuli for the hearing-impaired listeners were delivered using three amplification levels (National Acoustic Laboratories - Revised Profound prescription (NAL-RP) +25%, and NAL-RP +50%), while stimuli for the normal-hearing group were filtered to achieve matched audibility. SRM increased as audibility increased for all participants. Thus, it is concluded that reduced audibility of stimuli may be a significant factor in hearing-impaired adults' reduced SRM even when hearing loss is compensated for with linear gain. However, the SRM achieved by the normal hearers with simulated audibility loss was still significantly greater than that achieved by hearing-impaired listeners, suggesting other factors besides audibility may still play a role

What do people with aphasia want to be able to say? A content analysis of words identified as personally relevant by people with aphasia

Background Word finding is a common difficulty for people with aphasia. Targeting words that are relevant to the individual could maximise the usefulness and impact of word finding therapy. Aims To provide insights into words that people with aphasia perceive to be personally relevant. Methods and procedures 100 people with aphasia were each asked to identify 100 words that would be particularly important for them to be able to say. Two speech and language therapist researchers conducted a quantitative content analysis of the words selected. The words were coded into a framework of topics and subtopics. The frequency with which different words and topics were selected was then calculated. Outcomes and results 100 participants representing 20 areas of the United Kingdom ranged in age from 23 to 85 years. Word finding difficulties ranged from mild to severe. The sample of 9999 words selected for practice included 3095 different words in 27 topics. The majority of words selected (79.4%) were from the topics ‘food and drink’ (30.6%), ‘nature and gardening’ (10.3%), ‘entertainment’ (9.4%), ‘places’ (7.3%), ‘people’ (6.7%), ‘house’ (6.5%), ‘clothes’ (5.2%) and ‘travel’ (3.5%). The 100 words types chosen with the greatest frequency were identified. These account for 27 percent of the 9999 words chosen by the participants. Discussion Personally relevant vocabulary is unique to each individual and is likely to contain specific or specialist words for which material needs to be individually prepared. However there is some commonality in the words chosen by people with aphasia. This could inform pre-prepared materials for use in word finding therapy from which personally relevant words could be selected for practice

Revised Modelling of the Addition of Synchronous Chemotherapy to Radiotherapy in Squamous Cell Carcinoma of the Head and Neck-A Low ?

Background: The effect of synchronous chemotherapy in squamous cell carcinoma of the head and neck (SCCHN) has been modelled as additional Biologically Effective Dose (BED) or as a prolonged tumour cell turnover time during accelerated repopulation. Such models may not accurately predict the local control seen when hypofractionated accelerated radiotherapy is used with synchronous chemotherapy. Methods: For the purposes of this study three isoeffect relationships were assumed: Firstly, from the RTOG 0129 trial, synchronous cisplatin chemotherapy with 70 Gy in 35 fractions over 46 days results in equivalent local control to synchronous cisplatin chemotherapy with 36 Gy in 18# followed by 36 Gy in 24# (2# per day) over a total of 39 days. Secondly, in line with primary local control outcomes from the PET-Neck study, synchronous cisplatin chemotherapy with 70 Gy in 35# over 46 days results in equivalent local control to synchronous cisplatin chemotherapy delivered with 65 Gy in 30# over 39 days. Thirdly, from meta-analysis data, 70 Gy in 35# over 46 days with synchronous cisplatin results in equivalent local control to 84 Gy in 70# over 46 days delivered without synchronous chemotherapy. Using the linear quadratic equation the above isoeffect relationships were expressed algebraically to determine values of α, α/β, and k for SCCHN when treated with synchronous cisplatin using standard parameters for the radiotherapy alone schedule (α = 0.3 Gy−1, α/β = 10 Gy, and k = 0.42 Gy10day−1). Results: The values derived for α/β, α and k were 2 Gy, 0.20 and 0.21 Gy−1, and 0.65 and 0.71 Gy2day−1. Conclusions: Within the limitations of the assumptions made, this model suggests that accelerated repopulation may remain a significant factor when synchronous chemotherapy is delivered with radiotherapy in SCCHN. The finding of a low α/β for SCCHN treated with cisplatin suggests a greater tumour susceptibility to increasing dose per fraction and underlines the importance of the completion of randomized trials examining the role of hypofractionated acceleration in SCCHN

Interleukin-1β Produced in Response to Islet Autoantigen Presentation Differentiates T-Helper 17 Cells at the Expense of Regulatory T-Cells: Implications for the Timing of Tolerizing Immunotherapy

OBJECTIVE-The effectiveness of tolerizing immunotherapeutic strategies, such as anti-CD40L or dendritic cells (DCs), is greater when administered to young nonobese diabetic (NOD) mice than at peak insulitis. RelB(lo) DCs, generated in the presence of an nuclear factor-kappa B inhibitor, induce T-regulatory (Treg) cells and suppress inflammation in a model of rheumatoid arthritis. Interleukin (IL)-1 beta is overexpressed in humans and mice at risk of type 1 diabetes, dysregulates Treg cells, and accelerates diabetes in NOD mice. We investigated the relationship between IL-1 beta production and the response to RelB(lo) DCs in the prediabetic period

Cellular response to collagen-elastin composite materials.

Collagen is used extensively in tissue engineering due to its biocompatibility, near-universal tissue distribution, low cost and purity. However, native tissues are composites that include diverse extracellular matrix components, which influence strongly their mechanical and biological properties. Here, we provide important new findings on the differential regulation, by collagen and elastin, of the bio-response to the composite material. Soluble and insoluble elastin had differing effects on the stiffness and failure strength of the composite films. We established that Rugli cells bind elastin via EDTA-sensitive receptors, whilst HT1080 cells do not. These cells allowed us to probe the contribution of collagen alone (HT1080) and collagen plus elastin (Rugli) to the cellular response. In the presence of elastin, Rugli cell attachment, spreading and proliferation increased, presumably through elastin-binding receptors. By comparison, the attachment and spreading of HT1080 cells was modified by elastin inclusion, but without affecting their proliferation, indicating indirect modulation by elastin of the response of cells to collagen. These new insights highlight that access to elastin dominates the cellular response when elastin-binding receptors are present. In the absence of these receptors, modification of the collagen component and/or physical properties dictate the cellular response. Therefore, we can attribute the contribution of each constituent on the ultimate bioactivity of heterogeneous collagen-composite materials, permitting informed, systematic biomaterials design. Statement of Significance In recent years there has been a desire to replicate the complex extracellular matrix composition of tissues more closely, necessitating the need for composite protein-based materials. In this case both the physical and biochemical properties are altered with the addition of each component, with potential consequences on the cell. To date, the different contributions of each component have not been deconvolved, and instead the cell response to the scaffold as a whole has been observed. Instead, here, we have used specific cell lines, that are sensitive to specific components of an elastin-collagen composite, to resolve the bio-activity of each protein. This has shown that elastin-induced alteration of the collagen component can modulate early stage cell behaviour. By comparison the elastin component directly alters the cell response over the short and long term, but only where appropriate receptors are present on the cell. Due to the widespread use of collagen and elastin, we feel that this data permits, for the first time, the ability to systematically design collagen-composite materials to promote desired cell behaviour with associated advantages for biomaterials fabrication.This work was supported by the ERC Advanced Grant 320598 3D-E, EPSRC fellowship EP/N019938/1, and British Heart Foundation Special ProjectSP/15/7/31561 D. V. Bax was funded by the Peoples Programme of the EU 7th Framework Programme (RAE no: PIIF-GA-2013-624904)

Pelvic floor muscle training for women with pelvic organ prolapse: the PROPEL realist evaluation

Background Pelvic organ prolapse is estimated to affect 41–50% of women aged > 40 years. A multicentre randomised controlled trial of individualised pelvic floor muscle training found that pelvic floor muscle training was effective in reducing symptoms of prolapse, improved quality of life and showed clear potential to be cost-effective. Provision of pelvic floor muscle training for prolapse has continued to vary across the UK, with limited availability of specialist physiotherapists to deliver it. Objectives This project aimed to study the implementation and outcomes of different models of delivery to increase the service provision of pelvic floor muscle training, and to follow up treatment outcomes for the original trial participants. Design A realist evaluation of pelvic floor muscle training implementation conducted within three full case study sites and two partial case study sites; an observational prospective cohort study comparing patient-reported outcomes pre and post intervention in all five sites; and a long-term follow-up study linking previous trial participants to routine NHS hospital data. Setting The setting for the realist evaluation was pelvic floor muscle training service delivery models in three NHS sites. The setting for the patient-reported outcome measures study was pelvic floor muscle training services in five NHS sites. Methods Realist evaluation qualitative data were collected at four time points in three case study sites to understand the implementation models, uptake, adherence and impact. Interviews involved service managers/leads, consultants, staff delivering pelvic floor muscle training and women receiving pelvic floor muscle training. Main outcomes measures Patient-reported outcomes were collected at baseline and at 6 and 12 months across five sites, including the Pelvic Organ Prolapse Symptom Score, health-related quality of life (measured using the EuroQol-5 Dimensions, five-level version, questionnaire), prolapse severity (measured using the Pelvic Organ Prolapse Quantification System), urinary incontinence (measured using International Consultation on Incontinence Questionnaire – Urinary Incontinence Short Form) and need for further treatment. Results A total of 102 women were recruited to the patient-reported outcome measures cohort study (target, n = 120), and 65 women had matched baseline and 6-month Pelvic Organ Prolapse Symptom Scores. The mean Pelvic Organ Prolapse Symptom Score was 10.18 (standard deviation 5.63) at baseline and 6.98 (standard deviation 5.23) at 6 months, representing a statistically significant and clinically meaningful difference. There was no statistically significant difference between the outcomes obtained from delivery by specialist physiotherapists and the outcomes obtained from delivery by other health-care professionals (mean change in Pelvic Organ Prolapse Symptom Score: –3.95 vs. –2.81, respectively). Services delivered using higher-band physiotherapists only were more costly than services delivered using other staff mixes. The effect of the original pelvic floor muscle training intervention, over a post-intervention period of > 10 years, was a reduction in the odds of any treatment during follow-up (odds ratio 0.61, 95% confidence interval 0.37 to 0.99). The realist evaluation revealed stark differences in implementation. The site with a specialist physiotherapy service resisted change because of perceived threats to the specialist role and concerns about care quality. Pelvic floor muscle training delivery by other health-care staff was easier when there was a lack of any existing specialist service; staff had prior training and interest in pelvic health; staff had support, autonomy, time and resources to deliver pelvic floor muscle training as part of their core role; and surrounding services supported a flow of pelvic floor muscle training referrals. Limitations The number of available matched pre and post outcomes for women and the lack of Pelvic Organ Prolapse Quantification System examinations were limitations of this study. Conclusions It is possible to train different staff to effectively deliver pelvic floor muscle training to women. Women’s self-reported outcomes significantly improved across all service models. Training should be adequately tailored to differential skill mix needs. Future work Future work should include further implementation of pelvic floor muscle training and should include pre- and post-outcome data collection using the Pelvic Organ Prolapse Symptom Score

Effectiveness-implementation hybrid-2 randomised trial of a collaborative Shared Care Model for Detecting Neurodevelopmental Impairments after Critical Illness in Young Children (DAISY): pilot study protocol

INTRODUCTION In Australia, while paediatric intensive care unit (PICU) mortality has dropped to 2.2%, one in three survivors experience long-term neurodevelopmental impairment, limiting their life-course opportunities. Unlike other high-risk paediatric populations, standardised routine neurodevelopmental follow-up of PICU survivors is rare, and there is limited knowledge regarding the best methods. The present study intends to pilot a combined multidisciplinary, online screening platform and general practitioner (GP) shared care neurodevelopmental follow-up model to determine feasibility of a larger, future study. We will also assess the difference between neurodevelopmental vulnerability and parental stress in two intervention groups and the impact of child, parent, sociodemographic and illness/treatment risk factors on child and parent outcomes. METHODS AND ANALYSIS Single-centre randomised effectiveness-implementation (hybrid-2 design) pilot trial for parents of children aged ≥2 months and <4 years discharged from PICU after critical illness or injury. One intervention group will receive 6 months of collaborative shared care follow-up with GPs (supported by online outcome monitoring), and the other will be offered self-directed screening and education about post-intensive care syndrome and child development. Participants will be followed up at 1, 3 and 6 months post-PICU discharge. The primary outcome is feasibility. Secondary outcomes include neurodevelopmental vulnerability and parental stress. An implementation evaluation will analyse barriers to and facilitators of the intervention. ETHICS AND DISSEMINATION The study is expected to lead to a full trial, which will provide much-needed guidance about the clinical effectiveness and implementation of follow-up models of care for children after critical illness or injury. The Children's Health Queensland Human Research Ethics Committee approved this study. Dissemination of the outcomes of the study is expected via publication in a peer-reviewed journal, presentation at relevant conferences, and via social media, podcast presentations and open-access medical education resources. REGISTRATION DETAILS The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry as 'Pilot testing of a collaborative Shared Care Model for Detecting Neurodevelopmental Impairments after Critical Illness in Young Children' (the DAISY Pilot Study). TRIAL REGISTRATION NUMBER ACTRN12621000799853