Unpulsed UBV Optical Emission from the Crab Pulsar

Based on observations of the Crab pulsar using the TRIFFID high speed imaging photometer in the UBV bands using the Special Astrophysical Observatory's 6m telescope in the Russian Caucasus, we report the detection of pronounced emission during the so-called `off' phase of emission. Following de-extinction, this unpulsed component of emission is shown to be consistent with a power law with an exponent of alpha = -0.60 +/- 0.37, the uncertainty being dominated by the error associated with the independent CCD photometry used to reference the TRIFFID data. This suggests a steeper power law form than that reported elsewhere in the literature for the total integrated spectrum, which is essentially flat with alpha ~ 0.1, although the difference in this case is only significant at the ~ 2 sigma level. Deeper reference integrated and TRIFFID phase-resolved photometry in these bands in conjunction with further observations in the UV and R region would constrain this fit further.Comment: 26 pages, 2 figures, uses aasms4.sty, accepted for publication in the Astrophysical Journa

Using Administrative Data to Count Local Populations

There is growing evidence that official population statistics based on the decennial census are inaccurate at the local authority level—the fundamental administrative unit of the UK. This paper investigates the use of locally available administrative data sets for counting populations. The method uses truth tables for combining different data sources with different population coverage according to a defined and therefore replicable set of rules. The result is timelier and geographically more flexible data which is more cost-effective to produce than a survey-based census. Associated techniques for linking diverse data sources at individual and household level are briefly discussed. The methodology is then applied to administrative data from a London borough with about 170,000 people. The results are evaluated and compared with other population sources. The paper concludes by discussing potential improvements including scaling up the work to cover multiple local authorities. The practicalities of using alternative central government data sets are briefly considered. A sequel paper in this journal provides examples of key applications of this approach at local level

RESPOND – A patient-centred programme to prevent secondary falls in older people presenting to the emergency department with a fall: Protocol for a mixed methods programme evaluation.

Background Programme evaluations conducted alongside randomised controlled trials (RCTs) have potential to enhance understanding of trial outcomes. This paper describes a multi-level programme evaluation to be conducted alongside an RCT of a falls prevention programme (RESPOND). Objectives 1) To conduct a process evaluation in order to identify the degree of implementation fidelity and associated barriers and facilitators. 2) To evaluate the primary intended impact of the programme: participation in fall prevention strategies, and the factors influencing participation. 3) To identify the factors influencing RESPOND RCT outcomes: falls, fall injuries and ED re-presentations. Methods/ Design Five hundred and twenty eight community-dwelling adults aged 60–90 years presenting to two EDs with a fall will be recruited and randomly assigned to the intervention or standard care group. All RESPOND participants and RESPOND clinicians will be included in the evaluation. A mixed methods design will be used and a programme logic model will frame the evaluation. Data will be sourced from interviews, focus groups, questionnaires, clinician case notes, recruitment records, participant-completed calendars, hospital administrative datasets, and audio-recordings of intervention contacts. Quantitative data will be analysed via descriptive and inferential statistics and qualitative data will be interpreted using thematic analysis. Discussion The RESPOND programme evaluation will provide information about contextual and influencing factors related to the RCT outcomes. The results will assist researchers, clinicians, and policy makers to make decisions about future falls prevention interventions. Insights gained are likely to be transferable to preventive health programmes for a range of chronic conditions

Mechanical suppression of osteolytic bone metastases in advanced breast cancer patients: A randomised controlled study protocol evaluating safety, feasibility and preliminary efficacy of exercise as a targeted medicine

Background: Skeletal metastases present a major challenge for clinicians, representing an advanced and typically incurable stage of cancer. Bone is also the most common location for metastatic breast carcinoma, with skeletal lesions identified in over 80% of patients with advanced breast cancer. Preclinical models have demonstrated the ability of mechanical stimulation to suppress tumour formation and promote skeletal preservation at bone sites with osteolytic lesions, generating modulatory interference of tumour-driven bone remodelling. Preclinical studies have also demonstrated anti-cancer effects through exercise by minimising tumour hypoxia, normalising tumour vasculature and increasing tumoural blood perfusion. This study proposes to explore the promising role of targeted exercise to suppress tumour growth while concomitantly delivering broader health benefits in patients with advanced breast cancer with osteolytic bone metastases. Methods: This single-blinded, two-armed, randomised and controlled pilot study aims to establish the safety, feasibility and efficacy of an individually tailored, modular multi-modal exercise programme incorporating spinal isometric training (targeted muscle contraction) in 40 women with advanced breast cancer and stable osteolytic spinal metastases. Participants will be randomly assigned to exercise or usual medical care. The intervention arm will receive a 3-month clinically supervised exercise programme, which if proven to be safe and efficacious will be offered to the control-arm patients following study completion. Primary endpoints (programme feasibility, safety, tolerance and adherence) and secondary endpoints (tumour morphology, serum tumour biomarkers, bone metabolism, inflammation, anthropometry, body composition, bone pain, physical function and patient-reported outcomes) will be measured at baseline and following the intervention. Discussion: Exercise medicine may positively alter tumour biology through numerous mechanical and nonmechanical mechanisms. This randomised controlled pilot trial will explore the preliminary effects of targeted exercise on tumour morphology and circulating metastatic tumour biomarkers using an osteolytic skeletal metastases model in patients with breast cancer. The study is principally aimed at establishing feasibility and safety. If proven to be safe and feasible, results from this study could have important implications for the delivery of this exercise programme to patients with advanced cancer and sclerotic skeletal metastases or with skeletal lesions present in haematological cancers (such as osteolytic lesions in multiple myeloma), for which future research is recommended. Trial registration: anzctr.org.au, ACTRN-12616001368426. Registered on 4 October 2016

RESPOND – A patient-centred program to prevent secondary falls in older people presenting to the emergency department with a fall: Protocol for a multi-centre randomised controlled trial

Introduction: Participation in falls prevention activities by older people following presentation to the Emergency Department (ED) with a fall is suboptimal. This randomised controlled trial (RCT) will test the RESPOND program which is designed to improve older persons’ participation in falls prevention activities through delivery of patient-centred education and behaviour change strategies. Design and setting: An RCT at two tertiary referral EDs in Melbourne and Perth, Australia. Participants: Five-hundred and twenty eight community-dwelling people aged 60-90 years presenting to the ED with a fall and discharged home will be recruited. People who: require an interpreter or hands-on assistance to walk; live in residential aged care or >50 kilometres from the trial hospital; have terminal illness, cognitive impairment, documented aggressive behaviour or history of psychosis; are receiving palliative care; or are unable to use a telephone will be excluded. Methods: Participants will be randomly allocated to the RESPOND intervention or standard care control group. RESPOND incorporates: (1) home-based risk factor assessment; (2) education, coaching, goal setting, and follow-up telephone support for management of one or more of four risk factors with evidence of effective intervention; and (3) healthcare provider communication and community linkage delivered over six months. Primary outcomes are falls and fall injuries per-person-year. Discussion: RESPOND builds on prior falls prevention learnings and aims to help individuals make guided decisions about how they will manage their falls risk. Patient-centred models have been successfully trialled in chronic and cardiovascular disease however evidence to support this approach in falls prevention is limited. Trial registration. The protocol for this study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12614000336684)

Structure and elastic properties of Mg(OH)2_2 from density functional theory

The structure, lattice dynamics and mechanical properties of the magnesium hydroxide have been investigated with static density functional theory calculations as well as \it {ab initio} molecular dynamics. The hypothesis of a superstructure existing in the lattice formed by the hydrogen atoms has been tested. The elastic constants of the material have been calculated with static deformations approach and are in fair agreement with the experimental data. The hydrogen subsystem structure exhibits signs of disordered behaviour while maintaining correlations between angular positions of neighbouring atoms. We establish that the essential angular correlations between hydrogen positions are maintained to the temperature of at least 150 K and show that they are well described by a physically motivated probabilistic model. The rotational degree of freedom appears to be decoupled from the lattice directions above 30K

Pressure-induced oversaturation and phase transition in zeolitic imidazolate frameworks with remarkable mechanical stability.

Zeolitic imidazolate frameworks (ZIFs) 7 and 9 are excellent candidates for CO2 adsorption and storage. Here, high-pressure X-ray diffraction is used to further understand their potential in realistic industrial applications. ZIF-7 and ZIF-9 are shown be able to withstand high hydrostatic pressures whilst retaining their porosity and structural integrity through a new ferroelastic phase transition. This stability is attributed to the presence of sterically large organic ligands. Results confirm the notable influence of guest occupancy on the response of ZIFs to pressure; oversaturation of ZIFs with solvent molecules greatly decreases their compressibility and increases their resistance to amorphisation. By comparing the behaviours of both ZIFs under high pressure, it is demonstrated that their mechanical stability is not affected by metal substitution. The evacuated ZIF-7 phase, ZIF-7-II, is shown to be able to recover to the ZIF-7 structure with excellent resistance to pressure. Examining the pressure-related structural behaviours of ZIF-7 and ZIF-9, we have assessed the great industrial potential of ZIFs.This work was supported by the Cambridge Commonwealth, European and International Trust; China Scholarship Council; Trinity Hall, University of Cambridge; UK Science & Technology Facilities Council. We thank anonymous reviewers for their valuable suggestions on the improvement of this manuscript.This is the final version of the article. It first appeared from the Royal Society of Chemistry via http://dx.doi.org/10.1039/C4DT02680

FLORA: a novel method to predict protein function from structure in diverse superfamilies

Predicting protein function from structure remains an active area of interest, particularly for the structural genomics initiatives where a substantial number of structures are initially solved with little or no functional characterisation. Although global structure comparison methods can be used to transfer functional annotations, the relationship between fold and function is complex, particularly in functionally diverse superfamilies that have evolved through different secondary structure embellishments to a common structural core. The majority of prediction algorithms employ local templates built on known or predicted functional residues. Here, we present a novel method (FLORA) that automatically generates structural motifs associated with different functional sub-families (FSGs) within functionally diverse domain superfamilies. Templates are created purely on the basis of their specificity for a given FSG, and the method makes no prior prediction of functional sites, nor assumes specific physico-chemical properties of residues. FLORA is able to accurately discriminate between homologous domains with different functions and substantially outperforms (a 2–3 fold increase in coverage at low error rates) popular structure comparison methods and a leading function prediction method. We benchmark FLORA on a large data set of enzyme superfamilies from all three major protein classes (α, β, αβ) and demonstrate the functional relevance of the motifs it identifies. We also provide novel predictions of enzymatic activity for a large number of structures solved by the Protein Structure Initiative. Overall, we show that FLORA is able to effectively detect functionally similar protein domain structures by purely using patterns of structural conservation of all residues

Enhancing circulatory myokines and extracellular vesicle uptake with targeted exercise in patients with prostate cancer (the MYEX trial): A single-group crossover study

Introduction: Physical activity is associated with improved disease progression and cancer-specific survival in patients with prostate cancer (PCa). However, the mechanisms underlying these associations remain unclear, while the relative impact of exercise modes is unknown. This study aims to examine the differential impact of exercise mode on tumour-suppressive skeletal muscle-associated systemic molecules as well as their delivery mechanism. This study will compare the effects of the two main exercise modes, aerobic and resistance, on (1) circulatory myokine levels, (2) skeletal muscle-induced extracellular vesicle abundance and cargo contents, and (3) uptake of extracellular vesicles (EVs) in PCa cells in patients with localised or advanced PCa. Methods: A single-group cross-over design will be used for patients at opposite ends of the disease spectrum. A total of 32 patients (localised PCa, n = 16; metastatic castrate-resistant PCa, n = 16) will be recruited while capitalising on two ongoing studies. Ethics amendment has been approved for two ongoing trials to share data, implement the acute exercise sessions, and collect additional blood samples from patients. The patients will undertake two exercise sessions (aerobic only and resistance only) in random order one week apart. Blood will be collected before, after, and 30 min post-exercise. Circulating/EV-contained myokine levels (irisin, IL-6, IL-15, FGF-21, and SPARC) and plasma skeletal muscle-induced EVs will be measured using ELISA and flow cytometry. PCa cell line growth with or without collected plasma will be examined using PCa cell lines (LNCaP, DU-145, and PC-3), while evaluating cellular uptake of EVs. Ethics amendments have been approved for two capitalising studies to share data, implement acute exercise sessions and collect additional samples from the patients. Discussion: If findings show a differential impact of exercise mode on the establishment of an anti-cancer systemic environment, this will provide fundamental knowledge for developing targeted exercise prescriptions for patients with PCa across different disease stages. Findings will be reported in peer-reviewed publications and scientific conferences, in addition to working with national support groups to translate findings for the broader community. Trial registration: The registration for the two capitalising studies are NCT02730338 and ACTRN12618000225213