High-performance 3D waveguide architecture for astronomical pupil-remapping interferometry

The detection and characterisation of extra-solar planets is a major theme driving modern astronomy, with the vast majority of such measurements being achieved by Doppler radial-velocity and transit observations. Another technique -- direct imaging -- can access a parameter space that complements these methods, and paves the way for future technologies capable of detailed characterization of exoplanetary atmospheres and surfaces. However achieving the required levels of performance with direct imaging, particularly from ground-based telescopes which must contend with the Earth's turbulent atmosphere, requires considerable sophistication in the instrument and detection strategy. Here we demonstrate a new generation of photonic pupil-remapping devices which build upon the interferometric framework developed for the {\it Dragonfly} instrument: a high contrast waveguide-based device which recovers robust complex visibility observables. New generation Dragonfly devices overcome problems caused by interference from unguided light and low throughput, promising unprecedented on-sky performance. Closure phase measurement scatter of only $\sim 0.2^\circ$ has been achieved, with waveguide throughputs of $> 70\%$. This translates to a maximum contrast-ratio sensitivity (between the host star and its orbiting planet) at $1 \lambda/D$ (1$\sigma$ detection) of $5.3 \times 10^{-4}$ (when a conventional adaptive-optics (AO) system is used) or $1.8 \times 10^{-4}$ (for typical `extreme-AO' performance), improving even further when random error is minimised by averaging over multiple exposures. This is an order of magnitude beyond conventional pupil-segmenting interferometry techniques (such as aperture masking), allowing a previously inaccessible part of the star to planet contrast-separation parameter space to be explored

Heterologous prime-boost-boost immunisation of Chinese cynomolgus macaques using DNA and recombinant poxvirus vectors expressing HIV-1 virus-like particles

Background: There is renewed interest in the development of poxvirus vector-based HIV vaccines due to the protective effect observed with repeated recombinant canarypox priming with gp120 boosting in the recent Thai placebo-controlled trial. This study sought to investigate whether a heterologous prime-boost-boost vaccine regimen in Chinese cynomolgus macaques with a DNA vaccine and recombinant poxviral vectors expressing HIV virus-like particles bearing envelopes derived from the most prevalent clades circulating in sub-Saharan Africa, focused the antibody response to shared neutralising epitopes. Methods: Three Chinese cynomolgus macaques were immunised via intramuscular injections using a regimen composed of a prime with two DNA vaccines expressing clade A Env/clade B Gag followed by boosting with recombinant fowlpox virus expressing HIV-1 clade D Gag, Env and cholera toxin B subunit followed by the final boost with recombinant modified vaccinia virus Ankara expressing HIV-1 clade C Env, Gag and human complement protein C3d. We measured the macaque serum antibody responses by ELISA, enumerated T cell responses by IFN-gamma ELISpot and assessed seroneutralisation of HIV-1 using the TZM-bl beta-galactosidase assay with primary isolates of HIV-1. Results: This study shows that large and complex synthetic DNA sequences can be successfully cloned in a single step into two poxvirus vectors: MVA and FPV and the recombinant poxviruses could be grown to high titres. The vaccine candidates showed appropriate expression of recombinant proteins with the formation of authentic HIV virus-like particles seen on transmission electron microscopy. In addition the b12 epitope was shown to be held in common by the vaccine candidates using confocal immunofluorescent microscopy. The vaccine candidates were safely administered to Chinese cynomolgus macaques which elicited modest T cell responses at the end of the study but only one out of the three macaques elicited an HIV-specific antibody response. However, the antibodies did not neutralise primary isolates of HIV-1 or the V3-sensitive isolate SF162 using the TZM-bl b-galactosidase assay. Conclusions: MVA and FP9 are ideal replication-deficient viral vectors for HIV-1 vaccines due to their excellent safety profile for use in humans. This study shows this novel prime-boost-boost regimen was poorly immunogenic in Chinese cynomolgus macaques

Inorganic–organic nanocomposites of CdSe nanocrystals surface-modified with oligo- and poly(fluorene) moieties

We report a facile grafting-from strategy towards the synthesis of inorganic–organic composites of semiconductor nanocrystals and wide-bandgap polymers. Amino-functional fluorenes have been used as co-ligands for CdSe nanocrystals, thus enabling us to design their surface directly during the synthesis. Highly monodisperse, strongly emitting CdSe nanocrystals have been obtained. Subsequently, a straightforward Yamamoto C–C coupling protocol was used to carry out surface polymerisation, hence modifying CdSe nanocrystals with oligo- and poly(fluorene) moieties. Both amino-fluorene capped CdSe nanocrystals and the resulting nanocrystal–polymer composites were characterized in detail by optical and FT-IR spectroscopy, TEM, AFM, and gel permeation chromatography, showing their potential as novel functional inorganic–organic hybrid materials

Patient preferences and willingness-to-pay for a home or clinic based program of chronic heart failure management: findings from the which? trial

BACKGROUND Beyond examining their overall cost-effectiveness and mechanisms of effect, it is important to understand patient preferences for the delivery of different modes of chronic heart failure management programs (CHF-MPs). We elicited patient preferences around the characteristics and willingness-to-pay (WTP) for a clinic or home-based CHF-MP. METHODOLOGY/PRINCIPAL FINDINGS A Discrete Choice Experiment was completed by a sub-set of patients (n = 91) enrolled in the WHICH? trial comparing home versus clinic-based CHF-MP. Participants provided 5 choices between hypothetical clinic and home-based programs varying by frequency of nurse consultations, nurse continuity, patient costs, and availability of telephone or education support. Participants (aged 71±13 yrs, 72.5% male, 25.3% NYHA class III/IV) displayed two distinct preference classes. A latent class model of the choice data indicated 56% of participants preferred clinic delivery, access to group CHF education classes, and lower cost programs (p<0.05). The remainder preferred home-based CHF-MPs, monthly rather than weekly visits, and access to a phone advice service (p<0.05). Continuity of nurse contact was consistently important. No significant association was observed between program preference and participant allocation in the parent trial. WTP was estimated from the model and a dichotomous bidding technique. For those preferring clinic, estimated WTP was ≈AU$9-20 per visit; however for those preferring home-based programs, WTP varied widely (AU$15-105). CONCLUSIONS/SIGNIFICANCE Patient preferences for CHF-MPs were dichotomised between a home-based model which is more likely to suit older patients, those who live alone, and those with a lower household income; and a clinic-based model which is more likely to suit those who are more socially active and wealthier. To optimise the delivery of CHF-MPs, health care services should consider their patients’ preferences when designing CHF-MPs.Jennifer A. Whitty, Simon Stewart, Melinda J. Carrington, Alicia Calderone, Thomas Marwick, John D. Horowitz, Henry Krum, Patricia M. Davidson, Peter S. Macdonald, Christopher Reid, Paul A. Scuffha

Tissue quality assessment using a novel direct elasticity assessment device (the E-finger): a cadaveric study of prostatectomy dissection.

INTRODUCTION: Minimally invasive radical prostatectomy (RP) (robotic and laparoscopic), have brought improvements in the outcomes of RP due to improved views and increased degrees of freedom of surgical devices. Robotic and laparoscopic surgeries do not incorporate haptic feedback, which may result in complications secondary to inadequate tissue dissection (causing positive surgical margins, rhabdosphincter damage, etc). We developed a micro-engineered device (6 mm2 sized) [E-finger]) capable of quantitative elasticity assessment, with amplitude ratio, mean ratio and phase lag representing this. The aim was to assess the utility of the device in differentiating peri-prostatic tissue types in order to guide prostate dissection. MATERIAL AND METHODS: Two embalmed and 2 fresh frozen cadavers were used in the study. Baseline elasticity values were assessed in bladder, prostate and rhabdosphincter of pre-dissected embalmed cadavers using the micro-engineered device. A measurement grid was created to span from the bladder, across the prostate and onto the rhabdosphincter of fresh frozen cadavers to enable a systematic quantitative elasticity assessment of the entire area by 2 independent assessors. Tissue was sectioned along each row of elasticity measurement points, and stained with haematoxylin and eosin (H&E). Image analysis was performed with Image Pro Premier to determine the histology at each measurement point. RESULTS: Statistically significant differences in elasticity were identified between bladder, prostate and sphincter in both embalmed and fresh frozen cadavers (p = < 0.001). Intra-class correlation (ICC) reliability tests showed good reliability (average ICC = 0.851). Sensitivity and specificity for tissue identification was 77% and 70% respectively to a resolution of 6 mm2. CONCLUSIONS: This cadaveric study has evaluated the ability of our elasticity assessment device to differentiate bladder, prostate and rhabdosphincter to a resolution of 6 mm2. The results provide useful data for which to continue to examine the use of elasticity assessment devices for tissue quality assessment with the aim of giving haptic feedback to surgeons performing complex surgery

Ironbark: Developing a healthy community program for older Aboriginal people

Issue addressed: Programs by, with and for Aboriginal older people must be culturally safe and relevant. Successful elements include being Aboriginal specific and group based. Co-design with Aboriginal people and stakeholders is essential. We describe the co-design process of developing the Ironbark: Healthy Community program. Methods: Aboriginal ways of knowing, being and doing and yarning conversational methods guided the development process, during 2018. A desktop review provided details of current group characteristics and key community stakeholders. Stakeholder engagement regarding views about group operations, participants and benefits also occurred. Aboriginal Elders views of their groups were gathered through yarning circles in New South Wales (NSW). Grounded theory approach was used to ascertain key themes. Results: Initial engagement occurred with 13 different community stakeholders and organisations in three Australian states (NSW, South Australia (SA), Western Australia (WA)). Three yarning circles occurred with Elders from urban (N = 10), regional coastal (N = 10) and regional country (N = 4) groups. Six key themes were organised in three groups according to an Aboriginal ontology. 1. Knowing: groups provide opportunities to share knowledge and connect socially. Adequate program resourcing and sustainability are valued. 2. Being: groups strengthen culture, providing important social, emotional and other forms of support to age well. 3. Doing: previous program experiences inform perceptions for new program operations. Group venues and operational aspects should be culturally safe, acknowledging diversity among Elders, their preferences and community control. Themes were used to develop the program and its resource manual that were finalised with stakeholders, including steering committee approval. Conclusions: Stakeholder feedback at multiple stages and Aboriginal Elders’ perspectives resulted in a new co-designed community program involving weekly yarning circles and social activities. So what?: Co-design, guided by Aboriginal ways of knowing, being and doing, can develop programs relevant for Aboriginal people