A novel light source with tuneable uniformity of light distribution for artificial daylight photodynamic therapy

This project was supported by the University of St. Andrews through the Science and Technology Facilities Council (STFC) Impact Accelerator Award (IAA) and by the Laser Research and Therapy Fund (registered charity SC030850). P O’M is funded by Medi-lase (registered charity SC 037390) and the Alfred Stewart Trust.Objectives: Implementation of daylight photodynamic therapy (dPDT) is somewhat limited by variable weather conditions. Light sources have been employed to provide artificial dPDT indoors, with low irradiances and longer treatment times. Uniform light distribution across the target area is key to ensuring effective treatment, particularly for large areas. A novel light source is developed with tuneable direction of light emission in order to meet this challenge. Methods: Wavelength composition of the novel light source is controlled such that the protoporphyrin-IX (PpIX) weighed spectra of both the light source and daylight match. The uniformity of the light source is characterised on a flat surface, a model head and a model leg. For context, a typical conventional PDT light source is also characterised. Additionally, the wavelength uniformity across the treatment site is characterised. Results: The PpIX-weighted spectrum of the novel light source matches with PpIX-weighted daylight spectrum, with irradiance values within the bounds for effective dPDT. By tuning the direction of light emission, improvements are seen in the uniformity across large anatomical surfaces. Wavelength uniformity is discussed. Conclusions: We have developed a light source that addresses the challenges in uniform, multiwavelength light distribution for large area artificial dPDT across curved anatomical surfaces.PostprintPeer reviewe

Simulating Photodynamic Therapy for the Treatment of Glioblastoma using Monte Carlo Radiative Transport

Significance: Glioblastoma (GBM) is a rare but deadly form of brain tumor with a low median survival rate of 14.6 months, due to its resistance to treatment. An independent simulation of the INtraoperative photoDYnamic therapy for GliOblastoma (INDYGO) trial, a clinical trial aiming to treat the GBM resection cavity with photodynamic therapy (PDT) via a laser coupled balloon device, is demonstrated. Aim: To develop a framework providing increased understanding for the PDT treatment, its parameters, and their impact on the clinical outcome. Approach: We use Monte Carlo radiative transport techniques within a computational brain model containing a GBM to simulate light path and PDT effects. Treatment parameters (laser power, photosensitizer concentration, and irradiation time) are considered, as well as PDT’s impact on brain tissue temperature. Results: The simulation suggests that 39% of post-resection GBM cells are killed at the end of treatment when using the standard INDYGO trial protocol (light fluence = 200 J∕cm 2 at balloon wall) and assuming an initial photosensitizer concentration of 5 μM. Increases in treatment time and light power (light fluence = 400 J∕cm 2 at balloon wall) result in further cell kill but increase brain cell temperature, which potentially affects treatment safety. Increasing the p hotosensitizer concentration produces the most significant increase in cell kill, with 61% of GBM cells killed when doubling concentration to 10 μM and keeping the treatment time and power the same. According to these simulations, the standard trial protocol is reasonably well optimized with improvements in cell kill difficult to achieve without potentially dangerous increases in temperature. To improve treatment outcome, focus should be placed on improving the photosensitizer. Conclusions: With further development and optimization, the simulation could have potential clinical benefit and be used to help plan and optimize intraoperative PDT treatment for GBM.</p

Development of a predictive Monte Carlo radiative transfer model for ablative fractional skin lasers

L.M. would like to acknowledge the funding from EPSRC grant code: EP/K503162/1. P.O'M. is funded by Medi‐Lase (registered charity SC 037390) and the Alfred Stewart Trust'.It is possible to enhance topical drug delivery by pretreatment of the skin with ablative fractional lasers (AFLs). However, the parameters to use for a given AFL to achieve the desired depth of ablation or the desired therapeutic or cosmetic outcome are hard to predict. This leaves open the real possibility of overapplication or underapplication of laser energy to the skin. In this study, we developed a numerical model consisting of a Monte Carlo radiative transfer (MCRT) code coupled to a heat transfer and tissue damage algorithm. The simulation is designed to predict the depth effects of AFL on the skin, verified with in vitro experiments in porcine skin via optical coherence tomography (OCT) imaging. Ex vivo porcine skin is irradiated with increasing energies (50–400 mJ/pixel) from a CO2 AFL. The depth of microscopic treatment zones is measured and compared with our numerical model. The data from the OCT images and MCRT model complement each other well. Nonablative thermal effects on surrounding tissue are also discussed. This model, therefore, provides an initial step toward a predictive determination of the effects of AFL on the skin.Publisher PDFPeer reviewe

Simulating photodynamic therapy for the treatment of glioblastoma using Monte Carlo radiative transport

Funding: LF acknowledges financial support from the UK Research and Innovation (UKRI) Engineering and Physical Sciences Research Council (EPSRC) Centre for Doctoral Training in Applied Photonics (Grant No. EP/S022821/1) and the Laser Research and Therapy Fund (Grant No. SC030850).Significance Glioblastoma (GBM) is a rare but deadly form of brain tumor with a low median survival rate of 14.6 months, due to its resistance to treatment. An independent simulation of the INtraoperative photoDYnamic therapy for GliOblastoma (INDYGO) trial, a clinical trial aiming to treat the GBM resection cavity with photo- dynamic therapy (PDT) via a laser coupled balloon device, is demonstrated. Aim To develop a framework providing increased understanding for the PDT treatment, its parameters, and their impact on the clinical outcome. Approach We use Monte Carlo radiative transport techniques within a computational brain model containing a GBM to simulate light path and PDT effects. Treatment parameters (laser power, photosensitizer concentration, and irradiation time) are considered, as well as PDT’s impact on brain tissue temperature.  Results The simulation suggests that 39% of post-resection GBM cells are killed at the end of treatment when using the standard INDYGO trial protocol (light fluence = 200 J∕cm2 at balloon wall) and assuming an initial photosensitizer concentration of 5 μM. Increases in treatment time and light power (light fluence = 400 J∕cm2 at balloon wall) result in further cell kill but increase brain cell temperature, which potentially affects treatment safety. Increasing the p hotosensitizer concentration produces the most significant increase in cell kill, with 61% of GBM cells killed when doubling concentration to 10 μM and keeping the treatment time and power the same. According to these simulations, the standard trial protocol is reasonably well optimized with improvements in cell kill difficult to achieve without potentially dangerous increases in temperature. To improve treatment outcome, focus should be placed on improving the photosensitizer.  Conclusions With further development and optimization, the simulation could have potential clinical benefit and be used to help plan and optimize intraoperative PDT treatment for GBM.Peer reviewe

Housing and Ageing:Let’s get serious-“how do you plan for the future while addressing immediate chaos?"

This article presents findings from the Housing and Ageing programme conducted in 2018 that investigated how the housing sector can effectively plan for an ageing population. The project took a transdisciplinary approach to focus on new, critical insights into the process of decision making concerning housing and ageing across Scotland, England and Wales. A ‘Serious Game’ methodology was developed that explored over 200 policy maker, practitioner and service user perspectives. This was used as a framework to capture priorities, decisions, negotiations and processes that indicate how a ‘sense of place’ and ‘place belonging’ can influence the development of suitable housing for older people. Key housing provision challenges identified were tackling inequality, preserving autonomy, in(ter)dependence, empowerment and accessibility. Such challenges need consideration when strategically planning for the future. The findings recommend placing housing at the heart of service integration to support the co-production of decisions that emphasise the importance of working together across boundaries within social policy, service and stakeholder groups. A place-based approach can support the perception that we are all stakeholders in ageing

Process and impact of implementing a smoke-free policy in prisons in Scotland: TIPs mixed-methods study

Background: Prisons had partial exemption from the UK’s 2006/7 smoking bans in enclosed public spaces. They became one of the few workplaces with continuing exposure to second-hand smoke, given the high levels of smoking among people in custody. Despite the introduction of smoke-free prisons elsewhere, evaluations of such ‘bans’ have been very limited to date. Objective: The objective was to provide evidence on the process and impact of implementing a smoke-free policy across a national prison service. Design: The Tobacco in Prisons study was a three-phase, multimethod study exploring the periods before policy formulation (phase 1: pre announcement), during preparation for implementation (phase 2: preparatory) and after implementation (phase 3: post implementation). Setting: The study was set in Scotland’s prisons. Participants: Participants were people in custody, prison staff and providers/users of prison smoking cessation services. Intervention: Comprehensive smoke-free prison rules were implemented across all of Scotland’s prisons in November 2018. Main outcome measures: The main outcome measures were second-hand smoke levels, health outcomes and perspectives/experiences, including facilitators of successful transitions to smoke-free prisons. Data sources: The study utilised cross-sectional surveys of staff (total, n = 3522) and people in custody (total, n = 5956) in each phase; focus groups and/or one-to-one interviews with staff (n = 237 across 34 focus groups; n = 38 interviews), people in custody (n = 62 interviews), providers (n = 103 interviews) and users (n = 45 interviews) of prison smoking cessation services and stakeholders elsewhere (n = 19); measurements of second-hand smoke exposure (e.g. 369,208 minutes of static measures in residential areas at three time points); and routinely collected data (e.g. medications dispensed, inpatient/outpatient visits). Results: Measures of second-hand smoke were substantially (≈ 90%) reduced post implementation, compared with baseline, largely confirming the views of staff and people in custody that illicit smoking is not a major issue post ban. Several factors that contributed to the successful implementation of the smoke-free policy, now accepted as the ‘new normal’, were identified. E-cigarette use has become common, was recognised (by both staff and people in custody) to have facilitated the transition and raises new issues in prisons. The health economic analysis (lifetime model) demonstrated that costs were lower and the number of quality-adjusted life-years was larger for people in custody and staff in the ‘with smoke-free’ policy period than in the ‘without’ policy period, confirming cost-effectiveness against a £20,000 willingness-to-pay threshold. Limitations: The ability to triangulate between different data sources mitigated limitations with constituent data sets. Conclusions: To our knowledge, this is the first study internationally to analyse the views of prison staff and people in custody; objective measurements of second-hand smoke exposure and routine health and other outcomes before, during and after the implementation of a smoke-free prison policy; and to assess cost-effectiveness. The results are relevant to jurisdictions considering similar legislation, whether or not e-cigarettes are permitted. The study provides a model for partnership working and, as a multidimensional study of a national prison system, adds to a previously sparse evidence base internationally. Future work: Priorities are to understand how to support people in custody in remaining smoke free after release from prison, and whether or not interventions can extend benefits to their families; to evaluate new guidance supporting people wishing to reduce or quit vaping; and to understand how prison vaping practices/cultures may strengthen or weaken long-term reductions in smoking. Study registration: This study is registered as Research Registry 4802. Funding: This project was funded by the National Institute for Health Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 10, No. 1. See the NIHR Journals Library website for further project information

Early ultrasound surveillance of newly-created haemodialysis arteriovenous fistula

IntroductionWe assess if ultrasound surveillance of newly-created arteriovenous fistulas (AVFs) can predict nonmaturation sufficiently reliably to justify randomized controlled trial (RCT) evaluation of ultrasound-directed salvage intervention.MethodsConsenting adults underwent blinded fortnightly ultrasound scanning of their AVF after creation, with scan characteristics that predicted AVF nonmaturation identified by logistic regression modeling.ResultsOf 333 AVFs created, 65.8% matured by 10 weeks. Serial scanning revealed that maturation occurred rapidly, whereas consistently lower fistula flow rates and venous diameters were observed in those that did not mature. Wrist and elbow AVF nonmaturation could be optimally modeled from week 4 ultrasound parameters alone, but with only moderate positive predictive values (PPVs) (wrist, 60.6% [95% confidence interval, CI: 43.9–77.3]; elbow, 66.7% [48.9–84.4]). Moreover, 40 (70.2%) of the 57 AVFs that thrombosed by week 10 had already failed by the week 4 scan, thus limiting the potential of salvage procedures initiated by that scan’s findings to alter overall maturation rates. Modeling of the early ultrasound characteristics could also predict primary patency failure at 6 months; however, that model performed poorly at predicting assisted primary failure (those AVFs that failed despite a salvage attempt), partly because patency of at-risk AVFs was maintained by successful salvage performed without recourse to the early scan data.ConclusionEarly ultrasound surveillance may predict fistula maturation, but is likely, at best, to result in only very modest improvements in fistula patency. Power calculations suggest that an impractically large number of participants (>1700) would be required for formal RCT evaluation

The Zwicky Transient Facility: System Overview, Performance, and First Results

The Zwicky Transient Facility (ZTF) is a new optical time-domain survey that uses the Palomar 48 inch Schmidt telescope. A custom-built wide-field camera provides a 47 deg 2 field of view and 8 s readout time, yielding more than an order of magnitude improvement in survey speed relative to its predecessor survey, the Palomar Transient Factory. We describe the design and implementation of the camera and observing system. The ZTF data system at the Infrared Processing and Analysis Center provides near-real-time reduction to identify moving and varying objects. We outline the analysis pipelines, data products, and associated archive. Finally, we present on-sky performance analysis and first scientific results from commissioning and the early survey. ZTF’s public alert stream will serve as a useful precursor for that of the Large Synoptic Survey Telescope

The Zwicky Transient Facility: Science Objectives

The Zwicky Transient Facility (ZTF), a public–private enterprise, is a new time-domain survey employing a dedicated camera on the Palomar 48-inch Schmidt telescope with a 47 deg2 field of view and an 8 second readout time. It is well positioned in the development of time-domain astronomy, offering operations at 10% of the scale and style of the Large Synoptic Survey Telescope (LSST) with a single 1-m class survey telescope. The public surveys will cover the observable northern sky every three nights in g and r filters and the visible Galactic plane every night in g and r. Alerts generated by these surveys are sent in real time to brokers. A consortium of universities that provided funding (“partnership”) are undertaking several boutique surveys. The combination of these surveys producing one million alerts per night allows for exploration of transient and variable astrophysical phenomena brighter than r∼20.5 on timescales of minutes to years. We describe the primary science objectives driving ZTF, including the physics of supernovae and relativistic explosions, multi-messenger astrophysics, supernova cosmology, active galactic nuclei, and tidal disruption events, stellar variability, and solar system objects. © 2019. The Astronomical Society of the Pacific

The Zwicky Transient Facility: System Overview, Performance, and First Results

The Zwicky Transient Facility (ZTF) is a new optical time-domain survey that uses the Palomar 48 inch Schmidt telescope. A custom-built wide-field camera provides a 47 deg^2 field of view and 8 s readout time, yielding more than an order of magnitude improvement in survey speed relative to its predecessor survey, the Palomar Transient Factory. We describe the design and implementation of the camera and observing system. The ZTF data system at the Infrared Processing and Analysis Center provides near-real-time reduction to identify moving and varying objects. We outline the analysis pipelines, data products, and associated archive. Finally, we present on-sky performance analysis and first scientific results from commissioning and the early survey. ZTF's public alert stream will serve as a useful precursor for that of the Large Synoptic Survey Telescope