The clinical effectiveness and cost-effectiveness of ablative therapies in the management of liver metastases: systematic review and economic evaluation

Background: Many deaths from cancer are caused by metastatic burden. Prognosis and survival rates vary, but survival beyond 5 years of patients with untreated metastatic disease in the liver is rare. Treatment for liver metastases has largely been surgical resection, but this is feasible in only approximately 20–30% of people. Non-surgical alternatives to treat some liver metastases can include various forms of ablative therapies and other targeted treatments.Objectives: To evaluate the clinical effectiveness and cost-effectiveness of the different ablative and minimally invasive therapies for treating liver metastases.Data sources: Electronic databases including MEDLINE, EMBASE and The Cochrane Library were searched from 1990 to September 2011. Experts were consulted and bibliographies checked.Review methods: Systematic reviews of the literature were undertaken to appraise the clinical effectiveness and cost-effectiveness of ablative therapies and minimally invasive therapies used for people with liver metastases. Studies were any prospective study with sample size greater than 100 participants. A probabilistic model was developed for the economic evaluation of the technologies where data permitted.Results: The evidence assessing the clinical effectiveness and cost-effectiveness of ablative and other minimally invasive therapies was limited. Nine studies of ablative therapies were included in the review; each had methodological shortcomings and few had a comparator group. One randomised controlled trial (RCT) of microwave ablation versus surgical resection was identified and showed no improvement in outcomes compared with resection. In two prospective case series studies that investigated the use of laser ablation, mean survival ranged from 41 to 58 months. One cohort study compared radiofrequency ablation with surgical resection and five case series studies also investigated the use of radiofrequency ablation. Across these studies the median survival ranged from 44 to 52 months. Seven studies of minimally invasive therapies were included in the review. Two RCTs compared chemoembolisation with chemotherapy only. Overall survival was not compared between groups and methodological shortcomings mean that conclusions are difficult to make. Two case series studies of laser ablation following chemoembolisation were also included; however, these provide little evidence of the use of these technologies in combination. Three RCTs of radioembolisation were included. Significant improvements in tumour response and time to disease progression were demonstrated; however, benefits in terms of survival were equivocal. An exploratory survival model was developed using data from the review of clinical effectiveness. The model includes separate analyses of microwave ablation compared with surgery and radiofrequency ablation compared with surgery and one of radioembolisation in conjunction with hepatic artery chemotherapy compared with hepatic artery chemotherapy alone. Microwave ablation was associated with an incremental cost-effectiveness ratio (ICER) of £3664 per quality-adjusted life-year (QALY) gained, with microwave ablation being associated with reduced cost but also with poorer outcome than surgery. Radiofrequency ablation compared with surgical resection for solitary metastases < 3 cm was associated with an ICER of –£266,767 per QALY gained, indicating that radiofrequency ablation dominates surgical resection. Radiofrequency ablation compared with surgical resection for solitary metastases ? 3 cm resulted in poorer outcomes at lower costs and a resultant ICER of £2538 per QALY gained. Radioembolisation plus hepatic artery chemotherapy compared with hepatic artery chemotherapy was associated with an ICER of £37,303 per QALY gained.Conclusions: There is currently limited high-quality research evidence upon which to base any firm decisions regarding ablative therapies for liver metastases. Further trials should compare ablative therapies with surgery, in particular. A RCT would provide the most appropriate design for undertaking any further evaluation and should include a full economic evaluation, but the group to be randomised needs careful selection.Source of funding: Funding for this study was provided by the Health Technology Assessment programme of the National Institute for Health Research

Advances in local area optical data communication systems

This paper reviews optical fibre technology for local area optical communications systems. Technologies used in local systems include single and multimode fibre, single and multimode lasers, optical modulators, photodetectors, wavelength division multiplexing, multilevel modulation formats, electronic packet switching, electronic equalization and error correction. These methods have enabled the local area optical link data rate to increase from 0.1 Gb/s in 1990 to nearly a Tb/s in 2019. The challenges to increasing link data rates further, whilst reducing the transmitted power per bit, at reduced cost are discussed. Potential technical solutions and newly proposed methods which might address these challenges are highlighted

Amphiphilic block copolymers as stabilizers in emulsion polymerization: Effects of molecular weight dispersity and evidence of self-folding behavior

Emulsion polymerizations, used to produce many commodity materials, require stabilizing agents to prevent phase separation. Incorporation of these stabilizers in the final polymer may have negative effects on product properties, so the design of new stabilizers is being actively pursued. Amphiphilic diblock copolymers are a promising type of emulsion polymerization stabilizer and are the focus of this work (Fig. 1). First, the tolerance of an amphiphilic diblock copolymer stabilizer’s performance to high molecular weight dispersity and homopolymer impurity has been investigated. Polystyrene-b-poly(acrylic acid) block copolymers were studied due to their previously demonstrated efficacy as stabilizers in emulsion polymerization, and their similarity to commercially important polystyrene-r-poly(acrylic acid) stabilizers. Neither greater molecular weight dispersity nor homopolymer impurity was found to negatively impact the stabilization performance of these block copolymers, suggesting that the economically unfavorable conditions required to achieve low molecular weight dispersity and homopolymer impurity may be avoided. We then examined novel polystyrene-b-[polystyrene-r-poly(acrylic acid)] block-random copolymers which were shown to stabilize emulsion polymerizations with up to 50 weight percent solids content, exceeding what was possible using the polystyrene-b-poly(acrylic acid) block copolymers. Of even greater significance and scientific value is that the block-random copolymers were also observed to have unusual solution behavior, self-folding rather than self-assembling, to give single chain nanoparticles. Emulsion polymerizations stabilized by these block-random copolymers had a total particle surface area which was directly proportional to the stabilizer concentration and was unaffected by polymerization kinetics. A novel “seeded-coagulative” emulsion polymerization mechanism has been proposed to explain these results, which were unexplainable by any known emulsion polymerization mechanism. Please click Additional Files below to see the full abstrac

The Development Of An Interactive Industry/Academic Power Engineering Education Program At The University Of Missouri-Rolla

This paper describes the development of a unique andinno-vative program in power engineering education enhanced through an Industry/Academic interrelationship. This program is devoted to both the teaching and the practice of power engineering. The development of the Industry/Academic relationship and its value as a model for power engineering education are related. A summary of present and proposed future activities concludes the report. Copyright © 1978 by The Institute of Electrical and Electronics Engineers, Inc

Functional imaging and circulating biomarkers of response to regorafenib in treatment-refractory metastatic colorectal cancer patients in a prospective phase II study

Objective: Regorafenib demonstrated efficacy in patients with metastatic colorectal cancer (mCRC). Lack of predictive biomarkers, potential toxicities and cost-effectiveness concerns highlight the unmet need for better patient selection. Design: Patients with RAS mutant mCRC with biopsiable metastases were enrolled in this phase II trial. Dynamic contrast-enhanced (DCE) MRI was acquired pretreatment and at day 15 post-treatment. Median values of volume transfer constant (Ktrans), enhancing fraction (EF) and their product KEF (summarised median values of Ktrans× EF) were generated. Circulating tumour (ct) DNA was collected monthly until progressive disease and tested for clonal RAS mutations by digital-droplet PCR. Tumour vasculature (CD-31) was scored by immunohistochemistry on 70 sequential tissue biopsies. Results: Twenty-seven patients with paired DCE-MRI scans were analysed. Median KEF decrease was 58.2%. Of the 23 patients with outcome data, >70% drop in KEF (6/23) was associated with higher disease control rate (p=0.048) measured by RECIST V. 1.1 at 2 months, improved progression-free survival (PFS) (HR 0.16 (95% CI 0.04 to 0.72), p=0.02), 4-month PFS (66.7% vs 23.5%) and overall survival (OS) (HR 0.08 (95% CI 0.01 to 0.63), p=0.02). KEF drop correlated with CD-31 reduction in sequential tissue biopsies (p=0.04). RAS mutant clones decay in ctDNA after 8 weeks of treatment was associated with better PFS (HR 0.21 (95% CI 0.06 to 0.71), p=0.01) and OS (HR 0.28 (95% CI 0.07–1.04), p=0.06). Conclusions: Combining DCE-MRI and ctDNA predicts duration of anti-angiogenic response to regorafenib and may improve patient management with potential health/economic implications

The life cycle of stars and their planets from the high energy perspective

One of the key research themes identified by the Astro2020 decadal survey is Worlds and Suns in Context. The Advanced X-ray Imaging Satellite (AXIS) is a proposed NASA APEX mission that will become the prime high-energy instrument for studying star-planet connections from birth to death. This work explores the major advances in this broad domain of research that will be enabled by the AXIS mission, through X-ray observations of stars in clusters spanning a broad range of ages, flaring M-dwarf stars known to host exoplanets, and young stars exhibiting accretion interactions with their protoplanetary disks. In addition, we explore the ability of AXIS to use planetary nebulae, white dwarfs, and the Solar System to constrain important physical processes from the microscopic (e.g., charge exchange) to the macroscopic (e.g., stellar wind interactions with the surrounding interstellar medium).Comment: This White Paper is part of a series commissioned for the AXIS Probe Concept Missio

Developing One Health surveillance systems

The health of humans, domestic and wild animals, plants, and the environment are inter-dependent. Global anthropogenic change is a key driver of disease emergence and spread and leads to biodiversity loss and ecosystem function degradation, which are themselves drivers of disease emergence. Pathogen spill-over events and subsequent disease outbreaks, including pandemics, in humans, animals and plants may arise when factors driving disease emergence and spread converge. One Health is an integrated approach that aims to sustainably balance and optimize human, animal and ecosystem health. Conventional disease surveillance has been siloed by sectors, with separate systems addressing the health of humans, domestic animals, cultivated plants, wildlife and the environment. One Health surveillance should include integrated surveillance for known and unknown pathogens, but combined with this more traditional disease-based surveillance, it also must include surveillance of drivers of disease emergence to improve prevention and mitigation of spill-over events. Here, we outline such an approach, including the characteristics and components required to overcome barriers and to optimize an integrated One Health surveillance system.</p

Developing One Health surveillance systems

The health of humans, domestic and wild animals, plants, and the environment are inter-dependent. Global anthropogenic change is a key driver of disease emergence and spread and leads to biodiversity loss and ecosystem function degradation, which are themselves drivers of disease emergence. Pathogen spill-over events and subsequent disease outbreaks, including pandemics, in humans, animals and plants may arise when factors driving disease emergence and spread converge. One Health is an integrated approach that aims to sustainably balance and optimize human, animal and ecosystem health. Conventional disease surveillance has been siloed by sectors, with separate systems addressing the health of humans, domestic animals, cultivated plants, wildlife and the environment. One Health surveillance should include integrated surveillance for known and unknown pathogens, but combined with this more traditional disease-based surveillance, it also must include surveillance of drivers of disease emergence to improve prevention and mitigation of spill-over events. Here, we outline such an approach, including the characteristics and components required to overcome barriers and to optimize an integrated One Health surveillance system

The Zwicky Transient Facility: Data Processing, Products, and Archive

The Zwicky Transient Facility (ZTF) is a new robotic time-domain survey currently in progress using the Palomar 48-inch Schmidt Telescope. ZTF uses a 47 square degree field with a 600 megapixel camera to scan the entire northern visible sky at rates of ~3760 square degrees/hour to median depths of g ~ 20.8 and r ~ 20.6 mag (AB, 5sigma in 30 sec). We describe the Science Data System that is housed at IPAC, Caltech. This comprises the data-processing pipelines, alert production system, data archive, and user interfaces for accessing and analyzing the products. The realtime pipeline employs a novel image-differencing algorithm, optimized for the detection of point source transient events. These events are vetted for reliability using a machine-learned classifier and combined with contextual information to generate data-rich alert packets. The packets become available for distribution typically within 13 minutes (95th percentile) of observation. Detected events are also linked to generate candidate moving-object tracks using a novel algorithm. Objects that move fast enough to streak in the individual exposures are also extracted and vetted. The reconstructed astrometric accuracy per science image with respect to Gaia is typically 45 to 85 milliarcsec. This is the RMS per axis on the sky for sources extracted with photometric S/N >= 10. The derived photometric precision (repeatability) at bright unsaturated fluxes varies between 8 and 25 millimag. Photometric calibration accuracy with respect to Pan-STARRS1 is generally better than 2%. The products support a broad range of scientific applications: fast and young supernovae, rare flux transients, variable stars, eclipsing binaries, variability from active galactic nuclei, counterparts to gravitational wave sources, a more complete census of Type Ia supernovae, and Solar System objects.Comment: 30 pages, 16 figures, Published in PASP Focus Issue on the Zwicky Transient Facility (doi: 10.1088/1538-3873/aae8ac