Fluorescence probe techniques to monitor protein adsorption-induced conformation changes on biodegradable polymers

The study of protein adsorption and any associated conformational changes on interaction with biomaterials is of great importance in the area of implants and tissue constructs. This study aimed to evaluate some fluorescent techniques to probe protein conformation on a selection of biodegradable polymers currently under investigation for biomedical applications. Because of the fluorescence emanating from the polymers, the use of monitoring intrinsic protein fluorescence was precluded. A highly solvatochromic fluorescent dye, Nile red, and a well-known protein label, fluorescein isothiocyanate, were employed to study the adsorption of serum albumin to polycaprolactone and to some extent also to two starch-containing polymer blends (SPCL and SEVA-C). A variety of fluorescence techniques, steady state, time resolved, and imaging were employed. Nile red was found to leach from the protein, while fluorescein isothiocyanate proved useful in elucidating a conformational change in the protein and the observation of protein aggregates adsorbed to the polymer surface. These effects were seen by making use of the phenomenon of energy migration between the fluorescent tags to monitor interprobe distance and the use of fluorescence lifetime imaging to ascertain the surface packing of the protein on polymer

Delayed-onset disseminated BCG disease causing a multi-system illness with fatal mycotic aortic aneurysm

CASE: We report a case of disseminated BCG infection, diagnosed two years after BCG infusion for bladder cancer. Our patient, a 74-year-old male, was referred with an 18-month history of fevers, weight loss and intermittent confusion. Prior to referral, the patient had multiple hospital admissions for evaluation of fever of unknown origin, confusion, and fatigue. He was treated for several acute infections, whilst extensive investigations did not identify a focal cause of the persistent fever. During this period two aneurysms, iliac and aortic, were found and stented. Both were presumed mycotic, but no positive microbiology arose from either. He presented again with fever and confusion and was found to have a left sided pleural effusion, which was drained, and broad-spectrum antibiotics started, but his fever and inflammatory markers did not settle. Mycobacterium tuberculosis PCR on a pleural fluid sample returned a positive result, and later cultures from the same fluid grew Mycobacterium species which whole genome sequencing identified as Mycobacterium Bacillus Calmette-Guérin (BCG). Despite a number of adverse events with anti-BCG medications, the patient was established on four medications (rifampicin/isoniazid/ethambutol/levofloxacin) with symptomatic improvement. He re-presented four months later with abdominal pain and was found to have an inoperable leaking thoracic aortic sac from deterioration of his mycotic aneurysm. Following discussion with the patient and his family he was managed palliatively and died two days later. DISCUSSION: The learning points from this case are to consider disseminated BCG in patients presenting with pyrexia of unknown origin following reported intravesical BCG treatment for bladder malignancy in the years prior to presentation. Mycotic aneurysms are a rare but serious complication of disseminated BCG with a high mortality

Radiopaque drug-eluting embolisation beads as fiducial markers for stereotactic liver radiotherapy

OBJECTIVE: To determine the feasibility of using radiopaque (RO) beads as direct tumour surrogates for image-guided radiotherapy (IGRT) in patients with liver tumours after transarterial chemoembolisation (TACE). METHODS: A novel vandetanib-eluting RO bead was delivered via TACE as part of a first-in-human clinical trial in patients with either hepatocellular carcinoma or liver metastases from colorectal cancer. Following TACE, patients underwent simulated radiotherapy imaging with 4-dimensional computed tomography (4D-CT) and cone-beam CT (CBCT) imaging. RO beads were contoured using automated thresholding, and feasibility of matching between the simulated radiotherapy planning dataset (AVE-IP image from 4D data) and CBCT scans assessed. Additional kV, MV, helical CT and CBCT images of RO beads were obtained using an in-house phantom. Stability of RO bead position was assessed by comparing 4D-CT imaging to CT scans taken 6-20 days following TACE. RESULTS: Eight patients were treated and 4D-CT and CBCT images acquired. RO beads were visible on 4D-CT and CBCT images in all cases and matching successfully performed. Differences in centre of mass of RO beads between CBCT and simulated radiotherapy planning scans (AVE-IP dataset) were: 2.0 mm mediolaterally, 1.7 mm anteroposteriorally, 3.5 mm craniocaudally. RO beads in the phantom were visible on all imaging modalities assessed. RO bead position remained stable up to 29 days post-TACE. CONCLUSION: RO beads are visible on IGRT imaging modalities, showing minimal artefact. They can be used for on-set matching with CBCT and remain stable over time. ADVANCES IN KNOWLEDGE: The role of RO beads as fiducial markers for stereotactic liver radiotherapy is feasible and warrants further exploration as a combination therapy approach

VEROnA Protocol: A Pilot, Open-Label, Single-Arm, Phase 0, Window-of-Opportunity Study of Vandetanib-Eluting Radiopaque Embolic Beads (BTG-002814) in Patients With Resectable Liver Malignancies

BACKGROUND: Transarterial chemoembolization (TACE) is the current standard of care for patients with intermediate-stage hepatocellular carcinoma (HCC) and is also a treatment option for patients with liver metastases from colorectal cancer. However, TACE is not a curative treatment, and tumor progression occurs in more than half of the patients treated. Despite advances and technical refinements of TACE, including the introduction of drug-eluting beads-TACE, the clinical efficacy of TACE has not been optimized, and improved arterial therapies are required. OBJECTIVE: The primary objectives of the VEROnA study are to evaluate the safety and tolerability of vandetanib-eluting radiopaque embolic beads (BTG-002814) in patients with resectable liver malignancies and to determine concentrations of vandetanib and the N-desmethyl metabolite in plasma and resected liver following treatment with BTG-002814. METHODS: The VEROnA study is a first-in-human, open-label, single-arm, phase 0, window-of-opportunity study of BTG-002814 (containing 100 mg vandetanib) delivered transarterially, 7 to 21 days before surgery in patients with resectable liver malignancies. Eligible patients have a diagnosis of colorectal liver metastases, or HCC (Childs Pugh A), diagnosed histologically or radiologically, and are candidates for liver surgery. All patients are followed up for 28 days following surgery. Secondary objectives of this study are to evaluate the anatomical distribution of BTG-002814 on noncontrast-enhanced imaging, to evaluate histopathological features in the surgical specimen, and to assess changes in blood flow on dynamic contrast-enhanced magnetic resonance imaging following treatment with BTG-002814. Exploratory objectives of this study are to study blood biomarkers with the potential to identify patients likely to respond to treatment and to correlate the distribution of BTG-002814 on imaging with pathology by 3-dimensional modeling. RESULTS: Enrollment for the study was completed in February 2019. Results of a planned interim analysis were reviewed by a safety committee after the first 3 patients completed follow-up. The recommendation of the committee was to continue the study without any changes to the dose or trial design, as there were no significant unexpected toxicities related to BTG-002814. CONCLUSIONS: The VEROnA study is studying the feasibility of administering BTG-002814 to optimize the use of this novel technology as liver-directed therapy for patients with primary and secondary liver cancer. TRIAL REGISTRATION: ClinicalTrial.gov NCT03291379; https://clinicaltrials.gov/ct2/show/NCT03291379. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13696

Resonant nonlinear magneto-optical effects in atoms

In this article, we review the history, current status, physical mechanisms, experimental methods, and applications of nonlinear magneto-optical effects in atomic vapors. We begin by describing the pioneering work of Macaluso and Corbino over a century ago on linear magneto-optical effects (in which the properties of the medium do not depend on the light power) in the vicinity of atomic resonances, and contrast these effects with various nonlinear magneto-optical phenomena that have been studied both theoretically and experimentally since the late 1960s. In recent years, the field of nonlinear magneto-optics has experienced a revival of interest that has led to a number of developments, including the observation of ultra-narrow (1-Hz) magneto-optical resonances, applications in sensitive magnetometry, nonlinear magneto-optical tomography, and the possibility of a search for parity- and time-reversal-invariance violation in atoms.Comment: 51 pages, 23 figures, to appear in Rev. Mod. Phys. in Oct. 2002, Figure added, typos corrected, text edited for clarit

Differences between urban and rural hedges in England revealed by a citizen science project

Background: Hedges are oth ecologically and culturally important and are a distinctive feature of the British landscape. However the overall length of hedges across Great Britain is decreasing. Current challenges in studying hedges relate to the dominance of research on rural, as opposed to urban, hedges, and their variability and geographical breadth. To help address these challenges and to educate the public on the importance of hedge habitats for wildlife, in 2010 the Open Air Laboratories (OPAL) programme coordinated a hedge-focused citizen science survey. Results: Results from 2891 surveys were analysed. Woody plant species differed significantly between urban and rural areas. Beech, Holly, Ivy, Laurel, Privet and Yew were more commonly recorded in urban hedges whereas Blackthorn, Bramble, Dog Rose, Elder and Hawthorn were recorded more often in rural hedges. Urban and rural differences were shown for some groups of invertebrates. Ants, earwigs and shieldbugs were recorded more frequently in urban hedges whereas blowflies, caterpillars, harvestmen, other beetles, spiders and weevils were recorded more frequently in rural hedges. Spiders were the most frequently recorded invertebrate across all surveys. The presence of hard surfaces adjacent to the hedge was influential on hedge structure, number and diversity of plant species, amount of food available for wildlife and invertebrate number and diversity. In urban hedges with one adjacent hard surface, the food available for wildlife was significantly reduced and in rural hedges, one adjacent hard surface affected the diversity of invertebrates. Conclusions: This research highlights that urban hedges may be important habitats for wildlife and that hard surfaces may have an impact on both the number and diversity of plant species and the number and diversity of invertebrates. This study demonstrates that citizen science programmes that focus on hedge surveillance can work and have the added benefit of educating the public on the importance of hedgerow habitats

Changes in the distribution of red foxes (Vulpes vulpes) in urban areas in Great Britain: findings and limitations of a media-driven nationwide survey

Urbanization is one of the major forms of habitat alteration occurring at the present time. Although this is typically deleterious to biodiversity, some species flourish within these human-modified landscapes, potentially leading to negative and/or positive interactions between people and wildlife. Hence, up-to-date assessment of urban wildlife populations is important for developing appropriate management strategies. Surveying urban wildlife is limited by land partition and private ownership, rendering many common survey techniques difficult. Garnering public involvement is one solution, but this method is constrained by the inherent biases of non-standardised survey effort associated with voluntary participation. We used a television-led media approach to solicit national participation in an online sightings survey to investigate changes in the distribution of urban foxes in Great Britain and to explore relationships between urban features and fox occurrence and sightings density. Our results show that media-based approaches can generate a large national database on the current distribution of a recognisable species. Fox distribution in England and Wales has changed markedly within the last 25 years, with sightings submitted from 91% of urban areas previously predicted to support few or no foxes. Data were highly skewed with 90% of urban areas having <30 fox sightings per 1000 people km-2. The extent of total urban area was the only variable with a significant impact on both fox occurrence and sightings density in urban areas; longitude and percentage of public green urban space were respectively, significantly positively and negatively associated with sightings density only. Latitude, and distance to nearest neighbouring conurbation had no impact on either occurrence or sightings density. Given the limitations associated with this method, further investigations are needed to determine the association between sightings density and actual fox density, and variability of fox density within and between urban areas in Britain

On the Front Line of Community-Led Air Quality Monitoring

In this chapter, we explore the potential of community-led air quality monitoring. Community-led air quality monitoring differs from top-down monitoring in many aspects: it is focused on community needs and interests and a local problem and, therefore, has a limited geographical coverage as well as limited temporal coverage. However, localised air quality monitoring can potentially increase the spatial and temporal resolution of air quality information if there is a suitable information-sharing mechanism in place: information from multiple community-led activities can be shared at the city scale and used to augment official information. At the core of the chapter, we provide a detailed experiential description of the process of urban air quality practice, from which we draw our conclusion. We suggest that accessible and reliable community-led air quality monitoring can contribute to the understanding of local environmental issues and improve the dialogue between local authorities and communities about the impacts of air pollution on health and urban and transport planning. Document type: Part of book or chapter of boo