Specialist tissue viability services: a priority or a luxury?

During the 1980s, the number of tissue viability nurses (TVNs) rose steadily in the UK, in response to mismanagement of patients with wounds (Fletcher, 1995). Since this time, and in response to the quality agenda, the necessity of promoting a tissue viability service (TVS) that is able to meet the needs of a changing population, while being cost effective and offering interventions based on research and evidence, has grown. The drive to reduce avoidable harm in healthcare and to make efficiency savings is continuing, with TVS being one of the key areas to deliver these targets. However, across the UK we have a wide range of role descriptions and job titles, yet little clarification as to the qualifications and skills required to deliver a successful TVS. Infection control specialist nurses have a clear identity with concise role descriptions representing a range of pay bands. Arguably, this is because they are aligned with a medical specialty, whereas TV is not. The introduction of ‘Any Qualified Provider’ (Department of Health, 2011) has witnessed some services, including management of leg ulceration, being delivered by non-NHS providers at a reduced cost. So is TVS in danger of becoming more of a ‘nice thing’ rather than a priority

86 GHz Very Long Baseline Polarimetry of 3C273 and 3C279 with the Coordinated Millimeter VLBI Array

86 GHz Very Long Baseline Polarimetry probes magnetic field structures within the cores of Active Galactic Nuclei at higher angular resolutions and a spectral octave higher than previously achievable. Observations of 3C273 and 3C279 taken in April 2000 with the Coordinated Millimeter VLBI Array have resulted in the first total intensity (Stokes I) and linear polarization VLBI images reported of any source at 86 GHz. These results reveal the 86 GHz electric vector position angles within the jets of 3C273 and 3C279 to be orthogonal to each other, and the core of 3C273 to be unpolarized. If this lack of polarization is due to Faraday depolarization alone, the dispersion in rotation measure is >=90000 rad/m^2 for the core of 3C273.Comment: AASTeX v5.02; 10 pages; 4 figures; accepted for publication in the Astrophysical Journal Letter

Variability of the Centimeter-Submillimeter Spectrum and Polarization of 3C 273 during Outburst

Original article can be found at: http://www.journals.uchicago.edu/ApJ/--Copyright University of Chicago Press/ AASCentimeter to submillimeter total flux and polarization monitoring data are used to investigate the nature of a prominent flare in the quasar 3C 273 during 1995/6. After removal of the quiescent level, the resulting “flare spectra" are well fitted by a simple homogeneous synchrotron source model, which in turn allows the movement of the self-absorption turnover to be tracked during the flare. Both the flare amplitude/time delay relationship and the overall spectral evolution are qualitatively consistent with existing models. The early evolution of the spectrum is best determined and is shown to be in excellent agreement with the Compton stage of the Marscher & Gear shock model. However, the polarization behavior during the flare is different at millimeter and centimeter wavelengths and the observations are difficult to reconcile with a simple transverse shock. They are, however, consistent with a conical shock for which the observed polarization properties vary with distance along the jet. Such variations may be caused, for example, by a change in cone angle owing to disruption caused by the growing component of the magnetic field parallel to the jet axis or by a moderate change in viewing angle.Peer reviewe

Variability and polarization in the inner jet of 3C395

We present new results on the parsec-scale jet of the quasar 3C395, derived from VLBI polarization sensitive observations made in 1995.91 and 1998.50 at 8.4, 15.4 and 22.2 GHz. The observations show a complex one-sided jet extending up to 20 mas, with a projected magnetic field essentially aligned with the radio jet. The emission is strongly dominated, in total intensity and polarization, by the core and the inner jet region (of ~3 mas length). We have studied the details of this dominant region finding clear structural variations during this ~2.5 years period, in contrast with the apparent quietness of the jet structure inferred from lower resolution VLBI observations. We observe the ejection of a new component from the core and variations in the degree of polarization of the inner jet components. We estimate a high Faraday Rotation Measure close to the core, with a strong decrease along the inner jet.Comment: 7 pages, 4 figures, A&A in pres

Multimodal nanoparticle imaging agents: Design and applications

Molecular imaging, where the location of molecules or nanoscale constructs can be tracked in the body to report on disease or biochemical processes, is rapidly expanding to include combined modality or multimodal imaging. No single imaging technique can offer the optimum combination of properties (e.g. resolution, sensitivity, cost, availability). The rapid technological advances in hardware to scan patients, and software to process and fuse images, are pushing the boundaries of novel medical imaging approaches, and hand-in-hand with this is the requirement for advanced and specific multimodal imaging agents. These agents can be detected using a selection from radioisotope, magnetic resonance and optical imaging, among others. Nanoparticles offer great scope in this area as they lend themselves, via facile modification procedures, to act as multifunctional constructs. They have relevance as therapeutics and drug delivery agents that can be tracked by molecular imaging techniques with the particular development of applications in optically guided surgery and as radiosensitizers. There has been a huge amount of research work to produce nanoconstructs for imaging, and the parameters for successful clinical translation and validation of therapeutic applications are now becoming much better understood. It is an exciting time of progress for these agents as their potential is closer to being realized with translation into the clinic. The coming 5–10 years will be critical, as we will see if the predicted improvement in clinical outcomes becomes a reality. Some of the latest advances in combination modality agents are selected and the progression pathway to clinical trials analysed. This article is part of the themed issue ‘Challenges for chemistry in molecular imaging’

Development of PDT/PET theranostics: synthesis and biological evaluation of an ¹⁸F-radiolabeled water soluble porphyrin

Synthesis of the first water-soluble porphyrin radiolabeled with fluorine-18 is described: a new molecular theranostic agent which integrates the therapeutic selectivity of photodynamic therapy (PDT) with the imaging efficacy of positron emission tomography (PET). Generation of the theranostic was carried out through the conjugation of a cationic water-soluble porphyrin bearing an azide functionality to a fluorine-18 radiolabeled prosthetic bearing an alkyne functionality through click conjugation, with excellent yields obtained in both cold and hot synthesis. Biological evaluation of the synthesized structures shows the first example of an 18 F-radiolabeled porphyrin retaining photocytotoxicity following radiolabeling and demonstrable conjugate uptake and potential application as a radiotracer in vivo. The promising results gained from biological evaluation demonstrate the potential of this structure as a clinically relevant theranostic agent, offering exciting possibilities for the simultaneous imaging and photodynamic treatment of tumors

Polarimetric Observations of 15 AGNs at High Frequencies

Original paper can be found at: http://www.astrosociety.org/pubs/cs/328.html--Copyright Astronomical Society of the PacificWe have obtained total and polarized intensity images of 15 AGNs with the VLBA at 7 mm at 17 epochs from 25/26 March 1998 to 14 April 2001. The VLBA observations are accompanied at many epochs by simultaneous mea- surements of polarization at 1.35/0.85 mm as well as less frequent simultaneous optical polarization measurements. We discuss the similarities and complexities of polarization behavior at different frequencies along with the VLBI properties

A caspase-3 'death-switch' in colorectal cancer cells for induced and synchronous tumor apoptosis in vitro and in vivo facilitates the development of minimally invasive cell death biomarkers

Novel anticancer drugs targeting key apoptosis regulators have been developed and are undergoing clinical trials. Pharmacodynamic biomarkers to define the optimum dose of drug that provokes tumor apoptosis are in demand; acquisition of longitudinal tumor biopsies is a significant challenge and minimally invasive biomarkers are required. Considering this, we have developed and validated a preclinical 'death-switch' model for the discovery of secreted biomarkers of tumour apoptosis using in vitro proteomics and in vivo evaluation of the novel imaging probe [ 18 F]ML-10 for non-invasive detection of apoptosis using positron emission tomography (PET). The 'death-switch' is a constitutively active mutant caspase-3 that is robustly induced by doxycycline to drive synchronous apoptosis in human colorectal cancer cells in vitro or grown as tumor xenografts. Deathswitch induction caused caspase-dependent apoptosis between 3 and 24 hours in vitro and regression of 'death-switched' xenografts occurred within 24 h correlating with the percentage of apoptotic cells in tumor and levels of an established cell death biomarker (cleaved cytokeratin-18) in the blood. We sought to define secreted biomarkers of tumor apoptosis from cultured cells using Discovery Isobaric Tag proteomics, which may provide candidates to validate in blood. Early after caspase-3 activation, levels of normally secreted proteins were decreased (e.g. Gelsolin and Midkine) and proteins including CD44 and High Mobility Group protein B1 (HMGB1) that were released into cell culture media in vitro were also identified in the bloodstream of mice bearing death-switched tumors. We also exemplify the utility of the death-switch model for the validation of apoptotic imaging probes using [ 18 F]ML-10, a PET tracer currently in clinical trials. Results showed increased tracer uptake of [ 18 F]ML-10 in tumours undergoing apoptosis, compared with matched tumour controls imaged in the same animal. Overall, the death-switch model represents a robust and versatile tool for the discovery and validation of apoptosis biomarkers. © 2013 Macmillan Publishers Limited. All rights reserved

Assessing the Pedagogical Impact of the VaNTH Engineering Research Center on Faculty and Postdoctoral Professionals

From 1999 to 2007, the Vanderbilt-Northwestern-Texas-Harvard/MIT (VaNTH) Engineering Research Center focused on improving bioengineering education through the applications of learning science, learning technology, and assessment and evaluation within the domain of bioengineering. This paper discusses results from a survey to explore the impact of the VaNTH experience on participating faculty and postdoctoral professionals. The results note that respondents differed in their familiarity with and applications of dimensions of the “How People Learn” framework and in their operationalization of effective instruction after their participation in VaNTH. Implications for teaching and learning with the context of a Center model are discussed along with next steps for exploring the experiences of faculty and professionals engaged in the VaNTH ERC

New AMD3100 derivatives for CXCR4 chemokine receptor targeted molecular imaging studies: synthesis, anti-HIV-1 evaluation and binding affinities

CXCR4 is a target of growing interest for the development of new therapeutic drugs and imaging agents as its role in multiple disease states has been demonstrated. AMD3100, a CXCR4 chemokine receptor antagonist that is in current clinical use as a haematopoietic stem cell mobilising drug, has been widely studied for its anti-HIV properties, potential to inhibit metastatic spread of certain cancers and, more recently, its ability to chelate radiometals for nuclear imaging. In this study, AMD3100 is functionalised on the phenyl moiety to investigate the influence of the structural modification on the anti-HIV-1 properties and receptor affinity in competition with anti-CXCR4 monoclonal antibodies and the natural ligand for CXCR4, CXCL12. The effect of complexation of nickel(II) in the cyclam cavities has been investigated. Two amino derivatives were obtained and are suitable intermediates for conjugation reactions to obtain CXCR4 molecular imaging agents. A fluorescent probe (BODIPY) and a precursor for 18F (positron emitting isotope) radiolabelling were conjugated to validate this route to new CXCR4 imaging agents