In Vivo Mapping of Vascular Inflammation Using Multimodal Imaging

Plaque vulnerability to rupture has emerged as a critical correlate to risk of adverse coronary events but there is as yet no clinical method to assess plaque stability in vivo. In the search to identify biomarkers of vulnerable plaques an association has been found between macrophages and plaque stability--the density and pattern of macrophage localization in lesions is indicative of probability to rupture. In very unstable plaques, macrophages are found in high densities and concentrated in the plaque shoulders. Therefore, the ability to map macrophages in plaques could allow noninvasive assessment of plaque stability. We use a multimodality imaging approach to noninvasively map the distribution of macrophages in vivo. The use of multiple modalities allows us to combine the complementary strengths of each modality to better visualize features of interest. Our combined use of Positron Emission Tomography and Magnetic Resonance Imaging (PET/MRI) allows high sensitivity PET screening to identify putative lesions in a whole body view, and high resolution MRI for detailed mapping of biomarker expression in the lesions.Macromolecular and nanoparticle contrast agents targeted to macrophages were developed and tested in three different mouse and rat models of atherosclerosis in which inflamed vascular plaques form spontaneously and/or are induced by injury. For multimodal detection, the probes were designed to contain gadolinium (T1 MRI) or iron oxide (T2 MRI), and Cu-64 (PET). PET imaging was utilized to identify regions of macrophage accumulation; these regions were further probed by MRI to visualize macrophage distribution at high resolution. In both PET and MR images the probes enhanced contrast at sites of vascular inflammation, but not in normal vessel walls. MRI was able to identify discrete sites of inflammation that were blurred together at the low resolution of PET. Macrophage content in the lesions was confirmed by histology.The multimodal imaging approach allowed high-sensitivity and high-resolution mapping of biomarker distribution and may lead to a clinical method to predict plaque probability to rupture

Galaxy And Mass Assembly (GAMA): The Bright Void Galaxy Population in the Optical and Mid-IR

We examine the properties of galaxies in the Galaxies and Mass Assembly (GAMA) survey located in voids with radii $>10~h^{-1}$ Mpc. Utilising the GAMA equatorial survey, 592 void galaxies are identified out to z~0.1 brighter than $M_{r} = -18.4$, our magnitude completeness limit. Using the $W_{\rm{H\alpha}}$ vs. [NII]/H$\alpha$ (WHAN) line strength diagnostic diagram, we classify their spectra as star forming, AGN, or dominated by old stellar populations. For objects more massive than $5\times10^{9}$ M$_{\odot}$, we identify a sample of 26 void galaxies with old stellar populations classed as passive and retired galaxies in the WHAN diagnostic diagram, else they lack any emission lines in their spectra. When matched to WISE mid-IR photometry, these passive and retired galaxies exhibit a range of mid-IR colour, with a number of void galaxies exhibiting [4.6]-[12] colours inconsistent with completely quenched stellar populations, with a similar spread in colour seen for a randomly drawn non-void comparison sample. We hypothesise that a number of these galaxies host obscured star formation, else they are star forming outside of their central regions targeted for single fibre spectroscopy. When matched to a randomly drawn sample of non-void galaxies, the void and non-void galaxies exhibit similar properties in terms of optical and mid-IR colour, morphology, and star formation activity, suggesting comparable mass assembly and quenching histories. A trend in mid-IR [4.6]-[12] colour is seen, such that both void and non-void galaxies with quenched/passive colours <1.5 typically have masses higher than $10^{10}$ M$_{\odot}$, where internally driven processes play an increasingly important role in galaxy evolution

Galaxy And Mass Assembly (GAMA): The Bright Void Galaxy Population in the Optical and Mid-IR

We examine the properties of galaxies in the Galaxies and Mass Assembly (GAMA) survey located in voids with radii $>10~h^{-1}$ Mpc. Utilising the GAMA equatorial survey, 592 void galaxies are identified out to z~0.1 brighter than $M_{r} = -18.4$, our magnitude completeness limit. Using the $W_{\rm{H\alpha}}$ vs. [NII]/H$\alpha$ (WHAN) line strength diagnostic diagram, we classify their spectra as star forming, AGN, or dominated by old stellar populations. For objects more massive than $5\times10^{9}$ M$_{\odot}$, we identify a sample of 26 void galaxies with old stellar populations classed as passive and retired galaxies in the WHAN diagnostic diagram, else they lack any emission lines in their spectra. When matched to WISE mid-IR photometry, these passive and retired galaxies exhibit a range of mid-IR colour, with a number of void galaxies exhibiting [4.6]-[12] colours inconsistent with completely quenched stellar populations, with a similar spread in colour seen for a randomly drawn non-void comparison sample. We hypothesise that a number of these galaxies host obscured star formation, else they are star forming outside of their central regions targeted for single fibre spectroscopy. When matched to a randomly drawn sample of non-void galaxies, the void and non-void galaxies exhibit similar properties in terms of optical and mid-IR colour, morphology, and star formation activity, suggesting comparable mass assembly and quenching histories. A trend in mid-IR [4.6]-[12] colour is seen, such that both void and non-void galaxies with quenched/passive colours <1.5 typically have masses higher than $10^{10}$ M$_{\odot}$, where internally driven processes play an increasingly important role in galaxy evolution

Cancer survivors' experiences of using survivorship care plans: a systematic review of qualitative studies

Purpose: Cancer survivorship care plans (SCPs) are currently used in care settings to assist survivors during the transition from treatment to survivorship. In this paper, the experiences of cancer survivors are examined to provide their perspective of how survivorship care plans are used in practice. Methods: A systematic review and critical review of the qualitative literature regarding the experiences of cancer survivors using survivorship care plans was completed. Databases reviewed included CINAHL, AMED, Embase, MEDLINE, Informit, ProQuest, PsycINFO, ScienceDirect, Wiley Online Library, Scopus and Web of Science from 2000 to 2014.ResultsEleven qualitative studies were appraised for methodological quality and content. They revealed four key themes: stakeholders agreed that SCPs should be used as a key strategy for cancer survivors; there was a lack of consensus on the format, content and who should develop the SCP; cancer survivors do not consistently receive SCPs; and there was a lack of evidence to support the use of SCPs in practice. Conclusions: There is great potential for SCPs to assist cancer survivors and this is supported by the range of qualitative literature examined in this study. Further research is required to examine the many practical issues relating to the delivery of SCPs and how they may be used across a variety of care contexts as well as providing further evidence to support their use. Implications for Cancer Survivors: With further research, refinement and contributions made by survivors, health researchers and health care professionals, the survivorship care plan is proposed to be a useful and practical tool aimed at supporting the survivorship continuum of care

Non-integumentary melanosomes can bias reconstructions of the colours of fossil vertebrates

The soft tissues of many fossil vertebrates preserve evidence of melanosomes-micron-scale organelles that inform on integumentary coloration and communication strategies. In extant vertebrates, however, melanosomes also occur in internal tissues. Hence, fossil melanosomes may not derive solely from the integument and its appendages. Here, by analyzing extant and fossil frogs, we show that non-integumentary melanosomes have high fossilization potential, vastly outnumber those from the skin, and potentially dominate the melanosome films preserved in some fossil vertebrates. Our decay experiments show that non-integumentary melanosomes usually remain in situ provided that carcasses are undisturbed. Micron-scale study of fossils, however, demonstrates that non-integumentary melanosomes can redistribute through parts of the body if carcasses are disturbed by currents. Collectively, these data indicate that fossil melanosomes do not always relate to integumentary coloration. Integumentary and non-integumentary melanosomes can be discriminated using melanosome geometry and distribution. This is essential to accurate reconstructions of the integumentary colours of fossil vertebrates

Calibration of ultraviolet, mid-infrared and radio star formation rate indicators

We present calibrations for star formation rate indicators in the ultraviolet, mid-infrared and radio continuum bands, including one of the first direct calibrations of 150 MHz as a star formation rate indicator. Our calibrations utilize 66 nearby star forming galaxies with Balmer decrement corrected H-alpha luminosities, which span 5 orders of magnitude in star formation rate and have absolute magnitudes of -24<M_r<-12. Most of our photometry and spectrophotometry is measured from the same region of each galaxy, and our spectrophotometry has been validated with SDSS photometry, so our random and systematic errors are small relative to the intrinsic scatter seen in star formation rate indicator calibrations. We find WISE W4 (22.8 micron), Spitzer 24 micron and 1.4 GHz have tight correlations with Balmer decrement corrected H-alpha luminosity, with scatter of only 0.2 dex. Our calibrations are comparable to those from the prior literature for L* galaxies, but for dwarf galaxies our calibrations can give star formation rates that are far greater than those derived from much of the prior literature.M.J.I.B. acknowledges financial support from The Australian Research Council (FT100100280), the Monash Research Accelerator Program (MRA), the Monash Outside Studies Programme (OSP), and the University of Cambridge. Part of this work was undertaken while M.J.I.B. was on OSP (sabbatical) leave at the University of Cambridge, Swinburne University, and the University of Melbourne. M.B. was supported by the MINEDUC-UA project, code ANT 1655. Funding for SDSS-III has been provided by the Alfred P. Sloan Foundation, the Participating Institutions, the National Science Foundation, and the U.S. Department of Energy Office of Science. The SDSS-III Web site is http://www.sdss3.org/. SDSS-III is managed by the Astrophysical Research Consortium for the Participating Institutions of the SDSS-III Collaboration including the University of Arizona, the Brazilian Participation Group, Brookhaven National Laboratory, University of Cambridge, University of Florida, the French Participation Group, the German Participation Group, the Instituto de Astrofisica de Canarias, the Michigan State/Notre Dame/JINA Participation Group, Johns Hopkins University, Lawrence Berkeley National Laboratory, Max Planck Institute for Astrophysics, New Mexico State University, New York University, Ohio State University, Pennsylvania State University, University of Portsmouth, Princeton University, the Spanish Participation Group, University of Tokyo, University of Utah, Vanderbilt University, University of Virginia, University of Washington, and Yale University. The NASA-Sloan Atlas was created by Michael Blanton, with extensive help and testing from Eyal Kazin, Guangtun Zhu, Adrian Price-Whelan, John Moustakas, Demitri Muna, Renbin Yan, and Benjamin Weaver. Funding for the NASA-Sloan Atlas has been provided by the NASA Astrophysics Data Analysis Program (08-ADP08-0072) and the NSF (AST-1211644)

There Is No Safe Dose of Prions

Understanding the circumstances under which exposure to transmissible spongiform encephalopathies (TSEs) leads to infection is important for managing risks to public health. Based upon ideas in toxicology and radiology, it is plausible that exposure to harmful agents, including TSEs, is completely safe if the dose is low enough. However, the existence of a threshold, below which infection probability is zero has never been demonstrated experimentally. Here we explore this question by combining data and mathematical models that describe scrapie infections in mice following experimental challenge over a broad range of doses. We analyse data from 4338 mice inoculated at doses ranging over ten orders of magnitude. These data are compared to results from a within-host model in which prions accumulate according to a stochastic birth-death process. Crucially, this model assumes no threshold on the dose required for infection. Our data reveal that infection is possible at the very low dose of a 1000 fold dilution of the dose that infects half the challenged animals (ID50). Furthermore, the dose response curve closely matches that predicted by the model. These findings imply that there is no safe dose of prions and that assessments of the risk from low dose exposure are right to assume a linear relationship between dose and probability of infection. We also refine two common perceptions about TSE incubation periods: that their mean values decrease linearly with logarithmic decreases in dose and that they are highly reproducible between hosts. The model and data both show that the linear decrease in incubation period holds only for doses above the ID50. Furthermore, variability in incubation periods is greater than predicted by the model, not smaller. This result poses new questions about the sources of variability in prion incubation periods. It also provides insight into the limitations of the incubation period assay

Propagation of RML Prions in Mice Expressing PrP Devoid of GPI Anchor Leads to Formation of a Novel, Stable Prion Strain

PrPC, a host protein which in prion-infected animals is converted to PrPSc, is linked to the cell membrane by a GPI anchor. Mice expressing PrPC without GPI anchor (tgGPI- mice), are susceptible to prion infection but accumulate anchorless PrPSc extra-, rather than intracellularly. We investigated whether tgGPI− mice could faithfully propagate prion strains despite the deviant structure and location of anchorless PrPSc. We found that RML and ME7, but not 22L prions propagated in tgGPI− brain developed novel cell tropisms, as determined by the Cell Panel Assay (CPA). Surprisingly, the levels of proteinase K-resistant PrPSc (PrPres) in RML- or ME7-infected tgGPI− brain were 25–50 times higher than in wild-type brain. When returned to wild-type brain, ME7 prions recovered their original properties, however RML prions had given rise to a novel prion strain, designated SFL, which remained unchanged even after three passages in wild-type mice. Because both RML PrPSc and SFL PrPSc are stably propagated in wild-type mice we propose that the two conformations are separated by a high activation energy barrier which is abrogated in tgGPI− mice

Exploring Pathways for Building Trust in Vaccination and Strengthening Health System Resilience

Background: Trust is critical to generate and maintain demand for vaccines in low and middle income countries. However, there is little documentation on how health system insufficiencies affect trust in vaccination and the process of re-building trust once it has been compromised. We reflect on how disruptions to immunizations systems can affect trust in vaccination and can compromise vaccine utilization. We then explore key pathways for overcoming system vulnerabilities in order to restore trust, to strengthen the resilience of health systems and communities, and to promote vaccine utilization. Methods: Utilizing secondary data and a review of the literature, we developed a causal loop diagram (CLD) to map the determinants of building trust in immunizations. Using the CLD, we devised three scenarios to illustrate common vulnerabilities that compromise trust and pathways to strengthen trust and utilization of vaccines, specifically looking at weak health systems, harmful communication channels, and role of social capital. Spill-over effects, interactions and other dynamics in the CLD were then examined to assess leverage points to counter these vulnerabilities. Results: Trust in vaccination arises from the interactions among experiences with the health system, the various forms of communication and social capital – both external and internal to communities. When experiencing system-wide shocks such as the case in Ebola-affected countries, distrust is reinforced by feedback between the health and immunization systems where distrust often lingers even after systems are restored and spills over beyond vaccination in the broader health system. Vaccine myths or anti-vaccine movements reinforce distrust. Social capital – the collective value of social networks of community members – plays a central role in increasing levels of trust. Conclusions: Trust is important, yet underexplored, in the context of vaccine utilization. Using a CLD to illustrate various scenarios helped to explore how common health and vaccine vulnerabilities can reinforce and spill over distrust through vicious, reinforcing feedback. Restoring trust requires a careful balance between eliminating vulnerabilities and strengthening social capital and interactions among communication channels