The influence of perfusion solution on renal graft viability assessment

BACKGROUND: Kidneys from donors after cardiac or circulatory death are exposed to extended periods of both warm ischemia and intra-arterial cooling before organ recovery. Marshall’s hypertonic citrate (HOC) and Bretschneider’s histidine-tryptophan-ketoglutarate (HTK) preservation solutions are cheap, low viscosity preservation solutions used clinically for organ flushing. The aim of the present study was to evaluate the effects of these two solutions both on parameters used in clinical practice to assess organ viability prior to transplantation and histological evidence of ischemic injury after reperfusion. METHODS: Rodent kidneys were exposed to post-mortem warm ischemia, extended intra-arterial cooling (IAC) (up to 2 h) with preservation solution and reperfusion with either Krebs-Hensleit or whole blood in a transplant model. Control kidneys were either reperfused directly after retrieval or stored in 0.9% saline. Biochemical, immunological and histological parameters were assessed using glutathione-S-transferase (GST) enzymatic assays, polymerase chain reaction and mitochondrial electron microscopy respectively. Vascular function was assessed by supplementing the Krebs-Hensleit perfusion solution with phenylephrine to stimulate smooth muscle contraction followed by acetylcholine to trigger endothelial dependent relaxation. RESULTS: When compared with kidneys reperfused directly post mortem, 2 h of IAC significantly reduced smooth muscle contractile function, endothelial function and upregulated vascular cellular adhesion molecule type 1 (VCAM-1) independent of the preservation solution. However, GST release, vascular resistance, weight gain and histological mitochondrial injury were dependent on the preservation solution used. CONCLUSIONS: We conclude that initial machine perfusion viability tests, including ischemic vascular resistance and GST, are dependent on the perfusion solution used during in situ cooling. HTK-perfused kidneys will be heavier, have higher GST readings and yet reduced mitochondrial ischemic injury when compared with HOC-perfused kidneys. Clinicians should be aware of this when deciding which kidneys to transplant or discard

Exploring the Feasibility, Validity, and Reliability of DIGEST after Maxillectomy

https://openworks.mdanderson.org/sumexp23/1016/thumbnail.jp

The Void Galaxy Survey

The Void Galaxy Survey (VGS) is a multi-wavelength program to study $\sim$60 void galaxies. Each has been selected from the deepest interior regions of identified voids in the SDSS redshift survey on the basis of a unique geometric technique, with no a prior selection of intrinsic properties of the void galaxies. The project intends to study in detail the gas content, star formation history and stellar content, as well as kinematics and dynamics of void galaxies and their companions in a broad sample of void environments. It involves the HI imaging of the gas distribution in each of the VGS galaxies. Amongst its most tantalizing findings is the possible evidence for cold gas accretion in some of the most interesting objects, amongst which are a polar ring galaxy and a filamentary configuration of void galaxies. Here we shortly describe the scope of the VGS and the results of the full analysis of the pilot sample of 15 void galaxies.Comment: 9 pages, 6 figures. This is an extended version of a paper to appear in "Environment and the Formation of Galaxies: 30 years later", Proceedings of Symposium 2 of JENAM 2010, eds. I. Ferreras, A. Pasquali, ASSP, Springer. Version with highres figures at http://www.astro.rug.nl/~weygaert/vgs_jenam_weygaert.col.pd

The biological effects of subacute inhalation of diesel exhaust following addition of cerium oxide nanoparticles in atherosclerosis-prone mice

AbstractBackgroundCerium oxide (CeO2) nanoparticles improve the burning efficiency of fuel, however, little is known about health impacts of altered emissions from the vehicles.MethodsAtherosclerosis-prone apolipoprotein E knockout (ApoE−/−) mice were exposed by inhalation to diluted exhaust (1.7mg/m3, 20, 60 or 180min, 5 day/week, for 4 weeks), from an engine using standard diesel fuel (DE) or the same diesel fuel containing 9ppm cerium oxide nanoparticles (DCeE). Changes in hematological indices, clinical chemistry, atherosclerotic burden, tissue levels of inflammatory cytokines and pathology of the major organs were assessed.ResultsAddition of CeO2 to fuel resulted in a reduction of the number (30%) and surface area (10%) of the particles in the exhaust, whereas the gaseous co-pollutants were increased (6–8%). There was, however, a trend towards an increased size and complexity of the atherosclerotic plaques following DE exposure, which was not evident in the DCeE group. There were no clear signs of altered hematological or pathological changes induced by either treatment. However, levels of proinflammatory cytokines were modulated in a brain region and liver following DCeE exposure.ConclusionsThese results imply that addition of CeO2 nanoparticles to fuel decreases the number of particles in exhaust and may reduce atherosclerotic burden associated with exposure to standard diesel fuel. From the extensive assessment of biological parameters performed, the only concerning effect of cerium addition was a slightly raised level of cytokines in a region of the central nervous system. Overall, the use of cerium as a fuel additive may be a potentially useful way to limit the health effects of vehicle exhaust. However, further testing is required to ensure that such an approach is not associated with a chronic inflammatory response which may eventually cause long-term health effects

Airway and parenchymal strains during bronchoconstriction in the precision cut lung slice

The precision-cut lung slice (PCLS) is a powerful tool for studying airway reactivity, but biomechanical measurements to date have largely focused on changes in airway caliber. Here we describe an image processing tool that reveals the associated spatio-temporal changes in airway and parenchymal strains. Displacements of sub-regions within the PCLS are tracked in phase-contrast movies acquired after addition of contractile and relaxing drugs. From displacement maps, strains are determined across the entire PCLS or along user-specified directions. In a representative mouse PCLS challenged with 10−4M methacholine, as lumen area decreased, compressive circumferential strains were highest in the 50 μm closest to the airway lumen while expansive radial strains were highest in the region 50–100 μm from the lumen. However, at any given distance from the airway the strain distribution varied substantially in the vicinity of neighboring small airways and blood vessels. Upon challenge with the relaxant agonist chloroquine, although most strains disappeared, residual positive strains remained a long time after addition of chloroquine, predominantly in the radial direction. Taken together, these findings establish strain mapping as a new tool to elucidate local dynamic mechanical events within the constricting airway and its supporting parenchyma

SPARTAN: a global network to evaluate and enhance satellite-based estimates of ground-level particulate matter for global health applications

Ground-based observations have insufficient spatial coverage to assess long-term human exposure to fine particulate matter (PM2.5) at the global scale. Satellite remote sensing offers a promising approach to provide information on both short-and long-term exposure to PM2.5 at local-to-global scales, but there are limitations and outstanding questions about the accuracy and precision with which ground-level aerosol mass concentrations can be inferred from satellite remote sensing alone. A key source of uncertainty is the global distribution of the relationship between annual average PM2.5 and discontinuous satellite observations of columnar aerosol optical depth (AOD). We have initiated a global network of ground-level monitoring stations designed to evaluate and enhance satellite remote sensing estimates for application in health-effects research and risk assessment. This Surface PARTiculate mAtter Network (SPARTAN) includes a global federation of ground-level monitors of hourly PM2.5 situated primarily in highly populated regions and collocated with existing ground-based sun photometers that measure AOD. The instruments, a three-wavelength nephelometer and impaction filter sampler for both PM2.5 and PM10, are highly autonomous. Hourly PM2.5 concentrations are inferred from the combination of weighed filters and nephelometer data. Data from existing networks were used to develop and evaluate network sampling characteristics. SPARTAN filters are analyzed for mass, black carbon, water-soluble ions, and metals. These measurements provide, in a variety of regions around the world, the key data required to evaluate and enhance satellite-based PM2.5 estimates used for assessing the health effects of aerosols. Mean PM2.5 concentrations across sites vary by more than 1 order of magnitude. Our initial measurements indicate that the ratio of AOD to ground-level PM2.5 is driven temporally and spatially by the vertical profile in aerosol scattering. Spatially this ratio is also strongly influenced by the mass scattering efficiency.Fil: Snider, G.. Dalhousie University Halifax; CanadáFil: Weagle, C. L.. Dalhousie University Halifax; CanadáFil: Martin, R. V.. Dalhousie University Halifax; Canadá. University of Cambridge; Reino UnidoFil: van Donkelaar, A.. Dalhousie University Halifax; CanadáFil: Conrad, K.. Dalhousie University Halifax; CanadáFil: Cunningham, D.. Dalhousie University Halifax; CanadáFil: Gordon, C.. Dalhousie University Halifax; CanadáFil: Zwicker, M.. Dalhousie University Halifax; CanadáFil: Akoshile, C.. University of Ilorin; NigeriaFil: Artaxo, P.. Governo Do Estado de Sao Paulo; BrasilFil: Anh, N. X.. Vietnam Academy of Science and Technology. Institute of Geophysics; VietnamFil: Brook, J.. University of Toronto; CanadáFil: Dong, J.. Tsinghua University; ChinaFil: Garland, R. M.. North-West University; SudáfricaFil: Greenwald, R.. Rollins School of Public Health; Estados UnidosFil: Griffith, D.. Council for Scientific and Industrial Research; SudáfricaFil: He, K.. Tsinghua University; ChinaFil: Holben, B. N.. NASA Goddard Space Flight Center; Estados UnidosFil: Kahn, R.. NASA Goddard Space Flight Center; Estados UnidosFil: Koren, I.. Weizmann Institute Of Science Israel; IsraelFil: Lagrosas, N.. Manila Observatory, Ateneo de Manila University campus; FilipinasFil: Lestari, P.. Institut Teknologi Bandung; IndonesiaFil: Ma, Z.. Rollins School of Public Health; Estados UnidosFil: Vanderlei Martins, J.. University of Maryland; Estados UnidosFil: Quel, Eduardo Jaime. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rudich, Y.. Weizmann Institute Of Science Israel; IsraelFil: Salam, A.. University Of Dhaka; BangladeshFil: Tripathi, S. N.. Indian Institute Of Technology, Kanpur; IndiaFil: Yu, C.. Rollins School of Public Health; Estados UnidosFil: Zhang, Q.. Tsinghua University; ChinaFil: Zhang, Y.. Tsinghua University; ChinaFil: Brauer, M.. University of British Columbia; CanadáFil: Cohen, A.. Health Effects Institute; Estados UnidosFil: Gibson, M. D.. Dalhousie University Halifax; CanadáFil: Liu, Y.. Rollins School of Public Health; Estados Unido

Understanding a constellation of eight COVID-19 disease prevention behaviours using the COM-B model and the theoretical domains framework: a qualitative study using the behaviour change wheel

Background: The use of behavioural science and behaviour change within local authorities and public health has supported healthful change; as evidenced by its importance and contribution to reducing harm during the COVID-19 pandemic. It can provide valuable information to enable the creation of evidence-based intervention strategies, co-created with the people they are aimed at, in an effective and efficient manner. Aim: This study aimed to use the COM-B model to understand the Capability, Opportunity and Motivation of performing a constellation of eight COVID-19 disease prevention behaviours related to the slogans of ‘Hands, Face, Space, Fresh Air’; ‘Find, Isolate, Test, (FIT), and Vaccinate’ in those employed in workplaces identified as high risk for transmission of the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) to support intervention development. Methods: This qualitative study recruited twenty-three participants (16 female, 7 male), who were interviewed from three environments (schools, care homes, warehouses) across three local authorities. Semi-structured interviews were analysed using thematic analysis. Findings: Ten core themes were identified inductively; (1) knowledge and skills, (2) regulating the behaviour, (3) willingness to act, (4) necessity and concerns, (5) emotional impact, (6) conducive environment, (7) societal influence, (8) no longer united against COVID-19, (9) credible leadership, and (10) inconsistent adherence to COVID-19 prevention behaviours. Themes were then deductively mapped to the COM-B model of behaviour change and the theoretical domains framework and a logic model using the behaviour change wheel (BCW) was produced to inform intervention design. Conclusion: This study offers a novel approach to analysis that has included eight behaviours within a single thematic analysis and COM-B diagnosis. This will enable local authorities to direct limited resources to overarching priorities. Of key importance, was the need for supportive and credible leadership, alongside developing interventions collaboratively with the target audience. COVID-19 has had an emotional toll on those interviewed, however, promoting the value of disease prevention behaviours, over and above their costs, can facilitate behaviour. Developing knowledge and skills, through education, training, marketing and modelling can further facilitate behaviour. This supports guidance produced by the British Psychological Society COVID-19 behavioural science and disease prevention taskforce

Rare germline variants in DNA repair genes and the angiogenesis pathway predispose prostate cancer patients to develop metastatic disease

Background Prostate cancer (PrCa) demonstrates a heterogeneous clinical presentation ranging from largely indolent to lethal. We sought to identify a signature of rare inherited variants that distinguishes between these two extreme phenotypes. Methods We sequenced germline whole exomes from 139 aggressive (metastatic, age of diagnosis < 60) and 141 non-aggressive (low clinical grade, age of diagnosis ≥60) PrCa cases. We conducted rare variant association analyses at gene and gene set levels using SKAT and Bayesian risk index techniques. GO term enrichment analysis was performed for genes with the highest differential burden of rare disruptive variants. Results Protein truncating variants (PTVs) in specific DNA repair genes were significantly overrepresented among patients with the aggressive phenotype, with BRCA2, ATM and NBN the most frequently mutated genes. Differential burden of rare variants was identified between metastatic and non-aggressive cases for several genes implicated in angiogenesis, conferring both deleterious and protective effects. Conclusions Inherited PTVs in several DNA repair genes distinguish aggressive from non-aggressive PrCa cases. Furthermore, inherited variants in genes with roles in angiogenesis may be potential predictors for risk of metastases. If validated in a larger dataset, these findings have potential for future clinical application

Gas Accretion and Galactic Chemical Evolution: Theory and Observations

This chapter reviews how galactic inflows influence galaxy metallicity. The goal is to discuss predictions from theoretical models, but particular emphasis is placed on the insights that result from using models to interpret observations. Even as the classical G-dwarf problem endures in the latest round of observational confirmation, a rich and tantalizing new phenomenology of relationships between $M_*$, $Z$, SFR, and gas fraction is emerging both in observations and in theoretical models. A consensus interpretation is emerging in which star-forming galaxies do most of their growing in a quiescent way that balances gas inflows and gas processing, and metal dilution with enrichment. Models that explicitly invoke this idea via equilibrium conditions can be used to infer inflow rates from observations, while models that do not assume equilibrium growth tend to recover it self-consistently. Mergers are an overall subdominant mechanism for delivering fresh gas to galaxies, but they trigger radial flows of previously-accreted gas that flatten radial gas-phase metallicity gradients and temporarily suppress central metallicities. Radial gradients are generically expected to be steep at early times and then flattened by mergers and enriched inflows of recycled gas at late times. However, further theoretical work is required in order to understand how to interpret observations. Likewise, more observational work is needed in order to understand how metallicity gradients evolve to high redshifts.Comment: Invited review to appear in Gas Accretion onto Galaxies, Astrophysics and Space Science Library, eds. A. J. Fox & R. Dav\'e, to be published by Springer. 29 pages, 2 figure