NAU is abuzz about career

In 2013, NAU Career Development implemented a robust 3 year assessment strategy. Year One, showcased at the 2015 Assessment Fair, focused on assessing the Reach of our program. In Year Two, we continued to assess Reach and added measures of Perception, including satisfaction surveys targeted towards students, employers, and campus partners, as well as interviews with faculty. Assessing outcomes of both quantitative and qualitative data analyses, our results demonstrated something exciting….NAU is Abuzz about Career! The busy bees at NAU Career Development are having an impact, resulting in prepared students, engaged partners, and satisfied employers. Our data is reviewed throughout the year, and continues to inform future priorities and next steps. Come see what the buzz is about

Functional MRI Assessment of Renal Fibrosis in Rat Models

poster abstractIntroduction Renal fibrosis is a common consequence of chronic kidney diseases which affects a large population. Therefore, it is important to establish imaging based noninvasive biomarkers to monitor the progression or regression of renal fibrosis instead of biopsy. Magnetic resonance imaging (MRI) could provide both high spatial resolution and excellent tissue contrast for visualization of kidney morphology. Moreover, MRI is capable of assessing pseudo perfusion (Df) and perfusion fraction (Pf) with intra-voxel incoherent motion (IVIM) imaging (1), tissue oxygenation with T2* mapping (2), macromolecular composition with T1rho imaging (3) and kidney function (eGFR) with dynamic contrast enhanced (DCE) imaging (4). This study is aimed to evaluate the sensitivity of these MRI techniques to the renal fibrotic changes in a rat model. Methods A total of 4 rats were scanned at early (2-5 days) and late (25-35 days) time points after surgical intervention (unilateral ureteral obstruction to induce renal fibrosis) on a Siemens Tim Trio 3T scanner using an 80mm inner diameter 8-channel rat body coil (RAPID, USA) under a stable anesthetized condition. Axial images of 80mm FOV, 2mm slice thick and sub-millimeter in-place resolution were acquired for different functional MRI techniques with following parameters, respectively: IVIM with10 b-values of 0 - 750 s/mm2. T2*: with 10 TEs of 8 - 66 ms; T1rho: with 9 TSL times of 5 - 80 ms; DCE: with150 dynamic measurements at a temporal resolution of 1.01 s. before and after a 15s injection of 1.1 ml GD-DTPA through rat tail with a power injector. Functional data were processed and analyzed using custom MATLAB programs or analysis tools installed in the MRI console workstation. Results Figure 1 shows an anatomical image of the obstructed (R) and healthy (L) rat kidneys. Figures 2-4 show example T1rho map, IVIM Df map, and T2* map, respectively. Quantitative results based on ROI measurements are summarized in table 1. Changes consistent with the expected progression of fibrosis were observed in the obstructed kidney (R) while the healthy kidney (L) and muscle region remained stable. Figure 5 shows the DCE-MRI images at baseline as well as 45s, 95s and 240s after contrast infusion. The timing and intensity of signal changes are clearly different between two kidneys. Quantitative results of DCE-MRI data and comparison with PET study is reported in a separate abstract. Discussion High quality anatomical and functional images of rat kidney can be obtained on a clinical 3.0T MR scanner with dedicated small animal coils and optimized imaging techniques. The findings suggest that IVIM, T2*, T1rho and DCE can be used to assess and monitor different aspects of physiological changes in kidney fibrosis

The depolarisation properties of powerful extragalactic radio sources as a function of cosmic epoch

We use the observed polarisation properties of a sample of 26 powerful radio galaxies and radio-loud quasars to constrain the conditions in the Faraday screens local to the sources. We adopt the cosmological redshift, low-frequency radio luminosity and physical size of the large-scale radio structures as our `fundamental' parameters. We find no correlation of the radio spectral index with any of the fundamental parameters. The observed rotation measure is also independent of these parameters. The difference between the rotation measures of the two lobes of an individual source as well as the dispersion of the rotation measure show significant correlations with the source redshift, but not with the radio luminosity or source size. Thus the small-scale structure observed in the rotation measure is caused by a Faraday screen local to the sources. The observed asymmetries between the lobes of our sources show no significant trends with each other or other source properties. Finally, we show that the commonly used model for the depolarisation of synchrotron radio emission by foreground Faraday screens is inconsistent with our observations. We apply alternative models to our data and show that they require a strong increase of the dispersion of the rotation measure inside the Faraday screens with cosmological redshift. Correcting our observations with these models for redshift effects, we find a strong correlation of the depolarisation measure with redshift and a significantly weaker correlation with radio luminosity. All our results are consistent with a decrease in the order of the magnetic field structure of the Faraday screen local to the sources for increasing cosmological redshift. (abridged)Comment: 14 pages, 16 eps figures, accepted by MNRA

Magnetic Resonance Diffusion Tensor Imaging and Diffusion Compartmental Modeling in an Animal Model of Chronic Kidney Disease

poster abstractPurpose: According to National Health and Nutrition Examination Survey (NHANES), Chronic Kidney Disease (CKD) affects 25% of the US population over age 601. Renal fibrosis, a common pathological consequence of CKD, is a progressive process that ultimately leads to end-stage renal failure that requires dialysis or kidney transplantation2. There is a compelling need for non-invasive biomarkers that track changes in the tissue microenvironment associated with CKD. Several studies using magnetic resonance diffusion tensor imaging (DTI) have been proposed as imaging biomarkers for CKD3. In this study, in addition to DTI, we explored a diffusion-compartmental modeling technique4 to study the microstructures of hypoxia induced animal models of CKD. Method: Preparation of the animal CKD model: Experiments were performed in 4 Wistar Rats using protocols approved by the Institutional Animal Care and Use Committee (IACUC). Two days prior to the first magnetic resonance imaging (MRI) scan; surgical intervention in right renal artery was performed in all the animals to create hypoxia induced renal fibrosis. The MRI scans were repeated at an interval of approximately one month. During the imaging session, the rats were sedated and kept in head-first supine position. MRI imaging: The MRI diffusion pulse sequence was a single-shot spin-echo echo-planar imaging (SS-SE-EPI) sequence with multiple diffusion-weighting b-values (i.e. 3 shells with b-values of 150, 300 and 450 s/mm2) and multiple diffusion-weighting directions at each shell (i.e., 10, 19 and 30, respectively). Diffusion directions in each shell and in the projected sphere with all directions (i.e., total 59) were optimized for uniform diffusion sampling in the spherical space5. The repetition time (TR) is 2200 ms and echo time (TE) is 73.6 ms. A total of four signal averages was performed. The imaging parameters were field-of-view (FOV) = 128 x 64 mm, matrix size = 128 x 64, isotropic voxel size of 1 mm3, and 20 oblique coronal slices. Image data processing: DTI derived parameters including axial diffusivity (Da), radial diffusivity (Dr), mean diffusivity (MD), and fractional anisotropy (FA) were computed6. The diffusion compartmental model originally proposed for the brain called neutrite orientation dispersion and density imaging (NODDI)4 was modified to fit the water diffusivities of kidneys. The NODDI model with Watson stick framework produces the volume fraction of stick like diffusion compartment that may explain the active diffusion (transport) of water in the interstitial space between renal tubules, ellipsoid like diffusion compartment that may explain diffusion inside renal tubule, and a fast isotropic diffusion to account for the pseudo-diffusion term relating to bulk vascular flow. The normalized diffusion intensity was fit with a non-linear mathematical model given by A = (1-Viso) (VicAic+(1-Vic) Aec) + VisoAiso ; where Vic and Viso are the volume fraction of active water transport and free diffusion compartments in the kidney, respectively. Aic, Aec and Aiso are the normalized diffusion signal contribution from stick, tubule and free diffusion compartments, respectively. In the raw DW data, the b-value=0 volume clearly shows three distinct layers in the rat kidney representing the inner medulla, outer medulla and cortex (Figure1). Non-overlapping ROI's were constructed from the b-value =0 images. Figure 1: The DTI and Diffusion compartmental modeling parameter for RAT Kidney 2 days after surgical intervention. The Cortex (C), the Outer Medulla (OM) and Inner Medulla (IM) are shown in raw b0 maps. The orientation of the images follows radiology convention. Results: On post-surgical day 2, the overall water diffusivity (i.e., mean diffusivity (MD)) decreased significantly in the outer medullae and inner medullae of the surgical kidneys (Figure 2 B green bars). In the compartmental model, the volume fraction of the stick (interstitial) diffusion compartment (Vic) in right outer and inner medulla was significantly increased compared to the left (Figure 2A blue bars), whereas the volume fraction of water diffusion inside the tubules (Vec = (1-Vic)) decreased significantly. In addition, isotropic free diffusion compartment (Viso) was significantly lower in the inner medullae of the right kidneys. The axial diffusivity (Da) that may describe the diffusion parallel to the tubules decreased significantly in outer and inter medullae of the right surgical kidneys (Figure 2 B blue bars). The radial diffusivity (Dr) that may describe the water diffusion perpendicularly to the renal tubules decreased significantly in only the outer medullae of the right kidneys (Figure 2B gray bars). While FA shows high value in the inner medullae for both left and right kidneys, no significant results were found between left and right kidneys and between two time points. Over the one-month period of time, right inner medullae continued the significant changes in the diffusivity measurements (Figure 2C and D, right groups), but the diffusivities remained similar in the outer medullae (Figure 2 C and D, middle groups). No significant findings were found in the renal cortices between the right and left kidneys on post-surgical day 2 (Figure 2 A and B). Interestingly, the right renal cortices did have significant increase in Vic and decreases in Da, Dr, and MD over the one-month time period (Figure 2 C and D). Figure 2: Diffusion Compartmental (Figure 2A) and DTI (Figure 2B) parameters for Right Cortex (RC) and Left Cortex (LC), Right Outer Medulla (ROM) and Left Outer Medulla (LOM) and Right Inner Medulla (RIM) and Left Inner Medulla (LIM) on post-surgical day 2. (Figure 2C) Is the time series study of diffusion compartmental parameters and (Figure 2D) for DTI parameters for the right kidneys at post-surgical day 2 and 30, respectively. The bars represent diffusion measurements of all four rats. The overhead connecting lines represent significant statistical student t-test with p-value < 0.01. Discussions and Conclusion: The DTI and NODDI analogous diffusion compartment derived parameters are sensitive to the micro-structural changes in kidneys after surgical hypoxia intervention. The outer and inner medullae appear most sensitive to the surgical hypoxia intervention as early as post-surgical day 2. The preliminary result suggests that water diffusion decreases due to renal fibrosis, and more so inside the Henle tubules. In post-surgical day 30, renal cortices start to show changes in water diffusivities while inner medullae continue pathological changes. The NODDI compartmental model shows promising preliminary results in revealing renal microenvironments under the influences of hypoxia induced renal fibrosis. Further study is required to optimize and validate the model

In vivo UTE-MRI reveals positive effects of raloxifene on skeletal bound water in skeletally mature beagle dogs

Raloxifene positively affects mechanical properties of the bone matrix in part through modification of skeletal bound water. The goal of this study was to determine if raloxifene induced alterations in skeletal hydration could be measured in vivo using ultra-short echotime magnetic resonance imaging (UTE-MRI). Twelve skeletally mature female beagle dogs (n=6/group) were treated for 6 months with oral doses of saline vehicle (VEH, 1 ml/kg/day) or raloxifene (RAL, 0.5 mg/kg/day). Following six months of treatment, all animals underwent in vivo UTE-MRI of the proximal tibial cortical bone. UTE-MRI signal intensity versus echotime curves were analyzed by fitting a double exponential to determine the short and long relaxation times of water with the bone (dependent estimations of bound and free water, respectively). Raloxifene-treated animals had significantly higher bound water (+14%; p = 0.05) and lower free water (-20%) compared to vehicle-treated animals. These data provide the first evidence that drug-induced changes in skeletal hydration can be non-invasively assessed using UTE-MRI.Funding for this study was provided by NIH (AR 62002 and a BIRT supplement). Raloxifene was provided by through an MTA with Eli Lilly

Characterization of 11C-GSK1482160 for Targeting the P2X7 Receptor as a Biomarker for Neuroinflammation

The purinergic receptor subtype 7 (P2X7R) represents a novel molecular target for imaging neuroinflammation via PET. GSK1482160, a potent P2X7R antagonist, has high receptor affinity, high blood–brain barrier penetration, and the ability to be radiolabeled with 11C. We report the initial physical and biologic characterization of this novel ligand. Methods: 11C-GSK1482160 was synthesized according to published methods. Cell density studies were performed on human embryonic kidney cell lines expressing human P2X7R (HEK293-hP2X7R) and underwent Western blotting, an immunofluorescence assay, and radioimmunohistochemistry analysis using P2X7R polyclonal antibodies. Receptor density and binding potential were determined by saturation and association–disassociation kinetics, respectively. Peak immune response to lipopolysaccharide treatment in mice was determined in time course studies and analyzed via Iba1 and P2X7R Western blotting and Iba1 immunohistochemistry. Whole-animal biodistribution studies were performed on saline- or lipopolysaccharide-treated mice at 15, 30, and 60 min after radiotracer administration. Dynamic in vivo PET/CT was performed on the mice at 72 h after administration of saline, lipopolysaccharide, or lipopolysaccharide + blocking, and 2-compartment, 5-parameter tracer kinetic modeling of brain regions was performed. Results: P2X7R changed linearly with concentrations or cell numbers. For high-specific-activity 11C-GSK1482160, receptor density and Kd were 1.15 ± 0.12 nM and 3.03 ± 0.10 pmol/mg, respectively, in HEK293-hP2X7R membranes. Association constant kon, dissociation constant koff, and binding potential (kon/koff) in HEK293-hP2X7R cells were 0.2312 ± 0.01542 min−1⋅nM−1, 0.2547 ± 0.0155 min−1, and 1.0277 ± 0.207, respectively. Whole-brain Iba1 expression in lipopolysaccharide-treated mice peaked by 72 h on immunohistochemistry, and Western blot analysis of P2X7R for saline- and lipopolysaccharide-treated brain sections showed a respective 1.8- and 1.7-fold increase in signal enhancement at 72 h. Biodistribution of 11C-GSK1482160 in saline- and lipopolysaccharide-treated mice at 72 h was statistically significant across all tissues studied. In vivo dynamic 11C-GSK1482160 PET/CT of mice at 72 h after administration of saline, lipopolysaccharide, or lipopolysaccharide + blocking showed a 3.2-fold increase and 97% blocking by 30 min. The total distribution volumes for multiple cortical regions and the hippocampus showed statistically significant increases and were blocked by an excess of authentic standard GSK1482160. Conclusion: The current study provides compelling data that support the suitability of 11C-GSK1482160 as a radioligand targeting P2X7R, a biomarker of neuroinflammation

Evaluation of 11C-Acetate and 18 F-FDG PET/CT in mouse multidrug resistance gene-2 deficient mouse model of hepatocellular carcinoma

Background Hepatocellular carcinoma (HCC) remains a global health problem with unique diagnostic and therapeutic challenges, including difficulties in identifying the highest risk patients. Previous work from our lab has established the murine multidrug resistance-2 mouse (MDR2) model of HCC as a reasonable preclinical model that parallels the changes seen in human inflammatory associated HCC. The purpose of this study is to evaluate modalities of PET/CT in MDR2−/− mice in order to facilitate therapeutic translational studies from bench to bedside. Methods 18F-FDG and 11C-acetate PET/CT was performed on 12 m MDR2−/− mice (n = 3/tracer) with HCC and 12 m MDR2−/+ control mice (n = 3/tracer) without HCC. To compare PET/CT to biological markers of HCC and cellular function, serum alpha-fetoprotein (AFP), lysophosphatidic acid (LPA), cAMP and hepatic tumor necrosis factor α (TNFα) were quantified in 3-12 m MDR2−/− (n = 10) mice using commercially available ELISA analysis. To translate results in mice to patients 11C-acetate PET/CT was also performed in 8 patents suspected of HCC recurrence following treatment and currently on the liver transplant wait list. Results Hepatic18F-FDG metabolism was not significantly increased in MDR2−/− mice. In contrast, hepatic 11C-acetate metabolism was significantly elevated in MDR2−/− mice when compared to MDR2−/+ controls. Serum AFP and LPA levels increased in MDR2−/− mice contemporaneous with the emergence of HCC. This was accompanied by a significant decrease in serum cAMP levels and an increase in hepatic TNFα. In patients suspected of HCC recurrence there were 5 true positives, 2 true negatives and 1 suspected false 11C-acetate negative. Conclusions Hepatic 11C-acetate PET/CT tracks well with HCC in MDR2−/− mice and patients with underlying liver disease. Consequently 11C-acetate PET/CT is well suited to study 1) HCC emergence/progression in patients and 2) reduce animal numbers required to study new chemotherapeutics in murine models of HCC

Strengths and limitations of a tool for monitoring and evaluating First Peoples' health promotion from an ecological perspective

Background: An ecological approach to health and health promotion targets individuals and the environmental determinants of their health as a means of more effectively influencing health outcomes. The approach has potential value as a means to more accurately capture the holistic nature of Australian First Peoples’ health programs and the way in which they seek to influence environmental, including social, determinants of health. Methods: We report several case studies of applying an ecological approach to health program evaluation using a tool developed for application to mainstream public health programs in North America – Richard’s ecological coding procedure. Results: We find the ecological approach in general, and the Richard procedure specifically, to have potential for broader use as an approach to reporting and evaluation of health promotion programs. However, our experience applying this tool in academic and community-based program evaluation contexts, conducted in collaboration with First Peoples of Australia, suggests that it would benefit from cultural adaptations that would bring the ecological coding procedure in greater alignment with the worldviews of First Peoples and better identify the aims and strategies of local health promotion programs. Conclusions: Establishing the cultural validity of the ecological coding procedure is necessary to adequately capture the underlying program activities of community-based health promotion programs designed to benefit First Peoples, and its collaborative implementation with First Peoples supports a human rights approach to health program evaluation.Kevin Rowley, Joyce Doyle, Leah Johnston, Rachel Reilly, Leisa McCarthy, Mayatili Marika, Therese Riley, Petah Atkinson, Bradley Firebrace, Julie Calleja and Margaret Carg

A new search for distant radio galaxies in the Southern hemisphere -- III. Optical spectroscopy and analysis of the MRCR--SUMSS sample

We have compiled a sample of 234 ultra-steep-spectrum(USS)-selected radio sources in order to find high-redshift radio galaxies (HzRGs). The sample is in the southern sky at -40 deg < DEC < -30 deg which is the overlap region of the 408-MHz Revised Molonglo Reference Catalogue, 843-MHz Sydney University Molonglo Sky Survey (the MRCR--SUMSS sample) and the 1400-MHz NRAO VLA Sky Survey. This is the third in a series of papers on the MRCR--SUMSS sample. Here we present optical spectra from the ANU 2.3-m telescope, ESO New Technology Telescope and ESO Very Large Telescope for 52 of the identifications from Bryant et al. (2009, Paper II), yielding redshifts for 36 galaxies, 13 of which have z>2. We analyse the K-z distribution and compare 4-arcsec-aperture magnitudes with 64-kpc aperture magnitudes in several surveys from the literature; the MRCR--SUMSS sample is found to be consistent with models for 10^{11}-10^{12} solar mass galaxies. Dispersions about the fits in the K-z plot support passive evolution of radio galaxy hosts since z>3. By comparing USS-selected samples in the literature, we find that the resultant median redshift of the samples shown is not dependent on the flux density distribution or selection frequency of each sample. In addition, our finding that the majority of the radio spectral energy distributions remain straight over a wide frequency range suggests that a k-correction is not responsible for the success of USS-selection in identifying high redshift radio galaxies and therefore the steep radio spectra may be intrinsic to the source or a product of the environment. Two galaxies have been found to have both compact radio structures and strong self-absorption in the Ly-alpha line, suggesting they are surrounded by a dense medium...abridged.Comment: Accepted for MNRAS. 25 page