Characterization of A Type 1 Collagen Targeted PET Tracer

poster abstractRenal fibrosis occurs in many diseases of the kidney, including chronic kidney disease (CKD). Renal fibrosis is characterized by an excessive accumulation and deposition of extracellular matrix components, mainly type I collagen. Determination of the presence and extent of renal fibrosis may aid in the prediction of the long-term outcome of renal function in CKD. Biopsy is considered the gold standard in the diagnosis of renal fibrosis; however biopsy is inherently invasive and does not easily lend itself to following the disease thru time. A noninvasive technique such as PET would both allow the detection and monitoring of renal fibrosis progression. A type I collagen-specific cyclic peptide, EP-3533, has been identified and used as a contrast agent in MRI after conjugation with three Gd-DOTA chelates (Caravan et al 2007). To explore the potential for imaging with PET, which can provide a quantitative assessment of regional peptide localization, we have prepared an EP-3533 conjugate incorporating the NODAGA chelating agent at its amine terminus, and radiolabeled that conjugate with generator-produced positron-emitting 68Ga (68-minute half-life). In vitro association kinetics binding of the labeled peptide was performed in collagen type 1 coated plates, where 68GaDOTA-EP-3533 exhibited a Kd of 0.2 M for type I collagen. To better characterize the tracer in an animal model, renal fibrosis was induced in male Wistar rats by clamping the renal artery and vein of the left kidney for 50 minutes. Thus providing both a diseased and control kidney in each animal. Approximately 10 weeks after surgery both left (fibrotic) and right (normal) kidneys were resected and frozen and mounted in OTC for cryotomy. Longitudinal sections obtained from each kidney were used for autoradiography. ROI analysis found an approximate two- to four-fold region-dependent increase in binding in fibrotic tissue compared to normal. Collagen and non-collagen protein levels were determined in the same kidney sections that had been used for autoradiography using a commercially available staining assay. This assay yielded a 1.7-fold difference in collagen levels between normal and fibrotic tissue. Additionally, representative slices were stained with Sirius Red for histological evaluation. Preliminary data indicates that 68Ga-NODAGA-EP-3533 binds to collagen-rich tissue, consistent with the literature for Gd-DOTA-EP-3533. In vivo studies in an animal model of fibrosis are needed to further characterize this tracer and its potential for PET tracer detection and monitoring of Renal Fibrosis

Modifications of the Fine Structure of the Incisor Pulp of the Guinea Pig during Fxperimental Scurvy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68076/2/10.1177_00220345660450030301.pd

Heterogeneity of genetic parameters for calving difficulty in Holstein heifers in Ireland

Calving difficulty is a trait that greatly affects animal welfare, herd profitability, and the amount of labor required by cattle farmers. It is influenced by direct and maternal genetic components. Selection and breeding strategies can optimize the accuracy of genetic evaluations and correctly emphasize calving difficulty in multiple-trait indices provided there are accurate estimates of genetic parameters. In Ireland, large differences exist in the age at which heifers first give birth to calves. The objective of this study was to estimate genetic parameters for calving difficulty in first-parity Holsteins and to determine whether these differed with age of the heifer at calving. Transformed calving difficulty records for 18,798 Holstein heifers, which calved between January 2002 and May 2006, were analyzed using univariate, multitrait, and random regression linear sire-maternal grandsire models. The model that 1) fitted a second-order random regression of dam age at first parity for the direct component, 2) treated the maternal component as a single trait regardless of dam age, and 3) fitted a single residual variance component was optimal. Heritabilities for direct (0.13) and maternal (0.04) calving difficulty were significantly different from zero. These 2 components were moderately negatively correlated (¿0.47). Estimates of direct genetic variance and heritability were heterogeneous along the dam age trajectory, decreasing initially with dam age before subsequently increasing. Heritability estimates ranged between 0.11 and 0.37 and were higher for records with younger and older dams at parturition. Genetic correlations between the direct components of calving difficulty decreased from unity to 0.5 with increasing distance between dam ages at parturition. The results of this study indicated that heterogeneity of direct genetic variance existed for calving difficulty, depending on dam age at first parturition

Photo-production of Nucleon Resonances and Nucleon Spin Structure Function in the Resonance Region

The photo-production of nucleon resonances is calculated based on a chiral constituent quark model including both relativistic corrections H{rel} and two-body exchange currents, and it is shown that these effects play an important role. We also calculate the first moment of the nucleon spin structure function g1 (x,Q^2) in the resonance region, and obtain a sign-changing point around Q^2 ~ 0.27 {GeV}^2 for the proton.Comment: 23 pages, 5 figure

Solar coronal jets:observations, theory, and modeling

Coronal jets represent important manifestations of ubiquitous solar transients, which may be the source of significant mass and energy input to the upper solar atmosphere and the solar wind. While the energy involved in a jet-like event is smaller than that of “nominal” solar flares and coronal mass ejections (CMEs), jets share many common properties with these phenomena, in particular, the explosive magnetically driven dynamics. Studies of jets could, therefore, provide critical insight for understanding the larger, more complex drivers of the solar activity. On the other side of the size-spectrum, the study of jets could also supply important clues on the physics of transients close or at the limit of the current spatial resolution such as spicules. Furthermore, jet phenomena may hint to basic process for heating the corona and accelerating the solar wind; consequently their study gives us the opportunity to attack a broad range of solar-heliospheric problems

Effects of rapid prey evolution on predator-prey cycles

We study the qualitative properties of population cycles in a predator-prey system where genetic variability allows contemporary rapid evolution of the prey. Previous numerical studies have found that prey evolution in response to changing predation risk can have major quantitative and qualitative effects on predator-prey cycles, including: (i) large increases in cycle period, (ii) changes in phase relations (so that predator and prey are cycling exactly out of phase, rather than the classical quarter-period phase lag), and (iii) "cryptic" cycles in which total prey density remains nearly constant while predator density and prey traits cycle. Here we focus on a chemostat model motivated by our experimental system [Fussmann et al. 2000,Yoshida et al. 2003] with algae (prey) and rotifers (predators), in which the prey exhibit rapid evolution in their level of defense against predation. We show that the effects of rapid prey evolution are robust and general, and furthermore that they occur in a specific but biologically relevant region of parameter space: when traits that greatly reduce predation risk are relatively cheap (in terms of reductions in other fitness components), when there is coexistence between the two prey types and the predator, and when the interaction between predators and undefended prey alone would produce cycles. Because defense has been shown to be inexpensive, even cost-free, in a number of systems [Andersson and Levin 1999, Gagneux et al. 2006,Yoshida et al. 2004], our discoveries may well be reproduced in other model systems, and in nature. Finally, some of our key results are extended to a general model in which functional forms for the predation rate and prey birth rate are not specified.Comment: 35 pages, 8 figure

Alcohol consumption and perceptions of health risks during COVID-19: a qualitative study of middle-aged women in South Australia

Australian women's alcohol consumption has increased in frequency during COVID-19. Research suggests this is to cope with stress resulting from the pandemic and COVID-19 countermeasures that require social distancing. This is a critical public health concern because increased alcohol consumption, even for a short period, increases the myriad longer-term health risks associated with cumulative exposure to alcohol. This paper provides unique qualitative evidence of how health risk perceptions are re-focused toward the shorter-term during the pandemic, through analysis of interviews with 40 middle-aged Australian women (aged 45–64) representing a range of self-perceived drinking status' (“occasional”/“light”/“moderate”/“heavy”) before and then during the pandemic (n = 80 interviews). Our analysis captures women's risk horizons drifting away from the uncertain longer-term during COVID-19, toward the immediate need to “get through” the pandemic. We show how COVID-19 has increased the perceived value of consuming alcohol among women, particularly when weighed up against the social and emotional “costs” of reducing consumption. Our findings have implications for the delivery of alcohol-related health risk messages designed for middle-aged women both during, and into the recovery phases of the pandemic, who already consume more alcohol and experience more alcohol-related health risk than women in other age groups.Belinda Lunnay, Kristen Foley, Samantha B. Meyer, Megan Warin, Carlene Wilson, Ian Olver ... et al

Social class and changes in Australian women's affect and alcohol consumption during COVID-19

Introduction: Before the pandemic, mid-life women in Australia were among the “heaviest” female alcohol consumers, giving rise to myriad preventable health risks. This paper uses an innovative model of social class within a sample of Australian women to describe changes in affective states and alcohol consumption patterns across two time points during COVID-19. Methods: Survey data were collected from Australian mid-life women (45–64 years) at two time points during COVID-19—May 2020 (N = 1,218) and July 2020 (N = 799). We used a multi-dimensional model for measuring social class across three domains—economic capital (income, property and assets), social capital (social contacts and occupational prestige of those known socially), and cultural capital (level of participation in various cultural activities). Latent class analysis allowed comparisons across social classes to changes in affective states and alcohol consumption patterns reported at the two time points using alcohol consumption patterns as measured by the Alcohol Use Disorders Identification Test—Consumption (AUDIT-C) and its component items. Results: Seven social classes were constructed, characterized by variations in access to capital. Affective states during COVID-19 differed according to social class. Comparing between the survey time points, feeling fearful/anxious was higher in those with high economic and cultural capital and moderate social capital (“emerging affluent”). Increased depression was most prominent in the class characterized by the highest volumes of all forms of capital (“established affluent”). The social class characterized by the least capital (“working class”) reported increased prevalence of uncertainty, but less so for feeling fearful or anxious, or depressed. Women's alcohol consumption patterns changed across time during the pandemic. The “new middle” class—a group characterized by high social capital (but contacts with low prestige) and minimal economic capital—had increased AUDIT-C scores. Conclusion: Our data shows the pandemic impacted women's negative affective states, but not in uniform ways according to class. It may explain increases in alcohol consumption among women in the emerging affluent group who experienced increased feelings or fear and anxiety during the pandemic. This nuanced understanding of the vulnerabilities of sub-groups of women, in respect to negative affect and alcohol consumption can inform future pandemic policy responses designed to improve mental health and reduce the problematic use of alcohol. Designing pandemic responses segmented for specific audiences is also aided by our multi-dimensional analysis of social class, which uncovers intricate differences in affective states amongst sub-groups of mid-life women.Belinda Lunnay, Barbara Toson, Carlene Wilson, Emma R. Miller, Samantha Beth Meyer, Ian N. Olver, Kristen Foley, Jessica A. Thomas and Paul Russell War

COVID-19, alcohol consumption and stockpiling practises in midlife women: repeat surveys during lockdown in Australia and the United Kingdom

Introduction: This project examined the impact of COVID-19 and associated restrictions on alcohol practises (consumption and stockpiling), and perceptions of health risk among women in midlife (those aged 45–64 years). Methods: We collected online survey data from 2,437 midlife women in the United Kingdom (UK) and Australia in May 2020, recruited using a commercial panel, in the early days of mandated COVID-19 related restrictions in both countries. Participants were surveyed again (N = 1,377) in July 2020, at a time when COVID-19 restrictions were beginning to ease. The surveys included the Alcohol Use Disorder Identification Test—Consumption (AUDIT-C) and questions alcohol stockpiling. Analysis involved a range of univariate and multivariate techniques examining the impact of demographic variables and negative affect on consumption and acquisition outcomes. Results: In both surveys (May and July), UK women scored higher than Australian women on the AUDIT-C, and residence in the UK was found to independently predict stockpiling of alcohol (RR: 1.51; 95% CI: 1.20, 1.91). Developing depression between surveys (RR: 1.53; 95% CI: 1.14, 2.04) and reporting pessimism (RR: 1.42; 95% CI: 1.11, 1.81), and fear/anxiety (RR: 1.33; 95% CI: 1.05, 1.70) at the beginning of the study period also predicted stockpiling by the end of the lockdown. Having a tertiary education was protective for alcohol stockpiling at each time point (RR: 0.69; 95% CI: 0.54, 0.87). Conclusions: COVID-19 was associated with increases in risky alcohol practises that were predicted by negative emotional responses to the pandemic. Anxiety, pessimism and depression predicted stockpiling behaviour in UK and Australian women despite the many demographic and contextual differences between the two cohorts. Given our findings and the findings of others that mental health issues developed or were exacerbated during lockdown and may continue long after that time, urgent action is required to address a potential future pandemic of alcohol-related harms.Emma R. Miller, Ian N. Olver, Carlene J. Wilson, Belinda Lunnay, Samantha B. Meyer, Kristen Foley ... et al

Approximate k-state solutions to the Dirac-Yukawa problem based on the spin and pseudospin symmetry

Using an approximation scheme to deal with the centrifugal (pseudo-centrifugal) term, we solve the Dirac equation with the screened Coulomb (Yukawa) potential for any arbitrary spin-orbit quantum number {\kappa}. Based on the spin and pseudospin symmetry, analytic bound state energy spectrum formulas and their corresponding upper- and lower-spinor components of two Dirac particles are obtained using a shortcut of the Nikiforov-Uvarov method. We find a wide range of permissible values for the spin symmetry constant C_{s} from the valence energy spectrum of particle and also for pseudospin symmetry constant C_{ps} from the hole energy spectrum of antiparticle. Further, we show that the present potential interaction becomes less (more) attractive for a long (short) range screening parameter {\alpha}. To remove the degeneracies in energy levels we consider the spin and pseudospin solution of Dirac equation for Yukawa potential plus a centrifugal-like term. A few special cases such as the exact spin (pseudospin) symmetry Dirac-Yukawa, the Yukawa plus centrifugal-like potentials, the limit when {\alpha} becomes zero (Coulomb potential field) and the non-relativistic limit of our solution are studied. The nonrelativistic solutions are compared with those obtained by other methods.Comment: 21 pages, 6 figure