Multi-Purpose ESS/ITS Data Collection Sites

This document presents the results of a state-of-practice survey of transportation agencies that are installing intelligent transportation sensors (ITS) and other devices along with their environmental sensing stations (ESS) also referred to as roadway weather information system (RWIS) assets

The Properties of Radio Galaxies and the Effect of Environment in Large Scale Structures at z∼1z\sim1

In this study we investigate 89 radio galaxies that are spectroscopically-confirmed to be members of five large scale structures in the redshift range of $0.65 \le z \le 0.96$. Based on a two-stage classification scheme, the radio galaxies are classified into three sub-classes: active galactic nucleus (AGN), hybrid, and star-forming galaxy (SFG). We study the properties of the three radio sub-classes and their global and local environmental preferences. We find AGN hosts are the most massive population and exhibit quiescence in their star-formation activity. The SFG population has a comparable stellar mass to those hosting a radio AGN but are unequivocally powered by star formation. Hybrids, though selected as an intermediate population in our classification scheme, were found in almost all analyses to be a unique type of radio galaxies rather than a mixture of AGN and SFGs. They are dominated by a high-excitation radio galaxy (HERG) population. We discuss environmental effects and scenarios for each sub-class. AGN tend to be preferentially located in locally dense environments and in the cores of clusters/groups, with these preferences persisting when comparing to galaxies of similar colour and stellar mass, suggesting that their activity may be ignited in the cluster/group virialized core regions. Conversely, SFGs exhibit a strong preference for intermediate-density global environments, suggesting that dusty starbursting activity in LSSs is largely driven by galaxy-galaxy interactions and merging.Comment: 28 pages, 10 figures, accepted to MNRA

Vascular endothelial growth factor-A165b restores normal glomerular water permeability in a diphtheria-toxin mouse model of glomerular injury

BACKGROUND/AIMS:Genetic cell ablation using the human diphtheria toxin receptor (hDTR) is a new strategy used for analysing cellular function. Diphtheria toxin (DT) is a cytotoxic protein that leaves mouse cells relatively unaffected, but upon binding to hDTR it ultimately leads to cell death. We used a podocyte-specific hDTR expressing (Pod-DTR) mouse to assess the anti-permeability and cyto-protective effects of the splice isoform vascular endothelial growth factor (VEGF-A165b). METHODS:The Pod-DTR mouse was crossed with a mouse that over-expressed VEGF-A165b specifically in the podocytes (Neph-VEGF-A165b). Wild type (WT), Pod-DTR, Neph-VEGF-A165b and Pod-DTR X Neph-VEGF-A165b mice were treated with several doses of DT (1, 5, 100, and 1,000 ng/g bodyweight). Urine was collected and the glomerular water permeability (LpA/Vi) was measured ex vivo after 14 days. Structural analysis and podocyte marker expression were also assessed. RESULTS: Pod-DTR mice developed an increased glomerular LpA/Vi 14 days after administration of DT (all doses), which was prevented when the mice over-expressed VEGF-A165b. No major structural abnormalities, podocyte ablation or albuminuria was observed in Pod-DTR mice, indicating this to be a mild model of podocyte disease. However, a change in expression and localisation of nephrin within the podocytes was observed, indicating disruption of the slit diaphragm in the Pod-DTR mice. This was prevented in the Pod-DTR X Neph-VEGF-A165b mice. CONCLUSION: Although only a mild model of podocyte injury, over-expression of the anti-permeability VEGF-A165b isoform in the podocytes of Pod-DTR mice had a protective effect. Therefore, this study further highlights the therapeutic potential of VEGF-A165b in glomerular disease

Changes in skeletal collagen crosslinks and matrix hydration in high and low turnover chronic kidney disease

Chronic kidney disease (CKD) increases fracture risk. The results of this work point to changes in bone collagen and bone hydration as playing a role in bone fragility associated with CKD. INTRODUCTION: Clinical data have documented a clear increase in fracture risk associated with chronic kidney disease (CKD). Preclinical studies have shown reductions in bone mechanical properties although the tissue-level mechanisms for these differences remain unclear. The goal of this study was to assess collagen cross-links and matrix hydration, two variables known to affect mechanical properties, in animals with either high- or low-turnover CKD. METHODS: At 35 weeks of age (>75 % reduction in kidney function), the femoral diaphysis of male Cy/+ rats with high or low bone turnover rates, along with normal littermate (NL) controls, were assessed for collagen cross-links (pyridinoline (Pyd), deoxypyridinoline (Dpd), and pentosidine (PE)) using a high-performance liquid chromatography (HPLC) assay as well as pore and bound water per volume (pw and bw) using a 1H nuclear magnetic resonance (NMR) technique. Material-level biomechanical properties were calculated based on previously published whole bone mechanical tests. RESULTS: Cortical bone from animals with high-turnover disease had lower Pyd and Dpd cross-link levels (-21 % each), lower bw (-10 %), higher PE (+71 %), and higher pw (+46 %) compared to NL. Animals with low turnover had higher Dpd, PE (+71 %), and bw (+7 %) along with lower pw (-60 %) compared to NL. Both high- and low-turnover animals had reduced material-level bone toughness compared to NL animals as determined by three-point bending. CONCLUSIONS: These data document an increase in skeletal PE with advanced CKD that is independent of bone turnover rate and inversely related to decline in kidney function. Although hydration changes occur in both high- and low-turnover disease, the data suggest that nonenzymatic collagen cross-links may be a key factor in compromised mechanical properties of CKD.This work was supported by National Institutes of Health grants AR58005 (SM), DL100093 (CN), AR063157 (JSN), and the Indiana Clinical Translational Science Institute grant TR000162 (CN). The cross-link analysis is the result of work supported with resources and the use of facilities at the VA Tennessee Valley Healthcare System. All authors were involved in the design, conduct and analyses of the study. The authors would like to thank Drew Brown, Shannon Roy, and Kali O’Neill for technical assistance. We would also like to acknowledge the late Dr. Vincent H. Gattone II (1951-2013), who was instrumental in developing this animal model

Compromised vertebral structural and mechanical properties associated with progressive kidney disease and the effects of traditional pharmacological interventions

BACKGROUND/AIMS: Patients with chronic kidney disease mineral and bone disorder (CKD-MBD) have a significantly higher vertebral and non-vertebral fracture risk than the general population. Several preclinical models have documented altered skeletal properties in long bones, but few data exist for vertebral bone. The goal of this study was to examine the effects of progressive CKD on vertebral bone structure and mechanics and to determine the effects of treatment with either bisphosphonates or anti-sclerostin antibody in groups of animals with high or low PTH. METHODS: Animals with progressive kidney disease were left untreated, treated with calcium to lower PTH, zoledronic acid to lower remodeling without affecting PTH, anti-sclerostin antibody, or anti-sclerostin antibody plus calcium. Non-diseased, untreated littermates served as controls. Vertebral bone morphology (trabecular and cortical) and mechanical properties (structural and material-level) were assessed at 35 weeks of age by microCT and mechanical testing, respectively. RESULTS: CKD with high PTH resulted in 6-fold higher bone formation rate, significant reductions in the amount of trabecular and cortical bone, and compromised whole bone mechanical properties in the vertebra compared to normal animals. Treatments that reduced bone remodeling were effective in normalizing vertebral structure and mechanical properties only if the treatment reduced serum PTH. Similarly, treatment with anti-sclerostin antibody was effective in enhancing bone mass and mechanical properties but only if combined with PTH-suppressive treatment. CONCLUSIONS: CKD significantly altered both cortical and trabecular bone properties in the vertebra resulting in compromised mechanical properties and these changes can be normalized by interventions that involve reductions in PTH levels

Metabolic Syndrome Derived from Principal Component Analysis and Incident Cardiovascular Events: The Multi Ethnic Study of Atherosclerosis (MESA) and Health, Aging, and Body Composition (Health ABC).

Background. The NCEP metabolic syndrome (MetS) is a combination of dichotomized interrelated risk factors from predominantly Caucasian populations. We propose a continuous MetS score based on principal component analysis (PCA) of the same risk factors in a multiethnic cohort and compare prediction of incident CVD events with NCEP MetS definition. Additionally, we replicated these analyses in the Health, Aging, and Body composition (Health ABC) study cohort. Methods and Results. We performed PCA of the MetS elements (waist circumference, HDL, TG, fasting blood glucose, SBP, and DBP) in 2610 Caucasian Americans, 801 Chinese Americans, 1875 African Americans, and 1494 Hispanic Americans in the multiethnic study of atherosclerosis (MESA) cohort. We selected the first principal component as a continuous MetS score (MetS-PC). Cox proportional hazards models were used to examine the association between MetS-PC and 5.5 years of CVD events (n = 377) adjusting for age, gender, race, smoking and LDL-C, overall and by ethnicity. To facilitate comparison of MetS-PC with the binary NCEP definition, a MetS-PC cut point was chosen to yield the same 37% prevalence of MetS as the NCEP definition (37%) in the MESA cohort. Hazard ratio (HR) for CVD events were estimated using the NCEP and Mets-PC-derived binary definitions. In Cox proportional models, the HR (95% CI) for CVD events for 1-SD (standard deviation) of MetS-PC was 1.71 (1.54-1.90) (P < 0.0001) overall after adjusting for potential confounders, and for each ethnicity, HRs were: Caucasian, 1.64 (1.39-1.94), Chinese, 1.39 (1.06-1.83), African, 1.67 (1.37-2.02), and Hispanic, 2.10 (1.66-2.65). Finally, when binary definitions were compared, HR for CVD events was 2.34 (1.91-2.87) for MetS-PC versus 1.79 (1.46-2.20) for NCEP MetS. In the Health ABC cohort, in a fully adjusted model, MetS-PC per 1-SD (Health ABC) remained associated with CVD events (HR = 1.21, 95%CI 1.12-1.32) overall, and for each ethnicity, Caucasian (HR = 1.24, 95%CI 1.12-1.39) and African Americans (HR = 1.16, 95%CI 1.01-1.32). Finally, when using a binary definition of MetS-PC (cut point 0.505) designed to match the NCEP definition in terms of prevalence in the Health ABC cohort (35%), the fully adjusted HR for CVD events was 1.39, 95%CI 1.17-1.64 compared with 1.46, 95%CI 1.23-1.72 using the NCEP definition. Conclusion. MetS-PC is a continuous measure of metabolic syndrome and was a better predictor of CVD events overall and in individual ethnicities. Additionally, a binary MetS-PC definition was better than the NCEP MetS definition in predicting incident CVD events in the MESA cohort, but this superiority was not evident in the Health ABC cohort

A comparison of calcium to zoledronic acid for improvement of cortical bone in an animal model of CKD

Bone Biology Laboratory http://www.iupui.edu/~bonelab/ Department of Anatomy and Cell Biology Indiana University School of MedicinePatients with chronic kidney disease (CKD) have increased risk of fractures, yet the optimal treatment is unknown. In secondary analyses of large randomized trials, bisphosphonates have been shown to improve bone mineral density and reduce fractures. However, bisphosphonates are currently not recommended in patients with advanced kidney disease due to concern about over-suppressing bone remodeling, which may increase the risk of developing arterial calcification. In the present study we used a naturally occurring rat model of CKD with secondary hyperparathyroidism, the Cy/+ rat, and compared the efficacy of treatment with zoledronic acid, calcium given in water to simulate a phosphate binder, and the combination of calcium and zoledronic acid. Animals were treated beginning at 25 weeks of age (approximately 30% of normal renal function) and followed for ten weeks. The results demonstrate that both zoledronic acid and calcium improved bone volume by microCT and both equally suppressed mineral apposition rate, bone formation rate, and mineralizing surface of trabecular bone. In contrast, only calcium treatment with or without zoledronic acid improved cortical porosity and cortical biomechanical properties (ultimate load and stiffness) and lowered parathyroid hormone (PTH). However, only calcium treatment led to the adverse effects of increased arterial calcification and fibroblast growth factor 23 (FGF23). These results suggest zoledronic acid may improve trabecular bone volume in CKD in the presence of secondary hyperparathyroidism, but does not benefit extraskeletal calcification or cortical biomechanical properties. Calcium effectively reduces PTH and benefits both cortical and trabecular bone yet increases the degree of extra skeletal calcification.This work was supported by the NIH NIAMS R01 5R01AR058005 (SMM) and S10-RR023710 (microCT equipment grant). We thank Drew Brown for tissue dissections, CT scanning and analysis

Calcitriol suppression of parathyroid hormone fails to improve skeletal properties in an animal model of chronic kidney disease

BACKGROUND: Chronic kidney disease (CKD) leads to complex metabolic changes and an increased risk of fracture. Currently, calcitriol is the standard of care as it effectively suppresses parathyroid hormone (PTH) levels in CKD patients. While calcitriol and its analogs improve BMD and reduce fractures in the general population, the extension of these benefits to patients with advanced kidney disease is unclear. Here, the impact of calcitriol on the skeleton was examined in the setting of reduction in PTH. METHODS: Male Cy/+ rats, a PKD-like CKD model, were treated with either vehicle or calcitriol for 5 weeks. Their normal littermates served as controls. Animals were assessed for changes in mineral metabolism and skeletal parameters (microCT, histology, whole bone mechanics and bone quality). RESULTS: PTH levels were significantly higher (12-fold) in animals with CKD compared to normal controls. CKD animals also exhibited negative changes in bone structural and mechanical properties. Calcitriol treatment resulted in a 60% suppression of PTH levels in animals with CKD. Despite these changes, it had no impact on bone volume (cortical or cancellous), bone turnover, osteoclast number or whole bone mechanical properties. CONCLUSIONS: These data indicate that while calcitriol effectively lowered PTH in rats with CKD, it did little to prevent the negative effects of secondary hyperparathyroidism on the skeleton