Therapeutic Implications of PPAR γ

Osteosarcoma (OS) is the most common nonhematologic malignancy of bone in children and adults. Although dysregulation of tumor suppressor genes and oncogenes, such as Rb, p53, and the genes critical to cell cycle control, genetic stability, and apoptosis have been identified in OS, consensus genetic changes that lead to OS development are poorly understood. Disruption of the osteogenic differentiation pathway may be at least in part responsible for OS tumorigenesis. Current OS management involves chemotherapy and surgery. Peroxisome proliferator-activated receptor (PPAR) agonists and/or retinoids can inhibit OS proliferation and induce apoptosis and may inhibit OS growth by promoting osteoblastic terminal differentiation. Thus, safe and effective PPAR agonists and/or retinoid derivatives can be then used as adjuvant therapeutic drugs for OS therapy. Furthermore, these agents have the potential to be used as chemopreventive agents for the OS patients who undergo the resection of the primary bone tumors in order to prevent local recurrence and/or distal pulmonary metastasis

Confinement studies of neutral beam heated discharges in TFTR

The TFTR tokamak has reached its original machine design specifications (I/sub p/ = 2.5 MA and B/sub T/ = 5.2T). Recently, the D/sup 0/ neutral beam heating power has been increased to 6.3 MW. By operating at low plasma current (I/sub p/ approx. = 0.8 MA) and low density anti n/sub e/ approx. = 1 x 10/sup 19/m/sup -3/), high ion temperatures (9 +- keV) and rotation speeds (7 x 10/sup 5/ m/s) have been achieved during injection. At the opposite extreme, pellet injection into high current plasmas has been used to increase the line-average density to 8 x 10/sup 19/m/sup -3/ and the central density to 1.6 x 10/sup 20/m/sup -3// This wide range of operating conditions has enabled us to conduct scaling studies of the global energy confinement time in both ohmically and beam heated discharges as well as more detailed transport studies of the profile dependence. In ohmic discharges, the energy confinement time is observed to scale linearly with density only up to anti n/sub e/ approx. 4.5 x 10/sup 19/m/sup -3/ and then to increase more gradually, achieving a maximum value of approx. 0.45 s. In beam heated discharges, the energy confinement time is observed to decrease with beam power and to increase with plasma current. With P/sub b/ = 5.6 MW, anti n/sub e/ = 4.7 x 10/sup 19/m/sup -3/, I/sub p/ = 2.2 MA and B/sub T = 4.7T, the gross energy confinement time is 0.22 s and T/sub i/(0) = 4.8 keV. Despite shallow penetration of D/sup 0/ beams (at the beam energy less than or equal to 80 keV with low species yield), tau/sub E/(a) values are as large as those for H/sup 0/ injection, but central confinement times are substantially greater. This is a consequence of the insensitivity of the temperature and safety factor profile shapes to the heating profile. The radial variation of tau/sub E/ is even more pronounced with D/sup 0/ injection into high density pellet-injected plasmas. 25 refs

A spectroscopic study of impurity behavior in neutral-beam and ohmically heated TFTR discharges

Quantitative spectroscopic measurements of Z/sub eff/, impurity densities, and radiated power losses have been made for ohmic- and neutral-beam-heated TFTR discharges at a plasma current of 2.2 MA and toroidal field of 4.7 T. Variations in these quantities with line-average plasma density (anti n/sub e/) and beam power up to 5.6 MW are presented for discharges on a graphite movable limiter. A detailed discussion of the use of an impurity transport model to infer absolute impurity densities and radiative losses from line intensity and visible continuum measurements is given. These discharges were dominated by low-Z impurities with carbon having a considerably higher density than oxygen, except in high-anti n/sub e/ ohmic discharges, where the densities of carbon and oxygen were comparable. Metallic impurity concentrations and radiative losses were small, resulting in hollow radiated power profiles and fractions of the input power radiated being 30 to 50% for ohmic heating and 30% or less with beam heating. Spectroscopic estimates of the radiated power were in good agreement with bolometrically measured values. Due to an increase in the carbon density, Z/sub eff/ rose from 2.0 to 2.8 as the beam power increased from 0 to 5.6 MW, pointing to a potentially serious dilution of the neutron-producing plasma ions as the beam power increased. Both the low-Z and metallic impurity concentrations were approximately constant with minor radius, indicating no central impurity accumulation in these discharges

Neutral beam heating of detached plasmas in TFTR

Detached plasmas on TFTR have been heated with neutral beam auxiliary power for the first time. At beam powers above 2 MW the detached plasmas in TFTR expand and reattach to the limiters. Deuterium and/or impurity gas puffing can be used to maintain plasmas in the detached state at powers of over 5 MW. Transient events were observed in a number of these plasmas, including a confinement-related delay in evolution of the edge emissivity and some phenomena which appear similar to those seen in the H-mode. 16 refs., 5 figs

Development and Implementation of a Curricular-wide Electronic Portfolio System in a School of Pharmacy

The Feik School of Pharmacy collaborated with a commercial software development company to create a Web-based e-portfolio system to document student achievement of curricular outcomes and performance in pharmacy practice experiences. The multi-functional system also could be used for experiential site selection and assignment and continuing pharmacy education. The pharmacy school trained students, faculty members, and pharmacist preceptors to use the e-portfolio system. All pharmacy students uploaded the required number of documents and assessments to the program as evidence of achievement of each of the school's curricular outcomes and completion of pharmacy practice experiences

Plasma-material interactions in TFTR

This paper presents a summary of plasma-material interactions which influence the operation of TFTR with high current (less than or equal to 2 MA), ohmically heated and high power (approx. 10 MW), neutral-beam-heated plasmas. The conditioning procedures which are applied routinely to the first-wall hardware are reviewed. Fueling characteristics during gas, pellet, and neutral beam fueling are described. Recycling coefficients near unity are observed for most gas-fueled discharges. Gas-fueled discharges after helium discharge conditioning of the toroidal bumper limiter and discharges fueled by neutral beams and pellets show R < 1. In the vicinity of the gas-fueled density limit (at n/sub e/ = 5 to 6 x 10/sup +19/ m/sup -3/) values of less than or equal to 1.5. Increases in Z/eff of less than or equal to 1 have been observed with neutral beam heating of 10 MW. The primary low-Z impurity is carbon with concentrations decreasing from approx.10% to <1% with increasing n/sub e/. Oxygen densities tend to increase with n/sub e/, and at the ohmic plasma density limit oxygen and carbon concentrations are comparable. Chromium getter experiments and He/sup + +//D/sup +/ plasma comparisons indicate that the limiter is the primary source of carbon and that the vessel wall is a significant source of the oxygen impurity. Metallic impurities, consisting of the vacuum vessel metals (Ni, Fe, Cr), have significant (approx. 10/sup -4/ n/sub e/) concentrations only at low plasma densities (n/sub e/ < 10/sup +19/ m/sup -3/). The primary source of metallic impurities is most likely ion sputtering from metals deposited on the carbon limiter surface

Pain Location and Exacerbating Activities Associated with Treatment Success Following Basivertebral Nerve Ablation: An Aggregated Cohort Study of Multicenter Prospective Clinical Trial Data.

ObjectiveDevelop pain location "maps" and investigate the relationship between low back pain (LBP)-exacerbating activities and treatment response to basivertebral nerve radiofrequency ablation (BVN RFA) in patients with clinically suspected vertebral endplate pain (VEP).DesignAggregated cohort study of 296 patients treated with BVN RFA at 33 centers in three prospective trials.MethodsParticipant demographics, pain diagrams, and LBP-exacerbating activities were analyzed for predictors using stepwise logistic regression. Treatment success definitions were: (1) ≥50% LBP visual analog scale (VAS), (2) ≥15-point Oswestry Disability Index (ODI), and (3) ≥50% VAS or ≥15-point ODI improvements at 3 months post-BVN RFA.ResultsMidline LBP correlated with BVN RFA treatment success in individuals with clinically-suspected VEP. Duration of pain ≥5 years (OR 2.366), lack of epidural steroid injection within 6 months before BVN RFA (OR 1.800), lack of baseline opioid use (OR 1.965), LBP exacerbation with activity (OR 2.099), and a lack of LBP with spinal extension (OR 1.845) were factors associated with increased odds of treatment success. Regressions areas under the curve (AUCs) were under 70%, indicative of low predictive value.ConclusionsThis study demonstrates that midline LBP correlates with BVN RFA treatment success in individuals with VEP. While none of the regression models demonstrated strong predictive value, the pain location and exacerbating factors identified in this analysis may aid clinicians in identifying patients where VEP should be more strongly suspected. The use of objective imaging biomarkers (Type 1 and/or 2 Modic changes) and a correlating presentation of anterior spinal element pain remain the most useful patient selection factors for BVN RFA