Translational treatment paradigm for managing non‐unions secondary to radiation injury utilizing adipose derived stem cells and angiogenic therapy

BackgroundBony non‐unions arising in the aftermath of collateral radiation injury are commonly managed with vascularized free tissue transfers. Unfortunately, these procedures are invasive and fraught with attendant morbidities. This study investigated a novel, alternative treatment paradigm utilizing adipose‐derived stem cells (ASCs) combined with angiogenic deferoxamine (DFO) in the rat mandible.MethodsRats were exposed to a bioequivalent dose of radiation and mandibular osteotomy. Those exhibiting non‐unions were subsequently treated with surgical debridement alone or debridement plus combination therapy. Radiographic and biomechanical outcomes were assessed after healing.ResultsSignificant increases in biomechanical strength and radiographic metrics were observed in response to combination therapy (p < .05). Importantly, combined therapy enabled a 65% reduction in persisting non‐unions when compared to debridement alone.ConclusionWe support the continued investigation of this promising combination therapy in its potential translation for the management of radiation‐induced bony pathology. © 2015 Wiley Periodicals, Inc. Head Neck 38: E837–E843, 2016Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137613/1/hed24110.pd

Small molecule epigenetic screen identifies novel EZH2 and HDAC inhibitors that target glioblastoma brain tumor-initiating cells

Glioblastoma (GBM) is the most lethal and aggressive adult brain tumor, requiring the development of efficacious therapeutics. Towards this goal, we screened five genetically distinct patient-derived brain-tumor initiating cell lines (BTIC) with a unique collection of small molecule epigenetic modulators from the Structural Genomics Consortium (SGC). We identified multiple hits that inhibited the growth of BTICs in vitro, and further evaluated the therapeutic potential of EZH2 and HDAC inhibitors due to the high relevance of these targets for GBM. We found that the novel SAM-competitive EZH2 inhibitor UNC1999 exhibited low micromolar cytotoxicity in vitro on a diverse collection of BTIC lines, synergized with dexamethasone (DEX) and suppressed tumor growth in vivo in combination with DEX. In addition, a unique brain-penetrant class I HDAC inhibitor exhibited cytotoxicity in vitro on a panel of BTIC lines and extended survival in combination with TMZ in an orthotopic BTIC model in vivo. Finally, a combination of EZH2 and HDAC inhibitors demonstrated synergy in vitro by augmenting apoptosis and increasing DNA damage. Our findings identify key epigenetic modulators in GBM that regulate BTIC growth and survival and highlight promising combination therapies

The Relationship between Power and Level for Generic Unit Root Tests in Finite Samples.

The author shows that the maximum power of a generic unit root test against any stationary alternative is equal to the true level of the test. He then uses Monte Carlo methods to investigate the implications for several such tests. He shows patterns of rejection probabilities over a variety of unit root and stationary processes. He discusses the implications of these results for some of the uses of unit root tests in applied work. Copyright 1992 by John Wiley & Sons, Ltd.

Near common factors and confidence regions for present value models

The evidence for excess smoothness of aggregate consumption and excess volatility of stock prices is reexamined, using a method that nests parsimonious trend- and difference-stationary specifications of the forcing processes. The confidence interval for the present value of an innovation to labor income is found to be very wide, so that aggregate consumption may be anything from much too smooth to much too volatile. The confidence interval for the present value of an innovation to dividends is narrower and weakly supports excess volatility in the stock market.Econometric models

Yield curve forecasts of inflation: a cautionary tale

Long-term interest rates that are unusually high relative to shortterm interest rates are often seen to reflect market expectations of increasing inflation. Given that the term structure of interest rates (also called the yield curve) reacts to inflation expectations, does it do so in a reasonable manner? Does the term structure embody inflation forecasts that bear a sensible relationship to the iiaflation that in fact occurs? ; This article reviews the theoretical link between the term structure and inflation expectations, and then it provides empirical evidence on the link in light of the theory. It finds little evidence of a link between the term structure and future inflation at the horizon chosen for study, the relationship between one- and two-year interest rates and the one-year ahead change in the one-year inflation.Inflation (Finance) ; Interest rates

Near observational equivalence and persistence in GNP

The question of whether aggregate output is best described as a trend-stationary (TS) or as a difference-stationary (DS, or unit root) process continues to generate a substantial volume of research a dozen years after it was first raised by Nelson and Plosser (1982), including a recent paper by Rudebusch (1993). Rudebusch argues that "Based on the usual unit root tests, little can be said about the relative likelihood of the specific DS and TS models of real GNP." Rudebusch concludes by emphasizing "the importance of measuring the confidence intervals for estimates of persistence without conditioning on the TS or DS model." ; This paper provides a strong theoretical result on distinguishing TS and DS models, and gives confidence intervals for the GNP impulse response function that do not require such distinction. Theoretically, the paper shows that, in the absence of a priori specification restrictions, the classes of unit root and stationary processes are nearly observationally equivalent: no finite data sample can provide information on the TS/DS issue. The paper then shows how the principle of parsimony for time series model specification masks near observational equivalence and implicitly rules out plausible shapes for the univariate impulse response function. Finally, the paper provides confidence intervals for the GNP impulse response function using two methods that nest parsimonious TS and DS models.Gross national product

A wireless microwave telemetry data transfer technique for reciprocating and rotating components

Wireless microwave telemetry addresses the difficult issue of obtaining transducer outputs from reciprocating and rotating components through the use of advanced electronic components. This eliminates the requirements of a direct link between the transducer and the acquisition system. Accuracy of the transducer signal is maintained through the use of a doublefrequency modulation technique which provides temperature stability and a 20 point calibration of the complete system. Multiple transmitters can be usedfor larger applications and multiple antennas can be used to improve the signal strength and reduce the possibility of dropouts. Examples of automotive torque converter and piston temperature measurements are provided, showing the effectiveness of the wireless measuring technique. Copyright © 2008 by ASME