Model Uncertainty and Policy Evaluation: Some Theory and Empirics

This paper explores ways to integrate model uncertainty into policy evaluation. We first describe a general framework for the incorporation of model uncertainty into standard econometric calculations. This framework employs Bayesian model averaging methods that have begun to appear in a range of economic studies. Second, we illustrate these general ideas in the context of assessment of simple monetary policy rules for some standard New Keynesian specifications. The specifications vary in their treatment of expectations as well as in the dynamics of output and inflation. We conclude that the Taylor rule has good robustness properties, but may reasonably be challenged in overall quality with respect to stabilization by alternative simple rules that also condition on lagged interest rates, even though these rules employ parameters that are set without accounting for model uncertainty.

Policy Evaluation in Uncertain Economic Environments

This paper develops a decision-theoretic approach to policy analysis. We argue that policy evaluation should be conducted on the basis of two factors: the policymaker's preferences, and the conditional distribution of the outcomes of interest given a policy and available information. From this perspective, the common practice of conditioning on a particular model is often inappropriate, since model uncertainty is an important element of policy evaluation. We advocate the use of model averaging to account for model uncertainty and show how it may be applied to policy evaluation exercises. We illustrate our approach with applications to monetary policy and to growth policy.

Policy Evaluation in Uncertain Economic Environments

This paper develops a general framework for economic policy evaluation. Using ideas from statistical decision theory, it argues that conventional approaches fail to appropriately integrate econometric analysis into evaluation problems. Further, it is argued that evaluation of alternative policies should explicitly account for uncertainty about the appropriate model of the economy. The paper shows how to develop an explicitly decision-theoretic approach to policy evaluation and how to incorporate model uncertainty into such an analysis. The theoretical implications of model uncertainty are explored in a set of examples, with a specific focus on how to design policies that are robust against such uncertainty. Finally, the framework is applied to the evaluation of monetary policy rules and to the analysis of tariff reductions as a way to increase aggregate economic growth.macroeconomics, Policy Evaluation, Uncertain Economic Environments

Targeted muscle reinnervation for the management of pain in the setting of major limb amputation

The life altering nature of major limb amputations may be further complicated by neuroma formation in up to 60% of the estimated 2 million major limb amputees in the United States. This can be a source of pain and functional limitation of the residual limb. Pain associated with neuromas may limit prosthetic limb use, require reoperation, lead to opioid dependence, and dramatically reduce quality of life. A number of management options have been described including excision alone, excision with repair, excision with transposition, and targeted muscle reinnervation. Targeted muscle reinnervation has been shown to reduce phantom limb and neuroma pain for patients with upper and lower extremity amputations. It may be performed at the time of initial amputation to prevent pain development or secondarily for the treatment of established pain. Encouraging outcomes have been reported, and targeted muscle reinnervation is emerging as a leading surgical technique for pain prevention in patients undergoing major limb amputations and pain management in patients with pre-existing amputations

Mosaic analysis of stem cell function and wound healing in the mouse corneal epithelium

<p>Abstract</p> <p>Background</p> <p>The mouse corneal epithelium is a continuously renewing 5–6 cell thick protective layer covering the corneal surface, which regenerates rapidly when injured. It is maintained by peripherally located limbal stem cells (LSCs) that produce transient amplifying cells (TACs) which proliferate, migrate centripetally, differentiate and are eventually shed from the epithelial surface. LSC activity is required both for normal tissue maintenance and wound healing. Mosaic analysis can provide insights into LSC function, cell movement and cell mixing during tissue maintenance and repair. The present study investigates cell streaming during corneal maintenance and repair and changes in LSC function with age.</p> <p>Results</p> <p>The initial pattern of corneal epithelial patches in <it>XLacZ</it>^+/-X-inactivation mosaics was replaced after birth by radial stripes, indicating activation of LSCs. Stripe patterns (clockwise, anticlockwise or midline) were independent between paired eyes. Wound healing in organ culture was analysed by mosaic analysis of <it>XLacZ</it>^+/-eyes or time-lapse imaging of GFP mosaics. Both central and peripheral wounds healed clonally, with cells moving in from all around the wound circumference without significant cell mixing, to reconstitute striping patterns. Mosaic analysis revealed that wounds can heal asymmetrically. Healing of peripheral wounds produced stripe patterns that mimicked some aberrant striping patterns observed in unwounded corneas. Quantitative analysis provided no evidence for an uneven distribution of LSC clones but showed that corrected corneal epithelial stripe numbers declined with age (implying declining LSC function) but stabilised after 39 weeks.</p> <p>Conclusion</p> <p>Striping patterns, produced by centripetal movement, are defined independently and stochastically in individual eyes. Little cell mixing occurs during the initial phase of wound healing and the direction of cell movement is determined by the position of the wound and not by population pressure from the limbus. LSC function declines with age and this may reflect reduced LSCs numbers, more quiescent LSCs or a reduced ability of older stem cells to maintain tissue homeostasis. The later plateau of LSC function might indicate the minimum LSC function that is sufficient for corneal epithelial maintenance. Quantitative and temporal mosaic analyses provide new possibilities for studying stem cell function, tissue maintenance and repair.</p

Validation of a single biopsy approach and bolus protein feeding to determine myofibrillar protein synthesis in stable isotope tracer studies in humans

<p>Abstract</p> <p>Background</p> <p>Minimizing the number of muscle biopsies has important methodological implications and minimizes subject discomfort during a stable isotope amino acid infusion. We aimed to determine the reliability of obtaining a single muscle biopsy for the calculation of muscle protein fractional synthetic rate (FSR) as well as the amount of incorporation time necessary to obtain that biopsy after initiating a stable isotope infusion (Study 1). The calculation of muscle protein FSR requires tracer steady-state during the stable isotope infusion. Therefore, a second aim was to examine if steady-state conditions are compromised in the precursor pools (plasma free or muscle intracellular [IC]) after ingestion of a tracer enriched protein drink and after resistance exercise (Study 2).</p> <p>Methods</p> <p>Sixteen men (23 ± 3 years; BMI = 23.8 ± 2.2 kg/m², means ± SD) were randomized to perform Study 1 or Study 2 (n = 8, per study). Subjects received a primed, constant infusion of L-[<it>ring</it>-¹³C₆]phenylalanine coupled with muscle biopsies of the vastus lateralis to measure rates of myofibrillar protein synthesis (MPS). Subjects in Study 2 were fed 25 g of whey protein immediately after an acute bout of unilateral resistance exercise.</p> <p>Results</p> <p>There was no difference (P = 0.3) in rates of MPS determined using the steady-state precursor-product equation and determination of tracer incorporation between sequential biopsies 150 min apart or using plasma protein as the baseline enrichment, provided the infusion length was sufficient (230 ± 0.3 min). We also found that adding a modest amount of tracer (4% enriched), calculated based on the measured phenylalanine content of the protein (3.5%) in the drink, did not compromise steady-state conditions (slope of the enrichment curve not different from zero) in the plasma free or, more importantly, the IC pool (both P > 0.05).</p> <p>Conclusions</p> <p>These data demonstrate that the single biopsy approach yields comparable rates of muscle protein synthesis, provided a longer incorporation time is utilized, to that seen with a traditional two biopsy approach. In addition, we demonstrate that enriching protein-containing drinks with tracer does not disturb isotopic steady-state and thus both are reliable techniques to determine rates of MPS in humans.</p

The Formation of Kiloparsec-scale HI Holes in Dwarf Galaxies

The origin of kpc-scale holes in the atomic hydrogen (H i) distributions of some nearby dwarf irregular galaxies presents an intriguing problem. Star formation histories (SFHs) derived from resolved stars give us the unique opportunity to study past star-forming events that may have helped shape the currently visible Hi distribution. Our sample of five nearby dwarf irregular galaxies spans over an order of magnitude in both total Hi mass and absolute B-band magnitude and is at the low-mass end of previously studied systems. We use Very Large Array Hi line data to estimate the energy required to create the centrally dominant hole in each galaxy. We compare this energy estimate to the past energy released by the underlying stellar populations computed from SFHs derived from data taken with the Hubble Space Telescope. The inferred integrated stellar energy released within the characteristic ages exceeds our energy estimates for creating the holes in all cases, assuming expected efficiencies. Therefore, it appears that stellar feedback provides sufficient energy to produce the observed holes. However, we find no obvious signature of single star-forming events responsible for the observed structures when comparing the global SFHs of each galaxy in our sample to each other or to those of dwarf irregular galaxies reported in the literature. We also fail to find evidence of a central star cluster in FUV or Hα imaging. We conclude that large Hi holes are likely formed from multiple generations of star formation and only under suitable interstellar medium conditions

Rapid Heterotrophic Ossification with Cryopreserved Poly(ethylene glycol-) Microencapsulated BMP2-Expressing MSCs

Autologous bone grafting is the most effective treatment for long-bone nonunions, but it poses considerable risks to donors, necessitating the development of alternative therapeutics. Poly(ethylene glycol) (PEG) microencapsulation and BMP2 transgene delivery are being developed together to induce rapid bone formation. However, methods to make these treatments available for clinical applications are presently lacking. In this study we used mesenchymal stem cells (MSCs) due to their ease of harvest, replication potential, and immunomodulatory capabilities. MSCs were from sheep and pig due to their appeal as large animal models for bone nonunion. We demonstrated that cryopreservation of these microencapsulated MSCs did not affect their cell viability, adenoviral BMP2 production, or ability to initiate bone formation. Additionally, microspheres showed no appreciable damage from cryopreservation when examined with light and electron microscopy. These results validate the use of cryopreservation in preserving the viability and functionality of PEG-encapsulated BMP2-transduced MSCs