Relic gravitons from non-singular string cosmologies

In the context of the pre-Big Bang scenario of string cosmology, we propose a modified equation for the evolution of the tensor perturbations, which includes the full contribution of possible higher-order curvature and coupling corrections required to regularise the background evolution. We then discuss the high-frequency branch of the spectrum of primordial gravitons.Comment: Contribution to CAPP2000, Verbier (Switzerland),July 2000. To appear in the Proceedings (American Institute of Physics publication

On graviton production in braneworld cosmology

We study braneworlds in a five dimensional bulk, where cosmological expansion is mimicked by motion through AdS$_5$. We show that the five dimensional graviton reduces to the four dimensional one in the late time approximation of such braneworlds. Inserting a fixed regulator brane far from the physical brane, we investigate quantum graviton production due to the motion of the brane. We show that the massive Kaluza-Klein modes decouple completely from the massless mode and they are not generated at all in the limit where the regulator brane position goes to infinity. In the low energy limit, the massless four dimensional graviton obeys the usual 4d equation and is therefore also not generated in a radiation-dominated universe.Comment: 9 pages, minor changes, references correcte

Tachyonic perturbations in AdS5_5 orbifolds

We show that scalar as well as vector and tensor metric perturbations in the Randall-Sundrum II braneworld allow normalizable tachyonic modes, i.e., possible instabilities. These instabilities require nonvanishing initial anisotropic stresses on the brane. We show with a specific example that within the Randall-Sundrum II model, even though the tachyonic modes are excited, no instability develops. We argue, however, that in the cosmological context instabilities might in principle be present. We conjecture that the tachyonic modes are due to the singularity of the orbifold construction. We illustrate this with a simple but explicit toy model.Comment: 11 pages, matches published versio

Evolution of cosmological perturbations in non-singular string cosmologies

In a class of non-singular cosmologies derived from higher-order corrections to the low-energy bosonic string action, we derive evolution equations for the most general cosmological scalar, vector and tensor perturbations. In the large scale limit, the evolutions of both scalar and tensor perturbations are characterised by conserved quantities, the usual curvature perturbation in the uniform-field gauge and the tensor-type perturbed metric. The vector perturbation is not affected, being described by the conservation of the angular momentum of the fluid component in the absence of any additional dissipative process. For the scalar- and tensor-type perturbations, we show how, given a background evolution during kinetic driven inflation of the dilaton field, we can obtain the final power spectra generated from the vacuum quantum fluctuations of the metric and the dilaton field during the inflation.Comment: 11 pages, 2 figures, submitted to Phys. Rev.

Bone Marrow Concentrate (BMC) Therapy in Musculoskeletal Disorders: Evidence-Based Policy Position Statement of American Society of Interventional Pain Physicians (ASIPP)

BACKGROUND: The use of bone marrow concentrate (BMC) for treatment of musculoskeletal disorders has become increasingly popular over the last several years, as technology has improved along with the need for better solutions for these pathologies. The use of cellular tissue raises a number of issues regarding the US Food and Drug Administration\u27s (FDA) regulation in classifying these treatments as a drug versus just autologous tissue transplantation. In the case of BMC in musculoskeletal and spine care, this determination will likely hinge on whether BMC is homologous to the musculoskeletal system and spine. OBJECTIVES: The aim of this review is to describe the current regulatory guidelines set in place by the FDA, specifically the terminology around minimal manipulation and homologous use within Regulation 21 CFR Part 1271, and specifically how this applies to the use of BMC in interventional musculoskeletal medicine. METHODS: The methodology utilized here is similar to the methodology utilized in preparation of multiple guidelines employing the experience of a panel of experts from various medical specialties and subspecialties from differing regions of the world. The collaborators who developed these position statements have submitted their appropriate disclosures of conflicts of interest. Trustworthy standards were employed in the creation of these position statements. The literature pertaining to BMC, its effectiveness, adverse consequences, FDA regulations, criteria for meeting the standards of minimal manipulation, and homologous use were comprehensively reviewed using a best evidence synthesis of the available and relevant literature. RESULTS/Summary of Evidence: In conjunction with evidence-based medicine principles, the following position statements were developed: Statement 1: Based on a review of the literature in discussing the preparation of BMC using accepted methodologies, there is strong evidence of minimal manipulation in its preparation, and moderate evidence for homologous utility for various musculoskeletal and spinal conditions qualifies for the same surgical exemption. Statement 2: Assessment of clinical effectiveness based on extensive literature shows emerging evidence for multiple musculoskeletal and spinal conditions. • The evidence is highest for knee osteoarthritis with level II evidence based on relevant systematic reviews, randomized controlled trials and nonrandomized studies. There is level III evidence for knee cartilage conditions. • Based on the relevant systematic reviews, randomized trials, and nonrandomized studies, the evidence for disc injections is level III. • Based on the available literature without appropriate systematic reviews or randomized controlled trials, the evidence for all other conditions is level IV or limited for BMC injections. Statement 3: Based on an extensive review of the literature, there is strong evidence for the safety of BMC when performed by trained physicians with the appropriate precautions under image guidance utilizing a sterile technique. Statement 4: Musculoskeletal disorders and spinal disorders with related disability for economic and human toll, despite advancements with a wide array of treatment modalities. Statement 5: The 21st Century Cures Act was enacted in December 2016 with provisions to accelerate the development and translation of promising new therapies into clinical evaluation and use. Statement 6: Development of cell-based therapies is rapidly proliferating in a number of disease areas, including musculoskeletal disorders and spine. With mixed results, these therapies are greatly outpacing the evidence. The reckless publicity with unsubstantiated claims of beneficial outcomes having putative potential, and has led the FDA Federal Trade Commission (FTC) to issue multiple warnings. Thus the US FDA is considering the appropriateness of using various therapies, including BMC, for homologous use. Statement 7: Since the 1980\u27s and the description of mesenchymal stem cells by Caplan et al, (now called medicinal signaling cells), the use of BMC in musculoskeletal and spinal disorders has been increasing in the management of pain and promoting tissue healing. Statement 8: The Public Health Service Act (PHSA) of the FDA requires minimal manipulation under same surgical procedure exemption. Homologous use of BMC in musculoskeletal and spinal disorders is provided by preclinical and clinical evidence. Statement 9: If the FDA does not accept BMC as homologous, then it will require an Investigational New Drug (IND) classification with FDA (351) cellular drug approval for use. Statement 10: This literature review and these position statements establish compliance with the FDA\u27s intent and corroborates its present description of BMC as homologous with same surgical exemption, and exempt from IND, for use of BMC for treatment of musculoskeletal tissues, such as cartilage, bones, ligaments, muscles, tendons, and spinal discs. CONCLUSIONS: Based on the review of all available and pertinent literature, multiple position statements have been developed showing that BMC in musculoskeletal disorders meets the criteria of minimal manipulation and homologous use. KEY WORDS: Cell-based therapies, bone marrow concentrate, mesenchymal stem cells, medicinal signaling cells, Food and Drug Administration, human cells, tissues, and cellular tissue-based products, Public Health Service Act (PHSA), minimal manipulation, homologous use, same surgical procedure exemption

Genetic labeling of embryonically-born dentate granule neurons in young mice using the Penk Cre mouse line

Abstract The dentate gyrus (DG) of the hippocampus is a mosaic of dentate granule neurons (DGNs) accumulated throughout life. While many studies focused on the morpho-functional properties of adult-born DGNs, much less is known about DGNs generated during development, and in particular those born during embryogenesis. One of the main reasons for this gap is the lack of methods available to specifically label and manipulate embryonically-born DGNs. Here, we have assessed the relevance of the Penk Cre mouse line as a genetic model to target this embryonically-born population. In young animals, Penk Cre expression allows to tag neurons in the DG with positional, morphological and electrophysiological properties characteristic of DGNs born during the embryonic period. In addition, PenkCre+ cells in the DG are distributed in both blades along the entire septo-temporal axis. This model thus offers new possibilities to explore the functions of this underexplored population of embryonically-born DGNs