Autologous glioma cell vaccine admixed with interleukin-4 gene transfected fibroblasts in the treatment of patients with malignant gliomas

Background: The prognosis for malignant gliomas remains dismal. We addressed the safety, feasibility and preliminary clinical activity of the vaccinations using autologous glioma cells and interleukin (IL)-4 gene transfected fibroblasts. Methods: In University of Pittsburgh Cancer Institute (UPCI) protocol 95-033, adult participants with recurrent glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA) received gross total resection (GTR) of the recurrent tumors, followed by two vaccinations with autologous fibroblasts retrovirally transfected with TFG-IL4-Neo-TK vector admixed with irradiated autologous glioma cells. In UPCI 99-111, adult participants with newly diagnosed GBM or AA, following GTR and radiation therapy, received two intradermal vaccinations with the TFG-IL4-Neo-TK-transfected fibroblasts admixed with type-1 dendritic cells (DC) loaded with autologous tumor lysate. The participants were evaluated for occurrence of adverse events, immune response, and clinical response by radiological imaging. Results and Discussion: In UPCI 95-033, only 2 of 6 participants received the vaccinations. Four other participants were withdrawn from the trial because of tumor progression prior to production of the cellular vaccine. However, both participants who received two vaccinations demonstrated encouraging immunological and clinical responses. Biopsies from the local vaccine sites from one participant displayed IL-4 dose-dependent infiltration of CD4+ as well as CD8+ T cells. Interferon (IFN)-γ Enzyme-Linked Immuno-SPOT (ELISPOT) assay in another human leukocyte antigen (HLA)-A2+ participant demonstrated systemic T-cell responses against an HLA-A2-restricted glioma-associated antigen (GAA) epitope EphA2883-891. Moreover, both participants demonstrated clinical and radiological improvement with no evidence of allergic encephalitis, although both participants eventually succumbed with the tumor recurrence. In 99-111, 5 of 6 enrolled participants received scheduled vaccinations with no incidence of major adverse events. Monocyte-derived DCs produced high levels of IL-12 p70. Treatment was well tolerated; however, we were unable to observe detectable IFN-γ post-vaccine responses or prolonged progression-free survival in these participants. Conclusion: Feasibility challenges inherent in the generation of a patient-specific gene transfection-based vaccine strongly suggests the need for more practical formulations that would allow for the timely administration of vaccines. Nevertheless, successful generation of type-1 DCs and preliminary safety in the current study provide a strong rationale for further efforts to develop novel glioma vaccines. © 2007 Okada et al; licensee BioMed Central Ltd

Breed-Specific Hematological Phenotypes in the Dog: A Natural Resource for the Genetic Dissection of Hematological Parameters in a Mammalian Species

Remarkably little has been published on hematological phenotypes of the domestic dog, the most polymorphic species on the planet. Information on the signalment and complete blood cell count of all dogs with normal red and white blood cell parameters judged by existing reference intervals was extracted from a veterinary database. Normal hematological profiles were available for 6046 dogs, 5447 of which also had machine platelet concentrations within the reference interval. Seventy-five pure breeds plus a mixed breed control group were represented by 10 or more dogs. All measured parameters except mean corpuscular hemoglobin concentration (MCHC) varied with age. Concentrations of white blood cells (WBCs), neutrophils, monocytes, lymphocytes, eosinophils and platelets, but not red blood cell parameters, all varied with sex. Neutering status had an impact on hemoglobin concentration, mean corpuscular hemoglobin (MCH), MCHC, and concentrations of WBCs, neutrophils, monocytes, lymphocytes and platelets. Principal component analysis of hematological data revealed 37 pure breeds with distinctive phenotypes. Furthermore, all hematological parameters except MCHC showed significant differences between specific individual breeds and the mixed breed group. Twenty-nine breeds had distinctive phenotypes when assessed in this way, of which 19 had already been identified by principal component analysis. Tentative breed-specific reference intervals were generated for breeds with a distinctive phenotype identified by comparative analysis. This study represents the first large-scale analysis of hematological phenotypes in the dog and underlines the important potential of this species in the elucidation of genetic determinants of hematological traits, triangulating phenotype, breed and genetic predisposition

Control and Characterization of Individual Grains and Grain Boundaries in Graphene Grown by Chemical Vapor Deposition

The strong interest in graphene has motivated the scalable production of high quality graphene and graphene devices. Since large-scale graphene films synthesized to date are typically polycrystalline, it is important to characterize and control grain boundaries, generally believed to degrade graphene quality. Here we study single-crystal graphene grains synthesized by ambient CVD on polycrystalline Cu, and show how individual boundaries between coalescing grains affect graphene's electronic properties. The graphene grains show no definite epitaxial relationship with the Cu substrate, and can cross Cu grain boundaries. The edges of these grains are found to be predominantly parallel to zigzag directions. We show that grain boundaries give a significant Raman "D" peak, impede electrical transport, and induce prominent weak localization indicative of intervalley scattering in graphene. Finally, we demonstrate an approach using pre-patterned growth seeds to control graphene nucleation, opening a route towards scalable fabrication of single-crystal graphene devices without grain boundaries.Comment: New version with additional data. Accepted by Nature Material

Secondary osteosarcoma arising after treatment for childhood hematologic malignancies

Secondary osteosarcoma arising after the treatment of hematologic malignancies other than Hodgkin's lymphoma is rare. We report two cases of secondary osteosarcoma arising after treatment for childhood hematologic malignancies (non-Hodgkin's lymphoma and lymphoblastic leukemia). A 10-year-old boy, at the age of 3, was diagnosed with non-Hodgkin's lymphoma. He received chemotherapy, radiation, and bone-marrow transplantation and then was in complete remission. At 6 years, he complained of increasing pain of the right thigh and was diagnosed with osteoblastic osteosarcoma. A 26-year-old man, at the age of 6, was diagnosed as having acute lymphoblastic leukemia (ALL). He received chemotherapy, radiation, and peripheral blood stem cell transplantation (PBSCT). At 11 years after PBSCT, he visited with the complaint of left lumbar swelling. He was diagnosed with chondroblastic osteosarcoma. In both cases alkaline phosphatase (ALP) had already increased prior to the onset of the symptom. We should rule out secondary osteosarcoma at the abnormal elevation of ALP during clinical follow-up of patients after treatment of childhood hematologic malignancies

Fine Tuning in General Gauge Mediation

We study the fine-tuning problem in the context of general gauge mediation. Numerical analyses toward for relaxing fine-tuning are presented. We analyse the problem in typical three cases of the messenger scale, that is, GUT ($2\times10^{16}$ GeV), intermediate ($10^{10}$ GeV), and relatively low energy ($10^6$ GeV) scales. In each messenger scale, the parameter space reducing the degree of tuning as around 10% is found. Certain ratios among gluino mass, wino mass and soft scalar masses are favorable. It is shown that the favorable region becomes narrow as the messenger scale becomes lower, and tachyonic initial conditions of stop masses at the messenger scale are favored to relax the fine-tuning problem for the relatively low energy messenger scale. Our spectra would also be important from the viewpoint of the $\mu-B$ problem.Comment: 22 pages, 16 figures, comment adde

Sex, War, and Disease: The Role of Parasite Infection on Weapon Development and Mating Success in a Horned Beetle (Gnatocerus cornutus)

While parasites and immunity are widely believed to play important roles in the evolution of male ornaments, their potential influence on systems where male weaponry is the object of sexual selection is poorly understood. We experimentally infect larval broad-horned flour beetles with a tapeworm and study the consequent effects on: 1) adult male morphology 2) male-male contests for mating opportunities, and 3) induction of the innate immune system. We find that infection significantly reduces adult male size in ways that are expected to reduce mating opportunities in nature. The sum of our morphological, competition, and immunological data indicate that during a life history stage where no new resources are acquired, males allocate their finite resources in a way that increases future mating potential

Decoupling property of the supersymmetric Higgs sector with four doublets

In supersymmetric standard models with multi Higgs doublet fields, selfcoupling constants in the Higgs potential come only from the D-terms at the tree level. We investigate the decoupling property of additional two heavier Higgs doublet fields in the supersymmetric standard model with four Higgs doublets. In particular, we study how they can modify the predictions on the quantities well predicted in the minimal supersymmetric standard model (MSSM), when the extra doublet fields are rather heavy to be measured at collider experiments. The B-term mixing between these extra heavy Higgs bosons and the relatively light MSSM-like Higgs bosons can significantly change the predictions in the MSSM such as on the masses of MSSM-like Higgs bosons as well as the mixing angle for the two light CP-even scalar states. We first give formulae for deviations in the observables of the MSSM in the decoupling region for the extra two doublet fields. We then examine possible deviations in the Higgs sector numerically, and discuss their phenomenological implications.Comment: 26 pages, 24 figures, text sligtly modified,version to appear in Journal of High Energy Physic

Macular sensitivity and fixation patterns in normal eyes and eyes with uveitis with and without macular edema

PURPOSE: This study aims to investigate the relationship between macular sensitivity and thickness in eyes with uveitic macular edema (UME). DESIGN: This study is a prospective observational case series. METHODS: The setting for this study was clinical practice. The study included 59 (28 with UME, 31 without UME) eyes of 26 patients with uveitis and 19 eyes of 10 normal subjects. The procedure followed was fundus-related perimetry and retinal thickness map with an automated fundus perimetry/tomography system. Main outcome measures included quantification of macular sensitivity, fixation pattern, and relationship between macular sensitivity and thickness. RESULTS: Fixation stability revealed that 56 eyes (93.44%) had stable fixation (\u3e75% within the central 2° of point of fixation); three eyes (6.56%) were relatively unstable (75% located within 4°); and no eye had unstable fixation (50% of fixation point within 0.5 mm of foveal center); seven eyes (11.86%) had peri-central fixation location (25% \u3c 50% within 0.5 mm); and seven eyes (11.86%) had eccentric (280 μm. CONCLUSIONS: Perimetry quantification of macular sensitivity and retinal thickness, in association with other factors, may offer novel information regarding the impact of UME on retinal function

Sexuality throughout all the stages of pregnancy: experiences of expectant mothers

Objective: To explore and understand the sexual experiences of expectant mothers during their pregnancy. Methods: The study was carried out in two healthcare centers in the Almería Health District, in southern Spain. The participants included pregnant women who received prenatal care and/or maternity education. The inclusion criteria were being pregnant, maintaining sexual activity and agreeing to participate in the study. The exclusion criteria were having limitations on sexual activity by medical prescription. The sample consisted of 15 expectant women selected using a convenience sample, of which 5 took part in a focus group (FG) and 10 in in-depth interviews (IDI). Data was collected between the months of June and December 2016. Participants were contacted by the main researcher and an appointment was made to carry out the FGs or the IDIs. Results: Three main categories emerged: False beliefs and a holistic approach to sexuality during pregnancy, which is related to the concept of sexuality, false beliefs, and limited sexual counseling during pregnancy. Limitations: From fear at the beginning to physical diffi culty at the end, referring to the fluctuations in sexual desire as well as the physical changes that limit sexual activity. Adapting to changes: safe practices and satisfaction with one’s body image, which encompasses concerns about the risks and the relationship between body image and self-esteem. Conclusion: A lack of sexual counseling during pregnancy leads to the creation of false beliefs, which, together with physical changes, concerns about the risk, and fl uctuations in sexual desire and interest, bring about a decrease in sexual activity. But sexuality remains an important aspect of pregnancy, toward which the participants must adopt a broader approach, not limited to intercourse, and adopt sexual practices that are adapted to the physical and emotional changes that happen during this time

Properties of Graphene: A Theoretical Perspective

In this review, we provide an in-depth description of the physics of monolayer and bilayer graphene from a theorist's perspective. We discuss the physical properties of graphene in an external magnetic field, reflecting the chiral nature of the quasiparticles near the Dirac point with a Landau level at zero energy. We address the unique integer quantum Hall effects, the role of electron correlations, and the recent observation of the fractional quantum Hall effect in the monolayer graphene. The quantum Hall effect in bilayer graphene is fundamentally different from that of a monolayer, reflecting the unique band structure of this system. The theory of transport in the absence of an external magnetic field is discussed in detail, along with the role of disorder studied in various theoretical models. We highlight the differences and similarities between monolayer and bilayer graphene, and focus on thermodynamic properties such as the compressibility, the plasmon spectra, the weak localization correction, quantum Hall effect, and optical properties. Confinement of electrons in graphene is nontrivial due to Klein tunneling. We review various theoretical and experimental studies of quantum confined structures made from graphene. The band structure of graphene nanoribbons and the role of the sublattice symmetry, edge geometry and the size of the nanoribbon on the electronic and magnetic properties are very active areas of research, and a detailed review of these topics is presented. Also, the effects of substrate interactions, adsorbed atoms, lattice defects and doping on the band structure of finite-sized graphene systems are discussed. We also include a brief description of graphane -- gapped material obtained from graphene by attaching hydrogen atoms to each carbon atom in the lattice.Comment: 189 pages. submitted in Advances in Physic