A systematic review of treating recurrent head and neck cancer: a reintroduction of brachytherapy with or without surgery.

Purpose: To review brachytherapy use in recurrent head and neck carcinoma (RHNC) with focus on its efficacy and complication rates. Material and methods: A literature search of PubMed, Ovid, Google Scholar, and Scopus was conducted from 1990 to 2017. Publications describing treatment of RHNC with brachytherapy with or without surgery were included. The focus of this review is on oncologic outcomes and the safety of brachytherapy in the recurrent setting. Results: Thirty studies involving RHNC treatment with brachytherapy were reviewed. Brachytherapy as adjunctive treatment to surgical resection appears to be associated with an improved local regional control and overall survival, when compared with the published rates for re-irradiation utilizing external beam radiotherapy (RT) or brachytherapy alone. Safety data remains variable with different isotopes and dose rates with implantable brachytherapy demonstrating a tolerable side effect profile. Conclusions: Although surgery remains a mainstay treatment for RHNC, intraoperative interstitial brachytherapy delivery as adjunctive therapy may improve the treatment outcome and may be associated with fewer complication rates as compared to reirradiation using external beam radiotherapy. Further investigations are required to elucidate the role of brachytherapy for RHNC

Dose-related Effects of Salvinorin A in Humans: Dissociative, Hallucinogenic, and Memory Effects

RATIONALE: Salvinorin A is a kappa opioid agonist and the principal psychoactive constituent of the plant Salvia divinorum, which has increased in popularity as a recreational drug over the past decade. Few human studies have examined salvinorin A. OBJECTIVE: This double-blind, placebo-controlled study evaluated the dose-related effects of inhaled salvinorin A in individuals with histories of hallucinogen use. METHODS: Eight healthy hallucinogen-using adults inhaled up to 16 doses of salvinorin A (0.375 - 21 μg/kg) in ascending order. Physiological, behavioral, and subjective effects were assessed every 2 min for 60 min after administration. Qualitative subjective effects were assessed retrospectively via questionnaires at the end of sessions. Persisting effects were assessed 1 month later. RESULTS: Orderly dose-related effects peaked at 2 min and then rapidly dissipated, replicating previous findings. Subjective effects were intense, with maximal drug strength ratings or unresponsiveness frequently observed at high doses. Questionnaires assessing qualitative effects (Hallucinogen Rating Scale, Pharmacological Class Questionnaire) suggested some overlap with serotonergically mediated classic hallucinogens. Salvinorin A also produced dose-related dissociative effects and impairments in recall/recognition memory. At 1-month follow-up, there was no evidence of persisting adverse effects. Participants reported salvinorin A effects were qualitatively different from other drugs. CONCLUSIONS: Salvinorin A produces a unique profile of subjective and cognitive effects, including strong dissociative effects and memory impairment, which only partially overlap with classic hallucinogen effects. Along with nonhuman studies of salvinorin A, these results are important for understanding the neurobiology of the kappa opioid system and may ultimately have important therapeutic applications

Human psychopharmacology and dose-effects of salvinorin A, a kappa-opioid agonist hallucinogen present in the plant Salvia divinorum

Salvinorin A is a potent, selective nonnitrogenous kappa opioid agonist and the known psychoactive constituent of Salvia divinorum, a member of the mint family that has been used for centuries by Mazatec shamans of Mexico for divination and spiritual healing. Salvia divinorum has over the last several years gained increased popularity as a recreational drug. This is a double-blind, placebo controlled study of salvinorin A in 4 psychologically and physically healthy hallucinogen-using adults. Across sessions, participants inhaled 16 ascending doses of salvinorin A and 4 intermixed placebo doses under comfortable and supportive conditions. Doses ranged from 0.375 μg/kg to 21 μg/kg. Subject-rated drug strength was assessed every 2 minutes for 60 minutes after inhalation. Orderly time- and dose-related effects were observed. Drug strength ratings peaked at 2 minutes (first time point) and definite subjective effects were no longer present at approximately 20 minutes after inhalation. Dose-related increases were observed on questionnaire measures of mystical-type experience (Mysticism Scale) and subjective effects associated with classic serotonergic (5-HT2A) hallucinogens (Hallucinogen Rating Scale). Salvinorin A did not significantly increase heart rate or blood pressure. Participant narratives indicated intense experiences characterized by disruptions in vestibular and interoceptive signals (e.g., change in spatial orientation, pressure on the body) and unusual and sometimes recurring themes across sessions such as revisiting childhood memories, cartoon-like imagery, and contact with entities. Under these prepared and supportive conditions, salvinorin A occasioned a unique profile of subjective effects having similarities to classic hallucinogens, including mystical-type effects

A simple all-microwave entangling gate for fixed-frequency superconducting qubits

We demonstrate an all-microwave two-qubit gate on superconducting qubits which are fixed in frequency at optimal bias points. The gate requires no additional subcircuitry and is tunable via the amplitude of microwave irradiation on one qubit at the transition frequency of the other. We use the gate to generate entangled states with a maximal extracted concurrence of 0.88 and quantum process tomography reveals a gate fidelity of 81%

Effect of Piglet Age on Distress Associated with Gas Euthanasia, Neonate vs. Weaned

The objective of this study was to compare the effectiveness of euthanasia gases administered to 2 age groups of piglets: neonates (less than 3 days, n=160, BW 2.61 ± 0.81 kg) and weaned (16 to 24 days, n=160, BW 4.62 ± 0.76 kg). Two different gases were explored in this study: 100% CO2 and a 50:50 CO2:Argon (CA) gas mixture. Each gas was administered at 3 flow rates: 35%, 50% and Prefill + 20%, chamber volume exchange rate per minute. Latencies, durations and occurrence of behavior and physiologic changes were observed using direct observationand video. Neonate piglets were euthanized as quickly as or faster than weaned piglets for all gases and flow rates. For the neonate relative to the weaned piglet, average loss of posture over all gas treatments was 99 vs. 142 (seconds) and last movement was 360 vs. 392 (seconds). Neonates also displayed fewer incidences and shorter durations of behavioral indicators of distress and sensation relative to the weaned piglets. Thus concerns for gas euthanasia, when applied appropriately, are not greater for the neonate relative to the weaned piglet. Additionally, procedures developed to euthanize weaned piglets will likely be successful when applied for the neonate, but not viceversa

The Sage-Grouse Habitat Mortgage: Effective Conifer Management in Space and Time

AbstractManagement of conservation-reliant species can be complicated by the need to manage ecosystem processes that operate at extended temporal horizons. One such process is the role of fire in regulating abundance of expanding conifers that disrupt sage-grouse habitat in the northern Great Basin of the United States. Removing conifers by cutting has a beneficial effect on sage-grouse habitat. However, effects may last only a few decades because conifer seedlings are not controlled and the seed bank is fully stocked. Fire treatment may be preferred because conifer control lasts longer than for mechanical treatments. The amount of conservation needed to control conifers at large temporal and spatial scales can be quantified by multiplying land area by the time needed for conifer abundance to progress to critical thresholds (i.e., “conservation volume”). The contribution of different treatments in arresting conifer succession can be calculated by dividing conservation volume by the duration of treatment effect. We estimate that fire has approximately twice the treatment life of cutting at time horizons approaching 100 yr, but, has high up-front conservation costs due to temporary loss of sagebrush. Cutting has less up-front conservation costs because sagebrush is unaffected, but it is more expensive over longer management time horizons because of decreased durability. Managing conifers within sage-grouse habitat is difficult because of the necessity to maintain the majority of the landscape in sagebrush habitat and because the threshold for negative conifer effects occurs fairly early in the successional process. The time needed for recovery of sagebrush creates limits to fire use in managing sage-grouse habitat. Utilizing a combination of fire and cutting treatments is most financially and ecologically sustainable over long time horizons involved in managing conifer-prone sage-grouse habitat

Antigen-Drug Conjugates as a Novel Therapeutic Class for the Treatment of Antigen-Specific Autoimmune Disorders

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see doi.org/10.1021/acs.molpharmaceut.9b00063.Multiple sclerosis represents the world’s most common cause of neurological disability in young people and is attributed to a loss of immune tolerance toward proteins of the myelin sheath. Typical treatment options for MS patients involve immunomodulatory drugs, which act non-specifically, resulting in global immunosuppression. The study discussed herein aims to demonstrate the efficacy of antigen-specific immunotherapies involving conjugation of disease causing auto-antigen, PLP139–151, and a potent immunosuppressant, dexamethasone. Antigen-drug conjugates (AgDCs) were formed using copper-catalyzed azide-alkyne cycloaddition chemistry with the inclusion of a hydrolyzable linker to maintain activity of released dexamethasone. Subcutaneous administration of this antigen-drug conjugate to SJL mice induced with experimental autoimmune encephalomyelitis protected the mice from symptom onset throughout the 25-day study, demonstrating enhanced efficacy in comparison to dexamethasone treatment. These results highlight the benefits of co-delivery of auto-antigens with immunosuppressant drugs as AgDCs for the treatment of autoimmune diseases.National Institutes of Health Graduate Training Program in Dynamic Aspects of Chemical Biology Grant (T32 GM008545)Howard Rytting pre-doctoral fellowship from the Department of Pharmaceutical Chemistry at the University of KansasNational Institutes of Health Biotechnology Training Grant (NIH0073415)NIH Shared Instrumentation Grant # S10RR024664NSF Major Research Instrumentation Award # 162592

Genes regulated by estrogen in breast tumor cells in vitro are similarly regulated in vivo in tumor xenografts and human breast tumors

BACKGROUND: Estrogen plays a central role in breast cancer pathogenesis. Although many studies have characterized the estrogen regulation of genes using in vitro cell culture models by global mRNA expression profiling, it is not clear whether these genes are similarly regulated in vivo or how they might be coordinately expressed in primary human tumors. RESULTS: We generated DNA microarray-based gene expression profiles from three estrogen receptor α (ERα)-positive breast cancer cell lines stimulated by 17β-estradiol (E2) in vitro over a time course, as well as from MCF-7 cells grown as xenografts in ovariectomized athymic nude mice with E2 supplementation and after its withdrawal. When the patterns of genes regulated by E2 in vitro were compared to those obtained from xenografts, we found a remarkable overlap (over 40%) of genes regulated by E2 in both contexts. These patterns were compared to those obtained from published clinical data sets. We show that, as a group, E2-regulated genes from our preclinical models were co-expressed with ERα in a panel of ERα+ breast tumor mRNA profiles, when corrections were made for patient age, as well as with progesterone receptor. Furthermore, the E2-regulated genes were significantly enriched for transcriptional targets of the myc oncogene and were found to be coordinately expressed with Myc in human tumors. CONCLUSION: Our results provide significant validation of a widely used in vitro model of estrogen signaling as being pathologically relevant to breast cancers in vivo

Geographic Information System Data Analysis

Data was collected in order to further NASA Langley Research Center's Geographic Information System(GIS). Information on LaRC's communication, electrical, and facility configurations was collected. Existing data was corrected through verification, resulting in more accurate databases. In addition, Global Positioning System(GPS) points were used in order to accurately impose buildings on digitized images. Overall, this project will help the Imaging and CADD Technology Team (ICTT) prove GIS to be a valuable resource for LaRC