Propulsion Study for Small Transport Aircraft Technology (STAT)

Propulsion requirements were determined for 0.5 and 0.7 Mach aircraft. Sensitivity studies were conducted on both these aircraft to determine parametrically the influence of propulsion characteristics on aircraft size and direct operating cost (DOC). Candidate technology elements and design features were identified and parametric studies conducted to select the STAT advanced engine cycle. Trade off studies were conducted to determine those advanced technologies and design features that would offer a reduction in DOC for operation of the STAT engines. These features were incorporated in the two STAT engines. A benefit assessment was conducted comparing the STAT engines to current technology engines of the same power and to 1985 derivatives of the current technology engines. Research and development programs were recommended as part of an overall technology development plan to ensure that full commercial development of the STAT engines could be initiated in 1988

PAHs, PCBs, PBDEs and Pesticides in Cold-Pressed Vegetable Oils

The aim of this study was to investigate levels of polychlorinated biphenyls (marker and dioxin-like congeners), polycyclic aromatic hydrocarbons (EPA 15 + 1), polybrominated diphenyl ethers (14 predominant congeners) and pesticides (74 compounds) in various cold-pressed vegetable oils. Poppy seed oil, rapeseed oil, sesame seed oil, pumpkinseed oil, hempseed oil, linaire oil, borage oil and evening star oil were investigated. Results of this study revealed that concentrations of PCBs, PBDEs and PAHs were low in majority of the investigated samples. However, high concentrations of organophosphorus insecticides were found. Chlorpyrifos methyl and pirimiphos methyl were the pesticide residues most commonly found in the studied oils. Concentration of 15 + 1 EPA PAHs was within the 17.85–37.16 μg kg−1 range, concentration of (marker) PCBs varied from 127 to 24,882 pg g−1, dioxin-like TEQ values were below 0.1 pg TEQ g−1. Concentration of PBDEs was below LOQ in most cases

Transfer of PCDD/PCDF from contaminated soils to food and fodder crop plants

Measurement of the uptake of PCDD/PCDF by crop plants provides important information for the assessment of public health risks. Using various crops yielding different organs of economic importance, the following aspects were examined in field experiments: 1. extent of PCDD/PCDF transfer into plants from soils with different levels of contamination, 2. differences between plant species and organs in their ability to accumulate PCDD/PCDF, 3. influence of post-harvest processing (e.g. cleaning and peeling) on the PCDD/PCDF content of the economically important plant parts, and 4. possible measures to reduce the soil - plant (- animal)-transfer. (orig./BBR)SIGLEAvailable from TIB Hannover: D.Dt.F. QN1(4,41) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman

Transfer von Dioxinen aus unterschiedlich stark Dioxin-belasteten Boeden in Nahrungs- und Futterpflanzen Schlussbericht

Das Gesamtziel des Projektes war es zu untersuchen, wie sich unterschiedliche PCDD/PCDF-Belastungen von Boeden auf das Ausmass des Transfers Boden-Pflanze auswirken und welche Rolle hierbei verschiedene Bodeneigenschaften und Pflanzenarten spielen. Das wesentliche Ziel der Versuche der zweiten und dritten Vegetationsperiode (1991/1992) war die Ermittlung des Anteils der verschiedenen Kontaminationspfade an der Gesamtbelastung der Pflanzen. Die Ergebnisse zeigten, dass eine systemische Aufnahme und eine anschliessende Verlagerung von PCDD/PCDF in oberirdische Pflanzenteile nur in einem sehr geringen Ausmass stattfindet. Boeden mit einem hohen Anteil organischer Substanz und hoher KAK weisen tendenziell einen geringeren Transfer Boden-Pflanze auf als leichtere Boeden. In den meisten Regionen wird der Transfer Boden-Pflanze jedoch von atmogenen PCDD/PCDF-Eintraegen ueberlagert. Eine Aufnahme aus dem Boden verdampfender PCDD/PCDF in Pflanzensprosse ist unter Freilandbedingungen nicht messbar. Oberflaechliche Kontaminationen mit PCDD/PCDF-belasteten Bodenpartikeln erwiesen sich als unbedeutend fuer die Gesamtbelastung von Pflanzen mit PCDD/PCDF. (orig.)The objective of this project was to determine the extent of soil-plant transfer of PCDD/PCDF with regard to the degree of soil contamination, soil properties and plant species. The main objective of the second and third vegetation period (1991/1992) was to estimate the proportion of the various contamination pathways. According to the results, root uptake of PCDD/PCDF and subsequent translocation to the shoots occurs only to a very small extent. Soils high in organic matter and with a high CEC seem to exhibit the lowest soil-plant transfer. However, in most areas this pathway is superimposed by atmospheric depositions of PCDD/PCDF. Under outdoor conditions an uptake of PCDD/PCDF into aerial plant parts following volatilisation from the soil can not be detected. Plant surface contamination with soil particles is of minor importance for the total PCDD/PCDF contamination of plants. (orig.)SIGLEAvailable from TIB Hannover: F94B0385 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman

Assessment of gender representation in clinical trials leading to FDA approval for oncology therapeutics between 2014 and 2019: A systematic review-based cohort study

BACKGROUND: Ensuring representative data accrual in clinical trials is important to safeguard the generalizability of results and to minimize disparities in care. This study\u27s goal was to evaluate differences in gender representation in trials leading to US Food and Drug Administration (FDA) cancer drug approvals. METHODS: An observational study was conducted from January 2014 to April 2019 using PubMed and the National Institutes of Health trials registry for primary trial reports. The National Cancer Institute\u27s Surveillance, Epidemiology, and End Results program and US Census were consulted for national cancer incidence. The outcome was an enrollment incidence disparity (EID), which was calculated as the difference between male and female trial enrollment and national incidence, with positive values representing male overrepresentation. RESULTS: There were 149 clinical trials with 59,988 participants-60.3% and 39.7% were male and female, respectively-leading to 127 oncology drug approvals. The US incidence rates were 55.4% for men versus 44.6% for women. Gender representation varied by specific tumor type. Most notably, women were underrepresented in thyroid cancer (EID, +27.4%), whereas men were underrepresented in soft tissue cancer (EID, -26.1%). Overall, women were underrepresented when compared with expected incidence (EID, +4.9%; 42% of trials). CONCLUSIONS: For many specific tumor types, women are underrepresented in clinical trials leading to FDA oncology drug approvals. It is critical to better align clinical trial cohort demographics and the populations to which these data will be extrapolated. LAY SUMMARY: This study assesses whether gender disparities exist in clinical trials leading to US Food and Drug Administration (FDA) cancer drug approvals. From January 2014 to April 2019, 149 clinical trials leading to FDA oncology drug approvals showed 60.3% and 39.7% of the enrollees were male and female, respectively. Gender representation varied by specific tumor when compared with the expected incidence rate of cancer in the United States, although women were more often underrepresented. Increased efforts are needed with regard to ensuring equitable representation in oncology clinical trials

Radiotherapy after radical prostatectomy: Effect of timing of postprostatectomy radiation on functional outcomes

Introduction and objectiveThe timing of radiotherapy (RT) after prostatectomy is controversial, and its effect on sexual, urinary, and bowel function is unknown. This study seeks to compare patient-reported functional outcomes after radical prostatectomy (RP) and postprostatectomy radiation as well as elucidate the timing of radiation to allow optimal recovery of function.MethodsThe Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study is a prospective, population-based, observational study of men with localized prostate cancer. Patient-reported sexual, urinary, and bowel functional outcomes were measured using the 26-item Expanded Prostate Index Composite at baseline and at 6, 12, 36, and 60 months after enrollment. Functional outcomes were compared among men undergoing RP alone, post-RP adjuvant radiation (RP + aRT), and post-RP salvage radiation (RP + sRT) using multivariable models controlling for baseline clinical, demographic, and functional characteristics.ResultsAmong 1,482 CEASAR participants initially treated with RP for clinically localized prostate cancer, 11.5% (N = 170) received adjuvant (aRT, N = 57) or salvage (sRT, N = 113) radiation. Men who received post-RP RT had worse scores in all domains (sexual function [-9.0, 95% confidence interval {-14.5, -3.6}, P < 0.001], incontinence [-8.8, {-14.0, -3.6}, P < 0.001], irritative voiding [-5.9, {-9.0, -2.8}, P < 0.001], bowel irritative [-3.5, {-5.8, -1.2}, P = 0.002], and hormonal function [-4.5, {-7.2, -1.7}, P = 0.001]) compared to RP alone at 5 years of follow-up. Compared to men treated with RP alone in an adjusted linear model, sRT was associated with significantly worse scores in all functional domains. aRT was associated with significantly worse incontinence, urinary irritation, and hormonal function domain scores compared to RP alone at 5 years of follow-up. On multivariable modeling, RT administered approximately 24 months after RP was associated with the smallest decline in sexual domain score, with an adjusted mean decrease of 8.85 points (95% confidence interval [-19.8, 2.1]) from post-RP, pre-RT baseline.ConclusionsIn men with localized prostate cancer, post-RP RT was associated with significantly worse sexual, urinary, and bowel function domain scores at 5 years compared to RP alone. Radiation delayed for approximately 24 months after RP may be optimal for preserving erectile function compared to radiation administered closer to the time of RP

Aryl hydrocarbon receptor activation by cAMP vs. dioxin: Divergent signaling pathways

Even before the first vertebrates appeared on our planet, the aryl hydrocarbon receptor (AHR) gene was present to carry out one or more critical life functions. The vertebrate AHR then evolved to take on functions of detecting and responding to certain classes of environmental toxicants. These environmental pollutants include polycyclic aromatic hydrocarbons (e.g., benzo[a]pyrene), polyhalogenated hydrocarbons, dibenzofurans, and the most potent small-molecular-weight toxicant known, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin). After binding of these ligands, the activated AHR translocates rapidly from the cytosol to the nucleus, where it forms a heterodimer with aryl hydrocarbon nuclear translocator, causing cellular responses that lead to toxicity, carcinogenesis, and teratogenesis. The nuclear form of the activated AHR/aryl hydrocarbon nuclear translocator complex is responsible for alterations in immune, endocrine, reproductive, developmental, cardiovascular, and central nervous system functions whose mechanisms remain poorly understood. Here, we show that the second messenger, cAMP (an endogenous mediator of hormones, neurotransmitters, and prostaglandins), activates the AHR, moving the receptor to the nucleus in some ways that are similar to and in other ways fundamentally different from AHR activation by dioxin. We suggest that this cAMP-mediated activation may reflect the true endogenous function of AHR; disruption of the cAMP-mediated activation by dioxin, binding chronically to the AHR for days, weeks, or months, might be pivotal in the mechanism of dioxin toxicity. Understanding this endogenous activation of the AHR by cAMP may help in developing methods to counteract the toxicity caused by numerous environmental and food-borne toxic chemicals that act via the AHR