Effect of gaseous and solid simulated jet plumes on a 040A space shuttle launch configuration at Mach numbers from 1.6 to 2.2

An experimental investigation was conducted in a 9- by 7-foot supersonic wind tunnel to determine the effect of plume-induced flow separation and aspiration effects due to operation of both the orbiter and the solid rocket motors on a 0.019-scale model of the launch configuration of the space shuttle vehicle. Longitudinal and lateral-directional stability data were obtained at Mach numbers of 1.6, 2.0, and 2.2 with and without the engines operating. The plumes exiting from the engines were simulated by a cold gas jet supplied by an auxiliary 200 atmosphere air supply system, and by solid body plume simulators. Comparisons of the aerodynamic effects produced by these two simulation procedures are presented. The data indicate that the parameters most significantly affected by the jet plumes are the pitching moment, the elevon control effectiveness, the axial force, and the orbiter wing loads

Thirty-three years of ocean benthic warming along the U.S. Northeast Continental Shelf and Slope : patterns, drivers, and ecological consequences

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Journal of Geophysical Research: Oceans 122 (2017): 9399–9414, doi:10.1002/2017JC012953.The U.S. Northeast Continental Shelf is experiencing rapid warming, with potentially profound consequences to marine ecosystems. While satellites document multiple scales of spatial and temporal variability on the surface, our understanding of the status, trends, and drivers of the benthic environmental change remains limited. We interpolated sparse benthic temperature data along the New England Shelf and upper Slope using a seasonally dynamic, regionally specific multiple linear regression model that merged in situ and remote sensing data. The statistical model predicted nearly 90% of the variability of the data, resulting in a synoptic time series spanning over three decades from 1982 to 2014. Benthic temperatures increased throughout the domain, including in the Gulf of Maine. Rates of benthic warming ranged from 0.1 to 0.4°C per decade, with fastest rates occurring in shallow, nearshore regions and on Georges Bank, the latter exceeding rates observed in the surface. Rates of benthic warming were up to 1.6 times faster in winter than the rest of the year in many regions, with important implications for disease occurrence and energetics of overwintering species. Drivers of warming varied over the domain. In southern New England and the mid-Atlantic shallow Shelf regions, benthic warming was tightly coupled to changes in SST, whereas both regional and basin-scale changes in ocean circulation affect temperatures in the Gulf of Maine, the Continental Shelf, and Georges Banks. These results highlight data gaps, the current feasibility of prediction from remotely sensed variables, and the need for improved understanding on how climate may affect seasonally specific ecological processes.John D. and Catherine T. MacArthur Foundation Grant Number: 14–106159-000-CFP; National Aeronautics and Space Administration Grant Number: NNX14AP62

Persistence of low disease activity after tumour necrosis factor inhibitor (TNFi) discontinuation in patients with psoriatic arthritis.

OBJECTIVE: To determine the duration of clinical benefit among patients with psoriatic arthritis (PsA) discontinuing tumour necrosis factor inhibitor (TNFi) therapy while in low disease activity (LDA), and to identify patient characteristics associated with prolonged clinical benefit. METHODS: We performed an observational cohort study assessing patients with PsA from the Consortium of Rheumatology Researchers of North America (CORRONA) registry who had discontinued TNFi after achieving LDA, defined as clinical disease activity index (CDAI) score ≤10 and physician\u27s global assessment (PGA) of skin psoriasis ≤20/100. Kaplan-Meier method was used to estimate the duration of clinical benefit. RESULTS: Of the 5945 patients with PsA in CORRONA, 302 patients had discontinued TNFi (n=325) while in LDA and had follow-up data available. At time of discontinuation, mean PsA duration was 9.8 years, mean CDAI was 3.9, and mean duration of TNFi use was 1.5 years; 52.6% of patients had discontinued their first TNFi. Median time to loss of benefit was 29.2 months. 179 (55.1%) patients had persistent benefit at their previous clinic visit. An increased risk of losing clinical benefit was seen among patients with higher disease activity at discontinuation (CDAI≥3.2 vs CONCLUSIONS: Patients with PsA who achieve LDA may maintain clinical benefit after discontinuation of TNFi therapy

FRI0345 HEAD-TO-HEAD STUDY EVALUATING THE COMBINED ACR50/PASI100 TREATMENT RESPONSE OF IXEKIZUMAB VERSUS ADALIMUMAB: INDIVIDUAL PATIENT DATA FROM A RANDOMIZED, OPEN-LABEL STUDY IN BIOLOGIC-NAÏVE PATIENTS WITH PSORIATIC ARTHRITIS THROUGH WEEK 52

Background:Multiple biologic DMARDs (bDMARDs) are available for the treatment of psoriatic arthritis (PsA), but there are few direct comparisons of their efficacy and safety. In SPIRIT-H2H study, ixekizumab (IXE), a high-affinity monoclonal antibody selectively targeting IL-17A, was superior to adalimumab (ADA) at Week 24 for simultaneous achievement of ACR50 and 100% improvement from baseline in the Psoriasis Area and Severity Index (PASI 100) in patients (pts) with active PsA. Efficacy on other PsA domains was shown.1Objectives:To provide individual patient data demonstrating the simultaneous improvement in musculoskeletal and skin symptoms as assessed by American College of Rheumatology (ACR) response criteria and Psoriasis Area and Severity Index (PASI) percent improvement, respectively.Methods:Pts with active PsA fulfilling Classification for Psoriatic Arthritis (CASPAR) criteria, ≥3/66 tender and ≥3/68 swollen joints, ≥3% psoriasis body surface area (BSA) involvement, no prior treatment with bDMARDs, and prior inadequate response to ≥1 conventional synthetic DMARD (csDMARD), were randomized 1:1 to open-label IXE or ADA (label dosing according to presence/absence of moderate-to-severe psoriasis [baseline BSA≥10%, PASI≥12, and static Physician's Global Assessment≥3]) in Study I1F-MC-RHCF (NCT03151551). In this analysis, max ACRx was defined as the maximum ACRx response a patient can achieve where ACRx derivation follows the typical ACR response criteria: ≥x% improvement in both tender joint count (TJC) and swollen joint count (SJC) and ≥x% improvement in ≥3 of the 5 remaining components, Health Assessment Questionnaire-Disability Index total score (HAQ-DI), C-reactive protein (CRP), Patient Global Assessment (PatGA), Physician Global Assessment (PhyGA), and patient assessment of joint pain (patJP). Missing data were imputed using the last observation carried forward (LOCF) method.Results:At baseline, demographic and disease characteristics were similar across treatment groups. Mean baseline values for the ACR core data set were 20.2 (TJC), 10.4 (SJC), 63.8 (PatGA), 10.2 (CRP), 59.2 (PhyGA), 1.2 (HAQ-DI), and 61.0 (patJP). Mean PASI total score was 7.8. Figures 1 and 2 show the maximum ACR response by PASI percent improvement at Weeks 24 and 52, respectively. Independent of joint improvement, more ixekizumab-treated patients compared to adalimumab-treated patients achieved ≥PASI 90 (76.6% vs. 57.5% at week 24 and 83.0% vs. 59.6% at Week 52). Evaluation of patient-level data shows that while very few patients had joint improvement but little skin improvement (max ACRx≥50 and PASI<50; Figures 1 and 2) in both treatment arms (IXE: 1.8%; ADA: 1.4%), fewer patients treated with IXE had no to little improvement in both joint and skin symptoms (PASI<50 and max ACRx<50) than those treated with ADA at Week 24 (IXE: 3.6%; ADA: 13.3%). A similar pattern was observed at Week 52 (Figure 2).Conclusion:Ixekizumab treatment was superior to adalimumab when evaluating the combination of musculoskeletal and skin symptoms of PsA as measured by ACR response and PASI response.References:[1]Mease PJ, Smolen JS, Behrens F et al., Ann Rheum Dis 2019; 79(1):123-131.Disclosure of Interests:Arthur Kavanaugh Grant/research support from: AbbVie, Amgen, Eli Lilly, Novartis, Janssen, Pfizer, Gilead, UCB, Consultant of: AbbVie, Amgen, Eli Lilly, Novartis, Janssen, Pfizer, Gilead, UCB, Ennio Lubrano: None declared, Talia Muram Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Chen-Yen Lin Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Soyi Liu Leage Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Filip van den Bosch Consultant of: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Speakers bureau: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Lars Erik Kristensen Consultant of: UCB Pharma (Advisory Board), Sannofi (Advisory Board), Abbvie (Advisory Board), Biogen (Advisory Board), Speakers bureau: AbbVie, Amgen, Biogen, Bristol-Myers Squibb,Celgene, Eli Lilly, Gilead, Forward Pharma, Janssen Pharmaceuticals, MSD, Novartis, Pfizer, and UCB Pharm

Treatment recommendations for psoriatic arthritis

Objective: To develop comprehensive recommendations for the treatment of the various clinical manifestations of psoriatic arthritis (PsA) based on evidence obtained from a systematic review of the literature and from consensus opinion. Methods: Formal literature reviews of treatment for the most significant discrete clinical manifestations of PsA (skin and nails, peripheral arthritis, axial disease, dactylitis and enthesitis) were performed and published by members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). Treatment recommendations were drafted for each of the clinical manifestations by rheumatologists, dermatologists and PsA patients based on the literature reviews and consensus opinion. The level of agreement for the individual treatment recommendations among GRAPPA members was assessed with an online questionnaire. Results: Treatment recommendations were developed for peripheral arthritis, axial disease, psoriasis, nail disease, dactylitis and enthesitis in the setting of PsA. In rotal, 19 recommendations were drafted, and over 80% agreement was obtained on 16 of them. In addition, a grid that factors disease severity into each of the different disease manifestations was developed to help the clinician with treatment decisions for the individual patient from an evidenced-based perspective. Conclusions: Treatment recommendations for the cardinal physical manifestations of PsA were developed based on a literature review and consensus between rheumatologists and dermatologists. In addition, a grid was established to assist in therapeutic reasoning and decision making for individual patients. It is anticipated that periodic updates will take place using this framework as new data become available

Atmospheric and Fluvial Nutrients Fuel Algal Blooms in the East China Sea

Chinese coastal waters support vast fisheries and vital economies, but their productivity is threatened by increasingly frequent harmful algal blooms (HABs). Here we provide direct experimental evidence that atmospheric deposition, along with riverine input, opens new niches for bloom-forming dinoflagellates and diatoms in the East China Sea (ECS) by increasing the ratio of nitrogen to phosphorus (N:P), inducing severe P limitation, and altering trace metal micronutrient inventories. Remote sensing analysis of blooms in the region showed that dinoflagellate blooms were associated with increased aerosol optical thickness and decreased sea surface temperature, whereas diatom blooms were primarily associated with seasonally decreased temperature (e.g., during spring blooms). Bottle incubation experiments revealed that aerosol additions approximating 10 days of strong deposition increased iron availability and intensified P limitation, which together promoted dinoflagellate growth in offshore waters. Diatom growth was correlated with elevated trace metal and nutrient content from aerosols. Aerosols did not induce phytoplankton growth at a station within the Yangtze River plume where light was limiting, consistent with remote sensing observations that aerosol effects are stronger in offshore waters. Eutrophication and trace metal enrichment from Yangtze River discharge together with atmospheric deposition may underlie the transition from diatom-dominated spring blooms toward more frequent spring and summer dinoflagellate blooms that has occurred over the past three decades in the ECS

Prion protein lowering is a disease-modifying therapy across prion disease stages, strains and endpoints

Lowering of prion protein (PrP) expression in the brain is a genetically validated therapeutic hypothesis in prion disease. We recently showed that antisense oligonucleotide (ASO)-mediated PrP suppression extends survival and delays disease onset in intracerebrally prion-infected mice in both prophylactic and delayed dosing paradigms. Here, we examine the efficacy of this therapeutic approach across diverse paradigms, varying the dose and dosing regimen, prion strain, treatment timepoint, and examining symptomatic, survival, and biomarker readouts. We recapitulate our previous findings with additional PrP-targeting ASOs, and demonstrate therapeutic benefit against four additional prion strains. We demonstrate that \u3c25% PrP suppression is sufficient to extend survival and delay symptoms in a prophylactic paradigm. Rise in both neuroinflammation and neuronal injury markers can be reversed by a single dose of PrP-lowering ASO administered after the detection of pathological change. Chronic ASO-mediated suppression of PrP beginning at any time up to early signs of neuropathology confers benefit similar to constitutive heterozygous PrP knockout. Remarkably, even after emergence of frank symptoms including weight loss, a single treatment prolongs survival by months in a subset of animals. These results support ASO-mediated PrP lowering, and PrP-lowering therapeutics in general, as a promising path forward against prion disease

Techno-Economic Feasibility Analysis of a Fully Mobile Radiation Oncology System using Monte Carlo Simulation

PURPOSEDisparities in radiation oncology (RO) can be attributed to geographic location, socioeconomic status, race, sex, and other societal factors. One potential solution is to implement a fully mobile (FM) RO system to bring radiotherapy to rural areas and reduce barriers to access. We use Monte Carlo simulation to quantify techno-economic feasibility with uncertainty, using two rural Missouri scenarios.METHODSRecently, a semimobile RO system has been developed by building an o-ring linear accelerator (linac) into a mobile coach that is used for temporary care, months at a time. Transitioning to a more FM-RO system, which changes location within a given day, presents technical challenges including logistics and quality assurance. This simulation includes cancer census in both northern and southeastern Missouri, multiple treatment locations within a given day, and associated expenditures and revenues. A subset of patients with lung, breast, and rectal diseases, treated with five fractions, was simulated in the FM-RO system.RESULTSThe FM-RO can perform all necessary quality assurance tests as suggested in national medical physics guidelines within 1.5 hours, thus demonstrating technological feasibility. In northern and southeastern Missouri, five-fraction simulations\u27 net incomes were, in US dollars (USD), $1.55 ± 0.17 million (approximately 74 patients/year) and$3.65 USD ± 0.25 million (approximately 98 patients/year), respectively. The number of patients seen had the highest correlation with net income as well as the ability to break-even within the simulation. The model does not account for disruptions in care or other commonly used treatment paradigms, which may lead to differences in estimated economic return. Overall, the mobile system achieved a net benefit, even for the most negative simulation scenarios.CONCLUSIONOur simulations suggest technologic success and economic viability for a FM-RO system within rural Missouri and present an interesting solution to address other geographic disparities in access to radiotherapy