Guidance on Noncorticosteroid Systemic Immunomodulatory Therapy in Noninfectious Uveitis : Fundamentals Of Care for UveitiS (FOCUS) Initiative

Supplemental material available at www.aaojournal.org. Supported by AbbVie, Inc., and the Fundamentals of Care for Uveitis Initiative National Faculty. This manuscript was developed subsequent to an AbbVie-sponsored literature review of noninfectious, nonanterior uveitis. The meeting was conducted to understand the available literature regarding the management of patients with noninfectious, nonanterior uveitis. The program involved a total of 139 experts from 28 countries, who were selected for participation by AbbVie. However, AbbVie was not involved in the development of the manuscript. The authors maintained complete control over the content and this manuscript reflects the opinions of the authors. AbbVie selected the discussion participants and reviewed the final manuscript draft for scientific accuracy, but the authors determined the final content. All authors made substantial contributions to the article or critically revised it for important intellectual content and approved the final manuscript. AbbVie provided funding to invited participants, including honoraria for their attendance at the meetings. Travel to and from the meetings was reimbursed. No payments were made to the authors for the development of this manuscript. Dhinakaran Sambandan, PhD, and Shula Sarner, PhD, of Lucid Partners, Burleighfield House, Buckinghamshire, United Kingdom, provided medical writing and editorial support to the authors in the development of this manuscript; financial support for these services was provided by AbbVie. AbbVie reviewed the manuscript, but was not involved in the methodology, data collection and analysis, or completion of this manuscript.Peer reviewedPublisher PD

Comparison of different techniques for characterizing the diesel injector internal dimensions

[EN] The geometry of certain parts of diesel injectors is key to the injection, atomization and fuel-air mixing phenomena. Small variations on the geometrical parameters may have a strong influence on the aforementioned processes. Thus, OEMs need to assess their manufacturing tolerances, whereas researchers in the field (both experimentalists and modelers) rely on the accuracy of a certain metrology technique for their studies. In the current paper, an investigation of the capability of different experimental techniques to determine the geometry of a modern diesel fuel injector has been performed. For this purpose, three main elements of the injector have been evaluated: the control volume inlet and outlet orifices, together with the nozzle orifices. While the direct observation of the samples through an optical microscope is only possible for the simplest pieces, both Computed Tomography Scanning and the visualization of silicone molds technique have proven their ability to characterize the most complex internal shapes corresponding to the internal injector elements. Indeed, results indicate that the differences observed among these methodologies for the determination of the control volume inlet orifice diameter and the nozzle orifice dimensions are smaller than the uncertainties related to the experimental techniques, showing that they are both equally accurate. This implies that the choice of a given technique for the particular application of determining the geometry of diesel injectors can be done on the basis of availability, intrusion and costs, rather than on its accuracy.This work was partly sponsored by "Ministerio de Economia y Competitividad", of the Spanish Government, in the frame of the Project "Estudio de la interaccion chorro-pared en condiciones realistas de motor", Reference TRA2015-67679-c2-1-R.Salvador, FJ.; Gimeno, J.; De La Morena, J.; Carreres, M. (2018). Comparison of different techniques for characterizing the diesel injector internal dimensions. Experimental Techniques. 42(5):467-472. https://doi.org/10.1007/s40799-018-0246-1S467472425Mobasheri R, Peng Z, Mostafa S (2012) Analysis the effect of advanced injection strategies on engine performance and pollutant emissions in a heavy duty DI-diesel engine by CFD modeling. Int J Heat Fluid Flow 33(1):59–69Dhar A, Agarwal AK (2015) Experimental investigations of the effect of pilot injection on performance, emissions and combustion characteristics of Karanja biodiesel fuelled CRDI engine. Energy Convers Manag 93:357–366Mohan B, Yang W, Chou SK (2013) Fuel injection strategies for performance improvement and emissions reduction in compression ignition engines—a review. Renew Sust Energ Rev 28(x):664–676Petrovic V, Bracanovic Z, Grozdanic B, Petrovic S, Sazhin S, Knezevic D (2015) The design of a full flow dilution tunnel with a critical flow venturi for the measurement of diesel engine particulate emission. FME Trans 43(2):99–106Ilić Z, Rasuo B, Jovanović M, Janković D (2013) Impact of changing quality of air/fuel mixture during flight of a piston engine aircraft with respect to vibration low frequency spectrum. FME Trans 41(1):25–32Luján JM, Tormos B, Salvador FJ, Galgar K (2009) Comparative analysis of a DI diesel engine fuelled with biodiesel blends during the European MVEG-A cycle: Preliminaru study I. Biomass & Bioenergy 33(6–7):941–947Postrioti L, Mariani F, Battistoni M (2012) Experimental and numerical momentum flux evaluation of high pressure diesel spray. Fuel 98:149–163Payri R, Salvador FJ, Gimeno J, Venegas O (2016) A technique to match the refractive index of different diesel fuels with the refractive index of transparent materials to improve the experimental visualization. Exp Tech 40(1):261–269Duran SP, Porter JM, Parker TE (2015) Ballistic imaging of diesel sprays using a picosecond laser: characterization and demonstration. Appl Opt 54(7):1743Payri R, Salvador FJ, Gimeno J et al (2011) Flow regime effects on non-cavitating injection nozzles over spray behavior. Int J Heat Fluid Flow 32(1):273–284Koukouvinis P, Gavaises M, Li J, Wang L (2016) Large Eddy simulation of diesel injector including cavitation effects and correlation to erosion damage. Fuel 175:26–39Som S, Aggarwal SK (2010) Effects of primary breakup modeling on spray and combustion characteristics of compression ignition engines. Combust Flame 157(6):1179–1193Salvador FJ, De la Morena J, Martínez-López J, Jaramillo D (2017) Assessment of compressibility effects on internal nozzle flow in diesel injectors at very high injection pressures. Energy Convers Manag 132:221–230Salvador FJ, Gimeno J, de la Morena J, Martí-Aldaraví P (2012) Using one-dimensional modelling to analyze the influence of the use of biodiesels on the dynamic behaviour of solenoid-operated injectors in common rail systems: Results of the simulation and discussion. Energy Convers Manag 54(1):122–132Taghavifar H, Khalilarya S, Jafarmadar S, Baghery F (2016) 3-D numerical consideration of nozzle structure on combustion and emission characteristics of DI diesel injector. Appl Math Model 40(19–20):8630–8646Edelbauer W (2017) Numerical simulation of cavitating injector flow and liquid spray break-up by combination of Eulerian–Eulerian and volume-of-fluid methods. Comput Fluids 144:19–33Salvador FJ, Carreres M, Jaramillo D, Martínez-López J (2015) Comparison of microsac and VCO diesel injector nozzles in terms of internal nozzle flow characteristics. Energy Convers Manag 103:284–299Salvador FJ, Martínez-López J, Romero JV, Roselló MD (2013) Study of the influence of the needle eccentricity on the internal flow in diesel injector nozzles by computational fluid dynamics calculations. Int J Comput Math 91, no. June:24–31Payri R, Salvador FJ, Carreres M, De la Morena J (Apr. 2016) Fuel temperature influence on the performance of a last generation common-rail diesel ballistic injector. Part II: 1D model development, validation and analysis. Energy Convers Manag 114:376–391Salvador FJ, Hoyas S, Novella R, Martinez-López J (2011) Numerical simulation and extended validation of two-phase compressible flow in diesel injector nozzles. Proc Inst Mech Eng Part-D-J Automob Eng 225(D4):545–563Satkoski C, Shaver G (2011) Piezoelectric fuel injection: pulse-to-pulse coupling and flow rate estimation. IEEE/ASME Trans Mechatron 16(4):627–642Ferrari A, Mittica A (2016) Response of different injector typologies to dwell time variations and a hydraulic analysis of closely-coupled and continuous rate shaping injection schedules. Appl Energy 169:899–911Payri R, Salvador FJ, Gimeno J, De la Morena J (2011) Analysis of diesel spray atomization by means of a near-nozzle field visualization technique. At Sprays 21(9):753–774Li T, Moon S, Sato K, Yokohata H (Feb. 2017) A comprehensive study on the factors affecting near-nozzle spray dynamics of multi-hole GDI injectors. Fuel 190:292–302Yu W, Yang W, Zhao F (2017) Investigation of internal nozzle flow, spray and combustion characteristics fueled with diesel, gasoline and wide distillation fuel (WDF) based on a piezoelectric injector and a direct injection compression ignition engine. Appl Therm Eng 114:905–920Salvador FJ, Carreres M, Crialesi-Esposito M, Plazas AH (2017) Determination of critical operating and geometrical parameters in diesel injectors through one dimensional modelling, design of experiments and an analysis of variance. Proc Inst Mech Eng Part D J Automob EngMacian V, Bermúdez V, Payri R, Gimeno J (2003) New technique for determination of internal geometry of a diesel nozzle with the use of silicone methodology. Exp Tech 27, no April:39–43Piano A, Millo F, Postrioti L, Biscontini G, Cavicchi A, and Pesce FC, (2016) “Numerical and experimental assessment of a solenoid common-rail injector operation with advanced injection strategies,” SAE Int J Engines 9(1)Mitroglou N, Lorenzi M, Santini M, Gavaises M (2016) Application of X-ray micro-computed tomography on high-speed cavitating diesel fuel flows. Exp Fluids 57(11):1–14Kastengren AL, Tilocco FZ, Powell CF, Manin J, Pickett LM, Payri R, Bazyn T (2012) Engine combustion network (ECN): measurements of nozzle geometry and hydraulic behavior. At Sprays 22(12):1011–1052Otsu N (1979) A threshold selection method from gray-level histograms. IEEE Trans Syst Man Cybern 9(1):62–6

Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: fundamentals of care for uveitis (focus) initiative

Topic: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. Clinical Relevance: The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. Methods: An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic reviewof the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE,CINAHL,SCOPUS,BIOSIS, andWeb of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review.Atotal of 44 globally representativegroupmembersmet in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. Results: In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. Conclusions: Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents

In Vivo-Restricted and Reversible Malignancy Induced by Human Herpesvirus-8 KSHV: A Cell and Animal Model of Virally Induced Kaposi's Sarcoma

Transfection of a Kaposi's sarcoma (KS) herpesvirus (KSHV) Bacterial Artificial Chromosome (KSHVBac36) into mouse bone marrow endothelial lineage cells generates a cell (mECK36) that forms KS-like tumors in mice. mECK36 expressed most KSHV genes and were angiogenic, but didn't form colonies in soft agar. In nude mice, mECK36 formed KSHV-harboring vascularized spindle-cell sarcomas that were LANA+/podoplanin+, overexpressed VEGF and Angiopoietin ligands and receptors, and displayed KSHV and host transcriptomes reminiscent of KS. mECK36 that lost the KSHV episome reverted to non-tumorigenicity. siRNA suppression of KSHV vGPCR, an angiogenic gene up-regulated in mECK36 tumors, inhibited angiogenicity and tumorigenicity. These results show that KSHV malignancy is in vivo growth-restricted and reversible, defining mECK36 as a biologically sensitive animal model of KSHV-dependent KS

Plant trait and vegetation data along a 1314 m elevation gradient with fire history in Puna grasslands, Perú

Alpine grassland vegetation supports globally important biodiversity and ecosystems that are increasingly threatened by climate warming and other environmental changes. Trait-based approaches can support understanding of vegetation responses to global change drivers and consequences for ecosystem functioning. In six sites along a 1314 m elevational gradient in Puna grasslands in the Peruvian Andes, we collected datasets on vascular plant composition, plant functional traits, biomass, ecosystem fluxes, and climate data over three years. The data were collected in the wet and dry season and from plots with different fire histories. We selected traits associated with plant resource use, growth, and life history strategies (leaf area, leaf dry/wet mass, leaf thickness, specific leaf area, leaf dry matter content, leaf C, N, P content, C and N isotopes). The trait dataset contains 3,665 plant records from 145 taxa, 54,036 trait measurements (increasing the trait data coverage of the regional flora by 420%) covering 14 traits and 121 plant taxa (ca. 40% of which have no previous publicly available trait data) across 33 families

Country-level gender inequality is associated with structural differences in the brains of women and men

男女間の不平等と脳の性差 --男女間の不平等は脳構造の性差と関連する--. 京都大学プレスリリース. 2023-05-10.Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women’s worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7, 876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women’s brains and provide initial evidence for neuroscience-informed policies for gender equality

Country-level gender inequality is associated with structural differences in the brains of women and men

Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women's worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7,876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women's brains and provide initial evidence for neuroscience-informed policies for gender equality

Search for massive, long-lived particles using multitrack displaced vertices or displaced lepton pairs in pp collisions at √s = 8 TeV with the ATLAS detector

Many extensions of the Standard Model posit the existence of heavy particles with long lifetimes. This article presents the results of a search for events containing at least one long-lived particle that decays at a significant distance from its production point into two leptons or into five or more charged particles. This analysis uses a data sample of proton-proton collisions at √s=8  TeV corresponding to an integrated luminosity of 20.3  fb−1 collected in 2012 by the ATLAS detector operating at the Large Hadron Collider. No events are observed in any of the signal regions, and limits are set on model parameters within supersymmetric scenarios involving R-parity violation, split supersymmetry, and gauge mediation. In some of the search channels, the trigger and search strategy are based only on the decay products of individual long-lived particles, irrespective of the rest of the event. In these cases, the provided limits can easily be reinterpreted in different scenarios

Measurement of the correlation between the polar angles of leptons from top quark decays in the helicity basis at √s = 7 TeV using the ATLAS detector

A measurement of the correlations between the polar angles of leptons from the decay of pair-produced t and t̄ quarks in the helicity basis is reported, using proton-proton collision data collected by the ATLAS detector at the LHC. The dataset corresponds to an integrated luminosity of 4.6  fb−¹ at a center-of-mass energy of √s = 7  TeV collected during 2011. Candidate events are selected in the dilepton topology with large missing transverse momentum and at least two jets. The angles θ1 and θ2 between the charged leptons and the direction of motion of the parent quarks in the tt̄ rest frame are sensitive to the spin information, and the distribution of cosθ1 ⋅ cosθ2 is sensitive to the spin correlation between the t and t̄ quarks. The distribution is unfolded to parton level and compared to the next-to-leading order prediction. A good agreement is observed

Measurement of the CP-violating phase ϕs and the Bs0 meson decay width difference with Bs0 → J/ψϕ decays in ATLAS

A measurement of the Bs0 decay parameters in the Bs0 → J/ψϕ channel using an integrated luminosity of 14.3 fb−1 collected by the ATLAS detector from 8 TeV pp collisions at the LHC is presented. The measured parameters include the CP -violating phase ϕs, the decay width Γs and the width difference between the mass eigenstates ΔΓs. The values measured for the physical parameters are statistically combined with those from 4.9 fb−1 of 7 TeV data, leading to the following: ϕ s =−0.090±0.078(stat.)±0.041(syst.)rad ΔΓ s =0.085±0.011(stat.)±0.007(syst.)ps −1 Γ s =0.675±0.003(stat.)±0.003(syst.)ps −1 In the analysis the parameter ΔΓs is constrained to be positive. Results for ϕs and ΔΓs are also presented as 68% and 95% likelihood contours in the ϕs-ΔΓs plane. Also measured in this decay channel are the transversity amplitudes and corresponding strong phases. All measurements are in agreement with the Standard Model predictions