Dynamic nozzles for drop generators

received: 2015-06-03 accepted: 2015-10-16 published: 2015-11-03received: 2015-06-03 accepted: 2015-10-16 published: 2015-11-03This work was funded by the UK Engineering and Physical Sciences Research Council (Grant No. EP/H018913/1), the John Fell Oxford University Press Research Fund, and the Royal Society

Checkpoint inhibition reduces the threshold for Drug-Specific T-Cell priming and increases the incidence of sulfasalazine hypersensitivity

An emerging clinical issue associated with immune-oncology agents is the collateral effects on the tolerability of concomitant medications. One report of this phenomenon was the increased incidence of hypersensitivity reactions observed in patients receiving concurrent immune checkpoint inhibitors (ICIs) and sulfasalazine (SLZ). Thus, the aim of this study was to characterize the T cells involved in the pathogenesis of such reactions, and recapitulate the effects of inhibitory checkpoint blockade on de-novo priming responses to compounds within in vitro platforms. A regulatory competent human dendritic cell/T-cell coculture assay was used to model the effects of ICIs on de novo nitroso sulfamethoxazole- and sulfapyridine (SP) (the sulfonamide component of SLZ) hydroxylamine-specific priming responses. The role of T cells in the pathogenesis of the observed reactions was explored in 3 patients through phenotypic characterization of SP/sulfapyridine hydroxylamine (SPHA)-responsive T-cell clones (TCC), and assessment of cross-reactivity and pathways of T-cell activation. Augmentation of the frequency of responding drug-specific T cells and intensity of the T-cell response was observed with PD-1/PD-L1 blockade. Monoclonal populations of SP- and SPHA-responsive T cells were isolated from all 3 patients. A core secretory effector molecule profile (IFN-γ, IL-13, granzyme B, and perforin) was identified for SP and SPHA-responsive TCC, which proceeded through Pi and hapten mechanisms, respectively. Data presented herein provides evidence that drug-responsive T cells are effectors of hypersensitivity reactions observed in oncology patients administered ICIs and SLZ. Perturbation of drug-specific T-cell priming is a plausible explanation for clinical observations of how an increased incidence of these adverse events is occurring

Experimental Observation of Differences in the Dynamic Response of Newtonian and Viscoelastic Fluids

In this paper we present an experimental study of the dynamic responses of a Newtonian fluid and a Maxwellian fluid under an oscillating pressure gradient. We use laser Doppler anemometry in order to determine the velocity of each fluid inside a cylindrical tube. In the case of the Newtonian fluid, the dissipative nature is observed and the response obeys the Zhou and Sheng universality (PRB 39, 12027 (1989)). In the dynamic response of the Maxwellian fluid an enhancement at the frequencies predicted by the corresponding theory (PRE 58, 6323 (1998)) is observed.Comment: 5 pages, 4 Figures, paper to be published in Phys. Rev.

Evolution of Gaussian wave packets in capillary jets

A temporal analysis of the evolution of Gaussian wave packets in cylindrical capillary jets is presented through both a linear two-mode formulation and a one-dimensional nonlinear numerical scheme. These analyses are normally applicable to arbitrary initial conditions but our study focuses on pure-impulsive ones. Linear and nonlinear findings give consistent results in the stages for which the linear theory is valid. The inverse Fourier transforms representing the formal linear solution for the jet shape is both numerically evaluated and approximated by closed formulas. After a transient, these formulas predict an almost Gaussian-shape deformation with (i) a progressive drift of the carrier wave number to that given by the maximum of the Rayleigh dispersion relation, (ii) a progressive increase of its bell width, and (iii) a quasi-exponential growth of its amplitude. These parameters agree with those extracted from the fittings of Gaussian wave packets to the numerical simulations. Experimental results are also reported on near-Gaussian pulses perturbing the exit velocity of a 2 mm diameter water jet. The possibility of controlling the breakup location along the jet and other features, such as pinch-off simultaneity, are demonstrated

Cut-offs and response criteria for the Hospital Universitario la Princesa Index (HUPI) and their comparison to widely-used indices of disease activity in rheumatoid arthritis

Objective To estimate cut-off points and to establish response criteria for the Hospital Universitario La Princesa Index (HUPI) in patients with chronic polyarthritis. Methods Two cohorts, one of early arthritis (Princesa Early Arthritis Register Longitudinal PEARL] study) and other of long-term rheumatoid arthritis (Estudio de la Morbilidad y Expresión Clínica de la Artritis Reumatoide EMECAR]) including altogether 1200 patients were used to determine cut-off values for remission, and for low, moderate and high activity through receiver operating curve (ROC) analysis. The areas under ROC (AUC) were compared to those of validated indexes (SDAI, CDAI, DAS28). ROC analysis was also applied to establish minimal and relevant clinical improvement for HUPI. Results The best cut-off points for HUPI are 2, 5 and 9, classifying RA activity as remission if =2, low disease activity if >2 and =5), moderate if >5 and <9 and high if =9. HUPI''s AUC to discriminate between low-moderate activity was 0.909 and between moderate-high activity 0.887. DAS28''s AUCs were 0.887 and 0.846, respectively; both indices had higher accuracy than SDAI (AUCs: 0.832 and 0.756) and CDAI (AUCs: 0.789 and 0.728). HUPI discriminates remission better than DAS28-ESR in early arthritis, but similarly to SDAI. The HUPI cut-off for minimal clinical improvement was established at 2 and for relevant clinical improvement at 4. Response criteria were established based on these cut-off values. Conclusions The cut-offs proposed for HUPI perform adequately in patients with either early or long term arthritis