Precision engineering of micrometer and nanometer droplets for ultrasound imaging and therapy

The medical community has interest in improving techniques such as occlusion, therapeutics and imaging through the use of liquid perfluorocarbon droplets. The ability to create a monodispersed population of liquid perfluorocarbon droplets would have the added advantage of uniform acoustic activation parameters. A microfluidic device with a flow-focusing orifice allowed for uniform production of perfluoropentane droplets in the micron and submicron diameter range. These droplets are able to be stored for over two weeks while retaining distribution characteristics. The observed activation of the droplets shows the acoustic threshold as a function of droplet diameter with little variability. Results showed that microfluidic technology with a pressure controlled flow regulator will allow for greater manufacturing control of phase-change perfluorocarbons in the micron and sub-micron size range for acoustic droplet vaporization applications

Microfluidic Generation of Acoustically Active Nanodroplets

A microfluidic approach for the generation of perfluorocarbon nanodroplets as the primary emulsion with diameters as small as 300-400 nm is described. The system uses a pressure-controlled delivery of all reagents and increased viscosity in the continuous phase to drive the device into an advanced tip-streaming regime, which results in generation of droplets in the sub-micrometer range. Such nanodroplets may be appropriate for emerging biomedical applications

Precision Manufacture of Phase-Change Perfluorocarbon Droplets Using Microfluidics

Liquid perfluorocarbon droplets have been of interest in the medical acoustics community for use as acoustically activated particles for tissue occlusion, imaging, and therapeutics. To date, methods to produce liquid perfluorocarbon droplets typically result in a polydisperse size distribution. Since the threshold of acoustic activation is a function of diameter, there would be benefit from a monodisperse population to preserve uniformity in acoustic activation parameters. Through the use of a microfluidic device with flow focusing technology, the production of droplets of perfluoropentane with a uniform size distribution is demonstrated. Stability studies indicate that these droplets are stable in storage for at least two weeks. Acoustic studies illustrate the thresholds of vaporization as a function of droplet diameter, and a logarithmic relationship is observed between acoustic pressure and vaporization threshold within the size ranges studied. Droplets of uniform size have very little variability in acoustic vaporization threshold. Results indicate that microfluidic technology can enable greater manufacturing control of phase change perfluorocarbons for acoustic droplet vaporization applications

High-speed, clinical-scale microfluidic generation of stable phase-change droplets for gas embolotherapy

In this study we report on a microfluidic device and droplet formation regime capable of generating clinical-scale quantities of droplet emulsions suitable in size and functionality for in vivo therapeutics. By increasing the capillary number – based on the flow rate of the continuous outer phase – in our flow-focusing device, we examine three modes of droplet breakup: geometry-controlled, dripping, and jetting. Operation of our device in the dripping regime results in the generation of highly monodisperse liquid perfluoropentane droplets in the appropriate 3–6 µm range at rates exceeding 105 droplets per second. Based on experimental results relating droplet diameter and the ratio of the continuous and dispersed phase flow rates, we derive a power series equation, valid in the dripping regime, to predict droplet size by Dd ≅ 27(QC/QD)−5/12. The volatile droplets in this study are stable for weeks at room temperature yet undergo rapid liquid-to-gas phase transition, and volume expansion, above a uniform thermal activation threshold. The opportunity exists to potentiate locoregional cancer therapies such as thermal ablation and percutaneous ethanol injection using thermal or acoustic vaporization of these monodisperse phase-change droplets to intentionally occlude the vessels of a cancer

Flow-focusing regimes for accelerated production of monodisperse drug-loadable microbubbles toward clinical-scale applications

Ultrasound imaging often calls for the injection of contrast agents, micron-sized bubbles which echo strongly in blood and help distinguish vascularized tissue. Such microbubbles are also being augmented for targeted drug delivery and gene therapy, by the addition of surface receptors and therapeutic payloads. Unfortunately, conventional production methods yield a polydisperse population, whose nonuniform resonance and drug-loading are less than ideal. An alternative technique, microfluidic flow-focusing, is able to produce highly monodisperse microbubbles with stabilizing lipid membranes and drug-carrying oil layers. However, the published 1 kHz production rate for these uniform drug bubbles is very low compared to conventional methods, and must be improved before clinical use can be practical. In this study, flow-focusing production of oil-layered lipid microbubbles was tested up to 300 kHz, with coalescence suppressed by high lipid concentrations or inclusion of Pluronic F68 surfactant in the lipid solution. The transition between geometry-controlled and dripping production regimes was analysed, and production scaling was found to be continuous, with a power trend of exponent ~5/12 similar to literature. Unlike prior studies with this trend, however, scaling curves here were found to be pressure-dependent, particularly at lower pressure-flow equilibria (e.g. <15 psi). Adjustments in oil flow rate were observed to have a similar effect, akin to a pressure change of 1–3 psi. This analysis and characterization of high-speed dual-layer bubble generation will enable more-predictive production control, at rates practical for in vivo or clinical use

Ceremonies and Time in Shakespeare

This essay considers some moments in Shakespeare's texts which exemplify the Janus-faced quality of ceremonies: their enactment in the present looking backwards to past traditions and forwards to inaugurate new social relations. The argument draws on Victor Turner's theorization of ritual as an event that gives shape to “liminality,” that which “eludes or slips through the network of classification that normally locate states and positions in cultural space,” and argues that this applies to time as well. It also considers the construction of time in terms of kairos, a moment of time infused with meaning. The essay analyses ceremony in three Shakespearean genres. First, it examines Bertram's and Helena's ring exchange in All's Well That Ends Well as a “distended” ritual that collapses time. It then turns to Richard III, unpacking its complex sequence of ceremonies of betrothal, mourning, and sovereignty that are “continuously disrupted”. The final section describes the ceremonial time of romance in The Winter's Tale, unfolding the power invested in the kairotic time evoked by the oracle of Delphi, the sheep-shearing ceremony, and Paulina's “resurrection” of Hermione

Medicinal and ethnoveterinary remedies of hunters in Trinidad

BACKGROUND: Ethnomedicines are used by hunters for themselves and their hunting dogs in Trinidad. Plants are used for snakebites, scorpion stings, for injuries and mange of dogs and to facilitate hunting success. RESULTS: Plants used include Piper hispidum, Pithecelobium unguis-cati, Bauhinia excisa, Bauhinia cumanensis, Cecropia peltata, Aframomum melegueta, Aristolochia rugosa, Aristolochia trilobata, Jatropha curcas, Jatropha gossypifolia, Nicotiana tabacum, Vernonia scorpioides, Petiveria alliacea, Renealmia alpinia, Justicia secunda, Phyllanthus urinaria,Phyllanthus niruri,Momordica charantia, Xiphidium caeruleum, Ottonia ovata, Lepianthes peltata, Capsicum frutescens, Costus scaber, Dendropanax arboreus, Siparuma guianensis, Syngonium podophyllum, Monstera dubia, Solanum species, Eclipta prostrata, Spiranthes acaulis, Croton gossypifolius, Barleria lupulina, Cola nitida, Acrocomia ierensis (tentative ID). CONCLUSION: Plant use is based on odour, and plant morphological characteristics and is embedded in a complex cultural context based on indigenous Amerindian beliefs. It is suggested that the medicinal plants exerted a physiological action on the hunter or his dog. Some of the plants mentioned contain chemicals that may explain the ethnomedicinal and ethnoveterinary use. For instance some of the plants influence the immune system or are effective against internal and external parasites. Plant baths may contribute to the health and well being of the hunting dogs

Racial discrimination and telomere shortening among African Americans: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

ObjectiveTelomeres are protective sequences of DNA capping the ends of chromosomes that shorten over time. Leukocyte telomere length (LTL) is posited to reflect the replicative history of cells and general systemic aging of the organism. Chronic stress exposure leads to accelerated LTL shortening, which has been linked to increased susceptibility to and faster progression of aging-related diseases. This study examined longitudinal associations between LTL and experiences of racial discrimination, a qualitatively unique source of minority psychosocial stress, among African Americans.MethodData are from 391 African Americans in the Coronary Artery Risk Development in Young Adults (CARDIA) Telomere Ancillary Study. We examined the number of domains in which racial discrimination was experienced in relation to LTL collected in Years 15 and 25 (Y15: 2000/2001; Y25: 2010/2011). Multivariable linear regression examined if racial discrimination was associated with LTL. Latent change score analysis (LCS) examined changes in racial discrimination and LTL in relation to one another.ResultsControlling for racial discrimination at Y15, multivariable linear regression analyses indicated that racial discrimination at Y25 was significantly associated with LTL at Y25. This relationship remained robust after adjusting for LTL at Y15 (b = -.019, p = .015). Consistent with this finding, LCS revealed that increases in experiences of racial discrimination were associated with faster 10-year LTL shortening (b = -.019, p = .015).ConclusionsThis study adds to evidence that racial discrimination contributes to accelerated physiologic weathering and health declines among African Americans through its impact on biological systems, including via its effects on telomere attrition. (PsycINFO Database Record (c) 2020 APA, all rights reserved)