Focused ultrasound activation of systemically administered microbubbles is a noninvasive and localized drug delivery method that can increase vascular permeability to large molecular agents. Yet the range of acoustic parameters responsible for drug delivery remains unknown, and, thus, enhancing the delivery characteristics without compromising safety has proven to be difficult. We propose a new basis for ultrasonic pulse design in drug delivery through the blood-brain barrier (BBB) that uses principles of probability of occurrence and spatial distribution of cavitation in contrast to the conventionally applied magnitude of cavitation. The efficacy of using extremely short (2.3 μs) pulses was evaluated in 27 distinct acoustic parameter sets at low peak-rarefactional pressures (0.51 MPa or lower). The left hippocampus and lateral thalamus were noninvasively sonicated after administration of Definity microbubbles. Disruption of the BBB was confirmed by delivery of fluorescently tagged 3-, 10-, or 70-kDa dextrans. Under some conditions, dextrans were distributed homogeneously throughout the targeted region and accumulated at specific hippocampal landmarks and neuronal cells and axons. No histological damage was observed at the most effective parameter set. Our results have broadened the design space of parameters toward a wider safety window that may also increase vascular permeability. The study also uncovered a set of parameters that enhances the dose and distribution of molecular delivery, overcoming standard trade-offs in avoiding associated damage. Given the short pulses used similar to diagnostic ultrasound, new critical parameters were also elucidated to clearly separate therapeutic ultrasound from disruption-free diagnostic ultrasound.F ocused ultrasound (FUS) and microbubble-based drug delivery systems (DDSs) can increase the dose of an agent in a target volume and has potential in applications such as blood-brain barrier (BBB) disruption for the treatment of neurological diseases (1, 2), molecular and viral treatment of tumors (3), gene therapy for treating heart conditions (4), and enhancement of renal ultrafiltration (5). In each method, biologically inert and preformed microbubbles, with a lipid or polymer shell, a stabilized gas core, and a diameter less than 10 μm, are systemically administered and subsequently exposed to noninvasively delivered FUS pulses. Microbubbles within the target volume are "acoustically activated" in a complex range of behaviors known as acoustic cavitation. In stable cavitation, the microbubbles expand and contract with the acoustic pressure rarefaction and compression over several cycles (6). This activity has been associated with a range of bioeffects including displacement of the vessel wall through dilation and contractions (7,8). Large radial bubble expansions may induce inertial cavitation activity, which may lead to bubble collapse due to the inertia of the surrounding media and affect the vascular physiology (8). Each type and magnitude of cavitation activity results...

Lithium clusters Lin (n=5 to 20) were studied by Kohn–Sham theory with local spin density and gradient-corrected energy functionals. We used a Tabu Search algorithm for structure optimization. The lowest energy Lin isomers that we found fall in two categories: (i) the pentagonal bipyramid, icosahedron, and related structures which are typical of most pair potentials, and (ii) structures containing centered square antiprisms which are reminiscent of the bulk bcc structure and have two characteristic peaks in the pair distribution function, one near 2.60 Å and the other near 3.05 Å. Calculated isomer energies and vibrational frequencies suggest that, at room temperature, many cluster sizes should show liquidlike behavior or coexistence of multiple isomers. The number of unpaired electrons “M” as a function of cluster size “n” generally alternates between 0 (singlet) and 1 (doublet), but some cluster sizes display anomalous spin magnetic moments M(n); they are M(13)=5, M(16)=2, M(17)=3, and M(18)=2. The Li7, Li8, Li19, and Li20 clusters are particularly stable: they each have a very compact structure and a shape consistent with the ellipsoidal jellium model.

1 7 5 0 M a s s a c h u s e t t s a v e n u e , n W | W a s h i n g t o n , D c 2 0 0 3 6 -1 9 0 3 t e l : ( 2 0 2 ) 3 2 8 -9 0 0 0 | F a x : ( 2 0 2 ) 6 5 9 -3 2 2 5 | W W W . i i e . c o MThe Case for an International Reserve Diversification Standard Edwin M. Truman and Anna WongAbstract: Rumors about the actual or potential currency diversification of countries' foreign exchange holdings out of dollars are not a new phenomenon. This working paper argues that such concerns about reserve diversification are exaggerated. We present evidence that the extent of actual diversification has been modest to date. Nevertheless, the potential for reserve diversification adds volatility to foreign exchange markets and can catalyze abrupt exchange rate movements. We argue that policymakers acting in their own national interests can do something constructive to reduce the volatility introduced into foreign exchange and financial markets by rumors of large-scale international foreign exchange reserve diversification. We propose the voluntary adoption by major foreign exchange reserve holders in particular of an International Reserve Diversification Standard consisting of two elements: (1) routine disclosure of the currency composition of official foreign exchange holdings and (2) a commitment by each adherent to adjust gradually the actual currency composition of its reserves to any new benchmark for those holdings.

Background As countries continue to respond to the COVID-19 pandemic, the importance of ensuring that fair and equal access to healthcare for all is more urgent than ever. Policies that promote social capital building along all levels of society may offer an important avenue for improved healthcare delivery and health systems strengthening in the COVID-19 response. Main body In reference to the established and emerging literature on social capital and health, we explore the role of social capital in the COVID-19 health policy response. We analyse current research with respect to mental health, public health policy compliance, and the provision of care for vulnerable populations, and highlight how considerations of bonding, bridging, and linking capital can contribute to health systems strengthening in the context of the COVID-19 response and recovery effort. Conclusions This article argues that considerations of social capital – including virtual community building, fostering solidarity between high-risk and low-risk groups, and trust building between decision-makers, healthcare workers, and the public – offer a powerful frame of reference for understanding how response and recovery programs can be best implemented to effectively ensure the inclusive provision of COVID-19 health services.

Sophorolipids (SLs) offer an “environmentally friendly” alternative to chemically produced surfactants currently used in formulations for crude oil extraction, processing, and reclamation. Studies herein describe how sophorolipid structure influences its interfacial properties for environmentally and industrially relevant oil–water systems where the oil phase is Arabian light crude oil, paraffin oil, decane, hexadecane, a 1:1 vol/vol mixture of o‐xylene and 1,2‐dimethylcyclohexane, or a mixture of paraffin oil, o‐xylene, and 1,2‐dimethylcyclohexane (synthetic crude oil). SL‐hexyl ester (SL‐HE) reduces the crude oil–water interfacial tension (IFT) by 57 and 91% at 0.001 and 0.5 mg/mL, respectively. Crude oil displacement tests reveal that SL‐ethyl ester (SL‐EE) and SL‐HE contract a crude oil slick on water to about 20% of its starting volume allowing for easier burning of spilled crude oil on marine surfaces. Water retention and emulsion phase (e.g., o/w vs. w/o) are determined by SL‐structure/concentration, oil concentration, and oil composition to understand their performance for crude oil transportation and clean‐up. For the first time, w/o emulsions were obtained using SLs and their formation occurred after homogenization when the oil phase consisted of a 1:1 mixture of o‐xylene and 1,2‐dimethylcyclohexane. Generally, the performance of SL‐esters in the above studies was superior to that using Triton X‐100, a comparison nonionic surfactant. Hence, SL‐esters offer a valuable platform for tuning interfacial properties to optimize surfactant performance.