Successful Application of Large Microneedle Patches by Human Volunteers

We describe, for the first time, the design, production and evaluation of large microneedle patches. Such systems, based on 16 individual microneedle arrays (needle height 600 μm), were prepared from aqueous blends of 15% w/w Gantrez(®) S97 and 7.5% w/w poly(ethyleneglycol) 10,000 Da. Ester-based crosslinking was confirmed by FTIR and mechanical strength was good. Insertion depths in a validated skin model were approximately 500 μm. Ten human volunteers successfully self-inserted the microneedles of these larger patches in their skin, following appropriate instruction, as confirmed by transepidermal water loss measurements. The mean insertion depth ranged between 300 and 450 μm over the area of the large patches. That this was not significantly different to a single unit MN patch self-applied by the same volunteers is encouraging. Microneedle patch sizes much larger than the 1–2 cm(2) will be required if this technology is to be successfully translated to clinic for delivery of drug substances. The work described here suggests that use of such larger patches by patients can be successful, potentially opening up the possibility for a significant expansion of the size of the market for transdermal drug delivery

Sea-level rise will drive divergent sediment transport patterns on fore reefs and reef flats, potentially causing erosion on Atoll Islands

Author Posting. © American Geophysical Union, 2020. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Earth Surface 125 (2020): e2019JF005446, doi: 10.1029/2019JF005446.Atoll reef islands primarily consist of unconsolidated sediment, and their ocean‐facing shorelines are maintained by sediment produced and transported across their reefs. Changes in incident waves can alter cross‐shore sediment exchange and, thus, affect the sediment budget and morphology of atoll reef islands. Here we investigate the influence of sea level rise and projected wave climate change on wave characteristics and cross‐shore sediment transport across an atoll reef at Kwajalein Island, Republic of the Marshall Islands. Using a phase‐resolving model, we quantify the influence on sediment transport of quantities not well captured by wave‐averaged models, namely, wave asymmetry and skewness and flow acceleration. Model results suggest that for current reef geometry, sea level, and wave climate, potential bedload transport is directed onshore, decreases from the fore reef to the beach, and is sensitive to the influence of flow acceleration. We find that a projected 12% decrease in annual wave energy by 2100 CE has negligible influence on reef flat hydrodynamics. However, 0.5–2.0 m of sea level rise increases wave heights, skewness, and shear stress on the reef flat and decreases wave skewness and shear stress on the fore reef. These hydrodynamic changes decrease potential sediment inputs onshore from the fore reef where coral production is greatest but increase potential cross‐reef sediment transport from the outer reef flat to the beach. Assuming sediment production on the fore reef remains constant or decreases due to increasing ocean temperatures and acidification, these processes have the potential to decrease net sediment delivery to atoll islands, causing erosion.This study was supported by the Strategic Environmental Research and Development Program through awards SERDP: RC‐2334, and RC‐2336. Any use of trade, firm, or product names is for descriptive purposes only and does not imply endorsement by the U.S. Government.2021-03-2

Ariel - Volume 10 Number 3

Executive Editors Madalyn Schaefgen David Reich Business Manager David Reich News Editors Medical College Edward Zurad CAHS John Guardiani World Mark Zwanger Features Editors Meg Trexler Jim O\u27Brien Editorials Editor Jeffrey Banyas Photography and Sports Editor Stuart Singer Commons Editor Brenda Peterso

Hydrogel-forming microneedle arrays: Potential for use in minimally-invasive lithium monitoring

AbstractWe describe, for the first time, hydrogel-forming microneedle (s) (MN) arrays for minimally-invasive extraction and quantification of lithium in vitro and in vivo. MN arrays, prepared from aqueous blends of hydrolysed poly(methyl-vinylether-co-maleic anhydride) and crosslinked by poly(ethyleneglycol), imbibed interstitial fluid (ISF) upon skin insertion. Such MN were always removed intact. In vitro, mean detected lithium concentrations showed no significant difference following 30min MN application to excised neonatal porcine skin for lithium citrate concentrations of 0.9 and 2mmol/l. However, after 1h application, the mean lithium concentrations extracted were significantly different, being appropriately concentration-dependent. In vivo, rats were orally dosed with lithium citrate equivalent to 15mg/kg and 30mg/kg lithium carbonate, respectively. MN arrays were applied 1h after dosing and removed 1h later. The two groups, having received different doses, showed no significant difference between lithium concentrations in serum or MN. However, the higher dosed rats demonstrated a lithium concentration extracted from MN arrays equivalent to a mean increase of 22.5% compared to rats which received the lower dose. Hydrogel-forming MN clearly have potential as a minimally-invasive tool for lithium monitoring in outpatient settings. We will now focus on correlation between serum and MN lithium concentrations

Eustachian tube dysfunction: A diagnostic accuracy study and proposed diagnostic pathway.

BACKGROUND AND AIMS: Eustachian tube dysfunction (ETD) is a commonly diagnosed disorder of Eustachian tube opening and closure, which may be associated with severe symptoms and middle ear disease. Currently the diagnosis of obstructive and patulous forms of ETD is primarily based on non-specific symptoms or examination findings, rather than measurement of the underlying function of the Eustachian tube. This has proved problematic when selecting patients for treatment, and when designing trial inclusion criteria and outcomes. This study aims to determine the correlation and diagnostic value of various tests of ET opening and patient reported outcome measures (PROMs), in order to generate a recommended diagnostic pathway for ETD. METHODS: Index tests included two PROMs and 14 tests of ET opening (nine for obstructive, five for patulous ETD). In the absence of an accepted reference standard two methods were adopted to establish index test accuracy: expert panel diagnosis and latent class analysis. Index test results were assessed with Pearson correlation and principle component analysis, and test accuracy was determined. Logistic regression models assessed the predictive value of grouped test results. RESULTS: The expert panel diagnosis and PROMs results correlated with each other, but not with ET function measured by tests of ET opening. All index tests were found to be feasible in clinic, and acceptable to patients. PROMs had very poor specificity, and no diagnostic value. Combining the results of tests of ET function appeared beneficial. The latent class model suggested tympanometry, sonotubometry and tubomanometry have the best diagnostic performance for obstructive ETD, and these are included in a proposed diagnostic pathway. CONCLUSIONS: ETD should be diagnosed on the basis of clinical assessment and tests of ET opening, as PROMs have no diagnostic value. Currently diagnostic uncertainty exists for some patients who appear to have intermittent ETD clinically, but have negative index test results.M.S. received funding from the Cambridge Hearing Trus

Increased typhoon activity in the Pacific deep tropics driven by Little Ice Age circulation changes

Author Posting. © The Author(s), 2020. This is the author's version of the work. It is posted here by permission of Nature Research for personal use, not for redistribution. The definitive version was published in Bramante, J. F., Ford, M. R., Kench, P. S., Ashton, A. D., Toomey, M. R., Sullivan, R. M., Karnauskas, K. B., Ummenhofer, C. C., & Donnelly, J. P. (2020). Increased typhoon activity in the Pacific deep tropics driven by Little Ice Age circulation changes. Nature Geoscience, 13, 806–811. doi:10.1038/s41561-020-00656-2.The instrumental record reveals that tropical cyclone activity is sensitive to oceanic and atmospheric variability on inter-annual and decadal scales. However, our understanding of the influence of climate on tropical cyclone behaviour is restricted by the short historical record and the sparseness of prehistorical reconstructions, particularly in the western North Pacific, where coastal communities suffer loss of life and livelihood from typhoons annually. Here, to explore past regional typhoon dynamics, we reconstruct three millennia of deep tropical North Pacific cyclogenesis. Combined with existing records, our reconstruction demonstrates that low-baseline typhoon activity prior to 1350 ce was followed by an interval of frequent storms during the Little Ice Age. This pattern, concurrent with hydroclimate proxy variability, suggests a centennial-scale link between Pacific hydroclimate and tropical cyclone climatology. An ensemble of global climate models demonstrates a migration of the Pacific Walker circulation and variability in two Pacific climate modes during the Little Ice Age, which probably contributed to enhanced tropical cyclone activity in the tropical western North Pacific. In the next century, projected changes to the Pacific Walker circulation and expansion of the tropics will invert these Little Ice Age hydroclimate trends, potentially reducing typhoon activity in the deep tropical Pacific.This work was supported by the Strategic Environmental Research and Development Program (SERDP RC-2336). C.C.U. acknowledges support from NSF under AGS-1602455. We thank student intern D. Carter for extensive labwork on core LTD3. We acknowledge the WCRP’s Working Group on Coupled Modelling, which is responsible for CMIP, and we thank the climate modelling groups for producing and making available their model output. CMIP5 model output was provided by the WHOI CMIP5 Community Storage Server via their website: http://cmip5.whoi.edu/. Any use of trade, firm or product names is for descriptive purposes only and does not imply endorsement by the US Government.2021-05-1

Role of China in the Quest to Define and Control Severe Acute Respiratory Syndrome

China holds the key to solving many questions crucial to global control of severe acute respiratory syndrome (SARS). The disease appears to have originated in Guangdong Province, and the causative agent, SARS coronavirus, is likely to have originated from an animal host, perhaps sold in public markets. Epidemiologic findings, integral to defining an animal-human linkage, may then be confirmed by laboratory studies; once animal host(s) are confirmed, interventions may be needed to prevent further animal-to-human transmission. Community seroprevalence studies may help determine the basis for the decline in disease incidence in Guangdong Province after February 2002. China will also be able to contribute key data about how the causative agent is transmitted and how it is evolving, as well as identifying pivotal factors influencing disease outcome. There must be support for systematically addressing these fundamental questions in China and rapidly disseminating results

Eustachian tube dysfunction: A diagnostic accuracy study and proposed diagnostic pathway

<div><p>Background and aims</p><p>Eustachian tube dysfunction (ETD) is a commonly diagnosed disorder of Eustachian tube opening and closure, which may be associated with severe symptoms and middle ear disease. Currently the diagnosis of obstructive and patulous forms of ETD is primarily based on non-specific symptoms or examination findings, rather than measurement of the underlying function of the Eustachian tube. This has proved problematic when selecting patients for treatment, and when designing trial inclusion criteria and outcomes. This study aims to determine the correlation and diagnostic value of various tests of ET opening and patient reported outcome measures (PROMs), in order to generate a recommended diagnostic pathway for ETD.</p><p>Methods</p><p>Index tests included two PROMs and 14 tests of ET opening (nine for obstructive, five for patulous ETD). In the absence of an accepted reference standard two methods were adopted to establish index test accuracy: expert panel diagnosis and latent class analysis. Index test results were assessed with Pearson correlation and principle component analysis, and test accuracy was determined. Logistic regression models assessed the predictive value of grouped test results.</p><p>Results</p><p>The expert panel diagnosis and PROMs results correlated with each other, but not with ET function measured by tests of ET opening. All index tests were found to be feasible in clinic, and acceptable to patients. PROMs had very poor specificity, and no diagnostic value. Combining the results of tests of ET function appeared beneficial. The latent class model suggested tympanometry, sonotubometry and tubomanometry have the best diagnostic performance for obstructive ETD, and these are included in a proposed diagnostic pathway.</p><p>Conclusions</p><p>ETD should be diagnosed on the basis of clinical assessment and tests of ET opening, as PROMs have no diagnostic value. Currently diagnostic uncertainty exists for some patients who appear to have intermittent ETD clinically, but have negative index test results.</p></div

Parity Violating Measurements of Neutron Densities

Parity violating electron nucleus scattering is a clean and powerful tool for measuring the spatial distributions of neutrons in nuclei with unprecedented accuracy. Parity violation arises from the interference of electromagnetic and weak neutral amplitudes, and the $Z^0$ of the Standard Model couples primarily to neutrons at low $Q^2$. The data can be interpreted with as much confidence as electromagnetic scattering. After briefly reviewing the present theoretical and experimental knowledge of neutron densities, we discuss possible parity violation measurements, their theoretical interpretation, and applications. The experiments are feasible at existing facilities. We show that theoretical corrections are either small or well understood, which makes the interpretation clean. The quantitative relationship to atomic parity nonconservation observables is examined, and we show that the electron scattering asymmetries can be directly applied to atomic PNC because the observables have approximately the same dependence on nuclear shape.Comment: 38 pages, 7 ps figures, very minor changes, submitted to Phys. Rev.

Flux-Induced Vortex in Mesoscopic Superconducting Loops

We predict the existence of a quantum vortex for an unusual situation. We study the order parameter in doubly connected superconducting samples embedded in a uniform magnetic field. For samples with perfect cylindrical symmetry, the order parameter has been known for long and no vortices are present in the linear regime. However, if the sample is not symmetric, there exist ranges of the field for which the order parameter vanishes along a line, parallel to the field. In many respects, the behavior of this line is qualitatively different from that of the vortices encountered in type II superconductivity. For samples with mirror symmetry, this flux-induced vortex appears at the thin side for small fluxes and at the opposite side for large fluxes. We propose direct and indirect experimental methods which could test our predictions.Comment: 6 pages, Latex, 4 figs., uses RevTex, extended to situations far from cylindrical symmetr