Microneedle Arrays Allow Lower Microbial Penetration Than Hypodermic Needles In Vitro

Methods: In this study we determined, for the first time, the ability of microorganisms to traverse microneedle-induced holes using two different in vitro models.

Results: When employing Silescol® membranes, the numbers of Candida albicans, Pseudomonas aeruginosa and Staphylococcus epidermidis crossing the membranes were an order of magnitude lower when the membranes were punctured by microneedles rather than a 21G hypodermic needle. Apart from the movement of C. albicans across hypodermic needle-punctured membranes, where 40.2% of the microbial load on control membranes permeated the barrier over 24 h, the numbers of permeating microorganisms was less than 5% of the original microbial load on control membranes. Experiments employing excised porcine skin and radiolabelled microorganisms showed that the numbers of microorganisms penetrating skin beyond the stratum corneum were approximately an order of magnitude greater than the numbers crossing Silescol® membranes in the corresponding experiments. Approximately 103?cfu of each microorganism adhered to hypodermic needles during insertion. The numbers of microorganisms adhering to MN arrays were an order of magnitude higher in each case.

Conclusion: We have shown here that microneedle puncture resulted in significantly less microbial penetration than did hypodermic needle puncture and that no microorganisms crossed the viable epidermis in microneedle—punctured skin, in contrast to needle-punctured skin. Given the antimicrobial properties of skin, it is, therefore, likely that application of microneedle arrays to skin in an appropriate manner would not cause either local or systemic infection in normal circumstances in immune-competent patients. In supporting widespread clinical use of microneedle-based delivery systems, appropriate animal studies are now needed to conclusively demonstrate this in vivo. Safety in patients will be enhanced by aseptic or sterile manufacture and by fabricating microneedles from self-disabling materials (e.g. dissolving or biodegradable polymers) to prevent inappropriate or accidental reuse.

Subwavelength resolution for horizontal and vertical polarization by coupled arrays of oblate nanoellipsoids

A structure comprising a coupled pair of two-dimensional arrays of oblate plasmonic nanoellipsoids in a dielectric host medium is proposed as a superlens in the optical domain for both horizontal and vertical polarizations. By means of simulations it is demonstrated that a structure formed by silver nanoellipsoids is capable of restoring subwavelength features of the object for both polarizations at distances larger than half wavelength. The bandwidth of subwavelength resolution is in all cases very large (above 13%). (C) 2009 Optical Society of America

The Preboreal climate reversal and a subsequent solar-forced climate shift

Accurate chronologies are essential for linking palaeoclimate archives. Carbon-14 wiggle-match dating was used to produce an accurate chronology for part of an early Holocene peat sequence from the Borchert (The Netherlands). Following the Younger Dryas-Preboreal transition, two climatic shifts could be inferred. Around 11 400 cal. yr BP the expansion of birch (Betula) forest was interrupted by a dry continental phase with dominantly open grassland vegetation, coeval with the PBO (Preboreal Oscillation), as observed in the GRIP ice core. At 11 250 cal. yr BP a sudden shift to a humid climate occurred. This second change appears to be contemporaneous with: (i) a sharp increase of atmospheric C-14; (ii) a temporary decline of atmospheric CO2; and (iii) an increase in the GRIP Be-10 flux. The close correspondence with excursions of cosmogenic nuclides points to a decline in solar activity, which may have forced the changes in climate and vegetation at around 11 250 cal. yr BP. Copyright (C) 2004 John Wiley Sons, Ltd.

Changes in solar activity and Holocene climatic shifts derived from C-14 wiggle-match dated peat deposits

Closely spaced sequences of accelerator mass spectrometer (AMS) C-14 dates of peat deposits display century-scale wiggles which can be fitted to the radiocarbon calibration curve. By wiggle-matching such sequences, high-precision calendar age chronologies can be generated which show that changes in mire surface wetness during the Bronze Age/Iron Age transition (c. 850 cal. BC) and the 'Little Ice Age' (Wolf, Sporer, Maunder and Dalton Minima) occurred during periods of suddenly increasing atmospheric concentration of C-14. Replicate evidence from peat-based proxy climate indicators in northwest Europe suggest these changes in climate may have been driven by temporary declines of solar activity. Carbon-accumulation rates of two raised peat bogs in the UK and Denmark record low values during the 'Little Ice Age' which reflects reduced primary productivity of the peat-forming vegetation during these periods of climatic deterioration.

Evidence from northwest European bogs shows 'Little Ice Age' climatic changes driven by variations in solar activity

Fluctuations in Holocene atmospheric radiocarbon concentrations have been shown to be due to variations in solar activity. Analyses of both Be-10 and C-14 nuclides confirm that production-rate changes during the Holocene were largely modulated by solar activity. Analyses of peat samples from two intact European ombrotrophic bogs show that climatic deteriorations during the 'Little Ice Age' are associated with transitions to increasing atmospheric C-14 content due to greater C-14 production. Both ombrotrophic mires, which are positioned c. 800 km apart, register reactions to globally recorded C-14 fluctuations between AD 1449 and 1464 and an almost identical reaction between AD 1601 and 1604.

Design, optimisation and characterisation of polymeric microneedle arrays prepared by a novel laser-based micromoulding technique.

PURPOSE:
Design and evaluation of a novel laser-based method for micromoulding of microneedle arrays from polymeric materials under ambient conditions. The aim of this study was to optimise polymeric composition and assess the performance of microneedle devices that possess different geometries.
METHODS:
A range of microneedle geometries was engineered into silicone micromoulds, and their physicochemical features were subsequently characterised.
RESULTS:
Microneedles micromoulded from 20% w/w aqueous blends of the mucoadhesive copolymer Gantrez® AN-139 were surprisingly found to possess superior physical strength than those produced from commonly used pharma polymers. Gantrez® AN-139 microneedles, 600 µm and 900 µm in height, penetrated neonatal porcine skin with low application forces (>0.03 N per microneedle). When theophylline was loaded into 600 µm microneedles, 83% of the incorporated drug was delivered across neonatal porcine skin over 24 h. Optical coherence tomography (OCT) showed that drug-free 600 µm Gantrez® AN-139 microneedles punctured the stratum corneum barrier of human skin in vivo and extended approximately 460 µm into the skin. However, the entirety of the microneedle lengths was not inserted.
CONCLUSION:
In this study, we have shown that a novel laser engineering method can be used in micromoulding of polymeric microneedle arrays. We are currently carrying out an extensive OCT-informed study investigating the influence of microneedle array geometry on skin penetration depth, with a view to enhanced transdermal drug delivery from optimised laser-engineered Gantrez® AN-139 microneedles.

ROSA: A High-cadence, Synchronized Multi-camera Solar Imaging System

The Rapid Oscillations in the Solar Atmosphere (ROSA) instrument is a synchronized, six-camera high-cadence solar imaging instrument developed by Queen's University Belfast. The system is available on the Dunn Solar Telescope at the National Solar Observatory in Sunspot, New Mexico, USA, as a common-user instrument. Consisting of six 1k x 1k Peltier-cooled frame-transfer CCD cameras with very low noise (0.02 -aEuro parts per thousand 15 e s(-1) pixel(-1)), each ROSA camera is capable of full-chip readout speeds in excess of 30 Hz, or 200 Hz when the CCD is windowed. Combining multiple cameras and fast readout rates, ROSA will accumulate approximately 12 TB of data per 8 hours observing. Following successful commissioning during August 2008, ROSA will allow for multi-wavelength studies of the solar atmosphere at a high temporal resolution.

The Area Distribution of Solar Magnetic Bright Points

Magnetic bright points (MBPs) are among the smallest observable objects on the solar photosphere. A combination of G-band observations and numerical simulations is used to determine their area distribution. An automatic detection algorithm, employing one-dimensional intensity profiling, is utilized to identify these structures in the observed and simulated data sets. Both distributions peak at an area of approximate to 45,000 km(2), with a sharp decrease toward smaller areas. The distributions conform with log-normal statistics, which suggests that flux fragmentation dominates over flux convergence. Radiative magneto-convection simulations indicate an independence in the MBP area distribution for differing magnetic flux densities. The most commonly occurring bright point size corresponds to the typical width of inter-granular lanes.

Vorticity in the solar photosphere

Aims. We use magnetic and non-magnetic 3D numerical simulations of solar granulation and G-band radiative diagnostics from the resulting models to analyse the generation of small-scale vortex motions in the solar photosphere.
Methods. Radiative MHD simulations of magnetoconvection are used to produce photospheric models. Our starting point is a non-magnetic model of solar convection, where we introduce a uniform magnetic field and follow the evolution of the field in the simulated photosphere. We find two different types of photospheric vortices, and provide a link between the vorticity generation and the presence of the intergranular magnetic field. A detailed analysis of the vorticity equation, combined with the G-band radiative diagnostics, allows us to identify the sources and observational signatures of photospheric vorticity in the simulated photosphere.
Results. Two different types of photospheric vorticity, magnetic and non-magnetic, are generated in the domain. Non-magnetic vortices are generated by the baroclinic motions of the plasma in the photosphere, while magnetic vortices are produced by the magnetic tension in the intergranular magnetic flux concentrations. The two types of vortices have different shapes. We find that the vorticity is generated more efficiently in the magnetised model. Simulated G-band images show a direct connection between magnetic vortices and rotary motions of photospheric bright points, and suggest that there may be a connection between the magnetic bright point rotation and small-scale swirl motions observed higher in the atmosphere.

Abnormal rolls and regular arrays of disclinations in homeotropic electroconvection

We present the first quantitative verification of an amplitude description for systems with (nearly) spontaneously broken isotropy, in particular for the recently discovered abnormal-roll states. We also obtain a conclusive picture of the three-dimensional director configuration in a spatial period doubling phenomenon involving disclination loops. The first observation of two Lifshitz frequencies in electroconvection is reported.