High power visible light emitting diodes as pulsed excitation sources for biomedical photoacoustics

The use of visible light emitting diodes (LEDs) as an alternative to Q-switched lasers conventionally used as photoacoustic excitation sources has been explored. In common with laser diodes, LEDs offer the advantages of compact size, low cost and high efficiency. However, laser diodes suitable for pulsed photoacoustic generation are typically available only at wavelengths greater than 750nm. By contrast, LEDs are readily available at visible wavelengths below 650nm where haemoglobin absorption is significantly higher, offering the prospect of increased SNR for superficial vascular imaging applications. To demonstrate feasibility, a range of low cost commercially available LEDs operating in the 420-620nm spectral range were used to generate photoacoustic signals in physiologically realistic vascular phantoms. Overdriving with 200ns pulses and operating at a low duty cycle enabled pulse energies up to 10µJ to be obtained with a 620nm LED. By operating at a high pulse repetition frequency (PRF) in order to rapidly signal average over many acquisitions, this pulse energy was sufficient to generate detectable signals in a blood filled tube immersed in an Intralipid suspension (µs' = 1mm(-1)) at a depth of 15mm using widefield illumination. In addition, a compact four-wavelength LED (460nm, 530nm, 590nm, 620nm) in conjunction with a coded excitation scheme was used to illustrate rapid multiwavelength signal acquisition for spectroscopic applications. This study demonstrates that LEDs could find application as inexpensive and compact multiwavelength photoacoustic excitation sources for imaging superficial vascular anatomy. Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI

Large area laser scanning optical resolution photoacoustic microscopy using a fibre optic sensor

A laser scanning optical resolution photoacoustic microscopy (LS OR-PAM) system based on a stationary fibre optic sensor is described. The sensor comprises an optically resonant interferometric polymer cavity formed on the tip of a rounded single mode optical fibre. It provides low noise equivalent pressure (NEP = 68.7 Pa over a 20 MHz measurement bandwidth), a broad bandwidth that extends to 80 MHz and a near omnidirectional response. The latter is a significant advantage, as it allows large areas ( > 1cm 2 ) to be imaged without the need for translational mechanical scanning offering the potential for fast image acquisition. The system provides a lateral resolution of 8 µm, an axial resolution of 21 µm, and a field of view up to 10 mm × 10 mm. To demonstrate the system, in vivo 3D structural images of the microvasculature of a mouse ear were obtained, showing single capillaries overlaying larger vessels as well as functional images revealing blood oxygen saturation

Photoacoustic wavefront shaping with a long coherence length laser

Photoacoustic (PA) wavefront shaping (WS; PAWS) could allow focusing light deep in biological tissue. This could enable increasing the penetration depth of biomedical optical techniques including PA imaging. However, focussing at depth requires a light source of long coherence length (CL), presenting a challenge because the CLs of typical PA excitation lasers are short. To address this challenge, we developed a PAWS system based on an externally modulated external cavity laser with a long CL. The system was demonstrated by focussing light through rigid scattering media using both PAWS and optical WS. PAWS enabled focussing through diffusers with 8 × enhancements, while all-optical WS enabled focussing through various scattering media including a 5.8 mm thick tissue phantom. By enabling PAWS with increased coherence, the system could facilitate exploring the practical depth limits of PAWS, paving the way to focussing light deep in tissue

Modulation of porcine β-defensins 1 and 2 upon individual and combined Fusarium toxin exposure in a swine jejunal epithelial cell line

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Myocardial expression of a constitutively active alpha 1B-adrenergic receptor in transgenic mice induces cardiac hypertrophy.

Transgenic mice were generated by using the alpha-myosin heavy chain promoter coupled to the coding sequence of a constitutively active mutant alpha 1B-adrenergic receptor (AR). These transgenic animals demonstrated cardiac-specific expression of this alpha 1-AR with resultant activation of phospholipase C as shown by increased myocardial diacylglycerol content. A phenotype consistent with cardiac hypertrophy developed in adult transgenic mice with increased heart/body weight ratios, myocyte cross-sectional areas, and ventricular atrial natriuretic factor mRNA levels relative to nontransgenic controls. These transgenic animals may provide insight into the biochemical triggers that induce hypertrophy in cardiac disease and serve as a convenient experimental model for studies of this condition

The cost of congenital heart-disease in children and adults: a model for multicenter assessment of price and practice variation

Objective: To assess the cost of congenital heart disease (CHD) and to assess whether practice pattern or price was more responsible for variation

A re-evaluation of the Earth’s surface temperature response to radiative forcing

This is the final version. Available on open access from IOP Publishing via the DOI in this recordData availability statement: All the time-series data used in this analysis is freely available for research: http://cdiac.ornl.gov/trends/temp/jonescru/jones.html; www.pik-potsdam.de/~mmalte/rcps/; www.cgd.ucar.edu/cas/catalog/climind/AMO.html. The models in this paper have been inferred statistically from the data record available when the present study was initiated and they can change over time. The data that support the findings of this study are available upon reasonable request from the authorsThere is much current debate about the way in which the earth's climate and temperature are responding to anthropogenic and natural forcing. In this paper we re-assess the current evidence at the globally averaged level by adopting a generic 'data-based mechanistic' modelling strategy that incorporates statistically efficient parameter estimation. This identifies a low order, differential equation model that explains how the global average surface temperature variation responds to the influences of total radiative forcing (TRF). The model response includes a novel, stochastic oscillatory component with a period of about 55 years (range 51.6–60 years) that appears to be associated with heat energy interchange between the atmosphere and the ocean. These 'quasi-cycle' oscillations, which account for the observed pauses in global temperature increase around 1880, 1940 and 2001, appear to be related to ocean dynamic responses, particularly the Atlantic multidecadal oscillation. The model explains 90% of the variance in the global average surface temperature anomaly and yields estimates of the equilibrium climate sensitivity (ECS) (2.29 compfnC with 5%–95% range 2.11 compfnC to 2.49 compfnC) and the transient climate response (TCR) (1.56 compfnC with 5%–95% range 1.43 compfnC to 1.68 compfnC), both of which are smaller than most previous estimates. When a high level of uncertainty in the TRF is taken into account, the ECS and TCR estimates are unchanged but the ranges are increased to 1.43 compfnC to 3.14 compfnC and 0.99 compfnC to 2.16 compfnC, respectively.Engineering and Physical Sciences Research Council (EPSRC)Natural Environment Research Council (NERC)Newton Funded China Services Partnership (CSSP

A Case Study of Eukaryogenesis: The Evolution of Photoreception by Photolyase/Cryptochrome Proteins

Eukaryogenesis, the origin of the eukaryotes, is still poorly understood. Herein, we show how a detailed all-kingdom phylogenetic analysis overlaid with a map of key biochemical features can provide valuable clues. The photolyase/cryptochrome family of proteins are well known to repair DNA in response to potentially harmful effects of sunlight and to entrain circadian rhythms. Phylogenetic analysis of photolyase/cryptochrome protein sequences from a wide range of prokaryotes and eukaryotes points to a number of horizontal gene transfer events between ancestral bacteria and ancestral eukaryotes. Previous experimental research has characterised patterns of tryptophan residues in these proteins that are important for photoreception, specifically a tryptophan dyad, a canonical tryptophan triad, an alternative tryptophan triad, a tryptophan tetrad and an alternative tetrad. Our results suggest that the spread of the different triad and tetrad motifs across the kingdoms of life accompanied the putative horizontal gene transfers and is consistent with multiple bacterial contributions to eukaryogenesis

Quality of life utility values for hereditary haemochromatosis in Australia

Background: Hereditary hemochromatosis (HH) is a common autosomal recessive disorder amongst persons of northern European heritage. If untreated, iron accumulates in parenchymal tissues causing morbidity and mortality. As diagnosis often follows irreversible organ damage, screening programs have been suggested to increase early diagnosis. A lack of economic evidence has been cited as a barrier to establishing such a program. Previous analyses used poorly estimated utility values. This study sought to measure utilities directly from people with HH in Australia. Methods: Volunteers with HH were recruited to complete a web-based survey. Utility was assessed using the Assessment of Quality of Life 4D (AQOL-4D) instrument. Severity of HH was graded into four categories. Multivariable regression analysis was performed to identify parameters associated with HSUV. Results: Between November 2013 and November 2014, 221 people completed the survey. Increasing severity of HH was negatively associated with utility. Mean (standard deviation) utilities were 0.76 (0.21), 0.81 (0.18), 0.60 (0.27), and 0.50 (0.27) for categories 1-4 HH respectively. Lower mean utility was found for symptomatic participants (categories 3 and 4) compared with asymptomatic participants (0.583 v. 0.796). Self-reported HH-related symptoms were negatively associated with HSUV (r = -0.685). Conclusions: Symptomatic stages of HH and presence of multiple self-reported symptoms were associated with decreasing utility. Previous economic analyses have used higher utilities which likely resulted in underestimates of the cost effectiveness of HH interventions. The utilities reported in this paper are the most robust available, and will contribute to improving the validity of future economic models for HH

Large, high quality single-crystals of the new Topological Kondo Insulator, SmB6

SmB6 has recently been predicted to be a Topological Kondo Insulator, the first strongly correlated heavy fermion material to exhibit topological surface states. High quality crystals are necessary to investigate the topological properties of this material. Single crystal growth of the rare earth hexaboride, SmB6, has been carried out by the floating zone technique using a high power xenon arc lamp image furnace. Large, high quality single-crystals are obtained by this technique. The crystals produced by the floating zone technique are free of contamination from flux materials and have been characterised by resistivity and magnetisation measurements. These crystals are ideally suited for the investigation of both the surface and bulk properties of SmB6