Interventional multispectral photoacoustic imaging with a clinical ultrasound probe for discriminating nerves and tendons: an ex vivo pilot study

Abstract. Accurate and efficient identification of nerves is an essential component of peripheral nerve blocks. While ultrasound (US) imaging is increasingly used as a guidance modality, it often provides insufficient contrast for identifying nerves from surrounding tissues such as tendons. Electrical nerve stimulators can be used in conjunction with US imaging for discriminating nerves from surrounding tissues, but they are insufficient to reliably prevent neural punctures, so that alternative methods are highly desirable. In this study, an interventional multispectral photoacoustic (PA) imaging system was used to directly compare the signal amplitudes and spectra acquired from nerves and tendons ex vivo, for the first time. The results indicate that the system can provide significantly higher image contrast for discriminating nerves and tendons than that provided by US imaging. As such, photoacoustic imaging could be valuable as an adjunct to US for guiding peripheral nerve blocks

Laser induced nitrogen doping of zinc oxide

The p-n junction is the fundamental building block of many electronic and optoelectronic devices, including diodes, transistors, light emitting diodes (LEDs), solar cells, integrated circuits and many more. Of the many devices, UV LEDs based on wide bandgap semiconductor p-n homojunctions promise a plethora of widescale functionalities for use in a variety of important medical, environmental, and industrial applications. However, the development of low-cost, highly efficient materials for use in UV LEDs with emissions spanning across the UV spectrum is essential if such widescale applications are to be realised. Zinc oxide (ZnO) is a promising candidate for a low cost, non-toxic alternative material to Gallium Nitride (GaN) for use in UV LEDs. Yet, the desirable ZnO p-n homojunction remains elusive due to the current research bottleneck in achieving stable, reproducible, and high-quality p-type ZnO. Various research groups have investigated routes to achieving p-type doping in ZnO, but most of the materials developed exhibit poor crystalline quality with unstable and unreproducible p-type conductivity with high native point defect densities and in-active dopants. As such, several major research challenges must be addressed if the full potential and advantages of ZnO as a UV LED material are to be harnessed in real devices. These challenges include improving dopant solubility, minimising hole compensation by native defects or background impurities, and the production of shallow acceptor states with low ionisation energies for the realisation of high quality and stable p-type ZnO. To address these challenges, this work is devoted to the development of a robust and repeatable doping strategy to achieve high quality, stable, and controllable p-type ZnO material. A disruptive progression towards the realisation of such p-type conductivity in ZnO is demonstrated through the development of a Controlled Environment Excimer Laser Doping (CEELD) process conducted in a pressurised nitrogen (N) containing environment to induce high-level, stable and reproducible N acceptor doping in Atomic Layer Deposition (ALD) ZnO. It is revealed that CEELD can incorporate and promote N into preferential lattice sites in the film through co-doping with the high level of background impurity hydrogen (H) present in the as grown ALD films. Once the N is incorporated, the high laser energy density simultaneously breaks the N − H bond and provides enough thermal energy for the out-diffusion of the otherwise passivating H from the film, in turn activating N as an acceptor type dopant. Extensive characterisation of the electrical, optical, and compositional properties of the films is performed to further verify the achievement of CEELD induced p-type ZnO. The development of Ohmic contacts to the seed n- and p-type materials are investigated, and the seed materials implemented into simple p-n junction and thin film transistor (TFT) devices to further demonstrate the achievement of p-type ZnO. The CEELD process is then presented as a one-step, ultra-fast, low thermal budget, and highly selective doping strategy for the achievement of ultra-shallow p-n junctions for both lateral and laterally printed vertical p-n homojunction devices in ZnO

Parameterized lower bound and NP-completeness of some HH-free Edge Deletion problems

For a graph $H$, the $H$-free Edge Deletion problem asks whether there exist at most $k$ edges whose deletion from the input graph $G$ results in a graph without any induced copy of $H$. We prove that $H$-free Edge Deletion is NP-complete if $H$ is a graph with at least two edges and $H$ has a component with maximum number of vertices which is a tree or a regular graph. Furthermore, we obtain that these NP-complete problems cannot be solved in parameterized subexponential time, i.e., in time $2^{o(k)}\cdot |G|^{O(1)}$, unless Exponential Time Hypothesis fails.Comment: 15 pages, COCOA 15 accepted pape

No effect of arm exercise on diaphragmatic fatigue or ventilatory constraint in Paralympic athletes with cervical spinal cord injury

Cervical spinal cord injury (CSCI) results in a decrease in the capacity of the lungs and chest wall for pressure, volume, and airflow generation. We asked whether such impairments might increase the potential for exercise-induced diaphragmatic fatigue and mechanical ventilatory constraint in this population. Seven Paralympic wheelchair rugby players (mean ± SD peak oxygen uptake = 16.9 ± 4.9 ml·kg–1·min–1) with traumatic CSCI (C5–C7) performed arm-crank exercise to the limit of tolerance at 90% of their predetermined peak work rate. Diaphragm function was assessed before and 15 and 30 min after exercise by measuring the twitch transdiaphragmatic pressure (Pdi,tw) response to bilateral anterolateral magnetic stimulation of the phrenic nerves. Ventilatory constraint was assessed by measuring the tidal flow volume responses to exercise in relation to the maximal flow volume envelope. Pdi,tw was not different from baseline at any time after exercise (unpotentiated Pdi,tw = 19.3 ± 5.6 cmH2O at baseline, 19.8 ± 5.0 cmH2O at 15 min after exercise, and 19.4 ± 5.7 cmH2O at 30 min after exercise; P = 0.16). During exercise, there was a sudden, sustained rise in operating lung volumes and an eightfold increase in the work of breathing. However, only two subjects showed expiratory flow limitation, and there was substantial capacity to increase both flow and volume (<50% of maximal breathing reserve). In conclusion, highly trained athletes with CSCI do not develop exercise-induced diaphragmatic fatigue and rarely reach mechanical ventilatory constraint

A Field Training Guide for Human Subjects Research Ethics

Maria Merritt and colleagues report on a Field Training Guide for Human Subjects Research Ethics that they have developed to help train field workers in ethics for research

Accuracy of BRCA1/2 mutation prediction models for different ethnicities and genders: Experience in a southern Chinese cohort

Background: BRCA1/2 mutation prediction models (BRCAPRO, Myriad II, Couch, Shattuck-Eidens, BOADICEA) are well established in western cohorts to estimate the probability of BRCA1/2 mutations. Results: are conflicting in Asian populations. Most studies did not account for gender-specific prediction. We evaluated the performance of these models in a Chinese cohort, including males, before BRCA1/2 mutation testing. Methods: The five risk models were used to calculate the probability of BRCA mutations in probands with breast and ovarian cancers; 267 were non-BRCA mutation carriers (247 females and 20 males) and 43 were BRCA mutation carriers (38 females and 5 males). Results: Mean BRCA prediction scores for all models were statistically better for carriers than noncarriers for females but not for males. BRCAPRO overestimated the numbers of female BRCA1/2 mutation carriers at thresholds ≥20% but underestimated if <20%. BRCAPRO and BOADICEA underestimated the number of male BRCA1/2 mutation carriers whilst Myriad II underestimated the number of both male and female carriers. In females, BRCAPRO showed similar discrimination, as measured by the area under the receiver operator characteristic curve (AUC) for BRCA1/2 combined mutation prediction to BOADICEA, but performed better than BOADICEA in BRCA1 mutation prediction (AUC 93% vs. 87%). BOADICEA had the best discrimination for BRCA1/2 combined mutation prediction (AUC 87%) in males. Conclusions: The variation in model performance underscores the need for research on larger Asian cohorts as prediction models, and the possible need for customizing these models for different ethnic groups and genders. © The Author(s) 2012.published_or_final_versio

Global genomic analysis of microbial biotransformation of arsenic highlights the importance of arsenic methylation in environmental and human microbiomes

Arsenic is a ubiquitous toxic element, the global cycle of which is highly affected by microbial redox reactions and assimilation into organoarsenic compounds through sequential methylation reactions. While microbial biotransformation of arsenic has been studied for decades, the past years have seen the discovery of multiple new genes related to arsenic metabolism. Still, most studies focus on a small set of key genes or a small set of cultured microorganisms. Here, we leveraged the recently greatly expanded availability of microbial genomes of diverse organisms from lineages lacking cultivated representatives, including those reconstructed from metagenomes, to investigate genetic repertoires of taxonomic and environmental controls on arsenic metabolic capacities. Based on the collection of arsenic-related genes, we identified thirteen distinct metabolic guilds, four of which combine the aio and ars operons. We found that the best studied phyla have very different combinations of capacities than less well-studied phyla, including phyla lacking isolated representatives. We identified a distinct arsenic gene signature in the microbiomes of humans exposed or likely exposed to drinking water contaminated by arsenic and that arsenic methylation is important in soil and in human microbiomes. Thus, the microbiomes of humans exposed to arsenic have the potential to exacerbate arsenic toxicity. Finally, we show that machine learning can predict bacterial arsenic metabolism capacities based on their taxonomy and the environment from which they were sampled

Fiber optic photoacoustic probe with ultrasonic tracking for guiding minimally invasive procedures

In a wide range of clinical procedures, accurate placement of medical devices such as needles and catheters is critical to optimize patient outcomes. Ultrasound imaging is often used to guide minimally invasive procedures, as it can provide real-time visualization of patient anatomy and medical devices. However, this modality can provide low image contrast for soft tissues, and poor visualization of medical devices that are steeply angled with respect to the incoming ultrasound beams. Photoacoustic sensors can provide information about the spatial distributions of tissue chromophores that could be valuable for guiding minimally invasive procedures. In this study, a system for guiding minimally invasive procedures using photoacoustic sensing was developed. This system included a miniature photoacoustic probe with three optical fibers: one with a bare end for photoacoustic excitation of tissue, a second for photoacoustic excitation of an optically absorbing coating at the distal end to transmit ultrasound, and a third with a Fabry-Perot cavity at the distal end for receiving ultrasound. The position of the photoacoustic probe was determined with ultrasonic tracking, which involved transmitting pulses from a linear-array ultrasound imaging probe at the tissue surface, and receiving them with the fiber-optic ultrasound receiver in the photoacoustic probe. The axial resolution of photoacoustic sensing was better than 70 μm, and the tracking accuracy was better than 1 mm in both axial and lateral dimensions. By translating the photoacoustic probe, depth scans were obtained from different spatial positions, and two-dimensional images were reconstructed using a frequency-domain algorithm

Identification of BRCA1/2 Founder Mutations in Southern Chinese Breast Cancer Patients Using Gene Sequencing and High Resolution DNA Melting Analysis

Background: Ethnic variations in breast cancer epidemiology and genetics have necessitated investigation of the spectra of BRCA1 and BRCA2 mutations in different populations. Knowledge of BRCA mutations in Chinese populations is still largely unknown. We conducted a multi-center study to characterize the spectra of BRCA mutations in Chinese breast and ovarian cancer patients from Southern China. Methodology/Principal Findings: A total of 651 clinically high-risk breast and/or ovarian cancer patients were recruited from the Hong Kong Hereditary Breast Cancer Family Registry from 2007 to 2011. Comprehensive BRCA1 and BRCA2 mutation screening was performed using bi-directional sequencing of all coding exons of BRCA1 and BRCA2. Sequencing results were confirmed by in-house developed full high resolution DNA melting (HRM) analysis. Among the 451 probands analyzed, 69 (15.3%) deleterious BRCA mutations were identified, comprising 29 in BRCA1 and 40 in BRCA2. The four recurrent BRCA1 mutations (c.470_471delCT, c.3342_3345delAGAA, c.5406+1_5406+3delGTA and c.981_982delAT) accounted for 34.5% (10/29) of all BRCA1 mutations in this cohort. The four recurrent BRCA2 mutations (c.2808_2811delACAA, c.3109C>T, c.7436_7805del370 and c.9097_9098insA) accounted for 40% (16/40) of all BRCA2 mutations. Haplotype analysis was performed to confirm 1 BRCA1 and 3 BRCA2 mutations are putative founder mutations. Rapid HRM mutation screening for a panel of the founder mutations were developed and validated. Conclusion: In this study, our findings suggest that BRCA mutations account for a substantial proportion of hereditary breast/ovarian cancer in Southern Chinese population. Knowing the spectrum and frequency of the founder mutations in this population will assist in the development of a cost-effective rapid screening assay, which in turn facilitates genetic counseling and testing for the purpose of cancer risk assessment. © 2012 Kwong et al.published_or_final_versio