Search results for: Kayla Murray

Authors: Sa`ad M. Ismail, Hung-Hsun Yen, Christina M. Murray, Helen M. S. Davies

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The lumbosacral junction (where the 7th lumbar vertebra (L7) articulates with the sacrum) is a clinically important area in the dog. The 7th lumbar vertebra (L7) is normally shorter than other lumbar vertebrae, and it has been reported that variations in the L7 length may be associated with other abnormal anatomical findings. These variations included the reduction or absence of the portion of the median sacral crest. In this study, 53 greyhound cadavers were placed in right lateral recumbency, and two lateral radiographs were taken of the lumbosacral region for each greyhound. The length of the 6th lumbar (L6) vertebra and L7 were measured using radiographic measurement software and was defined to be the mean of three lines drawn from the caudal to the cranial edge of the L6 and L7 vertebrae (a dorsal, middle, and ventral line) between specific landmarks. Sacrocaudal fusion was found in 41.5% of the greyhounds. The mean values of the length of L6, L7, and the ratio of the L6/L7 length of the greyhounds with sacrocaudal fusion were all greater than those with standard sacrums (three sacral vertebrae). There was a significant difference (P < 0.05) in the mean values of the length of L7 between the greyhounds without sacrocaudal fusion (mean = 29.64, SD ± 2.07) and those with sacrocaudal fusion (mean = 30.86, SD ± 1.80), but, there was no significant difference in the mean value of the length of the L6 measurement. Among different types of sacrocaudal fusion, the longest L7 was found in greyhounds with sacrum type D, intermediate length in those with sacrum type B, and the shortest was found in those with sacrums type C, and the mean values of the ratio of the L6/L7 were 1.11 (SD ± 0.043), 1.15, (SD ± 0.025), and 1.15 (SD ± 0.011) for the types B, C, and D respectively. No significant differences in the mean values of the length of L6 or L7 were found among the different types of sacrocaudal fusion. The occurrence of sacrocaudal fusion might affect direct anatomically connected structures such as the L7. The variation in the length of L7 between greyhounds with sacrocaudal fusion and those without may reflect the possible sequences of the process of fusion. Variations in the length of the L7 vertebra in greyhounds may be associated with the occurrence of sacrocaudal fusion. The variation in the vertebral length may affect the alignment and biomechanical properties of the sacrum and may alter the loading. We concluded that any variations in the sacrum anatomical features might change the function of the sacrum or the surrounding anatomical structures.

Keywords: biomechanics, Greyhound, sacrocaudal fusion, locomotion, 6th Lumbar (L6) Vertebra, 7th Lumbar (L7) Vertebra, ratio of the L6/L7 length

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Authors: S. M. Ismail, H-H Yen, C. M. Murray, H. M. S. Davies

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A recent study reported a 33% incidence of complete sacrocaudal fusion in greyhounds compared to a 3% incidence in other dogs. In the dog, the median sacral crest is formed by the fusion of sacral spinous processes. Separation of the 1st spinous process from the median crest of the sacrum in the dog has been reported as a diagnostic tool of type one lumbosacral transitional vertebra (LTV). LTV is a congenital spinal anomaly, which includes either sacralization of the caudal lumbar part or lumbarization of the most cranial sacral segment of the spine. In this study, the absence or reduction of fusion (presence of separation) between the 1st and 2ndspinous processes of the median sacral crest has been identified in association with sacrocaudal fusion in the greyhound, without any feature of LTV. In order to provide quantitative data on the absence or reduction of fusion in the median sacral crest between the 1st and 2nd sacral spinous processes, in association with sacrocaudal fusion. 204 dog sacrums free of any pathological changes (192 greyhound, 9 beagles and 3 labradors) were grouped based on the occurrence and types of fusion and the presence, absence, or reduction in the median sacral crest between the 1st and 2nd sacral spinous processes., Sacrums were described and classified as follows: F: Complete fusion (crest is present), N: Absence (fusion is absent), and R: Short crest (fusion reduced but not absent (reduction). The incidence of sacrocaudal fusion in the 204 sacrums: 57% of the sacrums were standard (3 vertebrae) and 43% were fused (4 vertebrae). Type of sacrum had a significant (p < .05) association with the absence and reduction of fusion between the 1st and 2nd sacral spinous processes of the median sacral crest. In the 108 greyhounds with standard sacrums (3 vertebrae) the percentages of F, N and R were 45% 23% and 23% respectively, while in the 84 fused (4 vertebrae) sacrums, the percentages of F, N and R were 3%, 87% and 10% respectively and these percentages were significantly different between standard (3 vertebrae) and fused (4 vertebrae) sacrums (p < .05). This indicates that absence of spinous process fusion in the median sacral crest was found in a large percentage of the greyhounds in this study and was found to be particularly prevalent in those with sacrocaudal fusion – therefore in this breed, at least, absence of sacral spinous process fusion may be unlikely to be associated with LTV.

Keywords: greyhound, median sacral crest, sacrocaudal fusion, sacral spinous process

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Authors: Esther N. Maina, Anna Skowronska, Sridhar Chaganti, Malcolm A. Taylor, Paul G. Murray, Tatjana Stankovic

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Epstein-Barr virus (EBV) has been implicated in the pathogenesis of human tumours of B-cell origin. The demonstration that a proportion of Hodgkin lymphomas and all Burkitt’s lymphomas harbour EBV suggests that the virus contributes to the development of these malignancies. However, the mechanisms of lymphomagenesis remain largely unknown. To determine whether EBV causes DNA damage and alters DNA damage response in cells of EBV-driven lymphoma origin, Germinal Centre (GC) B cells were infected with EBV and DNA damage responses to gamma ionising radiation (IR) assessed at early time points (12hr – 72hr) after infection and prior to establishment of lymphoblastoid (LCL) cell lines. In the presence of EBV, we observed induction of spontaneous DNA DSBs and downregulation of ATM-dependent phosphorylation in response to IR. This downregulation coincided with reduced ability of infected cells to repair IR-induced DNA double-strand breaks, as measured by the kinetics of gamma H2AX, a marker of double-strand breaks, and by the tail moment of the comet assay. Furthermore, we found that alteration of DNA damage responses coincided with the expression of LMP-1 protein. The presence of the EBV virus did not affect the localization of the ATM-dependent DNA repair proteins to sites of damage but instead lead to an increased expression of PP5, a phosphatase that regulates ATM function. The impact of the virus on DNA repair was most prominent 24h after infection, suggesting that this time point is crucial for the viral establishment in B cells. Our results suggest that during an early infection EBV virus dampens crucial cellular responses to DNA double-strand breaks which facilitate successful viral infection, but at the same time might provide the mechanism for tumor development.

Keywords: EBV, ATM, DNA damage, germinal center cells

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Authors: Mehdi Khaki, Ehsan Forootan, Joseph Awange, Michael Kuhn

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Terrestrial water storage, as a source of freshwater, plays an important role in human lives. Hydrological models offer important tools for simulating and predicting water storages at global and regional scales. However, their comparisons with 'reality' are imperfect mainly due to a high level of uncertainty in input data and limitations in accounting for all complex water cycle processes, uncertainties of (unknown) empirical model parameters, as well as the absence of high resolution (both spatially and temporally) data. Data assimilation can mitigate this drawback by incorporating new sets of observations into models. In this effort, we use multi-mission satellite-derived remotely sensed observations to improve the performance of World-Wide Water Resources Assessment system (W3RA) hydrological model for estimating terrestrial water storages. For this purpose, we assimilate total water storage (TWS) data from the Gravity Recovery And Climate Experiment (GRACE) and surface soil moisture data from the Advanced Microwave Scanning Radiometer for the Earth Observing System (AMSR-E) into W3RA. This is done to (i) improve model estimations of water stored in ground and soil moisture, and (ii) assess the impacts of each satellite of data (from GRACE and AMSR-E) and their combination on the final terrestrial water storage estimations. These data are assimilated into W3RA using the Ensemble Square-Root Filter (EnSRF) filtering technique over Mississippi Basin (the United States) and Murray-Darling Basin (Australia) between 2002 and 2013. In order to evaluate the results, independent ground-based groundwater and soil moisture measurements within each basin are used.

Keywords: data assimilation, GRACE, AMSR-E, hydrological model, EnSRF

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Authors: Sa'ad M. Ismail, Hung-Hsun Yen, Christina M. Murray, Helen M. S. Davies

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In the dog, the median sacral crest is formed by the fusion of three sacral spinous processes. In greyhounds with standard sacrums, this fusion in the median sacral crest consists of the fusion of three sacral spinous processes while it consists of four in greyhounds with sacrocaudal fusion. In the present study, variations in the angulation of the first sacral spinous process in association with different types of sacrocaudal fusion in the greyhound were investigated. Sacrums were collected from 207 greyhounds (102 sacrums; type A (unfused) and 105 with different types of sacrocaudal fusion; types: B, C and D). Sacrums were cleaned by boiling and dried and then were placed on their ventral surface on a flat surface and photographed from the left side using a digital camera at a fixed distance. The first sacral spinous process angle (1st SPA) was defined as the angle formed between the cranial border of the cranial ridge of the first sacral spinous process and the line extending across the most dorsal surface points of the spinous processes of the S1, S2, and S3. Image-Pro Express Version 5.0 imaging software was used to draw and measure the angles. Two photographs were taken for each sacrum and two repeat measurements were also taken of each angle. The mean value of the 1st SPA in greyhounds with sacrocaudal fusion was less (98.99°, SD ± 11, n = 105) than those in greyhounds with standard sacrums (99.77°, SD ± 9.18, n = 102) but was not significantly different (P < 0.05). Among greyhounds with different types of sacrocaudal fusion the mean value of the 1st SPA was as follows: type B; 97.73°, SD ± 10.94, n = 39, type C: 101.42°, SD ± 10.51, n = 52, and type D: 94.22°, SD ± 11.30, n = 12. For all types of fusion these angles were significantly different from each other (P < 0.05). Comparing the mean value of the1st SPA in standard sacrums (Type A) with that for each type of fusion separately showed that the only significantly different angulation (P < 0.05) was between standard sacrums and sacrums with sacrocaudal fusion sacrum type D (only body fusion between the S1 and Ca1). Different types of sacrocaudal fusion were associated with variations in the angle of the first sacral spinous process. These variations may affect the alignment and biomechanics of the sacral area and the pattern of movement and/or the force produced by both hind limbs to the cranial parts of the body and may alter the loading of other parts of the body. We concluded that any variations in the sacrum anatomical features might change the function of the sacrum or surrounding anatomical structures during movement.

Keywords: angulation of first sacral spinous process, biomechanics, greyhound, locomotion, sacrocaudal fusion

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Authors: Kayla Belanger, Pascale Vigneron, Guy Schlatter, Bernard Devauchelle, Christophe Egles

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A severe injury to a peripheral nerve leads to its degeneration and the loss of sensory and motor function. To this day, there still lacks a more effective alternative to the autograft which has long been considered the gold standard for nerve repair. In order to overcome the numerous drawbacks of the autograft, tissue engineered biomaterials may be effective alternatives. Silk fibroin is a favorable biomaterial due to its many advantageous properties such as its biocompatibility, its biodegradability, and its robust mechanical properties. In this study, bio-mimicking multi-channeled nerve guidance conduits made of aligned nanofibers achieved by electrospinning were functionalized with signaling biomolecules and were tested in vitro and in vivo for nerve regeneration support. Silk fibroin (SF) extracted directly from silkworm cocoons was put in solution at a concentration of 10wt%. Poly(ethylene oxide) (PEO) was added to the resulting SF solution to increase solution viscosity and the following three electrospinning solutions were made: (1) SF/PEO solution, (2) SF/PEO solution with nerve growth factor and ciliary neurotrophic factor, and (3) SF/PEO solution with nerve growth factor and neurotrophin-3. Each of these solutions was electrospun into a multi-layer architecture to obtain mechanically optimized aligned nanofibrous mats. For in vitro studies, aligned fibers were treated to induce β-sheet formation and thoroughly rinsed to eliminate presence of PEO. Each material was tested using rat embryo neuron cultures to evaluate neurite extension and the interaction with bio-functionalized or non-functionalized aligned fibers. For in vivo studies, the mats were rolled into 5mm long multi-, micro-channeled conduits then treated and thoroughly rinsed. The conduits were each subsequently implanted between a severed rat sciatic nerve. The effectiveness of nerve repair over a period of 8 months was extensively evaluated by cross-referencing electrophysiological, histological, and movement analysis results to comprehensively evaluate the progression of nerve repair. In vitro results show a more favorable interaction between growing neurons and bio-functionalized silk fibers compared to pure silk fibers. Neurites can also be seen having extended unidirectionally along the alignment of the nanofibers which confirms a guidance factor for the electrospun material. The in vivo study has produced positive results for the regeneration of the sciatic nerve over the length of the study, showing contrasts between the bio-functionalized material and the non-functionalized material along with comparisons to the experimental control. Nerve regeneration has been evaluated not only by histological analysis, but also by electrophysiological assessment and motion analysis of two separate natural movements. By studying these three components in parallel, the most comprehensive evaluation of nerve repair for the conduit designs can be made which can, therefore, more accurately depict their overall effectiveness. This work was supported by La Région Picardie and FEDER.

Keywords: electrospinning, nerve guidance conduit, peripheral nerve regeneration, silk fibroin

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Authors: Lauren A. Bailey, Amber R. Childs, Nicola C. James, Murray I. Duncan, Alexander Winkler, Warren M. Potts

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For the persistence of fished populations in the Anthropocene, it is critical to predict how fished populations will respond to the coupled threats of exploitation and climate change for adaptive management. The resilience of fished populations will depend on their capacity for physiological plasticity and acclimatization in response to environmental shifts. However, there is evidence for the selection of physiological traits by capture fisheries. Hence, fish populations may have a limited scope for the rapid expansion of their tolerance ranges or physiological adaptation under fishing pressures. To determine the physiological vulnerability of fished populations in the Anthropocene, the metabolic performance was compared between a fished and spatially protected Chrysoblephus laticeps population in response to thermal variability. Individual aerobic scope phenotypes were quantified using intermittent flow respirometry by comparing changes in energy expenditure of each individual at ecologically relevant temperatures, mimicking variability experienced as a result of upwelling and downwelling events. The proportion of high and low-performance individuals were compared between the fished and spatially protected population. The fished population had limited aerobic scope phenotype diversity and fewer high-performance phenotypes, resulting in a significantly lower aerobic scope curve across low (10 °C) and high (24 °C) thermal treatments. The performance of fished populations may be compromised with predicted future increases in cold upwelling events. This requires the conservation of the physiologically fittest individuals in spatially protected areas, which can recruit into nearby fished areas, as a climate resilience tool.

Keywords: climate change, fish physiology, metabolic shifts, over-fishing, respirometry

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Authors: Vincent Murray

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The glycopeptide bleomycin is used in the treatment of testicular cancer, Hodgkin's lymphoma, and squamous cell carcinoma. Bleomycin damages and cleaves DNA in human cells, and this is considered to be the main mode of action for bleomycin's anti-tumor activity. In particular, double-strand breaks are thought to be the main mechanism for the cellular toxicity of bleomycin. Using Illumina next-generation DNA sequencing techniques, the genome-wide sequence specificity of bleomycin-induced double-strand breaks was determined in human cells. The degree of bleomycin cleavage was also assessed at the transcription start sites (TSSs) of actively transcribed genes and compared with non-transcribed genes. It was observed that bleomycin preferentially cleaved at the TSSs of actively transcribed human genes. There was a correlation between the degree of this enhanced cleavage at TSSs and the level of transcriptional activity. Bleomycin cleavage is also affected by chromatin structure and at TSSs, the peaks of bleomycin cleavage were approximately 200 bp apart. This indicated that bleomycin was able to detect phased nucleosomes at the TSSs of actively transcribed human genes. The genome-wide cleavage pattern of the bleomycin analogues 6′-deoxy-BLM Z and zorbamycin was also investigated in human cells. As found for bleomycin, these bleomycin analogues also preferentially cleaved at the TSSs of actively transcribed human genes. The cytotoxicity (IC₅₀ values) of these bleomycin analogues was determined. It was found that the degree of enhanced cleavage at TSSs was inversely correlated with the IC₅₀ values of the bleomycin analogues. This suggested that the level of cleavage at the TSSs of actively transcribed human genes was important for the cytotoxicity of bleomycin and analogues. Hence this study provided a deeper understanding of the cellular processes involved in the cancer chemotherapeutic activity of bleomycin.

Keywords: anti-tumour activity, bleomycin analogues, chromatin structure, genome-wide study, Illumina DNA sequencing

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Authors: Eirini Konstanta, Cedric Gouedard, Aggeliki Delimitsou, Stefania Patera, Samuel Murray

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Introduction: Quality reference DNA standards (QRS) for molecular testing by next-generation sequencing (NGS) are essential for accurate quantitation of copy number variations (CNV) for germline and variant allelic frequencies (VAF) for somatic analyses. Objectives: Presently, several molecular analytics for oncology patients are reliant upon quantitative metrics. Test validation and standardisation are also reliant upon the availability of surrogate control materials allowing for understanding test LOD (limit of detection), sensitivity, specificity. We have developed a dual calibration platform allowing for QRS pairs to be included in analysed DNA samples, allowing for accurate quantitation of CNV and VAF metrics within and between patient samples. Methods: QRS™ blocks up to 500nt were designed for common NGS panel targets incorporating ≥ 2 identification tags (IDTDNA.com). These were analysed upon spiking into gDNA, somatic, and ctDNA using a proprietary CalSuite™ platform adaptable to common LIMS. Results: We demonstrate QRS™ calibration reproducibility spiked to 5–25% at ± 2.5% in gDNA and ctDNA. Furthermore, we demonstrate CNV and VAF within and between samples (gDNA and ctDNA) with the same reproducibility (± 2.5%) in a clinical sample of lung cancer and HBOC (EGFR and BRCA1, respectively). CNV analytics was performed with similar accuracy using a single pair of QRS calibrators when using multiple single targeted sequencing controls. Conclusion: Dual paired QRS™ calibrators allow for accurate and reproducible quantitative analyses of CNV, VAF, intrinsic sample allele measurement, inter and intra-sample measure not only simplifying NGS analytics but allowing for monitoring clinically relevant biomarker VAF across patient ctDNA samples with improved accuracy.

Keywords: calibrator, CNV, gene copy number, VAF

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Authors: Vincent Murray

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The chromatin structure at the transcription start sites (TSSs) of genes is very important in the control of gene expression. In order for gene expression to occur, the chromatin structure at the TSS has to be altered so that the transcriptional machinery can be assembled and RNA transcripts can be produced. In particular, the nucleosome structure and positioning around the TSS has to be changed. Bleomycin is utilized as an anti-tumor agent to treat Hodgkin's lymphoma, squamous cell carcinoma, and testicular cancer. Bleomycin produces DNA damage in human cells and DNA strand breaks, especially double-strand breaks, are thought to be responsible for the cancer chemotherapeutic activity of bleomycin. Bleomycin is a large glycopeptide with molecular weight of approximately 1500 Daltons and hence its DNA strand cleavage activity can be utilized as a probe of chromatin structure. In this project, Illumina next-generation DNA sequencing technology was used to determine the position of DNA double-strand breaks at the TSSs of genes in intact cells. In this genome-wide study, it was found that bleomycin cleavage preferentially occurred at the TSSs of actively transcribed human genes in comparison with non-transcribed genes. There was a correlation between the level of enhanced bleomycin cleavage at TSSs and the degree of transcriptional activity. In addition, bleomycin was able to determine the position of nucleosomes at the TSSs of human genes. Bleomycin analogues were also utilized as probes of chromatin structure at the TSSs of human genes. In a similar manner to bleomycin, the bleomycin analogues 6′-deoxy-BLM Z and zorbamycin preferentially cleaved at the TSSs of human genes. Interestingly this degree of enhanced TSS cleavage inversely correlated with the cytotoxicity (IC50 values) of BLM analogues. This indicated that the degree of cleavage by bleomycin analogues at the TSSs of human genes was very important in the cytotoxicity of bleomycin and analogues. It also provided a deeper insight into the mechanism of action of this cancer chemotherapeutic agent since actively transcribed genes were preferentially targeted.

Keywords: anti-cancer activity, chromatin structure, cytotoxicity, gene expression, next-generation DNA sequencing

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Authors: Dejen Alemu, Murray E. Jennex, Temtim Assefa

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Agriculture is the mainstay of the Ethiopian economy; however, the sector is dominated by smallholder farmers resulting in land fragmentation and suffering from low productivity. Due to these issues, much effort has been put into the transformation of the sector to bring about more sustainable rural economic development. Technological advancements have been applied for the betterment of farmers resulting in the design of tools that are potentially capable of supporting the agricultural sector; however, their use and relevance are still alien to the local rural communities. The notion of the creating, capturing and sharing of knowledge has also been repetitively raised by many international donor agencies to transform the sector, yet the most current approaches to knowledge dissemination focus on knowledge that originates from the western view of scientific rationality while overlooking the role of indigenous knowledge (IK). Therefore, in agricultural knowledge management system (KMS) development, the integration of IKS with scientific knowledge is a critical success factor. The present study aims to contribute in the discourse on how to best integrate scientific and IK in agricultural KMS development. The conceptual framework of the research is anchored in concepts drawn from the theory of situated learning in communities of practice (CoPs): knowledge brokering. Using the KMS development practices of Ethiopian agricultural transformation agency as a case area, this research employed an interpretive analysis using primary and secondary qualitative data acquired through in-depth semi-structured interviews and participatory observations. As a result, concepts are identified for understanding the integration of the two major knowledge systems (i.e., indigenous and scientific knowledge) and participation of relevant stakeholders in particular the local farmers in agricultural KMS development through the roles of extension agent as a knowledge broker including crossing boundaries, in-between position, translation and interpretation, negotiation, and networking. The research shall have a theoretical contribution in addressing the incorporation of a variety of knowledge systems in agriculture and practically to provide insight for policy makers in agriculture regarding the importance of IK integration in agricultural KMS development and support marginalized small-scale farmers.

Keywords: communities of practice, indigenous knowledge, knowledge management system development, knowledge brokering

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Authors: R. O’Reilly Meehan, D. B. Murray

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In many practical situations, bubbles are dispersed in a liquid phase. Understanding these complex bubbly flows is therefore a key issue for applications such as shell and tube heat exchangers, mineral flotation and oxidation in water treatment. Although a large body of work exists for bubbles rising in an unbounded medium, that of bubbles rising in constricted geometries has received less attention. The particular case of a bubble sliding underneath an inclined surface is common to two-phase flow systems. The current study intends to expand this knowledge by performing experiments to quantify the streamwise flow structures associated with a single sliding air bubble under an inclined surface in quiescent water. This is achieved by means of two-dimensional, two-component particle image velocimetry (PIV), performed with a continuous wave laser and high-speed camera. PIV vorticity fields obtained in a plane perpendicular to the sliding surface show that there is significant bulk fluid motion away from the surface. The associated momentum of the bubble means that this wake motion persists for a significant time before viscous dissipation. The magnitude and direction of the flow structures in the streamwise measurement plane are found to depend on the point on its path through which the bubble enters the plane. This entry point, represented by a phase angle, affects the nature and strength of the vortical structures. This study reconstructs the vorticity field in the wake of the bubble, converting the field at different instances in time to slices of a large-scale wake structure. This is, in essence, Taylor’s ”frozen turbulence” hypothesis. Applying this to the vorticity fields provides a pseudo three-dimensional representation from 2-D data, allowing for a more intuitive understanding of the bubble wake. This study provides insights into the complex dynamics of a situation common to many engineering applications, particularly shell and tube heat exchangers in the nucleate boiling regime.

Keywords: bubbly flow, particle image velocimetry, two-phase flow, wake structures

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Authors: Yun Chen, Qihang Liu, Catherine Ticehurst, Chandrama Sarker, Fazlul Karim, Dave Penton, Ashmita Sengupta

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The application of ICESAT-2 altimetry data in river hydrology critically depends on the accuracy of the mean water surface elevation (WSE) at a virtual station (VS) where satellite observations intersect with water. The ICESAT-2 track generates multiple VSs as it crosses the different water bodies. The difficulties are particularly pronounced in large river basins where there are many tributaries and meanders often adjacent to each other. One challenge is to split photon segments along a beam to accurately partition them to extract only the true representative water height for individual elements. As far as we can establish, there is no automated procedure to make this distinction. Earlier studies have relied on human intervention or river masks. Both approaches are unsatisfactory solutions where the number of intersections is large, and river width/extent changes over time. We describe here an automated approach called “auto-segmentation”. The accuracy of our method was assessed by comparison with river water level observations at 10 different stations on 37 different dates along the Lower Murray River, Australia. The congruence is very high and without detectable bias. In addition, we compared different outlier removal methods on the mean WSE calculation at VSs post the auto-segmentation process. All four outlier removal methods perform almost equally well with the same R2 value (0.998) and only subtle variations in RMSE (0.181–0.189m) and MAE (0.130–0.142m). Overall, the auto-segmentation method developed here is an effective and efficient approach to deriving accurate mean WSE at river VSs. It provides a much better way of facilitating the application of ICESAT-2 ATL13 altimetry to rivers compared to previously reported studies. Therefore, the findings of our study will make a significant contribution towards the retrieval of hydraulic parameters, such as water surface slope along the river, water depth at cross sections, and river channel bathymetry for calculating flow velocity and discharge from remotely sensed imagery at large spatial scales.

Keywords: lidar sensor, virtual station, cross section, mean water surface elevation, beam/track segmentation

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Authors: Preetham Shankapal, Jill King, Kori Murray, Corby Martin, Paula Giselman, Jason Hicks, Owen Carmicheal

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Activation of reward and satiety networks in the brain while processing palatable food cues, as well as functional connectivity during rest has been studied using functional Magnetic Resonance Imaging of the brain in various obesity phenotypes. However, functional connectivity within the reward and satiety network during food cue processing is understudied. 14 obese individuals underwent two fMRI scans during viewing of Macronutrient Picture System images. Each scan included two blocks of images of High Sugar/High Fat (HSHF), High Carbohydrate/High Fat (HCHF), Low Sugar/Low Fat (LSLF) and also non-food images. Seed voxels within seven food reward relevant ROIs: Insula, putamen and cingulate, precentral, parahippocampal, medial frontal and superior temporal gyri were isolated based on a prior meta-analysis. Beta series correlation for task-related functional connectivity between these seed voxels and the rest of the brain was computed. Voxel-level differences in functional connectivity were calculated between: first and the second scan; individuals who saw novel (N=7) vs. Repeated (N=7) images in the second scan; and between the HC/HF, HSHF blocks vs LSLF and non-food blocks. Computations and analysis showed that during food image viewing, reward network ROIs showed significant functional connectivity with each other and with other regions responsible for attentional and motor control, including inferior parietal lobe and precentral gyrus. These functional connectivity values were heightened among individuals who viewed novel HS/HF images in the second scan. In the second scan session, functional connectivity was reduced within the reward network but increased within attention, memory and recognition regions, suggesting habituation to reward properties and increased recollection of previously viewed images. In conclusion it can be inferred that Functional Connectivity within reward network and between reward and other brain regions, varies by important experimental conditions during food photography viewing, including habituation to shown foods.

Keywords: fMRI, functional connectivity, task-based, beta series correlation

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Authors: Erick R. Bandala, Kebret Kebede, Nicole Johnson, Rebecca Murray, Destiny Green, John Mejia, Polioptro Martinez-Austria

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Summertemperature data from Clark County was collected and used to estimate two different heat-related indexes: the heat index (HI) and excess heat factor (EHF). These two indexes were used jointly with data of health-related deaths in Clark County to assess the effect of extreme heat on the exposed population. The trends of the heat indexes were then analyzed for the 2007-2016 decadeandthe correlation between heat wave episodes and the number of heat-related deaths in the area was estimated. The HI showed that this value has increased significantly in June, July, and August over the last ten years. The same trend was found for the EHF, which showed a clear increase in the severity and number of these events per year. The number of heat wave episodes increased from 1.4 per year during the 1980-2016 period to 1.66 per yearduring the 2007-2016 period. However, a different trend was found for heat-wave-event duration, which decreasedfrom an average of 20.4 days during the trans-decadal period (1980-2016) to 18.1 days during the most recent decade(2007-2016). The number of heat-related deaths was also found to increase from 2007 to 2016, with 2016 with the highest number of heat-related deaths. Both HI and the number of deaths showeda normal-like distribution for June, July, and August, with the peak values reached in late July and early August. The average maximum HI values better correlated with the number of deaths registered in Clark County than the EHF, probably because HI uses the maximum temperature and humidity in its estimation,whereas EHF uses the average medium temperature. However, it is worth testing the EHF of the study zone because it was reported to fit properly in the case of heat-related morbidity. For the overall period, 437 heat-related deaths were registered in Clark County, with 20% of the deaths occurring in June, 52% occurring in July, 18% occurring in August,and the remaining 10% occurring in the other months of the year. The most vulnerable subpopulation was people over 50 years old, for which 76% of the heat-related deaths were registered.Most of the cases were associated with heart disease preconditions. The second most vulnerable subpopulation was young adults (20-50), which accounted for 23% of the heat-related deaths. These deathswere associated with alcoholic/illegal drug intoxication.

Keywords: heat, health, hazards, workforce

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Authors: Murray Matarab Konzang

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Lae Port Development Project, Four Lane Highway and other development in the extraction industry which have direct road link to Lae City are predicted to have significant impact on its road network system. This paper evaluates Lae roads improvement program with forecast on planning, economic and the installation of bypasses to ease congestion, effective and convenient transport service for bulk goods and reduce travel time. Land-use transportation study and plans for local area traffic management scheme will be considered. City roads are faced with increased number of traffic and some inadequate road pavement width, poor transport plans, and facilities to meet this transportation demand. Lae also has drainage system which might not hold a 100 year flood. Proper evaluation, plan, design and intersection analysis is needed to evaluate road network system thus recommend improvement and estimate future growth. Repetitive and cyclic loading by heavy commercial vehicles with different axle configurations apply on the flexible pavement which weakens and tear the pavement surface thus small cracks occur. Rain water seeps through and overtime it creates potholes. Effective planning starts from experimental research and appropriate design standards to enable firm embankment, proper drains and quality pavement material. This paper will address traffic problems as well as road pavement, capacities of intersections, and pedestrian flow during peak hours. The outcome of this research will be to identify heavily trafficked road sections and recommend treatments to reduce traffic congestions, road classification, and proposal for bypass routes and improvement. First part of this study will describe transport or traffic related problems within the city. Second part would be to identify challenges imposed by traffic and road related problems and thirdly to recommend solutions after the analyzing traffic data that will indicate current capacities of road intersections and finally recommended treatment for improvement and future growth.

Keywords: Lae, road network, highway, vehicle traffic, planning

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Authors: Murray L. Ireland, Kevin J. Worrall, Rebecca Mackenzie, Thaleia Flessa, Euan McGookin, Douglas Thomson

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Robotic rovers which are designed to work in extra-terrestrial environments present a unique challenge in terms of the reliability and availability of systems throughout the mission. Should some fault occur, with the nearest human potentially millions of kilometres away, detection and identification of the fault must be performed solely by the robot and its subsystems. Faults in the system sensors are relatively straightforward to detect, through the residuals produced by comparison of the system output with that of a simple model. However, faults in the input, that is, the actuators of the system, are harder to detect. A step change in the input signal, caused potentially by the loss of an actuator, can propagate through the system, resulting in complex residuals in multiple outputs. These residuals can be difficult to isolate or distinguish from residuals caused by environmental disturbances. While a more complex fault detection method or additional sensors could be used to solve these issues, an alternative is presented here. Using inverse simulation (InvSim), the inputs and outputs of the mathematical model of the rover system are reversed. Thus, for a desired trajectory, the corresponding actuator inputs are obtained. A step fault near the input then manifests itself as a step change in the residual between the system inputs and the input trajectory obtained through inverse simulation. This approach avoids the need for additional hardware on a mass- and power-critical system such as the rover. The InvSim fault detection method is applied to a simple four-wheeled rover in simulation. Additive system faults and an external disturbance force and are applied to the vehicle in turn, such that the dynamic response and sensor output of the rover are impacted. Basic model-based fault detection is then employed to provide output residuals which may be analysed to provide information on the fault/disturbance. InvSim-based fault detection is then employed, similarly providing input residuals which provide further information on the fault/disturbance. The input residuals are shown to provide clearer information on the location and magnitude of an input fault than the output residuals. Additionally, they can allow faults to be more clearly discriminated from environmental disturbances.

Keywords: fault detection, ground robot, inverse simulation, rover

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Authors: Meghan E. Murray, Carri R. Tolmie

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This study aims to identify potential factors and widely applicable best practices that can contribute to improving corporate social responsibility (CSR) and corporate performance for firms by exploring the relationship between transformational leadership, spiritual intelligence, and emotional intelligence. Corporate social responsibility is when companies are cognizant of the impact of their actions on the economy, their communities, the environment, and the world as a whole while executing business practices accordingly. The prevalence of CSR has continuously strengthened over the past few years and is now a common practice in the business world, with such efforts coinciding with what stakeholders and the public now expect from corporations. Because of this, it is extremely important to be able to pinpoint factors and best practices that can improve CSR within corporations. One potential factor that may lead to improved CSR is spiritual intelligence (SQ), or the ability to recognize and live with a purpose larger than oneself. Spiritual intelligence is a measurable skill, just like emotional intelligence (EQ), and can be improved through purposeful and targeted coaching. This research project consists of two studies. Study 1 is a case study comparison of a benefit corporation and a non-benefit corporation. This study will examine the role of SQ and EQ as moderators in the relationship between the transformational leadership of employees within each company and the perception of each firm’s CSR and corporate performance. Project methodology includes creating and administering a survey comprised of multiple pre-established scales on transformational leadership, spiritual intelligence, emotional intelligence, CSR, and corporate performance. Multiple regression analysis will be used to extract significant findings from the collected data. Study 2 will dive deeper into spiritual intelligence itself by analyzing pre-existing data and identifying key relationships that may provide value to companies and their stakeholders. This will be done by performing multiple regression analysis on anonymized data provided by Deep Change, a company that has created an advanced, proprietary system to measure spiritual intelligence. Based on the results of both studies, this research aims to uncover best practices, including the unique contribution of spiritual intelligence, that can be utilized by organizations to help enhance their corporate social responsibility. If it is found that high spiritual and emotional intelligence can positively impact CSR effort, then corporations will have a tangible way to enhance their CSR: providing targeted employees with training and coaching to increase their SQ and EQ.

Keywords: corporate social responsibility, CSR, corporate performance, emotional intelligence, EQ, spiritual intelligence, SQ, transformational leadership

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Authors: Oday A. Al-Juhaishi, Sa`ad M. Ismail, Hung-Hsun Yen, Christina M. Murray, Helen M. S. Davies

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The functional anatomy of the fascia in the greyhound is still poorly understood, and incompletely described. The basic knowledge of fascia stems mainly from anatomical, histological and ultrastructural analyses. In this study, twelve specimens of hindlimbs from six fresh greyhound cadavers (3 male, 3 female) were used to examine the topographical relationships of the superficial fascia with the skin and underlying tissue. The first incision was made along the dorsal midline from the level of the thoracolumbar junction caudally to the level of the mid sacrum. The second incision was begun at the level of the first incision and extended along the midline of the lateral aspect of the hindlimb distally, to just proximal to the tarsus, and, the skin margins carefully separated to observe connective tissue links between the skin and superficial fascia, attachment points of the fascia and the relationships of the fascia with blood vessels that supply the skin. A digital camera was used to record the anatomical features as they were revealed. The dissections identified fibrous septa connecting the skin with the superficial fascia and deep fascia in specific areas. The presence of the adipose tissue was found to be very rare within the superficial fascia in these specimens. On the extensor aspects of some joints, a fusion between the superficial fascia and deep fascia was observed. This fusion created a subcutaneous bursa in the following areas: a prepatellar bursa of the stifle, a tarsal bursa caudal to the calcaneus bone, and an ischiatic bursa caudal to the ischiatic tuberosity. The evaluation of blood vessels showed that the perforating vessels passed through fibrous septa in a perpendicular direction to supply the skin, with the largest branch noted in the gluteal area. The attachment points between the superficial fascia and skin were mainly found in the region of the flexor aspect of the joints, such as caudal to the stifle joint. The numerous fibrous septa between the superficial fascia and skin that have been identified in some areas, may create support for the blood vessels that penetrate fascia and into the skin, while allowing for movement between the tissue planes. The subcutaneous bursae between the skin and the superficial fascia where it is fused with the deep fascia may be useful to decrease friction between moving areas. The adhesion points may be related to the integrity and loading of the skin. The attachment points fix the skin and appear to divide the hindlimb into anatomical compartments.

Keywords: attachment points, fibrous septa, greyhound, subcutaneous bursa, superficial fascia

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Authors: Dejen Alemu, Murray E. Jennex, Temtim Assefa

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This paper is investigated to understand the design, the use, and the consequence of Knowledge Management System (KMS) for knowledge systems sharing and integration. A KMS for knowledge systems sharing and integration is designed to meet the challenges raised by knowledge management researchers and practitioners: the technical, the human, and social factors. Agricultural KMS involves various members coming from different Communities of Practice (CoPs) who possess their own knowledge of multiple practices which need to be combined in the system development. However, the current development of the technology ignored the indigenous knowledge of the local communities, which is the key success factor for agriculture. This research employed the multi-methodological approach to KMS research in action research perspective which consists of four strategies: theory building, experimentation, observation, and system development. Using the KMS development practice of Ethiopian agricultural transformation agency as a case study, this research employed an interpretive analysis using primary qualitative data acquired through in-depth semi-structured interviews and participant observations. The Orlikowski's structuration model of technology has been used to understand the design, the use, and the consequence of the KMS. As a result, the research identified three basic components for the architecture of the shared KMS, namely, the people, the resources, and the implementation subsystems. The KMS were developed using web 2.0 tools to promote knowledge sharing and integration among diverse groups of users in a distributed environment. The use of a shared KMS allows users to access diverse knowledge from a number of users in different groups of participants, enhances the exchange of different forms of knowledge and experience, and creates high interaction and collaboration among participants. The consequences of a shared KMS on the social system includes, the elimination of hierarchical structure, enhance participation, collaboration, and negotiation among users from different CoPs having common interest, knowledge and skill development, integration of diverse knowledge resources, and the requirement of policy and guideline. The research contributes methodologically for the application of system development action research for understanding a conceptual framework for KMS development and use. The research have also theoretical contribution in extending structuration model of technology for the incorporation of variety of knowledge and practical implications to provide management understanding in developing strategies for the potential of web 2.0 tools for sharing and integration of indigenous knowledge.

Keywords: communities of practice, indigenous knowledge, participation, structuration model of technology, Web 2.0 tools

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Authors: Lauren A. Bailey, Amber R. Childs, Nicola C. James, Murray I. Duncan, Alexander Winkler, Warren M. Potts

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Changes in behaviour and physiology are the most important responses of marine life to anthropogenic impacts such as climate change and over-fishing. Behavioural changes (such as a shift in distribution or changes in phenology) can ensure that a species remains in an environment suited for its optimal physiological performance. However, if marine life is unable to shift their distribution, they are reliant on physiological adaptation (either by broadening their metabolic curves to tolerate a range of stressors or by shifting their metabolic curves to maximize their performance at extreme stressors). However, since there are links between fish physiology and behaviour, changes to either of these traits may have reciprocal interactions. This paper reviews the current knowledge of the links between the behaviour and physiology of fishes, discusses these in the context of exploitation and climate change, and makes recommendations for future research needs. The review revealed that our understanding of the links between fish behaviour and physiology is rudimentary. However, both are hypothesized to be linked to stress responses along the hypothalamic pituitary axis. The link between physiological capacity and behaviour is particularly important as both determine the response of an individual to a changing climate and are under selection by fisheries. While it appears that all types of capture fisheries are likely to reduce the adaptive potential of fished populations to climate stressors, angling, which is primarily associated with recreational fishing, may induce fission of natural populations by removing individuals with bold behavioural traits and potentially the physiological traits required to facilitate behavioural change. Future research should focus on assessing how the links between physiological capacity and behaviour influence catchability, the response to climate change drivers, and post-release recovery. The plasticity of phenotypic traits should be examined under a range of stressors of differing intensity in several species and life history stages. Future studies should also assess plasticity (fission or fusion) in the phenotypic structuring of social hierarchy and how this influences habitat selection. Ultimately, to fully understand how physiology is influenced by the selective processes driven by fisheries, long-term monitoring of the physiological and behavioural structure of fished populations, their fitness, and catch rates are required.

Keywords: climate change, metabolic shifts, over-fishing, phenotypic plasticity, stress response

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Authors: Joni Asitashvili, Eka Chabashvili, Maya Virsaladze, Alexander Chokhonelidze

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Studying the soundscape is a major challenge in many countries of the civilized world today. The sound environment and music itself are part of the Earth's ecosystem. Therefore, researching its positive or negative impact is important for a clean and healthy environment. The acoustics of nature gave people many musical ideas, and people enriched musical features and performance skills with the ability to imitate the surrounding sound. For example, a population surrounded by mountains invented the technique of antiphonal singing, which mimics the effect of an echo. Canadian composer Raymond Murray Schafer viewed the world as a kind of musical instrument with ever-renewing tuning. He coined the term "Soundscape" as a name of a natural environmental sound, including the sound field of the Earth. It can be said that from which the “music of nature” is constructed. In the 21st century, a new field–Ecomusicology–has emerged in the field of musical art to study the sound ecosystem and various issues related to it. Ecomusicology considers the interconnections between music, culture, and nature–According to the Aaron Allen. Eco-music is a field of ecomusicology concerning with the depiction and realization of practical processes using modern composition techniques. Finding an artificial sound source (instrumental or electronic) for the piece that will blend into the soundscape of Sound Oases. Creating a composition, which sounds in harmony with the vibrations of human, nature, environment, and micro- macrocosm as a whole; Currently, we are exploring the ambient sound of the Georgian urban and suburban environment to discover “Sound Oases" and compose Eco-music works. We called “Sound Oases" an environment with a specific sound of the ecosystem to use in the musical piece as an instrument. The most interesting examples of Eco-music are the round dances, which were already created in the BC era. In round dances people would feel the united energy. This urge to get united revealed itself in our age too, manifesting itself in a variety of social media. The virtual world, however, is not enough for a healthy interaction; we created plan of “contemporary round dance” in sound oasis, found during expedition in Georgian caves, where people interacted with cave's soundscape and eco-music, they feel each other sharing energy and listen to earth sound. This project could be considered a contemporary round dance, a long improvisation, particular type of art therapy, where everyone can participate in an artistic process. We would like to present research result of our eco-music experimental performance.

Keywords: eco-music, environment, sound, oasis

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Authors: Parker Murray, Marci Johnson, Tyson S. Burnham, Alina K. Fong, Mark D. Allen, Bruce McIff

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Purpose: Pathological dysregulation of Neurovascular Coupling (NVC) caused by mild traumatic brain injury (mTBI) is the predominant source of chronic post-concussion syndrome (PCS) symptomology. fNCI has the ability to localize dysregulation in NVC by measuring blood-oxygen-level-dependent (BOLD) signaling during the performance of fMRI-adapted neuropsychological evaluations. With fNCI, 57 brain areas consistently affected by concussion were identified as PCS neural markers, which were validated on large samples of concussion patients and healthy controls. These neuromarkers provide the basis for a computation of PCS severity which is referred to as the Severity Index Score (SIS). The SIS has proven valuable in making pre-treatment decisions, monitoring treatment efficiency, and assessing long-term stability of outcomes. Methods and Materials: After being scanned while performing various cognitive tasks, 476 concussed patients received an SIS score based on the neural dysregulation of the 57 previously identified brain regions. These scans provide an objective measurement of attentional, subcortical, visual processing, language processing, and executive functioning abilities, which were used as biomarkers for post-concussive neural dysregulation. Initial SIS scores were used to develop individualized therapy incorporating cognitive, occupational, and neuromuscular modalities. These scores were also used to establish pre-treatment benchmarks and measure post-treatment improvement. Results: Changes in SIS were calculated in percent change from pre- to post-treatment. Patients showed a mean improvement of 76.5 percent (σ= 23.3), and 75.7 percent of patients showed at least 60 percent improvement. Longitudinal reassessment of 24 of the patients, measured an average of 7.6 months post-treatment, shows that SIS improvement is maintained and improved, with an average of 90.6 percent improvement from their original scan. Conclusions: fNCI provides a reliable measurement of NVC allowing for identification of concussion pathology. Additionally, fNCI derived SIS scores direct tailored therapy to restore NVC, subsequently resolving chronic PCS resulting from mTBI.

Keywords: concussion, functional magnetic resonance imaging (fMRI), neurovascular coupling (NVC), post-concussion syndrome (PCS)

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Authors: R. Blythman, N. Jeffers, T. Persoons, D. B. Murray

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The exploitation of flow pulsation in micro- and mini-channels is a potentially useful technique for enhancing cooling of high-end photonics and electronics systems. It is thought that pulsation alters the thickness of the hydrodynamic and thermal boundary layers, and hence affects the overall thermal resistance of the heat sink. Although the fluid mechanics and heat transfer are inextricably linked, it can be useful to decouple the parameters to better understand the mechanisms underlying any heat transfer enhancement. Using two-dimensional, two-component particle image velocimetry, the current work intends to characterize the heat transfer mechanisms in pulsating flow with a mean Reynolds number of 48 by experimentally quantifying the hydrodynamics of a generic liquid-cooled channel geometry. Flows circulated through the test section by a gear pump are modulated using a controller to achieve sinusoidal flow pulsations with Womersley numbers of 7.45 and 2.36 and an amplitude ratio of 0.75. It is found that the transient characteristics of the measured velocity profiles are dependent on the speed of oscillation, in accordance with the analytical solution for flow in a rectangular channel. A large velocity overshoot is observed close to the wall at high frequencies, resulting from the interaction of near-wall viscous stresses and inertial effects of the main fluid body. The steep velocity gradients at the wall are indicative of augmented heat transfer, although the local flow reversal may reduce the upstream temperature difference in heat transfer applications. While unsteady effects remain evident at the lower frequency, the annular effect subsides and retreats from the wall. The shear rate at the wall is increased during the accelerating half-cycle and decreased during deceleration compared to steady flow, suggesting that the flow may experience both enhanced and diminished heat transfer during a single period. Hence, the thickness of the hydrodynamic boundary layer is reduced for positively moving flow during one half of the pulsation cycle at the investigated frequencies. It is expected that the size of the thermal boundary layer is similarly reduced during the cycle, leading to intervals of heat transfer enhancement.

Keywords: Heat transfer enhancement, particle image velocimetry, localized and time-resolved velocity, photonics and electronics cooling, pulsating flow, Richardson’s annular effect

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Authors: Murray Anderson, Galina Freed, Karli Jahn

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Trauma is increasingly recognized as an important construct that has health implications for those who struggle with various mental health issues. For those individuals who meet the criteria for a diagnosis of hoarding disorder (HD), many have experienced some form of trauma. Further, some of the therapeutic interventions for those with HD can further perpetuate or magnify the experience of trauma. Therefore, the aim of this scoping review is to identify and document the nature and extent of research evidence related to trauma as it connects with HD. This review was guided by the questions, ‘How can our understanding of the trauma cycle help us to better appreciate the experiences of individuals who hoard, and how will a trauma informed lens inform the interventions for hoarding disorder? A comprehensive literature search was performed to identify original studies that contained the words “hoarding” and “trauma.” PsychINFO”,''EBSCO host,” “CINAHL” and “PubMed” were searched between January 2005 and April 2021. Articles were screened by three reviewers. Data extracted included publication date, demographics, study design, type of analysis, and noted connections between hoarding and trauma. Of the 329 articles, all duplicates, articles on hoardings of animals, articles not in English, and those without full-text availability were removed. Five categories were found in the remaining 45 articles, including (a) traumatic and stressful life events; (b) the link between posttraumatic stress disorder, trauma, and hoarding; (c) the relationships between different comorbidities, trauma, and hoarding; (d) the lack of early emotional expression and other forms of parental deprivation; and (e) the role of attachment. Lastly, the literature explains how the links between hoarding and trauma are difficult to study due to the highly stigmatized identities with this population. The review provided strong support for the connections between the experience of trauma and HD. What is missing from the literature is the use of a trauma-informed lens to better account for the ways in which hoarding disorder is understood. Other missing pieces in the literature are the potential uses of a trauma-informed lens to enhance the therapeutic process, to understand and reduce treatment attrition, and to improve treatment outcomes. The application of a trauma informed lens could improve our understanding of effective interactions among clients, families, and communities and improve the education around hoarding-related matters. Exploring the connections between trauma and HD can improve therapeutic delivery and destigmatize the experience of dealing with clutter and hoarding concerns. This awareness can also provide health care professionals with both the language and skills to liberate them from a reductionist view on HD.

Keywords: hoarding, attachment, parental deprivation, trauma

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Authors: Olivia A. Wilson, Hannah E. Power, Murray Kendall

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Sydney Harbour is an iconic location with a dense population and low-lying development. On the east coast of Australia, facing the Pacific Ocean, it is exposed to several tsunamigenic trenches. This paper presents a component of the most detailed assessment of the potential for earthquake-generated tsunami impact on Sydney Harbour to date. Models in this study use dynamic tides to account for tide-tsunami interaction. Sydney Harbour’s tidal range is 1.5 m, and the spring tides from January 2015 that are used in the modelling for this study are close to the full tidal range. The tsunami wave trains modelled include hypothetical tsunami generated from earthquakes of magnitude 7.5, 8.0, 8.5, and 9.0 M_W from the Puysegur and New Hebrides trenches as well as representations of the historical 1960 Chilean and 2011 Tohoku events. All wave trains are modelled for the peak wave to coincide with both a low tide and a high tide. A single wave train, representing a 9.0 M_W earthquake at the Puysegur trench, is modelled for peak waves to coincide with every hour across a 12-hour tidal phase. Using the hydrodynamic model ANUGA, results are compared according to the impact parameters of inundation area, depth variation and current speeds. Results show that both maximum inundation area and depth variation are tide dependent. Maximum inundation area increases when coincident with a higher tide, however, hazardous inundation is only observed for the larger waves modelled: NH90high and P90high. The maximum and minimum depths are deeper on higher tides and shallower on lower tides. The difference between maximum and minimum depths varies across different tidal phases although the differences are slight. Maximum current speeds are shown to be a significant hazard for Sydney Harbour; however, they do not show consistent patterns according to tide-tsunami phasing. The maximum current speed hazard is shown to be greater in specific locations such as Spit Bridge, a narrow channel with extensive marine infrastructure. The results presented for Sydney Harbour are novel, and the conclusions are consistent with previous modelling efforts in the greater area. It is shown that tide must be a consideration for both tsunami modelling and emergency management planning. Modelling with peak tsunami waves coinciding with a high tide would be a conservative approach; however, it must be considered that maximum current speeds may be higher on other tides.

Keywords: emergency management, sydney, tide-tsunami interaction, tsunami impact

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Authors: Murray David Schane

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Though years of clinical encounters with patients with autism spectrum disorders and those with a schizoid personality the many defining diagnostic features shared between these conditions have been explored and current neurobiological differences have been reviewed; and, critical and different treatment strategies for each have been devised. The paper compares and contrasts the apparent similarities between autism spectrum disorders and the schizoid personality are found in these DSM descriptive categories: restricted range of social-emotional reciprocity; poor non-verbal communicative behavior in social interactions; difficulty developing and maintaining relationships; detachment from social relationships; lack of the desire for or enjoyment of close relationships; and preference for solitary activities. In this paper autism, fundamentally a communicative disorder, is revealed to present clinically as a pervasive aversive response to efforts to engage with or be engaged by others. Autists with the Asperger presentation typically have language but have difficulty understanding humor, irony, sarcasm, metaphoric speech, and even narratives about social relationships. They also tend to seek sameness, possibly to avoid problems of social interpretation. Repetitive behaviors engage many autists as a screen against ambient noise, social activity, and challenging interactions. Also in this paper, the schizoid personality is revealed as a pattern of social avoidance, self-sufficiency and apparent indifference to others as a complex psychological defense against a deep, long-abiding fear of appropriation and perverse manipulation. Neither genetic nor MRI studies have yet located the explanatory data that identifies the cause or the neurobiology of autism. Similarly, studies of the schizoid have yet to group that condition with those found in schizophrenia. Through presentations of clinical examples, the treatment of autists of the Asperger type is revealed to address the autist’s extreme social aversion which also precludes the experience of empathy. Autists will be revealed as forming social attachments but without the capacity to interact with mutual concern. Empathy will be shown be teachable and, as social avoidance relents, understanding of the meaning and signs of empathic needs that autists can recognize and acknowledge. Treatment of schizoids will be shown to revolve around joining empathically with the schizoid’s apprehensions about interpersonal, interactive proximity. Models of both autism and schizoid personality traits have yet to be replicated in animals, thereby eliminating the role of translational research in providing the kind of clues to behavioral patterns that can be related to genetic, epigenetic and neurobiological measures. But as these clinical examples will attest, treatment strategies have significant impact.

Keywords: autism spectrum, schizoid personality traits, neurobiological implications, critical diagnostic distinctions

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Authors: Adae Amoako, Daniel Montero, Peter Murray, George Pujalte

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We present a case of a 42-year-old, right-handed Caucasian male who presented to a medical orthopedics clinic with left wrist pain. The patient indicated that the pain started two months prior to the visit. He could only remember helping a friend move furniture prior to the onset of pain. Examination of the left wrist showed limited extension compared to the right. There was clicking with flexion and extension of the wrist on the dorsal aspect. Mild tenderness was noticed over the distal radioulnar joint. There was ulnar and radial deviation on provocation. Initial 4-view x-rays of the left wrist showed mild radiocarpal and scapho-trapezium-trapezoid (ST-T) osteoarthritis, with subchondral cysts seen in the lunate and scaphoid, with no obvious fractures. The patient was initially put in a wrist brace and diclofenac topical gel was prescribed for pain control, as a patient could not take non-steroidal anti-inflammatory drugs (NSAIDs) due to gastritis. Despite diclofenac topical gel use and bracing, symptoms remained, and a steroid injection with 1 mL of lidocaine with 10 mg of triamcinolone acetonide was performed under fluoroscopy. He obtained some relief but after 3 months, the injection had to be repeated. On 2-month follow up after the initial evaluation, symptoms persisted. Magnetic resonance imaging (MRI) was obtained which showed an abnormal T1 hypodense signal involving the proximal pole of the scaphoid and articular collapse proximally of the scaphoid, with marked irregularity of the overlying cartilage, suggesting a remote injury, findings consistent with avascular necrosis of the proximal pole of the scaphoid. A month after that, the patient had the left proximal pole of the scaphoid debrided and an intercompartmental supraretinacular artery vascularized. Pedicle bone graft reconstruction of the proximal pole of the left scaphoid was done. A non-vascularized autograft from the left radius was also applied. He was put in a thumb spica cast with the interphalangeal joint free for 6 weeks. On 6-week follow-up after surgery, the patient was healing well and could make a composite fist with his left hand. The diagnosis of Preiser’s disease is primarily based on radiological findings. Due to the fact that necrosis happens over a period of time, most AVNs are diagnosed at the late stages of the disease. There appear to be no specific guidelines on the management AVN of the scaphoid. In the past, immobilization and arthroscopic debridement had been used. Radial osteotomy has also been tried. Vascularized bone grafts have also been used to treat Preiser’s disease. In our patient, we used three of these treatment modalities, starting with conservative management with topical NSAIDS and immobilization, then debridement with vascularized bone grafts.

Keywords: wrist pain, avascular necrosis of the scaphoid, Preiser’s disease, vascularized bone grafts

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Authors: A. Delimitsou, C. Gouedard, E. Konstanta, A. Koletis, S. Patera, E. Manou, K. Spaho, S. Murray

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Background: There remains a lack of International Standard Control Reference materials for Next Generation Sequencing-based approaches or device calibration. We have designed and validated dsDNA biomimetic reference materials for targeted such approaches incorporating proprietary motifs (patent pending) for device/test calibration. They enable internal single-sample calibration, alleviating sample comparisons to pooled historical population-based data assembly or statistical modelling approaches. We have validated such an approach for BRCA Copy Number Variation analytics using iQRS™-CNVSUITE versus Mixed Ligation-dependent Probe Amplification. Methods: Standard BRCA Copy Number Variation analysis was compared between mixed ligation-dependent probe amplification and next generation sequencing using a cohort of 198 breast/ovarian cancer patients. Next generation sequencing based copy number variation analysis of samples spiked with iQRS™ dsDNA biomimetics were analysed using proprietary CNVSUITE software. Mixed ligation-dependent probe amplification analyses were performed on an ABI-3130 Sequencer and analysed with Coffalyser software. Results: Concordance of BRCA – copy number variation events for mixed ligation-dependent probe amplification and CNVSUITE indicated an overall sensitivity of 99.88% and specificity of 100% for iQRS™-CNVSUITE. The negative predictive value of iQRS-CNVSUITE™ for BRCA was 100%, allowing for accurate exclusion of any event. The positive predictive value was 99.88%, with no discrepancy between mixed ligation-dependent probe amplification and iQRS™-CNVSUITE. For device calibration purposes, precision was 100%, spiking of patient DNA demonstrated linearity to 1% (±2.5%) and range from 100 copies. Traditional training was supplemented by predefining the calibrator to sample cut-off (lock-down) for amplicon gain or loss based upon a relative ratio threshold, following training of iQRS™-CNVSUITE using spiked iQRS™ calibrator and control mocks. BRCA copy number variation analysis using iQRS™-CNVSUITE™ was successfully validated and ISO15189 accredited and now enters CE-IVD performance evaluation. Conclusions: The inclusion of a reference control competitor (iQRS™ dsDNA mimetic) to next generation sequencing-based sequencing offers a more robust sample-independent approach for the assessment of copy number variation events compared to mixed ligation-dependent probe amplification. The approach simplifies data analyses, improves independent sample data analyses, and allows for direct comparison to an internal reference control for sample-specific quantification. Our iQRS™ biomimetic reference materials allow for single sample copy number variation analytics and further decentralisation of diagnostics to single patient sample assessment.

Keywords: validation, diagnostics, oncology, copy number variation, reference material, calibration

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Authors: Sahar El Shair, Laura Greco, William Reay, Murray Cairns

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Background: Rheumatoid arthritis (RA) is a chronic, systematic, inflammatory, autoimmune disease that involves damages to joints and erosions to the associated bones and cartilage, resulting in reduced physical function and disability. RA is a multifactorial disorder influenced by heterogenous genetic and environmental factors. Whilst different medications have proven successful in reducing inflammation associated with RA, they often come with significant side effects and limited efficacy. To address this, the novel pharmagenic enrichment score (PES) algorithm was tested in self-reported RA patients from the UK Biobank (UKBB), which is a cohort of predominantly European ancestry, and identified individuals with a high genetic risk in clinically actionable biological pathways to identify novel opportunities for precision interventions and drug repurposing to treat RA. Methods and materials: Genetic association data for rheumatoid arthritis was derived from publicly available genome-wide association studies (GWAS) summary statistics (N=97173). The PES framework exploits competitive gene set enrichment to identify pathways that are associated with RA to explore novel treatment opportunities. This data is then integrated into WebGestalt, Drug Interaction database (DGIdb) and DrugBank databases to identify existing compounds with existing use or potential for repurposed use. The PES for each of these candidates was then profiled in individuals with RA in the UKBB (Ncases = 3,719, Ncontrols = 333,160). Results A total of 209 pathways with known drug targets after multiple testing correction were identified. Several pathways, including interferon gamma signaling and TID pathway (which relates to a chaperone that modulates interferon signaling), were significantly associated with self-reported RA in the UKBB when adjusting for age, sex, assessment centre month and location, RA polygenic risk and 10 principal components. These pathways have a major role in RA pathogenesis, including autoimmune attacks against certain citrullinated proteins, synovial inflammation, and bone loss. Encouragingly, many also relate to the mechanism of action of existing RA medications. The analyses also revealed statistically significant association between RA polygenic scores and self-reported RA with individual PES scorings, highlighting the potential utility of the PES algorithm in uncovering additional genetic insights that could aid in the identification of individuals at risk for RA and provide opportunities for more targeted interventions. Conclusions In this study, pharmacologically annotated genetic risk was explored through the PES framework to overcome inter-individual heterogeneity and enable precision drug repurposing in RA. The results showed a statistically significant association between RA polygenic scores and self-reported RA and individual PES scorings for 3,719 RA patients. Interestingly, several enriched PES pathways were targeted by already approved RA drugs. In addition, the analysis revealed genetically supported drug repurposing opportunities for future treatment of RA with a relatively safe profile.

Keywords: rheumatoid arthritis, precision medicine, drug repurposing, system biology, bioinformatics

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