Search results for: Parker Murray

Authors: Martyn Queen, Diane Crone, Andrew Parker, Saul Bloxham

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Rationale: There is a growing body of evidence that supports the use of physical activity during and after cancer treatment. However, activity levels for patients remain low. As more cancer patients are treated successfully, and treatment costs continue to escalate, physical activity may be a promising adjunct to a person-centred healthcare approach to recovery. Aim: The aim was to further understand how physical activity may enhance the recovery process for a group of mixed-site cancer patients. Objectives: The research investigated longitudinal changes in physical activity and perceived the quality of life between two and six month’s post-exercise interventions. It also investigated support systems that enabled patients to sustain these perceived changes. Method: The respondent cohort comprised 14 mixed-site cancer patients aged 43-70 (11 women, 3 men), who participated in a two-phase physical activity intervention that took place at a university in the South West of England. Phase 1 consisted of an eight-week structured physical activity programme; Phase 2 consisted of four months of non-supervised physical activity. Semi-structured interviews took place three times over six months with each participant. Grounded theory informed the data collection and analysis which, in turn, facilitated theoretical development. Findings: Our findings propose three theories on the impact of physical activity for recovering cancer patients: 1) Knowledge gained through a structured exercise programme can enable recovering cancer patients to independently sustain physical activity to four-month follow-up. 2) Sustaining physical activity for six months promotes positive changes in the quality of life indicators of chronic fatigue, self-efficacy, the ability to self-manage and energy levels. 3) Peer support from patients facilitates adherence to a structured exercise programme and support from a spouse, or life partner facilitates independently sustained physical activity to four-month follow-up. Conclusions: This study demonstrates that qualitative research can provide an evidence base that could be used to support future care plans for cancer patients. Findings also demonstrate that a physical activity intervention can be effective at helping cancer patients recover from the side effects of their treatment, and recommends that physical activity should become an adjunct therapy alongside traditional cancer treatments.

Keywords: physical activity, health, cancer recovery, quality of life, support systems, qualitative, grounded theory, person-centred healthcare

Procedia PDF Downloads 255

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

Procedia PDF Downloads 74

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

Procedia PDF Downloads 327

Authors: E. O. Clarke, O. J. Aderinola, O. A. Adeboyejo, M. A. Anetekhai

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Aims: The study is aimed at establishing the influence of some physical and chemical parameters on the abundance, distribution pattern and seasonal variations of the planktonic crustacean populations. Place and Duration of Study: A premier investigation into the dynamics of planktonic crustacean populations in Ologe lagoon was carried out from January 2011 to December 2012. Study Design: The study covered identification, temporal abundance, spatial distribution and diversity of the planktonic crustacea. Methodology: Standard techniques were used to collect samples from eleven stations covering five proximal satellite towns (Idoluwo, Oto, Ibiye, Obele, and Gbanko) bordering the lagoon. Data obtained were statistically analyzed using linear regression and hierarchical clustering. Results:Thirteen (13) planktonic crustacean populations were identified. Total percentage abundance was highest for Bosmina species (20%) and lowest for Polyphemus species (0.8%). The Pearson’s correlation coefficient (“r” values) between total planktonic crustacean population and some physical and chemical parameters showed that positive correlations having low level of significance occurred with salinity (r = 0.042) (sig = 0.184) and with surface water dissolved oxygen (r = 0.299) (sig = 0.155). Linear regression plots indicated that, the total population of planktonic crustacea were mainly influenced and only increased with an increase in value of surface water temperature (Rsq = 0.791) and conductivity (Rsq = 0.589). The total population of planktonic crustacea had a near neutral (zero correlation) with the surface water dissolved oxygen and thus, does not significantly change with the level of the surface water dissolved oxygen. The correlations were positive with NO3-N (midstream) at Ibiye (Rsq =0.022) and (downstream) Gbanko (Rsq =0.013), PO4-P at Ibiye (Rsq =0.258), K at Idoluwo (Rsq =0.295) and SO4-S at Oto (Rsq = 0.094) and Gbanko (Rsq = 0.457). The Berger-Parker Dominance Index (BPDI) showed that the most dominant species was Bosmina species (BPDI = 1.000), followed by Calanus species (BPDI = 1.254). Clusters by squared Euclidan distances using average linkage between groups showed proximities, transcending the borders of genera. Conclusion: The results revealed that planktonic crustacean population in Ologe lagoon undergo seasonal perturbations, were highly influenced by nutrient, metal and organic matter inputs from river Owoh, Agbara industrial estate and surrounding farmlands and were patchy in spatial distribution.

Keywords: diversity, dominance, perturbations, richness, crustacea, lagoon

Procedia PDF Downloads 686

Authors: Guler D. Uzel, Andrew G. Parker, Robert L. Mach, Adly Abd-Alla

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Several tsetse fly species (Diptera: Glossinidae) in natural or colonized populations can be infected with the salivary gland hypertrophy virus (SGHV), a circular dsDNA virus (Hytrosaviridae). The virus infection is mainly asymptomatic but, in some species under certain conditions, the infection can produce salivary gland hypertrophy (SGH) symptoms. In the laboratory colonized tsetse, flies with SGH have reduced fertility, which negatively affects colony performance. Therefore, a high prevalence of SGH in insect mass rearing represents a major challenge for tsetse control using the sterile insect technique. The main objective of this study is to analyze the impact of Glossina pallidipes SGHV infection in various tsetse species on mortality and productivity and its impact on the symbiotic bacteria. Hypertropied salivary glands (SG) were collected from G. pallidipes into phosphate buffered saline (PBS) to prepare suspension; 2 µl aliquots were injected into adults of several tsetse species (G. pallidipes (Gp), G. p. gambiensis (Gpg), G. brevipalpis (Gb), G. morsitans morsitans (Gmm), G. morsitans centralis (Gmc) and G. fuscipes (Gf)) and the change in virus and symbiont titers were analyzed using qPCR. The development of SGH in the F1 was detected by dissection 10 days after emergence and virus infection was confirmed by PCR. The impact of virus infection on fly mortality and productivity was recorded. 2 µl aliquots were also injected into 3rd instar larvae of the different species and the adult SGs assayed by PCR for virus. Virus positive SGs from each species were homogenized in PBS and pooled within species for injection into larvae of the same species. Flies injected with PBS were used as control. Injecting teneral flies with SGHV caused increasing virus titer over time in all species but no SGH was detected. Dissection of the F1 also showed no development of SGH except in Gp (the homologous host). Injection of SGHV did not have any impact on the prevalence of the tsetse symbionts, but an increase in Sodalis titer was observed correlated with fly age regardless of virus infection. The virus infection had a negative impact on productivity and mortality. SGHV injection into larvae of the different species produced SGHV infected glands in the adults determined by PCR with a rate of 60%, 27%, 16%, 7% and 7% for Gp, Gf, Gpg, Gmm and Gmc, respectively. Virus positive SGs observed in the heterologous species were smaller than SGH found in Gp. No virus positive SG was detected by PCR in Gb and no SGH was observed in any adults except in Gp. Injecting virus suspension from the virus positive SGs into conspecific larvae did not produce any adults with infected SGs (except in Gp). SGHV can infect all tested tsetse species. Although the virus can infect and increase in titer in other tsetse species and affect fly mortality and productivity, no vertical virus transmission was observed in other tsetse species with might indicate a transmission barrier in these species, and virus collected from flies injected as larvae was not infective by injection.

Keywords: DNA viruses, glossina, hytrosaviridae, symbiotic bacteria, tsetse

Procedia PDF Downloads 183

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

Procedia PDF Downloads 275

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

Procedia PDF Downloads 97

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

Procedia PDF Downloads 309

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

Procedia PDF Downloads 226

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

Procedia PDF Downloads 89

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

Procedia PDF Downloads 34

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

Procedia PDF Downloads 319

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

Procedia PDF Downloads 93

Authors: Neha P. Amin, Maliha Zainib, Sean Parker, Malcolm Mattes

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Purpose/Objectives: Combination immunotherapy (IT) and radiation therapy (RT) is an actively growing field of clinical investigation due to promising findings of synergistic effects from immune-mediated mechanisms observed in preclinical studies and clinical data from case reports of abscopal effects. While there are many ongoing trials of combined IT-RT, there are still limited data on toxicity and outcome optimization regarding RT dose, fractionation, and sequencing of RT with IT. Nivolumab (NIVO), an anti-PD-1 monoclonal antibody, has been rapidly adopted in the clinic over the past 2 years, resulting in more patients being considered for concurrent RT-NIVO. Knowledge about the toxicity profile of combined RT-NIVO is important for both the patient and physician when making educated treatment decisions. The acute toxicity profile of concurrent RT-NIVO was analyzed in this study. Materials/Methods: A retrospective review of all consecutive patients who received NIVO from 1/2015 to 5/2017 at 4 separate centers within two separate institutions was performed. Those patients who completed a course of RT from 1 day prior to initial NIVO infusion through 1 month after last NIVO infusion were considered to have received concurrent therapy and included in the subsequent analysis. Descriptive statistics are reported for patient/tumor/treatment characteristics and observed acute toxicities within 3 months of RT completion. Results: Among 261 patients who received NIVO, 46 (17.6%) received concurrent RT to 67 different sites. The median f/u was 3.3 (.1-19.8) months, and 11/46 (24%) were still alive at last analysis. The most common histology, RT prescription, and treatment site included non-small cell lung cancer (23/46, 50%), 30 Gy in 10 fractions (16/67, 24%), and central thorax/abdomen (26/67, 39%), respectively. 79% (53/67) of irradiated sites were treated with 3D-conformal technique and palliative dose-fractionation. Grade 3, 4, and 5 toxicities were experienced by 11, 1, and 2 patients, respectively. However all grade 4 and 5 toxicities were outside of the irradiated area and attributed to the NIVO alone, and only 4/11 (36%) of the grade 3 toxicities were attributed to the RT-NIVO. The irradiated site in these cases included the brain [2/10 (20%)] and central thorax/abdomen [2/19 (10.5%)], including one unexpected grade 3 pancreatitides following stereotactic body RT to the left adrenal gland. Conclusions: Concurrent RT-NIVO is generally well tolerated, though with potentially increased rates of severe toxicity when irradiating the lung, abdomen, or brain. Pending more definitive data, we recommend counseling patients on the potentially increased rates of side effects from combined immunotherapy and radiotherapy to these locations. Future prospective trials assessing fractionation and sequencing of RT with IT will help inform combined therapy recommendations.

Keywords: combined immunotherapy and radiation, immunotherapy, Nivolumab, toxicity of concurrent immunotherapy and radiation

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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: Manav Sabharwal, Ruda Rai Md, Candace Parker, James Ridley

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Wheat is one of the most commonly consumed grains worldwide, which contains gluten. Nowadays, gluten intake is considered to be a trigger for GRDs, including Celiac disease (CD), a common genetic disease affecting 1% of the US population, non-celiac gluten sensitivity (NCGS) and wheat allergy. NCGS is being recognized as an acquired gluten-sensitive enteropathy that is prevalent across age, ethnic and geographic groups. The cause of this entity is not fully understood, and recent studies suggest that it is more common in participants with irritable bowel syndrome (IBS), with iron deficiency anemia, symptoms of fatigue, and has considerable overlap in symptoms with IBS and Crohn’s disease. However, these studies were lacking in availability of complete serologies, imaging tests and/or pan-endoscopy. We performed a prospective study of 745 adult patients who presented to an outpatient clinic for evaluation of chronic upper gastro-intestinal symptoms and subsequently underwent an upper endoscopic (EGD) examination as standard of care. Evaluation comprised of comprehensive celiac antibody panel, inflammatory bowel disease (IBD) serologic markers, duodenal biopsies and Small Bowel Video Capsule Endoscopy (VCE), when available. At least 6 biopsy specimens were obtained from the duodenum and proximal jejunum during EGD, and CD3+ Intraepithelial lymphocytes (IELs) and villous architecture were evaluated by a single experienced pathologist, and VCE was performed by a single experienced gastroenterologist. Of the 745 patients undergoing EGD, 12% (93/745) patients showed elevated CD3+ IELs in the duodenal biopsies. 52% (387/745) completed a comprehensive CD panel and 7.2% (28/387) were positive for at least 1 CD antibody (Tissue transglutaminase (tTG), being the most common antibody in 65% (18/28)). Of these patients, 18% (5/28) showed increased duodenal CD3+ IELs, but 0% showed villous blunting or distortion to meet criteria for CD. Surprisingly, 43% (12/28) were positive for at 1 IBD serology (ASCA, ANCA or expanded IBD panel (LabCorp)). Of these 28 patients, 29% (8/28) underwent a SB VCE, of which 100 % (8/8) showed significant jejuno-ileal mucosal lesions diagnostic for IBD. Findings of abnormal CD antibodies (7.2%, 28/387) and increased CD3+ IELs on duodenal biopsy (12%, 93/745) were observed frequently in patients with UGI symptoms undergoing EGD in an outpatient clinic. None met criteria for CD, and a high proportion (43%, 12/28) showed evidence of overlap with IBD. This suggests a potential causal link of acquired GRDs to underlying inflammation and gut mucosal barrier disruption. Further studies to investigate a role for abnormal antigen presentation of dietary gluten to gut associated lymphoid tissue as a cause are justified. This may explain a high prevalence of GRDs in the population and correlation with IBS, IBD and other gut inflammatory disorders.

Keywords: celiac, gluten sensitive enteropathy, lymphocitic enteritis, IBS, IBD

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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: Amanullah Lagharil, Majid Ali Laghari, M. Qasim, Jan. M., Asif Khan, M. Hassan Agheem

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The Nagar Parkar area in southeastern Sindh is a part of the Thar Desert adjacent to the Runn of Kutchh, and covers 480 km2. It contains exposures of a variety of igneous rocks referred to as the Nagar Parkar Igneous Complex. The complex comprises rocks belonging to at least six phases of magmatism, from oldest to youngest: 1) amphibolitic basement rocks, 2) riebeckite-aegirine grey granite, 3) biotite-hornblende pink granite, 4) acid dykes, 5) rhyolite “plugs”, and basic dykes (Jan et al., 1997). The last three of these are not significant in volume. Radiometric dates are lacking but the grey and pink granites are petrographically comparable to the Siwana and Jalore plutons, respectively, emplaced in the Malani volcanic series. Based on these similarities and proximity, the phase 2 to 6 bodies in the Nagar Parkar may belong to the Late Proterozoic (720–745 Ma) Malani magmatism that covers large areas in western Rajasthan. Khan et al. (2007) have reported a 745 ±30 – 755 ±22 Ma U-Th-Pb age on monazite from the pink granite. The grey granite is essentially composed of perthitic feldspar (microperthite, mesoperthite), quartz, small amount of plagioclase and, characteristically, sodic minerals such as riebeckite and aegirine. A few samples lack aegirine. Fe-Ti oxide and minute, well-developed crystals of zircon occur in almost all the studied samples. Tourmaline, fluorite, apatite and rutile occur in only some samples and astrophyllite is rare. Allanite, sphene and leucoxene occur as minor accessories along with local epidote. The pink granite is mostly leucocratic, but locally rich in biotite (up to 7 %). It is essentially made up of microperthite and quartz, with local microcline, and minor plagioclase (albite-oligoclase). Some rocks contain sufficient oligoclase and can be called adamellite or quartz mozonite. Biotite and hornblende are main accessory minerals along with iron oxide, but in a few samples are without hornblende. Fayalitic olivine, zircon, sphene, apatite, tourmaline, fluorite, allanite and cassiterite occur as sporadic accessory minerals. Epidote, carbonate, sericite and muscovite are produced due to the alteration of feldspar. This work concerns the major element geochemistry and comparison of the principal granitic rocks of Nagar Parkar. According to the scheme of De La Roche et al. (1980), majority of the grey and pink granites classify as alkali granite, 20 % as granite and 10 % as granodiorite. When evaluated on the basis of Shand's indices (after Maniar and Piccoli, 1989), the grey and pink granites span all three fields (peralkaline, metaluminous and peraluminous). Of the analysed grey granites, 67 % classify as peralkaline, 20 % as peraluminous and 10 % as metaluminous, while 50 % of pink granites classify as peralkaline, 30 % metaluminous and 20 % peraluminous.

Keywords: petrography, nagar parker, granites, geological sciences

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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

Procedia PDF Downloads 264

Authors: Sara Parker, Kay Standing

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This paper will share insights into how menstruators bodies in Nepal are viewed and controlled in Nepal due to the deeply held stigmas and taboos that exist that frame menstrual blood as impure and polluting. It draws on a British Academy Global Challenges Research (BA/GCRF) funded project, ‘Dignity Without Danger,’ that ran from December 2019 to 2022. In Nepal, beliefs and myths around menstrual related practices prevail and vary in accordance to time, generation, caste and class. Physical seclusion and/or restrictions include the consumption of certain foods, the ability to touch certain people and objects, and restricted access to water sources. These restrictions not only put women at risk of poor health outcomes, but they also promote discrimination and challenge fundamental human rights. Despite the pandemic, a wealth of field research and creative outputs have been generated to help break the silence that surrounds menstruation and also highlights the complexity of addressing the harms associated with the exclusion from sacred and profane spaces that menstruators face. Working with locally recruited female research assistants, NGOS and brining together academics from the UK and Nepal, we explore the intersecting factors that impact on menstrual experiences and how they vary throughout Nepal. WE concur with Tamang that there is no such thing as a ‘Nepali Woman’, and there is no one narrative that captures the experiences of menstruators in Nepal. These deeply held beliefs and practices mean that menstruators are denied their right to a dignified menstruation. By being excluded from public and private spaces, such as temples and religious sites, as well as from kitchens and your own bedroom in your own home, these beliefs impact on individuals in complex and interesting ways. Existing research in Nepal by academics and activists demonstrates current programmes and initiatives do not fully address the misconceptions that underpin the exclusionary practices impacting on sexual and reproductive health, a sense of well being and highlight more work is needed in this area. Research has been conducted in all 7 provinces and through exploring and connecting disparate stories, artefacts and narratives, we will deepen understanding of the complexity of menstrual practices enabling local stakeholders to challenge exclusionary practices. By using creative methods to engage with stakeholders and share our research findings as well as highlighting the wealth of activism in Nepal. We highlight the importance of working with local communities, leaders and cutting across disciplines and agencies to promote menstrual justice and dignity. Our research findings and creative outputs that we share on social media channels such as Dignity Without Danger Facebook, Instagram and you tube stress the value of employing a collaborative action research approach to generate material which helps local people take control of their own narrative and change social relations that lead to harmful practices.

Keywords: menstruation, Nepal, stigma, social norms

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Authors: Molly Parker

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Unintended pregnancy rates in Australia are amongst the highest in the developed world. Women with Substance Use Disorder often have riskier sexual behavior with nil contraceptive use and face disproportionately higher unintended pregnancies and Sexually Transmitted Infections, alongside Substance Use in Pregnancy (SUP) climbing at an alarming rate. In an inner-city Drug and Alcohol (D&A) service, significant barriers to sexual and reproductive health services have been identified, aligning with research. Rapid pathways were created for women seeking D&A treatment to be referred to Sexual and Reproductive Health services for the administration of Long-acting reversible contraception (LARC) and sexual health screening. For clients attending a D&A service, this is an opportunistic time to offer sexual and reproductive health services. Collaboration and multidisciplinary team input between D&A and sexual health and reproductive services are paramount, with rapid referral pathways being identified as the main strategy to improve access to sexual and reproductive health support for this population. With this evidence, a rapid referral pathway was created for women using the D&A service to access LARC, particularly in view of fertility often returning once stable on D&A treatment. A closed-ended survey was used for D&A staff to identify gaps in reproductive health knowledge and views of referral accessibility. Results demonstrated a lack of knowledge of contraception and appropriate referral processes. A closed-ended survey for clients was created to establish the need and access to services and to quantify data. A follow-up data collection will be reviewed to access uptake and satisfaction of the intervention from clients. Sexual health screening access was also identified as a deficit, particularly concerning due to the higher rates of STIs in this cohort. A rapid referral pathway will be undergoing implementation, reducing risks of untreated STIS both pre and post-conception. Similarly, pre and post-intervention structured surveys will be used to identify client satisfaction from the pathway. Although currently in progress, the research and pathway aim to be completed by December 2023. This research and implementation of sexual and reproductive health pathways from the D&A service have significant health and well-being benefits to clients and the wider community, including possible fetal/infancy outcomes. Women now have rapid access to sexual and reproductive health services, with the aim of reducing unplanned pregnancies, poor outcomes associated with SUP, client/staff trauma from termination of pregnancy, and client/staff trauma following the assumption of care of the child due to substance use, the financial cost for out of home care as required, the poor outcomes of untreated STIs to the fetus in pregnancy and the spread of STIs in the wider community. As evidence suggests, the implementation of a streamlined referral process is required between D&A and sexual and reproductive health services and has positive feedback from both clinicians and clients in improving care.

Keywords: substance use in pregnancy, drug and alcohol, substance use disorder, sexual health, reproductive health, contraception, long-acting reversible contraception, neonatal abstinence syndrome, FASD, sexually transmitted infections, sexually transmitted infections pregnancy

Procedia PDF Downloads 26

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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Authors: Anna Höfer, Johannes Herrmann, Patrick Meybohm, Christopher Lotz

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Mitochondria are pivotal for energy supply and regulation of cellular functions. Deficiencies of mitochondrial metabolism have been implicated in diverse stressful conditions including infections. Platelets are key mediators for thrombo-inflammation during development and resolution of acute respiratory distress syndrome (ARDS). Previous data point to an exhausted platelet phenotype in critically-ill patients with coronavirus 19 disease (COVID-19) impacting the course of disease. The objective of this work was to characterize platelet mitochondrial metabolism in patients suffering from COVID-19 ARDSA longitudinal analysis of platelet mitochondrial metabolism in 24 patients with COVID-19 induced ARDS compared to 35 healthy controls (ctrl) was performed. Blood samples were analyzed at two time points (t1=day 1; t2=day 5-7 after study inclusion). The activity of mitochondrial citrate synthase was photometrically measured. The impact of oxidative stress on mitochondrial permeability was assessed by a photometric calcium-induced swelling assay and the activity of superoxide dismutase (SOD) by a SOD assay kit. The amount of protein carbonylation and the activity of mitochondria complexes I-IV were photometrically determined. Levels of interleukins (IL)-1α, IL-1β and tumor necrosis factor (TNF-) α were measured by a Multiplex assay kit. Median age was 54 years, 63 % were male and BMI was 29.8 kg/m2. SOFA (12; IQR: 10-15) and APACHE II (27; IQR: 24-30) indicated critical illness. Median Murray Score was 3.4 (IQR: 2.8-3.4), 21/24 (88%) required mechanical ventilation and V-V ECMO support in 14/24 (58%). Platelet counts in ARDS did not change during ICU stay (t1: 212 vs. t2: 209 x109/L). However, mean platelet volume (MPV) significantly increased (t1: 10.6 vs. t2: 11.9 fL; p<0.0001). Citrate synthase activity showed no significant differences between ctrl and ARDS patients. Calcium induced swelling was more pronounced in patients at t1 compared to t2 and to ctrl (50µM; t1: 0.006 vs. ctrl: 0.016 ΔOD; p=0.001). The amount of protein carbonylation as marker for irreversible proteomic modification constantly increased during ICU stay and compared to ctrl., without reaching significance. In parallel, superoxid dismutase activity gradually declined during ICU treatment vs. ctrl (t2: - 29 vs. ctrl.: - 17 %; p=0.0464). Complex I analysis revealed significantly stronger activity in ARDS vs. ctrl. (t1: 0.633 vs. ctrl.: 0.415 ΔOD; p=0.0086). There were no significant differences in complex II, III or IV activity in platelets from ARDS patients compared to ctrl. IL-18 constantly increased during the observation period without reaching significance. IL-1α and TNF-α did not differ from ctrl. However, IL-1β levels were significantly elevated in ARDS (t1: 16.8; t2: 16.6 vs. ctrl.: 12.4 pg/mL; p1=0.0335, p2=0.0032). This study reveals new insights in platelet mitochondrial metabolism during COVID-19 caused ARDS. it data point towards enhanced platelet activity with a pronounced turnover rate. We found increased activity of mitochondria complex I and evidence for enhanced oxidative stress. In parallel, protective mechanisms against oxidative stress were narrowed with elevated levels of IL-1β likely causing a pro-apoptotic environment. These mechanisms may contribute to platelet exhaustion in ARDS.

Keywords: acute respiratory distress syndrome (ARDS), coronavirus 19 disease (COVID-19), oxidative stress, platelet mitochondrial metabolism

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Authors: Walter E. Allen, Robert D. Murray

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Many large transit agencies have adopted RFID technology and electronic automatic fare collection (AFC) or smart card systems, but small and rural agencies remain tied to obsolete manual, cash-based fare collection. Small countries or transit agencies can benefit from the implementation of smart card AFC technology with the promise of increased passenger convenience, added passenger satisfaction and improved agency efficiency. For transit agencies, it reduces revenue loss, improves passenger flow and bus stop data. For countries, further implementation into security, distribution of social services or currency transactions can provide greater benefits. However, small countries or transit agencies cannot afford expensive proprietary smart card solutions typically offered by the major system suppliers. Deployment of Contactless Fare Media System (CFMS) Standard eliminates the proprietary solution, ultimately lowering the cost of implementation. Acumen Building Enterprise, Inc. chose the Yuma County Intergovernmental Public Transportation Authority (YCIPTA) existing proprietary YCAT smart card system to implement CFMS. The revised system enables the purchase of fare product online with prepaid debit or credit cards using the Payment Gateway Processor. Open and interoperable smart card standards for transit have been developed. During the 90-day Pilot Operation conducted, the transit agency gathered the data from the bus AcuFare 200 Card Reader, loads (copies) the data to a USB Thumb Drive and uploads the data to the Acumen Host Processing Center for consolidation of the data into the transit agency master data file. The transition from the existing proprietary smart card data format to the new CFMS smart card data format was transparent to the transit agency cardholders. It was proven that open standards and interoperability design can work and reduce both implementation and operational costs for small transit agencies or countries looking to expand smart card technology. Acumen was able to avoid the implementation of the Payment Card Industry (PCI) Data Security Standards (DSS) which is expensive to develop and costly to operate on a continuing basis. Due to the substantial additional complexities of implementation and the variety of options presented to the transit agency cardholder, Acumen chose to implement only the Directed Autoload. To improve the implementation efficiency and the results for a similar undertaking, it should be considered that some passengers lack credit cards and are averse to technology. There are more than 1,300 small and rural agencies in the United States. This grows by 10 fold when considering small countries or rural locations throughout Latin American and the world. Acumen is evaluating additional countries, sites or transit agency that can benefit from the smart card systems. Frequently, payment card systems require extensive security procedures for implementation. The Project demonstrated the ability to purchase fare value, rides and passes with credit cards on the internet at a reasonable cost without highly complex security requirements.

Keywords: automatic fare collection, near field communication, small transit agencies, smart cards

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Authors: J. D. Cabral, E. Murray, P. Turner, E. Hewitt, A. Ali, M. McConnell

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Worldwide demand for organ replacement and tissue regeneration is progressively increasing. Three-dimensional (3D) bioprinting, where a physical construct is produced using computer-aided design, is a promising tool to advance the tissue engineering and regenerative medicine fields. In this paper we describe two different approaches to developing 3D bioprinted constructs for use in tissue regeneration. Bioink development is critical in achieving the 3D biofabrication of functional, regenerative tissues. Hydrogels, cross-linked macromolecules that absorb large amounts of water, have received widespread interest as bioinks due to their relevant soft tissue mechanics, biocompatibility, and tunability. In turn, not only is bioink optimisation crucial, but the creation of vascularized tissues remains a key challenge for the successful fabrication of thicker, more clinically relevant bioengineered tissues. Among the various methodologies, cell-laden hydrogels are regarded as a favorable approach; and when combined with novel core/shell 3D bioprinting technology, an innovative strategy towards creating new vessel-like structures. In this work, we investigate this cell-based approach by using human umbilical endothelial cells (HUVECs) entrapped in a viscoelastic chitosan/dextran (CD)-based core hydrogel, printed simulataneously along with a gelatin methacrylate (GelMA) shell. We have expanded beyond our previously reported FDA approved, commercialised, post-surgical CD hydrogel, Chitogel®, by functionalizing it with cell adhesion and proteolytic peptides in order to promote bone marrow-derived mesenchymal stem cell (immortalized BMSC cell line, hTERT) and HUVECs growth. The biocompatibility and biodegradability of these cell lines in a 3D bioprinted construct is demonstrated. Our studies show that particular peptide combinations crosslinked within the CD hydrogel was found to increase in vitro growth of BMSCs and HUVECs by more than two-fold. These gels were then used as a core bioink combined with the more mechanically robust, UV irradiated GelMA shell bioink, to create 3D regenerative, vessel-like scaffolds with high print fidelity. As well, microporous MEW scaffolds made from milk proteins blended with PCL were found to show promising bioactivity, exhibiting a significant increase in keratinocyte (HaCaTs) and fibroblast (normal human dermal fibroblasts, NhDFs) cell migration and proliferation when compared to PCL only scaffolds. In conclusion, our studies indicate that a peptide functionalized CD hydrogel bioink reinforced with a GelMA shell is biocompatible, biodegradable, and an appropriate cell delivery vehicle in the creation of regenerative 3D constructs. In addition, a novel 3D printing technique, melt electrowriting (MEW), which allows fabrication of micrometer fibre meshes, was used to 3D print polycaprolactone (PCL) and bioactive milk protein, lactorferrin (LF) and whey protein (WP), blended scaffolds for potential skin regeneration applications. MEW milk protein/PCL scaffolds exhibited high porosity characteristics, low overall biodegradation, and rapid protein release. Human fibroblasts and keratinocyte cells were seeded on to the scaffolds. Scaffolds containing high concentrations of LF and combined proteins (LF+WP) showed improved cell viability over time as compared to PCL only scaffolds. This research highlights two scaffolds made using two different 3D printing techniques using a combination of both natural and synthetic biomaterial components in order to create regenerative constructs as potential chronic wound treatments.

Keywords: biomaterials, hydrogels, regenerative medicine, 3D bioprinting

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