Search results for: Andrew Nicholas

Authors: Ketaki D. Belsare, Nicholas F. Polizzi, Lior Shtayer, William F. DeGrado

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Nature utilizes metalloproteins to perform chemical transformations with activities and selectivities that have long been the inspiration for design principles in synthetic and biological systems. The chemical reactivities of metalloproteins are directly linked to local environment effects produced by the protein matrix around the metal cofactor. A complete understanding of how the protein matrix provides these interactions would allow for the design of functional metalloproteins. The de novo computational design of proteins have been successfully used in design of active sites that bind metals like di-iron, zinc, copper containing cofactors; however, precisely designing active sites that can bind small molecule ligands (e.g., substrates) along with metal cofactors is still a challenge in the field. The de novo computational design of a functional metalloprotein that contains a purposefully designed substrate binding site would allow for precise control of chemical function and reactivity. Our research strategy seeks to elucidate the design features necessary to bind the cofactor protoporphyrin IX (hemin) in close proximity to a substrate binding pocket in a four helix bundle. First- and second-shell interactions are computationally designed to control orientation, electronic structure, and reaction pathway of the cofactor and substrate. The design began with a parameterized helical backbone that positioned a single histidine residue (as an axial ligand) to receive a second-shell H-bond from a Threonine on the neighboring helix. The metallo-cofactor, hemin was then manually placed in the binding site. A structural feature, pi-bulge was introduced to give substrate access to the protoporphyrin IX. These de novo metalloproteins are currently being tested for their activity towards hydroxylation and epoxidation. The de novo designed protein shows hydroxylation of aniline to 4-aminophenol. This study will help provide structural information of utmost importance in understanding de novo computational design variables impacting the functional activities of a protein.

Keywords: metalloproteins, protein design, de novo protein, biocatalysis

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Authors: Andrew Anis Fakhrey Mosaad

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Objectives: Physiotherapy in the intensive care unit (ICU) improves patient outcomes. We aimed to determine the characteristics of physiotherapy practice and critical barriers to applying physiotherapy in ICUs. Materials and Methods: A 54-item survey for determining the characteristics physiotherapists and physiotherapy applications in the ICU was developed. The survey was electronically sent to potential participants through the Turkish Physiotherapy Association network. Sixty-five physiotherapists (47F and 18M; 23–52 years; ICU experience: 6.0±6.2 years) completed the survey. The data were analyzed using quantitative and qualitative methods. Results: The duration of ICU practice was 3.51±2.10 h/day. Positioning (90.8%), active exercises (90.8%), breathing exercises (89.2%), passive exercises (87.7%), and percussion (87.7%) were the most commonly used applications. The barriers were related to physiotherapists (low level of employment and practice, lack of shift); patients (unwillingness, instability, participation restriction); teamwork (lack of awareness and communication); equipment (inadequacy, non-priority to purchase); and legal (reimbursement, lack of direct physiotherapy access, non-recognition of autonomy) procedures. Conclusion: The most common interventions were positioning, active, passive, breathing exercises, and percussion. Critical barriers toward physiotherapy are multifactorial and related to physiotherapists, patients, teams, equipment, and legal procedures. Physiotherapist employment, service maintenance, and multidisciplinary teamwork should be considered for physiotherapy effectiveness in ICUs.

Keywords: intensive care units, physical therapy, physiotherapy, exercises

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Authors: Robbie C. Murchison, Ibrahim Küçükdemiral, Andrew Cowell

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Thermal effects are the largest source of dimensional error in precision machining, and a major proportion is caused by ambient temperature variation. The use of coolant is a primary means of mitigating these effects, but there has been limited work on coolant temperature control. This research critically explored whether CNC-machine coolant refrigeration systems adapted to actively compensate for ambient temperature variation could increase machining accuracy. Accuracy data were collected from operators’ checklists for a CNC 5-axis mill and statistically reduced to bias and precision metrics for observations of one day over a sample period of 27 days. Temperature data were collected using three USB dataloggers in ambient air, the chiller inflow, and the chiller outflow. The accuracy and temperature data were analysed using Pearson correlation, then the thermodynamics of the system were described using system identification with MATLAB. It was found that 75% of thermal error is reflected in the hot coolant temperature but that this is negligibly dependent on ambient temperature. The effect of the coolant refrigeration process on hot coolant outflow temperature was also found to be negligible. Therefore, the evidence indicated that it would not be beneficial to adapt coolant chillers to compensate for ambient temperature variation. However, it is concluded that hot coolant outflow temperature is a robust and accessible source of thermal error data which could be used for prevention strategy evaluation or as the basis of other thermal error strategies.

Keywords: CNC manufacturing, machine-tool, precision machining, thermal error

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Authors: Ali Alotaibi, Francis Edum-Fotwe, Andrew Price /

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Mega construction projects create buildings and major infrastructure to respond to work and life requirements while playing a vital role in promoting any nation’s economy. However, the industry is often criticised for not balancing economic, environmental and social dimensions of their projects, with emphasis typically on one aspect to the detriment of the others. This has resulted in many negative impacts including environmental pollution, waste throughout the project lifecycle, low productivity, and avoidable accidents. The identification of comprehensive Social Responsibility (SR) indicators, which combine social, environmental and economic aspects, is urgently needed. This is particularly the case in the context of the Kingdom of Saudi Arabia (KSA), which often has mega public construction projects. The aim of this paper is to develop a set of wide-ranging SR indicators which encompass social, economic and environmental aspects unique to the KSA. A qualitative approach was applied to explore relevant indicators through a review of the existing literature, international standards and reports. A list of appropriate indicators was developed, and its comprehensiveness was corroborated by interviews with experts on mega construction projects working with SR concepts in the KSA. The findings present 39 indicators and their metrics, covering 10 economic, 12 environmental and 17 social aspects of SR mapped against their references. These indicators are a valuable reference for decision-makers and academics in the KSA to understand factors related to SR in mega construction projects. The indicators are related to mega construction projects within the KSA and require validation in a real case scenario or within a different industry to demonstrate their generalisability.

Keywords: social responsibility, construction projects, economic, social, environmental, indicators

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Authors: Andrew Enaifoghe

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Municipalities are the most fundamental units of governance, and they are responsible for providing basic services and supporting growth in the areas they rule. South African local government is primarily understood in terms of service delivery, and the South African constitution provides municipalities with the responsibility of mobilizing economic resources, to better the lives of all people. Essential public services are the primary pillars of enhanced quality of life, and appropriate supplies of safe water and sanitation are required for life, well-being, and human dignity. Therefore, having access to basic services is directly tied to social inclusion and social capital, and towns' inability to offer services can have a negative influence on social and economic growth. The problem of service delivery is seen as one of the biggest challenges facing South African municipalities today. This study attempts to assess South African municipal service delivery. Focusing on the main causes of service delivery challenges, the study also looks at the impact of these challenges to identify ways to minimize such challenges by introducing legal instruments such as municipal budgeting and annual reports. A qualitative design was adopted, and data were collected using a desktop technique and analyzed based on content. While public engagement in municipal affairs is required by law, considerable work has to be done to ensure successful participation. Finally, municipalities were deemed to need to do more to improve human capacity to offer services.

Keywords: municipalities, service delivery, corruption, monitoring, South Africa

Procedia PDF Downloads 117

Authors: Nicholas Pearce, Eun-jin Kim

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Pathologies of the cardiovascular (CV) system remain a serious and deadly health problem for human society. Computational modelling provides a relatively accessible tool for diagnosis, treatment, and research into CV disorders. However, numerical models of the CV system have largely focused on the function of the ventricles, frequently overlooking the behaviour of the atria. Furthermore, in the study of the pressure-volume relationship of the heart, which is a key diagnosis of cardiac vascular pathologies, previous works often evoke popular yet questionable time-varying elastance (TVE) method that imposes the pressure-volume relationship instead of calculating it consistently. Despite the convenience of the TVE method, there have been various indications of its limitations and the need for checking its validity in different scenarios. A model of the combined left ventricle (LV) and left atrium (LA) is presented, which consistently considers various feedback mechanisms in the heart without having to use the TVE method. Specifically, a synergistic model of the left ventricle is extended and modified to include the function of the LA. The synergy of the original model is preserved by modelling the electro-mechanical and chemical functions of the micro-scale myofiber for the LA and integrating it with the microscale and macro-organ-scale heart dynamics of the left ventricle and CV circulation. The atrioventricular node function is included and forms the conduction pathway for electrical signals between the atria and ventricle. The model reproduces the essential features of LA behaviour, such as the two-phase pressure-volume relationship and the classic figure of eight pressure-volume loops. Using this model, disorders in the internal cardiac electrical signalling are investigated by recreating the mechano-electric feedback (MEF), which is impossible where the time-varying elastance method is used. The effects of AV node block and slow conduction are then investigated in the presence of an atrial arrhythmia. It is found that electrical disorders and arrhythmia in the LA degrade the CV system by reducing the cardiac output, power, and heart rate.

Keywords: cardiovascular system, left atrium, numerical model, MEF

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Authors: Nicholas Bayfield, Liam Bibo, Charley Budgeon, Robert Larbalestier, Tom Briffa

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Introduction: Stress hyperglycaemia is common following cardiac surgery. Its optimal management is uncertain and may differ by diabetic status. This study assesses the in-hospital glycaemic management of cardiac surgery patients and associated postoperative outcomes. Methods: A retrospective cohort analysis of all patients undergoing cardiac surgery at Fiona Stanley Hospital from February 2015 to May 2019 was undertaken. Management and outcomes of hyperglycaemia following cardiac surgery were assessed. Follow-up was assessed to 1 year postoperatively. Multivariate regression modelling was utilised. Results: 1050 non-diabetic patients and 689 diabetic patients were included. In the non-diabetic cohort, patients with mild (peak blood sugar level [BSL] < 14.3), transient stress hyperglycaemia managed without insulin were not at an increased risk of wound-related morbidity (P=0.899) or mortality at 1 year (P=0.483). Insulin management was associated with wound-related readmission to hospital (P=0.004) and superficial sternal wound infection (P=0.047). Prolonged or severe stress hyperglycaemia was predictive of hospital re-admission (P=0.050) but not morbidity or mortality (P=0.546). Diabetes mellitus was an independent risk factor 1-year mortality (OR; 1.972 [1.041–3.736], P=0.037), graft harvest site wound infection (OR; 1.810 [1.134–2.889], P=0.013) and wound-related readmission (OR; 1.866 [1.076–3.236], P=0.026). In diabetics, postoperative peak BSL > 13.9mmol/L was predictive of graft harvest site infections (OR; 3.528 [1.724-7.217], P=0.001) and wound-related readmission OR; 3.462 [1.540-7.783], P=0.003) regardless of modality of management. A peak BSL of 10.0-13.9 did not increase the risk of morbidity/mortality compared to a peak BSL of < 10.0 (P=0.557). Diabetics with a peak BSL of 13.9 or less did not have significantly increased morbidity/mortality outcomes compared to non-diabetics (P=0.418). Conclusion: In non-diabetic patients, transient mild stress hyperglycaemia following cardiac surgery does not uniformly require treatment. In diabetic patients, postoperative hyperglycaemia with peak BSL exceeding 13.9mmol/L was associated with wound-related morbidity and hospital readmission following cardiac surgery.

Keywords: cardiac surgery, pulmonary embolism, pulmonary embolectomy, cardiopulmonary bypass

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Authors: Okanta Andrew, Richmond Kweku Frempong

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As mobile networks are upgraded with technologies like WAP, GPRS and UMTS to deliver next-generation multimedia services, so are the banks and other financial institutions also getting ready to unleash the financial products on the mobile platform to meet growing demand for mobile based application services. Hence, the onset of Unstructured Supplementary Services (USSD) Banking which would make banking services available at anywhere, anytime through a string of interactive SMS sessions between a mobile device and an application server of a service provider. The aim of this studies was to find out whether the public will accept the sim banking service when it is implemented. Our target group includes: Working class. E. g. Businessmen/women, office workers, fishermen, market women, teachers etc. Nonworking class. E. g. Students (Tertiary, Senior High School), housewives. etc. The survey was in the form of a questionnaire and a verbal interview (video) which was to investigate their idea about the current banking system and the yet to be introduced sim banking concept. Meanwhile, some challenges accompanied the progression of data gathering because some populace showed reluctance in freeing their information. One other suggestion was that government should put measures against foremost challenges obstructing sim banking in Ghana counter to computers hackers. Government and individual have a key role to undertake to give suitable support to facelift the sim banking industry in the country. It was also suggested that Government put strong regulations on the use of sim banking products and services to streamline all the activities and also create awareness of the need for sim banking and emphasize its relevance in the aspect of national GDP.

Keywords: banking, mobile banking, SIM banking, mobile banking in Ghana

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Authors: Andrew Tan Hwee Chye, Yeo Zhen Ning

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This study aims to meta-analyse clinical studies comparing femoral tunnel position (FTP), femoral tunnel length (FTL) and graft bending angle (GBA) of single-bundle Anterior Cruciate Ligament (ACL) reconstruction using Transtibial (TT), Anteromedial (AM) and Outside-in (OI) techniques. A meta-analysis comparing the FTP, FTL and GBA of single-bundle ACL reconstruction utilising the TT, AM and OI was performed. Prospective Comparative Studies (PCS) and Retrospective Comparative Studies (RCS) from PubMed, Cochrane Library, and Embase were included. A total of 17 studies were included in this study. TT had the longest FTL, when compared to AM (Mean difference = 7.38, 95% CI: 3.76 to 11.00, P < 0.001) and OI (Mean difference = 9.47, 95% CI: 4.89 to 14.05, P < 0.001). In the deep-to-shallow direction, the OI resulted in a significantly deeper femoral tunnel as compared to the TT (Mean difference = 4.36, 95% CI: 1.39 to 7.33, P = 0.004) (Figure 6B). The AM technique also contributed to a significantly lower tunnel position as compared to the OI technique (Mean difference = 2.34, 95% CI: 0.76 to 3.92, P = 0.004). There were no significant differences in the graft bending angle between TT, AM and OI techniques. AM and OI techniques provide a more anatomical position as compared to the TT. Although FTL in the TT is longer than the AM and OI, all three techniques exceed the critical length of 25mm. There are no differences in the GBA between the three techniques.

Keywords: femoral tunnel position, femoral tunnel length, anterior cruciate ligament, transtibial, graft bending angle, anteromedial, outside-in

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Authors: Onyedikachi Ulelu, Andrew P. Longstaff, Simon Fletcher, Simon Parkinson

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The widespread interest in 'Industry 4.0' or 'digital manufacturing' has led to significant research requiring the acquisition of data from sensors, instruments, and machine signals. In-depth research then identifies methods of analysis of the massive amounts of data generated before and during manufacture to solve a particular problem. The ultimate goal is for industrial Internet of Things (IIoT) data to be processed automatically to assist with either visualisation or autonomous system decision-making. However, the collection and processing of data in an industrial environment come with a cost. Little research has been undertaken on how to specify optimally what data to capture, transmit, process, and store at various levels of an edge-cloud network. The first step in this specification is to categorise IIoT data for efficient and effective use. This paper proposes the required attributes and classification to take manufacturing digital data from various sources to determine the most suitable location for data processing on the edge-cloud network. The proposed classification framework will minimise overhead in terms of network bandwidth/cost and processing time of machine tool data via efficient decision making on which dataset should be processed at the ‘edge’ and what to send to a remote server (cloud). A fast-and-frugal heuristic method is implemented for this decision-making. The framework is tested using case studies from industrial machine tools for machine productivity and maintenance.

Keywords: data classification, decision making, edge computing, industrial IoT, industry 4.0

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Authors: May Khei Hu, Kevin Leong, Fu Siong Ng, Nicholas Peter

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Introduction: Sympathetic stimulation has been recognised as a potent stimulus of arrhythmogenesis in various cardiac pathologies, possibly by augmenting dispersion of repolarisation. The effects of sympathetic stimulation in healthy subjects however remain unclear. It is, therefore, crucial to first establish the effects of physiological stress on dispersion of repolarisation in healthy subjects before understanding these effects in pathological cardiac conditions. We hypothesised that activation-recovery interval (ARI; which is a surrogate of action potential duration) and dispersion of repolarisation decrease on sympathetic stimulation. Methods: Eight patients aged 18-55 years with structurally normal hearts underwent head-up tilt test (HUTT) and exercise tolerance test (ETT) while wearing the electrocardiographic imaging (ECGi) vest. Patients later underwent CT scan and the epicardial potentials are reconstructed using the ECGi software. Activation and recovery times were determined from the acquired electrograms. ARI was calculated and later corrected using Bazett’s formula. Global and regional dispersion of repolarisation were determined from standard deviation of the corrected ARI (ARIc). One-way analysis of variance (ANOVA) and Wilcoxon test were used to evaluate statistical significance. Results: Global ARIc increased significantly [p<0.01] when patients were tilted upwards but decreased significantly after five minutes [p<0.01]. A subsequent post- hoc analysis revealed that the decrease in R-R was more substantial compared to the change in ARI, resulting in the observed increase in ARIc. Global ARIc decreased on peak exercise [p<0.01] but increased on recovery [p<0.01]. Global dispersion increased significantly on peak exercise [p<0.05] although there were no significant changes in regional dispersion. There were no significant changes in both global and regional dispersion during tilt. Conclusion: ARIc decreases upon sympathetic stimulation in healthy subjects. Global dispersion of repolarisation increases upon exercise although there were no changes in global or regional dispersion during orthostatic stress.

Keywords: dispersion of repolarisation, sympathetic stimulation, Head-up tilt test (HUTT), Exercise tolerance test (ETT), Electrocardiographic imaging (ECGi)

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Authors: Nicholas Bayfield, Liam Bibo, Kaushelandra Rathore, Lucas Sanders, Mark Newman

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INTRODUCTION: Surgical pulmonary embolectomy is an established therapy for acute pulmonary embolism causing right heart dysfunction and haemodynamic instability. Massive intraoperative airway haemorrhage is a rare complication of pulmonary embolectomy. We present our institutional experience with massive airway haemorrhage complicating pulmonary embolectomy and discuss optimal therapeutic strategies. METHODS: A retrospective review of emergent surgical pulmonary embolectomy patients was undertaken. Cases complicated by massive intra-operative airway haemorrhage were identified. Intra- and peri-operative management strategies were analysed and discussed. RESULTS: Of 76 patients undergoing emergent or salvage pulmonary embolectomy, three cases (3.9%) of massive intraoperative airway haemorrhage were identified. Haemorrhage always began on weaning from cardiopulmonary bypass. Successful management strategies involved intraoperative isolation of the side of bleeding, occluding the affected airway with an endobronchial blocker, institution of veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) and reversal of anticoagulation. Running the ECMO without heparinisation allows coagulation to occur. Airway haemorrhage was controlled within 24 hours of operation in all patients, allowing re-institution of dual lung ventilation and decannulation from ECMO. One case in which positive end-expiratory airway pressure was trialled initially was complicated by air embolism. Although airway haemorrhage was controlled successfully in all cases, all patients died in-hospital for reasons unrelated to the airway haemorrhage. CONCLUSION: Massive intraoperative airway haemorrhage during pulmonary embolectomy is a rare complication with potentially catastrophic outcomes. Re-perfusion alveolar and capillary injury is the likely aetiology. With a systematic approach to management, airway haemorrhage can be well controlled intra-operatively and often resolves within 24 hours. Stopping blood flow to the pulmonary arteries and support of oxygenation by the institution of VA ECMO is important. This management has been successful in our 3 cases.

Keywords: pulmonary embolectomy, cardiopulmonary bypass, cardiac surgery, pulmonary embolism

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Authors: Andrew Thayer, Courtney Rondeau, Paraskevi Papadopoulou

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The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) gene-editing technologies have generated considerable discussion about the applications and ethics of their use. However, no consistent guidelines for using CRISPR technologies have been developed -nor common legislation passed related to gene editing, especially as it is connected to genetically modified organisms (GMOs) in the European Union. The recent announcement that the first babies with CRISPR-edited genes were born, along with new studies exploring CRISPR’s applications in treating thalassemia, sickle-cell anemia, cancer, and certain forms of blindness, have demonstrated that the technology is developing faster than the policies needed to control it. Therefore, it can be seen that a reasonable and coherent regulatory framework for the use of CRISPR in human somatic and germline cells is necessary to ensure the ethical use of the technology in future years. The European Union serves as a unique region of interconnected countries without a standard set of regulations or legislation for CRISPR gene-editing. We posit that the EU would serve as a suitable model in comparing the legislations of its affiliated countries in order to understand the practicality and effectiveness of adopting majority-approved practices. Additionally, we present a proposed set of guidelines which could serve as a basis in developing a consistent regulatory framework for the EU countries to implement but also act as a good example for other countries to adhere to. Finally, an additional, multidimensional framework of smart solutions is proposed with which all stakeholders are engaged to become better-informed citizens.

Keywords: CRISPR, ethics, regulatory framework, European legislation

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Authors: Robert Vanderburg, Michael Cowling, Nicholas Gibson

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Mathematics is one of the core subjects taught in the Australian K-12 education system and is considered an important component for future studies in areas such as engineering and technology. In addition to this, Australia has been a world leader in distance education due to the vastness of its geographic landscape. Despite this, research is still needed on distance math instruction. Even though delivery of curriculum has given way to online studies, and there is a resultant push for computer-based (PC, tablet, smartphone) math instruction, much instruction still involves practice problems similar to those original curriculum packs, without the ability for students to self-regulate their learning using the full interactive capabilities of these devices. Given this need, this paper addresses issues students have during online instruction. This study consists of 32 students struggling with mathematics enrolled in a math tutorial conducted in an online setting. The study used a case study design to understand some of the blockades hindering the students’ success. Data was collected by tracking students practice and quizzes, tracking engagement of the site, recording one-on-one tutorials, and collecting data from interviews with the students. Results revealed that when students have cognitively straining tasks in an online instructional setting, the first thing to dissipate was their ability to self-regulate. The results also revealed that instructors could ameliorate the situation and provided useful data on strategies that could be used for designing future online tasks. Specifically, instructors could utilize cognitive dissonance strategies to reduce the cognitive drain of the tasks online. They could segment the instruction process to reduce the cognitive demands of the tasks and provide in-depth self-regulatory training, freeing mental capacity for the mathematics content. Finally, instructors could provide specific scheduling and assignment structure changes to reduce the amount of student centered self-regulatory tasks in the class. These findings will be discussed in more detail and summarized in a framework that can be used for future work.

Keywords: digital education, distance education, mathematics education, self-regulation

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Authors: Andrew Enaifoghe

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The study examined the role of public management development in enhancing public service delivery in the South African local government. The study believes that the ultimate empowerment of the third tier sphere of governments in South Africa remains the instrument required to enhance both national and continental development. This over the year has been overwhelmed with problems and imbalance related to ethical practice, accountability and the functional local government system and the machinery itself. The study finds that imbalances are being strengthened by a lack of understanding and unanimity as to what a public management development in a democratic system is and how it should work to achieve the dividends of democracy in delivering public goods. Studies indicated that the magnitudes are widespread corruption and misrepresentations of government priorities; both of which weaken the ability of governments to enhance broad-based economic growth and social well-being of the people. This study addressed the problem of public management and accountable local government. The study indicates the need for citizens’ participation in the decision-making process in delivering public service in South Africa and how its accountability mechanism supports good governance. The study concludes that good and ethical watersheds in South Africa have since reached such proportions that social pressure, the pressure from the government and various institutions have to re-consider where they stand regarding ethics, ethical behaviour, accountability and professionalism in delivering public goods to the people at the local municipal government.

Keywords: accountability, development, democratic system, South Africa

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Authors: Daphine Namara, Jeremy I. Schwartz, Andrew K. Tusubira, Willi McFarland, Caroline Birungi, Fred C. Semitala, Martin Muddu

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Emerging evidence suggests a possible association between hyperglycemia and dolutegravir (DTG), a preferred first-line antiretroviral agent in sub-Saharan Africa (SSA). There is a need for rigorous studies to validate this association in the face of increasing DTG use and the burden of non-communicable diseases among people living with HIV (PLHIV). We conducted a case-control study to assess the risk of hyperglycemia associated with the use of DTG among PLHIV attending Mulago ISS Clinic in Kampala. Cases had hyperglycemia, while controls had no hyperglycemia, as confirmed by fasting plasma glucose and oral glucose tolerance tests. Demographic, laboratory, and clinical data were collected using interviewer-administered questionnaires and medical record abstraction. The analysis compared cases and controls on DTG use prior to diagnosis of hyperglycemia while controlling for potential confounders using multivariable logistic regression. We included 204 cases and 231 controls. In multivariable analysis, patients with prior DTG use had seven times greater odds of subsequent diagnosis of hyperglycemia compared to those who had non-DTG-based regimens (adjusted odds ratio [aOR] 7.01, 95% CI 1.96-25.09). The odds of hyperglycemia also increased with age (56 years and above vs. 18-35, aOR 12.38, 95% CI 3.79-40.50) and hypertension (aOR 5.78, 95% CI 2.53-13.21). Our study demonstrates a strong association between prior DTG exposure and subsequent diagnosis of hyperglycemia. Given the benefits of DTG, wide-scale use, and the growing burden of diabetes mellitus (DM) in SSA, there is a need for systematic screening for hyperglycemia and consideration of alternate regimens for those at risk for DM.

Keywords: HIV, hyperglycemia, doluteravir, diabetes

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Authors: Japnoor Garcha, Andrew P. Smith

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There has been a significant increase in the prevalence and estimates of neurodevelopmental disorders specially autism spectrum disorders in the last decade. The literature has seen increasing research on understanding well-being and mental health. The current studies have focused on seeing the impact of mental health and well-being in autism spectrum disorders and ADHD both with and without a diagnosis. To further understand the association and interaction of well-being and mental health with autism and ADHD a survey was given to 560 secondary school students. The survey used the well-being process questionnaire, the autism spectrum quotient, the ADHD self-report scale, and the strengths and difficulties questionnaire. The analysis conducted using SPSS showed that there was a significant correlation between anxiety, depression, AQ and ADHD. Anxiety and depression were also significantly correlated with all well-being and SDQ variables. The regression analysis showed that anxiety was significantly associated with positive well-being, negative well-being, emotional problems and prosocial behaviour whereas depression was significantly associated with positive well-being, negative well-being, physical health, flourishing, conduct problems, emotional problems and peer problems. This interaction led to the formation of a combined variable to see what impact the variables of anxiety, depression, AQ and ADHD would have coupled together. Further analysis showed that the combined variable was significantly correlated with all outcome variables. The regression analysis showed that the Combined variable was significantly correlated with emotional problems, and hyperactivity, stress, negative coping, psychological capital and sleepiness.

Keywords: AQ, adhd, sdq, well-being, combined variable

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Authors: Caspar S. Carson, Gabriel W. Prather, Nicholas E. Wong, Jeffery R. Anton, William H. McCoy

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Cutibacterium acnes is a commensal bacterium found on human skin that has been linked to acne. C. acnes can also be an opportunistic pathogen when it infiltrates the body during surgery. This pathogen can cause dangerous infections of medical implants, such as shoulder replacements, leading to life-threatening blood infections. Compounding this issue, C. acnes resistance to many antibiotics has become an increasing problem worldwide, creating a need for special forms of treatment. C. acnes expresses the protein RoxP, and it requires this protein to colonize human skin. Though this protein is required for C. acnes skin colonization, its function is not yet understood. Inhibition of RoxP function might be an effective treatment for C. acnes infections. To develop such reagents, the McCoy Laboratory generated four unique anti-RoxP antibodies. Preliminary studies in the McCoy Lab have established that each antibody binds a distinct site on RoxP. To assess the potential of these antibodies as therapeutics, it is necessary to specifically characterize these antibody epitopes and evaluate them in assays that assess their ability to inhibit RoxP-dependent C. acnes growth. To provide material for these studies, an antibody expression construct, Fv-clasp(v2), was adapted to encode anti-RoxP antibody sequences. The author hypothesizes that this expression strategy can produce sufficient amounts of >95% pure antibody fragments for further characterization of these antibodies. Four anti-RoxP Fv-clasp(v2) expression constructs (pET vector-based) were transformed into E. coli BL21-Gold(DE3) cells and a small-scale expression and purification trial was performed for each construct to evaluate anti-RoxP Fv-clasp(v2) yield and purity. Successful expression and purification of these antibody constructs will allow for their use in structural studies, such as protein crystallography and cryogenic electron microscopy. Such studies would help to define the antibody binding sites on RoxP, which could then be leveraged in the development of certain methods to treat C. acnes infection through RoxP inhibition.

Keywords: structural biology, protein expression, infectious disease, antibody, therapeutics, E. coli

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Authors: Kan Yu, Khui Hung Lee, Eben Afrifa-Yamoah, Jing Guo, Katrina Harrison, Jack Goldblatt, Nicholas Pachter, Jitian Xiao, Guicheng Brad Zhang

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Background and Significance of the Study: Congenital Heart Defects (CHDs) are the most common malformation at birth and one of the leading causes of infant death. Although the exact etiology remains a significant challenge, epigenetic modifications, such as DNA methylation, are thought to contribute to the pathogenesis of congenital heart defects. At present, no existing DNA methylation biomarkers are used for early detection of CHDs. The existing CHD diagnostic techniques are time-consuming and costly and can only be used to diagnose CHDs after an infant was born. The present study employed a machine learning technique to analyse genome-wide methylation data in children with and without CHDs with the aim to find methylation biomarkers for CHDs. Methods: The Illumina Human Methylation EPIC BeadChip was used to screen the genome‐wide DNA methylation profiles of 24 infants diagnosed with congenital heart defects and 24 healthy infants without congenital heart defects. Primary pre-processing was conducted by using RnBeads and limma packages. The methylation levels of top 600 genes with the lowest p-value were selected and further investigated by using a random forest approach. ROC curves were used to analyse the sensitivity and specificity of each biomarker in both training and test sample sets. The functionalities of selected genes with high sensitivity and specificity were then assessed in molecular processes. Major Findings of the Study: Three genes (MIR663, FGF3, and FAM64A) were identified from both training and validating data by random forests with an average sensitivity and specificity of 85% and 95%. GO analyses for the top 600 genes showed that these putative differentially methylated genes were primarily associated with regulation of lipid metabolic process, protein-containing complex localization, and Notch signalling pathway. The present findings highlight that aberrant DNA methylation may play a significant role in the pathogenesis of congenital heart defects.

Keywords: biomarker, congenital heart defects, DNA methylation, random forest

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Authors: Karissa Graham, Andrew Campbell-Lloyd

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The deep inferior epigastric artery perforator flap (DIEP) is used to reconstruct large volumes of tissue. The DIEP flap is based on the deep inferior epigastric artery (DIEA) and vein. Accurate knowledge of the anatomy of these vessels allows for efficient dissection of the flap, minimal damage to surrounding tissue, and a well vascularized flap. A 54 year old lady was assessed for bilateral delayed autologous reconstruction with DIEP free flaps. The right DIEA was consistent with the described anatomy. The left DIEA had a vessel branching shortly after leaving the external iliac artery and before entering the muscle. This independent branch entered the muscle and had a long intramuscular course to the largest perforator. The main DIEA vessel demonstrated a type II branching pattern but had perforators that were too small to have a viable DIEP flap. There were no communicating arterial branches between the independent vessel and DIEA, however, there was one venous communication between them. A muscle sparing transverse rectus abdominis muscle flap was raised using the main periumbilical perforator from the independent vessel. Our case report demonstrated an unreported anatomical variant of the DIEA. A few anatomical variants have been described in the literature, including a unilateral absent DIEA and peritoneal-cutaneous perforators that had no connection to the DIEA. Doing a pre-operative CTA helps to identify these rare anatomical variations, which leads to safer, more efficient, and effective operating.

Keywords: aberrant anatomy, CT angiography, DIEP anatomy, free flap

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Authors: Grace McCambridge, Alanna Keady, Madhur Agrawal, Dequina Nicholas Alvarado, Barbara Nikolajczyk, Leena Panneerseelan-Bharath

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Age is a non-modifiable risk factor for the inflammation that underlies pathologies such as type 2 diabetes mellitus (T2DM). Inflammation, as indicated by circulating cytokines, rises in aging, but mechanisms that promote this ‘inflammaging’ remain poorly defined. Furthermore, downstream consequences of inflammaging, including the development of an inflammatory profile that predicts comorbidities like T2DM, remain speculative. We tested the possibility that natural aging-associated changes in autophagy, a process that is compromised in both aging and T2DM, regulates inflammatory profiles in older subjects. Our data showed that circulating CD4⁺ T cells from older compared to younger subjects have (i) defects in autophagy; (ii) higher mitochondria accumulation; (iii) a failure to metabolically shift from oxidative phosphorylation to anaerobic glycolysis upon αCD3/CD28 activation; (iv) more reactive oxygen species (ROS) accumulation; and (v) a cytokine profile that recapitulates the Th17 profile that predicts T2DM. ROS scavenging in cells from older subjects restored mitochondrial mass and membrane potential (indicators of improved autophagy) and reduced Th17 cytokines to amounts made by T cells from younger subjects. Knock-down of the autophagy protein Atg3 in T cells from younger subjects increased mitochondrial accumulation and Th17 cytokines. To begin translating these findings to clinical practice, we showed that physiological concentrations of the diabetes drug metformin (100 µM) added in vitro enhanced autophagy, prevented mitochondria and ROS accumulation, increased anaerobic glycolysis, and decreased Th17 cytokines in activated CD4⁺ T cells from older subjects. Metformin therefore improves autophagy and multiple downstream pro-inflammatory mechanisms CD4⁺ T cells from older subjects. We conclude that autophagy improvement ameliorates the development of a T2DM-predictive Th17 profile in aging, and thus holds promise for delay or prevention of aging-associated metabolic decline.

Keywords: autophagy, mitochondrial turnover, ROS, glycolysis

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Authors: Giulia Magi Meconi, Nicholas Ballard, José M. Asua, Ronen Zangi

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Experimental and computational studies are combined to elucidate the adsorption proprieties of ionic and nonionic surfactants on hydrophobic polymer surface such us poly(styrene). To present these two types of surfactants, sodium dodecyl sulfate and poly(ethylene glycol)-block-poly(ethylene), commonly utilized in emulsion polymerization, are chosen. By applying quartz crystal microbalance with dissipation monitoring it is found that, at low surfactant concentrations, it is easier to desorb (as measured by rate) ionic surfactants than nonionic surfactants. From molecular dynamics simulations, the effective, attractive force of these nonionic surfactants to the surface increases with the decrease of their concentration, whereas, the ionic surfactant exhibits mildly the opposite trend. The contrasting behavior of ionic and nonionic surfactants critically relies on two observations obtained from the simulations. The first is that there is a large degree of interweavement between head and tails groups in the adsorbed layer formed by the nonionic surfactant (PEO/PE systems). The second is that water molecules penetrate this layer. In the disordered layer, these nonionic surfactants generate at the surface, only oxygens of the head groups present at the interface with the water phase or oxygens next to the penetrating waters can form hydrogen bonds. Oxygens inside this layer lose this favorable energy, with a magnitude that increases with the surfactants density at the interface. This reduced stability of the surfactants diminishes their driving force for adsorption. All that is shown to be in accordance with experimental results on the dynamics of surfactants desorption. Ionic surfactants assemble into an ordered structure and the attraction to the surface was even slightly augmented at higher surfactant concentration, in agreement with the experimentally determined adsorption isotherm. The reason these two types of surfactants behave differently is because the ionic surfactant has a small head group that is strongly hydrophilic, whereas the head groups of the nonionic surfactants are large and only weakly attracted to water.

Keywords: emulsion polymerization process, molecular dynamics simulations, polymer surface, surfactants adsorption

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Authors: Yuanhong Zhao, Qingping Yang, Andrew Fox, Tao Zhang

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Post-occupancy evaluation (POE) is a systematic approach to assess the actual building performance after the building has been occupied for some time. In this paper, a structured POE assessment was conducted using the building use survey (BUS) methodology in two higher educational buildings in the United Kingdom. This study aims to help close the building performance gap, provide optimized building operation suggestions, and to improve occupants’ satisfaction level. In this research, the questionnaire survey investigated the influences of environmental factors on user satisfaction from the main aspects of building overall design, thermal comfort, perceived control, indoor environment quality for noise, lighting, ventilation, and other non-environmental factors, such as the background information about age, sex, time in buildings, workgroup size, and so on. The results indicate that the occupant satisfaction level with the main aspects of building overall design, indoor environment quality, and thermal comfort in summer and winter on both two buildings, which is lower than the benchmark data. The feedback of this POE assessment has been reported to the building management team to allow managers to develop high-performance building operation plans. Finally, this research provided improvement suggestions to the building operation system to narrow down the performance gap and improve the user work experience satisfaction and productivity level.

Keywords: building performance assessment systems, higher educational buildings, post-occupancy evaluation, user satisfaction

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Authors: Aisling Eves, Andrew Pieri, Ross McLean, Nerys Forester

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Background: The breast unit local guideline recommends that 12 cores should be used in a stereotactic-guided biopsy to diagnose DCIS. Twelve cores are regarded to provide good diagnostic value without removing more breast tissue than necessary. This study aimed to determine compliance with guidelines and investigated how the number of cores impacted upon the re-excision rate and size discrepancies. Methods: This single-centre retrospective cohort study of 72 consecutive breast screened patients with <15mm DCIS on radiological report underwent stereotactic-guided core biopsy and subsequent surgical excision. Clinical, radiological, and histological data were collected over 5 years, and ASCO guidelines for margin involvement of <2mm was used to guide the need for re-excision. Results: Forty-six (63.9%) patients had <12 cores taken, and 26 (36.1%) patients had ≥12 cores taken. Only six (8.3%) patients had 12 cores taken in their stereotactic biopsy. Incomplete surgical excision was seen in 17 patients overall (23.6%), and of these patients, twelve (70.6%) had fewer than 12 cores taken (p=0.55 for the difference between groups). Mammogram and biopsy underestimated the size of the DCIS in this subgroup by a median of 15mm (range: 6-135mm). Re-excision was required in 9 patients (12.5%), and five patients (6.9%) were found to have invasive ductal carcinoma on excision (80% had <12 cores, p=0.43). Discussion: There is poor compliance with the breast unit local guidelines and higher rates of re-excision in patients who did not have ≥12 cores taken. Taking ≥12 cores resulted in fewer missed invasive cancers lower incomplete excision and re-excision rates.

Keywords: stereotactic core biopsy, DCIS, breast screening, Re-excision rates, core biopsy

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Authors: Njabulo Ncube, Elena Kulinskaya, Nicholas Steel, Dmitry Pshezhetskiy

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Life expectancy in the United Kingdom (UK) has been near constant since 2010, particularly for the individuals of 65 years and older. This trend has been also noted in several other countries. This slowdown in the increase of life expectancy was concurrent with the increase in the number of deaths caused by non-communicable diseases. Of particular concern is the world-wide exponential increase in the number of diabetes related deaths. Previous studies have reported increased mortality hazards among diabetics compared to non-diabetics, and on the differing effects of antidiabetic drugs on mortality hazards. This study aimed to estimate the all-cause mortality hazards and related life expectancies among type 2 diabetes (T2DM) patients in the UK using the time-variant Gompertz-Cox model with frailty. The study also aimed to understand the major causes of the change in life expectancy growth in the last decade. A total of 221 182 (30.8% T2DM, 57.6% Males) individuals aged 50 years and above, born between 1930 and 1960, inclusive, and diagnosed between 2000 and 2016, were selected from The Health Improvement Network (THIN) database of the UK primary care data and followed up to 31 December 2016. About 13.4% of participants died during the follow-up period. The overall all-cause mortality hazard ratio of T2DM compared to non-diabetic controls was 1.467 (1.381-1.558) and 1.38 (1.307-1.457) when diagnosed between 50 to 59 years and 60 to 74 years, respectively. The estimated life expectancies among T2DM individuals without further comorbidities diagnosed at the age of 60 years were 2.43 (1930-1939 birth cohort), 2.53 (1940-1949 birth cohort) and 3.28 (1950-1960 birth cohort) years less than those of non-diabetic controls. However, the 1950-1960 birth cohort had a steeper hazard function compared to the 1940-1949 birth cohort for both T2DM and non-diabetic individuals. In conclusion, mortality hazards for people with T2DM continue to be higher than for non-diabetics. The steeper mortality hazard slope for the 1950-1960 birth cohort might indicate the sub-population contributing to a slowdown in the growth of the life expectancy.

Keywords: T2DM, Gompetz-Cox model with frailty, all-cause mortality, life expectancy

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Authors: Raymond Xu, Ashley Hua, Andrew Wang, Yuru Lin

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During COVID-19, the depression rate has increased dramatically. Young adults are most vulnerable to the mental health effects of the pandemic. Lower-income families have a higher ratio to be diagnosed with depression than the general population, but less access to clinics. This research aims to achieve early depression detection at low cost, large scale, and high accuracy with an interdisciplinary approach by incorporating clinical practices defined by American Psychiatric Association (APA) as well as multimodal AI framework. The proposed approach detected the nine depression symptoms with Natural Language Processing sentiment analysis and a symptom-based Lexicon uniquely designed for young adults. The experiments were conducted on the multimedia survey results from adolescents and young adults and unbiased Twitter communications. The result was further aggregated with the facial emotional cues analyzed by the Convolutional Neural Network on the multimedia survey videos. Five experiments each conducted on 10k data entries reached consistent results with an average accuracy of 88.31%, higher than the existing natural language analysis models. This approach can reach 300+ million daily active Twitter users and is highly accessible by low-income populations to promote early depression detection to raise awareness in adolescents and young adults and reveal complementary cues to assist clinical depression diagnosis.

Keywords: artificial intelligence, COVID-19, depression detection, psychiatric disorder

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Authors: Georgia Hopley, Andrew Murray, Alan Macpherson

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Objectives: This study aims to (i) assess the prevalence of symptoms of mental health disorders among a cohort of professional golfers, (ii) compare prevalence values with data from the general population and other elite athlete cohorts, and (iii) assess how players cope with mental health problems and players’ opinions on the mental health support services available to them. Methods: Players competing on the 2020 Challenge Tour (n=261) were sent a questionnaire that assessed symptoms of depression, distress, anxiety, sleep disturbance, and obsessive-compulsive disorder. Questions were also included to assess coping behaviors and opinions on current support measures. Results: The two-week symptom prevalence was 10.3% for depression, 51.7% for distress, 8.6% for anxiety, 10.3% for sleep disturbance, 13.8% for obsessive thoughts, and 27.6% for compulsive behavior. The prevalence of symptoms is comparable with other elite athlete cohorts, and symptoms of anxiety and distress were reported more frequently than in the general population. 67% of players who had experienced a mental health issue did not seek professional help at the time, and 61% of players did not think sufficient support was available to them. Conclusion: Mental health problems are prevalent among elite golfers; however, this study demonstrates that the majority of players do not seek help from professionally accredited practitioners. Following the discussion of this study, the European Tour Group now provides a 24/7 mental health crisis hotline for players and has educated staff members on how to identify players with mental health issues and signpost them to the appropriate support.

Keywords: elite athletes, golf, mental health, sport science, sport psychiatry

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Authors: Thampi Rawther, Jack Cecire, Andrew Sutherland

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Introduction: CT facilitates the diagnosis of potentially life-threatening injuries and facilitates early management. There is evidence that reduced CT acquisition time reduces mortality and length of hospital stay. Currently, there are variable recommendations for ideal timing. Indeed, the NHS standard contract for a major trauma service and STAG both recommend immediate access to CT within a maximum time of 60min and appropriate reporting within 60min of the scan. At Coffs Harbour Health Campus (CHHC), a CT radiographer is on site between 8am-11pm. Aim: To investigate the average time to CT at CHHC and assess for any significant relationship between time to CT and injury severity score (ISS) or time of triage. Method: All major trauma calls between Jan 2021-Oct 2021 were audited (N=87). Patients were excluded if they went from ED to the theatre. Time to CT is defined as the time between triage to the timestamp on the first CT image. Median and interquartile range was used as a measure of central tendency as the data was not normally distributed, and Chi-square test was used to determine association. Results: The median time to CT is 51.5min (IQR 40-74). We found no relationship between time to CT and ISS (P=0.18) and time of triage to time to CT (P=0.35). We compared this to other centres such as John Hunter Hospital and Gold Coast Hospital. We found that the median CT acquisition times were 76min (IQR 52-115) and 43min, respectively. Conclusion: This shows an avenue for improvement given 35% of CT’s were >30min. Furthermore, being proactive and aware of time to CT as an important factor to trauma management can be another avenue for improvement. Based on this, we will re-audit in 12-24months to assess if any improvement has been made.

Keywords: imaging, rural surgery, trauma surgery, improvement

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Authors: Sagar Ghos, Andrew E. Elaryan, Syed Ashik Ali, Musharraf Zaman, Mohammed Ashiqur Rahman

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Achieving desired density during construction is an important indicator of pavement quality. Insufficient compaction often compromises pavement performance and service life. Intelligent compaction (IC) is an emerging technology for monitoring compaction quality during the construction of asphalt pavements. This paper aims to provide an overview of findings from four case studies in Oklahoma involving the compaction quality of asphalt pavements, namely SE 44th St project (Project 1) and EOC Turnpike project (Project 2), Highway 92 project (Project 3), and 108th Avenue project (Project 4). For this purpose, an IC technology, the intelligent compaction analyzer (ICA), developed at the University of Oklahoma, was used to evaluate compaction quality. Collected data include GPS locations, roller vibrations, roller speed, the direction of movement, and temperature of the asphalt mat. The collected data were analyzed using a widely used software, VETA. The average densities for Projects 1, 2, 3 and 4, were found as 89.8%, 91.50%, 90.7% and 87.5%, respectively. The maximum densities were found as 94.6%, 95.8%, 95.9%, and 89.7% for Projects 1, 2, 3, and 4, respectively. It was observed that the ICA estimated densities correlated well with the field core densities. The ICA results indicated that at least 90% of the asphalt mats were subjected to at least two roller passes. However, the number of passes required to achieve the desired density (94% to 97%) differed from project to project depending on the underlying layer. The results of these case studies show both opportunities and challenges in using IC for monitoring compaction quality during construction in real-time.

Keywords: asphalt pavement construction, density, intelligent compaction, intelligent compaction analyzer, intelligent compaction measure value

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Authors: Yan Lu, Song Hong, Janakiraman Udaiyappan, Aarti Nagayach, Quoc-Viet A. Duong, Masao Morita, Shun Saito, Yuichi Kobayashi, Yuhai, Zhao, Hongying Peng, Nicholas B. Pham, Walter J Lukiw, Christopher A. Vuong, Nicolas G. Bazan

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Aims: Neurodegeneration and behavior dysfunction occurs in patients with Alzheimer's Disease (AD), and as the disease progresses many patients develop cognitive impairment. 5XFAD mouse model of AD is widely used to study AD pathogenesis and treatment. This study aimed to investigate the effect of maresin like 1 (MaR-L1) treatment in AD pathology using 5XFAD mice. Methods: We tested 12-month-old male 5XFAD mice and wild type control mice treated with MaR-L1 in a battery of behavioral tasks. We performed open field test, beam walking test, clasping test, inverted grid test, acetone test, marble burring test, elevated plus maze test, cross maze test and novel object recognition test. We also studied neuronal loss, amyloid β burden, and inflammation in the brains of 5XFAD mice using immunohistology and Western blotting. Results: MaR-L1 treatment to the 5XFAD mice showed improved cognitive function of 5XFAD mice. MaR-L1 showed decreased anxiety behavior in open field test and marble burring test, increased muscular strength in the beam walking test, clasping test and inverted grid test. Cognitive function was improved in MaR-L1 treated 5XFAD mice in the novel object recognition test. MaR-L1 prevented neuronal loss and aberrant inflammation. Conclusion: Our finding suggests that behavioral abnormalities were normalized by the administration of MaR-L1 and the neuroprotective role of MaR-L1 in the AD. It also indicates that MaR-L1 treatment is able to prevent and or ameliorate neuronal loss and aberrant inflammation. Further experiments to validate the results are warranted using other AD models in the future.

Keywords: Alzheimer's disease, motor and cognitive behavior, 5XFAD mice, Maresin Like 1, microglial cell, astrocyte, neurodegeneration, inflammation, resolution of inflammation

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