Search results for: Benjamin James
Commenced in January 2007
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Edition: International
Paper Count: 498

Search results for: Benjamin James

48 Persistent Ribosomal In-Frame Mis-Translation of Stop Codons as Amino Acids in Multiple Open Reading Frames of a Human Long Non-Coding RNA

Authors: Leonard Lipovich, Pattaraporn Thepsuwan, Anton-Scott Goustin, Juan Cai, Donghong Ju, James B. Brown

Abstract:

Two-thirds of human genes do not encode any known proteins. Aside from long non-coding RNA (lncRNA) genes with recently-discovered functions, the ~40,000 non-protein-coding human genes remain poorly understood, and a role for their transcripts as de-facto unconventional messenger RNAs has not been formally excluded. Ribosome profiling (Riboseq) predicts translational potential, but without independent evidence of proteins from lncRNA open reading frames (ORFs), ribosome binding of lncRNAs does not prove translation. Previously, we mass-spectrometrically documented translation of specific lncRNAs in human K562 and GM12878 cells. We now examined lncRNA translation in human MCF7 cells, integrating strand-specific Illumina RNAseq, Riboseq, and deep mass spectrometry in biological quadruplicates performed at two core facilities (BGI, China; City of Hope, USA). We excluded known-protein matches. UCSC Genome Browser-assisted manual annotation of imperfect (tryptic-digest-peptides)-to-(lncRNA-three-frame-translations) alignments revealed three peptides hypothetically explicable by 'stop-to-nonstop' in-frame replacement of stop codons by amino acids in two ORFs of the lncRNA MMP24-AS1. To search for this phenomenon genomewide, we designed and implemented a novel pipeline, matching tryptic-digest spectra to wildcard-instead-of-stop versions of repeat-masked, six-frame, whole-genome translations. Along with singleton putative stop-to-nonstop events affecting four other lncRNAs, we identified 24 additional peptides with stop-to-nonstop in-frame substitutions from multiple positive-strand MMP24-AS1 ORFs. Only UAG and UGA, never UAA, stop codons were impacted. All MMP24-AS1-matching spectra met the same significance thresholds as high-confidence known-protein signatures. Targeted resequencing of MMP24-AS1 genomic DNA and cDNA from the same samples did not reveal any mutations, polymorphisms, or sequencing-detectable RNA editing. This unprecedented apparent gene-specific violation of the genetic code highlights the importance of matching peptides to whole-genome, not known-genes-only, ORFs in mass-spectrometry workflows, and suggests a new mechanism enhancing the combinatorial complexity of the proteome. Funding: NIH Director’s New Innovator Award 1DP2-CA196375 to LL.

Keywords: genetic code, lncRNA, long non-coding RNA, mass spectrometry, proteogenomics, ribo-seq, ribosome, RNAseq

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47 The Mitigation of Quercetin on Lead-Induced Neuroinflammation in a Rat Model: Changes in Neuroinflammatory Markers and Memory

Authors: Iliyasu Musa Omoyine, Musa Sunday Abraham, Oladele Sunday Blessing, Iliya Ibrahim Abdullahi, Ibegbu Augustine Oseloka, Nuhu Nana-Hawau, Animoku Abdulrazaq Amoto, Yusuf Abdullateef Onoruoiza, Sambo Sohnap James, Akpulu Steven Peter, Ajayi Abayomi

Abstract:

The neuroprotective role of inflammation from detrimental intrinsic and extrinsic factors has been reported. However, the overactivation of astrocytes and microglia due to lead toxicity produce excessive pro-inflammatory cytokines, mediating neurodegenerative diseases. The present study investigated the mitigatory effects of quercetin on neuroinflammation, correlating with memory function in lead-exposed rats. In this study, Wistar rats were administered orally with Quercetin (Q: 60 mg/kg) and Succimer as a standard drug (S: 10 mg/kg) for 21 days after lead exposure (Pb: 125 mg/kg) of 21 days or in combination with Pb, once daily for 42 days. Working and reference memory was assessed using an Eight-arm radial water maze (8-ARWM). The changes in brain lead level, the neuronal nitric oxide synthase (nNOS) activity, and the level of neuroinflammatory markers such as tumour necrosis factor-alpha (TNF-α) and Interleukin 1 Beta (IL-1β) were determined. Immunohistochemically, astrocyte expression was evaluated. The results showed that the brain level of lead was increased significantly in lead-exposed rats. The expression of astrocytes increased in the CA3 and CA1 regions of the hippocampus, and the levels of brain TNF-α and IL-1β increased in lead-exposed rats. Lead impaired reference and working memory by increasing reference memory errors and working memory incorrect errors in lead-exposed rats. However, quercetin treatment effectively improved memory and inhibited neuroinflammation by reducing astrocytes’ expression and the levels of TNF-α and IL-1β. The expression of astrocytes and the levels of TNF-α and IL-1β correlated with memory function. The possible explanation for quercetin’s anti-neuroinflammatory effect is that it modulates the activity of cellular proteins involved in the inflammatory response; inhibits the transcription factor of nuclear factor-kappa B (NF-κB), which regulates the expression of proinflammatory molecules; inhibits kinases required for the synthesis of Glial fibrillary acidic protein (GFAP) and modifies the phosphorylation of some proteins, which affect the structure and function of intermediate filament proteins; and, lastly, induces Cyclic-AMP Response Element Binding (CREB) activation and neurogenesis as a compensatory mechanism for memory deficits and neuronal cell death. In conclusion, the levels of neuroinflammatory markers negatively correlated with memory function. Thus, quercetin may be a promising therapy in neuroinflammation and memory dysfunction in populations prone to lead exposure.

Keywords: lead, quercetin, neuroinflammation, memory

Procedia PDF Downloads 45
46 Inconsistent Effects of Landscape Heterogeneity on Animal Diversity in an Agricultural Mosaic: A Multi-Scale and Multi-Taxon Investigation

Authors: Chevonne Reynolds, Robert J. Fletcher, Jr, Celine M. Carneiro, Nicole Jennings, Alison Ke, Michael C. LaScaleia, Mbhekeni B. Lukhele, Mnqobi L. Mamba, Muzi D. Sibiya, James D. Austin, Cebisile N. Magagula, Themba’alilahlwa Mahlaba, Ara Monadjem, Samantha M. Wisely, Robert A. McCleery

Abstract:

A key challenge for the developing world is reconciling biodiversity conservation with the growing demand for food. In these regions, agriculture is typically interspersed among other land-uses creating heterogeneous landscapes. A primary hypothesis for promoting biodiversity in agricultural landscapes is the habitat heterogeneity hypothesis. While there is evidence that landscape heterogeneity positively influences biodiversity, the application of this hypothesis is hindered by a need to determine which components of landscape heterogeneity drive these effects and at what spatial scale(s). Additionally, whether diverse taxonomic groups are similarly affected is central for determining the applicability of this hypothesis as a general conservation strategy in agricultural mosaics. Two major components of landscape heterogeneity are compositional and configurational heterogeneity. Disentangling the roles of each component is important for biodiversity conservation because each represents different mechanisms underpinning variation in biodiversity. We identified a priori independent gradients of compositional and configurational landscape heterogeneity within an extensive agricultural mosaic in north-eastern Swaziland. We then tested how bird, dung beetle, ant and meso-carnivore diversity responded to compositional and configurational heterogeneity across six different spatial scales. To determine if a general trend could be observed across multiple taxa, we also tested which component and spatial scale was most influential across all taxonomic groups combined, Compositional, not configurational, heterogeneity explained diversity in each taxonomic group, with the exception of meso-carnivores. Bird and ant diversity was positively correlated with compositional heterogeneity at fine spatial scales < 1000 m, whilst dung beetle diversity was negatively correlated to compositional heterogeneity at broader spatial scales > 1500 m. Importantly, because of these contrasting effects across taxa, there was no effect of either component of heterogeneity on the combined taxonomic diversity at any spatial scale. The contrasting responses across taxonomic groups exemplify the difficulty in implementing effective conservation strategies that meet the requirements of diverse taxa. To promote diverse communities across a range of taxa, conservation strategies must be multi-scaled and may involve different strategies at varying scales to offset the contrasting influences of compositional heterogeneity. A diversity of strategies are likely key to conserving biodiversity in agricultural mosaics, and we have demonstrated that a landscape management strategy that only manages for heterogeneity at one particular scale will likely fall short of management objectives.

Keywords: agriculture, biodiversity, composition, configuration, heterogeneity

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45 Traumatic Brain Injury Neurosurgical Care Continuum Delays in Mulago Hospital in Kampala Uganda

Authors: Silvia D. Vaca, Benjamin J. Kuo, Joao Ricardo Nickenig Vissoci, Catherine A. Staton, Linda W. Xu, Michael Muhumuza, Hussein Ssenyonjo, John Mukasa, Joel Kiryabwire, Henry E. Rice, Gerald A. Grant, Michael M. Haglund

Abstract:

Background: Patients with traumatic brain injury (TBI) can develop rapid neurological deterioration from swelling and intracranial hematomas, which can result in focal tissue ischemia, brain compression, and herniation. Moreover, delays in management increase the risk of secondary brain injury from hypoxemia and hypotension. Therefore, in TBI patients with subdural hematomas (SDHs) and epidural hematomas (EDHs), surgical intervention is both necessary and time sensitive. Significant delays are seen along the care continuum in low- and middle-income countries (LMICs) largely due to limited healthcare capacity to address the disproportional rates of TBI in Sub Saharan Africa (SSA). While many LMICs have subsidized systems to offset surgical costs, the burden of securing funds by the patients for medications, supplies, and CT diagnostics poses a significant challenge to timely surgical interventions. In Kampala Uganda, the challenge of obtaining timely CT scans is twofold: logistical and financial barriers. These bottlenecks contribute significantly to the care continuum delays and are associated with poor TBI outcomes. Objective: The objectives of this study are to 1) describe the temporal delays through a modified three delays model that fits the context of neurosurgical interventions for TBI patients in Kampala and 2) investigate the association between delays and mortality. Methods: Prospective data were collected for 563 TBI patients presenting to a tertiary hospital in Kampala from 1 June – 30 November 2016. Four time intervals were constructed along five time points: injury, hospital arrival, neurosurgical evaluation, CT results, and definitive surgery. Time interval differences among mild, moderate and severe TBI and their association with mortality were analyzed. Results: The mortality rate of all TBI patients presenting to MNRH was 9.6%, which ranged from 4.7% for mild and moderate TBI patients receiving surgery to 81.8% for severe TBI patients who failed to receive surgery. The duration from injury to surgery varied considerably across TBI severity with the largest gap seen between mild TBI (174 hours) and severe TBI (69 hours) patients. Further analysis revealed care continuum differences for interval 3 (neurosurgical evaluation to CT result) and 4 (CT result to surgery) between severe TBI patients (7 hours for interval 3 and 24 hours for interval 4) and mild TBI patients (19 hours for interval 3, and 96 hours for interval 4). These post-arrival delays were associated with mortality for mild (p=0.05) and moderate TBI (p=0.03) patients. Conclusions: To our knowledge, this is the first analysis using a modified 'three delays' framework to analyze the care continuum of TBI patients in Uganda from injury to surgery. We found significant associations between delays and mortality for mild and moderate TBI patients. As it currently stands, poorer outcomes were observed for these mild and moderate TBI patients who were managed non-operatively or failed to receive surgery while surgical services were shunted to more severely ill patients. While well intentioned, high mortality rates were still observed for the severe TBI patients managed surgically. These results suggest the need for future research to optimize triage practices, understand delay contributors, and improve pre-hospital logistical referral systems.

Keywords: care continuum, global neurosurgery, Kampala Uganda, LMIC, Mulago, traumatic brain injury

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44 Comparison of Two Home Sleep Monitors Designed for Self-Use

Authors: Emily Wood, James K. Westphal, Itamar Lerner

Abstract:

Background: Polysomnography (PSG) recordings are regularly used in research and clinical settings to study sleep and sleep-related disorders. Typical PSG studies are conducted in professional laboratories and performed by qualified researchers. However, the number of sleep labs worldwide is disproportionate to the increasing number of individuals with sleep disorders like sleep apnea and insomnia. Consequently, there is a growing need to supply cheaper yet reliable means to measure sleep, preferably autonomously by subjects in their own home. Over the last decade, a variety of devices for self-monitoring of sleep became available in the market; however, very few have been directly validated against PSG to demonstrate their ability to perform reliable automatic sleep scoring. Two popular mobile EEG-based systems that have published validation results, the DREEM 3 headband and the Z-Machine, have never been directly compared one to the other by independent researchers. The current study aimed to compare the performance of DREEM 3 and the Z-Machine to help investigators and clinicians decide which of these devices may be more suitable for their studies. Methods: 26 participants have completed the study for credit or monetary compensation. Exclusion criteria included any history of sleep, neurological or psychiatric disorders. Eligible participants arrived at the lab in the afternoon and received the two devices. They then spent two consecutive nights monitoring their sleep at home. Participants were also asked to keep a sleep log, indicating the time they fell asleep, woke up, and the number of awakenings occurring during the night. Data from both devices, including detailed sleep hypnograms in 30-second epochs (differentiating Wake, combined N1/N2, N3; and Rapid Eye Movement sleep), were extracted and aligned upon retrieval. For analysis, the number of awakenings each night was defined as four or more consecutive wake epochs between sleep onset and termination. Total sleep time (TST) and the number of awakenings were compared to subjects’ sleep logs to measure consistency with the subjective reports. In addition, the sleep scores from each device were compared epoch-by-epoch to calculate the agreement between the two devices using Cohen’s Kappa. All analysis was performed using Matlab 2021b and SPSS 27. Results/Conclusion: Subjects consistently reported longer times spent asleep than the time reported by each device (M= 448 minutes for sleep logs compared to M= 406 and M= 345 minutes for the DREEM and Z-Machine, respectively; both ps<0.05). Linear correlations between the sleep log and each device were higher for the DREEM than the Z-Machine for both TST and the number of awakenings, and, likewise, the mean absolute bias between the sleep logs and each device was higher for the Z-Machine for both TST (p<0.001) and awakenings (p<0.04). There was some indication that these effects were stronger for the second night compared to the first night. Epoch-by-epoch comparisons showed that the main discrepancies between the devices were for detecting N2 and REM sleep, while N3 had a high agreement. Overall, the DREEM headband seems superior for reliably scoring sleep at home.

Keywords: DREEM, EEG, seep monitoring, Z-machine

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43 Analysis of the Outcome of the Treatment of Osteoradionecrosis in Patients after Radiotherapy for Head and Neck Cancer

Authors: Petr Daniel Kovarik, Matt Kennedy, James Adams, Ajay Wilson, Andy Burns, Charles Kelly, Malcolm Jackson, Rahul Patil, Shahid Iqbal

Abstract:

Introduction: Osteoradionecrosis (ORN) is a recognised toxicity of radiotherapy (RT) for head and neck cancer (HNC). Existing literature lacks any generally accepted definition and staging system for this toxicity. Objective: The objective is to analyse the outcome of the surgical and nonsurgical treatments of ORN. Material and Method: Data on 2303 patients treated for HNC with radical or adjuvant RT or RT-chemotherapy from January 2010 - December 2021 were retrospectively analysed. Median follow-up to the whole group of patients was 37 months (range 0–148 months). Results: ORN developed in 185 patients (8.1%). The location of ORN was as follows; mandible=170, maxilla=10, and extra oral cavity=5. Multiple ORNs developed in 7 patients. 5 patients with extra oral cavity ORN were excluded from treatment analysis as the management is different. In 180 patients with oral cavity ORN, median follow-up was 59 months (range 5–148 months). ORN healed in 106 patients, treatment failed in 74 patients (improving=10, stable=43, and deteriorating=21). Median healing time was 14 months (range 3-86 months). Notani staging is available in 158 patients with jaw ORN with no previous surgery to the mandible (Notani class I=56, Notani class II=27, and Notani class III=76). 28 ORN (mandible=27, maxilla=1; Notani class I=23, Notani II=3, Notani III=1) healed spontaneously with a median healing time 7 months (range 3–46 months). In 20 patients, ORN developed after dental extraction, in 1 patient in the neomandible after radical surgery as a part of the primary treatment. In 7 patients, ORN developed and spontaneously healed in irradiated bone with no previous surgical/dental intervention. Radical resection of the ORN (segmentectomy, hemi-mandibulectomy with fibula flap) was performed in 43 patients (all mandible; Notani II=1, Notani III=39, Notani class was not established in 3 patients as ORN developed in the neomandible). 27 patients healed (63%); 15 patients failed (improving=2, stable=5, deteriorating=8). The median time from resection to healing was 6 months (range 2–30 months). 109 patients (mandible=100, maxilla=9; Notani I=3, Notani II=23, Notani III=35, Notani class was not established in 9 patients as ORN developed in the maxilla/neomandible) were treated conservatively using a combination of debridement, antibiotics and Pentoclo. 50 patients healed (46%) with a median healing time 14 months (range 3–70 months), 59 patients are recorded with persistent ORN (improving=8, stable=38, deteriorating=13). Out of 109 patients treated conservatively, 13 patients were treated with Pentoclo only (all mandible; Notani I=6, Notani II=3, Notani III=3, 1 patient with neomandible). In total, 8 patients healed (61.5%), treatment failed in 5 patients (stable=4, deteriorating=1). Median healing time was 14 months (range 4–24 months). Extra orally (n=5), 3 cases of ORN were in the auditory canal and 2 in mastoid. ORN healed in one patient (auditory canal after 32 months. Treatment failed in 4 patients (improving=3, stable=1). Conclusion: The outcome of the treatment of ORN remains in general, poor. Every effort should therefore be made to minimise the risk of development of this devastating toxicity.

Keywords: head and neck cancer, radiotherapy, osteoradionecrosis, treatment outcome

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42 Doctor-Patient Interaction in an L2: Pragmatic Study of a Nigerian Experience

Authors: Ayodele James Akinola

Abstract:

This study investigated the use of English in doctor-patient interaction in a university teaching hospital from a southwestern state in Nigeria with the aim of identifying the role of communication in an L2, patterns of communication, discourse strategies, pragmatic acts, and contexts that shape the interaction. Jacob Mey’s Pragmatic Acts notion complemented with Emanuel and Emanuel’s model of doctor-patient relationship provided the theoretical standpoint. Data comprising 7 audio-recorded doctors-patient interactions were collected from a University Hospital in Oyo state, Nigeria. Interactions involving the use of English language were purposefully selected. These were supplemented with patients’ case notes and interviews conducted with doctors. Transcription was patterned alongside modified Arminen’s notations of conversation analysis. In the study, interaction in English between doctor and patients has the preponderance of direct-translation, code-mixing and switching, Nigerianism and use of cultural worldviews to express medical experience. Irrespective of these, three patterns communication, namely the paternalistic, interpretive, and deliberative were identified. These were exhibited through varying discourse strategies. The paternalistic model reflected slightly casual conversational conventions and registers. These were achieved through the pragmemic activities of situated speech acts, psychological and physical acts, via patients’ quarrel-induced acts, controlled and managed through doctors’ shared situation knowledge. All these produced empathising, pacifying, promising and instructing practs. The patients’ practs were explaining, provoking, associating and greeting in the paternalistic model. The informative model reveals the use of adjacency pairs, formal turn-taking, precise detailing, institutional talks and dialogic strategies. Through the activities of the speech, prosody and physical acts, the practs of declaring, alerting and informing were utilised by doctors, while the patients exploited adapting, requesting and selecting practs. The negotiating conversational strategy of the deliberative model featured in the speech, prosody and physical acts. In this model, practs of suggesting, teaching, persuading and convincing were utilised by the doctors. The patients deployed the practs of questioning, demanding, considering and deciding. The contextual variables revealed that other patterns (such as phatic and informative) are also used and they coalesced in the hospital within the situational and psychological contexts. However, the paternalistic model was predominantly employed by doctors with over six years in practice, while the interpretive, informative and deliberative models were found among registrar and others below six years of medical practice. Doctors’ experience, patients’ peculiarities and shared cultural knowledge influenced doctor-patient communication in the study.

Keywords: pragmatics, communication pattern, doctor-patient interaction, Nigerian hospital situation

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41 Use of Socially Assistive Robots in Early Rehabilitation to Promote Mobility for Infants with Motor Delays

Authors: Elena Kokkoni, Prasanna Kannappan, Ashkan Zehfroosh, Effrosyni Mavroudi, Kristina Strother-Garcia, James C. Galloway, Jeffrey Heinz, Rene Vidal, Herbert G. Tanner

Abstract:

Early immobility affects the motor, cognitive, and social development. Current pediatric rehabilitation lacks the technology that will provide the dosage needed to promote mobility for young children at risk. The addition of socially assistive robots in early interventions may help increase the mobility dosage. The aim of this study is to examine the feasibility of an early intervention paradigm where non-walking infants experience independent mobility while socially interacting with robots. A dynamic environment is developed where both the child and the robot interact and learn from each other. The environment involves: 1) a range of physical activities that are goal-oriented, age-appropriate, and ability-matched for the child to perform, 2) the automatic functions that perceive the child’s actions through novel activity recognition algorithms, and decide appropriate actions for the robot, and 3) a networked visual data acquisition system that enables real-time assessment and provides the means to connect child behavior with robot decision-making in real-time. The environment was tested by bringing a two-year old boy with Down syndrome for eight sessions. The child presented delays throughout his motor development with the current being on the acquisition of walking. During the sessions, the child performed physical activities that required complex motor actions (e.g. climbing an inclined platform and/or staircase). During these activities, a (wheeled or humanoid) robot was either performing the action or was at its end point 'signaling' for interaction. From these sessions, information was gathered to develop algorithms to automate the perception of activities which the robot bases its actions on. A Markov Decision Process (MDP) is used to model the intentions of the child. A 'smoothing' technique is used to help identify the model’s parameters which are a critical step when dealing with small data sets such in this paradigm. The child engaged in all activities and socially interacted with the robot across sessions. With time, the child’s mobility was increased, and the frequency and duration of complex and independent motor actions were also increased (e.g. taking independent steps). Simulation results on the combination of the MDP and smoothing support the use of this model in human-robot interaction. Smoothing facilitates learning MDP parameters from small data sets. This paradigm is feasible and provides an insight on how social interaction may elicit mobility actions suggesting a new early intervention paradigm for very young children with motor disabilities. Acknowledgment: This work has been supported by NIH under grant #5R01HD87133.

Keywords: activity recognition, human-robot interaction, machine learning, pediatric rehabilitation

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40 Elevated Celiac Antibodies and Abnormal Duodenal Biopsies Associated with IBD Markers: Possible Role of Altered Gut Permeability and Inflammation in Gluten Related Disorders

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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39 Leadership Education for Law Enforcement Mid-Level Managers: The Mediating Role of Effectiveness of Training on Transformational and Authentic Leadership Traits

Authors: Kevin Baxter, Ron Grove, James Pitney, John Harrison, Ozlem Gumus

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The purpose of this research is to determine the mediating effect of effectiveness of the training provided by Northwestern University’s School of Police Staff and Command (SPSC), on the ability of law enforcement mid-level managers to learn transformational and authentic leadership traits. This study will also evaluate the leadership styles, of course, graduates compared to non-attendees using a static group comparison design. The Louisiana State Police pay approximately $40,000 in salary, tuition, housing, and meals for each state police lieutenant attending the 10-week program of the SPSC. This school lists the development of transformational leaders as an increasing element. Additionally, the SPSC curriculum addresses all four components of authentic leadership - self-awareness, transparency, ethical/moral, and balanced processing. Upon return to law enforcement in roles of mid-level management, there are questions as to whether or not students revert to an “autocratic” leadership style. Insufficient evidence exists to support claims for the effectiveness of management training or leadership development. Though it is widely recognized that transformational styles are beneficial to law enforcement, there is little evidence that suggests police leadership styles are changing. Police organizations continue to hold to a more transactional style (i.e., most senior police leaders remain autocrats). Additionally, research in the application of transformational, transactional, and laissez-faire leadership related to police organizations is minimal. The population of the study is law enforcement mid-level managers from various states within the United States who completed leadership training presented by the SPSC. The sample will be composed of 66 active law enforcement mid-level managers (lieutenants and captains) who have graduated from SPSC and 65 active law enforcement mid-level managers (lieutenants and captains) who have not attended SPSC. Participants will answer demographics questions, Multifactor Leadership Questionnaire, Authentic Leadership Questionnaire, and the Kirkpatrick Hybrid Evaluation Survey. Analysis from descriptive statistics, group comparison, one-way MANCOVA, and the Kirkpatrick Evaluation Model survey will be used to determine training effectiveness in the four levels of reaction, learning, behavior, and results. Independent variables are SPSC graduates (two groups: upper and lower) and no-SPSC attendees, and dependent variables are transformational and authentic leadership scores. SPSC graduates are expected to have higher MLQ scores for transformational leadership traits and higher ALQ scores for authentic leadership traits than SPSC non-attendees. We also expect the graduates to rate the efficacy of SPSC leadership training as high. This study will validate (or invalidate) the benefits, costs, and resources required for leadership development from a nationally recognized police leadership program, and it will also help fill the gap in the literature that exists between law enforcement professional development and transformational and authentic leadership styles.

Keywords: training effectiveness, transformational leadership, authentic leadership, law enforcement mid-level manager

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38 Use of Extended Conversation to Boost Vocabulary Knowledge and Soft Skills in English for Employment Classes

Authors: James G. Matthew, Seonmin Huh, Frank X. Bennett

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English for Specific Purposes, ESP, aims to equip learners with necessary English language skills. Many ESP programs address language skills for job performance, including reading job related documents and oral proficiency. Within ESP is English for occupational purposes, EOP, which centers around developing communicative competence for the globalized workplace. Many ESP and EOP courses lack the content needed to assist students to progress at work, resulting in the need to create lexical compilation for different professions. It is important to teach communicative competence and soft skills for real job-related problem situations and address the complexities of the real world to help students to be successful in their professions. ESP and EOP research is therefore trying to balance both profession-specific educational contents as well as international multi-disciplinary language skills for the globalized workforce. The current study will build upon the existing discussion by developing pedagogy to assist students in their career through developing a strong practical command of relevant English vocabulary. Our research question focuses on the pedagogy two professors incorporated in their English for employment courses. The current study is a qualitative case study on the modes of teaching delivery for EOP in South Korea. Two foreign professors teaching at two different universities in South Korea volunteered for the study to explore their teaching practices. Both professors’ curriculums included the components of employment-related concept vocabulary, business presentations, CV/resume and cover letter preparation, and job interview preparation. All the pre-made recorded video lectures, live online class sessions with students, teachers’ lesson plans, teachers’ class materials, students’ assignments, and midterm and finals video conferences were collected for data analysis. The study then focused on unpacking representative patterns in their teaching methods. The professors used their strengths as native speakers to extend the class discussion from narrow and restricted conversations to giving students broader opportunities to practice authentic English conversation. The methods of teaching utilized three main steps to extend the conversation. Firstly, students were taught concept vocabulary. Secondly, the vocabulary was then combined in speaking activities where students had to solve scenarios, and the students were required to expand on the given forms of words and language expressions. Lastly, the students had conversations in English, using the language learnt. The conversations observed in both classes were those of authentic, expanded English communication and this way of expanding concept vocabulary lessons into extended conversation is one representative pedagogical approach that both professors took. Extended English conversation, therefore, is crucial for EOP education.

Keywords: concept vocabulary, english as a foreign language, english for employment, extended conversation

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37 Defining the Tipping Point of Tolerance to CO₂-Induced Ocean Acidification in Larval Dusky Kob Argyrosomus japonicus (Pisces: Sciaenidae)

Authors: Pule P. Mpopetsi, Warren M. Potts, Nicola James, Amber Childs

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Increased CO₂ production and the consequent ocean acidification (OA) have been identified as one of the greatest threats to both calcifying and non-calcifying marine organisms. Traditionally, marine fishes, as non-calcifying organisms, were considered to have a higher tolerance to near-future OA conditions owing to their well-developed ion regulatory mechanisms. However, recent studies provide evidence to suggest that they may not be as resilient to near-future OA conditions as previously thought. In addition, earlier life stages of marine fishes are thought to be less tolerant than juveniles and adults of the same species as they lack well-developed ion regulatory mechanisms for maintaining homeostasis. This study focused on the effects of near-future OA on larval Argyrosomus japonicus, an estuarine-dependent marine fish species, in order to identify the tipping point of tolerance for the larvae of this species. Larval A. japonicus in the present study were reared from the egg up to 22 days after hatching (DAH) under three treatments. The three treatments, (pCO₂ 353 µatm; pH 8.03), (pCO₂ 451 µatm; pH 7.93) and (pCO₂ 602 µatm; pH 7.83) corresponded to levels predicted to occur in year 2050, 2068 and 2090 respectively under the Intergovernmental Panel on Climate Change (IPCC) Representative Concentration Pathways (IPCC RCP) 8.5 model. Size-at-hatch, growth, development, and metabolic responses (standard and active metabolic rates and metabolic scope) were assessed and compared between the three treatments throughout the rearing period. Five earlier larval life stages (hatchling – flexion/post-flexion) were identified by the end of the experiment. There were no significant differences in size-at-hatch (p > 0.05), development or the active metabolic (p > 0.05) or metabolic scope (p > 0.05) of fish in the three treatments throughout the study. However, the standard metabolic rate was significantly higher in the year 2068 treatment but only at the flexion/post-flexion stage which could be attributed to differences in developmental rates (including the development of the gills) between the 2068 and the other two treatments. Overall, the metabolic scope was narrowest in the 2090 treatment but varied according to life stage. Although not significantly different, metabolic scope in the 2090 treatment was noticeably lower at the flexion stage compared to the other two treatments, and the development appeared slower, suggesting that this could be the stage most prone to OA. The study concluded that, in isolation, OA levels predicted to occur between 2050 and 2090 will not negatively affect size-at-hatch, growth, development, and metabolic responses of larval A. japonicus up to 22 DAH (flexion/post-flexion stage). The present study also identified the tipping point of tolerance (where negative impacts will begin) in larvae of the species to be between the years 2090 and 2100.

Keywords: climate change, ecology, marine, ocean acidification

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36 Elevated Systemic Oxidative-Nitrosative Stress and Cerebrovascular Function in Professional Rugby Union Players: The Link to Impaired Cognition

Authors: Tom S. Owens, Tom A. Calverley, Benjamin S. Stacey, Christopher J. Marley, George Rose, Lewis Fall, Gareth L. Jones, Priscilla Williams, John P. R. Williams, Martin Steggall, Damian M. Bailey

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Introduction and aims: Sports-related concussion (SRC) represents a significant and growing public health concern in rugby union, yet remains one of the least understood injuries facing the health community today. Alongside increasing SRC incidence rates, there is concern that prior recurrent concussion may contribute to long-term neurologic sequelae in later-life. This may be due to an accelerated decline in cerebral perfusion, a major risk factor for neurocognitive decline and neurodegeneration, though the underlying mechanisms remain to be established. The present study hypothesised that recurrent concussion in current professional rugby union players would result in elevated systemic oxidative-nitrosative stress, reflected by a free radical-mediated reduction in nitric oxide (NO) bioavailability and impaired cerebrovascular and cognitive function. Methodology: A longitudinal study design was adopted across the 2017-2018 rugby union season. Ethical approval was obtained from the University of South Wales Ethics Committee. Data collection is ongoing, and therefore the current report documents result from the pre-season and first half of the in-season data collection. Participants were initially divided into two subgroups; 23 professional rugby union players (aged 26 ± 5 years) and 22 non-concussed controls (27 ± 8 years). Pre-season measurements were performed for cerebrovascular function (Doppler ultrasound of middle cerebral artery velocity (MCAv) in response to hypocapnia/normocapnia/hypercapnia), cephalic venous concentrations of the ascorbate radical (A•-, electron paramagnetic resonance spectroscopy), NO (ozone-based chemiluminescence) and cognition (neuropsychometric tests). Notational analysis was performed to assess contact in the rugby group throughout each competitive game. Results: 1001 tackles and 62 injuries, including three concussions were observed across the first half of the season. However, no associations were apparent between number of tackles and any injury type (P > 0.05). The rugby group expressed greater oxidative stress as indicated by increased A•- (P < 0.05 vs. control) and a subsequent decrease in NO bioavailability (P < 0.05 vs. control). The rugby group performed worse in the Ray Auditory Verbal Learning Test B (RAVLT-B, learning, and memory) and the Grooved Pegboard test using both the dominant and non-dominant hands (visuomotor coordination, P < 0.05 vs. control). There were no between-group differences in cerebral perfusion at baseline (MCAv: 54 ± 13 vs. 59 ± 12, P > 0.05). Likewise, no between-group differences in CVRCO2Hypo (2.58 ± 1.01 vs. 2.58 ± 0.75, P > 0.05) or CVRCO2Hyper (2.69 ± 1.07 vs. 3.35 ± 1.28, P > 0.05) were observed. Conclusion: The present study identified that the rugby union players are characterized by impaired cognitive function subsequent to elevated systemic-oxidative-nitrosative stress. However, this appears to be independent of any functional impairment in cerebrovascular function. Given the potential long-term trajectory towards accelerated cognitive decline in populations exposed to SRC, prophylaxis to increase NO bioavailability warrants consideration.

Keywords: cognition, concussion, mild traumatic brain injury, rugby

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35 The Routes of Human Suffering: How Point-Source and Destination-Source Mapping Can Help Victim Services Providers and Law Enforcement Agencies Effectively Combat Human Trafficking

Authors: Benjamin Thomas Greer, Grace Cotulla, Mandy Johnson

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Human trafficking is one of the fastest growing international crimes and human rights violations in the world. The United States Department of State (State Department) approximates some 800,000 to 900,000 people are annually trafficked across sovereign borders, with approximately 14,000 to 17,500 of these people coming into the United States. Today’s slavery is conducted by unscrupulous individuals who are often connected to organized criminal enterprises and transnational gangs, extracting huge monetary sums. According to the International Labour Organization (ILO), human traffickers collect approximately $32 billion worldwide annually. Surpassed only by narcotics dealing, trafficking of humans is tied with illegal arms sales as the second largest criminal industry in the world and is the fastest growing field in the 21st century. Perpetrators of this heinous crime abound. They are not limited to single or “sole practitioners” of human trafficking, but rather, often include Transnational Criminal Organizations (TCO), domestic street gangs, labor contractors, and otherwise seemingly ordinary citizens. Monetary gain is being elevated over territorial disputes and street gangs are increasingly operating in a collaborative effort with TCOs to further disguise their criminal activity; to utilizing their vast networks, in an attempt to avoid detection. Traffickers rely on a network of clandestine routes to sell their commodities with impunity. As law enforcement agencies seek to retard the expansion of transnational criminal organization’s entry into human trafficking, it is imperative that they develop reliable trafficking mapping of known exploitative routes. In a recent report given to the Mexican Congress, The Procuraduría General de la República (PGR) disclosed, from 2008 to 2010 they had identified at least 47 unique criminal networking routes used to traffic victims and that Mexico’s estimated domestic victims number between 800,000 adults and 20,000 children annually. Designing a reliable mapping system is a crucial step to effective law enforcement response and deploying a successful victim support system. Creating this mapping analytic is exceedingly difficult. Traffickers are constantly changing the way they traffic and exploit their victims. They swiftly adapt to local environmental factors and react remarkably well to market demands, exploiting limitations in the prevailing laws. This article will highlight how human trafficking has become one of the fastest growing and most high profile human rights violations in the world today; compile current efforts to map and illustrate trafficking routes; and will demonstrate how the proprietary analytical mapping analysis of point-source and destination-source mapping can help local law enforcement, governmental agencies and victim services providers effectively respond to the type and nature of trafficking to their specific geographical locale. Trafficking transcends state and international borders. It demands an effective and consistent cooperation between local, state, and federal authorities. Each region of the world has different impact factors which create distinct challenges for law enforcement and victim services. Our mapping system lays the groundwork for a targeted anti-trafficking response.

Keywords: human trafficking, mapping, routes, law enforcement intelligence

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34 Internet of Assets: A Blockchain-Inspired Academic Program

Authors: Benjamin Arazi

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Blockchain is the technology behind cryptocurrencies like Bitcoin. It revolutionizes the meaning of trust in the sense of offering total reliability without relying on any central entity that controls or supervises the system. The Wall Street Journal states: “Blockchain Marks the Next Step in the Internet’s Evolution”. Blockchain was listed as #1 in Linkedin – The Learning Blog “most in-demand hard skills needed in 2020”. As stated there: “Blockchain’s novel way to store, validate, authorize, and move data across the internet has evolved to securely store and send any digital asset”. GSMA, a leading Telco organization of mobile communications operators, declared that “Blockchain has the potential to be for value what the Internet has been for information”. Motivated by these seminal observations, this paper presents the foundations of a Blockchain-based “Internet of Assets” academic program that joins under one roof leading application areas that are characterized by the transfer of assets over communication lines. Two such areas, which are pillars of our economy, are Fintech – Financial Technology and mobile communications services. The next application in line is Healthcare. These challenges are met based on available extensive professional literature. Blockchain-based assets communication is based on extending the principle of Bitcoin, starting with the basic question: If digital money that travels across the universe can ‘prove its own validity’, can this principle be applied to digital content. A groundbreaking positive answer here led to the concept of “smart contract” and consequently to DLT - Distributed Ledger Technology, where the word ‘distributed’ relates to the non-existence of reliable central entities or trusted third parties. The terms Blockchain and DLT are frequently used interchangeably in various application areas. The World Bank Group compiled comprehensive reports, analyzing the contribution of DLT/Blockchain to Fintech. The European Central Bank and Bank of Japan are engaged in Project Stella, “Balancing confidentiality and auditability in a distributed ledger environment”. 130 DLT/Blockchain focused Fintech startups are now operating in Switzerland. Blockchain impact on mobile communications services is treated in detail by leading organizations. The TM Forum is a global industry association in the telecom industry, with over 850 member companies, mainly mobile operators, that generate US$2 trillion in revenue and serve five billion customers across 180 countries. From their perspective: “Blockchain is considered one of the digital economy’s most disruptive technologies”. Samples of Blockchain contributions to Fintech (taken from a World Bank document): Decentralization and disintermediation; Greater transparency and easier auditability; Automation & programmability; Immutability & verifiability; Gains in speed and efficiency; Cost reductions; Enhanced cyber security resilience. Samples of Blockchain contributions to the Telco industry. Establishing identity verification; Record of transactions for easy cost settlement; Automatic triggering of roaming contract which enables near-instantaneous charging and reduction in roaming fraud; Decentralized roaming agreements; Settling accounts per costs incurred in accordance with agreement tariffs. This clearly demonstrates an academic education structure where fundamental technologies are studied in classes together with these two application areas. Advanced courses, treating specific implementations then follow separately. All are under the roof of “Internet of Assets”.

Keywords: blockchain, education, financial technology, mobile telecommunications services

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33 Metal-Semiconductor Transition in Ultra-Thin Titanium Oxynitride Films Deposited by ALD

Authors: Farzan Gity, Lida Ansari, Ian M. Povey, Roger E. Nagle, James C. Greer

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Titanium nitride (TiN) films have been widely used in variety of fields, due to its unique electrical, chemical, physical and mechanical properties, including low electrical resistivity, chemical stability, and high thermal conductivity. In microelectronic devices, thin continuous TiN films are commonly used as diffusion barrier and metal gate material. However, as the film thickness decreases below a few nanometers, electrical properties of the film alter considerably. In this study, the physical and electrical characteristics of 1.5nm to 22nm thin films deposited by Plasma-Enhanced Atomic Layer Deposition (PE-ALD) using Tetrakis(dimethylamino)titanium(IV), (TDMAT) chemistry and Ar/N2 plasma on 80nm SiO2 capped in-situ by 2nm Al2O3 are investigated. ALD technique allows uniformly-thick films at monolayer level in a highly controlled manner. The chemistry incorporates low level of oxygen into the TiN films forming titanium oxynitride (TiON). Thickness of the films is characterized by Transmission Electron Microscopy (TEM) which confirms the uniformity of the films. Surface morphology of the films is investigated by Atomic Force Microscopy (AFM) indicating sub-nanometer surface roughness. Hall measurements are performed to determine the parameters such as carrier mobility, type and concentration, as well as resistivity. The >5nm-thick films exhibit metallic behavior; however, we have observed that thin film resistivity is modulated significantly by film thickness such that there are more than 5 orders of magnitude increment in the sheet resistance at room temperature when comparing 5nm and 1.5nm films. Scattering effects at interfaces and grain boundaries could play a role in thickness-dependent resistivity in addition to quantum confinement effect that could occur at ultra-thin films: based on our measurements the carrier concentration is decreased from 1.5E22 1/cm3 to 5.5E17 1/cm3, while the mobility is increased from < 0.1 cm2/V.s to ~4 cm2/V.s for the 5nm and 1.5nm films, respectively. Also, measurements at different temperatures indicate that the resistivity is relatively constant for the 5nm film, while for the 1.5nm film more than 2 orders of magnitude reduction has been observed over the range of 220K to 400K. The activation energy of the 2.5nm and 1.5nm films is 30meV and 125meV, respectively, indicating that the TiON ultra-thin films are exhibiting semiconducting behaviour attributing this effect to a metal-semiconductor transition. By the same token, the contact is no longer Ohmic for the thinnest film (i.e., 1.5nm-thick film); hence, a modified lift-off process was developed to selectively deposit thicker films allowing us to perform electrical measurements with low contact resistance on the raised contact regions. Our atomic scale simulations based on molecular dynamic-generated amorphous TiON structures with low oxygen content confirm our experimental observations indicating highly n-type thin films.

Keywords: activation energy, ALD, metal-semiconductor transition, resistivity, titanium oxynitride, ultra-thin film

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32 Engineering Economic Analysis of Implementing a Materials Recovery Facility in Jamaica: A Green Industry Approach towards a Sustainable Developing Economy

Authors: Damian Graham, Ashleigh H. Hall, Damani R. Sulph, Michael A. James, Shawn B. Vassell

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This paper assesses the design and feasibility of a Materials Recovery Facility (MRF) in Jamaica as a possible green industry approach to the nation’s economic and solid waste management problems. Jamaica is a developing nation that is vulnerable to climate change that can affect its blue economy and tourism on which it is heavily reliant. Jamaica’s National Solid Waste Management Authority (NSWMA) collects only a fraction of all the solid waste produced annually which is then transported to dumpsites. The remainder is either burnt by the population or disposed of illegally. These practices negatively impact the environment, threaten the sustainability of economic growth from blue economy and tourism and its waste management system is predominantly a cost centre. The implementation of an MRF could boost the manufacturing sector, contribute to economic growth, and be a catalyst in creating a green industry with multiple downstream value chains with supply chain linkages. Globally, there is a trend to reuse and recycle that created an international market for recycled solid waste. MRFs enable the efficient sorting of solid waste into desired recoverable materials thus providing a gateway for entrance to the international trading of recycled waste. Research into the current state and effort to improve waste management in Jamaica in contrast with the similar and more advanced territories are outlined. The study explores the concept of green industrialization and its applicability to vulnerable small state economies like Jamaica. The study highlights the possible contributions and benefits derived from MRFs as a seeding factory that can anchor the reverse and forward logistics of other green industries as part of a logistic-cantered economy. Further, the study showcases an engineering economic analysis that assesses the viability of the implementation of an MRF in Jamaica. This research outlines the potential cost of constructing and operating an MRF and provides a realistic cash flow estimate to establish a baseline for profitability. The approach considers quantitative and qualitative data, assumptions, and modelling using industrial engineering tools and techniques that are outlined. Techniques of facility planning, system analysis and operations research with a focus on linear programming techniques are expressed. Approaches to overcome some implementation challenges including policy, technology and public education are detailed. The results of this study present a reasonable judgment of the prospects of incorporating an MRF to improve Jamaica’s solid waste management and contribute to socioeconomic and environmental benefits and an alternate pathway for economic sustainability.

Keywords: engineering-economic analysis, facility design, green industry, MRF, manufacturing, plant layout, solid-waste management, sustainability, waste disposal

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31 A Prospective Neurosurgical Registry Evaluating the Clinical Care of Traumatic Brain Injury Patients Presenting to Mulago National Referral Hospital in Uganda

Authors: Benjamin J. Kuo, Silvia D. Vaca, Joao Ricardo Nickenig Vissoci, Catherine A. Staton, Linda Xu, Michael Muhumuza, Hussein Ssenyonjo, John Mukasa, Joel Kiryabwire, Lydia Nanjula, Christine Muhumuza, Henry E. Rice, Gerald A. Grant, Michael M. Haglund

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Background: Traumatic Brain Injury (TBI) is disproportionally concentrated in low- and middle-income countries (LMICs), with the odds of dying from TBI in Uganda more than 4 times higher than in high income countries (HICs). The disparities in the injury incidence and outcome between LMICs and resource-rich settings have led to increased health outcomes research for TBIs and their associated risk factors in LMICs. While there have been increasing TBI studies in LMICs over the last decade, there is still a need for more robust prospective registries. In Uganda, a trauma registry implemented in 2004 at the Mulago National Referral Hospital (MNRH) showed that RTI is the major contributor (60%) of overall mortality in the casualty department. While the prior registry provides information on injury incidence and burden, it’s limited in scope and doesn’t follow patients longitudinally throughout their hospital stay nor does it focus specifically on TBIs. And although these retrospective analyses are helpful for benchmarking TBI outcomes, they make it hard to identify specific quality improvement initiatives. The relationship among epidemiology, patient risk factors, clinical care, and TBI outcomes are still relatively unknown at MNRH. Objective: The objectives of this study are to describe the processes of care and determine risk factors predictive of poor outcomes for TBI patients presenting to a single tertiary hospital in Uganda. Methods: Prospective data were collected for 563 TBI patients presenting to a tertiary hospital in Kampala from 1 June – 30 November 2016. Research Electronic Data Capture (REDCap) was used to systematically collect variables spanning 8 categories. Univariate and multivariate analysis were conducted to determine significant predictors of mortality. Results: 563 TBI patients were enrolled from 1 June – 30 November 2016. 102 patients (18%) received surgery, 29 patients (5.1%) intended for surgery failed to receive it, and 251 patients (45%) received non-operative management. Overall mortality was 9.6%, which ranged from 4.7% for mild and moderate TBI to 55% for severe TBI patients with GCS 3-5. Within each TBI severity category, mortality differed by management pathway. Variables predictive of mortality were TBI severity, more than one intracranial bleed, failure to receive surgery, high dependency unit admission, ventilator support outside of surgery, and hospital arrival delayed by more than 4 hours. Conclusions: The overall mortality rate of 9.6% in Uganda for TBI is high, and likely underestimates the true TBI mortality. Furthermore, the wide-ranging mortality (3-82%), high ICU fatality, and negative impact of care delays suggest shortcomings with the current triaging practices. Lack of surgical intervention when needed was highly predictive of mortality in TBI patients. Further research into the determinants of surgical interventions, quality of step-up care, and prolonged care delays are needed to better understand the complex interplay of variables that affect patient outcome. These insights guide the development of future interventions and resource allocation to improve patient outcomes.

Keywords: care continuum, global neurosurgery, Kampala Uganda, LMIC, Mulago, prospective registry, traumatic brain injury

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30 Post Harvest Fungi Diversity and Level of Aflatoxin Contamination in Stored Maize: Cases of Kitui, Nakuru and Trans-Nzoia Counties in Kenya

Authors: Gachara Grace, Kebira Anthony, Harvey Jagger, Wainaina James

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Aflatoxin contamination of maize in Africa poses a major threat to food security and the health of many African people. In Kenya, aflatoxin contamination of maize is high due to the environmental, agricultural and socio-economic factors. Many studies have been conducted to understand the scope of the problem, especially at pre-harvest level. This research was carried out to gather scientific information on the fungi population, diversity and aflatoxin level during the post-harvest period. The study was conducted in three geographical locations of; Kitui, Kitale and Nakuru. Samples were collected from storage structures of farmers and transported to the Biosciences eastern and central Africa (BecA), International Livestock and Research Institute (ILRI) hub laboratories. Mycoflora was recovered using the direct plating method. A total of five fungal genera (Aspergillus, Penicillium, Fusarium, Rhizopus and Bssyochlamys spp.) were isolated from the stored maize samples. The most common fungal species that were isolated from the three study sites included A. flavus at 82.03% followed by A.niger and F.solani at 49% and 26% respectively. The aflatoxin producing fungi A. flavus was recovered in 82.03% of the samples. Aflatoxin levels were analysed on both the maize samples and in vitro. Most of the A. flavus isolates recorded a high level of aflatoxin when they were analysed for presence of aflatoxin B1 using ELISA. In Kitui, all the samples (100%) had aflatoxin levels above 10ppb with a total aflatoxin mean of 219.2ppb. In Kitale, only 3 samples (n=39) had their aflatoxin levels less than 10ppb while in Nakuru, the total aflatoxin mean level of this region was 239.7ppb. When individual samples were analysed using Vicam fluorometer method, aflatoxin analysis revealed that most of the samples (58.4%) had been contaminated. The means were significantly different (p=0.00<0.05) in all the three locations. Genetic relationships of A. flavus isolates were determined using 13 Simple Sequence Repeats (SSRs) markers. The results were used to generate a phylogenetic tree using DARwin5 software program. A total of 5 distinct clusters were revealed among the genotypes. The isolates appeared to cluster separately according to the geographical locations. Principal Coordinates Analysis (PCoA) of the genetic distances among the 91 A. flavus isolates explained over 50.3% of the total variation when two coordinates were used to cluster the isolates. Analysis of Molecular Variance (AMOVA) showed a high variation of 87% within populations and 13% among populations. This research has shown that A. flavus is the main fungal species infecting maize grains in Kenya. The influence of aflatoxins on human populations in Kenya demonstrates a clear need for tools to manage contamination of locally produced maize. Food basket surveys for aflatoxin contamination should be conducted on a regular basis. This would assist in obtaining reliable data on aflatoxin incidence in different food crops. This would go a long way in defining control strategies for this menace.

Keywords: aflatoxin, Aspergillus flavus, genotyping, Kenya

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29 Online Monitoring and Control of Continuous Mechanosynthesis by UV-Vis Spectrophotometry

Authors: Darren A. Whitaker, Dan Palmer, Jens Wesholowski, James Flaherty, John Mack, Ahmad B. Albadarin, Gavin Walker

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Traditional mechanosynthesis has been performed by either ball milling or manual grinding. However, neither of these techniques allow the easy application of process control. The temperature may change unpredictably due to friction in the process. Hence the amount of energy transferred to the reactants is intrinsically non-uniform. Recently, it has been shown that the use of Twin-Screw extrusion (TSE) can overcome these limitations. Additionally, TSE enables a platform for continuous synthesis or manufacturing as it is an open-ended process, with feedstocks at one end and product at the other. Several materials including metal-organic frameworks (MOFs), co-crystals and small organic molecules have been produced mechanochemically using TSE. The described advantages of TSE are offset by drawbacks such as increased process complexity (a large number of process parameters) and variation in feedstock flow impacting on product quality. To handle the above-mentioned drawbacks, this study utilizes UV-Vis spectrophotometry (InSpectroX, ColVisTec) as an online tool to gain real-time information about the quality of the product. Additionally, this is combined with real-time process information in an Advanced Process Control system (PharmaMV, Perceptive Engineering) allowing full supervision and control of the TSE process. Further, by characterizing the dynamic behavior of the TSE, a model predictive controller (MPC) can be employed to ensure the process remains under control when perturbed by external disturbances. Two reactions were studied; a Knoevenagel condensation reaction of barbituric acid and vanillin and, the direct amidation of hydroquinone by ammonium acetate to form N-Acetyl-para-aminophenol (APAP) commonly known as paracetamol. Both reactions could be carried out continuously using TSE, nuclear magnetic resonance (NMR) spectroscopy was used to confirm the percentage conversion of starting materials to product. This information was used to construct partial least squares (PLS) calibration models within the PharmaMV development system, which relates the percent conversion to product to the acquired UV-Vis spectrum. Once this was complete, the model was deployed within the PharmaMV Real-Time System to carry out automated optimization experiments to maximize the percentage conversion based on a set of process parameters in a design of experiments (DoE) style methodology. With the optimum set of process parameters established, a series of PRBS process response tests (i.e. Pseudo-Random Binary Sequences) around the optimum were conducted. The resultant dataset was used to build a statistical model and associated MPC. The controller maximizes product quality whilst ensuring the process remains at the optimum even as disturbances such as raw material variability are introduced into the system. To summarize, a combination of online spectral monitoring and advanced process control was used to develop a robust system for optimization and control of two TSE based mechanosynthetic processes.

Keywords: continuous synthesis, pharmaceutical, spectroscopy, advanced process control

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28 Facilitating the Learning Environment as a Servant Leader: Empowering Self-Directed Student Learning

Authors: Thomas James Bell III

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Pedagogy is thought of as one's philosophy, theory, or teaching method. This study examines the science of learning, considering the forced reconsideration of effective pedagogy brought on by the aftermath of the 2020 coronavirus pandemic. With the aid of various technologies, online education holds challenges and promises to enhance the learning environment if implemented to facilitate student learning. Behaviorism centers around the belief that the instructor is the sage on the classroom stage using repetition techniques as the primary learning instrument. This approach to pedagogy ascribes complete control of the learning environment and works best for students to learn by allowing students to answer questions with immediate feedback. Such structured learning reinforcement tends to guide students' learning without considering learners' independence and individual reasoning. And such activities may inadvertently stifle the student's ability to develop critical thinking and self-expression skills. Fundamentally liberationism pedagogy dismisses the concept that education is merely about students learning things and more about the way students learn. Alternatively, the liberationist approach democratizes the classroom by redefining the role of the teacher and student. The teacher is no longer viewed as the sage on the stage but as a guide on the side. Instead, this approach views students as creators of knowledge and not empty vessels to be filled with knowledge. Moreover, students are well suited to decide how best to learn and which areas improvements are needed. This study will explore the classroom instructor as a servant leader in the twenty-first century, which allows students to integrate technology that encapsulates more individual learning styles. The researcher will examine the Professional Scrum Master (PSM I) exam pass rate results of 124 students in six sections of an Agile scrum course. The students will be separated into two groups; the first group will follow a structured instructor-led course outlined by a course syllabus. The second group will consist of several small teams (ten or fewer) of self-led and self-empowered students. The teams will conduct several event meetings that include sprint planning meetings, daily scrums, sprint reviews, and retrospective meetings throughout the semester will the instructor facilitating the teams' activities as needed. The methodology for this study will use the compare means t-test to compare the mean of an exam pass rate in one group to the mean of the second group. A one-tailed test (i.e., less than or greater than) will be used with the null hypothesis, for the difference between the groups in the population will be set to zero. The major findings will expand the pedagogical approach that suggests pedagogy primarily exist in support of teacher-led learning, which has formed the pillars of traditional classroom teaching. But in light of the fourth industrial revolution, there is a fusion of learning platforms across the digital, physical, and biological worlds with disruptive technological advancements in areas such as the Internet of Things (IoT), artificial intelligence (AI), 3D printing, robotics, and others.

Keywords: pedagogy, behaviorism, liberationism, flipping the classroom, servant leader instructor, agile scrum in education

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27 Attracting Tourists: Architecture for Tourism during the Period of Korean Empire, 1897–1910

Authors: Lina Shinhwa Koo

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The Korean Empire, or Daehanjeguk, was proclaimed by King Gojong (1852–1919) in 1897 with the aim of promoting its sovereignty as a nation-state amid the political situation with threats from neighbouring countries, such as Japan and Russia. The Korean Empire period (1897–1910), which lasted until 1910, when Japan annexed Korea, is a pivotal time in the modern history of Korea. It was also during the period when many infrastructures for tourism, including transportation and lodging systems, were established. Throughout the Korean Empire period, tourists from Japan and Euro-American countries popularly visited Korea after it opened its doors relatively recently. The government of the Korean Empire also actively engaged with foreign officials and professionals. Train stations were built to connect Busan, where foreigners first arrived through the port of Jemulpo, with Seoul, the capital of Korea. In addition, hotels were built to accommodate the increasing number of tourists. Shedding new light on the modern architectural history of Korea, this paper discusses buildings that were made for tourism during the Korean Empire period to examine the historical background behind the tourism development in Korea and the concept of travelling related to architecture history. Foreigners came to Korea for varying reasons, from ethnographic research and diplomacy to business and missionary. They also played a key role in the transportation and hotel businesses. For instance, American entrepreneur James R. Morse received a concession to construct a railway between Busan and Seoul in 1896, which was later granted to a Japanese firm. Japanese entrepreneurs came to Korea and built hotels, such as Daebul Hotel in Incheon and Paseonggwan in Seoul. Sontag Hotel, Station Hotel and Hotel du Palais, all located in central areas of Seoul, were owned by German, British and French entrepreneurs, respectively. Each building showed distinctive architectural elements. For example, Sontag Hotel was built in Russian architectural style, whereas Paseonggwan was created with a combination of Japanese and European styles. Such various architectural designs indicated the multicultural urban scenes of the Korean Empire at the time. The existing scholarship has paid more attention to the royal buildings built during the Korean Empire period, such as Seokjojeon of the Duksu Palace. However, it is important to study the tourism-related architecture that reflected the societal situation of the Korean Empire when contrasting ideologies, landscapes, historical narratives and political tensions intertwined and co-existed. Examining both textual and visual resources, such as news articles and photographs, this paper surveys architectural styles and the trajectories of selective examples of hotels and train stations within the discussion of temporality and spatiality in the discipline of social science. In doing so, one can re-assess the history of the Korean Empire as the intersection of modern and traditional, intrinsic and extrinsic and national and international.

Keywords: Korean empire, modern Korean architecture, tourism, hotel, train station

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26 Knowledge and Practices on Waste Disposal Management Among Medical Technology Students at National University – Manila

Authors: John Peter Dacanay, Edison Ramos, Cristopher James Dicang

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Waste management is a global concern due to increasing waste production from changing consumption patterns and population growth. Proper waste disposal management is a critical aspect of public health and environmental protection. In the healthcare industry, medical waste is generated in large quantities, and if not disposed of properly, it poses a significant threat to human health and the environment. Efficient waste management conserves natural resources and prevents harm to human health, and implementing an effective waste management system can save human lives. The study aimed to assess the level of awareness and practices on waste disposal management, highlighting the understanding of proper disposal, potential hazards, and environmental implications among Medical Technology students. This would help to provide more recommendations for improving waste management practices in healthcare settings as well as for better waste management practices in educational institutions. From the collected data, a female of 21 years of age stands out among the respondents. With the frequency and percentage of medical technology students' knowledge of laboratory waste management being high, it indicates that all respondents demonstrated a solid understanding of proper disposal methods, regulations, risks, and handling procedures related to laboratory waste. That said, the findings emphasize the significance of education and awareness programs in equipping individuals involved in laboratory practices with the necessary knowledge to handle and dispose of hazardous and infectious waste properly. Most respondents demonstrate positive practices or are highly mannered in laboratory waste management, including proper segregation and disposal in designated containers. However, there are concerns about the occasional mixing of waste types, emphasizing the reiteration of proper waste segregation. Students show a strong commitment to using personal protective equipment and promptly cleaning up spills. Some students admit to improper disposal due to rushing, highlighting the importance of time management and safety prioritization. Overall, students follow protocols for hazardous waste disposal, indicating a responsible approach. The school's waste management system is perceived as adequate, but continuous assessment and improvement are necessary. Encouraging reporting of issues and concerns is crucial for ongoing improvement and risk mitigation. The analysis reveals a moderate positive relationship between the respondents' knowledge and practices regarding laboratory waste management. The statistically significant correlation with a p-value of 0.26 (p-value 0.05) suggests that individuals with higher levels of knowledge tend to exhibit better practices. These findings align with previous research emphasizing the pivotal role of knowledge in influencing individuals' behaviors and practices concerning laboratory waste management. When individuals possess a comprehensive understanding of proper procedures, regulations, and potential risks associated with laboratory waste, they are more inclined to adopt appropriate practices. Therefore, fostering knowledge through education and training is essential in promoting responsible and effective waste management in laboratory settings.

Keywords: waste disposal management, knowledge, attitude, practices

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25 Cobb Angle Measurement from Coronal X-Rays Using Artificial Neural Networks

Authors: Andrew N. Saylor, James R. Peters

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Scoliosis is a complex 3D deformity of the thoracic and lumbar spines, clinically diagnosed by measurement of a Cobb angle of 10 degrees or more on a coronal X-ray. The Cobb angle is the angle made by the lines drawn along the proximal and distal endplates of the respective proximal and distal vertebrae comprising the curve. Traditionally, Cobb angles are measured manually using either a marker, straight edge, and protractor or image measurement software. The task of measuring the Cobb angle can also be represented by a function taking the spine geometry rendered using X-ray imaging as input and returning the approximate angle. Although the form of such a function may be unknown, it can be approximated using artificial neural networks (ANNs). The performance of ANNs is affected by many factors, including the choice of activation function and network architecture; however, the effects of these parameters on the accuracy of scoliotic deformity measurements are poorly understood. Therefore, the objective of this study was to systematically investigate the effect of ANN architecture and activation function on Cobb angle measurement from the coronal X-rays of scoliotic subjects. The data set for this study consisted of 609 coronal chest X-rays of scoliotic subjects divided into 481 training images and 128 test images. These data, which included labeled Cobb angle measurements, were obtained from the SpineWeb online database. In order to normalize the input data, each image was resized using bi-linear interpolation to a size of 500 × 187 pixels, and the pixel intensities were scaled to be between 0 and 1. A fully connected (dense) ANN with a fixed cost function (mean squared error), batch size (10), and learning rate (0.01) was developed using Python Version 3.7.3 and TensorFlow 1.13.1. The activation functions (sigmoid, hyperbolic tangent [tanh], or rectified linear units [ReLU]), number of hidden layers (1, 3, 5, or 10), and number of neurons per layer (10, 100, or 1000) were varied systematically to generate a total of 36 network conditions. Stochastic gradient descent with early stopping was used to train each network. Three trials were run per condition, and the final mean squared errors and mean absolute errors were averaged to quantify the network response for each condition. The network that performed the best used ReLU neurons had three hidden layers, and 100 neurons per layer. The average mean squared error of this network was 222.28 ± 30 degrees2, and the average mean absolute error was 11.96 ± 0.64 degrees. It is also notable that while most of the networks performed similarly, the networks using ReLU neurons, 10 hidden layers, and 1000 neurons per layer, and those using Tanh neurons, one hidden layer, and 10 neurons per layer performed markedly worse with average mean squared errors greater than 400 degrees2 and average mean absolute errors greater than 16 degrees. From the results of this study, it can be seen that the choice of ANN architecture and activation function has a clear impact on Cobb angle inference from coronal X-rays of scoliotic subjects.

Keywords: scoliosis, artificial neural networks, cobb angle, medical imaging

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24 Management of Femoral Neck Stress Fractures at a Specialist Centre and Predictive Factors to Return to Activity Time: An Audit

Authors: Charlotte K. Lee, Henrique R. N. Aguiar, Ralph Smith, James Baldock, Sam Botchey

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Background: Femoral neck stress fractures (FNSF) are uncommon, making up 1 to 7.2% of stress fractures in healthy subjects. FNSFs are prevalent in young women, military recruits, endurance athletes, and individuals with energy deficiency syndrome or female athlete triad. Presentation is often non-specific and is often misdiagnosed following the initial examination. There is limited research addressing the return–to–activity time after FNSF. Previous studies have demonstrated prognostic time predictions based on various imaging techniques. Here, (1) OxSport clinic FNSF practice standards are retrospectively reviewed, (2) FNSF cohort demographics are examined, (3) Regression models were used to predict return–to–activity prognosis and consequently determine bone stress risk factors. Methods: Patients with a diagnosis of FNSF attending Oxsport clinic between 01/06/2020 and 01/01/2020 were selected from the Rheumatology Assessment Database Innovation in Oxford (RhADiOn) and OxSport Stress Fracture Database (n = 14). (1) Clinical practice was audited against five criteria based on local and National Institute for Health Care Excellence guidance, with a 100% standard. (2) Demographics of the FNSF cohort were examined with Student’s T-Test. (3) Lastly, linear regression and Random Forest regression models were used on this patient cohort to predict return–to–activity time. Consequently, an analysis of feature importance was conducted after fitting each model. Results: OxSport clinical practice met standard (100%) in 3/5 criteria. The criteria not met were patient waiting times and documentation of all bone stress risk factors. Importantly, analysis of patient demographics showed that of the population with complete bone stress risk factor assessments, 53% were positive for modifiable bone stress risk factors. Lastly, linear regression analysis was utilized to identify demographic factors that predicted return–to–activity time [R2 = 79.172%; average error 0.226]. This analysis identified four key variables that predicted return-to-activity time: vitamin D level, total hip DEXA T value, femoral neck DEXA T value, and history of an eating disorder/disordered eating. Furthermore, random forest regression models were employed for this task [R2 = 97.805%; average error 0.024]. Analysis of the importance of each feature again identified a set of 4 variables, 3 of which matched with the linear regression analysis (vitamin D level, total hip DEXA T value, and femoral neck DEXA T value) and the fourth: age. Conclusion: OxSport clinical practice could be improved by more comprehensively evaluating bone stress risk factors. The importance of this evaluation is demonstrated by the population found positive for these risk factors. Using this cohort, potential bone stress risk factors that significantly impacted return-to-activity prognosis were predicted using regression models.

Keywords: eating disorder, bone stress risk factor, femoral neck stress fracture, vitamin D

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23 A Taxonomy of Professional Engineering Attributes for Tackling Global Humanitarian Challenges

Authors: Georgia Kremmyda, Angelos Georgoulas, Yiannis Koumpouros, James T. Mottram

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There is a growing interest in enhancing the creativity and problem-solving ability of engineering students by expanding their engagement to complex, interdisciplinary problems such as environmental issues, resilience to man-made and natural disasters, global health matters, water needs, increased energy demands, and other global humanitarian challenges. Tackling societal challenges requires knowledgeable and erudite engineers who can handle, combine, transform and create innovative, affordable and sustainable solutions. This view simultaneously complements and challenges current conceptions of an emerging educational movement that, almost without exception, are underpinned by calls for competitive economic growth and technological development. This article reveals a taxonomy of humanitarian attributes to be enabled to professional engineers, through reformed curricula and innovative pedagogies, which once implemented and integrated efficiently in higher engineering education, they will provide students and educators with opportunities to explore interdependencies and connections between resources, sustainable design, societal needs, and the natural environment and to critically engage with implicit and explicit facets of disciplinary identity. The research involves carrying out a study on (a) current practices, best practices and barriers in knowledge organisation, content, and hierarchy in graduate engineering programmes, (b) best practices associated with teaching and research in engineering education around the world, (c) opportunities inherent in general reforms of graduate engineering education and inherent in integrating the humanitarian context throughout engineering education programmes, and, (d) an overarching taxonomy of professional attributes for tackling humanitarian challenges. Research methods involve state-of-the-art literature review on engineering education and pedagogy to resource thematic findings on current status in engineering education worldwide, and qualitative research through three practice dialogue workshops, run in Asia (Vietnam, Indonesia and Bangladesh) involving a variety of national, international and local stakeholders (industries; NGOs, governmental organisations). Findings from this study provide evidence on: (a) what are the professional engineering attributes (skills, experience, knowledge) needed for tackling humanitarian challenges; (b) how we can integrate other disciplines and professions to engineering while defining the professional attributes of engineers who are capable of tackling humanitarian challenges. The attributes will be linked to those discipline(s) and profession(s) that are more likely to enforce the attributes (removing the assumption that engineering education as it stands at the moment can provide all attributes), and; (c) how these attributes shall be supplied; what kind of pedagogies or training shall take place beyond current practices. Acknowledgment: The study is currently in progress and is being undertaken in the framework of the project ENHANCE - ENabling Humanitarian Attributes for Nurturing Community-based Engineering (project No: 598502-EEP-1-2018-1-UK-EPPKA2-CBHE-JP (2018-2582/001-001), funded by the Erasmus + KA2 Cooperation for innovation and the exchange of good practices – Capacity building in the field of Higher Education.

Keywords: professional engineering attributes, engineering education, taxonomy, humanitarian challenges, humanitarian engineering

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22 Numerical and Experimental Comparison of Surface Pressures around a Scaled Ship Wind-Assisted Propulsion System

Authors: James Cairns, Marco Vezza, Richard Green, Donald MacVicar

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Significant legislative changes are set to revolutionise the commercial shipping industry. Upcoming emissions restrictions will force operators to look at technologies that can improve the efficiency of their vessels -reducing fuel consumption and emissions. A device which may help in this challenge is the Ship Wind-Assisted Propulsion system (SWAP), an actively controlled aerofoil mounted vertically on the deck of a ship. The device functions in a similar manner to a sail on a yacht, whereby the aerodynamic forces generated by the sail reach an equilibrium with the hydrodynamic forces on the hull and a forward velocity results. Numerical and experimental testing of the SWAP device is presented in this study. Circulation control takes the form of a co-flow jet aerofoil, utilising both blowing from the leading edge and suction from the trailing edge. A jet at the leading edge uses the Coanda effect to energise the boundary layer in order to delay flow separation and create high lift with low drag. The SWAP concept has been originated by the research and development team at SMAR Azure Ltd. The device will be retrofitted to existing ships so that a component of the aerodynamic forces acts forward and partially reduces the reliance on existing propulsion systems. Wind tunnel tests have been carried out at the de Havilland wind tunnel at the University of Glasgow on a 1:20 scale model of this system. The tests aim to understand the airflow characteristics around the aerofoil and investigate the approximate lift and drag coefficients that an early iteration of the SWAP device may produce. The data exhibits clear trends of increasing lift as injection momentum increases, with critical flow attachment points being identified at specific combinations of jet momentum coefficient, Cµ, and angle of attack, AOA. Various combinations of flow conditions were tested, with the jet momentum coefficient ranging from 0 to 0.7 and the AOA ranging from 0° to 35°. The Reynolds number across the tested conditions ranged from 80,000 to 240,000. Comparisons between 2D computational fluid dynamics (CFD) simulations and the experimental data are presented for multiple Reynolds-Averaged Navier-Stokes (RANS) turbulence models in the form of normalised surface pressure comparisons. These show good agreement for most of the tested cases. However, certain simulation conditions exhibited a well-documented shortcoming of RANS-based turbulence models for circulation control flows and over-predicted surface pressures and lift coefficient for fully attached flow cases. Work must be continued in finding an all-encompassing modelling approach which predicts surface pressures well for all combinations of jet injection momentum and AOA.

Keywords: CFD, circulation control, Coanda, turbo wing sail, wind tunnel

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21 Pharmacokinetics and Safety of Pacritinib in Patients with Hepatic Impairment and Healthy Volunteers

Authors: Suliman Al-Fayoumi, Sherri Amberg, Huafeng Zhou, Jack W. Singer, James P. Dean

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Pacritinib is an oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CSF1R. In clinical studies, pacritinib was well tolerated with clinical activity in patients with myelofibrosis. The most frequent adverse events (AEs) observed with pacritinib are gastrointestinal (diarrhea, nausea, and vomiting; mostly grade 1-2 in severity) and typically resolve within 2 weeks. A human ADME mass balance study demonstrated that pacritinib is predominantly cleared via hepatic metabolism and biliary excretion (>85% of administered dose). The major hepatic metabolite identified, M1, is not thought to materially contribute to the pharmacological activity of pacritinib. Hepatic diseases are known to impair hepatic blood flow, drug-metabolizing enzymes, and biliary transport systems and may affect drug absorption, disposition, efficacy, and toxicity. This phase 1 study evaluated the pharmacokinetics (PK) and safety of pacritinib and the M1 metabolite in study subjects with mild, moderate, or severe hepatic impairment (HI) and matched healthy subjects with normal liver function to determine if pacritinib dosage adjustments are necessary for patients with varying degrees of hepatic insufficiency. Study participants (aged 18-85 y) were enrolled into 4 groups based on their degree of HI as defined by Child-Pugh Clinical Assessment Score: mild (n=8), moderate (n=8), severe (n=4), and healthy volunteers (n=8) matched for age, BMI, and sex. Individuals with concomitant renal dysfunction or progressive liver disease were excluded. A single 400 mg dose of pacritinib was administered to all participants. Blood samples were obtained for PK evaluation predose and at multiple time points postdose through 168 h. Key PK parameters evaluated included maximum plasma concentration (Cmax), time to Cmax (Tmax), area under the plasma concentration time curve (AUC) from hour zero to last measurable concentration (AUC0-t), AUC extrapolated to infinity (AUC0-∞), and apparent terminal elimination half-life (t1/2). Following treatment, pacritinib was quantifiable for all study participants at 1 h through 168 h postdose. Systemic pacritinib exposure was similar between healthy volunteers and individuals with mild HI. However, there was a significant difference between those with moderate and severe HI and healthy volunteers with respect to peak concentration (Cmax) and plasma exposure (AUC0-t, AUC0-∞). Mean Cmax decreased by 47% and 57% respectively in participants with moderate and severe HI vs matched healthy volunteers. Similarly, mean AUC0-t decreased by 36% and 45% and mean AUC0-∞ decreased by 46% and 48%, respectively in individuals with moderate and severe HI vs healthy volunteers. Mean t1/2 ranged from 51.5 to 74.9 h across all groups. The variability on exposure ranged from 17.8% to 51.8% across all groups. Systemic exposure of M1 was also significantly decreased in study participants with moderate or severe HI vs. healthy participants and individuals with mild HI. These changes were not significantly dissimilar from the inter-patient variability in these parameters observed in healthy volunteers. All AEs were grade 1-2 in severity. Diarrhea and headache were the only AEs reported in >1 participant (n=4 each). Based on these observations, it is unlikely that dosage adjustments would be warranted in patients with mild, moderate, or severe HI treated with pacritinib.

Keywords: pacritinib, myelofibrosis, hepatic impairment, pharmacokinetics

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20 QIP: Introducing a Dedicated Ozurdex Clinic

Authors: Vaisnavy Govindasamy, Saba Ishrat

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Introduction: The Dexamethasone Intravitreal Implant 0.7 mg (OzurdexTM, Allergan®) is a biodegradable corticosteroid implant approved by the FDA for managing diabetic macular edema (DMO), macular edema following branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO), and posterior segment non-infectious uveitis. This implant can release dexamethasone over a six-month period, exhibiting peak effectiveness between 60 and 90 days post-administration. The intravitreal injection should be performed under sterile conditions. At James Cook University Hospital (JCUH), Ozurdex injections are currently administered in the Vitreo-Retinal (VR) theatre. This study aimed to evaluate the feasibility and potential advantages of establishing a dedicated clinic for Ozurdex administration separate from the VR theatre setting. Method: Retrospectively, data of all Ozurdex injections administered between October 2021 to October 2022 was collected from operating theatre registers at JCUH. Data pertaining to the indications for Ozurdex; waiting times from referral date to date of injection; duration of theatre time consumed; and post-injection complications were collected from electronic notes. The resources needed to establish a dedicated Ozurdex clinic were evaluated. Over a six-month period from October 2023 to March 2024, we gathered data on utilization of theatre 28. Results: A total of 135 Ozurdex injections were administered. Among the indications, uveitis represented 47.3% of cases, DMO with 23.6% and RVO with 22.9%. Remaining cases lacked sufficient data. Each Ozurdex injection procedure consumed 15 minutes in the VR theatre list. Complications arose in 5% of injections, totaling 7 cases. These included glaucoma, ocular hypertension, subconjunctival haemorrhage and implant migration. Waiting times averaged 6 weeks from date for referral to procedure date. We also found that, on an average theatre 28 was offered but remained unused for 4 days, totalling eight sessions in a month. Analysis: Establishing a sperate Ozurdex clinic would improve the quality of patient care in following ways: 1.Decrease injection waiting times (currently averaging 6 weeks), leading to better visual outcomes. 2.Free up approximately three hours of theatre time in Vitreo-Retina theatres each month, allowing for 3-4 additional surgeries. Reduce waiting times for critical retinal surgeries and enhance visual outcomes. 3.Provide additional training opportunities for trainees and retina fellows, improving their skills. 4.Optimize the use of empty theatre slots (theatre 28) currently experiencing underutilization of resources. Conclusion: These findings support the implementation of a separate clinic for administering Ozurdex injections at JCUH. It is evident that introducing a dedicated clinic will enhance operational efficiency, optimise resource utilsation, and improve overall quality of care for patients undergoing this treatment.

Keywords: opthalmology, ozurdex, efficiency, complication

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19 Performance and Limitations of Likelihood Based Information Criteria and Leave-One-Out Cross-Validation Approximation Methods

Authors: M. A. C. S. Sampath Fernando, James M. Curran, Renate Meyer

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Model assessment, in the Bayesian context, involves evaluation of the goodness-of-fit and the comparison of several alternative candidate models for predictive accuracy and improvements. In posterior predictive checks, the data simulated under the fitted model is compared with the actual data. Predictive model accuracy is estimated using information criteria such as the Akaike information criterion (AIC), the Bayesian information criterion (BIC), the Deviance information criterion (DIC), and the Watanabe-Akaike information criterion (WAIC). The goal of an information criterion is to obtain an unbiased measure of out-of-sample prediction error. Since posterior checks use the data twice; once for model estimation and once for testing, a bias correction which penalises the model complexity is incorporated in these criteria. Cross-validation (CV) is another method used for examining out-of-sample prediction accuracy. Leave-one-out cross-validation (LOO-CV) is the most computationally expensive variant among the other CV methods, as it fits as many models as the number of observations. Importance sampling (IS), truncated importance sampling (TIS) and Pareto-smoothed importance sampling (PSIS) are generally used as approximations to the exact LOO-CV and utilise the existing MCMC results avoiding expensive computational issues. The reciprocals of the predictive densities calculated over posterior draws for each observation are treated as the raw importance weights. These are in turn used to calculate the approximate LOO-CV of the observation as a weighted average of posterior densities. In IS-LOO, the raw weights are directly used. In contrast, the larger weights are replaced by their modified truncated weights in calculating TIS-LOO and PSIS-LOO. Although, information criteria and LOO-CV are unable to reflect the goodness-of-fit in absolute sense, the differences can be used to measure the relative performance of the models of interest. However, the use of these measures is only valid under specific circumstances. This study has developed 11 models using normal, log-normal, gamma, and student’s t distributions to improve the PCR stutter prediction with forensic data. These models are comprised of four with profile-wide variances, four with locus specific variances, and three which are two-component mixture models. The mean stutter ratio in each model is modeled as a locus specific simple linear regression against a feature of the alleles under study known as the longest uninterrupted sequence (LUS). The use of AIC, BIC, DIC, and WAIC in model comparison has some practical limitations. Even though, IS-LOO, TIS-LOO, and PSIS-LOO are considered to be approximations of the exact LOO-CV, the study observed some drastic deviations in the results. However, there are some interesting relationships among the logarithms of pointwise predictive densities (lppd) calculated under WAIC and the LOO approximation methods. The estimated overall lppd is a relative measure that reflects the overall goodness-of-fit of the model. Parallel log-likelihood profiles for the models conditional on equal posterior variances in lppds were observed. This study illustrates the limitations of the information criteria in practical model comparison problems. In addition, the relationships among LOO-CV approximation methods and WAIC with their limitations are discussed. Finally, useful recommendations that may help in practical model comparisons with these methods are provided.

Keywords: cross-validation, importance sampling, information criteria, predictive accuracy

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