Search results for: Kathryn H. Yull

Authors: Kathryn H. Yull, Lina T. Al Kury, Frank Christopher Howarth

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Cardiovascular diseases are frequently reported in patients with Type-1 Diabetes mellitus (DM). In addition to changes in cardiac muscle inotropy, electrical abnormalities are also commonly observed in these patients. In the present study, using streptozotocin (STZ) rat model of Type-1 DM, we have characterized the changes in L-type calcium channel activity in single atrioventricular nodal (AVN) myocytes. Ionic currents were recorded from AVN myocytes isolated from the hearts of control rats and from those with STZ-induced diabetes. Patch-clamp recordings were used to assess changes in cellular electrical activity in individual myocytes. Type-1 DM significantly altered the cellular characteristics of L-type calcium current (ICaL). A reduction in peak ICaL density was observed, with no corresponding changes in the activation parameters of the current. ICaL also exhibited faster time-dependent inactivation in AVN myocytes from diabetic rats. A negative shift in the voltage dependence of inactivation was also evident. These findings demonstrate that experimentally–induced type-1 DM significantly alters AVN L-type calcium channel cellular electrophysiology. The changes in ion channel activity may underlie the abnormalities in the cardiac electrical function that contribute to the high mortality levels in patients with DM.

Keywords: cardiac, ion-channel, diabetes, atrioventricular node, calcium channel

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Authors: Lan Yang, Kathryn Cormican, Ming Yu

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ISO/IEC/IEEE 15288: 2015, Systems and Software Engineering - System Life Cycle Processes is an international standard that provides generic top-level process descriptions to support systems engineering (SE). However, the processes defined in the standard needs improvement to lift integrity and consistency. The goal of this research is to explore the way by building an ontology model for the SE standard to manage the knowledge of SE. The ontology model gives a whole picture of the SE knowledge domain by building connections between SE concepts. Moreover, it creates a hierarchical classification of the concepts to fulfil different requirements of displaying and analysing SE knowledge.

Keywords: knowledge management, model-based systems engineering, ontology modelling, systems engineering ontology

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Authors: Kathryn Watson

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In 2020 North Carolina passed legislation mandating all educators be trained in identifying, referring, and supporting students showing signs of mental health issues, drug use, suicidal ideation, and sex trafficking. This study collected survey responses from 226 educators in North Carolina to better understand their perspectives on the legislation and their self-efficacy in supporting student mental health needs. Key findings of the study reveal that the mandated trainings increased educator awareness of student mental health, and higher awareness was linked to higher self-efficacy in supporting student mental health needs. Additionally, the results showed that educators who identify as Black had lower levels of self-efficacy in supporting student mental health. Additionally, rural educators were least likely to support the legislation in comparison to their urban and suburban counterparts. These findings can help inform policymakers in evaluating the policy and district decision-makers in selecting and implementing school-based mental health training.

Keywords: school-based mental health, education policy, student health, North Carolina, K-12 education

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Authors: Vanessa R. Ralph, Kathryn N. Hosbein, Megan Y. Deshaye, Paulette Vincent-Ruz

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The language of the statement “persistent achievement gaps between demographic groups” communicates much about the philosophies inherent to the author. In this synthesis of two flagship journals of Chemistry Education Research: Chemistry Education Research and Practice and the Journal of Chemical Education, the use and investigation of equity was examined by the language, epistemology, and methodologies of the researchers. Findings include a considerable increase in the use and investigation of equity in these journals following the years 2012 and 2020. While an increase in consciousness of equity was apparent, epistemologies were stagnated. The majority reflects a deficit-oriented perspective wherein deficits are attributed to students as a “lack of achievement” inherent to specific “demographic groups” and minimized as “gaps” rather than systemic inequities. The lack of epistemological progress may be the result of reading and citing literature within discipline-based education research, failing to acknowledge the efforts propagated for decades by equity theory advancement in disciplines of sociology and psychology. To envision liberated educational systems across the globe, one must first contend with the biases within.

Keywords: liberating education research, philosophy of research, synthesis, review

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Authors: Kathryn Norgang, Sarah Howrath, Auni Idi Muhire, Pacifique Umubyeyi

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Description : A group of nurses address the shortage of trained staff to respond to critical patients at Rwanda Military Hospital (RMH) by developing a training program and a resuscitation response team. Members of the group who received the training when it first launched are now trainer of trainers; all components of the training program are organized and delivered by RMH staff-the clinical mentor only provides adjunct support. This two day training is held quarterly at RMH; basic life support and exposure to interventions for advanced care are included in the test and skills sign off. Seventy staff members have received the training this year alone. An increased number of admission/transfer to ICU due to successful resuscitation attempts is noted. Lessons learned: -Number of staff trained 2012-2014 (to be verified). -Staff who train together practice with greater collaboration during actual resuscitation events. -Staff more likely to initiate BLS if peer support is present-more staff trained equals more support. -More access to Advanced Cardiac Life Support training is necessary now that the cadre of BLS trained staff is growing. Conclusions: Increased access to training, peer support, and collaborative practice are effective strategies to strengthening resuscitation capacity within a hospital.

Keywords: resuscitation, basic life support, capacity building, resuscitation response teams, nurse trainer of trainers

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Authors: Dung V. H. Pham, Kathryn Cullen

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Introduction: 40% of adolescents with major depression (MDD) are unresponsive to 1st line antidepressant treatment. The neural mechanism underlying treatment-responsive and treatment-resistant depression in adolescent are unclear. Amygdala is important for emotion processing and has been implicated in mood disorders. Past research has shown abnormal amygdala connectivity in adolescents with MDD. This research study changes in amygdala resting-state functional connectivity to find neural correlates of successful antidepressant treatment. Methods: Thirteen adolescents aged 12-19 underwent rfMRI before and after 8-week antidepressant treatment and completed BDI-II at each scan. A whole-brain approach, using anatomically defined amygdala ROIs (1) identified brain regions that are highly synchronous with the amygdala, (2) correlated neural changes with changes in overall depression and specific symptom clusters within depression. Results: Some neural correlates were common across domains: (1) decreased amygdala RSFC with the default mode network (posterior cingulate, precuneus) is associated with improvement in overall depression and many symptom clusters, (2) increased amygdala RSFC with fusiform gyrus is associated with symptom improvement across many symptom clusters. We also found unique neural changes associated with symptom improvement in each symptom cluster. Conclusion: This is the first preliminary study that looks at neural correlates of antidepressant treatment response to overall depression as well as different clusters of symptoms of depression. The finding suggests both overlapping and distinct neural mechanisms underlying improvement in each symptom clusters within depression. Some brain regions found are also implicated in MDD among adults in previous literature.

Keywords: depression, adolescents, fMRI, antidepressants

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Authors: M. Munirul Islam, Makhduma Khatun M., Janet M. Peerson, Tahmeed Ahmed, M. Abid Hossain Mollah, Kathryn G. Dewey, Kenneth H. Brown

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Information is required on the effects of dietary energy density (ED) and feeding frequency (FF) of complementary foods (CF) on food consumption during individual meals and time expended in child feeding. We evaluated the effects of varied ED and FF of CFs on food intake and time required for child feeding during individual meals. During 9 separate, randomly ordered dietary periods lasting 3-6 days each, we measured self-determined intakes of porridges by 18 healthy, breastfed children 8-11 mo old who were fed coded porridges with energy densities of 0.5, 1.0 or 1.5 kcal/g, during 3, 4, or 5 meals/d. CF intake was measured by weighing the feeding bowl before and after every meal. Children consumed greater amounts of CFs per meal when they received diets with lower ED (p = 0.044) and fewer meals per day (p < 0.001). Food intake was less during the first meal of the day than the other meals. Greater time was expended per meal when fewer meals were offered. Time expended per meal did not vary by ED, but the children ate the lower ED diets faster (p = 0.019). Food intake velocity was also greater when more meals were offered per day (p = 0.005). These results provide further evidence of young children’s ability to regulate their energy intakes, even during infancy; and they convey information on factors that affect the amount of time that caregivers must devote to child feeding.

Keywords: complementary foods, energy density, feeding frequency, young children

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Authors: Tei Kim, Brooklynn McNeil, Kathryn Dunn, Douglas I. Walker

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To better characterize the relationship between complex chemical exposures and disease, our laboratory uses an approach that combines low-cost, polydimethylsiloxane (silicone) wristband samplers that absorb many of the chemicals we are exposed to with untargeted high-resolution mass spectrometry (HRMS) to characterize 1000’s of chemicals at a time. In studies with human populations, these wristbands can provide an important measure of our environment: however, there is a need to use this approach in large cohorts to study exposures associated with the disease. To facilitate the use of silicone samplers in large scale population studies, the goal of this research project was to establish automated sample preparation methods that improve throughput, robustness, and scalability of analytical methods for silicone wristbands. Using the Opentron OT2 automated liquid platform, which provides a low-cost and opensource framework for automated pipetting, we created two separate workflows that translate the manual wristband preparation method to a fully automated protocol that requires minor intervention by the operator. These protocols include a sequence generation step, which defines the location of all plates and labware according to user-specified settings, and a transfer protocol that includes all necessary instrument parameters and instructions for automated solvent extraction of wristband samplers. These protocols were written in Python and uploaded to GitHub for use by others in the research community. Results from this project show it is possible to establish automated and open source methods for the preparation of silicone wristband samplers to support profiling of many environmental exposures. Ongoing studies include deployment in longitudinal cohort studies to investigate the relationship between personal chemical exposure and disease.

Keywords: bioinformatics, automation, opentrons, research

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Authors: Benjamin L. Freidman, Sally L. Gras, Ian Snape, Geoff W. Stevens, Kathryn A. Mumford

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Increasing transportation and storage of petroleum hydrocarbons in Antarctic and sub-Antarctic regions have resulted in frequent accidental spills. Migrating petroleum hydrocarbon spills can have a significant impact on terrestrial and marine ecosystems in cold regions, as harsh environmental conditions result in heightened sensitivity to pollution. This migration of contaminants has led to the development of Permeable Reactive Barriers (PRB) for application in cold regions. PRB’s are one of the most practical technologies for on-site or in-situ groundwater remediation in cold regions due to their minimal energy, monitoring and maintenance requirements. The Main Power House site has been used as a fuel storage and power generation area for the Macquarie Island research station since at least 1960. Soil analysis at the site has revealed Total Petroleum Hydrocarbon (TPH) (C9-C28) concentrations as high as 19,000 mg/kg soil. Groundwater TPH concentrations at this site can exceed 350 mg/L TPH. Ongoing migration of petroleum hydrocarbons into the neighbouring marine ecosystem resulted in the installation of a ‘funnel and gate’ PRB in November 2014. The ‘funnel and gate’ design successfully intercepted contaminated groundwater and analysis of TPH retention and biodegradation on PRB media are currently underway. Installation of the PRB facilitates research aimed at better understanding the contribution of particle attached biofilms to the remediation of groundwater systems. Bench-scale PRB system analysis at The University of Melbourne is currently examining the role biofilms play in petroleum hydrocarbon degradation, and how controlled release nutrient media can heighten the metabolic activity of biofilms in cold regions in the presence of low temperatures and low nutrient groundwater.

Keywords: groundwater, petroleum, Macquarie island, funnel and gate

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Authors: Kathryn Strachan, Sameer Otoom, Amal AL-Gallaf, Ahmed Al Ansari

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Introduction: Introducing a reliable method to select graduates for an award in higher education can be challenging but is not impossible. Multisource feedback (MSF) is a popular assessment tool that relies on evaluations of different groups of people, including physicians and non-physicians. It is useful for assessing several domains, including professionalism, communication and collaboration and may be useful for selecting the best interns to receive a University award. Methods: 16 graduates responded to an invitation to participate in the student award, which was conducted by the Royal College of Surgeons of Ireland-Bahrain Medical University of Bahrain (RCSI Bahrain) using the MSF process. Five individuals from the following categories rated each participant: physicians, nurses, and fellow students. RCSI Bahrain graduates were assessed in the following domains; professionalism, communication, and collaboration. Mean and standard deviation were calculated and the award was given to the graduate who scored the highest among his/her colleagues. Cronbach’s coefficient was used to determine the questionnaire’s internal consistency and reliability. Factor analysis was conducted to examine for the construct validity. Results: 16 graduates participated in the RCSI-Bahrain interns’ award based on the MSF process, giving us a 16.5% response rate. The instrument was found to be suitable for factor analysis and showed 3 factor solutions representing 79.3% of the total variance. Reliability analysis using Cronbach’s α reliability of internal consistency indicated that the full scale of the instrument had high internal consistency (Cronbach’s α 0.98). Conclusion: This study found the MSF process to be reliable and valid for selecting the best graduates for the interns’ awards. However, the low response rates may suggest that the process is not feasible for allowing the majority of the students to participate in the selection process. Further research studies may be required to support the feasibility of the MSF process in selecting graduates for the university award.

Keywords: MSF, RCSI, validity, Bahrain

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Authors: Gary Pattemore, Michael Edgar, Andrew Job, Marina Auad, Kathryn Job

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As critical commodities become more scarce, significant time and resources have been used to better understand complicated ore bodies and extract their full potential. These challenging ore bodies provide several pain points for geologists and engineers to overcome, poor handling of these issues flows downs stream to the processing plant affecting throughput rates and recovery. Many open cut mines utilise blast hole drilling to extract additional information to feed back into the modelling process. This method requires samples to be collected during or after blast hole drilling. Samples are then sent for assay with turnaround times varying from 1 to 12 days. This method is time consuming, costly, requires human exposure on the bench and collects elemental data only. To address this challenge, research has been undertaken to utilise hyperspectral imaging across a broad spectrum to scan samples, collars or take down hole measurements for minerals and moisture content and grade abundances. Automation of this process using unmanned vehicles and on-board processing reduces human in pit exposure to ensure ongoing safety. On-board processing allows data to be integrated into modelling workflows with immediacy. The preliminary results demonstrate numerous direct and indirect benefits from this new technology, including rapid and accurate grade estimates, moisture content and mineralogy. These benefits allow for faster geo modelling updates, better informed mine scheduling and improved downstream blending and processing practices. The paper presents recommendations for implementation of the technology in open cut mining environments.

Keywords: grade control, hyperspectral scanning, artificial intelligence, autonomous mining, machine learning

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Authors: Kathryn Redmond, Mojdeh Asadollahi Pajouh, Grace Panther, Rick Evans, Stacey Kulesza, Jia Liang

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An on-going focus in engineering education research is on increasing the number of women in engineering. While the number of women participating in engineering project teams has increased over the past five years, the number of women enrolled in engineering colleges remains stagnant. Previous studies have explored why the number of women enrolled in engineering colleges remains small. In doing so, researchers focused primarily on negative experiences women encountered. Instead of looking at negative experiences, which can further deter women from entering the field, the aim of this study is to explore the personal and institutional factors that allow women to succeed and thrive in undergraduate engineering programs. There are two research questions addressed in this paper. The first is: what are the personal traits and characteristics that allow women to thrive in engineering? The other is: what are the institutional policies and culture, as well as micro-level behaviors on project teams, that influence the environment for women to thrive in engineering? Two women studying engineering at an R1 university were interviewed. Each woman was interviewed three times for a total of six interviews. The phenomenographic interviews focused on the lived experiences of the participants to better understand thriving in engineering. The first interview focused on the women’s personal life and background, the second on their learning journey and project team experiences, and the third focused on videos the women took through a method called Photovoice. Interviews were transcribed, and an inductive thematic analysis was conducted. Four themes were identified. Multiple coders were utilized to ensure trustworthiness and increase interrater reliability. Results indicate that thriving women have supportive families, experienced gender biases, and enjoy hands-on engineering and creating a final product. These traits and experiences may help inspire younger women to pursue engineering degrees and can help inform institutions as they make policy changes to support women. Additional women will be recruited from four different universities to further develop a theoretical framework to help inform institutions in how they can support women to thrive in engineering.

Keywords: diversity, inclusion, project teams, women in engineering

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Authors: Akunna Agunwah, Kevin Gallimore, Kathryn Kinmond

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Entrepreneurship is widely associated and seen as a vehicle for economic growth; however, different scholars have studied entrepreneurship from various perspectives, resulting in multiple definitions. It is surprising to know most entrepreneurship definition does not incorporate growth as part of their definition of entrepreneurship. Economic growth is engineered by the activities of the entrepreneurs. The purpose of the present theoretical study is to explore the working practices of the successful entrepreneurs towards achieving business growth by understanding the experiences of the entrepreneur using the Theory of Planned Behaviour (TPB) as a lens. Ten successful entrepreneurs in the North West of England in various business sectors were interviewed using semi-structured interview method. The recorded audio interviews transcribed and subsequently evaluated using the thematic deductive technique (qualitative approach). The themes were examined using Theory of Planned Behaviour to ascertain the presence of the three intentional antecedents (attitude, subjective norms, and perceived behavioural control). The findings categorised in two folds, firstly, it was observed that the three intentional antecedents, which make up Theory of Planned Behaviour were evident in the transcript. Secondly, the entrepreneurs are most concerned with achieving a state of freedom and realising their visions and ambitions. Nevertheless, the entrepreneur employed these intentional antecedents to enhance business growth. In conclusion, the work presented here showed a novel way of understanding the working practices and experiences of the entrepreneur using the theory of planned behaviour in qualitative approach towards enhancing business growth. There exist few qualitative studies in entrepreneurship research. In addition, this work applies a novel approach to studying the experience of the entrepreneurs by examining the working practices of the successful entrepreneurs in the North-West England through the lens of the theory of planned behaviour. Given the findings regarding TPB as a lens in the study, the entrepreneur does not differentiate between the categories of the antecedents reasonably sees them as processes that can be utilised to enhance business growth.

Keywords: business growth, experience, interpretive, theory of planned behaviour

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Authors: Kathryn L. Duncan, Charles A. Kuntz, James O. Simcock

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A surgical approach to the cranium for treatment of frontal lobe and olfactory bulb neoplasia in dogs is described in this report, which provided excellent access for visualisation and removal of gross neoplastic tissue. An 8-year-old spayed female Shih Tzu crossbreed dog (dog 1) and a 13-year-old neutered male Miniature Fox Terrier (dog 2) were evaluated for removal of neoplasms involving both the frontal lobe and olfactory bulb. Both dogs presented with abnormal neurological clinical signs, decreased menace responses, and behavioural changes. Additionally, dog 2 presented with compulsive circling and generalized tonic-clonic seizure activity. Computed tomography was performed in both dogs, and MRI was also performed in dog 1. Imaging was consistent with frontal lobe and olfactory bulb neoplasia. A transorbital frontal bone craniectomy, with orbital ligament desmotomy and ventrolateral retraction of the globe, was performed in both cases without complication. Dog 1 had a focal area of lysis in the frontal bone adjacent to the neoplasm in the frontal lobe. The presence of the bone defect provided part of the impetus for this approach, as it would permit resection of the lytic bone. In addition, the neoplasms would be surgically accessible without encountering interposed brain parenchyma, reducing the risk of iatrogenic injury. Both dogs were discharged from the hospital within 72 hours post-operatively, both with normal mentation. Case 1 had a histopathologic diagnosis of malignant anaplastic neoplasm. The tumour recurred 101d postoperatively, and the patient was euthanized. Case 2 was diagnosed with a meningioma and was neurologically normal at 294d postoperatively. This transorbital surgical approach allowed successful removal of the intracranial frontal lobe and olfactory bulb neoplasms in 2 dogs. This approach should be considered for dogs with lateralized frontal lobe and olfactory bulb neoplasms that are closely associated with the suborbital region of the frontal bone.

Keywords: neurosurgery, small animal surgery, surgical oncology, veterinary neurology

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Authors: Muhammad Afzal, Shahbaz Mushtaq, Duc-Anh-An-Vo, Kathryn Reardon Smith, Thanh Ma

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Climate change has become one of the most challenging environmental issues in the 21st century. Climate change-induced natural disasters, especially floods, are the major factors of livelihood vulnerability, impacting millions of individuals worldwide. Evaluating and mitigating the effects of floods requires an in-depth understanding of the relationship between vulnerability and livelihood capital assets. Using an integrated approach, sustainable livelihood framework, and system thinking approach, the study developed a conceptual model of a generalized livelihood system in District Rajanpur, Pakistan. The model visualizes the livelihood vulnerability system as a whole and identifies the key feedback loops likely to influence the livelihood vulnerability. The study suggests that such conceptual models provide effective communication and understanding tools to stakeholders and decision-makers to anticipate the problem and design appropriate policies. It can also serve as an evaluation technique for rural livelihood policy and identify key systematic interventions. The key finding of the study reveals that household income, health, and education are the major factors behind the livelihood vulnerability of the rural poor of District Rajanpur. The Pakistani government tried to reduce the livelihood vulnerability of the region through different income, health, and education programs, but still, many changes are required to make these programs more effective especially during the flood times. The government provided only cash to vulnerable and marginalized families through income support programs, but this study suggests that along with the cash, the government must provide seed storage facilities and access to crop insurance to the farmers. Similarly, the government should establish basic health units in villages and frequent visits of medical mobile vans should be arranged with advanced medical lab facilities during and after the flood.

Keywords: livelihood vulnerability, rural communities, flood, sustainable livelihood framework, system dynamics, Pakistan

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Authors: Kathryn L. Duncan, Charles A. Kuntz, Alessandra C. Santamaria, James O. Simcock

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Access to megavoltage radiation therapy for small animals is limited in many locations around the world. This can preclude the use of palliative radiation therapy for the treatment of appendicular osteosarcoma in dogs. The objective of this study was to retrospectively assess the adverse effects and survival times of dogs with appendicular osteosarcoma that were treated with hypofractionated orthovoltage radiation therapy and adjunctive carboplatin chemotherapy administered via a single subcutaneous infusion. Medical records were reviewed retrospectively to identify client-owned dogs with spontaneously occurring appendicular osteosarcoma that was treated with palliative orthovoltage radiation therapy and a single subcutaneous infusion of carboplatin. Data recorded included signalment, tumour location, results of diagnostic imaging, haematologic and serum biochemical analyses, adverse effects of radiation therapy and chemotherapy, and survival times. Kaplan-Meier survival analysis was performed, and log-rank analysis was used to determine the impact of specific patient variables on survival time. Twenty-three dogs were identified that met the inclusion criteria. Median survival time for dogs was 182 days. Eleven dogs had adverse haematologic effects, 3 had adverse gastrointestinal effects, 6 had adverse effects at the radiation site and 7 developed infections at the carboplatin infusion site. No statistically significant differences were identified in survival times based on sex, tumour location, development of infection, or pretreatment serum alkaline phosphatase. Median survival time and incidence of adverse effects were comparable to those previously reported in dogs undergoing palliative radiation therapy with megavoltage or cobalt radiation sources and conventional intravenous carboplatin chemotherapy. The use of orthovoltage palliative radiation therapy may be a reasonable alternative to megavoltage radiation in locations where access is limited.

Keywords: radiotherapy, veterinary oncology, chemotherapy, osteosarcoma

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Authors: Akunna Agunwah, Kevin Gallimore, Kathryn Kinnmond

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Entrepreneurship and project management are widely associated and seen as a vehicle for economic growth, but are studied separately. A few authors have considered the interconnectivity existing between these two fields, but relatively little empirical data currently exist in the literature. The purpose of the present empirical study is to explore whether successful entrepreneurs utilise project management approaches in enhancing enterprise growth by understanding the working practices and experiences of the entrepreneurs’ using the Theory of Planned Behaviour (TPB) as a lens. In order to understand those experiences, ten successful entrepreneurs in various business sectors in the North West of England were interviewed through a face-to-face semi-structured interview method. The collected audio tape-recorded data was transcribed and analysed using the deductive thematic technique (qualitative approach). The themes were viewed through the lens of Theory of Planned Behaviour to identify the three intentional antecedents (attitude, subjective norms, and perceived behavioural control) and to understand how they relate to the project management approaches (Planning, execution, and monitoring). The findings are twofold, the first evidence of the three intentional antecedents, which make up Theory of Planned Behaviour was present. Secondly, the analysis of project management approaches themes (planning, execution, and monitoring) using the lens of the theory of planned behaviour shows evidence of the three intentional antecedents. There were more than one intentional antecedents found in a particular project management theme, which indicates that the entrepreneur does utilise these approaches without categorising them into definite themes. However, the entrepreneur utilised these intentional antecedents as processes to enhanced business growth. In conclusion, the work presented here showed a way of understanding the interconnectivity between entrepreneurship and project management towards enhancing enterprise growth by examining the working practices and experiences of the successful entrepreneurs in the North-West England.

Keywords: business growth, entrepreneurship, project management approaches, theory of planned behaviour

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Authors: Kathryn Rooney, Kaitlyn Eddy, Evan Landers, Weihui Li

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The international mortality rate for neonates and infants has been declining at a disproportionally low rate when compared to the overall decline in child mortality in recent decades. A significant portion of infant deaths could be prevented with the implementation of low-cost and easy to use physiological monitoring devices, by enabling early identification of symptoms before they progress into life-threatening illnesses. The oral diagnostic device discussed in this paper serves to continuously monitor the key vital signs of body temperature, respiratory rate, heart rate, and oxygen saturation. The device mimics an infant pacifier, designed to be easily tolerated by infants as well as orthodontically inert. The fundamental measurements are gathered via thermistors and a pulse oximeter, each encapsulated in medical-grade silicone and wired internally to a microcontroller chip. The chip then translates the raw measurements into physiological values via an internal algorithm, before outputting the data to a liquid crystal display screen and an Android application. Additionally, a biological sample collection chamber is incorporated into the internal portion of the device. The movement within the oral chamber created by sucking on the pacifier-like device pushes saliva through a small check valve in the distal end, where it is accumulated and stored. The collection chamber can be easily removed, making the sample readily available to be tested for various diseases and analytes. With the vital sign monitoring and sample collection offered by this device, abnormal fluctuations in physiological parameters can be identified and appropriate medical care can be sought. This device enables preventative diagnosis for infants who may otherwise have gone undiagnosed, due to the inaccessibility of healthcare that plagues vast numbers of underprivileged populations.

Keywords: neonate mortality, infant mortality, low-cost diagnostics, vital signs, saliva testing, preventative care

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Authors: Andrea Parisi, Samantha Vilkins, Luis Furuya-Kanamori, John A. Crump, Benjamin P. Howden, Darren Gray, Kathryn Glass, Martyn Kirk

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Objectives: Salmonella is a leading cause of foodborne enterocolitis worldwide. Nontyphoidal Salmonella (NTS) infections that are Multi-Drug Resistant (MDR) (non-susceptible to ≥1 agent in ≥3 antimicrobial categories) may result in more severe outcomes, although these effects have not been systematically examined. We conducted a systematic review and meta-analysis to examine impacts of MDR NTS on health in high-income settings. Methods: We systematically reviewed the literature from scientific databases, including PubMed, Scopus and grey literature sources, using PRISMA guidelines. We searched for data from case-control studies, cohorts, outbreaks, reports and theses, imposing no language restriction. We included only publications from January 1990 to September 2016 from high income countries as classified by World Bank. We extracted data from papers on duration of illness, hospitalisation rates, morbidity and mortality for MDR and non-MDR NTS strains. Results: After removing duplicates, the initial search revealed 4258 articles. After further screening, we identified 16 eligible studies for the systematic review, and 9 of these were included in meta-analysis. NTS serotypes differed among the reported studies but serotype Typhimurium, Enteritidis, Newport and Heidelberg were among the most often reported as MDR pathogens. Salmonella infections that were MDR were associated with excess bloodstream infections (OR 1.63; 95%CI 1.18-2.26), excess hospitalisations (OR 2.77; 95%CI 1.47-5.21) and higher mortality (OR 3.54; 95%CI 1.10-11.40). Conclusions: MDR NTS infections are a serious public health concern. With the emergence of MDR Salmonella strains in the high-income countries, it is crucial to restrict the use of antimicrobials both in animals and humans, and intervene to prevent foodborne infections.

Keywords: Antimicrobial Resistance, Bloodstream Infection, Health Outcomes, Hospitalisation, Invasive Disease, Multi-Drug Resistance (MDR), Mortality, Nontyphoidal Salmonella

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Authors: Fadia Gafri, Kathryn Mckintosh, Louise Young, Alan Harvey, Simon Mackay, Andrew Paul, Robin Plevin

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Nuclear factor-kappa B (NF-κB) is a ubiquitous transcription factor found originally to play a key role in regulating inflammation. However considerable evidence links this pathway to the suppression of apoptosis, cellular transformation, proliferation and invasion (Aggarwal et al., 2006). Moreover, recent studies have also linked inflammation to cancer progression making NF-κB overall a promising therapeutic target for drug discovery (Dobrovolskaia & Kozlov, 2005). In this study we examined the effect of the natural product canthin-6-one (SU182) as part of a CRUK small molecule drug discovery programme for effects upon the NF-κB pathway. Initial studies demonstrated that SU182 was found to have good potency against the inhibitory kappa B kinases (IKKs) at 30M in vitro. However, at concentrations up to 30M, SU182 had no effect upon TNFα stimulated loss in cellular IκBα or p65 phosphorylation in the keratinocyte cell line NCTC2544. Nevertheless, 30M SU182 reduced TNF-α / PMA-induced NF-κB-linked luciferase reporter activity to (22.9 ± 5%) and (34.6± 3 %, P<0.001) respectively, suggesting an action downstream of IKK signalling. Indeed, SU182 neither decreased NF-κB-DNA binding as assayed by EMSA nor prevented the translocation of p65 (NF-κB) to the nucleus assessed by immunofluorescence and subcellular fractionation. In addition to the inhibition of transcriptional activity of TNFα-induced NF-κB reporter activity SU182 significantly reduced PMA-induced AP-1-linked luciferase reporter activity to about (48± 9% at 30M, P<0.001) . This mode of inhibition was not sufficient to prevent the activation of NF-κB dependent induction of other proteins such as COX-2 and iNOS, or activated MAP kinases (p38, JNK and ERK1/2) in LPS stimulated RAW 264.7 macrophages. Taken together these data indicate the potential for SU182 to interfere with the transcription factors NF-κB and AP-1 at transcriptional level. However, no potential anti-inflammatory effect was indicated, further investigation for other NF-κB dependent proteins linked to survival are also required to identify the exact mechanism of action.

Keywords: Canthin-6-one, NF-κB, AP-1, phosphorylation, Nuclear translocation, DNA-binding activity, inflammatory proteins.

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Authors: Tony Feng, Rea Thomson, Kathryn Greenslade, Ross Medine, Jennifer Easterbrook, Calum Arthur, Matilda Powell-bowns

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There are clear guidelines on taking group and screen samples (G&S) for elective arthroplasty and major trauma. However, there is limited guidance on blood grouping for other trauma patients. The purpose of this study was to review the level of blood grouping at a major trauma centre and validate a protocol that limits the expensive processing of G&S samples. After reviewing the national guidance on transfusion samples in orthopaedic patients, data was prospectively collected for all orthopaedic admissions in the Royal Infirmary of Edinburgh between January to February 2023. The cause of admission, number of G&S samples processed on arrival and need for red cells was collected using the hospital blood bank. A new protocol was devised based on a multidisciplinary meeting which limited the requirement for G&S samples only to presentations in “category X”, including neck-of-femur fractures (NOFs), pelvic fractures and major trauma. A re-audit was completed between April and May after departmental education and institution of this protocol. 759 patients were admitted under orthopaedics in the major trauma centre across two separate months. 47% of patients were admitted with presentations falling in category X (354/759) and patients in this category accounted for 88% (92/104) of those requiring post-operative red cell transfusions. Of these, 51% were attributed to NOFs (47/92). In the initial audit, 50% of trauma patients outwith category X had samples sent (116/230), estimated to cost £3800. Of these 230 patients, 3% required post-operative transfusions (7/230). In the re-audit, 23% of patients outwith category X had samples sent (40/173), estimated to cost £1400, of which 3% (5/173) required transfusions. None of the transfusions in these patients in either audit were related to their operation and the protocol achieved an estimated cost saving of £2400 over one month. This study highlights the importance of sending samples for patients with certain categories of orthopaedic trauma (category X) due to the high demand for post-operative transfusions. However, the absence of transfusion requirements in other presentations suggests over-testing. While implementation of the new protocol has markedly reduced over-testing, additional interventions are required to reduce this further.

Keywords: blood transfusion, quality improvement, orthopaedics, trauma

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Authors: Kathryn Nderitu, Atunga Nyachieo, Ezekiel Mecha

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Introduction: Solanum nigrum , also known as black nightshade, biosynthesizes various phytochemical compounds with various pharmacological activities, including treating cardiovascular diseases and type 2 diabetes, among others. Materials and Methods: To assess the anti-obesity effects of Solanum nigrum using high-fat-fed diet rats, Sprague Dawley male rats (n = 35) of weights 160–180 g were assigned randomly into seven groups comprising n = 5 rats each. Each group was fed for 11 weeks as follows: normal group (normal chow rat feed); high-fat diet control (HFD); HFD and standard drug (Orlistat 30 mg/kg bw); HFD and methanolic extract 150 mg/kgbw; HFD and methanolic extract 300 mg/kgbw; HFD and dichloromethane extract 150 mg/kgbw; HFD and dichloromethane extract 300 mg/kgbw. Body mass index and food intake were monitored per week, and an oral glucose tolerance test was measured in weeks 5 and 10. Lipid profiles, liver function tests, adipose tissue, liver weights, and phytochemical analysis of Solanum nigrum were later carried out. Results: High-fat diet control group rats exhibited a significant increase in body mass index (BMI), while rats administered with leaf extracts of Solanum nigrum showed a reduction in BMI. Both low doses of dichloromethane (150 mg/kgbw) and high doses of methanol extracts (300 mg/kgbw) showed a better reduction in BMI than the other treatment groups. A significant decrease (p <0.05) in low-density lipoprotein-cholesterol, triglycerides, and cholesterol was observed among the rats administered with Solanum nigrum extracts compared to those of HFD control. Moreover, the HFD control group significantly increased liver and adipose tissue weights compared to other treatment groups (p<0.05). Solanum nigrum also decreased glycemic levels and normalized the hepatic enzymes of HFD control. However, food intake among the groups showed no significant difference (p>0.05). Qualitative analysis of Solanum nigrum leaf extracts indicated the presence of various bioactive compounds associated with anti-obesity. Conclusion: These results validate the use of Solanum nigrum in controlling obesity.

Keywords: solanum nigrum, High fat diet, phytocompounds, obesity

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Authors: Agatha Bebbington, Terry Tetley, Kathryn Hadler

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Background: Astronauts will set foot on the Moon later this decade, and are at high risk of lunar dust inhalation. Freshly-fractured lunar dust produces reactive oxygen species in solution, which are known to cause cellular damage and inflammation. Cytotoxicity and inflammatory mediator release was measured in pulmonary alveolar epithelial cells (cells that line the gas-exchange zone of the lung) exposed to a lunar dust simulant, LMS-1. It was hypothesised that freshly-fractured LMS-1 would result in increased cytotoxicity and inflammatory mediator release, owing to the angular morphology and high reactivity of fractured particles. Methods: A human alveolar epithelial type 1-like cell line (TT1) and a human macrophage-like cell line (THP-1) were exposed to 0-200μg/ml of unground, aged-ground, and freshly-ground LMS-1 (screened at <22μm). Cell viability, cytotoxicity, and inflammatory mediator release (IL-6, IL-8) were assessed using MMT, LDH, and ELISA assays, respectively. LMS-1 particles were characterised for their size, surface area, and morphology before and after grinding. Results: Exposure to LMS-1 particles did not result in overt cytotoxicity in either TT1 epithelial cells or THP-1 macrophage-like cells. A dose-dependent increase in IL-8 release was observed in TT1 cells, whereas THP-1 cell exposure, even at low particle concentrations, resulted in increased IL-8 release. Both cytotoxic and pro-inflammatory responses were most marked and significantly greater in TT1 and THP-1 cells exposed to freshly-fractured LMS-1. Discussion: LMS-1 is a novel lunar dust simulant; this is the first study to determine its toxicological effects on respiratory cells in vitro. An increased inflammatory response in TT1 and THP-1 cells exposed to ground LMS-1 suggests that low particle size, increased surface area, and angularity likely contribute to toxicity. Conclusions: Evenlow levels of exposure to LMS-1 could result in alveolar inflammation. This may have pathological consequences for astronauts exposed to lunar dust on future long-duration missions. Future research should test the effect of low-dose, intermittent lunar dust exposure on the respiratory system.

Keywords: lunar dust, LMS-1, lunar dust simulant, long-duration space travel, lunar dust toxicity

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Authors: Tarek K. Jalouta, Jolietta R. Holliman, Kathryn R. Burke, Kathleen M. Bewley-Thomas

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Background: Chronic hepatitis C virus (HCV) infection is one of the leading causes of liver cirrhosis and hepatocellular carcinoma. In the United States, HCV screening awareness, treatment, and linkage to care are under continues ascending progress. However, still millions of people are asymptomatically infected and undiagnosed yet. Through this community mission, we sought to identify the best and the newest strategies to identify those infected people to educate them, link them to care and cure them. Methods: We have identified patients that did not have a prior HCV screening in our Electronic medical record (EMR) including all our different hospital locations (South Suburban Chicago, Northern, Western and Central Indiana). Providing education to all Primary care/Gastroenterology/Infectious diseases providers and staff in the clinic to increase awareness of the HCV screening. Health-related quality of life, chronic clinical complications, and demographics data were collected for each patient. All outcomes of HCV antibody-reactive and HCV RNA–positive results were identified and statistically analyzed. Results: From July 2016 to July 2018 we screened 35,720 individuals of birth cohort in our different Franciscan’s health medical centers. Of the screened population, 986 (2.7%) individuals were HCV AB-reactive. Of those, 319 (1%) patients were HCV RNA-positive, and 264 patients were counseled and linked to providers. 34 patients initiated anti-HCV therapy with successful treatment. Conclusions: Our HCV screening augmentation project considered the largest screening program in the Midwest. Augmenting the HCV screening process through creating a Best Practice Alert (BPA) in the EMR (Epic Sys.) and point of care testing could be helpful. Although continued work is required, our team is working on increase screening through adding HCV test to CBC-Panels in Emergency Department settings, phone calls to all birth cohort individuals through Robo-Calling System aimed to reach 75,000 individuals by 2019. However, a better linkage to care and referral monitoring system to all HCV RNA positive patients is still needed, and access to therapy, especially for uninsured patients, is challenging.

Keywords: chronic hepatitis C, chronic hepatitis C treatment, chronic hepatitis C screening, chronic hepatitis C prevention, liver cancer

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Authors: Lauren Kathryn Stretch

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A study was conducted in the underprivileged setting of Nelson Mandela Bay, South Africa in order to monitor the progress of learners whose teachers receive training through the Early Inspiration Training Programme. Through tracking children’s growth & development, the effectiveness of the practitioner-training programme, which focuses on empowering women from underprivileged communities in South Africa, was analyzed. The aim was to identify impact & reach and to assess the effectiveness of this intervention programme through identifying impact on children’s growth and development. A Pre- and Post-Test was administered on about 850 young children in Pre-Grade R and Grade R classes in order to understand children’s ability level & the growth that would be evident as a result of effective teacher training. A pre-test evaluated the level of each child’s abilities, including physical-motor development, language, and speech development, cognitive development including visual perceptual skills, social-emotional development & play development. This was followed by a random selection of the classes of children into experimental and control groups. The experimental group’s teachers (practitioners) received 8-months of training & intervention, as well as mentorship & support. After the 8-month training programme, children from the experimental & control groups underwent post-assessment. The results indicate that the impact of effective practitioner training and enhancing a deep understanding of stimulation on young children, that this understanding is implemented in the classroom, highlighting the areas of growth & development in the children whose teachers received additional training & support, as compared to those who did not receive additional training. Monitoring & Evaluation systems not only track children’s ability levels, but also have a core focus on reporting systems, mentorship and providing ongoing support. As a result of the study, an Online Application (for Apple or Android Devices) was developed which is used to track children’s growth via age-appropriate assessments. The data is then statistically analysed to provide direction for relevant & impactful intervention. The App also focuses on effective reporting strategies, structures, and implementation to support organizations working with young children & maximize on outcomes.

Keywords: early childhood development, developmental child assessments, online application, monitoring and evaluating online

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Authors: Spencer Liu, William Chan, Marlena Komatz, Tommy Ramos, Mark Trentalange, Faye Rim, Dae Kim, Mary Kelly, Samuel Schuessler, Roberta Stack, Justas Lauzadis, Kathryn DelPizzo, Seth Waldman, Alexandra Sideris

Abstract:

Background & Significance: The increasing prevalence of cannabis use in the United States has important safety considerations in the perioperative setting, as chronic or heavy preoperative cannabis use may increase the risk of intraoperative complications, postoperative nausea and vomiting (PONV), increased postoperative pain levels, and acute side effects associated with cannabis use cessation. In this retrospective chart review study, we sought to determine the prevalence of self-reported cannabis use in the past 5-years at a single institution in New York City. We hypothesized that there is an increasing prevalence of preoperative self-reported cannabis use among adult and adolescent patients undergoing orthopedic surgery. Methods: After IRB approval for this retrospective study, surgical cases performed on patients 12 years of age and older at the hospital’s main campus and two ambulatory surgery centers between January 1st, 2018, and December 31st, 2023, with preoperatively self-disclosed cannabis use entered in the social history intake form were identified using the tool SlicerDicer in Epic. Case and patient characteristics were extracted, and trends in utilization over time were assessed by the Cochran-Armitage trend test. Results: Overall, the prevalence of self-reported cannabis use increased from 6.6% in 2018 to 10.6% in 2023. By age group, the prevalence of self-reported cannabis use among adolescents remained consistently low (2018: 2.6%, 2023: 2.6%) but increased with significant evidence for a linear trend (p < 0.05) within every adult age group. Among adults, patients who were 18-24 years old (2018: 18%, 2023: 20.5%) and 25-34 years old (2018: 15.9%, 2023: 24.2%) had the highest prevalences of disclosure, whereas patients who were 75 years of age or older had the lowest prevalence of disclosure (2018: 1.9%, 2023: 4.6%). Patients who were 25-34 years old had the highest percent difference in disclosure rates of 8.3%, which corresponded to a 52.2% increase from 2018 to 2023. The adult age group with the highest percent change was patients who were 75 years of age or older, with a difference of 2.7%, which corresponded to a 142.1% increase from 2018 to 2023. Conclusions: These trends in preoperative self-reported cannabis use among patients undergoing orthopedic surgery have important implications for perioperative care and clinical outcomes. Efforts are underway to refine and standardize cannabis use data capture at our institution.

Keywords: orthopedic surgery, cannabis, postoperative pain, postoperative nausea

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Authors: Peter J. Fusco, Dave M. Mathew, Chris Mathew, Kenneth H. Levy, Kathryn S. Varghese, Stephanie Salazar-Restrepo, Serena M. Mathew, Sofia Khaja, Eamon Vega, Mia Polizzi, Alyssa Mullane, Adham Ahmed

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Background: Laparoscopic (LS) removal of neuroblastomas in children has been reported to offer favorable outcomes compared to the conventional open thoracotomy (OT) procedure. Critical perioperative measures such as blood loss, operative time, length of stay, and time to postoperative chemotherapy have all supported laparoscopic use rather than its more invasive counterpart. Herein, a pairwise meta-analysis was performed comparing perioperative outcomes between LS and OT in thoracoabdominal neuroblastoma cases. Methods: A comprehensive literature search was performed on PubMed, Ovid EMBASE, and Scopus databases to identify studies comparing the outcomes of pediatric patients with thoracoabdominal neuroblastomas undergoing resection via OT or LS. After deduplication, 4,227 studies were identified and subjected to initial title screening with exclusion and inclusion criteria to ensure relevance. When studies contained overlapping cohorts, only the larger series were included. Primary outcomes include estimated blood loss (EBL), hospital length of stay (LOS), and mortality, while secondary outcomes were tumor recurrence, post-operative complications, and operation length. The “meta” and “metafor” packages were used in R, version 4.0.2, to pool risk ratios (RR) or standardized mean differences (SMD) in addition to their 95% confidence intervals in the random effects model via the Mantel-Haenszel method. Heterogeneity between studies was assessed using the I² test, while publication bias was assessed via funnel plot. Results: The pooled analysis included 209 patients from 5 studies (141 OT, 68 LS). Of the included studies, 2 originated from the United States, 1 from Toronto, 1 from China, and 1was from a Japanese center. Mean age between study cohorts ranged from 2.4 to 5.3 years old, with female patients occupying between 30.8% to 50% of the study populations. No statistically significant difference was found between the two groups for LOS (SMD -1.02; p=0.083), mortality (RR 0.30; p=0.251), recurrence(RR 0.31; p=0.162), post-operative complications (RR 0.73; p=0.732), or operation length (SMD -0.07; p=0.648). Of note, LS appeared to be protective in the analysis for EBL, although it did not reach statistical significance (SMD -0.4174; p= 0.051). Conclusion: Despite promising literature assessing LS removal of pediatric neuroblastomas, results showed it was non-superior to OT for any explored perioperative outcomes. Given the limited comparative data on the subject, it is evident that randomized trials are necessary to further the efficacy of the conclusions reached.

Keywords: laparoscopy, neuroblastoma, thoracoabdominal, thoracotomy

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Authors: Kathryn McMillan

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A recent study of 8500 adult Australians aged 16 and over revealed 62% had experienced childhood maltreatment. In response to multiple recommendations by bodies such as the Australian Law Reform Commission, parliamentary reports and stakeholder input, a number of key initiatives have been developed to grapple with the difficulties of a federal-state system and to screen and triage high-risk families navigating their way through the court system. The Lighthouse Project (LHP) is a world-first initiative of the Federal Circuit and Family Courts in Australia (FCFOCA) to screen family law litigants for major risk factors, including family violence, child abuse, alcohol or substance abuse and mental ill-health at the point of filing in all applications that seek parenting orders. It commenced on 7 December 2020 on a pilot basis but has now been expanded to 15 registries across the country. A specialist risk screen, Family DOORS, Triage has been developed – focused on improving the safety and wellbeing of families involved in the family law system safety planning and service referral, and ¬ differentiated case management based on risk level, with the Evatt List specifically designed to manage the highest risk cases. Early signs are that this approach is meeting the needs of families with multiple risks moving through the Court system. Before the LHP, there was no data available about the prevalence of risk factors experienced by litigants entering the family courts and it was often assumed that it was the litigation process that was fueling family violence and other risks such as suicidality. Data from the 2022 FCFCOA annual report indicated that in parenting proceedings, 70% alleged a child had been or was at risk of abuse, 80% alleged a party had experienced Family Violence, 74 % of children had been exposed to Family Violence, 53% alleged through substance misuse by party children had caused or was at risk of causing harm to children and 58% of matters allege mental health issues of a party had caused or placed a child at risk of harm. Those figures reveal the significant overlap between child protection and family violence, both of which are under the responsibility of state and territory governments. Since 2020, a further key initiative has been the co-location of child protection and police officials amongst a number of registries of the FCFOCA. The ability to access in a time-effective way details of family violence or child protection orders, weapons licenses, criminal convictions or proceedings is key to managing issues across the state and federal divide. It ensures a more cohesive and effective response to family law, family violence and child protection systems.

Keywords: child protection, family violence, parenting, risk screening, triage.

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Authors: Kathryn Ewing

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Safe and accessible public spaces are vital elements of our South African cities. Public spaces hold the potential to act as important, vibrant places for learning, exchange, and practice. Public walkways, however, are some of the most neglected and extremely dangerous public spaces experienced in the local neighborhood of Gugulethu in Cape Town. Walkways feel insignificant, being recognized as informal and undetermined or retain complex fragments of formal erven. They are generally out of sight connecting minor streets and informal settlements. Community residents refer to the walkways as unsafe and dirty spaces. Local authorities allocate minimal to no municipal budgets nor maintenance plans resulting in a lack of basic services, particularly lighting and green infrastructure. ‘The Walkway Project’ presents a series of urban stories collected from co-design workshops, emotional mapping exercises, and fieldwork, including urban walks and urban talks. The narrative interprets the socio-spatial practice and complexity of informal public space in Gugulethu, Cape Town. The Walkway Project research, interrelated to the Master of Urban Design teaching and design-research studio, has a strong focus on participatory and engaged learning and action research methodology within a deliberate pedagogy. A consolidated urban design implementation plan exposes the impact and challenges of waste and water, opening the debate on relevant local solutions for resilience and safety in Cape Town. A small and neglected passage connecting two streets, commonly referred to as iThemba Walkway, is presented as a case study to show-case strategic urban design intervention strategies for urban upgrading. The iThemba walkway is a community-driven project that demonstrates active and responsible co-design and participatory development opportunities. In March 2021, when visited on an urban walk, the public space was covered by rubble and solid waste. By April 2021, the community cleaned the walkway and created an accessible passage for the school children to pass. Numerous co-design workshops have taken place over the past year. The walkway has emerged as a public space upgrading project facilitated, motivated, and implemented by multiple local partners and residents. Social maps from urban walks and talks illustrate the transformation of iThemba Walkway into an inclusive, safe, resilient, and sustainable urban space, linked to Sustainable Development Goal number 11, sustainable cities and communities. The outcomes of the upgrading project facilitate a deeper understanding of co-design methods, urban upgrading processes, and monitoring of public space and informal urbanism.

Keywords: informal, public space, resilience, safety, upgrade, walkways

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Authors: Hannah R. Devens, Phillip L. Davidson, Dione Deaker, Kathryn E. Smith, Gregory A. Wray, Maria Byrne

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Marine invertebrate species with calcifying larvae are especially vulnerable to ocean acidification (OA) caused by rising atmospheric CO₂ levels. Acidic conditions can delay development, suppress metabolism, and decrease the availability of carbonate ions in the ocean environment for skeletogenesis. These stresses often result in increased larval mortality, which may lead to significant ecological consequences including alterations to the larval settlement, population distribution, and genetic connectivity. Importantly, many of these physiological and developmental effects are caused by genetic and molecular level changes. Although many studies have examined the effect of near-future oceanic pH levels on gene expression in marine invertebrates, little is known about the impact of OA on gene expression in a developmental context. Here, we performed mRNA-sequencing to investigate the impact of environmental acidity on gene expression across three developmental stages in the sea urchin Heliocidaris erythrogramma. We collected RNA from gastrula, early larva, and 1-day post-metamorphic juvenile sea urchins cultured at present-day and predicted future oceanic pH levels (pH 8.1 and 7.7, respectively). We assembled an annotated reference transcriptome encompassing development from egg to ten days post-metamorphosis by combining these data with datasets from two previous developmental transcriptomic studies of H. erythrogramma. Differential gene expression and time course analyses between pH conditions revealed significant alterations to developmental transcription that are potentially associated with pH stress. Consistent with previous investigations, genes involved in biomineralization and ion transport were significantly upregulated under acidic conditions. Differences in gene expression between the two pH conditions became more pronounced post-metamorphosis, suggesting a development-dependent effect of OA on gene expression. Furthermore, many differences in gene expression later in development appeared to be a result of broad downregulation at pH 7.7: of 539 genes differentially expressed at the juvenile stage, 519 of these were lower in the acidic condition. Time course comparisons between pH 8.1 and 7.7 samples also demonstrated over 500 genes were more lowly expressed in pH 7.7 samples throughout development. Of the genes exhibiting stage-dependent expression level changes, over 15% of these diverged from the expected temporal pattern of expression in the acidic condition. Through these analyses, we identify novel candidate genes involved in development, metabolism, and transcriptional regulation that are possibly affected by pH stress. Our results demonstrate that pH stress significantly alters gene expression dynamics throughout development. A large number of genes differentially expressed between pH conditions in juveniles relative to earlier stages may be attributed to the effects of acidity on transcriptional regulation, as a greater proportion of mRNA at this later stage has been nascent transcribed rather than maternally loaded. Also, the overall downregulation of many genes in the acidic condition suggests that OA-induced developmental delay manifests as suppressed mRNA expression, possibly from lower transcription rates or increased mRNA degradation in the acidic environment. Further studies will be necessary to determine in greater detail the extent of OA effects on early developing marine invertebrates.

Keywords: development, gene expression, ocean acidification, RNA-sequencing, sea urchins

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