Search results for: Caroline Howard

Authors: Iman Farasat, Howard M. Salis

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Engineered genetic circuits reprogram cellular behavior to act as living computers with applications in detecting cancer, creating self-controlling artificial tissues, and dynamically regulating metabolic pathways. Phenemenological models are often used to simulate and design genetic circuit behavior towards a desired behavior. While such models assume that each circuit component’s function is modular and independent, even small changes in a circuit (e.g. a new promoter, a change in transcription factor expression level, or even a new media) can have significant effects on the circuit’s function. Here, we use statistical thermodynamics to account for the several factors that control transcriptional regulation in bacteria, and experimentally demonstrate the model’s accuracy across 825 measurements in several genetic contexts and hosts. We then employ our first principles model to design, experimentally construct, and characterize a family of signal amplifying genetic circuits (genetic OpAmps) that expand the dynamic range of cell sensors. To develop these models, we needed a new approach to measuring the in vivo binding free energies of transcription factors (TFs), a key ingredient of statistical thermodynamic models of gene regulation. We developed a new high-throughput assay to measure RNA polymerase and TF binding free energies, requiring the construction and characterization of only a few constructs and data analysis (Figure 1A). We experimentally verified the assay on 6 TetR-homolog repressors and a CRISPR/dCas9 guide RNA. We found that our binding free energy measurements quantitatively explains why changing TF expression levels alters circuit function. Altogether, by combining these measurements with our biophysical model of translation (the RBS Calculator) as well as other measurements (Figure 1B), our model can account for changes in TF binding sites, TF expression levels, circuit copy number, host genome size, and host growth rate (Figure 1C). Model predictions correctly accounted for how these 8 factors control a promoter’s transcription rate (Figure 1D). Using the model, we developed a design framework for engineering multi-promoter genetic circuits that greatly reduces the number of degrees of freedom (8 factors per promoter) to a single dimensionless unit. We propose the Ptashne (Pt) number to encapsulate the 8 co-dependent factors that control transcriptional regulation into a single number. Therefore, a single number controls a promoter’s output rather than these 8 co-dependent factors, and designing a genetic circuit with N promoters requires specification of only N Pt numbers. We demonstrate how to design genetic circuits in Pt number space by constructing and characterizing 15 2-repressor OpAmp circuits that act as signal amplifiers when within an optimal Pt region. We experimentally show that OpAmp circuits using different TFs and TF expression levels will only amplify the dynamic range of input signals when their corresponding Pt numbers are within the optimal region. Thus, the use of the Pt number greatly simplifies the genetic circuit design, particularly important as circuits employ more TFs to perform increasingly complex functions.

Keywords: transcription factor, synthetic biology, genetic circuit, biophysical model, binding energy measurement

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Authors: Wiolene Montanari Nordi, Debora Botequio Moretti, Mariana Caroline Pontin, Jessica Pampolini, Raul Machado-Neto

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Gills are organs responsible for respiration and osmoregulation between the fish internal environment and water. Under stress conditions, oxidative response and gill plasticity to attempt to increase gas exchange area are noteworthy, compromising the physiological processes and therefore fish health. Colostrum is a dietary source of nutrients, immunoglobulin, antioxidant and bioactive molecules, essential for immunological protection and development of the gastrointestinal epithelium. The hypothesis of this work is that antioxidant factors present in the colostrum, unprecedentedly tested in gills, can minimize or reduce the alteration of its epithelium structure of juvenile pacu (Piaractus mesopotamicus) subjected to high stocking density. The histological changes in the gills architecture were characterized by the frequency, incidence and severity of the tissue alteration and ionic status. Juvenile (50 kg fish/m3) were fed with pelleted diets containing 0, 10, 20 or 30% of lyophilized bovine colostrum (LBC) inclusion and at 30 experimental days, gill and blood samples were collected in eight fish per treatment. The study revealed differences in the type, frequency and severity (histological alterations index – HAI) of tissue alterations among the treatments, however, no distinct differences in the incidence of alteration (mean alteration value – MAV) were observed. The main histological changes in gill were elevation of the lamellar epithelium, excessive cell proliferation of the filament and lamellar epithelium causing total or partial melting of the lamella, hyperplasia and hypertrophy of lamellar and filament epithelium, uncontrolled thickening of filament and lamellar tissues, mucous and chloride cells presence in the lamella, aneurysms, vascular congestion and presence of parasites. The MAV obtained per treatment were 2.0, 2.5, 1.8 and 2.5 to fish fed diets containing 0, 10, 20 and 30% of LBC inclusion, respectively, classifying the incidence of gill alterations as slightly to moderate. The severity of alteration of individual fish of treatment 0, 10 and 20% LBC ranged values from 5 to 40 (HAI average of 20.1, 17.5 and 17.6, respectively, P > 0.05), and differs from 30% LBC, that ranged from 6 to 129 (HAI mean of 77.2, P < 0.05). The HAI value in the treatments 0, 10 and 20% LBC reveals gill tissue with injuries classified from slightly to moderate, while in 30% LBC moderate to severe, consequence of the onset of necrosis in the tissue of two fish that compromises the normal functioning of the organ. In relation to frequency of gill alterations, evaluated according to absence of alterations (0) to highly frequent (+++), histological alterations were observed in all evaluated fish, with a trend of higher frequency in 0% LBC. The concentration of Na+, Cl-, K+ and Ca2+ did not changed in all treatments (P > 0.05), indicating similar capacity of ion exchange. The concentrations of bovine colostrum used in diets of present study did not impair the alterations observed in the gills of juvenile pacu.

Keywords: histological alterations of gill tissue, ionic status, lyophilized bovine colostrum, optical microscopy

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Authors: Victor Pena Ribeiro, Caroline Arruda, Jennyfer Andrea Aldana Mejia, Jairo Kenupp Bastos

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Leishmaniasis is a serious health problem around the world. The treatment of infected individuals with pentavalent antimonial drugs is the main therapeutic strategy. However, they present high toxicity and persistence side effects. Therefore, the discovery of new and safe natural-derived therapeutic agents against leishmaniasis is important. Propolis is a resin of viscous consistency produced by Apis mellifera bees from parts of plants. The main types of Brazilian propolis are green, red, yellow and brown. Thus, the aim of this work was to investigate the chemical composition and leishmanicidal properties of a brown propolis (BP). For this purpose, the hydroalcoholic crude extract of BP was obtained and was fractionated by liquid-liquid chromatography. The chemical profile of the extract and its fractions were obtained by HPLC-UV-DAD. The fractions were submitted to preparative HPLC chromatography for isolation of the major compounds of each fraction. They were analyzed by NMR for structural determination. The volatile compounds were obtained by hydrodistillation and identified by GC/MS. Promastigote forms of Leishmania amazonensis were cultivated in M199 medium and then 2×106 parasites.mL-1 were incubated in 96-well microtiter plates with the samples. The BP was dissolved in dimethyl sulfoxide (DMSO) and diluted into the medium, to give final concentrations of 1.56, 3.12, 6.25, 12.5, 25 and 50 µg.mL⁻¹. The plates were incubated at 25ºC for 24 h, and the lysis percentage was determined by using a Neubauer chamber. The bioassays were performed in triplicate, using a medium with 0.5% DMSO as a negative control and amphotericin B as a positive control. The leishimnicidal effect against promastigote forms was also evaluated at the same concentrations. Cytotoxicity experiments also were performed in 96-well plates against normal (CHO-k1) and tumor cell lines (AGP01 and HeLa) using XTT colorimetric method. Phenolic compounds, flavonoids, and terpenoids were identified in brown propolis. The major compounds were identified as follows: p-coumaric acid (24.6%) for a methanolic fraction, Artepelin-C (29.2%) for ethyl acetate fraction and the compounds of hexane fraction are in the process of structural elucidation. The major volatile compounds identified were β-caryophyllene (10.9%), germacrene D (9.7%), nerolidol (10.8%) and spathulenol (8.5%). The propolis did not show cytotoxicity against normal cell lines (CHO) with IC₅₀ > 100 μg.mL⁻¹, whereas the IC₅₀ < 10 μg.mL⁻¹ showed a potential against the AGP01 cell line, propolis did not demonstrate cytotoxicity against HeLa cell lines IC₅₀ > 100 μg.mL⁻¹. In the determination of the leishmanicidal activity, the highest (50 μg.mL⁻¹) and lowest (1.56 μg.mL⁻¹) concentrations of the crude extract caused the lysis of 76% and 45% of promastigote forms of L. amazonensis, respectively. To the amastigote form, the highest (50 μg.mL⁻¹) and lowest (1.56 μg.mL⁻¹) concentrations caused the mortality of 89% and 75% of L. amazonensis, respectively. The IC₅₀ was 2.8 μg.mL⁻¹ to amastigote form and 3.9 μg.mL⁻¹ to promastigote form, showing a promising activity against Leishmania amazonensis.

Keywords: amastigote, brown propolis, cytotoxicity, promastigote

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Authors: Caroline M. B. De Araujo, Helenise A. Do Nascimento, Claudia J. Da S. Cavalcanti, Mauricio A. Da Motta Sobrinho, Maria F. Pimentel

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Oil production is often followed by the joint production of water and gas. During the journey up to the surface, due to severe conditions of temperature and pressure, the mixing between these three components normally occurs. Thus, the three phases separation process must be one of the first steps to be performed after crude oil extraction, where the water-oil separation is the most complex and important step, since the presence of water into the process line can increase corrosion and hydrates formation. A wide range of methods can be applied in order to proceed with oil-water separation, being more commonly used: flotation, hydrocyclones, as well as the three phase separator vessels. Facing what has been presented so far, it is the aim of this paper to study a system consisting of a three-phase separator, evaluating the influence of three variables: temperature, working pressure and separator type, for two types of oil (light and heavy), by performing two factorial design plans 23, in order to find the best operating condition. In this case, the purpose is to obtain the greatest oil flow rate in the product stream (m3/h) as well as the lowest percentage of water in the oil stream. The simulation of the three-phase separator was performed using Aspen Hysys®2006 simulation software in stationary mode, and the evaluation of the factorial experimental designs was performed using the software Statistica®. From the general analysis of the four normal probability plots of effects obtained, it was observed that interaction effects of two and three factors did not show statistical significance at 95% confidence, since all the values were very close to zero. Similarly, the main effect "separator type" did not show significant statistical influence in any situation. As in this case, it has been assumed that the volumetric flow of water, oil and gas were equal in the inlet stream, the effect separator type, in fact, may not be significant for the proposed system. Nevertheless, the main effect “temperature” was significant for both responses (oil flow rate and mass fraction of water in the oil stream), considering both light and heavy oil, so that the best operation condition occurs with the temperature at its lowest level (30oC), since the higher the temperature, the liquid oil components pass into the vapor phase, going to the gas stream. Furthermore, the higher the temperature, the higher the formation water vapor, so that ends up going into the lighter stream (oil stream), making the separation process more difficult. Regarding the “working pressure”, this effect showed to be significant only for the oil flow rate, so that the best operation condition occurs with the pressure at its highest level (9bar), since a higher operating pressure, in this case, indicated a lower pressure drop inside the vessel, generating lower level of turbulence inside the separator. In conclusion, the best-operating condition obtained for the proposed system, at the studied range, occurs for temperature is at its lowest level and the working pressure is at its highest level.

Keywords: factorial experimental design, oil production, simulation, three-phase separator

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Authors: Sarah Faulkner, Patrick Faulkner, Caroline Ellison

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Improved mental and physical health, community connection, and increased life satisfaction has been strongly associated with bike riding for those with and without a disability. However, much evidence suggests that people living with a disability face increased barriers to engaging in cycling compared to members of the general population. People with an intellectual disability often live more sedentary and socially isolated lives that negatively impact their mental and physical health, as well as life satisfaction. This paper is based on preliminary findings from a three-year intervention cycling project funded by the South Australian Government. The cycling project was developed in partnership with community stakeholders that provided weekly instruction, training, and support to individuals living with intellectual disabilities to increase their capacity in cycling. This project aimed to support people living with intellectual disabilities to foster and facilitate improved physical and mental health, confidence, and independence and enhance social networking through their engagement in community cycling. The program applied principles of social role valorisation (SRV) theory as its guiding framework. Preliminary data collected is based on qualitative interviews with over 50 program participants, results from two participant wellness questionnaires, as well as a perceptually regulated exercise test administered throughout the project implementation. Preliminary findings are further supplemented with ethnographic analyses by the researchers who took a phenology of life experience approach. Preliminary findings of the program suggest a variety of social motivations behind participants' desire to learn cycling that acknowledges previous barriers to engagement and cycling’s role to address feelings of loneliness and social isolation. Meaningful health benefits can be achieved as demonstrated by increases in predicted V02 max measures, suggesting that physical intervention can not only improve physical health outcomes but also provide a variety of other social benefits. Initial engagement in the project has demonstrated an increase in participants' sense of confidence, well-being, and physical fitness. Implementation of the project in partnership with a variety of community stakeholders has identified a number of critical factors and processes necessary for future service replication, sustainability, and success. Findings from this intervention study contribute to the development of a knowledge base on how best to support individuals living with an intellectual disability to partake in bike riding and increase positive outcomes associated with their capacity building, social interaction, increased physical activity, physical health, and mental well-being. The initial findings of this study provide critical academic insights into the social and physical benefits of cycling for people living with a disability, as well as practical advice for future human service applications.

Keywords: cycling, disability, social inclusion, capacity building

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Authors: Caroline McDonald-Harker, Julie Drolet

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Abstract— In the last six years Canada In the last six years Canada has experienced two major and catastrophic environmental disasters– the 2013 Southern Alberta flood and the 2016 Fort McMurray, Alberta wildfire. These two disasters resulted in damages exceeding 12 billion dollars, the costliest disasters in Canadian history. In the aftermath of these disasters, many families faced the loss of homes, places of employment, schools, recreational facilities, and also experienced social, emotional, and psychological difficulties. Children and youth are among the most vulnerable to the devastating effects of disasters due to the physical, cognitive, and social factors related to their developmental life stage. Yet children and youth also have the capacity to be resilient and act as powerful catalyst for change in their own lives and wider communities following disaster. Little is known, particularly from a sociological perspective, about the specific factors that contribute to resilience in children and youth, and effective ways to support their overall health and well-being. This paper focuses on the voices and experiences of children and youth residing in these two disaster-affected communities in Alberta, Canada and specifically examines: 1) How children and youth’s lives are impacted by the tragedy, devastation, and upheaval of disaster; 2) Ways that children and youth demonstrate resilience when directly faced with the adversarial circumstances of disaster; and 3) The cumulative internal and external factors that contribute to bolstering and supporting resilience among children and youth post-disaster. This paper discusses the characteristics associated with high levels of resilience in 183 children and youth ages 5 to 17 based on quantitative and qualitative data obtained through a mix methods approach. Child and youth participants were administered the Children and Youth Resilience Measure (CYRM-28) in order to examine factors that influence resilience processes including: individual, caregiver, and context factors. The CYRM-28 was then supplemented with qualitative interviews with children and youth to contextualize the CYRM-28 resiliency factors and provide further insight into their overall disaster experience. Findings reveal that high levels of resilience among child and youth participants is associated with both individual factors and caregiver factors, specifically positive outlook, effective communication, peer support, and physical and psychological caregiving. Individual and caregiver factors helped mitigate the negative effects of disaster, thus bolstering resilience in children and youth. This paper discusses the implications that these findings have for understanding the specific mechanisms that support the resiliency processes and overall recovery of children and youth following disaster; the importance of bridging the gap between children and youth’s needs and the services and supports provided to them post-disaster; and the need to develop resiliency processes and practices that empower children and youth as active agents of change in their own lives following disaster. These findings contribute to furthering knowledge about pragmatic and representative changes to resources, programs, and policies surrounding disaster response, recovery, and mitigation.

Keywords: children and youth, disaster, environment, resilience

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Authors: Henry Nicholas Lee, George Thomas, Juliana Johari, Carmilla Freddie, Caroline Val Madin

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Research in comparative and international education often provides value-laden views of an education system within and in between other countries. These views are frequently used by policy makers or educators to explore similarities and differences for, among others, benchmarking purposes. In this study, a comparison is made between Malaysia and England, focusing on the process of writing children went through to create a text, using a multimodal theoretical framework to analyse this comparison. The main purpose is political in nature as it served as an answer to Malaysia’s call for benchmarking of best practices for language learning. Furthermore, the focus on writing in this study adds into more empirical findings about early writers’ writing development and writing improvement, especially for children at the ages of 5-9. In research, comparative studies in English as a Second Language (ESL) writing pedagogy – particularly in Malaysia since the introduction of the Standard- based English Language Curriculum (KSSR) in 2011 as a draft and its full implementation in 2017; reviewed 2018 KSSR-CEFR aligned – has not been done comparatively. In theory, a multimodal theoretical framework somehow allows a logical comparison between first language and ESL which would provide useful insights to illuminate the writing process between Malaysia and England. The comparisons are not representative because of the different school systems in both countries. So far, the literature informs us that the curriculum for language learning is very much emphasised on children’s linguistic abilities, which include their proficiency and mastery of the language, its conventions, and technicalities. However, recent empirical findings suggested that literacy in its concepts and characters need change. In view of this suggestion, the comparison will look at how the process of writing is implemented through the five modes of communication: linguistic, visual, aural, spatial, and gestural. This project draws on data from Malaysia and England, involving 10 teachers, 26 classroom observations, 20 lesson plans, 20 interviews, and 20 brief conversations with teachers. The research focused upon 20 primary children of different genders aged 5-9, and in addition to primary data descriptions, 40 children’s works, 40 brief classroom conversations, 30 classroom photographs, and 30 school compound photographs were undertaken to investigate teachers and children’s use of modes and semiotic resources to design a text. The data were analysed by means of within-case analysis, cross-case analysis, and constant comparative analysis, with an initial stage of data categorisation, followed by general and specific coding, which clustered the data into thematic groups. The study highlights the importance of teachers’ and children’s engagement and interaction with various modes of communication, an adaptation from the English approaches to teaching writing within the KSSR framework and providing ‘voice’ to ESL writers to ensure that both have access to the knowledge and skills required to make decisions in developing multimodal texts and artefacts.

Keywords: comparative education, early writers, KSSR, multimodal theoretical framework, writing development

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Authors: Julien Monnier, Isabelle Mouton, Francois Buy, Adrien Michel, Sylvain Ringeval, Joel Malaplate, Caroline Toffolon, Bernard Marini, Audrey Lechartier

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Chosen to design and assemble massive components for nuclear industry, the 316 Nb austenitic stainless steel (also called 316 Nb) suits well this function thanks to its mechanical, heat and corrosion handling properties. However, these properties might change during steel’s life due to thermal ageing causing changes within its microstructure. Our main purpose is to determine if the 316 Nb will keep its mechanical properties after an exposition to industrial temperatures (around 300 °C) during a long period of time (< 10 years). The 316 Nb is composed by different phases, which are austenite as main phase, niobium-carbides, and ferrite remaining from the ferrite to austenite transformation during the process. Our purpose is to understand thermal ageing effects on the material microstructure and properties and to submit a model predicting the evolution of 316 Nb properties as a function of temperature and time. To do so, based on Fe-Cr and 316 Nb phase diagrams, we studied the thermal ageing of 316 Nb steel alloys (1%v of ferrite) and welds (10%v of ferrite) for various temperatures (350, 400, and 450 °C) and ageing time (from 1 to 10.000 hours). Higher temperatures have been chosen to reduce thermal treatment time by exploiting a kinetic effect of temperature on 316 Nb ageing without modifying reaction mechanisms. Our results from early times of ageing show no effect on steel’s global properties linked to austenite stability, but an increase of ferrite hardness during thermal ageing has been observed. It has been shown that austenite’s crystalline structure (cfc) grants it a thermal stability, however, ferrite crystalline structure (bcc) favours iron-chromium demixion and formation of iron-rich and chromium-rich phases within ferrite. Observations of thermal ageing effects on ferrite’s microstructure were necessary to understand the changes caused by the thermal treatment. Analyses have been performed by using different techniques like Atomic Probe Tomography (APT) and Differential Scanning Calorimetry (DSC). A demixion of alloy’s elements leading to formation of iron-rich (α phase, bcc structure), chromium-rich (α’ phase, bcc structure), and nickel-rich (fcc structure) phases within the ferrite have been observed and associated to the increase of ferrite’s hardness. APT results grant information about phases’ volume fraction and composition, allowing to associate hardness measurements to the volume fractions of the different phases and to set up a way to calculate α’ and nickel-rich particles’ growth rate depending on temperature. The same methodology has been applied to DSC results, which allowed us to measure the enthalpy of α’ phase dissolution between 500 and 600_°C. To resume, we started from mechanical and macroscopic measurements and explained the results through microstructural study. The data obtained has been match to CALPHAD models’ prediction and used to improve these calculations and employ them to predict 316 Nb properties’ change during the industrial process.

Keywords: stainless steel characterization, atom probe tomography APT, vickers hardness, differential scanning calorimetry DSC, thermal ageing

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Authors: Antonela Matana, Dubravka Brdar, Vesela Torlak, Marijana Popovic, Ivana Gunjaca, Ozren Polasek, Vesna Boraska Perica, Maja Barbalic, Ante Punda, Caroline Hayward, Tatijana Zemunik

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Parathyroid hormone (PTH) plays a critical role in the regulation of bone mineral metabolism and calcium homeostasis. Higher PTH levels are associated with heart failure, hypertension, coronary artery disease, cardiovascular mortality and poorer bone health. A twin study estimated that 60% of the variation in PTH concentrations is genetically determined. Only one GWAS of PTH concentration has been reported to date. Identified loci explained 4.5% of the variance in circulating PTH, suggesting that additional genetic variants remain undiscovered. Therefore, the aim of this study was to identify novel genetic variants associated with PTH levels in a general population. We have performed a GWAS meta-analysis on 2596 individuals originating from three Croatian cohorts: City of Split and the Islands of Korčula and Vis, within a large-scale project of “10,001 Dalmatians”. A total of 7 411 206 variants, imputed using the 1000 Genomes reference panel, with minor allele frequency ≥ 1% and Rsq ≥ 0.5 were analyzed for the association. GWAS within each data set was performed under an additive model, controlling for age, gender and relatedness. Meta-analysis was conducted using the inverse-variance fixed-effects method. Furthermore, to identify sex-specific effects, we have conducted GWAS meta-analyses analyzing males and females separately. In addition, we have performed biological pathway analysis. Four SNPs, representing one locus, reached genome-wide significance. The most significant SNP was rs11099476 on chromosome 4 (P=1.15x10-8), which explained 1.14 % of the variance in PTH. The SNP is located near the protein-coding gene RASGEF1B. Additionally, we detected suggestive association with SNPs, rs77178854 located on chromosome 2 in the DPP10 gene (P=2.46x10-7) and rs481121 located on chromosome 1 (P=3.58x10-7) near the GRIK1 gene. One of the top hits detected in the main meta-analysis, intron variant rs77178854 located within DPP10 gene, reached genome-wide significance in females (P=2.21x10-9). No single locus was identified in the meta-analysis in males. Fifteen biological pathways were functionally enriched at a P<0.01, including muscle contraction, ion homeostasis and cardiac conduction as the most significant pathways. RASGEF1B is the guanine nucleotide exchange factor, known to be associated with height, bone density, and hip. DPP10 encodes a membrane protein that is a member of the serine proteases family, which binds specific voltage-gated potassium channels and alters their expression and biophysical properties. In conclusion, we identified 2 novel loci associated with PTH levels in a general population, providing us with further insights into the genetics of this complex trait.

Keywords: general population, genome-wide association analysis, parathyroid hormone, single nucleotide polymorphisms.

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Authors: Caroline Atef Shoukry Tadros

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Massive Urbanization growth threatens the sustainability of cities and the quality of city life. This raised the need for an alternate model of sustainability, so we need to plan the future cities in a smarter way with smarter mobility. Smart Mobility planning applications are solutions that use digital technologies and infrastructure advances to improve the efficiency, sustainability, and inclusiveness of urban transportation systems. They can contribute to meeting the needs of Urbanization growth by addressing the challenges of traffic congestion, pollution, accessibility, and safety in cities. Some example of a Smart Mobility planning application are Mobility-as-a-service: This is a service that integrates different transport modes, such as public transport, shared mobility, and active mobility, into a single platform that allows users to plan, book, and pay for their trips. This can reduce the reliance on private cars, optimize the use of existing infrastructure, and provide more choices and convenience for travelers. MaaS Global is a company that offers mobility-as-a-service solutions in several cities around the world. Traffic flow optimization: This is a solution that uses data analytics, artificial intelligence, and sensors to monitor and manage traffic conditions in real-time. This can reduce congestion, emissions, and travel time, as well as improve road safety and user satisfaction. Waycare is a platform that leverages data from various sources, such as connected vehicles, mobile applications, and road cameras, to provide traffic management agencies with insights and recommendations to optimize traffic flow. Logistics optimization: This is a solution that uses smart algorithms, blockchain, and IoT to improve the efficiency and transparency of the delivery of goods and services in urban areas. This can reduce the costs, emissions, and delays associated with logistics, as well as enhance the customer experience and trust. ShipChain is a blockchain-based platform that connects shippers, carriers, and customers and provides end-to-end visibility and traceability of the shipments. Autonomous vehicles: This is a solution that uses advanced sensors, software, and communication systems to enable vehicles to operate without human intervention. This can improve the safety, accessibility, and productivity of transportation, as well as reduce the need for parking space and infrastructure maintenance. Waymo is a company that develops and operates autonomous vehicles for various purposes, such as ride-hailing, delivery, and trucking. These are some of the ways that Smart Mobility planning applications can contribute to meeting the needs of the Urbanization growth. However, there are also various opportunities and challenges related to the implementation and adoption of these solutions, such as the regulatory, ethical, social, and technical aspects. Therefore, it is important to consider the specific context and needs of each city and its stakeholders when designing and deploying Smart Mobility planning applications.

Keywords: smart mobility planning, smart mobility applications, smart mobility techniques, smart mobility tools, smart transportation, smart cities, urbanization growth, future smart cities, intelligent cities, ICT information and communications technologies, IoT internet of things, sensors, lidar, digital twin, ai artificial intelligence, AR augmented reality, VR virtual reality, robotics, cps cyber physical systems, citizens design science

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Authors: V. Howard, R. Maguire, S. Corrigan

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Background: Type 1 Diabetes (T1D) is a chronic autoimmune disease, typically diagnosed in childhood. T1D puts an enormous strain on families; controlling blood-glucose in children is difficult and the consequences of poor control for patient health are significant. Successful illness management and better health outcomes can be dependent on quality of caregiving. On diagnosis, parent-caregivers face a steep learning curve as T1D care requires a significant level of knowledge to inform complex decision making throughout the day. The majority of illness management is carried out in the home setting, independent of clinical health providers. Parent-caregivers vary in their level of knowledge and their level of engagement in applying this knowledge in the practice of illness management. Enabling researchers to quantify these aspects of the caregiver experience is key to identifying targets for psychosocial support interventions, which are desirable for reducing stress and anxiety in this highly burdened cohort, and supporting better health outcomes in children. Currently, there are limited tools available that are designed to capture this information. Where tools do exist, they are not comprehensive and do not adequately capture the lived experience. Objectives: Development of quantitative tools, informed by lived experience, to enable researchers gather data on parent-caregiver knowledge and engagement, which accurately represents the experience/cohort and enables exploration of questions that are of real-world value to the cohort themselves. Methods: This research employed an engaged approach to address the problem of quantifying two key aspects of caregiver diabetes management: Knowledge and engagement. The research process was multi-staged and iterative. Stage 1: Working from a constructivist standpoint, literature was reviewed to identify relevant questionnaires, scales and single-item measures of T1D caregiver knowledge and engagement, and harvest candidate questionnaire items. Stage 2: Aggregated findings from the review were circulated among a PPI (patient and public involvement) expert panel of caregivers (n=6), for discussion and feedback. Stage 3: In collaboration with the expert panel, data were interpreted through the lens of lived experience to create a long-list of candidate items for novel questionnaires. Items were categorized as either ‘knowledge’ or ‘engagement’. Stage 4: A Delphi-method process (iterative surveys) was used to prioritize question items and generate novel questions that further captured the lived experience. Stage 5: Both questionnaires were piloted to refine wording of text to increase accessibility and limit socially desirable responding. Stage 6: Tools were piloted using an online survey that was deployed using an online peer-support group for caregivers for Juveniles with T1D. Ongoing Research: 123 parent-caregivers completed the survey. Data analysis is ongoing to establish face and content validity qualitatively and through exploratory factor analysis. Reliability will be established using an alternative-form method and Cronbach’s alpha will assess internal consistency. Work will be completed by early 2024. Conclusion: These tools will enable researchers to gain deeper insights into caregiving practices among parents of juveniles with T1D. Development was driven by lived experience, illustrating the value of engaged research at all levels of the research process.

Keywords: caregiving, engaged research, juvenile type 1 diabetes, quantified engagement and knowledge

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Authors: Caroline Smith, Professor Debi Bhattacharya, Sion Scott

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Introduction: Oropharyngeal Dysphagia (OD) effects around 15% of older people, however it is often unrecognised and under diagnosed until they are hospitalised. There is a need for primary care healthcare practitioners (HCPs) to assume a proactive role in identifying and managing OD to prevent adverse outcomes such as aspiration pneumonia. Understanding the determinants of primary care HCPs undertaking this new behaviour provides the intervention targets for addressing. This realist review, underpinned by the Theoretical Domains Framework (TDF), aims to synthesise relevant literature and develop programme theories to understand what interventions work, how they work and under what circumstances to facilitate HCPs to prevent harm from OD. Combining realist methodology with behavioural science will permit conceptualisation of intervention components as theoretical behavioural constructs, thus informing the design of a future behaviour change intervention. Furthermore, through the TDF’s linkage to a taxonomy of behaviour change techniques, we will identify corresponding behaviour change techniques to include in this intervention. Methods & analysis: We are following the five steps for undertaking a realist review: 1) clarify the scope 2) Literature search 3) appraise and extract data 4) evidence synthesis 5) evaluation. We have searched Medline, Google scholar, PubMed, EMBASE, CINAHL, AMED, Scopus and PsycINFO databases. We are obtaining additional evidence through grey literature, snowball sampling, lateral searching and consulting the stakeholder group. Literature is being screened, evaluated and synthesised in Excel and Nvivo. We will appraise evidence in relation to its relevance and rigour. Data will be extracted and synthesised according to its relation to Initial programme theories (IPTs). IPTs were constructed after the preliminary literature search, informed by the TDF and with input from a stakeholder group of patient and public involvement advisors, general practitioners, speech and language therapists, geriatricians and pharmacists. We will follow the Realist and Meta-narrative Evidence Syntheses: Evolving Standards (RAMESES) quality and publication standards to report study results. Results: In this ongoing review our search has identified 1417 manuscripts with approximately 20% progressing to full text screening. We inductively generated 10 IPTs that hypothesise practitioners require: the knowledge to spot the signs and symptoms of OD; the skills to provide initial advice and support; and access to resources in their working environment to support them conducting these new behaviours. We mapped the 10 IPTs to 8 TDF domains and then generated a further 12 IPTs deductively using domain definitions to fulfil the remaining 6 TDF domains. Deductively generated IPTs broadened our thinking to consider domains such as ‘Emotion,’ ‘Optimism’ and ‘Social Influence’, e.g. If practitioners perceive that patients, carers and relatives expect initial advice and support, then they will be more likely to provide this, because they will feel obligated to do so. After prioritisation with stakeholders using a modified nominal group technique approach, a maximum of 10 IPTs will progress to test against the literature.

Keywords: behaviour change, deglutition disorders, primary healthcare, realist review

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Authors: Caroline Seo, Jennifer Stephens, Kirstin H. Heinrich

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Background: Clostridiodes (formerly Clostridium) difficile infection (CDI) is an anaerobic, spore-forming bacterium with manifestations including diarrhea, pseudomembranous colitis and toxic megacolon. Despite general understanding that CDI may be associated with marked burden on patients’ health, there has been limited information available on the humanistic burden of CDI. The objective of this literature review was to summarize the published data on the humanistic burden of CDI globally, in order to better inform future research efforts and increase awareness of the patient perspective in this disease. Methods: A comprehensive literature review of the past 15 years (2002-2017) was conducted using MEDLINE, Embase and Cumulative Index of Nursing and Allied Health Literature. Additional searches were conducted from conference proceedings (2015-2017). Articles selected were studies specifically designed to examine the humanistic burden of illness associated with adult patients with CDI. Results: Of 3,325 articles or abstracts identified, 33 remained after screening and full text review. Sixty percent (60%) were published in 2016 or 2017. Data from the United States or Western Europe were most common. Data from Brazil, Canada, China and Spain also exist. Thirteen (13) studies used validated patient-reported outcomes instruments, mostly EQ-5D utility and SF-36 generic instruments. Three (3) studies used CDI-specific instruments (CDiff32, CDI-DaySyms). The burden of CDI impacts patients in multiple health-related quality of life (HRQOL) domains. SF-36 domains with the largest decrements compared to other GI diarrheal diseases (IBS-D and Crohn’s) were role physical, physical functioning, vitality, social functioning, and role emotional. Reported EQ-5D utilities for CDI ranged from 0.35-0.42 compared to 0.65 in Crohn’s and 0.72 in IBS-D. The majority of papers addressed physical functioning and mental health domains (67% for both). Across various studies patients reported weakness, lack of appetite, sleep disturbance, functional dependence, and decreased activities of daily lives due to the continuous diarrhea. Due to lack of control over this infection, CDI also impacts the psychological and emotional quality of life of the patients. Patients reported feelings of fear, anxiety, frustration, depression, and embarrassment. Additionally, the type of disease (primary vs. recurrent) may impact mental health. One study indicated that there is a decrement in SF-36 mental scores in patients with recurrent CDI, in comparison to patients with primary CDI. Other domains highlighted by these studies include pain (27%), social isolation (27%), vitality and fatigue (24%), self-care (9%), and caregiver burden (0%). Two studies addressed work productivity, with 1 of these studies reporting that CDI patients had the highest work productivity and activity impairment scores among the gastrointestinal diseases. No study specifically included caregiver self-report. However, 3 studies did provide mention of patients’ worry on how their diagnosis of CDI would impact family, caregivers, and/or friends. Conclusions: Despite being a serious public health issue there has been a paucity of research on the HRQOL among those with CDI. While progress is being made, gaps exist in understanding the burden on patients, caregivers, and families. Future research is warranted to aid understanding of the CDI patient perspective.

Keywords: burden, Clostridiodes, difficile, humanistic, infection

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Authors: Tim Crocker-Buque, Sandra Mounier-Jack, Natasha Howard

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Background: Due to both the increasing scale and speed of urbanisation, urban areas in low and middle-income countries (LMICs) host increasingly large populations of under-immunized children, with the additional associated risks of rapid disease transmission in high-density living environments. Multiple interdependent factors are associated with these coverage disparities in urban areas and most evidence comes from relatively few countries, e.g., predominantly India, Kenya, Nigeria, and some from Pakistan, Iran, and Brazil. This study aimed to identify, describe, and assess the main tools used to measure or improve coverage of immunisation services in poor urban areas. Methods: Authors used a qualitative review design, including academic and non-academic literature, to identify tools used to improve coverage of public health interventions in urban areas. Authors selected and extracted sources that provided good examples of specific tools, or categories of tools, used in a context relevant to urban immunization. Diagnostic (e.g., for data collection, analysis, and insight generation) and programme tools (e.g., for investigating or improving ongoing programmes) and interventions (e.g., multi-component or stand-alone with evidence) were selected for inclusion to provide a range of type and availability of relevant tools. These were then prioritised using a decision-analysis framework and a tool selection guide for programme managers developed. Results: Authors reviewed tools used in urban immunisation contexts and tools designed for (i) non-immunization and/or non-health interventions in urban areas, and (ii) immunisation in rural contexts that had relevance for urban areas (e.g., Reaching every District/Child/ Zone). Many approaches combined several tools and methods, which authors categorised as diagnostic, programme, and intervention. The most common diagnostic tools were cross-sectional surveys, key informant interviews, focus group discussions, secondary analysis of routine data, and geographical mapping of outcomes, resources, and services. Programme tools involved multiple stages of data collection, analysis, insight generation, and intervention planning and included guidance documents from WHO (World Health Organisation), UNICEF (United Nations Children's Fund), USAID (United States Agency for International Development), and governments, and articles reporting on diagnostics, interventions, and/or evaluations to improve urban immunisation. Interventions involved service improvement, education, reminder/recall, incentives, outreach, mass-media, or were multi-component. The main gaps in existing tools were an assessment of macro/policy-level factors, exploration of effective immunization communication channels, and measuring in/out-migration. The proposed framework uses a problem tree approach to suggest tools to address five common challenges (i.e. identifying populations, understanding communities, issues with service access and use, improving services, improving coverage) based on context and available data. Conclusion: This study identified many tools relevant to evaluating urban LMIC immunisation programmes, including significant crossover between tools. This was encouraging in terms of supporting the identification of common areas, but problematic as data volumes, instructions, and activities could overwhelm managers and tools are not always suitably applied to suitable contexts. Further research is needed on how best to combine tools and methods to suit local contexts. Authors’ initial framework can be tested and developed further.

Keywords: health equity, immunisation, low and middle-income countries, poverty, urban health

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Authors: Denis Jordan, Daniel Golkowski, Mathias Lukas, Katharina Merz, Caroline Mlynarcik, Max Maurer, Valentin Riedl, Stefan Foerster, Eberhard F. Kochs, Andreas Bender, Ruediger Ilg

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Introduction: So far, clinical assessments that rely on behavioral responses to differentiate coma states or even predict outcome in coma patients are unreliable, e.g. because of some patients’ motor disabilities. The present study was aimed to provide prognosis in coma patients using markers from electroencephalogram (EEG), blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) and [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET). Unsuperwised principal component analysis (PCA) was used for multimodal integration of markers. Methods: Approved by the local ethics committee of the Technical University of Munich (Germany) 20 patients (aged 18-89) with severe brain damage were acquired through intensive care units at the Klinikum rechts der Isar in Munich and at the Therapiezentrum Burgau (Germany). At the day of EEG/fMRI/PET measurement (date I) patients (<3.5 month in coma) were grouped in the minimal conscious state (MCS) or vegetative state (VS) on the basis of their clinical presentation (coma recovery scale-revised, CRS-R). Follow-up assessment (date II) was also based on CRS-R in a period of 8 to 24 month after date I. At date I, 63 channel EEG (Brain Products, Gilching, Germany) was recorded outside the scanner, and subsequently simultaneous FDG-PET/fMRI was acquired on an integrated Siemens Biograph mMR 3T scanner (Siemens Healthineers, Erlangen Germany). Power spectral densities, permutation entropy (PE) and symbolic transfer entropy (STE) were calculated in/between frontal, temporal, parietal and occipital EEG channels. PE and STE are based on symbolic time series analysis and were already introduced as robust markers separating wakefulness from unconsciousness in EEG during general anesthesia. While PE quantifies the regularity structure of the neighboring order of signal values (a surrogate of cortical information processing), STE reflects information transfer between two signals (a surrogate of directed connectivity in cortical networks). fMRI was carried out using SPM12 (Wellcome Trust Center for Neuroimaging, University of London, UK). Functional images were realigned, segmented, normalized and smoothed. PET was acquired for 45 minutes in list-mode. For absolute quantification of brain’s glucose consumption rate in FDG-PET, kinetic modelling was performed with Patlak’s plot method. BOLD signal intensity in fMRI and glucose uptake in PET was calculated in 8 distinct cortical areas. PCA was performed over all markers from EEG/fMRI/PET. Prognosis (persistent VS and deceased patients vs. recovery to MCS/awake from date I to date II) was evaluated using the area under the curve (AUC) including bootstrap confidence intervals (CI, *: p<0.05). Results: Prognosis was reliably indicated by the first component of PCA (AUC=0.99*, CI=0.92-1.00) showing a higher AUC when compared to the best single markers (EEG: AUC<0.96*, fMRI: AUC<0.86*, PET: AUC<0.60). CRS-R did not show prediction (AUC=0.51, CI=0.29-0.78). Conclusion: In a multimodal analysis of EEG/fMRI/PET in coma patients, PCA lead to a reliable prognosis. The impact of this result is evident, as clinical estimates of prognosis are inapt at time and could be supported by quantitative biomarkers from EEG, fMRI and PET. Due to the small sample size, further investigations are required, in particular allowing superwised learning instead of the basic approach of unsuperwised PCA.

Keywords: coma states and prognosis, electroencephalogram, entropy, functional magnetic resonance imaging, machine learning, positron emission tomography, principal component analysis

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Authors: Caroline Spencer, Suzanne Cross, Dudley McArdle, Frank Archer

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Objectives: The evolution of the Victorian Compendium of Community-Based Resilience Building Case Studies and its capacity to help communities implement activities that encourage adaptation to disaster risk reduction and promote community resilience in rural and urban locations provide this paper's objectives. Background: Between 2012 and 2019, community groups presented at the Monash University Disaster Resilience Initiative (MUDRI) 'Advancing Community Resilience Annual Forums', provided opportunities for communities to impart local resilience activities, how to solve challenges and share unforeseen learning and be considered for inclusion in the Compendium. A key tenet of the Compendium encourages compiling and sharing of grass-roots resilience building activities to help communities before, during, and after unexpected emergencies. The online Compendium provides free access for anyone wanting to help communities build expertise, reduce program duplication, and save valuable community resources. Identifying case study features across the emergency phases and analyzing critical success factors helps communities understand what worked and what did not work to achieve success and avoid known barriers. International exemplars inform the Compendium, which represents an Australian first and enhances Victorian community resilience initiatives. Emergency Management Victoria provided seed funding for the Compendium. MUDRI matched this support and continues to fund the project. A joint Steering Committee with broad-based user input and Human ethics approval guides its continued growth. Methods: A thematic analysis of the Compendium identified case study features, including critical success factors. Results: The Compendium comprises 38 case studies, representing all eight Victorian regions. Case studies addressed emergency phases, before (29), during (7), and after (17) events. Case studies addressed all hazards (23), bushfires (11), heat (2), fire safety (1), and house fires (1). Twenty case studies used a framework. Thirty received funding, of which nine received less than $20,000 and five received more than $100,000. Twenty-nine addressed a whole of community perspective. Case studies revealed unique and valuable learning in diverse settings. Critical success factors included strong governance; board support, leadership, and trust; partnerships; commitment, adaptability, and stamina; community-led initiatives. Other success factors included a paid facilitator and local government support; external funding, and celebrating success. Anecdotally, we are aware that community groups reference Compendium and that its value adds to community resilience planning. Discussion: The Compendium offers an innovative contribution to resilience research and practice. It augments the seven resilience characteristics to strengthen and encourage communities as outlined in the Statewide Community Resilience Framework for Emergency Management; brings together people from across sectors to deliver distinct, yet connected actions to strengthen resilience as a part of the Rockefeller funded Resilient Melbourne Strategy, and supports communities and economies to be resilient when a shock occurs as identified in the recently published Australian National Disaster Risk Reduction Framework. Each case study offers learning about connecting with community and how to increase their resilience to disaster risks and to keep their community safe from unexpected emergencies. Conclusion: The Compendium enables diverse communities to adopt or adapt proven resilience activities, thereby preserving valuable community resources and offers the opportunity to extend to a national or international Compendium.

Keywords: case study, community, compendium, disaster risk reduction, resilience

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