Search results for: Jude Harrison

Authors: Ubani Onyedikachi, Atagana Harrison Ifeanyichukwu, Thantsha Mapitsi Silvester

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Components of oil sludge (PAHs) are known cytotoxic, mutagenic and potentially carcinogenic compounds also bacteria and fungi have been found to degrade PAHs to innocuous compounds. This study is aimed at measuring the effect of pig, cow, horse and poultry manures on the degradation in selected PAHs present in oil sludge. Soil spiked with oil sludge was co-composted differently with each manure in a ratio of 2:1 (w/w) spiked soil: manure and wood-chips in a ratio of 2:1 (w/v) spiked soil: wood-chips. Control was set up similar as the one above but without manure. The mixtures were incubated for 10 months at room temperature. Compost piles were turned weekly and moisture level was maintained at between 50% and 70%. Moisture level, pH, temperature, CO2 evolution and oxygen consumption were measured monthly and the ash content at the end of experimentation. Highest temperature reached was 27.5 °C in all compost heaps, pH ranged from 5.5 to 7.8 and CO2 evolution was highest in poultry manure at 18.78μg/dwt/day. Microbial growth and activities were enhanced; bacteria identified were Bacillus, Arthrobacter and Staphylococcus species. Percentage reduction in PAHs was measured using automated soxhlet extractor with Dichloromethane coupled with gas chromatography/mass spectrometry (GC/MS). Results from PAH measurements showed reduction between 77% and 99%. Co-composting of spiked soils with animal manures enhanced the reduction in PAHs.

Keywords: animal manures, bioremediation, co-composting, oil refinery sludge, PAHs

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Authors: Matthew Omoniyi Adebola, Jude E Amadi

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Ground nut (Arachis hypogaea) is one of the most popular commercial crops in Nigeria. Its suc-cessful production has been drastically affected by early leaf spot disease caused by Mycosphae-rella arachidis Deighton. In vitro control of the pathogen by six medicinal plants (Entada afri-cana, Vitex doniana, Lawsonia inermis, Azadirachta indica, Acalypha hispida and Nuaclea lati-folia) was assessed in this study. The extracts of the plants were prepared using cold and hot wa-ter and alcohol. The pathogen was isolated from ground nut infected with early leaf spot disease. The results revealed a great significant difference (P<0.05) in yield of extracts between cold water, hot water, and alcohol extracts. A significant difference (P<0.05) was observed in percentage concentrations of the various phytochemical constituents present in the extracts. Flavonoids per-centage concentration was the highest (0.68 - 1.95%) followed by saponnin(0.09-1.53%) in N. latifolia extracts. Steroiods had the least percentage concentrations (0.00- 0.09%)followed by terpenoids(0.02–0.71%) and proanthocyannin (0.05 – 0.86%). N. latifolia extracts produced the highest percentage concentrations (0.07–1.95%) of all the phytochemicals followed by A. indi-ca(0.05–1.64%)and least concentrations were obtained in A. hispidia(0.09 – 0.87%)and V. do-niana (0.00–0.88%). The extracts inhibited spore germination and growth of M. arachidis. The inhibition by alcohol extracts was high and significantly different (P>0.05) from cold and hot water extracts. Alcohol extract of L. inermis gave 100% spore germination inhibition followed by N. latifolia and A.indica with 97.75% and 85.60% inhibition respectively. Therefore, field trials of these six medicinal plants on the control of early leaf spot disease of ground nut are rec-ommended.

Keywords: groundnut, phytochemicals, medicinal plants, extracts, inhibition

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Authors: Milton Ayoki, Edward Bbaale

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This paper analyses the relationship between innovation and employment at firm level with the objective of understanding the contribution of the different innovation strategies in fostering employment growth in Uganda. We use National Innovation Survey (micro-data of 705 Ugandan firms) for the period 2011-2014 and follow closely Harrison et al. (2014) structured approach, and relate employment growth to process innovations and to the growth of sales separately due to innovative and unchanged products. We find positive effects of product innovation on employment at firm level, while process innovation has no discernable impact on employment. Although there is evidence to suggest displacement of labour in some cases where firms only introduce new process, this effect is compensated by growth in employment from new products, which for most firms are introduced simultaneously with new process. Results suggest that source of innovation as well as size of innovating firms or end users of innovation matter for job growth. Innovation that develops from within the firm itself (user) and involving larger firms has greater impact on employment than that developed from outside or coming from within smaller firms. In addition, innovative firms are one and half times more likely to survive in the innovation driven economy environment than those that do not innovate. These results have important implications for policymakers and stakeholders in innovation ecosystem. Supporting policies need to be correctly tailored since the impacts depend on the innovation strategy (type) and characteristics and sector of the innovative firms (small, large, industry, etc.). Policies to spur investment, particularly in innovative sectors and firms with high growth potential would have long lasting effects on job creation. JEL Classification: D24, J0, J20, L20, O30.

Keywords: employment, process innovation, product innovation, Sub-Saharan Africa

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Authors: Nana Segu Acquaah-Harrison, James Osei Mensah, Richard Aidoo, David Amponsah, Amy Buah, Gilbert Aboagye

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The study aimed at assessing the feasibility of commercial meat rabbit production in the Kumasi Metropolis of Ghana. Structured and unstructured questionnaires were utilized in obtaining information from two hundred meat consumers and 15 meat rabbit farmers. Data were analyzed using Net Present Value (NPV), Internal Rate of Return (IRR), Benefit Cost Ratio (BCR)/Profitability Index (PI) technique, percentages and chi-square contingency test. The study found that the current demand for rabbit meat is low (36%). The desirable nutritional attributes of rabbit meat and other socio economic factors of meat consumers make the potential demand for rabbit meat high (69%). It was estimated that GH¢5,292 (approximately $ 2672) was needed as a start-up capital for a 40-doe unit meat rabbit farm in Kumasi Metropolis. The cost of breeding animals, housing and equipment formed 12.47%, 53.97% and 24.87% respectively of the initial estimated capital. A Net Present Value of GH¢ 5,910.75 (approximately $ 2984) was obtained at the end of the fifth year, with an internal rate return and profitability index of 70% and 1.12 respectively. The major constraints identified in meat rabbit production were low price of rabbit meat, shortage of fodder, pest and diseases, high cost of capital, high cost of operating materials and veterinary care. Based on the analysis, it was concluded that meat rabbit production is feasible in the Kumasi Metropolis of Ghana. The study recommends embarking on mass advertisement; farmer association and adapting to new technologies in the production process will help to enhance productivity.

Keywords: feasibility, commercial meat rabbit, production, Kumasi, Ghana

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Authors: Nur Azreena Idris, Soh Kheang Loh, Harrison Lau Lik Nang, Yuen May Choo, Eminour Muzalina Mustafa, Vijaysri Vello, Cheng Yau Tan, Siew Moi Phang

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It is estimated that about 0.65-0.67 m3 of palm oil mill effluent (POME) is generated when one tonne of fresh fruit bunches is processed. Owning to the high content of nutrients in POME, it has high potential as a medium for microalgae growth. This study attempted determining the growth rate, biomass productivity and biochemical composition of microalgae (Chlorella sp.) grown in different POME concentrations i.e. 6.25%, 12.5%, 25% and 50% at outdoor conditions using a 200-mL capacity high rate algae pond (HRAP) and 2 closed photobioreactors (PBRs) i.e. annular and flat panel. The strain, Chlorella sp. grown on 12.5% of POME in flat panel PBR exhibited the highest specific growth rate of 0.32/day and biomass productivity (27.1 mg/L/day) followed by those in HRAP and annular PBR. It further showed that a good growth of Chlorella sp. in 12.5% of POME could sufficiently reduce the nutrients of POME such as phosphate (PO4), nitrate (NO3), nitrite (NO2) and chemical oxygen demand (COD). The extracted algal oil from POME culture showed that the saturated fatty acids decreased while polyunsaturated fatty acids increased compared to those cultured in standard culture medium (Bold’s Basal medium). The biochemical compositions of the algae grown in flat panel PBR were the highest with lipid, protein and carbohydrate productivity of 17.91 mg/L/day, 34.65 mg/L/day and 21.44 mg/L/day, respectively. The microalgae cultivation in diluted POME had not only shown potential as biodiesel feedstock based on the fatty acids profile but also the ability to reduce pollutants e.g. PO4, NO3, NO2 and COD in biological wastewater treatment.

Keywords: wastewater treatment, photobioreactors, biomass productivity, specific growth rate

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Authors: Akpobome Harrison

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Community radio serves as a potent vehicle for amplifying local voices and driving community progress worldwide. It facilitates grassroots communication, empowers residents, and significantly contributes to social, cultural, and economic development. This study investigates the pivotal roles of community radio in elevating local voices and advancing development within Emuoha, Obio-Akpor, and Ikwerre Local Government Areas in Rivers State. Employing a quantitative methodology, the research involved random sampling of respondents via questionnaires. The findings underscore the transformative power of community radio in promoting local voices and fostering development, particularly within Rivers State. Moreover, community radio platforms empower marginalized populations, providing them with a voice and an opportunity to actively participate in the media landscape, share their stories, and express their concerns. This empowerment holds the potential to enhance civic engagement and communal harmony. Community radio stations often prioritize local news, events, and subjects that may not receive adequate coverage in mainstream media, thus facilitating the dissemination of vital community information, including local news, weather updates, and emergency alerts. In light of these observations, this paper advocates for the encouragement of community radio by both the state government and private media entities to facilitate seamless information dissemination. Additionally, the paper highlights the significant role played by the use of Pidgin English as a communication tool, particularly in providing understanding and a voice to marginalized individuals in rural communities.

Keywords: community radio, local voices, marginalized populations, information dissemination, pidgin english, grassroots communication

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Authors: Yuan Long, Fabrizio Ceschin, David Harrison

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Environmental sustainability is under the threat of excessive single-use plastic packaging waste, and current waste management fails to address this issue. Therefore, it has led to a reidentification of the alternative, which can curb the packaging waste without reducing social needs. Reusable packaging represents a circular approach to close the loop of consumption in which packaging can stay longer in the system to satisfy social needs. However, the implementation of reusable packaging is fragmented and lacks systematic approaches. The product-service system (PSS) is widely regarded as a sustainable business model innovation for embracing circular consumption. As a result, applying PSS to reusable packaging solutions will be promising to address the packaging waste issue. This paper aims at filling the knowledge gap relating to apply PSS to reusable packaging solutions and provide a strategic design tool that could support packaging professionals to design reusable packaging solutions. The methodology of this paper is case studies and workshops to provide a design tool. The respondents are packaging professionals who are packaging consultants, NGO professionals, and entrepreneurs. 57 cases collected show that 15 archetypal models operate in the market. Subsequently, a polarity diagram is developed to embrace those 15 archetypal models, and a total number of 24 experts were invited for the workshop to evaluate the design tool. This research finally provides a strategic design tool to support packaging professionals to design reusable packaging solutions. The application of the tool is to support the understanding of the reusable packaging solutions, analyzing the markets, identifying new opportunities, and generate new business models. The implication of this research is to provide insights for academics and businesses in terms of tackling single-use packaging waste and build a foundation for further development of the reusable packaging solution tool.

Keywords: environmental sustainability, product-service system, reusable packaging, design tool

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Authors: Benjamin Bonsu Bruce, Marian Dorcas Quain David Appiah-Kubi, Gertrude Osei-Diko, Harrison Kwame Dapaah

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Taro [Colocasia esculenta (L.) Schott] is a major staple food and remains a significant crop to many cultural and agricultural customs worldwide. In Ghana, taro is mostly propagated using vegetative material, which is conserved in field collection and recycled from their farms to establish new fields. However, this practice promotes the accumulation of systemic pathogens. Prior exposure to pests and subsequent expression of disease symptoms can also be a huge constraint to sustainable conservation and utilization of taro genetic resources. In vitro, slow growth is one of the most promising techniques to be utilized for conservation. The objective of this study was to find a medium-term in vitro conservation protocol for local and exotic taro genotypes. The medium-term conservation study was conducted using actively growing shoots obtained from in vitro cultures. Explants were cultured to full strength in complete Murashige and Skoog medium supplemented with Mannitol at different concentrations (0g/l, 20g/l, 25g/l, and 30g/l). Another medium that was tested as an additional treatment is the White’s medium. The highest number of shoots (6.33) and leaves (22.67) occurred on medium containing 20 and 25g/l mannitol in genotype SAO 006 as compared to other genotypes, whereas 30g/l mannitol was the best to restrict growth for the entire 6 months period in terms of shoot height (22.50cm). The study reveals that mannitol supplemented culture media could reduce the growth of Colocasia plantlets, especially in stem height. Culture growth following 6 months of conservation, showed that healthy shoot cultures of Taro were obtained after 6 months of storage in a medium containing 20gl⁻¹ and 25gl⁻¹ mannitol.

Keywords: complete murashige, skoog medium, culture conditions, mannitol, slow growth conservation

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Authors: Catherine Harrison

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Faced with arrest, imprisonment and the denazification process in 1945, Tübingen University’s Professor of Theology, Gerhard Kittel, refused to abandon the “Christian” antisemitism which he had first expounded in his Die Judenfrage [The Jewish Question] (1933 and 1934). At the heart of this paper is a critical engagement with Die Judenfrage, the first in English. Putting Die Judenfrage into dialogue with Kittel’s 1946, Meine Verteidigung [My Defence] (1945-6) exposes the remarkable consistency of Kittel’s idiosyncratic but closely argued Christian theology of antisemitism. Girdling his career as a foremost theologian, antisemite and enthusiastic supporter of Hitler and the NSDAP, the consistency between Die Judenfrage and Meine Verteidigung attests Kittel’s consistent and authentic, intellectual position. In both texts, he claims to be advancing Christian, as opposed to “vulgar” or racial, antisemitism. Yet, in the thirteen years which divide them, Kittel had mediated contact with Nazi illuminati Rudolph Hess, Alfred Rosenberg, Winnifred Wagner, Josef Goebbels and Baldur von Schirach, through his publications in various antisemitic journals. The paper argues: Die Judenfrage, as both a text and as a theme, is axiomatic to Kittel’s defence statement; and that Die Judenfrage constitutes the template of Kittel’s arcane, personal “Christian” antisemitism of which Meine Verteidigung is a faithful impression. Both are constructed on the same theologically chimeric and abstruse hypotheses regarding Volk, Spätjudentum [late Judaism] and Heilgeschichte [salvation history]. Problematising these and other definitional vagaries that make up Kittel’s “Christian” antisemitism highlight the remarkable theoretical consistency between Die Judenfrage and Meine Verteidigung. It is concluded that a deadly synergy of Nazi racial antisemitism and the New Testament antisemitism shaped Kittel’s judgement to the degree that, despite the slipstream of concentration camp footage which was shaking the foundations of post-war German academia, Meine Verteidigung is a simple restatement of the antisemitsm conveyed in Die Judenfrage.

Keywords: Gerhard Kittel, Third Reich theology, the Jewish Question, Nazi antisemitism

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Authors: Carlo Cogliati

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The study of the relationship of philosophical reason with the religious domain has been very much a concern for many of the Western philosophical and theological traditions. In this essay, I will suggest a proposal for an Eastern philosophy of religion based on Nishida’s contradictory identity of the two: philosophy soku hi (is, and yes is not) religion. This will pose a challenge to the traditional Western contents and methods of the discipline. This paper aims to serve three purposes. First, I will critically assess Charlesworth’s typology of the relation between philosophy and religion in the West: philosophy as/for/against/about/after religion. I will also engage Harrison’s call for a global philosophy of religion(s) and argue that, although it expands the scope and the range of the questions to address, it is still Western in its method. Second, I will present Nishida’s logic of absolutely contradictory self-identity as the instrument to transcend the dichotomous pair of identity and contradiction: ‘A is A’ and ‘A is not A’. I will then explain how this ‘concrete’ logic of the East, as opposed to the ‘formal’ logic of the West, exhibits at best the bilateral dynamic relation between philosophy and religion. Even as Nishida argues for the non-separability of the two, he is also aware and committed to their mutual non-reducibility. Finally, I will outline the resulting new relation between God and creatures. Nishida in his philosophy soku hi religion replaces the traditional Western dualistic concept of God with the Eastern non-dualistic understanding of God as “neither transcendent nor immanent, and at the same time both transcendent and immanent.” God is therefore a self-identity of contradiction, nowhere and yet everywhere present in the world of creatures. God as absolute being is also absolute nothingness: the world of creatures is the expression of God’s absolute self-negation. The overreaching goal of this essay is to offer an alternative to traditional Western approaches to philosophy of religion based on Nishida’s logic of absolutely contradictory self-identity, as an example of philosophical and religious counter(influence). The resulting relationship between philosophy and religion calls for a revision of traditional concepts and methods. The outcome is not to reformulate the Eastern predilection to not sharply distinguish philosophical thought from religious enlightenment rather to bring together philosophy and religion in the place of identity and difference.

Keywords: basho, Nishida Kitaro, shukyotetsugaku, soku hi, zettai mujunteki jikodoitsu no ronri

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Authors: Joseph Lillington, Tom Gout, Mike Harrison, Ian Farnan

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The vitrification of high-level nuclear waste within borosilicate glass and its incorporation within a multi-barrier repository deep underground is widely accepted as the preferred disposal method. However, for this to happen, any safety case will require validation that the initially localized radionuclides will not be considerably released into the near/far-field. Therefore, accurate mechanistic models are necessary to predict glass dissolution, and these should be robust to a variety of incorporated waste species and leaching test conditions, particularly given substantial variations across international waste-streams. Here, machine learning is used to predict glass material properties (viscosity, density) and glass leaching model parameters from large-scale industrial data. A variety of different machine learning algorithms have been compared to assess performance. Density was predicted solely from composition, whereas viscosity additionally considered temperature. To predict suitable glass leaching model parameters, a large simulated dataset was created by coupling MATLAB and the chemical reactive-transport code HYTEC, considering the state-of-the-art GRAAL model (glass reactivity in allowance of the alteration layer). The trained models were then subsequently applied to the large-scale industrial, experimental data to identify potentially appropriate model parameters. Results indicate that ensemble methods can accurately predict viscosity as a function of temperature and composition across all three industrial datasets. Glass density prediction shows reliable learning performance with predictions primarily being within the experimental uncertainty of the test data. Furthermore, machine learning can predict glass dissolution model parameters behavior, demonstrating potential value in GRAAL model development and in assessing suitable model parameters for large-scale industrial glass dissolution data.

Keywords: machine learning, predictive modelling, pattern recognition, radioactive waste glass

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Authors: Riaz Ahmed Mangrio

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Reduplication in Urdu-Hindi affects all major word categories, particles, and even nonsensical words. It conveys a variety of meanings, including distribution, emphasis, iteration, adjectival and adverbial. This study will primarily discuss reduplicative structures of nonsensical words in Urdu-Hindi and then briefly look at some examples from other Indo-Aryan languages to introduce the debate regarding the same structures in them. The goal of this study is to present counter-evidence against Keane (2005: 241), who claims “the base in the cases of lexical and phrasal echo reduplication is always independently meaningful”. However, Urdu-Hindi reduplication derives meaningful compounds from nonsensical words e.g. gũ mgũ (A) ‘silent and confused’ and d̪əb d̪əb-a (N) ‘one’s fear over others’. This needs a comprehensive examination to see whether and how the various structures form patterns of a base-reduplicant relationship or, rather, they are merely sub lexical items joining together to form a word pattern of any grammatical category in content words. Another interesting theoretical question arises within the Optimality framework: in an OT analysis, is it necessary to identify one of the two constituents as the base and the other as reduplicant? Or is it best to consider this a pattern, but then how does this fit in with an OT analysis? This may be an even more interesting theoretical question. Looking for the solution to such questions can serve to make an important contribution. In the case at hand, each of the two constituents is an independent nonsensical word, but their echo reduplication is nonetheless meaningful. This casts significant doubt upon Keane’s (2005: 241) observation of some examples from Hindi and Tamil reduplication that “the base in cases of lexical and phrasal echo reduplication is always independently meaningful”. The debate on the point becomes further interesting when the triplication of nonsensical words in Urdu-Hindi e.g. aẽ baẽ ʃaẽ (N) ‘useless talk’ is also seen, which is equally important to discuss. The example is challenging to Harrison’s (1973) claim that only the monosyllabic verbs in their progressive forms reduplicate twice to result in triplication, which is not the case with the example presented. The study will consist of a thorough descriptive analysis of the data for the purpose of documentation, and then there will be OT analysis.

Keywords: reduplication, urdu-hindi, nonsensical, optimality theory

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Authors: Nyong Princely Awazi, Gadinga Walter Forje, Barnabas Neba Nfornkah, Ndzifon Jude Kimengsi

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Ecotourism is documented as a sustainable measure of bridging conservation goals and livelihood sustenance around protected areas, due to its ability of not just providing alternative livelihood, but also in providing the necessary resources that can help finance conservation initiatives. In Cameroon, all ecotourism activities around national parks are aimed at generating revenue through the conservation service while providing sustainable livelihood options to the local population. There exists an information lacuna regarding the contribution of ecotourism finances to conservation efforts in the country. This study was aimed at establishing the contribution of ecotourism finances to conservation initiatives in and around the Campo Ma’an National Park (CMNP). Data were collected through the administering of 120 structured questionnaires to ecotourism actors and 15 key/expert interviews with tourism and conservation actors in the Campo Ma’an landscape. Chi-square test, Spearman’s rank correlation and regressions were used for data analysis. The study revealed that the main sources of ecotourism financing to the park service are through entrance fees, cameras and vehicle fees paid by tourists as well as ecotourism project financing through NGOs. Calculations from the tourism register of the park showed that the park was able to raise as much as 1,576,000 FCFA (US$ 3,152) annually. It was further established that ecotourism revenue has not greatly supported conservation, with 54% of respondents perceiving ecotourism not contributing to biodiversity conservation. Chi Square test results highlighted poor ecotourism governance, low level of ecotourism development, corruption from park management staff, obsolete nature of the current finance law on the management of protected area revenue as key factors hindering ecotourism financing in conservation. For ecotourism financing to contribute to biodiversity conservation in the CMNP and in Cameroon’s protected areas, the government needs to revise the finance law on the management of revenue generated from protected areas, improve park governance to fight corruption and enhance transparency, invest in the development and marketing of the Campo Ma’an national park as a tourism destination in the country.

Keywords: Cameroon, Campo Ma’an National Park, conservation, ecotourism, ecotourism financing

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

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

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

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Authors: Humphrey Agevi, Harrison Tsingalia, Richard Onwonga, Shem Kuyah

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Most of the world ecosystems have been affected by the effects of climate change. Efforts have been made to mitigate against climate change effects. While most studies have been done in forest ecosystems and pure plant plantations, trees on farms including agroforestry have only received attention recently. Agroforestry systems and tree cover on agricultural lands make an important contribution to climate change mitigation but are not systematically accounted for in the global carbon budgets. This study sought to: (i) determine tree diversity in different agroforestry practices; (ii) determine tree biomass in different agroforestry practices. Study area was determined according to the Land degradation surveillance framework (LSDF). Two study sites were established. At each of the site, a 5km x 10km block was established on a map using Google maps and satellite images. Way points were then uploaded in a GPS helped locate the blocks on the ground. In each of the blocks, Nine (8) sentinel clusters measuring 1km x 1km were randomized. Randomization was done in a common spreadsheet program and later be downloaded to a Global Positioning System (GPS) so that during surveys the researchers were able to navigate to the sampling points. In each of the sentinel cluster, two farm boundaries were randomly identified for convenience and to avoid bias. This led to 16 farms in Kakamega South and 16 farms in Kakamega North totalling to 32 farms in Kakamega Site. Species diversity was determined using Shannon wiener index. Tree biomass was determined using allometric equation. Two agroforestry practices were found; homegarden and hedgerow. Species diversity ranged from 0.25-2.7 with a mean of 1.8 ± 0.10. Species diversity in homegarden ranged from 1-2.7 with a mean of 1.98± 0.14. Hedgerow species diversity ranged from 0.25-2.52 with a mean of 1.74± 0.11. Total Aboveground Biomass (AGB) determined was 13.96±0.37 Mgha-1. Homegarden with the highest abundance of trees had higher above ground biomass (AGB) compared to hedgerow agroforestry. This study is timely as carbon budgets in the agroforestry can be incorporated in the global carbon budgets and improve the accuracy of national reporting of greenhouse gases.

Keywords: agroforestry, allometric equations, biomass, climate change

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Authors: Dona Shaini Abhilasha Nanayakkara, Kurugamage Jude Pravinda Gregory Perera

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E-commerce platforms have revolutionized the shopping experience, offering convenient ways for consumers to make purchases. To improve interactions with customers and optimize marketing strategies, it is essential for businesses to understand user behavior, preferences, and needs on these platforms. This paper focuses on recommending businesses to customize interactions with users based on their behavioral patterns, leveraging data-driven analysis and machine learning techniques. Businesses can improve engagement and boost the adoption of e-commerce platforms by aligning behavioral patterns with user goals of usability and satisfaction. We propose TheAnalyzer, a clustering-based system designed to enhance business productivity by analyzing user-profiles and improving human-computer interaction. The Analyzer seamlessly integrates with business applications, collecting relevant data points based on users' natural interactions without additional burdens such as questionnaires or surveys. It defines five key user analytics as features for its dataset, which are easily captured through users' interactions with e-commerce platforms. This research presents a study demonstrating the successful distinction of users into specific groups based on the five key analytics considered by TheAnalyzer. With the assistance of domain experts, customized business rules can be attached to each group, enabling The Analyzer to influence business applications and provide an enhanced personalized user experience. The outcomes are evaluated quantitatively and qualitatively, demonstrating that utilizing TheAnalyzer’s capabilities can optimize business outcomes, enhance customer satisfaction, and drive sustainable growth. The findings of this research contribute to the advancement of personalized interactions in e-commerce platforms. By leveraging user behavioral patterns and analyzing both new and existing users, businesses can effectively tailor their interactions to improve customer satisfaction, loyalty and ultimately drive sales.

Keywords: data clustering, data standardization, dimensionality reduction, human computer interaction, user profiling

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Authors: Gaoyang Meng, Philip Harrison

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When manufacturing composite laminates, the fibre directions within the laminate are never perfectly straight and inevitably contain some degree of stochastic in-plane waviness or ‘meandering’. In this work we aim to understand the relationship between the degree of meandering of the fibre paths, and the resulting uncertainty in the laminate’s final mechanical properties. To do this, a numerical tool is developed to automatically generate meandering fibre paths in each of the laminate's 8 plies (using Matlab) and after mapping this information into finite element simulations (using Abaqus), the statistical variability of the tensile mechanical properties of a [45°/90°/-45°/0°]s carbon/epoxy (IM7/8552) laminate is predicted. The stiffness, first ply failure strength and ultimate failure strength are obtained. Results are generated by inputting the degree of variability in the fibre paths and the laminate is then examined in all directions (from 0° to 359° in increments of 1°). The resulting predictions are output as flower (polar) plots for convenient analysis. The average fibre orientation of each ply in a given laminate is determined by the laminate layup code [45°/90°/-45°/0°]s. However, in each case, the plies contain increasingly large amounts of in-plane waviness (quantified by the standard deviation of the fibre direction in each ply across the laminate. Four different amounts of variability in the fibre direction are tested (2°, 4°, 6° and 8°). Results show that both the average tensile stiffness and the average tensile strength decrease, while the standard deviations increase, with an increasing degree of fibre meander. The variability in stiffness is found to be relatively insensitive to the rotation angle, but the variability in strength is sensitive. Specifically, the uncertainty in laminate strength is relatively low at orientations centred around multiples of 45° rotation angle, and relatively high between these rotation angles. To concisely represent all the information contained in the various polar plots, rotation-angle dependent Weibull distribution equations are fitted to the data. The resulting equations can be used to quickly estimate the size of the errors bars for the different mechanical properties, resulting from the amount of fibre directional variability contained within the laminate. A longer term goal is to use these equations to quickly introduce realistic variability at the component level.

Keywords: advanced composite laminates, FE simulation, in-plane waviness, tensile properties, uncertainty quantification

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Authors: E. V. Fakhrutdinova, K. R. Maksimova, P. B. Chursin

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At the present stage of the society progress the health care is an integral part of both the economic system and social, while in the second case the medicine is a major component of a number of basic and necessary social programs. Since the foundation of the health system are highly qualified health professionals, it is logical proposition that increase of doctor`s professionalism improves the effectiveness of the system as a whole. Professionalism of the doctor is a collection of many components, essential role played by such personal-psychological factors as honesty, willingness and desire to help people, and motivation. A number of researchers consider motivation as an expression of basic human needs that have passed through the “filter” which is a worldview and values learned in the process of socialization by the individual, to commit certain actions designed to achieve the expected result. From this point of view a number of researchers propose the following classification of highly skilled employee’s needs: 1. the need for confirmation the competence (setting goals that meet the professionalism and receipt of positive emotions in their decision), 2. The need for independence (the ability to make their own choices in contentious situations arising in the process carry out specialist functions), 3. The need for ownership (in the case of health care workers, to the profession and accordingly, high in the eyes of the public status of the doctor). Nevertheless, it is important to understand that in a market economy a significant motivator for physicians (both legal and natural persons) is to maximize its own profits. In the case of health professionals duality motivational structure creates an additional contrast, as in the public mind the image of the ideal physician; usually a altruistically minded person thinking is not primarily about their own benefit, and to assist others. In this context, the question of the real motivation of health workers deserves special attention. The survey conducted by the American researcher Harrison Terni for the magazine "Med Tech" in 2010 revealed the opinion of more than 200 medical students starting courses, and the primary motivation in a profession choice is "desire to help people", only 15% said that they want become a doctor, "to earn a lot". From the point of view of most of the classical theories of motivation this trend can be called positive, as intangible incentives are more effective. However, it is likely that over time the opinion of the respondents may change in the direction of mercantile motives. Thus, it is logical to assume that well-designed system of motivation of doctor`s labor should be based on motivational foundations laid during training in higher education.

Keywords: motivation, quality of working life, health system, personal-psychological factors, motivational structure

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Authors: Mary Deyo, Zmara Harrison

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This study reports the outcomes of an 8-week experiential learning program for 6 adults with Intellectual and Developmental Disabilities (IDD) at a day habilitation program. The intervention foci for this program include executive function, language learning in the domains of expressive, receptive, and pragmatic language, and quality of life. The interprofessional collaboration aimed at supporting adults with IDD to reach person-centered, functional goals across skill domains is critical. This study is a significant addition to the speech-language pathology literature in that it examines a therapy method that potentially meets this need while targeting domains within the speech-language pathology scope of practice. Communication therapy was provided during highly valued and meaningful hands-on learning experiences, referred to as the Garden Club, which incorporated all aspects of planting and caring for a garden as well as related journaling, sensory, cooking, art, and technology-based activities. Direct care staff and an undergraduate research assistant were trained by SLP to be impactful language guides during their interactions with participants in the Garden Club. SLP also provided direct therapy and modeling during Garden Club. Research methods used in this study included a mixed methods analysis of a literature review, a quasi-experimental implementation of communication therapy in the context of experiential learning activities, Quality of Life participant surveys, quantitative pre- post- data collection and linear mixed model analysis, qualitative data collection with qualitative content analysis and coding for themes. Outcomes indicated overall positive changes in expressive vocabulary, following multi-step directions, sequencing, problem-solving, planning, skills for building and maintaining meaningful social relationships, and participant perception of the Garden Project’s impact on their own quality of life. Implementation of this project also highlighted supports and barriers that must be taken into consideration when planning similar projects. Overall findings support the use of experiential learning projects in day habilitation programs for adults with IDD, as well as additional research to deepen understanding of best practices, supports, and barriers for implementation of experiential learning with this population. This research provides an important contribution to research in the fields of speech-language pathology and other professions serving adults with IDD by describing an interprofessional experiential learning program with positive outcomes for executive function, language learning, and quality of life.

Keywords: experiential learning, adults, intellectual and developmental disabilities, expressive language, receptive language, pragmatic language, executive function, communication therapy, day habilitation, interprofessionalism, quality of life

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

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

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

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Authors: Richard Harrison

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Developing competency in mathematics and related critical thinking skills is essential to the education of undergraduate students of Science, Technology, Engineering and Mathematics (STEM). Recently, the HE sector has been impacted by a seemingly widening disconnect between the mathematical competency of incoming first-year STEM students and their entrance qualification tariffs. Despite relatively high grades in A-Level Mathematics, students may initially lack fundamental skills in key areas such as algebraic manipulation and have limited capacity to apply problem solving strategies. Compounded by compensatory measures applied to entrance qualifications during the pandemic, there has been an associated decline in student performance on introductory university mathematics modules. In the UK, a number of online resources have been developed to help scaffold the transition to university mathematics. However, in general, these do not offer a structured learning journey focused on individual developmental needs, nor do they offer an experience coherent with the teaching and learning characteristics of the destination institution. In order to address some of these issues, a bespoke framework has been designed and implemented on our VLE in the Faculty of Engineering & Physical Sciences (FEPS) at the University of Surrey. Called the FEPS Maths Support Framework, it was conceived to scaffold the mathematical development of individuals prior to entering the university and during the early stages of their transition to undergraduate studies. More than 90% of our incoming STEM students voluntarily participate in the process. Students complete a set of initial diagnostic questions in the late summer. Based on their performance and feedback on these questions, they are subsequently guided to self-select specific mathematical topic areas for review using our proprietary resources. This further assists students in preparing for discipline related diagnostic tests. The framework helps to identify students who are mathematically weak and facilitates early intervention to support students according to their specific developmental needs. This paper presents a summary of results from a rich data set captured from the framework over a 3-year period. Quantitative data provides evidence that students have engaged and developed during the process. This is further supported by process evaluation feedback from the students. Ranked performance data associated with seven key mathematical topic areas and eight engineering and science discipline areas reveals interesting patterns which can be used to identify more generic relative capabilities of the discipline area cohorts. In turn, this facilitates evidence based management of the mathematical development of the new cohort, informing any associated adjustments to teaching and learning at a more holistic level. Evidence is presented establishing our framework as an effective early intervention strategy for addressing the sector-wide issue of supporting the mathematical development of STEM students transitioning to HE

Keywords: competency, development, intervention, scaffolding

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Authors: Alexander Harrison Greer, Edward King, Elijah Lee, Safa Obuz, Ruhao Sun, Aditya Sardesai, Toby Ma, Daniel Chow, Bryce Broadus, Calvin Costner, Troy Barnes, Biagio DeSimone, Yeshwin Sankuratri, Yiheng Chen, Holly Golecki

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Although a relatively new field, soft robotics is experiencing a rise in applicability in the secondary school setting through The Soft Robotics Toolkit, shared fabrication resources and a design competition. Exposing students outside of university research groups to this rapidly growing field allows for development of the soft robotics industry in new and imaginative ways. Soft robotic actuators have remained difficult to implement in classrooms because of their relative cost or difficulty of fabrication. Traditionally, a two-part molding system is used; however, this configuration often results in delamination. In an effort to make soft robotics more accessible to young students, we aim to develop a simple, single-mold method of fabricating soft robotic actuators from common household materials. These actuators are made by embedding a soluble polymer insert into silicone. These inserts can be made from hand-cut polystyrene, 3D-printed polyvinyl alcohol (PVA) or acrylonitrile butadiene styrene (ABS), or molded sugar. The insert is then dissolved using an appropriate solvent such as water or acetone, leaving behind a negative form which can be pneumatically actuated. The resulting actuators are seamless, eliminating the instability of adhering multiple layers together. The benefit of this approach is twofold: it simplifies the process of creating a soft robotic actuator, and in turn, increases its effectiveness and durability. To quantify the increased durability of the single-mold actuator, it was tested against the traditional two-part mold. The single-mold actuator could withstand actuation at 20psi for 20 times the duration when compared to the traditional method. The ease of fabrication of these actuators makes them more accessible to hobbyists and students in classrooms. After developing these actuators, they were applied, in collaboration with a ceramics teacher at our school, to a glove used to transfer nuanced hand motions used to throw pottery from an expert artist to a novice. We quantified the improvement in the users’ pottery-making skill when wearing the glove using image analysis software. The seamless actuators proved to be robust in this dynamic environment. Seamless soft robotic actuators created by high school students show the applicability of the Soft Robotics Toolkit for secondary STEM education and outreach. Making students aware of what is possible through projects like this will inspire the next generation of innovators in materials science and robotics.

Keywords: pneumatic actuator fabrication, soft robotic glove, soluble polymers, STEM outreach

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Authors: D. Dixon, J. Nicol, J. A. Coulter, E. Harrison

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The ease with which they can be functionalized, combined with their excellent biocompatibility, make gold nanoparticles (AuNPs) ideal candidates for various applications in nanomedicine. Indeed several promising treatments are currently undergoing human clinical trials (CYT-6091 and Auroshell). A successful nanoparticle treatment must first evade the immune system, then accumulate within the target tissue, before enter the diseased cells and delivering the payload. In order to create a clinically relevant drug delivery system, contrast agent or radiosensitizer, it is generally necessary to functionalize the AuNP surface with multiple groups; e.g. Polyethylene Glycol (PEG) for enhanced stability, targeting groups such as antibodies, peptides for enhanced internalization, and therapeutic agents. Creating and characterizing the biological response of such complex systems remains a challenge. The two commonly used methods to attach multiple groups to the surface of AuNPs are the creation of a mixed monolayer, or by binding groups to the AuNP surface using a bi-functional PEG linker. While some excellent in-vitro and animal results have been reported for both approaches further work is necessary to directly compare the two methods. In this study AuNPs capped with both PEG and a Receptor Mediated Endocytosis (RME) peptide were prepared using both mixed monolayer and PEG linker approaches. The PEG linker used was SH-PEG-SGA which has a thiol at one end for AuNP attachment, and an NHS ester at the other to bind to the peptide. The work builds upon previous studies carried out at the University of Ulster which have investigated AuNP synthesis, the influence of PEG on stability in a range of media and investigated intracellular payload release. 18-19nm citrate capped AuNPs were prepared using the Turkevich method via the sodium citrate reduction of boiling 0.01wt% Chloroauric acid. To produce PEG capped AuNPs, the required amount of PEG-SH (5000Mw) or SH-PEG-SGA (3000Mw Jenkem Technologies) was added, and the solution stirred overnight at room temperature. The RME (sequence: CKKKKKKSEDEYPYVPN, Biomatik) co-functionalised samples were prepared by adding the required amount of peptide to the PEG capped samples and stirring overnight. The appropriate amounts of PEG-SH and RME peptide were added to the AuNP to produce a mixed monolayer consisting of approximately 50% PEG and 50% RME. The PEG linker samples were first fully capped with bi-functional PEG before being capped with RME peptide. An increase in diameter from 18-19mm for the ‘as synthesized’ AuNPs to 40-42nm after PEG capping was observed via DLS. The presence of PEG and RME peptide on both the mixed monolayer and PEG linker co-functionalized samples was confirmed by both FTIR and TGA. Bi-functional PEG linkers allow the entire AuNP surface to be capped with PEG, enabling in-vitro stability to be achieved using a lower molecular weight PEG. The approach also allows the entire outer surface to be coated with peptide or other biologically active groups, whilst also offering the promise of enhanced biological availability. The effect of mixed monolayer versus PEG linker attachment on both stability and non-specific protein corona interactions was also studied.

Keywords: nanomedicine, gold nanoparticles, PEG, biocompatibility

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Authors: Rijnbout-St.James Willem, Lindner Volkhard, Scholand Mary Beth, Ashton M. Tillett, Di Gennaro Michael Jude, Smith Silvia Enrica

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Introduction: Fibrosing lung diseases are characterized by changes in the lung interstitium and are classified based on etiology: 1) environmental/exposure-related, 2) autoimmune-related, 3) sarcoidosis, 4) interstitial pneumonia, and 4) idiopathic. Among interstitial lung diseases (ILD) idiopathic forms, idiopathic pulmonary fibrosis (IPF) is the most severe. Pathogenesis of IPF is characterized by an increased presence of proinflammatory mediators, resulting in alveolar injury, where injury to alveolar epithelium precipitates an increase in collagen deposition, subsequently thickening the alveolar septum and decreasing gas exchange. Identifying biomarkers implicated in the pathogenesis of lung fibrosis is key to developing new therapies and improving the efficacy of existing therapies. The transforming growth factor-beta (TGF-B1), a mediator of tissue repair associated with WNT5A signaling, is partially responsible for fibroblast proliferation in ILD and is the target of Pirfenidone, one of the antifibrotic therapies used for patients with IPF. Canonical TGF-B signaling is mediated by the proteins SMAD 2/3, which are, in turn, indirectly regulated by Collagen Triple Helix Repeat Containing 1 (CTHRC1). In this study, we tested the following hypotheses: 1) CTHRC1 is more elevated in the ILD cohort compared to unaffected controls, and 2) CTHRC1 is differently expressed among ILD types. Material and Methods: CTHRC1 levels were measured by ELISA in 171 plasma samples from the deidentified University of Utah ILD cohort. Data represent a cohort of 131 ILD-affected participants and 40 unaffected controls. CTHRC1 samples were categorized by a pulmonologist based on affectation status and disease subtypes: IPF (n = 45), sarcoidosis (4), nonspecific interstitial pneumonia (16), hypersensitivity pneumonitis (n = 7), interstitial pneumonia (n=13), autoimmune (n = 15), other ILD - a category that includes undifferentiated ILD diagnoses (n = 31), and unaffected controls (n = 40). We conducted a single-factor ANOVA of plasma CTHRC1 levels to test whether CTHRC1 variance among affected and non-affected participants is statistically significantly different. In-silico analysis was performed with Ingenuity Pathway Analysis® to characterize the role of CTHRC1 in the pathway of lung fibrosis. Results: Statistical analyses of CTHRC1 in plasma samples indicate that the average CTHRC1 level is significantly higher in ILD-affected participants than controls, with the autoimmune ILD being higher than other ILD types, thus supporting our hypotheses. In-silico analyses show that CTHRC1 indirectly activates and phosphorylates SMAD3, which in turn cross-regulates TGF-B1. CTHRC1 also may regulate the expression and transcription of TGFB-1 via WNT5A and its regulatory relationship with CTNNB1. Conclusion: In-silico pathway analyses demonstrate that CTHRC1 may be an important biomarker in ILD. Analysis of plasma samples indicates that CTHRC1 expression is positively associated with ILD affectation, with autoimmune ILD having the highest average CTHRC1 values. While characterizing CTHRC1 levels in plasma can help to differentiate among ILD types and predict response to Pirfenidone, the extent to which plasma CTHRC1 level is a function of ILD severity or chronicity is unknown.

Keywords: interstitial lung disease, CTHRC1, idiopathic pulmonary fibrosis, pathway analyses

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Authors: Bonnie R. Brammall, Rhonda M. Garad, Helena J. Teede, Cheryce L. Harrison

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Introduction: Reproductive aged women are at high-risk for accelerated weight gain and obesity development, with pregnancy recognised as a critical contributory life phase. Healthy lifestyle interventions during the preconception and antenatal period improve maternal and infant health outcomes. Yet, interventions from preconception through to postpartum and translation and implementation into real-world healthcare settings remain limited. OptimalMe is a randomised, hybrid implementation effectiveness study of evidence-based healthy lifestyle intervention. Here, we report engagement, acceptability of the intervention during preconception, and self-reported behaviour change outcomes as a result of the preconception phase of the intervention. Methods: Reproductive aged women who upgraded their private health insurance to include pregnancy and birth cover, signalling a pregnancy intention, were invited to participate. Women received access to an online portal with preconception health and lifestyle modules, goal-setting and behaviour change tools, monthly SMS messages, and two coaching sessions (randomised to video or phone) prior to pregnancy. Results: Overall n=527 expressed interest in participating. Of these, n=33 did not meet inclusion criteria, n=8 were not contactable for eligibility screening, and n=177 failed to engage after the screening, leaving n=309 who were enrolled in OptimalMe and randomised to intervention delivery method. Engagement with coaching sessions dropped by 25% for session two, with no difference between intervention groups. Women had a mean (SD) age of 31.7 (4.3) years and, at baseline, a self-reported mean BMI of 25.7 (6.1) kg/m², with 55.8% (n=172) of a healthy BMI. Behaviour was sub-optimal with infrequent self-weighing (38.1%), alcohol consumption prevalent (57.1%), sub-optimal pre-pregnancy supplementation (61.5%), and incomplete medical screening. Post-intervention 73.2% of women reported engagement with a GP for preconception care and improved lifestyle behaviour (85.5%), since starting OptimalMe. Direct pre-and-post comparison of individual participant data showed that of 322 points of potential change (up-to-date cervical screening, elimination of high-risk behaviours [alcohol, drugs, smoking], uptake of preconception supplements and improved weighing habits) 158 (49.1%) points of change were achieved. Health coaching sessions were found to improve accountability and confidence, yet further personalisation and support were desired. Engagement with video and phone sessions was comparable, having similar impacts on behaviour change, and both methods were well accepted and increased women's accountability. Conclusion: A low-intensity digital health and lifestyle program with embedded health coaching can improve the uptake of preconception care and lead to self-reported behaviour change. This is the first program of its kind to reach an otherwise healthy population of women planning a pregnancy. Women who were otherwise healthy showed divergence from preconception health and lifestyle objectives and benefited from the intervention. OptimalMe shows promising results for population-based behaviour change interventions that can improve preconception lifestyle habits and increase engagement with clinical health care for pregnancy preparation.

Keywords: preconception, pregnancy, preventative health, weight gain prevention, self-management, behaviour change, digital health, telehealth, intervention, women's health

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Authors: Shanna Swart, Caryn Fenner, Athanasios Kotsiopoulos, Susan Harrison

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Linear alkanes are produced as by-products from the increasing use of gas-to-liquid fuel technologies for synthetic fuel production and offer great potential for value addition. Their current use as low-value fuels and solvents do not maximize this potential. Therefore, attention has been drawn towards direct activation of these aliphatic alkanes to more useful products such as alcohols, aldehydes, carboxylic acids and derivatives. Cytochrome P450 monooxygenases (P450s) can be used for activation of these aliphatic alkanes using whole-cells or cell-free systems. Some limitations of whole-cell systems include reduced mass transfer, stability and possible side reactions. Since the P450 systems are little studied as cell-free systems, they form the focus of this study. Challenges of a cell-free system include co-factor regeneration, substrate availability and enzyme stability. Enzyme immobilization offers a positive outlook on this dilemma, as it may enhance stability of the enzyme. In the present study, 2 different P450s (CYP153A6 and CYP102A1) as well as the relevant accessory enzymes required for electron transfer (ferredoxin and ferredoxin reductase) and co-factor regeneration (glucose dehydrogenase) have been expressed in E. coli and purified by metal affinity chromatography. Glucose dehydrogenase (GDH), was used as a model enzyme to assess the potential of various enzyme immobilization strategies including; surface attachment on MagReSyn® microspheres with various functionalities and on electrospun nanofibers, using self-assembly based methods forming Cross Linked Enzymes (CLE), Cross Linked Enzyme Aggregates (CLEAs) and spherezymes as well as in a sol gel. The nanofibers were synthesized by electrospinning, which required the building of an electrospinning machine. The nanofiber morphology has been analyzed by SEM and binding will be further verified by FT-IR. Covalent attachment based methods showed limitations where only ferredoxin reductase and GDH retained activity after immobilization which were largely attributed to insufficient electron transfer and inactivation caused by the crosslinkers (60% and 90% relative activity loss for the free enzyme when using 0.5% glutaraldehyde and glutaraldehyde/ethylenediamine (1:1 v/v), respectively). So far, initial experiments with GDH have shown the most potential when immobilized via their His-tag onto the surface of MagReSyn® microspheres functionalized with Ni-NTA. It was found that Crude GDH could be simultaneously purified and immobilized with sufficient activity retention. Immobilized pure and crude GDH could be recycled 9 and 10 times, respectively, with approximately 10% activity remaining. The immobilized GDH was also more stable than the free enzyme after storage for 14 days at 4˚C. This immobilization strategy will also be applied to the P450s and optimized with regards to enzyme loading and immobilization time, as well as characterized and compared with the free enzymes. It is anticipated that the proposed immobilization set-up will offer enhanced enzyme stability (as well as reusability and easy recovery), minimal mass transfer limitation, with continuous co-factor regeneration and minimal enzyme leaching. All of which provide a positive outlook on this robust multi-enzyme system for efficient activation of linear alkanes as well as the potential for immobilization of various multiple enzymes, including multimeric enzymes for different bio-catalytic applications beyond alkane activation.

Keywords: alkane activation, cytochrome P450 monooxygenase, enzyme catalysis, enzyme immobilization

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Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

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Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

Procedia PDF Downloads 156