Search results for: academic profile in chemistry

Authors: Karen L. Lindsay, Sonja Entringer, Claudia Buss, Pathik D. Wadhwa

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Maternal nutrition and stress are independently recognized as among the most important factors that influence prenatal biology, with implications for fetal development and poor pregnancy outcomes. While there is substantial evidence from non-pregnancy human and animal studies that a complex, bi-directional relationship exists between nutrition and stress, to the author’s best knowledge, their interaction in the context of pregnancy has been significantly understudied. The aim of this study is to assess the interaction between maternal psychological stress and diet quality across pregnancy and its effects on biomarkers of prenatal insulin resistance and inflammation. This is a prospective longitudinal study of N=235 women carrying a healthy, singleton pregnancy, recruited from prenatal clinics of the University of California, Irvine Medical Center. Participants completed a 4-day ambulatory assessment in early, middle and late pregnancy, which included multiple daily electronic diary entries using Ecological Momentary Assessment (EMA) technology on a dedicated study smartphone. The EMA diaries gathered moment-level data on maternal perceived stress, negative mood, positive mood and quality of social interactions. The numerical scores for these variables were averaged across each study time-point and converted to Z-scores. A single composite variable for 'STRESS' was computed as follows: (Negative mood+Perceived stress)–(Positive mood+Social interaction quality). Dietary intakes were assessed by three 24-hour dietary recalls conducted within two weeks of each 4-day assessment. Daily nutrient and food group intakes were averaged across each study time-point. The Alternative Healthy Eating Index adapted for pregnancy (AHEI-P) was computed for early, middle and late pregnancy as a validated summary measure of diet quality. At the end of each 4-day ambulatory assessment, women provided a fasting blood sample, which was assayed for levels of glucose, insulin, Interleukin (IL)-6 and Tumor Necrosis Factor (TNF)-α. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was computed. Pearson’s correlation was used to explore the relationship between maternal STRESS and AHEI-P within and between each study time-point. Linear regression was employed to test the association of the stress-diet interaction (STRESS*AHEI-P) with the biological markers HOMA-IR, IL-6 and TNF-α at each study time-point, adjusting for key covariates (pre-pregnancy body mass index, maternal education level, race/ethnicity). Maternal STRESS and AHEI-P were significantly inversely correlated in early (r=-0.164, p=0.018) and mid-pregnancy (-0.160, p=0.019), and AHEI-P from earlier gestational time-points correlated with later STRESS (early AHEI-P x mid STRESS: r=-0.168, p=0.017; mid AHEI-P x late STRESS: r=-0.142, p=0.041). In regression models, the interaction term was not associated with HOMA-IR or IL-6 at any gestational time-point. The stress-diet interaction term was significantly associated with TNF-α according to the following patterns: early AHEI-P*early STRESS vs early TNF-α (p=0.005); early AHEI-P*early STRESS vs mid TNF-α (p=0.002); early AHEI-P*mid STRESS vs mid TNF-α (p=0.005); mid AHEI-P*mid STRESS vs mid TNF-α (p=0.070); mid AHEI-P*late STRESS vs late TNF-α (p=0.011). Poor diet quality is significantly related to higher psychosocial stress levels in pregnant women across gestation, which may promote inflammation via TNF-α. Future prenatal studies should consider the combined effects of maternal stress and diet when evaluating either one of these factors on pregnancy or infant outcomes.

Keywords: diet quality, inflammation, insulin resistance, nutrition, pregnancy, stress, tumor necrosis factor-alpha

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Authors: Irene Kalemaki, Ioanna Garefi

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Social Innovation Education (SIE) is a new educational approach that aims to empower students to take action for a more democratic and sustainable society. Conceptually and pedagogically wise, it is situated at the intersection of Enterprise Education and Citizenship Education as it aspires to i) combine action with activism, ii) personal development with collective efficacy, iii) entrepreneurial mindsets with democratic values and iv) individual competences with collective competences. This paper abstract presents the work of the NEMESIS project, funded by H2020, that aims to design, test and validate the first consolidated approach for embedding Social Innovation Education in schools of primary and secondary education. During the academic year 2018-2019, eight schools from five European countries experimented with different approaches and methodologies to incorporate SIE in their settings. This paper reports briefly on these attempts and discusses the wider educational philosophy underlying these interventions with a particular focus on analyzing the learning outcomes and impact on students. That said, this paper doesn’t only report on the theoretical and practical underpinnings of SIE, but most importantly, it provides evidence on the impact of SIE on students. In terms of methodology, the study took place from September 2018 to July 2019 in eight schools from Greece, Spain, Portugal, France, and the UK involving directly 56 teachers, 1030 students and 69 community stakeholders. Focus groups, semi-structured interviews, classroom observations as well as students' written narratives were used to extract data on the impact of SIE on students. The overall design of the evaluation activities was informed by a realist approach, which enabled us to go beyond “what happened” and towards understanding “why it happened”. Research findings suggested that SIE can benefit students in terms of their emotional, cognitive, behavioral and agentic engagement. Specifically, the emotional engagement of students was increased because through SIE interventions; students voice was heard, valued, and acted upon. This made students feel important to their school, increasing their sense of belonging, confidence and level of autonomy. As regards cognitive engagement, both students and teachers reported positive outcomes as SIE enabled students to take ownership of their ideas to drive their projects forward and thus felt more motivated to perform in class because it felt personal, important and relevant to them. In terms of behavioral engagement, the inclusive environment and the collective relationships that were reinforced through the SIE interventions had a direct positive impact on behaviors among peers. Finally, with regard to agentic engagement, it has been observed that students became very proactive which was connected to the strong sense of ownership and enthusiasm developed during collective efforts to deliver real-life social innovations. Concluding, from a practical and policy point of view these research findings could encourage the inclusion of SIE in schools, while from a research point of view, they could contribute to the scientific discourse providing evidence and clarity on the emergent field of SIE.

Keywords: education, engagement, social innovation, students

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Authors: Sandra Hartl, Meena Chavan

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This paper presents the outcome of a four year Ph.D. research on cross-cultural conflict management in transnational business relationships. An important and complex problem about managing conflicts that arise across cultures in business relationships is investigated, and conflict resolution strategies are identified. This paper particularly focuses on transnational relationships within a Chinese, German and Middle Eastern framework. Unlike many papers on this issue which have been built on experiments with international MBA students, this research provides real-life cases of cross-cultural conflicts which are not easy to capture. Its uniqueness is underpinned as the real case data was gathered by interviewing top executives at management positions in large multinational corporations through a qualitative case study method approach. This paper makes a valuable contribution to the theory of cross-cultural conflicts, and despite the sensitivity, this research primarily presents real-time business data about breaches of contracts between two counterparties engaged in transnational operating organizations. The overarching aim of this research is to identify the degree of significance for the cultural factors and the communication factors embedded in cross-cultural business conflicts. It questions from a cultural perspective what factors lead to the conflicts in each of the cases, what the causes are and the role of culture in identifying effective strategies for resolving international disputes in an increasingly globalized business world. The results of 20 face to face interviews are outlined, which were conducted, recorded, transcribed and then analyzed using the NVIVO qualitative data analysis system. The outcomes make evident that the factors leading to conflicts are broadly organized under seven themes, which are communication, cultural difference, environmental issues, work structures, knowledge and skills, cultural anxiety and personal characteristics. When evaluating the causes of the conflict it is to notice that these are rather multidimensional. Irrespective of the conflict types (relationship or task-based conflict or due to individual personal differences), relationships are almost always an element of all conflicts. Cultural differences, which are a critical factor for conflicts, result from different cultures placing different levels of importance on relationships. Communication issues which are another cause of conflict also reflect different relationships styles favored by different cultures. In identifying effective strategies for solving cross-cultural business conflicts this research identifies that solutions need to consider the national cultures (country specific characteristics), organizational cultures and individual culture, of the persons engaged in the conflict and how these are interlinked to each other. Outcomes identify practical dispute resolution strategies to resolve cross-cultural business conflicts in reference to communication, empathy and training to improve cultural understanding and cultural competence, through the use of mediation. To conclude, the findings of this research will not only add value to academic knowledge of cross-cultural conflict management across transnational businesses but will also add value to numerous cross-border business relationships worldwide. Above all it identifies the influence of cultures and communication and cross-cultural competence in reducing cross-cultural business conflicts in transnational business.

Keywords: business conflict, conflict management, cross-cultural communication, dispute resolution

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Authors: Veenu Bala, Yashpal S. Chhonker, Bhavana Kushwaha, Rabi S. Bhatta, Gopal Gupta, Vishnu L. Sharma

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According to UNAIDS 2013 estimate nearly 52% of all individuals living with HIV are now women of reproductive age (15–44 years). Seventy-five percent cases of HIV acquisition are through heterosexual contacts and sexually transmitted infections (STIs), attributable to unsafe sexual behaviour. Each year, an estimated 500 million people acquire atleast one of four STIs: chlamydia, gonorrhoea, syphilis and trichomoniasis. Trichomonas vaginalis (TV) is exclusively sexually transmitted in adults, accounting for 30% of STI cases and associated with pelvic inflammatory disease (PID), vaginitis and pregnancy complications in women. TV infection resulted in impaired vaginal milieu, eventually favoring HIV transmission. In the absence of an effective prophylactic HIV vaccine, prevention of new infections has become a priority. It was thought worthwhile to integrate HIV prevention and reproductive health services including unintended pregnancy protection for women as both are related with unprotected sex. Initially, nonoxynol-9 (N-9) had been proposed as a spermicidal agent with microbicidal activity but on the contrary it increased HIV susceptibility due to surfactant action. Thus, to accomplish an urgent need of novel woman controlled non-detergent microbicidal spermicides benzenepropanamine analogues have been synthesized. At first, five benzenepropanamine-dithiocarbamate hybrids have been synthesized and evaluated for their spermicidal, anti-Trichomonas and anti-fungal activities along with safety profiling to cervicovaginal cells. In order to further enhance the scope of above study benzenepropanamine was hybridized with thiourea as to introduce anti-HIV potential. The synthesized hybrid molecules were evaluated for their reverse transcriptase (RT) inhibition, spermicidal, anti-Trichomonas and antimicrobial activities as well as their safety against vaginal flora and cervical cells. simulated vaginal fluid (SVF) stability and pharmacokinetics of most potent compound versus N-9 was examined in female Newzealand (NZ) rabbits to observe its absorption into systemic circulation and subsequent exposure in blood plasma through vaginal wall. The study resulted in the most promising compound N-butyl-4-(3-oxo-3-phenylpropyl) piperazin-1-carbothioamide (29) exhibiting better activity profile than N-9 as it showed RT inhibition (72.30 %), anti-Trichomonas (MIC, 46.72 µM against MTZ susceptible and MIC, 187.68 µM against resistant strain), spermicidal (MEC, 0.01%) and antifungal activity (MIC, 3.12–50 µg/mL) against four fungal strains. The high safety against vaginal epithelium (HeLa cells) and compatibility with vaginal flora (lactobacillus), SVF stability and least vaginal absorption supported its suitability for topical vaginal application. Docking study was performed to gain an insight into the binding mode and interactions of the most promising compound, N-butyl-4-(3-oxo-3-phenylpropyl) piperazin-1-carbothioamide (29) with HIV-1 Reverse Transcriptase. The docking study has revealed that compound (29) interacted with HIV-1 RT similar to standard drug Nevirapine. It may be concluded that hybridization of benzenepropanamine and thiourea moiety resulted into novel lead with multiple activities including RT inhibition. A further lead optimization may result into effective vaginal microbicides having spermicidal, anti-Trichomonas, antifungal and anti-HIV potential altogether with enhanced safety to cervico-vaginal cells in comparison to Nonoxynol-9.

Keywords: microbicidal, nonoxynol-9, reverse transcriptase, spermicide

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Authors: Irina-Emily Hansen, Ola Jon Mork

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The European economic growth strategy and supporting it framework for research and innovation highlight the importance of nurturing new open innovation in order to strengthen Europe’s competitiveness. One of the main approaches to enhance innovation in European society is the Triple Helix model that centres on science- industry collaboration where the universities are assigned the managerial role. In spite of the defined collaboration strategy, the collaboration between academics and in-dustry in Europe has still many challenges. Many of them are explained by culture difference: academic culture aims towards scientific knowledge, while businesses are oriented towards pro-duction and profitable results; also execution of collaborative projects is seen differently by part-ners involved. That proves that traditional management strategies applied to collaboration between researchers and businesses are not effective. There is a need for dynamic strategies that can support the interaction between researchers and industry intensifying knowledge co-creation and contributing to development of national innovation system (NIS) by incorporating individual, organizational and inter-organizational learning. In order to find a good subject to follow, the researchers of a given paper have investigated one of the most rapidly developing knowledge-based, innovation society, Singapore. Singapore does not dispose much land- or sea- resources that normally provide income for any country. Therefore, Singapore was forced to think differently and build society on resources that are available: talented people and knowledge. Singapore has during the last twenty years developed attracting high rated university camps, research institutions and leading industrial companies from all over the world. This article elucidates and elaborates Singapore’s national innovation strategies from Knowledge Management perspective. The research is done on the variety of organizations that enable and support knowledge development in this state: governmental research and development (R&D) centers in universities, private talent incubators for entrepreneurs, and industrial companies with own R&D departments. The research methods are based on presentations, documents, and visits at a number of universities, research institutes, innovation parks, governmental institutions, industrial companies and innovation exhibitions in Singapore. In addition, a literature review of science articles is made regarding the topic. The first finding is that objectives of collaboration between researchers, entrepreneurs and industry in Singapore correspond primary goals of the state: knowledge- and economy growth. There are common objectives for all stakeholders on all national levels. The second finding is that Singapore has enabled system on a national level that supports innovation the entire way from fostering or capturing the new knowledge, providing knowledge exchange and co-creation to application of it in real-life. The conclusion is that innovation means not only new idea, but also the enabling mechanism for its execution and the marked-oriented approach in order that new knowledge can be absorbed in society. The future research can be done with regards to application of Singapore knowledge management strategy in innovation to European countries.

Keywords: knowledge management strategy, national innovation system, research industry and business collaboration, knowledge enabling

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Authors: Emanuela Chiarella, Annamaria Aloisio, Nisticò Clelia, Maria Mesuraca

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ZNF521 is a stem cell-associated transcription co-factor, that plays a crucial role in the homeostatic regulation of the stem cell compartment in the hematopoietic, osteo-adipogenic, and neural system. In normal hematopoiesis, primary human CD34+ hematopoietic stem cells display typically a high expression of ZNF521, while its mRNA levels rapidly decrease when these progenitors progress towards erythroid, granulocytic, or B-lymphoid differentiation. However, most acute myeloid leukemias (AMLs) and leukemia-initiating cells keep high ZNF521 expression. In particular, AMLs are often characterized by chromosomal translocations involving the Mixed Lineage Leukemia (MLL) gene, which MLL gene includes a variety of fusion oncogenes arisen from genes normally required during hematopoietic development; once they are fused, they promote epigenetic and transcription factor dysregulation. The chromosomal translocation t(9;11)(p21-22;q23), fusing the MLL gene with AF9 gene, results in a monocytic immune phenotype with an aggressive course, frequent relapses, and a short survival time. To better understand the dysfunctional transcriptional networks related to genetic aberrations, AML gene expression profile datasets were queried for ZNF521 expression and its correlations with specific gene rearrangements and mutations. The results showed that ZNF521 mRNA levels are associated with specific genetic aberrations: the highest expression levels were observed in AMLs involving t(11q23) MLL rearrangements in two distinct datasets (MILE and den Boer); elevated ZNF521 mRNA expression levels were also revealed in AMLs with t(7;12) or with internal rearrangements of chromosome 16. On the contrary, relatively low ZNF521 expression levels seemed to be associated with the t(8;21) translocation, that in turn is correlated with the AML1-ETO fusion gene or the t(15;17) translocation and in AMLs with FLT3-ITD, NPM1, or CEBPα double mutations. Invitro, we found that the enforced co-expression of ZNF521 in cord blood-derived CD34+ cells induced a significant proliferative advantage, improving MLL-AF9 effects on the induction of proliferation and the expansion of leukemic progenitor cells. Transcriptome profiling of CD34+ cells transduced with either MLL-AF9, ZNF521, or a combination of the two transgenes highlighted specific sets of up- or down-regulated genes that are involved in the leukemic phenotype, including those encoding transcription factors, epigenetic modulators, and cell cycle regulators as well as those engaged in the transport or uptake of nutrients. These data enhance the functional cooperation between ZNF521 and MA9, resulting in the development, maintenance, and clonal expansion of leukemic cells. Finally, silencing of ZNF521 in MLL-AF9-transformed primary CD34+ cells inhibited their proliferation and led to their extinction, as well as ZNF521 silencing in the MLL-AF9+ THP-1 cell line resulted in an impairment of their growth and clonogenicity. Taken together, our data highlight ZNF521 role in the control of self-renewal and in the immature compartment of malignant hematopoiesis, which, by altering the gene expression landscape, contributes to the development and/or maintenance of AML acting in concert with the MLL-AF9 fusion oncogene.

Keywords: AML, human zinc finger protein 521 (hZNF521), mixed lineage leukemia gene (MLL) AF9 (MLLT3 or LTG9), cord blood-derived hematopoietic stem cells (CB-CD34+)

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Authors: M. Reza Hashemi, Chris Small, Scott Hayward

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The Northeast Coast of the US faces damaging effects of coastal flooding and winds due to Atlantic tropical and extratropical storms each year. Historically, several large storm events have produced substantial levels of damage to the region; most notably of which were the Great Atlantic Hurricane of 1938, Hurricane Carol, Hurricane Bob, and recently Hurricane Sandy (2012). The objective of this study was to develop an integrated modeling system that could be used as a forecasting/hindcasting tool to evaluate and communicate the risk coastal communities face from these coastal storms. This modeling system utilizes the ADvanced CIRCulation (ADCIRC) model for storm surge predictions and the Simulating Waves Nearshore (SWAN) model for the wave environment. These models were coupled, passing information to each other and computing over the same unstructured domain, allowing for the most accurate representation of the physical storm processes. The coupled SWAN-ADCIRC model was validated and has been set up to perform real-time forecast simulations (as well as hindcast). Modeled storm parameters were then passed to a coastal risk assessment tool. This tool, which is generic and universally applicable, generates spatial structural damage estimate maps on an individual structure basis for an area of interest. The required inputs for the coastal risk model included a detailed information about the individual structures, inundation levels, and wave heights for the selected region. Additionally, calculation of wind damage to structures was incorporated. The integrated coastal risk assessment system was then tested and applied to Charlestown, a small vulnerable coastal town along the southern shore of Rhode Island. The modeling system was applied to Hurricane Sandy and a synthetic storm. In both storm cases, effect of natural dunes on coastal risk was investigated. The resulting damage maps for the area (Charlestown) clearly showed that the dune eroded scenarios affected more structures, and increased the estimated damage. The system was also tested in forecast mode for a large Nor’Easters: Stella (March 2017). The results showed a good performance of the coupled model in forecast mode when compared to observations. Finally, a nearshore model XBeach was then nested within this regional grid (ADCIRC-SWAN) to simulate nearshore sediment transport processes and coastal erosion. Hurricane Irene (2011) was used to validate XBeach, on the basis of a unique beach profile dataset at the region. XBeach showed a relatively good performance, being able to estimate eroded volumes along the beach transects with a mean error of 16%. The validated model was then used to analyze the effectiveness of several erosion mitigation methods that were recommended in a recent study of coastal erosion in New England: beach nourishment, coastal bank (engineered core), and submerged breakwater as well as artificial surfing reef. It was shown that beach nourishment and coastal banks perform better to mitigate shoreline retreat and coastal erosion.

Keywords: ADCIRC, coastal flooding, storm surge, coastal risk assessment, living shorelines

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Authors: Bruno Biagianti, Angela Tseng, Kathy Wannaviroj, Allison Corlett, Megan DuBois, Kyu Lee, Suma Jacob

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Background: ASD is characterized by pervasive Sensory Processing Abnormalities (SPA) and social cognitive deficits that persist throughout the course of the illness and have been linked to functional abnormalities in specific neural systems that underlie the perception, processing, and representation of sensory information. SPA and social cognitive deficits are associated with difficulties in interpersonal relationships, poor development of social skills, reduced social interactions and lower academic performance. Importantly, they can hamper the effects of established evidence-based psychological treatments—including PEERS (Program for the Education and Enrichment of Relationship Skills), a parent/caregiver-assisted, 16-weeks social skills intervention—which nonetheless requires a functional brain capable of assimilating and retaining information and skills. As a matter of fact, some adolescents benefit from PEERS more than others, calling for strategies to increase treatment response rates. Objective: We will present interim data on CICADAS (Care Improving Cognition for ADolescents on the Autism Spectrum)—a clinician-assisted, closed-loop technology mobile application for adolescents with ASD. Via ten mobile assessments, CICADAS captures data on sensory processing abnormalities and associated cognitive deficits. These data populate a machine learning algorithm that tailors the delivery of ten neuroplasticity-based social cognitive training (NB-SCT) exercises targeting sensory processing abnormalities. Methods: In collaboration with the Autism Spectrum and Neurodevelopmental Disorders Clinic at the University of Minnesota, we conducted a fully remote, three-arm, randomized crossover trial with adolescents with ASD to document the acceptability of CICADAS and evaluate its potential as a stand-alone treatment or as a treatment enhancer of PEERS. Twenty-four adolescents with ASD (ages 11-18) have been initially randomized to 16 weeks of PEERS + CICADAS (Arm A) vs. 16 weeks of PEERS + computer games vs. 16 weeks of CICADAS alone (Arm C). After 16 weeks, the full battery of assessments has been remotely administered. Results: We have evaluated the acceptability of CICADAS by examining adherence rates, engagement patterns, and exit survey data. We found that: 1) CICADAS is able to serve as a treatment enhancer for PEERS, inducing greater improvements in sensory processing, cognition, symptom reduction, social skills and behaviors, as well as the quality of life compared to computer games; 2) the concurrent delivery of PEERS and CICADAS induces greater improvements in study outcomes compared to CICADAS only. Conclusion: While preliminary, our results indicate that the individualized assessment and treatment approach designed in CICADAS seems effective in inducing adaptive long-term learning about social-emotional events. CICADAS-induced enhancement of processing and cognition facilitates the application of PEERS skills in the environment of adolescents with ASD, thus improving their real-world functioning.

Keywords: ASD, social skills, cognitive training, mobile app

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Authors: Sarah Reker, Christiane H. Kellner

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From the perspective of people with disabilities, inequalities can also emerge from spatial segregation, the lack of social contacts or limited economic resources. In order to reduce or even eliminate these disadvantages and increase general well-being, community-based participation as well as decentralisation efforts within exclusively residential homes is essential. Therefore, the new research project “Index for participation development and quality of life for persons with disabilities”(TeLe-Index, 2014-2016), which is anchored at the Technische Universität München in Munich and at a large residential complex and service provider for persons with disabilities in the outskirts of Munich aims to assist the development of community-based living environments. People with disabilities should be able to participate in social life beyond the confines of the institution. Since a diverse society is a society in which different individual needs and wishes can emerge and be catered to, the ultimate goal of the project is to create an environment for all citizens–regardless of disability, age or ethnic background–that accommodates their daily activities and requirements. The UN-Convention on the Rights of Persons with Disabilities, which Germany also ratified, postulates the necessity of user-centered design, especially when it comes to evaluating the individual needs and wishes of all citizens. Therefore, a multidimensional approach is required. Based on this insight, the structure of the town-like center will be remodeled to open up the community to all people. This strategy should lead to more equal opportunities and open the way for a much more diverse community. Therefore, macro-level research questions were inspired by quality of life theory and were formulated as follows for different dimensions: •The user dimension: what needs and necessities can we identify? Are needs person-related? Are there any options to choose from? What type of quality of life can we identify? The economic dimension: what resources (both material and staff-related) are available in the region? (How) are they used? What costs (can) arise and what effects do they entail? •The environment dimension: what “environmental factors” such as access (mobility and absence of barriers) prove beneficial or impedimental? In this context, we have provided academic supervision and support for three projects (the construction of a new school, inclusive housing for children and teenagers with disabilities and the professionalization of employees with person-centered thinking). Since we cannot present all the issues of the umbrella-project within the conference framework, we will be focusing on one project more in-depth, namely “Outpatient Housing Options for Children and Teenagers with Disabilities”. The insights we have obtained until now will enable us to present the intermediary results of our evaluation. The most central questions pertaining to this part of the research were the following: •How have the existing network relations been designed? •What meaning (or significance) does the existing service offers and structures have for the everyday life of an external residential group? These issues underpinned the environmental analyses as well as the qualitative guided interviews and qualitative network analyses we carried out.

Keywords: decentralisation, environmental analyses, outpatient housing options for children and teenagers with disabilities, qualitative network analyses

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Authors: Alaa Abdellatif, Gabrièle Breda

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Background. Advanced therapy medicinal products (ATMPs) are innovative therapies that mainly target orphan diseases and high unmet medical needs. ATMP includes gene therapy medicinal products (GTMP), somatic cell therapy medicinal products (CTMP), and tissue-engineered therapies (TEP). Since legislation opened the way in 2007, 25 ATMPs have been approved in the EU, which is about the same amount as the U.S. Food and Drug Administration. However, not all of the ATMPs that have been approved have successfully reached the market and retained their approval. Objectives. We aim to understand all the factors limiting the market access to very promising therapies in a systemic approach, to be able to overcome these problems, in the future, with scientific, regulatory and commercial innovations. Further to recent reviews that focus either on specific countries, products, or dimensions, we will address all the challenges faced by ATMP development today. Methodology. We used mixed methods and a multi-level approach for data collection. First, we performed an updated academic literature review on ATMP development and their scientific and market access challenges (papers published between 2018 and April 2023). Second, we analyzed industry feedback from cell and gene therapy webinars and white papers published by providers and pharmaceutical industries. Finally, we established a comparative analysis of the regulatory guidelines published by EMA and the FDA for ATMP approval. Results: The main challenges in bringing these therapies to market are the high development costs. Developing ATMPs is expensive due to the need for specialized manufacturing processes. Furthermore, the regulatory pathways for ATMPs are often complex and can vary between countries, making it challenging to obtain approval and ensure compliance with different regulations. As a result of the high costs associated with ATMPs, challenges in obtaining reimbursement from healthcare payers lead to limited patient access to these treatments. ATMPs are often developed for orphan diseases, which means that the patient population is limited for clinical trials which can make it challenging to demonstrate their safety and efficacy. In addition, the complex manufacturing processes required for ATMPs can make it challenging to scale up production to meet demand, which can limit their availability and increase costs. Finally, ATMPs face safety and efficacy challenges: dangerous adverse events of these therapies like toxicity related to the use of viral vectors or cell therapy, starting material and donor-related aspects. Conclusion. As a result of our mixed method analysis, we found that ATMPs face a number of challenges in their development, regulatory approval, and commercialization and that addressing these challenges requires collaboration between industry, regulators, healthcare providers, and patient groups. This first analysis will help us to address, for each challenge, proper and innovative solution(s) in order to increase the number of ATMPs approved and reach the patients

Keywords: advanced therapy medicinal products (ATMPs), product development, market access, innovation

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Authors: Jihong Liang, Huiling Feng, Linqing Ma, Tianjiao Qi

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Confucius is the first sage in Chinese culture. Confucianism, the theories represented by Confucius, has long been at the core of Chinese traditional society, as the dominating political ideology of centralized feudal monarchy for more than two thousand years. Confucius Worship Ceremony held in the Confucian Temple in Qufu (Confucius’s birthplace), which is dedicated to commemorate Confucius and other 170 elites in Confucianism with a whole set of formal rites, pertains to “Auspicious Rites”, which worship heaven and earth, humans and ghosts. It was first a medium-scaled ritual activity but then upgraded to the supreme one at national level in the Qing Dynasty. As a national event, it was celebrated by Emperor as well as common intellectuals in traditional China. The Ceremony can be solemn and respectful, with prescribed and complicated procedures, well-prepared utensil and matched offerings operated in rhythm with music and dances. Each participant has his place, and everyone follows the specified rules. This magnificent ritual Ceremony, while embedded with rich culture connotation, actually symbolizes the social acknowledgment for orthodox culture represented by Confucianism. Rites reflected in this Ceremony, is one of the most important features of Chinese culture, serving as the key bond in the identification and continuation of Chinese culture. These rites and ritual ceremonies, as culture memories themselves, are not only treasures of China, but of the whole world. However, while the ancient Chinese Rite has been one of the thorniest and most complicated topics for academics, the more regrettable is that due to their interruption in practice and historical changes, these rites and ritual ceremonies have already become a vague language in today’s academic discourse and strange terms of the past for common people. Luckily, we, today, by virtue of modern digital technology, may be able to reproduce these ritual ceremonies, as most of them can still be found in ancient manuscripts, through which Chinese ancestors tell the beauty and gravity of their dignified rites and more importantly, their spiritual pursuits with vivid language and lively pictures. This research, based on review and interpretation of the ancient literature, intends to construct the ancient ritual ceremonies, with the Confucius Worship Ceremony as a case and by use of digital technology. Using 3D technology, the spatial scenes in the Confucian Temple can be reconstructed by virtual reality; the memorial tablet exhibited in the temple by GIS and different rites in the ceremonies by animation technology. With reference to the lyrics, melodies and lively pictures recorded in ancient scripts, it is also possible to reproduce the live dancing site. Also, image rendering technology can help to show the life experience and accomplishments of Confucius. Finally, lining up all the elements in a multimedia narrative form, a complete digitalized Confucius Worship Ceremony can be reproduced, which will provide an excellent virtual experience that goes beyond time and space by bringing its audience back to that specific historical time. This digital project, once completed, will play an important role in the inheritance and dissemination of cultural heritage.

Keywords: Confucius worship ceremony, multimedia narrative form, GIS, visual representation

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Authors: Pedro M. Rodrigues, Claudia Raposo, Denise Schrama, Marco Cerqueira

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Farmed fish welfare is a very recent concept, widely discussed among the scientific community. Consumers’ interest regarding farmed animal welfare standards has significantly increased in the last years posing a huge challenge to producers in order to maintain an equilibrium between good welfare principles and productivity, while simultaneously achieve public acceptance. The major bottleneck of standard aquaculture is to impair considerably fish welfare throughout the production cycle and with this, the quality of fish protein. Welfare assessment in farmed fish is undertaken through the evaluation of fish stress responses. Primary and secondary stress responses include release of cortisol and glucose and lactate to the blood stream, respectively, which are currently the most commonly used indicators of stress exposure. However, the reliability of these indicators is highly dubious, due to a high variability of fish responses to an acute stress and the adaptation of the animal to a repetitive chronic stress. Our objective is to use comparative proteomics to identify and validate a fingerprint of proteins that can present an more reliable alternative to the already established welfare indicators. In this way, the culture conditions will improve and there will be a higher perception of mechanisms and metabolic pathway involved in the produced organism’s welfare. Due to its high economical importance in Portuguese aquaculture Gilthead seabream will be the elected species for this study. Protein extracts from Gilthead Seabream fish muscle, liver and plasma, reared for a 3 month period under optimized culture conditions (control) and induced stress conditions (Handling, high densities, and Hipoxia) are collected and used to identify a putative fish welfare protein markers fingerprint using a proteomics approach. Three tanks per condition and 3 biological replicates per tank are used for each analisys. Briefly, proteins from target tissue/fluid are extracted using standard established protocols. Protein extracts are then separated using 2D-DIGE (Difference gel electrophoresis). Proteins differentially expressed between control and induced stress conditions will be identified by mass spectrometry (LC-Ms/Ms) using NCBInr (taxonomic level - Actinopterygii) databank and Mascot search engine. The statistical analysis is performed using the R software environment, having used a one-tailed Mann-Whitney U-test (p < 0.05) to assess which proteins were differentially expressed in a statistically significant way. Validation of these proteins will be done by comparison of the RT-qPCR (Quantitative reverse transcription polymerase chain reaction) expressed genes pattern with the proteomic profile. Cortisol, glucose, and lactate are also measured in order to confirm or refute the reliability of these indicators. The identified liver proteins under handling and high densities induced stress conditions are responsible and involved in several metabolic pathways like primary metabolism (i.e. glycolysis, gluconeogenesis), ammonia metabolism, cytoskeleton proteins, signalizing proteins, lipid transport. Validition of these proteins as well as identical analysis in muscle and plasma are underway. Proteomics is a promising high-throughput technique that can be successfully applied to identify putative welfare protein biomarkers in farmed fish.

Keywords: aquaculture, fish welfare, proteomics, welfare biomarkers

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Authors: Ali Aqa Mohammad Jawad

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Taking a relational approach, this paper analyzes the causal mechanisms associated with successful mobilization and rapid demobilization of the Enlightening Movement in post-2001 Afghanistan. The movement emerged after the state-owned Da Afghan Bereshna Sherkat (DABS) decided to divert the route for the Turkmenistan-Uzbekistan-Tajikistan-Afghanistan-Pakistan (TUTAP) electricity project. The grid was initially planned to go through the Hazara-inhabited province of Bamiyan, according to Afghanistan’s Power Sector Master Plan. The reroute served as an aide-mémoire of historical subordination to other ethno-religious groups for the Hazara community. It was also perceived as deprivation from post-2001 development projects, financed by international aid. This torched the accumulated grievances, which then gave birth to the Enlightening Movement. The movement had a successful mobilization. However, it demobilized after losing much of its mobilizing capabilities through an amalgamation of external and internal relational factors. The successful mobilization yet rapid demobilization constitutes the puzzle of this paper. From the theoretical perspective, this paper is significant as it establishes the applicability of contentious politics theory to protest mobilizations that occurred in Afghanistan, a context-specific, characterized by ethnic politics. Both primary and secondary data are utilized to address the puzzle. As for the primary resources, media coverage, interviews, reports, public media statements of the movement, involved in contentious performances, and data from Social Networking Services (SNS) are used. The covered period is from 2001-2018. As for the secondary resources, published academic articles and books are used to give a historical account of contentious politics. For data analysis, a qualitative comparative historical method is utilized to uncover the causal mechanisms associated with successful mobilization and rapid demobilization of the Movement. In this pursuit, both mobilization and demobilization are considered as larger political processes that could be decomposed to constituent mechanisms. Enlightening Movement’s framing and campaigns are first studied to uncover the associated mechanisms. Then, to avoid introducing some ad hoc mechanisms, the recurrence of mechanisms is checked against another case. Mechanisms qualify as robust if they are “recurrent” in different episodes of contention. Checking the recurrence of causal mechanisms is vital as past contentious events tend to reinforce future events. The findings of this paper suggest that the public sphere in Afghanistan is drastically different from Western democracies known as the birthplace of social movements. In Western democracies, when institutional politics did not respond, movement organizers occupied the public sphere, undermining the legitimacy of the government. In Afghanistan, the public sphere is ethicized. Considering the inter- and intra-relational dynamics of ethnic groups in Afghanistan, the movement reduced to an erosive inter- and intra-ethnic conflict. This undermined the cohesiveness of the movement, which then kicked-off its demobilization process.

Keywords: enlightening movement, contentious politics, mobilization, demobilization

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Authors: Chieh-Ning Lan, Tzu-Shin Lin, Kun-Hao Lin

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Chinese handwriting skill is one of the basic skills of school-age children in Taiwan, which helps them to learn most academic subjects. Differ from the alphabetic language system, Chinese written language is a logographic script with a complicated 2-dimensional character structure as a morpheme. Visuospatial ability places a great role in Chinese handwriting to maintain good proportion and alignment of these interwoven strokes. In Taiwan, school-age students faced the challenge to recognize and write down Chinese characters, especially in children with written expression difficulties (CWWDs). In this study, we developed an instructional app to help CWWDs practice Chinese handwriting skills, and we aimed to apply the mobile assisted language learning (MALL) system in clinical writing strategies. To understand the feasibility and satisfaction of this auxiliary instructional writing app, we investigated the perceive and value both from school-age students and the clinic therapists, who were the target users and the experts. A group of 8 elementary school children, as well as 8 clinic therapists, were recruited. The school-age students were asked to go through a paper-based instruction and were asked to score the visual expression based on their graphic preference; the clinic therapists were asked to watch an introductive video of this instructional app and complete the online formative questionnaire. In the results of our study, from the perspective of user interface design, school-age students were more attracted to cartoon-liked pictures rather than line drawings or vivid photos. Moreover, compared to text, pictures which have higher semantic transparency were more commonly chosen by children. In terms of the quantitative survey from clinic therapists, they were highly satisfied with this auxiliary instructional writing app, including the concepts such as visual design, teaching contents, and positive reinforcement system. Furthermore, the qualitative results also suggested comprehensive positive feedbacks on the teaching contents and the feasibility of integrating the app into clinical treatments. Interestingly, we found that clinic therapists showed high agreement in approving CWWDs’ writing ability with using orthographic knowledge; however, in the qualitative section, clinic therapists pointed out that CWWDs usually have relative insufficient background knowledge in Chinese character orthographic rules, which because it is not a key-point in conventional handwriting instruction. Also, previous studies indicated that conventional Chinese reading and writing instructions were lacked of utilizing visual-spatial arrangement strategies. Based on the sharing experiences from all participants, we concluded several interesting topics that are worth to dedicate to in the future. In this undergoing app system, improvement and revision will be applied into the system design, and will establish a better and more useful instructional system for CWWDs within their treatments; enlightened by the opinions related to learning content, the importance of orthographic knowledge in Chinese character recognition should be well discussed and involved in CWWDs’ intervention in the future.

Keywords: auxiliary instructional app, children with writing difficulties, Chinese handwriting, orthographic knowledge

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Authors: Sofia Quaglia, Carmine Di Martino, Brendan Tierney

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Artificial Intelligence (A.I.) constitutes various aspects of modern life, from the Machine Learning algorithms predicting the stocks on Wall streets to the killing of belligerents and innocents alike on the battlefield. Moreover, the end goal is to create autonomous A.I.; this means that the presence of humans in the decision-making process will be absent. The question comes naturally: when an A.I. does something wrong when its behavior is harmful to the community and its actions go against the law, which is to be held responsible? This research’s subject matter in A.I. and Robot Ethics focuses mainly on Robot Rights and its ultimate objective is to answer the questions: (i) What is the function of rights? (ii) Who is a right holder, what is personhood and the requirements needed to be a moral agent (therefore, accountable for responsibility)? (iii) Can an A.I. be a moral agent? (ontological requirements) and finally (iv) if it ought to be one (ethical implications). With the direction to answer this question, this research project was done via a collaboration between the School of Computer Science in the Technical University of Dublin that oversaw the technical aspects of this work, as well as the Department of Philosophy in the University of Milan, who supervised the philosophical framework and argumentation of the project. Firstly, it was found that all rights are positive and based on consensus; they change with time based on circumstances. Their function is to protect the social fabric and avoid dangerous situations. The same goes for the requirements considered necessary to be a moral agent: those are not absolute; in fact, they are constantly redesigned. Hence, the next logical step was to identify what requirements are regarded as fundamental in real-world judicial systems, comparing them to that of ones used in philosophy. Autonomy, free will, intentionality, consciousness and responsibility were identified as the requirements to be considered a moral agent. The work went on to build a symmetrical system between personhood and A.I. to enable the emergence of the ontological differences between the two. Each requirement is introduced, explained in the most relevant theories of contemporary philosophy, and observed in its manifestation in A.I. Finally, after completing the philosophical and technical analysis, conclusions were drawn. As underlined in the research questions, there are two issues regarding the assignment of moral agency to artificial agent: the first being that all the ontological requirements must be present and secondly being present or not, whether an A.I. ought to be considered as an artificial moral agent. From an ontological point of view, it is very hard to prove that an A.I. could be autonomous, free, intentional, conscious, and responsible. The philosophical accounts are often very theoretical and inconclusive, making it difficult to fully detect these requirements on an experimental level of demonstration. However, from an ethical point of view it makes sense to consider some A.I. as artificial moral agents, hence responsible for their own actions. When considering artificial agents as responsible, there can be applied already existing norms in our judicial system such as removing them from society, and re-educating them, in order to re-introduced them to society. This is in line with how the highest profile correctional facilities ought to work. Noticeably, this is a provisional conclusion and research must continue further. Nevertheless, the strength of the presented argument lies in its immediate applicability to real world scenarios. To refer to the aforementioned incidents, involving the murderer of innocents, when this thesis is applied it is possible to hold an A.I. accountable and responsible for its actions. This infers removing it from society by virtue of its un-usability, re-programming it and, only when properly functioning, re-introducing it successfully

Keywords: artificial agency, correctional system, ethics, natural agency, responsibility

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Authors: Roshni Raha, Kavya P., Gayathri M.

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India, with a humongous population, remains the world's poorest developing nation in terms of nutritional status, with iron deficiency anaemia (IDA) affecting the population. Despite efforts over the past decades, India's anaemia prevalence has not been reduced. Researchers are interested in developing therapies that will minimize the typical side effects of oral iron and optimize iron salts-based treatment through delivery methods based on the physiology of hepcidin regulation. However, they need to come up with iron therapies that will prevent making the infection worse. This article explores using bio-nanotechnology as the alternative, promising substitution of providing iron supplements for the treatment of diarrhoea and gut inflammation in kids and pregnant women. This article is an exploratory study using a literature survey and secondary research from review papers. In the realm of biotechnology, nanoparticles have become extremely famous due to unexpected variations in surface characteristics caused by particle size. Particle size distribution and shape exhibit unusual, enhanced characteristics when reduced to nanoscale. The article attempts to develop a model for a nanotechnology based solution in iron fortification to combat the problems of diarrhoea and gut inflammation. Certain dimensions that have been considered in the model include the size, shape, source, and biosynthesis of the iron nanoparticles. Another area of investigation addressed in the article is the cost-effective biocompatible production of these iron nanoparticles. Studies have demonstrated that a substantial reduction of metal ions to form nanoparticles from the bulk metal occurs in plants because of the presence of a wide diversity of biomolecules. Using this concept, the paper investigates the effectiveness and impact of how similar sources can be used for the biological synthesis of iron nanoparticles. Results showed that iron particles, when prepared in nano-metre size, offer potential advantages. When the particle size of the iron compound decreases and attains nano configuration, its surface area increases, which further improves its solubility in the gastric acid, leading to higher absorption, higher bioavailability, and producing the least organoleptic changes in food. It has no negative effects and possesses a safe, effective profile to reduce IDA. Considering all the parameters, it has been concluded that iron particles in nano configuration serve as alternative iron supplements for the complete treatment of IDA. Nanoparticles of ferric phosphate, ferric pyrophosphate, and iron oxide are the choices of iron supplements. From a sourcing perspective, the paper concludes green sources are the primary sources for the biological synthesis of iron nanoparticles. It will also be a cost-effective strategy since our goal is to treat the target population in rural India. Bio-nanotechnology serves as an alternative and promising substitution for iron supplements due to its low cost, excellent bioavailability, and strong organoleptic properties. One area of future research can be to explore the type of size and shape of iron nanoparticles that would be suitable for the different age groups of pregnant women and children and whether it would be influenced based on the topography in certain areas.

Keywords: anemia, bio-nanotechnology, iron-fortification, nanoparticle

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Authors: Lacramioara Ochiuz, Aurelia Vasile, Iulian Stoleriu, Cristina Ghiciuc, Maria Ignat

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Topical administration of chemotherapeutic agents (eg. carmustine, bexarotene, mechlorethamine etc.) in local treatment of cutaneous T-cell lymphoma (CTCL) is accompanied by multiple side effects, such as contact hypersensitivity, pruritus, skin atrophy or even secondary malignancies. A known method of reducing the side effects of anticancer agent is the development of modified drug release systems using drug incapsulation in biocompatible nanoporous inorganic matrices, such as mesoporous MCM-41 silica. Mesoporous MCM-41 silica is characterized by large specific surface, high pore volume, uniform porosity, and stable dispersion in aqueous medium, excellent biocompatibility, in vivo biodegradability and capacity to be functionalized with different organic groups. Therefore, MCM-41 is an attractive candidate for a wide range of biomedical applications, such as controlled drug release, bone regeneration, protein immobilization, enzymes, etc. The main advantage of this material lies in its ability to host a large amount of the active substance in uniform pore system with adjustable size in a mesoscopic range. Silanol groups allow surface controlled functionalization leading to control of drug loading and release. This study shows (I) the amino-grafting optimization of mesoporous MCM-41 silica matrix by means of co-condensation during synthesis and post-synthesis using APTES (3-aminopropyltriethoxysilane); (ii) loading the therapeutic agent (carmustine) obtaining a modified drug release systems; (iii) determining the profile of in vitro carmustine release from these systems; (iv) assessment of carmustine release kinetics by fitting on four mathematical models. Obtained powders have been described in terms of structure, texture, morphology thermogravimetric analysis. The concentration of the therapeutic agent in the dissolution medium has been determined by HPLC method. In vitro dissolution tests have been done using cell Enhancer in a 12 hours interval. Analysis of carmustine release kinetics from mesoporous systems was made by fitting to zero-order model, first-order model Higuchi model and Korsmeyer-Peppas model, respectively. Results showed that both types of highly ordered mesoporous silica (amino grafted by co-condensation process or post-synthesis) are thermally stable in aqueous medium. In what regards the degree of loading and efficiency of loading with the therapeutic agent, there has been noticed an increase of around 10% in case of co-condensation method application. This result shows that direct co-condensation leads to even distribution of amino groups on the pore walls while in case of post-synthesis grafting many amino groups are concentrated near the pore opening and/or on external surface. In vitro dissolution tests showed an extended carmustine release (more than 86% m/m) both from systems based on silica functionalized directly by co-condensation and after synthesis. Assessment of carmustine release kinetics revealed a release through diffusion from all studied systems as a result of fitting to Higuchi model. The results of this study proved that amino-functionalized mesoporous silica may be used as a matrix for optimizing the anti-cancer topical therapy by loading carmustine and developing prolonged-release systems.

Keywords: carmustine, silica, controlled, release

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Authors: Wendy De Gomez

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The University of Waterloo is situated in central Canada in the Province of Ontario- one hour from the metropolitan city of Toronto. For over 30 years, it has held Canada’s top spot as the most innovative university; and has been consistently ranked in the top 25 computer science and top 50 engineering schools in the world. Waterloo benefits from the federal government’s over 100 domestic innovation policies which have assisted in the country’s 15th place global ranking in the World Intellectual Property Organization’s (WIPO) 2022 Global Innovation Index. Yet undoubtedly, the University of Waterloo’s unique characteristics are what propels its innovative creativeness forward. This paper will provide a contextual definition of innovation in higher education and then demonstrate the five operational attributes that contribute to the University of Waterloo’s innovative reputation. The methodology is based on statistical analyses obtained from ranking bodies such as the QS World University Rankings, a secondary literature review related to higher education innovation in Canada, and case studies that exhibit the operationalization of the attributes outlined below. The first attribute is geography. Specifically, the paper investigates the network structure effect of the Toronto-Waterloo high-tech corridor and the resultant industrial relationships built there. The second attribute is University Policy 73-Intellectal Property Rights. This creator-owned policy grants all ownership to the creator/inventor regardless of the use of the University of Waterloo property or funding. Essentially, through the incentivization of IP ownership by all researchers, further commercialization and entrepreneurship are formed. Third, this IP policy works hand in hand with world-renowned business incubators such as the Accelerator Centre in the dedicated research and technology park and velocity, a 14-year-old facility that equips and guides founders to build and scale companies. Communitech, a 25-year-old provincially backed facility in the region, also works closely with the University of Waterloo to build strong teams, access capital, and commercialize products. Fourth, Waterloo’s co-operative education program contributes 31% of all co-op participants to the Canadian economy. Home to the world’s largest co-operative education program, data shows that over 7,000 from around the world recruit Waterloo students for short- and long-term placements- directly contributing to the student’s ability to learn and optimize essential employment skills when they graduate. Finally, the students themselves at Waterloo are exceptional. The entrance average ranges from the low 80s to the mid-90s depending on the program. In computer, electrical, mechanical, mechatronics, and systems design engineering, to have a 66% chance of acceptance, the applicant’s average must be 95% or above. Singularly, none of these five attributes could lead to the university’s outstanding track record of innovative creativity, but when bundled up into a 1000 acre- 100 building main campus with 6 academic faculties, 40,000+ students, and over 1300 world-class faculty, the recipe for success becomes quite evident.

Keywords: IP policy, higher education, economy, innovation

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Authors: Arti Singh, Carolyn Jenkins, Oyedunni S. Arulogun, Mayowa O. Owolabi, Fred S. Sarfo, Bruce Ovbiagele, Enzinne Sylvia

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Background: Stroke, the leading cause of adult-onset disability and the second leading cause of death, is a major public health concern particularly pertinent in Sub-Saharan Africa (SSA), where nearly 80% of all global stroke mortalities occur. The Stroke Investigative Research and Education Network (SIREN) seeks to comprehensively characterize the genomic, sociocultural, economic, and behavioral risk factors for stroke and to build effective teams for research to address and decrease the burden of stroke and other non communicable diseases in SSA. One of the first steps to address this goal was to effectively engage the communities that suffer the high burden of disease in SSA. This study describes how the SIREN project engaged six sites in Ghana and Nigeria over the past three years, describing the community engagement activities that have arisen since inception. Aim: The aim of community engagement (CE) within SIREN is to elucidate information about knowledge, attitudes, beliefs, and practices (KABP) about stroke and its risk factors from individuals of African ancestry in SSA, and to educate the community about stroke and ways to decrease disabilities and deaths from stroke using socioculturally appropriate messaging and messengers. Methods: Community Advisory Board (CABs), Focus Group Discussions (FGDs) and community outreach programs. Results: 27 FGDs with 168 participants including community heads, religious leaders, health professionals and individuals with stroke among others, were conducted, and over 60 CE outreaches have been conducted within the SIREN performance sites. Over 5,900 individuals have received education on cardiovascular risk factors and about 5,000 have been screened for cardiovascular risk factors during the outreaches. FGDs and outreach programs indicate that knowledge of stroke, as well as risk factors and follow-up evidence-based care is limited and often late. Other findings include: 1) Most recognize hypertension as a major risk factor for stroke. 2) About 50% report that stroke is hereditary and about 20% do not know organs affected by stroke. 3) More than 95% willing to participate in genetic testing research and about 85% willing to pay for testing and recommend the test to others. 4) Almost all indicated that genetic testing could help health providers better treat stroke and help scientists better understand the causes of stroke. The CABs provided stakeholder input into SIREN activities and facilitated collaborations among investigators, community members and stakeholders. Conclusion: The CE core within SIREN is a first-of-its kind public outreach engagement initiative to evaluate and address perceptions about stroke and genomics by patients, caregivers, and local leaders in SSA and has implications as a model for assessment in other high-stroke risk populations. SIREN’s CE program uses best practices to build capacity for community-engaged research, accelerate integration of research findings into practice and strengthen dynamic community-academic partnerships within our communities. CE has had several major successes over the past three years including our multi-site collaboration examining the KABP about stroke (symptoms, risk factors, burden) and genetic testing across SSA.

Keywords: community advisory board, community engagement, focus groups, outreach, SSA, stroke

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Authors: Eleni Karasavvidou

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Social and anthropological research, parallel to Gender Studies, highlighted the relationship between social structures and symbolic forms as an important field of interaction and recording of 'social trends.' Since the study of representations can contribute to the understanding of the social functions and power relations, they encompass. This ‘mirage,’ however, has not only to do with the representations themselves but also with the ways they are received and the film or critical narratives that are established as dominant or alternative. Cinema and the criticism of its cultural products are no exception. Even in the rapidly changing media landscape of the 21st century, movies remain an integral and widespread part of popular culture, making films an extremely powerful means of 'legitimizing' or 'delegitimizing' visions of domination and commonsensical gender stereotypes throughout society. And yet it is film criticism, the 'language per se,' that legitimizes, reinforces, rewards and reproduces (or at least ignores) the stereotypical depictions of female roles that remain common in the realm of film images. This creates the need for this issue to have emerged (also) in academic research questioning gender criteria in film reviews as part of the effort for an inclusive art and society. Qualitative content analysis is used to examine female roles in selected Oscar-nominated films against their reviews from leading websites and newspapers. This method was chosen because of the complex nature of the depictions in the films and the narratives they evoke. The films were divided into basic scenes depicting social functions, such as love and work relationships, positions of power and their function, which were analyzed by content analysis, with borrowings from structuralism (Gennette) and the local/universal images of intercultural philology (Wierlacher). In addition to the measurement of the general ‘representation-time’ by gender, other qualitative characteristics were also analyzed, such as: speaking time, sayings or key actions, overall quality of the character's action in relation to the development of the scenario and social representations in general, as well as quantitatively (insufficient number of female lead roles, fewer key supporting roles, relatively few female directors and people in the production chain and how they might affect screen representations. The quantitative analysis in this study was used to complement the qualitative content analysis. Then the focus shifted to the criteria of film criticism and to the rhetorical narratives that exclude or highlight in relation to gender identities and functions. In the criteria and language of film criticism, stereotypes are often reproduced or allegedly overturned within the framework of apolitical "identity politics," which mainly addresses the surface of a self-referential cultural-consumer product without connecting it more deeply with the material and cultural life. One of the prime examples of this failure is the Bechtel Test, which tracks whether female characters speak in a film regardless of whether women's stories are represented or not in the films analyzed. If perceived unbiased male filmmakers still fail to tell truly feminist stories, the same is the case with the criteria of criticism and the related interventions.

Keywords: representations, context analysis, reviews, sexist stereotypes

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Authors: Sunayana Basu Mallik, Shishira Prakash

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The inclusion of Rights of Author (Moral and Personal Rights) resonate the century long battle of rights of authors, composers, performers across developed and developing countries (whether following civil law or common law systems). But, the juxtaposition of author’s special, moral, personal rights within the legislative framework of Copyright statutes (Indian Copyright Act, 1957, applicable statutes) underscores the foundational role of the right which goes to the root of the constitutional structure of India and philosophies of political and literary leaders like Mahatma Gandhi and Gurudeb Rabindranath Tagore. In the pre-independence era when the concept of moral rights was unknown to both England and India’s statutory laws, the strategic deployment method of Gandhi, his ideologies and thoughts scripted the concept of moral rights for authors/composers. The preservation of Rabindric Style (Characteristic Tagore’s vocal renditions) by Vishwabharati University (successor in interest for Tagore’s literary and musical compositions) prior to the Copyright Amendment of 1999 recognizing Author’s Special Rights in line with 6bis of Berne Convention invigorates the fact that the right existed intrinsically prior to the legislative amendment. The paper would in addition to the academic probe carry out an empirical enquiry of the institution’s (Navjivan Trust and Vishwa Bharati University’s) reasoning on the same. The judicial discourse and transforming constitutional ideals between 1950s till date in India alludes Moral Rights to be an essential legal right which have been reasoned by Indian Courts based on the underlying philosophies in culture, customs, religion wherein composers and literary figures have played key roles in enlightening and encouraging the members of society through their literary, musical and artistic work during pre-independence renaissance of India. The discourses have been influenced by the philosophies reflected in the preamble of the Indian constitution, ‘socialist, secular, democratic republic’ and laws of other civil law countries. Lastly, the paper would analyze the adjudication process and witness involvement in ascertaining violations of moral rights and further summarize the indigenous and country specific economic thoughts that often chisel decisions on moral rights of authors, composers, performers which sometimes intersect with author’s right of privacy and against defamation. The exclusivity contracts or other arrangements between authors, composers and publishing companies not only have an erosive effect on each thread of moral rights but irreparably dents factors that promote creativity. The paper would also be review these arrangements in view of the principles of unjust enrichment, unfair trade practices, anti-competitive behavior and breach of Section 27 (Restrain of Trade) of Indian Contract Act, 1857. The paper will thus lay down the three pillars on which author’s rights in India should namely rest, (a) political and judicial discourse evolving principles supporting moral rights of authors; (b) amendment and insertion of Section 57 of the Copyright Act, 1957; (c) overall constitutional framework supporting author’s rights.

Keywords: copyright, moral rights, performer’s rights, personal rights

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Authors: Etibar Guliyev

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The breakdown of the Soviet Union in 1991 has led to a considerable rise in the religious self-consciousness of Muslim population of the Central Asia. Additionally, huge amount of money spent by various states further facilitated the spread of religious ideas. According to some sources, Saudi Arabia spent 87 billion dollars to propagate Wahhabism abroad during two decades, whereas the Communist Party of the Soviet Union spent just over 7 billion dollars to spread its ideology worldwide between 1921 and 1991. As the result, today once a remote area from international politics has turned into third major source of recruitment of fighters for global terrorist organizations. In order to illustrate to scope of the involvement of the Central Asian residents in international terrorist networks it is enough to mention the name of Colonel Gulmorod Khalimov, the former head of the Tajik special police forces who served as ISIS war minister between 2016 and 2017. The importance of the topic stems from the fact that the above-mentioned republics with a territory of 4 million square km and the population of around 80 million people borders Russia, Iran Afghanistan and China. Moreover, the fact that political and military activities motivated with religious feelings in those countries have implications not only for domestic but also for regional and global political relations and all of them has root in politics of religions adds value to the research. This research aims to provide an in-depth analyses of the marked features of the state policies to regulate religious activities and approach this question both from individual, domestic, regional and global levels of analyses. The research will enable us to better understand what implications have the state of religious freedom in post-Soviet Muslim republics for international relations and the rise of global jihadi terrorism. The paper tries to find a linkage between the mentioned terror attacks and underground rise of religious extremism in Central Asia. This research is based on multiple research methods, mainly on qualitative one. The process tracing method is also employed to review religious policies implemented from 1918-1991 and after the collapse of the Soviet Union in a chronological way. In terms of the quantitative method, it chiefly will be used in a bid to process various statistics disseminated in academic and official sources. The research mostly explored constructivist, securitization and social movement theories. Findings of the research suggests that the endemic problems peculiar to authoritarian regimes of Central Asia such as crackdown on the expression of religious believe and any kind of opposition, economic decline, instrumental use of religion and corruption and tribalism further accelerated the recruitment problem. Paper also concludes that the Central Asian states in some cases misused counter-terrorism campaign as a pretext to further restrict freedom of faith in their respective countries.

Keywords: identity, political Islam, religious extremism, security, terrorism

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Authors: Orit Wolf

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Classical music performance is undergoing a profound transformation, marked by a confluence of technological advancements and evolving cultural dynamics. This academic paper explores the multifaceted changes and challenges faced by classical music performance, considering the impact of artificial intelligence (AI) along with other vital factors shaping this evolution. In the contemporary era, classical music is experiencing shifts in performance practices. This paper delves into these changes, emphasizing the need for adaptability within the classical music world. From repertoire selection and concert formats to artistic expression, performers and institutions navigate a delicate balance between tradition and innovation. We explore how these changes impact the authenticity and vitality of classical music performances. Furthermore, the influence of AI in the classical music concert world cannot be underestimated. AI technologies are making inroads into various aspects, from composition assistance to rehearsal and live performances. This paper examines the transformative effects of AI, considering how it enhances precision, adaptability, and creative exploration for musicians. We explore the implications for composers, performers, and the overall concert experience while addressing ethical concerns and creative opportunities. In addition to AI, there is the importance of cross-genre interactions within the classical music sphere. Mash-ups and collaborations with artists from diverse musical backgrounds are redefining the boundaries of classical music and creating works that resonate with a wider and more diverse audience. The benefits of cross-pollination in classical music seem crucial, offering a fresh perspective to listeners. As an active concert artist, Orit Wolf will share how the expectations of classical music audiences are evolving. Modern concertgoers seek not only exceptional musical performances but also immersive experiences that may involve technology, multimedia, and interactive elements. This paper examines how classical musicians and institutions are adapting to these changing expectations, using technology and innovative concert formats to deliver a unique and enriched experience to their audiences. As these changes and challenges reshape the classical music world, the need for a harmonious coexistence of tradition, technology, and innovation becomes evident. Musicians, composers, and institutions are striving to find a balance that ensures classical music remains relevant in a rapidly changing cultural landscape while maintaining the value it brings to compositions and audiences. This paper, therefore, aims to explore the evolving trends in classical music performance. It considers the influence of AI as one element within the broader context of change, highlighting the necessity of adaptability, cross-genre interactions, and a response to evolving audience expectations. By doing so, the classical music world can navigate this transformative period while preserving its timeless traditions and adding value to both performers and listeners. Orit Wolf, an international concert pianist, fulfils her vision to bring this music in new ways to mass audiences and will share her personal and professional experience as an artist who goes on stage and makes disruptive concerts.

Keywords: cross culture collaboration, music performance and ai, classical music in the digital age, classical concerts, innovation and technology, performance innovation, audience engagement in classical concerts

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Authors: Bronwen Wade

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Over the last half-century, child welfare systems have increasingly relied on quantitative risk assessment tools, such as actuarial or predictive risk tools. These tools are developed by performing statistical analysis of how attributes captured in administrative data are related to future child maltreatment. Some scholars argue that attributes in administrative data can serve as proxies for race and that quantitative risk assessment tools reify racial bias in decision-making. Others argue that these tools provide more “objective” and “scientific” guides for decision-making instead of subjective social worker judgment. This study performs a systematic review of the literature on the impact of quantitative risk assessment tools on racial disproportionality; it examines methodological biases in work on this topic, summarizes key findings, and provides suggestions for further work. A search of CINAHL, PsychInfo, Proquest Social Science Premium Collection, and the ProQuest Dissertations and Theses Collection was performed. Academic and grey literature were included. The review includes studies that use quasi-experimental methods and development, validation, or re-validation studies of quantitative risk assessment tools. PROBAST (Prediction model Risk of Bias Assessment Tool) and CHARMS (CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies) were used to assess the risk of bias and guide data extraction for risk development, validation, or re-validation studies. ROBINS-I (Risk of Bias in Non-Randomized Studies of Interventions) was used to assess for bias and guide data extraction for the quasi-experimental studies identified. Due to heterogeneity among papers, a meta-analysis was not feasible, and a narrative synthesis was conducted. 11 papers met the eligibility criteria, and each has an overall high risk of bias based on the PROBAST and ROBINS-I assessments. This is deeply concerning, as major policy decisions have been made based on a limited number of studies with a high risk of bias. The findings on racial disproportionality have been mixed and depend on the tool and approach used. Authors use various definitions for racial equity, fairness, or disproportionality. These concepts of statistical fairness are connected to theories about the reason for racial disproportionality in child welfare or social definitions of fairness that are usually not stated explicitly. Most findings from these studies are unreliable, given the high degree of bias. However, some of the less biased measures within studies suggest that quantitative risk assessment tools may worsen racial disproportionality, depending on how disproportionality is mathematically defined. Authors vary widely in their approach to defining and addressing racial disproportionality within studies, making it difficult to generalize findings or approaches across studies. This review demonstrates the power of authors to shape policy or discourse around racial justice based on their choice of statistical methods; it also demonstrates the need for improved rigor and transparency in studies of quantitative risk assessment tools. Finally, this review raises concerns about the impact that these tools have on child welfare systems and racial disproportionality.

Keywords: actuarial risk, child welfare, predictive risk, racial disproportionality

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Authors: Dahunsi Michael Oluseyi

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This paper aims to extensively examine eco-city planning and urban design in Lagos, Nigeria. It will delve into the city's developments, challenges, and potential solutions to offer insights for sustainable urban growth within the rapidly expanding urban landscape. The research will scrutinize recent innovations, emerging trends, and practical remedies to promote ecological sustainability within an urban framework. It will encompass a more in-depth review of current literature, case studies, and qualitative analyses, thereby augmenting the depth and breadth of the research. The objectives are to assess the current eco-city planning initiatives and urban design trends in Lagos, Nigeria, considering the city's unique characteristics and challenges. To identify and analyze the challenges encountered during the implementation of eco-friendly urban developments in Lagos, to explore and evaluate the innovative and practical solutions that are implemented to promote sustainability within the city, to provide comprehensive insights and actionable recommendations for policymakers, urban planners, and other stakeholders involved in sustainable urban development in Lagos, the rapid urbanization of Lagos has brought forth a myriad of challenges, including a burgeoning population, inadequate infrastructure, waste management issues, and environmental pollution. Eco-city planning has emerged as a promising approach to addressing these obstacles, striving to create urban spaces that are more habitable, resource-efficient, and environmentally friendly. This research holds substantial importance in exploring the application of eco-city planning principles within a megacity like Lagos. Analyzing recent innovations, trends, concerns, challenges, and solutions provides invaluable insights for policymakers, urban planners, and stakeholders dedicated to fostering sustainable urban development. The methodologies employed in this research are structured to embrace a multifaceted and intricate approach, aiming to facilitate a comprehensive understanding of the complexities inherent in eco-city planning and urban design in Lagos, Nigeria. This methodological framework is designed to encompass various diverse strategies and analytical tools to effectively capture the multidimensional aspects of sustainable urban development. It involves an in-depth analysis of academic publications, governmental reports, and urban planning documents to highlight global eco-city planning trends and gather Lagos-specific insights through a detailed exploration of eco-friendly initiatives and projects in Lagos to evaluate successes, challenges, and strategies for addressing environmental concerns by engaging key stakeholders, including urban planners, policymakers, environmental experts, and residents, to collect firsthand perspectives, concerns, and insights. Also, a thorough analysis will be carried out on data collected from literature reviews, case studies, interviews, and surveys used to extract prevalent patterns, challenges, and innovative solutions from diverse sources. This study aims to contribute to the discourse on sustainable urban development by offering a comprehensive analysis of eco-city planning in Lagos and providing practical recommendations for a more sustainable urban future.

Keywords: eco-friendly, innovation, sustainability, stakeholders

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Authors: Rosie Cooper, Tracey Chantler, Ellen Pringle, Sadie Bell, Emily Edmundson, Heidi Nielsen, Sheila Roberts, Michael Edelstein, Sandra Mounier Jack

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Introduction: In line with the National Health Service’s (NHS) long-term plan, the NHS is looking to implement more digital health interventions. This study explores a case study in this area: a digital intervention used by NHS Trusts in London to consent adolescents for Human Papilloma Virus (HPV) immunisation. Methods: The electronic consent intervention was implemented in 14 secondary schools in inner city, London. These schools were statistically matched with 14 schools from the same area that were consenting using paper forms. Schools were matched on deprivation and English as an additional language. Consent form return rates and HPV vaccine uptake were compared quantitatively between intervention and matched schools. Data from observations of immunisation sessions and school feedback forms were analysed thematically. Individual and group interviews were undertaken with implementers parents and adolescents and a focus group with adolescents were undertaken and analysed thematically. Results: Twenty-eight schools (14 e-consent schools and 14 paper consent schools) comprising 3219 girls (1733 in paper consent schools and 1486 in e-consent schools) were included in the study. The proportion of pupils eligible for free school meals, with English as an additional language and students' ethnicity profile, was similar between the e-consent and paper consent schools. Return of consent forms was not increased by the implementation of the e-consent intervention. There was no difference in the proportion of pupils that were vaccinated at the scheduled vaccination session between the paper (n=14) and e-consent (n=14) schools (80.6% vs. 81.3%, p=0.93). The transition to using the system was not straightforward, whilst schools and staff understood the potential benefits, they found it difficult to adapt to new ways of working which removed some level or control from schools. Part of the reason for lower consent form return in e-consent schools was that some parents found the intervention difficult to use due to limited access to the internet, finding it hard to open the weblink, language barriers, and in some cases, the system closed a few days prior to sessions. Adolescents also highlighted the potential for e-consent interventions to by-pass their information needs. Discussion: We would advise caution against dismissing the e-consent intervention because it did not achieve its goal of increasing the return of consent forms. Given the problems embedding a news service, it was encouraging that HPV vaccine uptake remained stable. Introducing change requires stakeholders to understand, buy in, and work together with others. Schools and staff understood the potential benefits of using e-consent but found the new ways of working removed some level of control from schools, which they found hard to adapt to, possibly suggesting implementing digital technology will require an embedding process. Conclusion: The future direction of the NHS will require implementation of digital technology. Obtaining electronic consent from parents could help streamline school-based adolescent immunisation programmes. Findings from this study suggest that when implementing new digital technologies, it is important to allow for a period of embedding to enable them to become incorporated in everyday practice.

Keywords: consent, digital, immunisation, prevention

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Authors: Qurat Ul Ain Saleem, Kanwal Ameen

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The library and information science discipline is universally known as a feminist profession. It is considered a suitable field for females in Pakistan like a few other fields such as teaching and healthcare. It is also reflected through the uneven enrollment at graduate levels in library schools across the country as there are more females as compared to males. However, that uneven ratio does not really translate in the profession after passing out. There are more males in the professional as compared to females, as well as males can be seen on managerial and administrative posts majorly. A few females who joined the perception remain underrated and are hardly seen at managerial or administrative positions in the academic libraries. Therefore, this study was designed to highlight the perceptions of those females who have joined the profession to identify the issues related to equality faced by them as a professional. A qualitative research design based on a semi-structured interview was selected as an appropriate method to achieve the objectives of this study. Female librarians working in the higher education commission’s recognized public and private sector universities of Punjab, Pakistan, were selected as the population for this study. Female librarians shared that inequalities and discrimination based on face value, experience, communication, and relationship with the manager are common at their workplaces. They added that managers prefer male professionals to deal with delegation or presentations though we both can do that. Female professionals from the private sector believed that library managers make final hiring and selection decisions based on job duties and gender. However, the one with strong references will be preferred for the job. Also, private-sector employees suffered more prejudice due to the non-availability of proper patterns of promotions and increments. The government personnel said there is always a proper board/procedure for hiring and promotions; therefore, it is difficult for them to identify any inequality. Participants were dissatisfied with their managers for not allowing them to attend training and conferences. The majority of participants from the private sector said they wouldn't speak up to prejudice because they are afraid of losing their jobs and their voice is lost in a male-dominated society where males hold numerous authoritative positions and females are considered less competent. Nonetheless, the discrimination and inequalities affected the work motivation and enthusiasm of employees. Therefore, organizations should not discriminate against the staff in terms of facilities and benefits. The sample may not represent the true picture of gender equality in university libraries of Pakistan due to less number of participants and limited geographical boundaries. It is also assumed that some females may refrain from disclosing factual information or some may exaggerate the facts as a large number of participants requested to become part of the study. Equal opportunities should be offered to female library professionals to uplift and involve them to mitigate the perception of gender dominance. The organizations or immediate authorities should allow their staff to participate in training opportunities to learn modern practices to better serve the community.

Keywords: equality-workplace, libraries as workplace, female professionals, librarians-Pakistan

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Authors: Ainura Tursunalieva, Irene Hudson

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Continuous improvement of both the quality and safety of health care is an important goal in Australia and internationally. The intensive care unit (ICU) receives patients with a wide variety of and severity of illnesses. Accurately identifying patients at risk of developing complications or dying is crucial to increasing healthcare efficiency. Thus, it is essential for clinicians and researchers to have a robust framework capable of evaluating the risk profile of a patient. ICU scoring systems provide such a framework. The Acute Physiology and Chronic Health Evaluation III and the Simplified Acute Physiology Score II are ICU scoring systems frequently used for assessing the severity of acute illness. These scoring systems collect multiple risk factors for each patient including physiological measurements then render the assessment outcomes of individual risk factors into a single numerical value. A higher score is related to a more severe patient condition. Furthermore, the Mortality Probability Model II uses logistic regression based on independent risk factors to predict a patient’s probability of mortality. An important overlooked limitation of SAPS II and MPM II is that they do not, to date, include interaction terms between a patient’s vital signs. This is a prominent oversight as it is likely there is an interplay among vital signs. The co-existence of certain conditions may pose a greater health risk than when these conditions exist independently. One barrier to including such interaction terms in predictive models is the dimensionality issue as it becomes difficult to use variable selection. We propose an innovative scoring system which takes into account a dependence structure among patient’s vital signs, such as systolic and diastolic blood pressures, heart rate, pulse interval, and peripheral oxygen saturation. Copulas will capture the dependence among normally distributed and skewed variables as some of the vital sign distributions are skewed. The estimated dependence parameter will then be incorporated into the traditional scoring systems to adjust the points allocated for the individual vital sign measurements. The same dependence parameter will also be used to create an alternative copula-based model for predicting a patient’s probability of mortality. The new copula-based approach will accommodate not only a patient’s trajectories of vital signs but also the joint dependence probabilities among the vital signs. We hypothesise that this approach will produce more stable assessments and lead to more time efficient and accurate predictions. We will use two data sets: (1) 250 ICU patients admitted once to the Chui Regional Hospital (Kyrgyzstan) and (2) 37 ICU patients’ agitation-sedation profiles collected by the Hunter Medical Research Institute (Australia). Both the traditional scoring approach and our copula-based approach will be evaluated using the Brier score to indicate overall model performance, the concordance (or c) statistic to indicate the discriminative ability (or area under the receiver operating characteristic (ROC) curve), and goodness-of-fit statistics for calibration. We will also report discrimination and calibration values and establish visualization of the copulas and high dimensional regions of risk interrelating two or three vital signs in so-called higher dimensional ROCs.

Keywords: copula, intensive unit scoring system, ROC curves, vital sign dependence

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Authors: Bar Y. Ainuz, Harry M. Salinas, Aleeza Ali, Eli B. Levitt, Austin J. Pourmoussa, Antoun Bouz, Miguel A. Medina

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Introduction: Breast conservation therapy remains the mainstay surgical treatment for early breast cancer. Oncoplastic techniques, in conjunction with lumpectomy and adjuvant radiotherapy, have been demonstrated to achieve good aesthetic results without adversely affecting cancer outcomes in the treatment of patients with macromastia or significant ptosis. In our patient population, many women present for breast conservation with pre-existing cosmetic implants or with breast volumes too small for soft tissue, only oncoplastic techniques. Our study evaluated a consecutive series of patients presenting for breast conservation undergoing concomitant oncoplastic-augmentation-mastopexy (OAM) with a contralateral augmentation-mastopexy for symmetry. Methods: OAM surgical technique involves simultaneous lumpectomy with exchange or placement of implants, oncoplastic mastopexy, and concomitant contralateral augmentation mastopexy for symmetry. Patients undergoing lumpectomy for breast conservation as outpatients were identified via retrospective chart review at a high volume private academic affiliated community-based cancer center. Patients with ptosis and either pre-existing breast implants or insufficient breast volume undergoing oncoplastic implant placement (or exchange) and mastopexy were included in the study. Operative details, aesthetic outcomes, and complications were assessed. Results: Over a continuous three-year period, with a two-surgeon cohort, 30 consecutive patients (56 breasts, 4 unilateral procedures) were identified. Patients had an average age of 52.5 years and an average BMI of 27.5, with 40% smokers or former smokers. The average operative time was 2.5 hours, the average implant size removed was 352 cc, and the average implant size placed was 300 cc. All new implants were smooth silicone, with the majority (92%) placed in a retropectoral fashion. 40% of patients received chemotherapy, and 80% of patients received whole breast adjuvant photon radiotherapy with a total radiation dose of either 42.56 or 52.56 Gy. The average and median length of follow-up were both 8.2 months. Of the 24 patients that received radiotherapy, 21% had asymmetry due to capsular contracture. A total of 7 patients (29.2%) underwent revisions for either positive margins (12.5%), capsular contracture (8.3%), implant loss (4.2%), or cosmetic concerns (4.2%). One patient developed a pulmonary embolism in the acute postoperative period and was treated with anticoagulant therapy. Conclusion: Oncoplastic augmentation mastopexy is a safe technique with good aesthetic outcomes and acceptable complication rates for ptotic patients with breast cancer and a paucity of breast volume or pre-existing implants who wish to pursue breast-conserving therapy. The revision rates compare favorably with single-stage cosmetic augmentation procedures as well as other oncoplastic techniques described in the literature. The short-term capsular contracture rates seem lower than the rates in patients undergoing radiation after mastectomy and implant-based reconstruction. Long term capsular contractures and revision rates are too early to know in this cohort.

Keywords: breast conserving therapy, oncoplastic augmentation mastopexy, capsular contracture, breast reconstruction

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Authors: Thanthrige Thiunuwan Priyathilaka, Don Anushka Sandaruwan Elvitigala, Bong-Soo Lim, Hyung-Bok Jeong, Jehee Lee

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Toll like receptors (TLRs) are a phylogeneticaly conserved family of pattern recognition receptors, which participates in the host immune responses against various pathogens and pathogen derived mitogen. TLR21, a non-mammalian type, is almost restricted to the fish species even though those can be identified rarely in avians and amphibians. Herein, this study was carried out to identify and characterize TLR21 from rock bream (Oplegnathus fasciatus) designated as RbTLR21, at transcriptional and genomic level. In this study, the full length cDNA and genomic sequence of RbTLR21 was identified using previously constructed cDNA sequence database and BAC library, respectively. Identified RbTLR21 sequence was characterized using several bioinformatics tools. The quantitative real time PCR (qPCR) experiment was conducted to determine tissue specific expressional distribution of RbTLR21. Further, transcriptional modulation of RbTLR21 upon the stimulation with Streptococcus iniae (S. iniae), rock bream iridovirus (RBIV) and Edwardsiella tarda (E. tarda) was analyzed in spleen tissues. The complete coding sequence of RbTLR21 was 2919 bp in length which can encode a protein consisting of 973 amino acid residues with molecular mass of 112 kDa and theoretical isoelectric point of 8.6. The anticipated protein sequence resembled a typical TLR domain architecture including C-terminal ectodomain with 16 leucine rich repeats, a transmembrane domain, cytoplasmic TIR domain and signal peptide with 23 amino acid residues. Moreover, protein folding pattern prediction of RbTLR21 exhibited well-structured and folded ectodomain, transmembrane domain and cytoplasmc TIR domain. According to the pair wise sequence analysis data, RbTLR21 showed closest homology with orange-spotted grouper (Epinephelus coioides) TLR21with 76.9% amino acid identity. Furthermore, our phylogenetic analysis revealed that RbTLR21 shows a close evolutionary relationship with its ortholog from Danio rerio. Genomic structure of RbTLR21 consisted of single exon similar to its ortholog of zebra fish. Sevaral putative transcription factor binding sites were also identified in 5ʹ flanking region of RbTLR21. The RBTLR 21 was ubiquitously expressed in all the tissues we tested. Relatively, high expression levels were found in spleen, liver and blood tissues. Upon induction with rock bream iridovirus, RbTLR21 expression was upregulated at the early phase of post induction period even though RbTLR21 expression level was fluctuated at the latter phase of post induction period. Post Edwardsiella tarda injection, RbTLR transcripts were upregulated throughout the experiment. Similarly, Streptococcus iniae induction exhibited significant upregulations of RbTLR21 mRNA expression in the spleen tissues. Collectively, our findings suggest that RbTLR21 is indeed a homolog of TLR21 family members and RbTLR21 may be involved in host immune responses against bacterial and DNA viral infections.

Keywords: rock bream, toll like receptor 21 (TLR21), pattern recognition receptor, genomic characterization

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