Search results for: legal progression

Authors: Nurkhairul Bariyah Baharun, Afzan Adam, Reena Rahayu Md Zin

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Tumor microenvironment (TME) in breast cancer is mainly composed of cancer cells, immune cells, and stromal cells. The interaction between cancer cells and their microenvironment plays an important role in tumor development, progression, and treatment response. The TME in breast cancer includes tumor-infiltrating lymphocytes (TILs) that are implicated in killing tumor cells. TILs can be found in tumor stroma (sTILs) and within the tumor (iTILs). TILs in triple negative breast cancer (TNBC) have been demonstrated to have prognostic and potentially predictive value. The international Immune-Oncology Biomarker Working Group (TIL-WG) had developed a guideline focus on the assessment of sTILs using hematoxylin and eosin (H&E)-stained slides. According to the guideline, the pathologists use “eye balling” method on the H&E stained- slide for sTILs assessment. This method has low precision, poor interobserver reproducibility, and is time-consuming for a comprehensive evaluation, besides only counted sTILs in their assessment. The TIL-WG has therefore recommended that any algorithm for computational assessment of TILs utilizing the guidelines provided to overcome the limitations of manual assessment, thus providing highly accurate and reliable TILs detection and classification for reproducible and quantitative measurement. This study is carried out to develop a TNBC digital whole slide image (WSI) dataset from H&E-stained slides and IHC (CD4+ and CD8+) stained slides. TNBC cases were retrieved from the database of the Department of Pathology, Hospital Canselor Tuanku Muhriz (HCTM). TNBC cases diagnosed between the year 2010 and 2021 with no history of other cancer and available block tissue were included in the study (n=58). Tissue blocks were sectioned approximately 4 µm for H&E and IHC stain. The H&E staining was performed according to a well-established protocol. Indirect IHC stain was also performed on the tissue sections using protocol from Diagnostic BioSystems PolyVue™ Plus Kit, USA. The slides were stained with rabbit monoclonal, CD8 antibody (SP16) and Rabbit monoclonal, CD4 antibody (EP204). The selected and quality-checked slides were then scanned using a high-resolution whole slide scanner (Pannoramic DESK II DW- slide scanner) to digitalize the tissue image with a pixel resolution of 20x magnification. A manual TILs (sTILs and iTILs) assessment was then carried out by the appointed pathologist (2 pathologists) for manual TILs scoring from the digital WSIs following the guideline developed by TIL-WG 2014, and the result displayed as the percentage of sTILs and iTILs per mm² stromal and tumour area on the tissue. Following this, we aimed to develop an automated digital image scoring framework that incorporates key elements of manual guidelines (including both sTILs and iTILs) using manually annotated data for robust and objective quantification of TILs in TNBC. From the study, we have developed a digital dataset of TNBC H&E and IHC (CD4+ and CD8+) stained slides. We hope that an automated based scoring method can provide quantitative and interpretable TILs scoring, which correlates with the manual pathologist-derived sTILs and iTILs scoring and thus has potential prognostic implications.

Keywords: automated quantification, digital pathology, triple negative breast cancer, tumour infiltrating lymphocytes

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Authors: Urrutia Fernando, López Jessica, Sánchez Carlos, San Antonio Thalía

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Ecuador, as a signatory country of the convention of the rights of persons with disabilities (CRPD) has, in the recent years, strengthened the structures and legal framework required to protect this minority comprised of 13.2% of its total population. However, the reality is that this group has disproportionately low earnings and low educational attainment in comparison with the general population. The main struggles, to promote job placement of wheelchairs users, are environmental discrimination caused by accessibility in structures and transportation, this mainly due to the cost, for private and public entities, of performing the reasonable accommodation they require. It is widely known that product development and production is needed to support effective implementation of the CRPD and that walking and standing are the major life activities, in this context the objective of this investigation is to promote job placement of wheelchair user in the province of Tungurahua by means of the design, production and marketing of a customized stand up wheelchair. Exploratory interviews and measurements were performed in a representative sample of working age wheelchairs users that develop their disability after achieving their physical maturity and that are capable of performing professional activities with their upper limbs, this in order to detect the user’s preference and determine the local economic and anthropometric parameters to be included in the wheelchair design. The findings reveal factors that uniquely impact quality of life and development for people with a mobility disability within the context of the province, first that transportation is a big issue since public buses does not have accessibility for wheelchair users and the absence of curb cuts and the presence of trash bins over the sidewalks among other hinders an economic independent mobility, second that the proposal based in the idea of modifying the wheelchairs to make it able to overcome certain obstacles helps people in wheelchair to improve their independent living and by reducing the costs of modification for the employer could improve their chances of finding work.

Keywords: anthropometrics, job placement, stand up wheelchair, user centered design

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Authors: Norazilawati Binti Md Dahlal, Nabiila Binti Mat Yusoff, Anis Najiha Binti Ahmad

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With the increasing demand for halal products, there is a growing emphasis on ensuring their quality and adherence to halal standards. However, the vulnerability of halal goods to fraud and adulteration poses a significant challenge to the integrity of the halal industry. Whistleblowers play a pivotal role in safeguarding the safety and integrity of halal food by exposing wrongdoings, misconduct, and fraudulent practices. This study explores the implementation of whistleblowing practices aligned with halal and toyyib principles to effectively address halal food fraud issues. Whistleblowing is defined as the act of disclosing information about misconduct, immorality, or unlawful activities to relevant authorities or the public. Although whistleblowing is universally recognized as beneficial, it exposes whistleblowers to substantial risks, including career setbacks, reputation damage, and personal safety threats. Despite legal protections, whistleblowers often face retaliation and hesitancy to come forward. By integrating the principles of halal and toyyib, which encompass the physical and spiritual as well as material and supernatural elements, effective whistleblowing practices can be developed. These principles include the physical characteristic of the product in accordance with Shari’ah law (P1); products that are sourced ethically and responsibly (P2); Products that meet high standard of quality and safety (P3); functioning as servant and caliph of Allah in managing according to Allah's commands and prohibitions (P4); not excessively wasteful or extravagant (P5); positive moral and spiritual implications associated with the product (P6); and aimed at achieving prosperity in both this life and the Hereafter (P7). Employing a quantitative research approach, this study examines Islamic primary data sources and secondary data sources to investigate the prevalence and impact of whistleblowing in the halal industry. By analyzing the principles of halal and toyyib and exploring the importance of whistleblowing effective whistleblowing practices, this research aims to enhance our understanding of promoting accountability and justice within the halal industry from an Islamic perspective.

Keywords: whistleblowing, halal and toyyib, food fraud, halal integrity, Islamic practices

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Authors: Silvia A. Magalhaes, Vasco P. De Freitas, Jose L. Alexandre

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Most of the European literature concerning energy efficiency and thermal comfort of dwellings assumes permanent heating and focuses on energy-saving measures. European National regulations are designed for those permanent comfort conditions. On the other hand, very few studies focus on the effect of the improvement measures in comfort reduction, for free-floating conditions or intermittent heating, in fuel poverty vulnerable countries. In Portugal, only 21% of the household energy consumptions (and 10% of the cost) are spent in space heating, while, on average European bills, this value rises to 67%. The mild climate, but mainly fuel poverty and cultural background, justifies these low heating practices. This study proposes a “passive discomfort” index definition, considering free-floating temperatures or with intermittent heating profiles (more realistic conditions), putting the focus on comfort rather than energy consumption (which is low for these countries). The aim is to compare both energy (regarding the legal framework of national regulation) and comfort (considering realistic conditions of use) to identify some correlation. It was developed an experimental campaign of indoor thermal conditions in a 19th building located in Porto with several apartments. One dwelling was chosen as a case study to carry out a sensitivity analysis. The results are discussed comparing both theoretical energy consumption (energy rates from national regulation) and discomfort (new index defined), for different insulation thicknesses, orientations, and intermittent heating profiles. The results show that the different passive options (walls insulation and glazing options) have a small impact on winter discomfort, which is always high for low heating profiles. Moreover, it was shown that the insulation thickness on walls has no influence, and the minimum insulation thickness considered is enough to achieve the same impact on discomfort reduction. Plus, for these low heating profiles, other conditions are critical, as the orientation. Finally, there isn’t an unequivocal relation between the energy label and the discomfort index. These and other results are surprising when compared with the most usual approaches, which assume permanent heating.

Keywords: dwellings in historical buildings, low-heating countries, mild climates, thermal comfort

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Authors: Maddalena Arigoni, Maria Luisa Ratto, Raffaele A. Calogero, Luca Alessandri

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The presence of tumor heterogeneity, where distinct cancer cells exhibit diverse morphological and phenotypic profiles, including gene expression, metabolism, and proliferation, poses challenges for molecular prognostic markers and patient classification for targeted therapies. Understanding the causes and progression of cancer requires research efforts aimed at characterizing heterogeneity, which can be facilitated by evolving single-cell sequencing technologies. However, analyzing single-cell data necessitates computational methods that often lack objective validation. Therefore, the establishment of benchmarking datasets is necessary to provide a controlled environment for validating bioinformatics tools in the field of single-cell oncology. Benchmarking bioinformatics tools for single-cell experiments can be costly due to the high expense involved. Therefore, datasets used for benchmarking are typically sourced from publicly available experiments, which often lack a comprehensive cell annotation. This limitation can affect the accuracy and effectiveness of such experiments as benchmarking tools. To address this issue, we introduce omics benchmark experiments designed to evaluate bioinformatics tools to depict the heterogeneity in single-cell tumor experiments. We conducted single-cell RNA sequencing on six lung cancer tumor cell lines that display resistant clones upon treatment of EGFR mutated tumors and are characterized by driver genes, namely ROS1, ALK, HER2, MET, KRAS, and BRAF. These driver genes are associated with downstream networks controlled by EGFR mutations, such as JAK-STAT, PI3K-AKT-mTOR, and MEK-ERK. The experiment also featured an EGFR-mutated cell line. Using 10XGenomics platform with cellplex technology, we analyzed the seven cell lines together with a pseudo-immunological microenvironment consisting of PBMC cells labeled with the Biolegend TotalSeq™-B Human Universal Cocktail (CITEseq). This technology allowed for independent labeling of each cell line and single-cell analysis of the pooled seven cell lines and the pseudo-microenvironment. The data generated from the aforementioned experiments are available as part of an online tool, which allows users to define cell heterogeneity and generates count tables as an output. The tool provides the cell line derivation for each cell and cell annotations for the pseudo-microenvironment based on CITEseq data by an experienced immunologist. Additionally, we created a range of pseudo-tumor tissues using different ratios of the aforementioned cells embedded in matrigel. These tissues were analyzed using 10XGenomics (FFPE samples) and Curio Bioscience (fresh frozen samples) platforms for spatial transcriptomics, further expanding the scope of our benchmark experiments. The benchmark experiments we conducted provide a unique opportunity to evaluate the performance of bioinformatics tools for detecting and characterizing tumor heterogeneity at the single-cell level. Overall, our experiments provide a controlled and standardized environment for assessing the accuracy and robustness of bioinformatics tools for studying tumor heterogeneity at the single-cell level, which can ultimately lead to more precise and effective cancer diagnosis and treatment.

Keywords: single cell omics, benchmark, spatial transcriptomics, CITEseq

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Authors: Briohny H. Spencer, Russ Chess-Williams, Catherine McDermott, Shailendra Anoopkumar-Dukie, David Christie

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Background: Prostate cancer is the second most common cancer diagnosed in men worldwide and the most prevalent in Australian men. In 2015, it was estimated that approximately 18,000 new cases of prostate cancer were diagnosed in Australia. Currently, for localised disease, androgen depravation therapy (ADT) and radiotherapy are a major part of the curative management of prostate cancer. ADT acts to reduce the levels of circulating androgens, primarily testosterone and the locally produced androgen, dihydrotestosterone (DHT), or by preventing the subsequent activation of the androgen receptor. Thus, the growth of the cancerous cells can be reduced or ceased. Radiation techniques such as brachytherapy (radiation delivered directly to the prostate by transperineal implant) or external beam radiation therapy (exposure to a sufficient dose of radiation aimed at eradicating malignant cells) are also common techniques used in the treatment of this condition. Radiotherapy (RT) has significant limitations, including reduced effectiveness in treating malignant cells present in hypoxic microenvironments leading to radio-resistance and poor clinical outcomes and also the significant side effects for the patients. Alpha1-adrenoceptor antagonists are used for many prostate cancer patients to control lower urinary tract symptoms, due to the progression of the disease itself or may arise as an adverse effect of the radiotherapy treatment. In Australia, a significant number (not a majority) of patients receive a α1-ADR antagonist and four drugs are available including prazosin, terazosin, alfuzosin and tamsulosin. There is currently limited published data on the effects of α1-ADR antagonists during radiotherapy, but it suggests these medications may improve patient outcomes by enhancing the effect of radiotherapy. Aim: To determine the impact of α1-ADR antagonists treatments on time to biochemical relapse following radiotherapy. Methods: A retrospective study of male patients receiving radiotherapy for biopsy-proven localised prostate cancer was undertaken to compare cancer outcomes for drug-naïve patients and those receiving α1-ADR antagonist treatments. Ethical approval for the collection of data at Genesis CancerCare QLD was obtained and biochemical relapse (defined by a PSA rise of >2ng/mL above the nadir) was recorded in months. Rates of biochemical relapse, prostate specific antigen doubling time (PSADT) and Kaplan-Meier survival curves were also compared. Treatment groups were those receiving α1-ADR antagonists treatment before or concurrent with their radiotherapy. Data was statistically analysed using One-way ANOVA and results expressed as mean ± standard deviation. Major findings: The mean time to biochemical relapse for tamsulosin, prazosin, alfuzosin and controls were 45.3±17.4 (n=36), 41.5±19.6 (n=11), 29.3±6.02 (n=6) and 36.5±17.6 (n=16) months respectively. Tamsulosin, prazosin but not alfuzosin delayed time to biochemical relapse although the differences were not statistically significant. Conclusion: Preliminary data for the prior and/or concurrent use of tamsulosin and prazosin showed a positive trend in delaying time to biochemical relapse although no statistical significance was shown. Larger clinical studies are indicated and with thousands of patient records yet to be analysed, it may determine if there is a significant effect of these drugs on control of prostate cancer.

Keywords: alpha1-adrenoceptor antagonists, biochemical relapse, prostate cancer, radiotherapy

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Authors: F. Heyecan Giritli, Gizem Akgül

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Because of the raising population of world; the need for houses, buildings and infrastructures are increasing rapidly. Energy and water consumption, waste production continues to increase. If this situation of resources continues, there will be a significant loss for next generations. Therefore, there are a lot of researches and solutions developed in the world. Also sustainability criteria are collected together by some countries to serve construction industry with certification systems. Sustainable building production process’s scope requires different path from traditional building production process. Moreover, the key objective of sustainable buildings is that the process includes whole life cycle duration. The process approaches from the decision of the project to the end of it; so the project team is needed from the beginning of the integrated project delivery model. Further more, by defining project team at the beginning of the project provides communication among the team members and defined problem solving and decision making methods. In this research includes the certification systems among the world to comprehend the head lines and assessment criteria. Therefore, it is understand that usually all green building criteria have the same contents. The aim of this research is to assess the sustainable project stakeholder’ perceptions in Turkish construction industry from the point of occupation, job title and years of experience. Therefore, a survey is made to assess the perceptions of each attendant. In Turkey, sustainability criteria are not clearly defined; on the other hand some regulations like waste management, energy efficiency are made by legal agencies. LEED certification system is the most popular system in Turkey that has attended and certificated. From the LEED official data, it’s understood that 308 project registered in Turkey. Therefore, LEED sustainability criteria are used in the survey. Head lines of LEED certification criteria; sustainable sites, water efficiency, energy and atmosphere, material and resources, indoor environmental quality, innovation and regional priority are indicated to assess the perceptions of survey participants. Moreover, only surveying of criteria are not enough; so the equipment, methods, risks and benefits also considered.

Keywords: LEED, sustainability, perceptions, stakeholders, construction, Turkey, risk, benefit

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Authors: Wassamon Kun-Amornpong

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When a financial crisis occurs, there will be a law and regulatory reform in order to manage the turmoil and prevent a future crisis. One of the most important regulatory efforts to help cope with systemic risk and a financial crisis is the third version of the Basel Accord. Basel III has introduced some measures and tools (e.g., systemic risk buffer, countercyclical buffer, capital conservation buffer and liquidity risk) in order to mitigate systemic risk. Nevertheless, the effectiveness of these measures in Basel III in adequately addressing the problem of contagious runs that can quickly spread throughout the financial system is questionable. This paper seeks to contribute to the knowledge regarding the role of the Basel Accords in mitigating systemic risk. The research question is to what extent the Basel Accords can help control systemic risk in the financial markets? The paper tackles this question by analysing the concept of systemic risk. It will then examine the weaknesses of the Basel Accords before and after the Global financial crisis in 2008. Finally, it will suggest some possible solutions in order to improve the Basel Accord. The rationale of the study is the fact that academic works on systemic risk and financial crises are largely studied from economic or financial perspective. There is comparatively little research from the legal and regulatory perspective. The finding of the paper is that there are some problems in all of the three pillars of the Basel Accords. With regards to Pillar I, the risk model is excessively complex while the benefits of its complexity are doubtful. Concerning Pillar II, the effectiveness of the risk-based supervision in preventing systemic risk still depends largely upon its design and implementation. Factors such as organizational culture of the regulator and the political context within which the risk-based supervision operates might be a barrier against the success of Pillar II. Meanwhile, Pillar III could not provide adequate market discipline as market participants do not always act in a rational way. In addition, the too-big-to-fail perception reduced the incentives of the market participants to monitor risks. There has been some development in resolution measure (e.g. TLAC and MREL) which might potentially help strengthen the incentive of the market participants to monitor risks. However, those measures have some weaknesses. The paper argues that if the weaknesses in the three pillars are resolved, it can be expected that the Basel Accord could contribute to the mitigation of systemic risk in a more significant way in the future.

Keywords: Basel accords, financial regulation, risk-based supervision, systemic risk

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Authors: Philipp Galkin

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Government policy is a critical factor in the understanding of energy markets. Regardless, it is rarely approached systematically from a research perspective. Gaining a precise understanding of what policies exist, their intended outcomes, geographical extent, duration, evolution, etc. would enable the research community to answer a variety of questions that, for now, are either oversimplified or ignored. Policy, on its surface, also seems a rather unstructured and qualitative undertaking. There may be quantitative components, but incorporating the concept of policy analysis into quantitative analysis remains a challenge. The KAPSARC Energy Policy Database (KEPD) is intended to address these two energy policy research limitations. Our approach is to represent policies within a quantitative library of the specific policy measures contained within a set of legal documents. Each of these measures is recorded into the database as a single entry characterized by a set of qualitative and quantitative attributes. Initially, we have focused on the major laws at the national level that regulate coal in China. However, KAPSARC is engaged in various efforts to apply this methodology to other energy policy domains. To ensure scalability and sustainability of our project, we are exploring semantic processing using automated computer algorithms. Automated coding can provide a more convenient input data for human coders and serve as a quality control option. Our initial findings suggest that the methodology utilized in KEPD could be applied to any set of energy policies. It also provides a convenient tool to facilitate understanding in the energy policy realm enabling the researcher to quickly identify, summarize, and digest policy documents and specific policy measures. The KEPD captures a wide range of information about each individual policy contained within a single policy document. This enables a variety of analyses, such as structural comparison of policy documents, tracing policy evolution, stakeholder analysis, and exploring interdependencies of policies and their attributes with exogenous datasets using statistical tools. The usability and broad range of research implications suggest a need for the continued expansion of the KEPD to encompass a larger scope of policy documents across geographies and energy sectors.

Keywords: China, energy policy, policy analysis, policy database

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Authors: Iñaki Iturria, Pasquale Russo, Montserrat Nacher-Vázquez, Giuseppe Spano, Paloma López, Miguel Angel Pardo

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Introduction: It is known that some Lactic Acid Bacteria (LAB) present an interesting probiotic effect. Probiotic bacteria stimulate host resistance to microbial pathogens and thereby aid in immune response, and modulate the host's immune responses to antigens with a potential to down-regulate hypersensitivity reactions. Therefore, probiotic therapy is valuable against intestinal infections and may be beneficial in the treatment of Inflammatory Bowel Disease (IBD). Several in vitro tests are available to evaluate the probiotic potential of a LAB strain. However, an in vivo model is required to understand the interaction between the host immune system and the bacteria. During the last few years, zebrafish (Danio rerio) has gained interest as a promising vertebrate model in this field. This organism has been extensively used to study the interaction between the host and the microbiota, as well as the host immune response under several microbial infections. In this work, we report on the use of the zebrafish model to investigate in vivo the colonizing ability and the immunomodulatory effect of probiotic LAB. Methods: Lactobacillus strains belonging to different LAB species were fluorescently tagged and used to colonize germ-free zebrafish larvae gastrointestinal tract (GIT). Some of the strains had a well-documented probiotic effect (L. acidophilus LA5); while others presented an exopolysaccharide (EPS) producing phenotype, thus allowing evaluating the influence of EPS in the colonization and immunomodulatory effect. Bacteria colonization was monitored for 72 h by direct observation in real time using fluorescent microscopy. CFU count per larva was also evaluated at different times. The immunomodulatory effect was assessed analysing the differential expression of several innate immune system genes (MyD88, NF-κB, Tlr4, Il1β and Il10) by qRT- PCR. The anti-inflammatory effect was evaluated using a chemical enterocolitis zebrafish model. The protective effect against a pathogen was also studied. To that end, a challenge test was developed using a fluorescently tagged pathogen (Vibrio anguillarum-GFP+). The progression of the infection was monitored up to 3 days using a fluorescent stereomicroscope. Mortality rates and CFU counts were also registered. Results and conclusions: Larvae exposed to EPS-producing bacteria showed a higher fluorescence and CFU count than those colonized with no-EPS phenotype LAB. In the same way, qRT-PCR results revealed an immunomodulatory effect on the host after the administration of the strains with probiotic activity. A downregulation of proinflammatory cytoquines as well as other cellular mediators of inflammation was observed. The anti-inflammatory effect was found to be particularly marked following exposure to LA% strain, as well as EPS producing strains. Furthermore, the challenge test revealed a protective effect of probiotic administration. As a matter of fact, larvae fed with probiotics showed a decrease in the mortality rate ranging from 20 to 35%. Discussion: In this work, we developed a promising model, based on the use of gnotobiotic zebrafish coupled with a bacterial fluorescent tagging in order to evaluate the probiotic potential of different LAB strains. We have successfully used this system to monitor in real time the colonization and persistence of exogenous LAB within the gut of zebrafish larvae, to evaluate their immunomodulatory effect and for in vivo competition assays. This approach could bring further insights into the complex microbial-host interactions at intestinal level.

Keywords: gnotobiotic, immune system, lactic acid bacteria, probiotics, zebrafish

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Authors: Clinton Adas

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Antibiotic resistance has been identified by the World Health Organisation as a real possibility for the 21st Century. While many factors contribute to this, one of the more significant is industrial animal farming and its effect on the food chain and environment. Livestock consumes a significant portion of antibiotics sold globally, and these are used to make animals grow faster for profit purposes, to prevent illness caused by inhumane living conditions, and to treat disease when it breaks out. Many of these antibiotics provide little benefit to animals, and most are the same as those used by humans - including those deemed critical to human health that should therefore be used sparingly. Antibiotic resistance contributes to growing numbers of illnesses and death in humans, and the excess usage of these medications results in waste that enters the environment and is harmful to many ecological processes. This combination of antimicrobial resistance and environmental degradation furthermore harms the economic well-being and prospects of many. Using an interdisciplinary approach including medical, environmental, economic, and legal studies, the paper evaluates the dynamic between animal welfare and commerce and argues that while animal welfare is not of great concern to many, this approach is ultimately harming human welfare too. It is, however, proposed that both could be addressed under a One Health and Welfare approach, as we cannot continue to ignore the linkages between animals, the environment, and people. The evaluation of industrial animal farming is therefore considered through three aspects – the environmental impact, which is measured by pollution that causes environmental degradation; the human impact, which is measured by the rise of illnesses from pollution and antibiotics resistance; and the economic impact, which is measured through costs to the health care system and the financial implications of industrial farming on the economic well-being of many. These three aspects are considered in light of the Sustainable Development Goals that provide additional tangible metrics to evidence the negative impacts. While the research addresses the welfare of farmed animals, there is potential for these principles to be extrapolated into other contexts, including wildlife and habitat protection. It must be noted that while the question of animal rights in industrial animal farming is acknowledged and of importance, this is a separate matter that is not addressed here.

Keywords: animal and human welfare, industrial animal farming, one health and welfare, sustainable development goals

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Authors: S. Blanchard, D. Beladjine, K. Beddiar

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Since 2015, the arrival of BIM in the building sector in France has turned the corporation world upside down. Not only constructive practices have been impacted, but also the uses and the men who have undergone important changes. Thus, the new collaborative mode generated by the BIM and the digital model has challenged the supremacy of some construction actors because the process involves working together taking into account the needs of other contributors. New BIM tools have emerged and actors in the act of building must take ownership of them. It is in this context that under the impetus of a European directive and the French government's encouragement of new missions and job profiles have. Moreover, concurrent engineering requires that each actor can advance at the same time as the others, at the whim of the information that reaches him, and the information he has to transmit. However, in the French legal system around public procurement, things are not planned in this direction. Also, a consequent evolution must take place to adapt to the methodology. The new missions generated by the BIM in France require a good mastery of the tools and the process. Also, to meet the objectives of the BIM approach, it is possible to define a typical job profile around the BIM, adapted to the various sectors concerned. The multitude of job offers using the same terms with very different objectives and the complexity of the proposed missions motivated by our approach. In order to reinforce exchanges with professionals or specialists, we carried out a statistical study to answer this problem. Five topics are discussed around the business area: the BIM in the company, the function (business), software used and BIM missions practiced (39 items). About 1400 professionals were interviewed. These people work in companies (micro businesses, SMEs, and Groups) of construction, engineering offices or, architectural agencies. 77% of respondents have the status of employees. All participants are graduated in their trade, the majority having level 1. Most people have less than a year of experience in BIM, but some have 10 years. The results of our survey help to understand why it is not possible to define a single type of BIM Manager. Indeed, the specificities of the companies are so numerous and complex and the missions so varied, that there is not a single model for a function. On the other hand, it was possible to define 3 main professions around the BIM (Manager, Coordinator and Modeler) and 3 main missions for the BIM Manager (deployment of the method, assistance to project management and management of a project).

Keywords: BIM manager, BIM modeler, BIM coordinator, project management

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Authors: Peter Falanga

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During the process of de-Stalinization that began in 1956 with the Twentieth Congress of the Soviet Communist Party, many filmmakers in Hungary chose to explore their country’s political discomforts by using Socialist Realism as a negative model against which they could react to the dominating ideology. A renewed national film industry and a more permissive political regime would allow filmmakers to take to task the plight of the preceding generation who had experienced the fatal political turmoil of both World Wars and the purges of Stalin. What follows is no longer the multigenerational unity found in Socialist Realism wherein both the old and the young embrace Stalin’s revolutionary optimism; instead, the protagonists are parentless, and thus their connection to the previous generation is partially severed. In these films, violent historical forces leave one generation to search for both a connection with their family’s past, and for moral guidance to direct their future. István Szabó’s Father (1966), Márta Mészáros Diary for My Children (1984), and Pál Gábor’s Angi Vera (1978) each consider the fraught relationship between successive generations through the lens of postwar youth. A characteristic each of their protagonist’s share is that they are all missing one or both parents, and cope with familial loss either through recalling memories of their parents in dream-like sequences, or, in the case of Angi Vera, through embracing the surrogate paternalism that the Communist Party promises to provide. This paper considers the argument these films present about the progress of Hungarian history, and how this topic is explored in more recent films that similarly focus on the transmission of generational values. Scholars such as László Strausz and John Cunningham have written on the continuous concern with the transmission of generational values in more recent films such as István Szabó’s Sunshine (1999), Béla Tarr’s Werckmeister Harmonies (2000), György Pálfi’s Taxidermia (2006), Ágnes Kocsis’ Pál Adrienn (2010), and Kornél Mundruczó’s Evolution (2021). These films, they argue, make intimate portrayals of the various sweeping political changes in Hungary’s history and question how these epochs or events have impacted Hungarian identities. If these films attempt to personalize historical shifts of Hungary, then what is the significance of featuring characters who have lost one or both parents? An attempt to understand this coherent trend in Hungarian cinema will profit from examining the earlier, celebrated films of Szabó, Mészáros, and Gábor, who inaugurated this preoccupation with generational values. The pervasive interplay of dreams and memory in their films invites an additional element to their argument concerning historical progression. This paper incorporates Richard Teniman’s notion of the “dialectics of memory” in which memory is in a constant process of negation and reinvention to explain why these Directors prefer to explore Hungarian identity through the disarranged form of psychological realism over the linear causality structure of historical realism.

Keywords: film theory, Eastern European Studies, film history, Eastern European History

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Authors: Christopher Okechukwu Ndukwe

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This paper investigates and categorizes the flexural damage mechanisms in composite materials caused by mesoscopic out-of-plane buckle defects that occur during the initial stage of the resin transfer molding (RTM) process. The findings of this study have significant practical implications for the manufacturing and use of composite materials, as they provide a deeper understanding of these damage mechanisms and their analysis. During the initial stage of shaping a preform, alterations, and distortions in the reinforcement sample can significantly lead to defects, such as buckling, especially when forming double-curvature geometries. These recurring mesoscopic defects have been investigated using a specialized laboratory bench designed to reproduce buckle defects like those found in complex geometric shapes, such as tetrahedrons. The study examined two sample configurations with buckle defects in the longitudinal and transverse directions alongside a reference sample for comparison. An acoustic emission (AE) system, a well-regarded non-contact method for monitoring structural health, was used to analyze the mechanical behavior of material samples in detail. An unsupervised K-means algorithm was employed to classify the damage mechanisms—such as matrix cracking, interface damage, and fiber breakage linked to the samples' failure. A standard was established based on three AE parameters: absolute energy, amplitude, and the number of AE events. This standard helped identify the origin and sequence of damage propagation. Initially, the results of the AE parameters were superimposed with the flexural loading curves to pinpoint the loading phases during which damage began and the specific points at which the samples ultimately failed. The normalized density of AE events related to different damage mechanisms was evaluated by analyzing the number of AE events within the amplitude domain of the AE signals. The ranges of the identified damage mechanisms in the amplitude plane illustrate the progression and order of load transfer among the elements of the composite material. In the reference sample, the AE event signals corresponding to the three classes of damage mechanisms partially overlap with adjacent signals. In contrast, the two defective sample configurations showed that the overlapping AE event signals for the respective damage mechanisms converged within the intermediate damage mode area at specific points, depending on the sample configuration. The convergence points in the samples with transverse defects were identified relatively earlier than in the other samples. Low and high amplitude ranges characterize the matrix cracking and fiber breakage damage mechanisms. The low amplitude damage occurred over a more extended length, while the high amplitude damage began much earlier. This results in the signals from both damage mechanisms converging at the center of the interface damage zone. This convergence suggests that all individual composite components fail concurrently at specific points in the defective samples, resulting in rapid fragmentation and ultimately contributing to failure. Overall, the results show that mesoscopic out-of-plane buckling in all directions affects the composite's flexural response, with more severe effects observed when the load is applied transversely.

Keywords: acoustic emission, composite reinforcement, damage mechanisms, mesoscopic buckle defects

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Authors: George Leventakis, George Kokkinis, Nikos Moustakidis, George Papalexandratos, Ioanna Vasiliadou

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Enhancing the feeling of public safety and crime prevention are tasks customarily assigned to the Police. Police departments have, however, recognized that traditional ways of policing methods are becoming obsolete; Community Policing (CP) philosophy; however, when applied appropriately, leads to seamless collaboration between various stakeholders like the Police, NGOs and the general public and provides the opportunity to identify risks, assist in solving problems of crime, disorder, safety and crucially contribute to improving the quality of life for everyone in a community. Social Media, on the other hand, due to its high level of infiltration in modern life, constitutes a powerful mechanism which offers additional and direct communication channels to reach individuals or communities. These channels can be utilized to improve the citizens’ perception of the Police and to capture individual and community needs, when their feedback is taken into account by Law Enforcement Agencies (LEAs) in a structured and coordinated manner. This paper presents research conducted under INSPEC²T (Inspiring CitizeNS Participation for Enhanced Community PoliCing AcTions), a project funded by the European Commission’s research agenda to bridge the gap between CP as a philosophy and as an organizational strategy, capitalizing on the use of Social Media. The project aims to increase transparency, trust, police accountability, and the role of civil society. It aspires to build strong, trusting relationships between LEAs and the public, supporting two-way, contemporary communication while at the same time respecting anonymity of all affected parties. Results presented herein summarize the outcomes of four online multilingual surveys, focus group interviews, desktop research and interviews with experts in the field of CP practices. The above research activities were conducted in various EU countries aiming to capture requirements of end users from diverse backgrounds (social, cultural, legal and ethical) and determine public expectations regarding CP, community safety and crime prevention.

Keywords: community partnerships, next generation community policing, social media, public safety

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Authors: Nandini Paliwal

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Since aviation industry is one of the fastest growing sectors of the world economy, states depend on the air transport industry to maintain or stimulate economic growth. It significantly promotes and contributes to the economic well-being of every nation as well as world in general. Because of the continuous and rapid growth in civil aviation, it is inevitably leading to congested skies, flight delays and most alarmingly, a decrease in the safety of air navigation facilities. Safety is one of the most important concerns of aviation industry that has been unanimously recognised across the whole world. The available capacity of the air navigation system is not sufficient for the demand that is being generated. It has been indicated by forecast that the current growth in air traffic has the potential of causing delays in 20% of flights by 2020 unless changes are brought in the current system. Therefore, a safe, orderly and expeditious air navigation system is needed at the national and global levels, which, requires the implementation of an air traffic management (hereinafter referred as ‘ATM’) system to ensure an optimum flow of air traffic by utilising and enhancing capabilities provided by technical advances. The objective of this paper is to analyse the applicability of national regulations in case of liability arising out of air traffic management services and whether the current legal regime is sufficient to cover multilateral agreements including the Single European Sky regulations. In doing so, the paper will examine the international framework mainly the Article 28 of the Chicago Convention and its relevant annexes to determine the responsibility of states for providing air navigation services. Then, the paper will discuss the difference between the concept of responsibility and liability under the air law regime and how states might claim sovereign immunity for the functions of air traffic management. Thereafter, the paper will focus on the cross border agreements including the bilateral and multilateral agreements. In the end, the paper will address the scheme of Single European Sky and the need for an international convention dealing with the liability of air navigation service providers. The paper will conclude with some suggestions for unification of the laws at an international level dealing with liability of air navigation service providers and the requirement of enhanced co-operation among states in order to keep pace with technological advances.

Keywords: air traffic management, safety, single European sky, co-operation

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Authors: Leila H. Khiabani, Mohammadreza Vafaee, Farshad Hashemzadeh

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Industrial waste management regulates different stages of production, storage, transfer, recycling and waste disposal. There are several common practices for industrial waste management. However, due to various local health, economic, social, environmental and aesthetic considerations, the most optimal principles and measures often vary at each specific industrial zone. In addition, waste management strategies are heavily impacted by local administrative, legal, and financial regulations. In this study, a hybrid qualitative and quantitative research methodology has been designed for waste management planning in an industrial city. Firstly, following a qualitative research methodology, the most relevant waste management strategies for the specific industrial city were identified through interviews with environmental planning and waste management experts. Forty experts participated in this study. Alborz industrial city in Iran, which hosts more than one thousand industrial units in nine hundred acres, was chosen as the sample industrial city in this study. The findings from the expert interviews at the first phase were then used to design a quantitative questionnaire for the second phase of the study. The aim of the questionnaire was to quantify the relative impact of different waste management strategies in the sample industrial city. Eight waste management strategies and three implementation policies were included in the questionnaire. The experts were asked to rank the relative effectiveness of each strategy for environmental planning of the sample industrial city. They were also asked to rank the relative effectiveness of each planning policy on each of the waste management strategies. In the end, the weighted average of all the responses was calculated to identify the most effective waste management strategy and planning policies for the sample industrial city. The results suggested that among the eight suggested waste management strategies, industrial composting is the most effective (31%) strategy based on the collective evaluation of the local expert. Additionally, the results suggested that the most effective policy (58%) in the city’s environmental planning is to reduce waste generation by prolonging the effective life of industrial products using higher quality and recyclable materials. These findings can provide useful expert guidelines for prioritization between different waste management strategies in the city’s overall environmental planning roadmap. The findings may also be applicable to similar industrial cities. In addition, a similar methodology can be utilized in the environmental planning of other industrial cities.

Keywords: environmental planning, industrial city, quantitative research, waste management

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Authors: Andrey Makarov

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This article will focus on the development of antitrust policy in transition economies in the context of preventing explicit and tacit collusion. Experience of BRICS, CIS (Ukraine, Kazakhstan) and CEE countries (Bulgaria, Hungary, Latvia, Lithuania, Poland, Romania, Slovakia, Slovenia, Czech Republic, Estonia) in the creation of antitrust institutions was analyzed, including both legislation and enforcement practice. Most of these countries in the early 90th were forced to develop completely new legislation in the field of protection of competition and it is important to compare different ways of building antitrust institutions and policy results. The article proposes a special approach to evaluation of preventing collusion mechanisms. This approach takes into account such enforcement problems as: classification problems (tacit vs explicit collusion, vertical vs horizontal agreements), flexibility of prohibitions (the balance between “per se” vs “rule of reason” approaches de jure and in practice), design of sanctions, private enforcement challenge, leniency program mechanisms, the role of antitrust authorities etc. The analysis is conducted using both official data, published by competition authorities, and expert assessments. The paper will show how the integration process within the EU predetermined some aspects of the development of antitrust policy in CEE countries, including the trend of the use of "rule of reason" approach. Simultaneously was analyzed the experience of CEE countries in special mechanisms of government intervention. CIS countries in the development of antitrust policy followed more or less original ways, without such a great impact from the European Union, more attention will be given to Russian experience in this field, including the analysis of judicial decisions in antitrust cases. Main problems and challenges for transition economies in this field will be shown, including: Legal uncertainty problem; Problem of rigidity of prohibitions; Enforcement priorities of the regulator; Interaction of administrative and criminal law, limited effectiveness of criminal sanctions in the antitrust field; The effectiveness of leniency program design; Private enforcement challenge.

Keywords: collusion, antitrust policy, leniency program, transition economies, Russia, CEE

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Authors: Caroline Bradbury-Jones, Maria Clark, Eleanor Molloy, Nicki Ward

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Background: Significant developments in the protection of Lesbian, Gay, Bisexual, Transgender and Queer (LGBTQ) rights culminated in their inclusion in the Equality Act 2010. This provides legal protection against discrimination including the Public Sector Equality Duty requiring public bodies to consider all individuals when carrying out their day-to-day work. In the UK, whilst the Higher Education sector has made some commitment to eliminating discrimination and addressing LGBTQ inclusivity, there are two particular problems specifically affecting students on professional programmes: -All students will come into contact with LGBTQ patients/clients/students and need to be equipped to respond appropriately to their diverse needs but evidence suggests that this is not always the case. -Many LGBTQ students have specific concerns on professional placements; often ‘going back in the closet’ or feeling uncertain how to respond to questions about their personal lives and being reticent to challenge discrimination against LGBTQ patients/clients/students for fear of reprisal. Study aim: To investigate how best to prepare all students to deal with the issue of gender and sexual diversity and to support LGBTQ students in negotiating (non) disclosure in practice placements. Methods: This multi-method study was conducted in 2017 in the UK. It comprised a student survey, focus group interview with students and a national benchmarking exercise. Findings: Preliminary findings are that there is considerable variation across professional programmes regarding the preparation of students to respond to LGBTQ issues. Similarly, there is considerable difference between the level of preparedness experienced by students irrespective of whether they identify as LGBTQ. Discussion: Nationally there are a number of ‘best practice’ examples that we share in this presentation. These contain important details and guidance about how to better prepare university students for professional practice, and to contribute to eliminating discrimination and addressing LGBTQ inclusivity. Conclusions: The presentation will appeal to delegates who are interested in the equality agenda regarding LGBTQ people. The study findings will be discussed and debated to explore their impact on higher education and learning and to identify ways to integrate best practice into professional curricula across the UK and beyond.

Keywords: diversity, equality, practice, sexuality, students, university

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Authors: Masami Usui

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After 9/11, the American literary scene was confronted with new perspectives that enabled both writers and readers to recognize the hidden aspects of their political, economic, legal, social, and cultural phenomena. There appeared an argument over new and challenging multicultural aspects after 9/11 and this argument is presented by a tension of space related to 9/11. In Amy Waldman’s the Submission (2011), designing both the memorial park and the family network has a significant meaning in establishing the progress of understanding from multiple perspectives. The most intriguing and controversial topic of racism is reflected in the Submission, where one young architect’s blind entry to the competition for the memorial of Ground Zero is nominated, yet he is confronted with strong objections and hostility as soon as he turns out to be a Muslim named Mohammad Khan. This ‘Khan’ issue, immediately enlarged into a social controversial issue on American soil, causes repeated acts of hostility to Muslim women by ignorant citizens all over America. His idea of the park is to design a new concept of tracing the cultural background of the open space. Against his will, his name is identified as the ‘ingredient’ of the networking of the resistant community with his supporters: on the other hand, the post 9/11 hysteria and victimization is presented in such family associations as the Angry Family Members and Grieving Family Members. These rapidly expanding networks, whether political or not, constructed by the internet, embody the contemporary societal connection and representation. The contemporary quest for the significance of human relationships is recognized as a quest for global peace. Designing both the memorial park and the communication networks strengthens a process of facing the shared conflicts and healing the survivors’ trauma. The tension between the idea and networking of the Garden for the memorial site and the collapse of Ground Zero signifies the double mission of the site: to establish the space to ease the wounded and to remember the catastrophe. Reading the design of these icons of 9/11 in the Submission means that decoding the myth of globalization and its representations in this century.

Keywords: American literature, cultural studies, globalization, literature of catastrophe

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Authors: Tonya P. Bowers

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Background: The community/patient-focused quality improvement (QI) project has resolved a clinical problem using a quantitative design evaluating behavior change practices in a convenience sample from a multi-cultural congregation in a faith-based setting. AD is a legal document that speaks for the patient when they are unable to speak for themselves. The AD provides detailed information regarding critical medical decisions on behalf of the patient if they’re unable to make decisions themselves. The goal of an AD is to improve EOL care renderings that align with the patient’s desires. The AD diminishes anxiety and stress associated with making difficult EOL care decisions for patients and their families. Method: The project has two intervention strategies: pre-intervention and post-intervention formative surveys and a final summative survey. Most of the data collection takes place during implementation. The Let’s Talk About It Program utilized an online meeting platform for presentation. Participants were asked to complete informed consent and surveys via an online portal. Education included slide presentation, Advance Directive demonstration, video clips, discussions and 1:1 assistance with AD completion with a project manager. Results: Considering the overwhelming likelihood responses where 87.5% identified they “definitely would” hold an End-Of-Life conversation with their healthcare provider or family, and 81.25% indicated their likelihood that they “definitely would” complete an advance directive. In addition, the final summative post-intervention survey (n-14) also demonstrated an overwhelming 93% positive response. Which undoubtedly demonstrates favorable outcomes for the project. Conclusion: the Let’s Talk About It Program demonstrated effectiveness in improving participants' attitudes and acceptance towards Advance Directives and expanding End-of-Life care discussions. Emphasis on program sustainment within the church is imperative in fostering continued awareness and improved health outcomes for the local community with low health literacy.

Keywords: advance directive, end of life, advance care planning, palliative care, low health literacy, faith-based

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Authors: Anuruddhi Edirisinghe, Anusha Edirisinghe, Maithree Wicramasinghe, Sagarika Kannangara, Annista Wijayanayake

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SGBV which refer to acts of inflicting physical, mental or sexual harm or sufferings that deprive a person’s liberty based on one’s gender or sexuality is known to occur in various forms. Ragging in educational institutions can often be one such form of SGBV. Ragging related SGBV is a growing problem despite various legal, policy and programme initiatives introduced over the years. While the punishment of perpetrators through the criminal justice system is expected to bring a deterrent effect, other strategies such as awareness-raising, attitudinal changes, and the empowerment of students to say no to ragging and SGBV will lead to enlightened attitudes about the practice in universities. Thus, effective regular prevention programmes are the need of the hour. The objectives of the paper are to engage with the case of a female fresher subjected to verbal abuse, physical assault and sexual harassment due to events which started as a result of wearing a trouser to the university during the ragging season. The case came to the limelight since a complaint was made to the police and 10 students were arrested under the anti-ragging act. This led to dividend opinions among the student population and a backlash from the student union. Simultaneously, this resulted in the society demanding the stricter implementation of laws and the punishment of perpetrators. The university authority appointed a task force comprising of academics, non-academics, parents, community leaders, stakeholders and students to draw up an action plan to respond to the immediate situation as well as future prevention. The paper will also discuss the implementation of task force plan. The paper is based on interviews with those involved with the issue and the experiences of the task force members and is expected to provide an in-depth understanding of the intricacies and complications associated with dealing with a contentious problem such as ragging. Given the political and ethical issues involved with insider research as well as the sensationalism of the topic, maximum care will be taken to safeguard the interests of those concerned.

Keywords: fresher, sexual and gender based violence (SGBV), sexual harassment, ragging

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Authors: Paul Licina, Emma M. Johnston, David Lisle, Mark Young, Chris Brady

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Background: Lumbar pars pathology is a common cause of pain in the growing spine. It can be seen in young athletes participating in at-risk sports and can affect sporting performance and long-term health due to its resistance to traditional management. There is a current lack of consensus of classification and treatment for pars injuries. Previous systems used CT to stage pars defects but could not assess early stress reactions. A modified classification is proposed that considers findings on MRI, significantly improving early treatment guidance. The treatment protocol is designed for patients aged 5 to 19 years. Method: Clinical screening identifies patients with a low, medium, or high index of suspicion for lumbar pars injury using patient age, sport participation and pain characteristics. MRI of the at-risk cohort enables augmentation of existing CT-based classification while avoiding ionising radiation. Patients are classified into five categories based on MRI findings. A type 0 lesion (stress reaction) is present when CT is normal and MRI shows high signal change (HSC) in the pars/pedicle on T2 images. A type 1 lesion represents the ‘early defect’ CT classification. The group previously referred to as a 'progressive stage' defect on CT can be split into 2A and 2B categories. 2As have HSC on MRI, whereas 2Bs do not. This distinction is important with regard to healing potential. Type 3 lesions are terminal stage defects on CT, characterised by pseudarthrosis. MRI shows no HSC. Results: Stress reactions (type 0) and acute fractures (1 and 2a) can heal and are treated in a custom-made hard brace for 12 weeks. It is initially worn 23 hours per day. At three weeks, patients commence basic core rehabilitation. At six weeks, in the absence of pain, the brace is removed for sleeping. Exercises are progressed to positions of daily living. Patients with continued pain remain braced 23 hours per day without exercise progression until becoming symptom-free. At nine weeks, patients commence supervised exercises out of the brace for 30 minutes each day. This allows them to re-learn muscular control without rigid support of the brace. At 12 weeks, bracing ceases and MRI is repeated. For patients with near or complete resolution of bony oedema and healing of any cortical defect, rehabilitation is focused on strength and conditioning and sport-specific exercise for the full return to activity. The length of this final stage is approximately nine weeks but depends on factors such as development and level of sports participation. If significant HSC remains on MRI, CT scan is considered to definitively assess cortical defect healing. For these patients, return to high-risk sports is delayed for up to three months. Chronic defects (2b and 3) cannot heal and are not braced, and rehabilitation follows traditional protocols. Conclusion: Appropriate clinical screening and imaging with MRI can identify pars pathology early. In those with potential for healing, we propose hard bracing and appropriate rehabilitation as part of a multidisciplinary management protocol. The validity of this protocol will be tested in future studies.

Keywords: adolescents, MRI classification, pars interticularis, treatment protocol

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Authors: Elvin P. Chizenga, Heidi Abrahamse

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Cancer cell resistance to therapy is the main cause of treatment failures and the poor prognosis of cancer convalescence. The progression of cervical cancer to other parts of the genitourinary system and the reported recurrence rates are overwhelming. Current treatments, including surgery, chemo and radiation have been inefficient in eradicating the tumor cells. These treatments are also associated with poor prognosis and reduced quality of life, including fertility loss. This has inspired the need for the development of new treatment modalities to eradicate cervical cancer successfully. Photodynamic Therapy (PDT) is a modern treatment modality that induces cell death by photochemical interactions of light and a photosensitizer, which in the presence of molecular oxygen, yields a set of chemical reactions that generate Reactive Oxygen Species (ROS) and other free radical species causing cell damage. Enhancing PDT using modified drug delivery can increase the concentration of the photosensitizer in the tumor cells, and this has the potential to maximize its therapeutic efficacy. In cervical cancer, all infected cells constitutively express genes of the E6 and E7 HPV viral oncoproteins, resulting in high concentrations of E6 and E7 in the cytoplasm. This provides an opportunity for active targeting of cervical cancer cells using immune-mediated drug delivery to maximize therapeutic efficacy. The use of nanoparticles in PDT has also proven effective in enhancing therapeutic efficacy. Gold nanoparticles (AuNps) in particular, are explored for their use in biomedicine due to their biocompatibility, low toxicity, and enhancement of drug uptake by tumor cells. In this present study, a biomolecule comprising of AuNPs, anti-E6 monoclonal antibodies, and Aluminium Phthalocyanine photosensitizer was synthesized for use in targeted PDT of cervical cancer. The AuNp-Anti-E6-Sulfonated Aluminium Phthalocyanine mix (AlPcSmix) photosensitizing biomolecule was synthesized by coupling AuNps and anti-E6 monoclonal antibodies to the AlPcSmix via Polyethylene Glycol (PEG) chemical links. The final product was characterized using Transmission Electron Microscope (TEM), Zeta Potential, Uv-Vis Spectrophotometry, Fourier Transform Infrared Spectroscopy (FTIR), and X-ray diffraction (XRD), to confirm its chemical structure and functionality. To observe its therapeutic role in treating cervical cancer, cervical cancer cells, HeLa cells were seeded in 3.4 cm² diameter culture dishes at a concentration of 5x10⁵ cells/ml, in vitro. The cells were treated with varying concentrations of the photosensitizing biomolecule and irradiated using a 673.2 nm wavelength of laser light. Post irradiation cellular responses were performed to observe changes in morphology, viability, proliferation, cytotoxicity, and cell death pathways induced. Dose-Dependent response of the cells to treatment was demonstrated as significant morphologic changes, increased cytotoxicity, and decreased cell viability and proliferation This study presented a synthetic biomolecule for targeted PDT of cervical cancer. The study suggested that PDT using this AuNp- Anti-E6- AlPcSmix photosensitizing biomolecule is a very effective treatment method for the eradication of cervical cancer cells, in vitro. Further studies in vivo need to be conducted to support the use of this biomolecule in treating cervical cancer in clinical settings.

Keywords: anti-E6 monoclonal antibody, cervical cancer, gold nanoparticles, photodynamic therapy

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Authors: Xuan Pang, Alvin L. Lee, Peggy Glatthaar

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Libraries across the world have been an innovation engine of creativity and opportunityin many decades. The on-going global epidemiology outbreak and health crisis experience illuminates potential reforms, rethinking beyond traditional library operations and services. Controlled Digital Lending (CDL) is one of the emerging technologies libraries used to deliver information digitally in support of online learning and teachingand make educational materials more affordable and more accessible. CDL became a popular term in the United States of America (USA) as a result of a white paper authored by Kyle K. Courtney (Harvard University) and David Hansen (Duke University). The paper gave the legal groundwork to explore CDL: Fair Use, First Sale Doctrine, and Supreme Court rulings. Library professionals implemented this new technology to fulfill their users’ needs. Three libraries in the state of Florida (University of Florida, Florida Gulf Coast University, and Florida A&M University) started a conversation about how to develop strategies to make CDL work possible at each institution. This paper shares the stories of piloting and initiating a CDL program to ensure students have reliable, affordable access to course materials they need to be successful. Additionally, this paper offers an overview of the emerging trends of Controlled Digital Lending in the USA and demonstrates the development of the CDL platforms, policies, and implementation plans. The paper further discusses challenges and lessons learned and how each institution plans to sustain the program into future library services. The fundamental mission of the library is providing users unrestricted access to library resources regardless of their physical location, disability, health status, or other circumstances. The professional due diligence of librarians, as information professionals, is to makeeducational resources more affordable and accessible.CDL opens a new frontier of library services as a mechanism for library practice to enhance user’s experience of using libraries’ services. Libraries should consider exploring this tool to distribute library resources in an effective and equitable way. This new methodology has potential benefits to libraries and end users.

Keywords: controlled digital lending, emerging technologies, equitable access, collaborations

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Authors: Vassiliki Drosou, Theoni Oikonomou

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EU-SOLARIS will form a new legal entity to explore and implement improved rules and procedures for Research Infrastructures (RI) for Concentrated Solar Thermal (CST) and solar chemistry technologies, in order to optimize RI development and R&D coordination. It is expected to be the first of its kind, where industrial needs and private funding will play a significant role. The success of EU-SOLARIS initiative will be the establishment of a new governance body, aided by sustainable financial models. EU-SOLARIS is expected to be an important tool, which will provide the most complete, high quality scientific infrastructure portfolio at international level and to facilitate researchers' access to highly specialised research infrastructure through a single access point. This will be accomplished by linking scientific communities, industry and universities involved in the CST sector. The access to be offered by EU-SOLARIS will guarantee the direct contact of experienced scientists with newcomers and interested students. The set of RIs participating in EU-SOLARIS will offer access to state of the art infrastructures, high-quality services, and will enable users to conduct high quality research. Access to these facilities will contribute to the enhancement of the European research area by: -Opening installations to European and non-European scientists, coming from both academia and industry, thus improving co-operation. -Improving scientific critical mass in domains where knowledge is now widely dispersed. -Generating strong Europe-wide R&D project consortia, increasing the competitiveness of each member alone. EU-SOLARIS will be created in the framework of a European project, co-funded by the 7th Framework Programme of the European Union –whose initiative is to foster, contribute and promote the scientific and technological development of the CST and solar chemistry technologies. Primary objective of EU-SOLARIS is to contribute to the improvement of the state of the art of these technologies with the aim of preserving and reinforcing the European leadership in this field, in which EU-SOLARIS is expected to be a valuable instrument. EU-SOLARIS scope, activities, objectives, current status and vision will be given in the article. Moreover, the rules, processes and criteria regulating the access to the research infrastructures included in EU-SOLARIS will be presented.

Keywords: concentrated solar thermal (CST) technology, renewable energy sources, research infrastructures, solar chemistry

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Authors: Neelofar, Khursheed Alam, Jamal Ahmad

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Protein modification in diabetes mellitus may lead to early glycation products (EGPs) or amadori product as well as advanced glycation end products (AGEs). Early glycation involves the reaction of glucose with N-terminal and lysyl side chain amino groups to form Schiff’s base which undergoes rearrangements to form more stable early glycation product known as Amadori product. After Amadori, the reactions become more complicated leading to the formation of advanced glycation end products (AGEs) that interact with various AGE receptors, thereby playing an important role in the long-term complications of diabetes. Millard reaction or nonenzymatic glycation reaction accelerate in diabetes due to hyperglycation and alter serum protein’s structure, their normal functions that lead micro and macro vascular complications in diabetic patients. In this study, Human Serum Albumin (HSA) with a constant concentration was incubated with different concentrations of glucose at 370C for a week. At 4th day, Amadori product was formed that was confirmed by colorimetric method NBT assay and TBA assay which both are authenticate early glycation product. Conformational changes in native as well as all samples of Amadori albumin with different concentrations of glucose were investigated by various biophysical and biochemical techniques. Main biophysical techniques hyperchromacity, quenching of fluorescence intensity, FTIR, CD and SDS-PAGE were used. Further conformational changes were observed by biochemical assays mainly HMF formation, fructoseamine, reduction of fructoseamine with NaBH4, carbonyl content estimation, lysine and arginine residues estimation, ANS binding property and thiol group estimation. This study find structural and biochemical changes in Amadori modified HSA with normal to hyperchronic range of glucose with respect to native HSA. When glucose concentration was increased from normal to chronic range biochemical and structural changes also increased. Highest alteration in secondary and tertiary structure and conformation in glycated HSA was observed at the hyperchronic concentration (75mM) of glucose. Although it has been found that Amadori modified proteins is also involved in secondary complications of diabetes as AGEs but very few studies have been done to analyze the conformational changes in Amadori modified proteins due to early glycation. Most of the studies were found on the structural changes in Amadori protein at a particular glucose concentration but no study was found to compare the biophysical and biochemical changes in HSA due to early glycation with a range of glucose concentration at a constant incubation time. So this study provide the information about the biochemical and biophysical changes occur in Amadori modified albumin at a range of glucose normal to chronic in diabetes. Although many implicates currently in use i.e. glycaemic control, insulin treatment and other chemical therapies that can control many aspects of diabetes. However, even with intensive use of current antidiabetic agents more than 50 % of diabetic patient’s type 2 suffers poor glycaemic control and 18 % develop serious complications within six years of diagnosis. Experimental evidence related to diabetes suggests that preventing the nonenzymatic glycation of relevant proteins or blocking their biological effects might beneficially influence the evolution of vascular complications in diabetic patients or quantization of amadori adduct of HSA by authentic antibodies against HSA-EGPs can be used as marker for early detection of the initiation/progression of secondary complications of diabetes. So this research work may be helpful for the same.

Keywords: diabetes mellitus, glycation, albumin, amadori, biophysical and biochemical techniques

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Authors: Antonella Di Sotto, Cinzia Ingallina, Caterina Fraschetti, Simone Circi, Marcello Locatelli, Simone Carradori, Gabriela Mazzanti, Luisa Mannina, Silvia Di Giacomo

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Cannabis sativa L. is one of the oldest cultivated plant species known not only for its voluptuous use but also for the wide application in food, textile, and therapeutic industries. Recently, the progress of biotechnologies applied to medicinal plants has allowed to produce different hemp varieties with low content of psychotropic phytoconstituents (tetrahydrocannabinol < 0.2% w/v), thus leading to a renewed industrial and therapeutic interest for this plant. In this context, in order to discover new potential remedies of pharmaceutical and/or nutraceutical interest, the chemopreventive properties of different organic and hydroalcoholic extracts, obtained from the inflorescences of C. sativa L. var. USO31, collected in June and September harvesting, were assessed. Particularly, the antimutagenic activity towards the oxidative DNA-damage induced by tert-butyl hydroperoxide (t-BOOH) was evaluated, and the DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid) radical scavenging power of the samples were assessed as possible mechanisms of antimutagenicity. Furthermore, the ability of the extracts to inhibit the glucose-6-phosphate dehydrogenase (G6PD), whose overexpression has been found to play a critical role in neoplastic transformation and tumor progression, has been studied as a possible chemopreventive strategy. A careful phytochemical characterization of the extracts for phenolic and terpenoid composition has been obtained by high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) methods. Under our experimental condition, all the extracts were found able to interfere with the tBOOH-induced mutagenicity in WP2uvrAR strain, although with different potency and effectiveness. The organic extracts from both the harvesting periods were found to be the main effective antimutagenic samples, reaching about a 55% inhibition of the tBOOH-mutagenicity at the highest concentration tested (250 μg/ml). All the extracts exhibited radical scavenger activity against DPPH and ABTS radicals, with a higher potency of the hydroalcoholic samples. The organic extracts were also able to inhibit the G6PD enzyme, being the samples from September harvesting the highly potent (about 50% inhibition respect to the vehicle). At the phytochemical analysis, all the extracts resulted to contain both polar and apolar phenolic compounds. The HPLC analysis revealed the presence of catechin and rutin as the major constituents of the hydroalcoholic extracts, with lower levels of quercetin and ferulic acid. The monoterpene carvacrol was found to be an ubiquitarian constituent. At GC-MS analysis, different terpenoids, among which caryophyllene sesquiterpenes, were identified. This evidence suggests a possible role of both polyphenols and terpenoids in the chemopreventive properties of the extracts from the inflorescences of C. sativa var. USO31. According to the literature, carvacrol and caryophyllene sesquiterpenes can contribute to the strong antimutagenicity although the role of all the hemp phytocomplex cannot be excluded. In conclusion, present results highlight a possible interest for the inflorescences of C. sativa var. USO31 as source of bioactive molecules and stimulate further studies in order to characterize its possible application for nutraceutical and pharmaceutical purposes.

Keywords: antimutagenicity, glucose-6-phosphate dehydrogenase, hemp inflorescences, nutraceuticals, sesquiterpenes

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Authors: Vichayada Laohapiboolkul

Abstract:

Introduction: As the legal use of cannabis is being widely accepted throughout the world, medical cannabis has been explored in order to become an alternative cure for patients. Tetrahydrocannabinol (THC) and Cannabidiol (CBD) are natural cannabinoids found in the Cannabis plant which is proved to have positive treatment for various diseases and symptoms such as chronic pain, neuropathic pain, spasticity resulting from multiple sclerosis, reduce cancer-associated pain, autism spectrum disorders (ASD), dementia, cannabis and opioid dependence, psychoses/schizophrenia, general social anxiety, posttraumatic stress disorder, anorexia nervosa, attention-deficit hyperactivity disorder, and Tourette's disorder. Regardless of all the medical benefits, THC, if not metabolized, can lead to mild up to severe adverse drug reactions (ADR). The enzyme CYP2C19 was found to be one of the metabolizers of THC. However, the suballele CYP2C19*2 manifests as a poor metabolizer which could lead to higher levels of THC than usual, possibly leading to various ADRs. Objective: The aim of this study was to investigate the distribution of CYP2C19, specifically CYP2C19*2, genes in Thai patients treated with medical cannabis along with adverse drug reactions. Materials and Methods: Clinical data and EDTA whole blood for DNA extraction and genotyping were collected from patients for this study. CYP2C19*2 (681G>A, rs4244285) genotyping was conducted using the Real-time PCR (ABI, Foster City, CA, USA). Results: There were 42 medical cannabis-induced ADRs cases and 18 medical cannabis tolerance controls who were included in this study. A total of 60 patients were observed where 38 (63.3%) patients were female and 22 (36.7%) were male, with a range of age approximately 19 - 87 years. The most apparent ADRs for medical cannabis treatment were dry mouth/dry throat (76.7%), followed by tachycardia (70%), nausea (30%) and a few arrhythmias (10%). In the total of 27 cases, we found a frequency of 18 CYP2C19*1/*1 alleles (normal metabolizers, 66.7%), 8 CYP2C19*1/*2 alleles (intermediate metabolizers, 29.6%) and 1 CYP2C19*2/*2 alleles (poor metabolizers, 3.7%). Meanwhile, 63.6% of CYP2C19*1/*1, 36.3% and 0% of CYP2C19*1/*2 and *2/*2 in the tolerance controls group, respectively. Conclusions: This is the first study to confirm the distribution of CYP2C19*2 allele and the prevalence of poor metabolizer genes in Thai patients who received medical cannabis for treatment. Thus, CYP2C19 allele might serve as a pharmacogenetics marker for screening before initiating treatment.

Keywords: medical cannabis, adverse drug reactions, CYP2C19, tetrahydrocannabinol, poor metabolizer

Procedia PDF Downloads 103

Authors: Olanrewaju O. Adeojo

Abstract:

The constitutional system of government provides for the federating units of the Federal Republic of Nigeria, the States and the Local Councils under a governing structure of the Executive, the Legislature and the Judiciary with attendant distinct powers and spheres of influence. The legislative powers of the Federal Republic of Nigeria and of a State are vested in the National Assembly and House of Assembly of the State respectively. The Local council exercises legislative powers in clearly defined matters as provided by the Constitution. Though, the executive as constituted by the President and the Governor are charged with the powers of execution and administration, the legislature is empowered to ensure that such powers are duly exercised in accordance with the provisions of the Constitution. The vast areas do not make oversight functions indefinite and more importantly the purpose for the exercise of the powers are circumscribed. It include, among others, any matter with respect to which it has power to make laws. Indeed, the law provides for the competence of the legislature to procure evidence, examine all persons as witnesses, to summon any person to give evidence and to issue a warrant to compel attendance in matters relevant to the subject matter of its investigation. The exercise of functions envisaged by the Constitution seem to an extent to be literal because it lacks power of enforcing the outcome. Furthermore, the docility of the legislature is apparent in a situation where the agency or authority being called in to question is part of the branch of government to enforce sanctions. The process allows for cover up and obstruction of justice. The oversight functions are not functional in a situation where the executive is overbearing. The friction, that ensues, between the Legislature and the Executive in an attempt by the former to project the spirit of a constitutional mandate calls for concern. It is needless to state a power that can easily be frustrated. To an extent, the arm of government with coercive authority seems to have over shadowy effect over the laid down functions of the legislature. Recourse to adjudication by the Judiciary had not proved to be of any serious utility especially in a clime where the wheels of justice grinds slowly, as in Nigeria, due to the nature of the legal system. Consequently, the law and the Constitution, drawing lessons from other jurisdiction, need to insulate the legislative oversight from the vagaries of the executive. A strong and virile Constitutional Court that determines, within specific time line, issues pertaining to the oversight functions of the legislative power, is apposite.

Keywords: constitution, legislative, oversight, power

Procedia PDF Downloads 130