Search results for: small crack locating

Authors: Maryam S. Ghoraishi, John E. Hawk, Thomas Thundat

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Understanding liquid properties in small scale has become important in recent decades as immerging new microelectromechanical systems (MEMS) devices have been widely used for micro pumps, drug delivery, and many other laboratory-on-microchips analysis. Often in microfluidic devices, fluids are transported electrokinetically. Therefore, extensive knowledge of fluid flow, heat transport, electrokinetics and electrochemistry are key to successful lab on a chip design. Among different microfluidic devices, recently developed hollow channel cantilever offers an ideal platform to study different fluid properties simultaneously without drastic decrease in quality factor which normally occurs when traditional cantilevers operate in the liquid phase. Using hollow channel cantilever, we monitor changes in density and viscosity of liquid while simultaneously investigating dielectric properties of alcohol water binary mixtures. Considerable research has been conducted on alcohol-water mixtures since such a mixture is a typical prototype for biomolecules, Micelle formation, and structural stability of proteins (to name a few). Here we show that hollow channel cantilever can be employed to investigate dielectric properties of ethanol/water mixtures in different concentrations. We study dynamic amplitude shifts of hollow channel cantilever oscillation at different concentrations of ethanol/water for different voltages. Our results show how interactions between solute and solvent, and possibly cluster formation, could change dielectric properties and dipole reorientation of the mixture, as well as the resulting force on the hollow cantilever. For comparison, we also examine higher conductivity ionic mixtures of sodium sulfate solution under the same conditions as low conductivity ethanol/water mixtures. We will show the results from systematic investigation of solvent effects on dielectric properties of the binary mixture. We will also address the question of resolution limits in dielectric study of analyte molecules imposed by solvent concentrations.

Keywords: dielectric constant, cantilever sensors, ethanol water mixtures, low frequency

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Authors: Sarthak Kumar Jena, Chandra Sekhar Mishra, Prabina Rajib

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Purpose: This paper aims to derive undervaluation signal from the insiders trading of Indian companies where the ownership is complex and concentrated, investors protection is weak, and the insider rules and regulations are not stringent like developed country. This study examines the relationship between insider trading with short term and long term abnormal return. The study also examines the relationship between insider trading and the actual share repurchase by the firm. Methodology: A sample of 78 companies over the period 2008-2013 are analyzed in the study due to not availability of insider data in Indian context. For preliminary analysis T-test and Wilcoxon rank sum test is used to find the difference between the insider trading before and after the share repurchase announcement. Tobit model is used to find out whether insider trading influence shares repurchase decisions or not. Return on the basis of market model and buy hold are calculated in the previous year and the following year of share repurchase announcement. Findings: The paper finds that insider trading around share repurchase is more than control firms and there is positive and significant difference in insider buying between the previous year of share buyback announcement and the following year of buyback announcement. Insider buying before share repurchase announcement has a positive influence on share repurchase decisions. We find insider buying has a positive and significant relationship with announcement return, whereas insider selling has a negative significant relationship with announcement return. Actual share repurchase and program completion also depend on insider trading before share repurchase. Research limitation: The study is constrained by the small sample size, so the results should be viewed by keeping this limitation in mind. Originality: The paper is to our best knowledge the first study based on Indian context to extend the insider trading literature to share repurchase event and examine insider trading to find out undervaluation signal associated with insider buying.

Keywords: insider trading, buyback, open market share repurchase, signalling

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Authors: Kebron Abich Asnake

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The outbreak of COVID-19 has had far-reaching socio-economic consequences globally, and Ethiopia is no exception. This abstract provides a summary of a research study on the socio-economic impact of COVID-19 in Ethiopia. The study analyzes the health impact, economic repercussions, social consequences, government response measures, and opportunities for post-crisis recovery. In terms of health impact, the research explores the spread and transmission of the virus, the capacity and response of the healthcare system, and the mortality rate, with a focus on vulnerable populations. The economic impact analysis entails investigating the contraction of the GDP, employment and income loss, disruption in key sectors such as agriculture, tourism, and manufacturing, and the specific implications for small and medium-sized enterprises (SMEs), foreign direct investment, and remittances. The social impact section looks at the disruptions in education and the digital divide, food security and nutrition challenges, increased poverty and inequality, gender-based violence, and mental health issues. The research also examines the measures taken by the Ethiopian government, including health and safety regulations, economic stimulus packages, social protection programs, and support for vulnerable populations. Furthermore, the study outlines long-term recovery prospects, social cohesion, and community resilience challenges. It highlights the need to strengthen the healthcare system and finds a balance between health and economic priorities. The research concludes by presenting recommendations for policy-makers and stakeholders, emphasizing opportunities for post-crisis recovery such as diversification of the economy, enhanced healthcare infrastructure, investment in digital infrastructure and technology, and support for domestic tourism and local industries. This research provides valuable insights into the socio-economic impact of COVID-19 in Ethiopia, offering a comprehensive analysis of the challenges faced and potential pathways towards recovery.

Keywords: impact, covid, ethiopia, health

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Authors: Ranjot Kaur, Om P. Katare, Anupama Sharma, Sarah R. Dennison, Kamalinder K. Singh, Bhupinder Singh

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Respiratory microbial infections being among the top leading cause of death worldwide are difficult to treat as the microbes reside deep inside the airways, where only a small fraction of drug can access after traditional oral or parenteral routes. As a result, high doses of drugs are required to maintain drug levels above minimum inhibitory concentrations (MIC) at the infection site, unfortunately leading to severe systemic side-effects. Therefore, delivering antimicrobials directly to the respiratory tract provides an attractive way out in such situations. In this context, current study embarks on the systematic development of lung lia pid-modified chitosan nanoparticles for inhalation of voriconazole. Following the principles of quality by design, the chitosan nanoparticles were prepared by ionic gelation method and further coated with major lung lipid by precipitation method. The factor screening studies were performed by fractional factorial design, followed by optimization of the nanoparticles by Box-Behnken Design. The optimized formulation has a particle size range of 170-180nm, PDI 0.3-0.4, zeta potential 14-17, entrapment efficiency 45-50% and drug loading of 3-5%. The presence of a lipid coating was confirmed by FESEM, FTIR, and X-RD. Furthermore, the nanoparticles were found to be safe upto 40µg/ml on A549 and Calu-3 cell lines. The quantitative and qualitative uptake studies also revealed the uptake of nanoparticles in lung epithelial cells. Moreover, the data from Spraytec and next-generation impactor studies confirmed the deposition of nanoparticles in lower airways. Also, the interaction of nanoparticles with DPPC monolayers signifies its biocompatibility with lungs. Overall, the study describes the methodology and potential of lipid-coated chitosan nanoparticles in futuristic inhalation nanomedicine for the management of pulmonary aspergillosis.

Keywords: dipalmitoylphosphatidylcholine, nebulization, DPPC monolayers, quality-by-design

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Authors: Moiseenko F. V., Volkov N. M., Zhabina A. S., Stepanova E. O., Kirillov A. V., Myslik A. V., Artemieva E. V., Agranov I. R., Oganesyan A. P., Egorenkov V. V., Abduloeva N. H., Aleksakhina S. Yu., Ivantsov A. O., Kuligina E. S., Imyanitov E. N., Moiseyenko V. M.

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Analysis of ctDNA in patients with NSCLC is an emerging biomarker. Multiple research efforts of quantitative or at least qualitative analysis before and during the first periods of treatment with TKI showed the prognostic value of ctDNA clearance. Still, these important results are not incorporated in clinical standards. We evaluated the role of ctDNA in EGFR-mutated NSCLC receiving first-line TKI. Firstly, we analyzed sequential plasma samples from 30 patients that were collected before intake of the first tablet (at baseline) and at 6, 12, 24, 36, and 48 hours after the “starting point.” EGFR-M+ allele was measured by ddPCR. Afterward, we included sequential qualitative analysis of ctDNA with cobas® EGFR Mutation Test v2 from 99 NSCLC patients before the first dose, after 2 and 4 months of treatment, and on progression. Early response analysis showed the decline of EGFR-M+ level in plasma within the first 48 hours of treatment in 11 subjects. All these patients showed objective tumor response. 10 patients showed either elevation of EGFR-M+ plasma concentration (n = 5) or stable content of circulating EGFR-M+ after the start of the therapy (n = 5); only 3 of these patients achieved an objective response (p = 0.026) when compared to the former group). The rapid decline of plasma EGFR-M+ DNA concentration also predicted for longer PFS (13.7 vs. 11.4 months, p = 0.030). Long-term ctDNA monitoring showed clinically significant heterogeneity of EGFR-mutated NSCLC treated with 1st line TKIs in terms of progression-free and overall survival. Patients without detectable ctDNA at baseline (N = 32) possess the best prognosis on the duration of treatment (PFS: 24.07 [16.8-31.3] and OS: 56.2 [21.8-90.7] months). Those who achieve clearance after two months of TKI (N = 42) have indistinguishably good PFS (19.0 [13.7 – 24.2]). Individuals who retain ctDNA after 2 months (N = 25) have the worst prognosis (PFS: 10.3 [7.0 – 13.5], p = 0.000). 9/25 patients did not develop ctDNA clearance at 4 months with no statistical difference in PFS from those without clearance at 2 months. Prognostic heterogeneity of EGFR-mutated NSCLC should be taken into consideration in planning further clinical trials and optimizing the outcomes of patients.

Keywords: NSCLC, EGFR, targeted therapy, ctDNA, prognosis

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Authors: W. Assaad, D. Wilmink, H. R. Pasaribu, H. J. M. Geijselaers

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Shell has developed a mono-diameter well concept for oil and gas wells as opposed to the traditional telescopic well design. A Mono-diameter well design allows well to have a single inner diameter from the surface all the way down to reservoir to increase production capacity, reduce material cost and reduce environmental footprint. This is achieved by expansion of liners (casing string) concerned using an expansion tool (e.g. a cone). Since the well is drilled in stages and liners are inserted to support the borehole, overlap sections between consecutive liners exist which should be expanded. At overlap, the previously inserted casing which can be expanded or unexpanded is called the host casing and the newly inserted casing is called the expandable casing. When the cone enters the overlap section, an expandable casing is expanded against a host casing, a cured cement layer and formation. In overlap expansion, ironing or lengthening may appear instead of shortening in the expandable casing when the pressure exerted by the host casing, cured cement layer and formation exceeds a certain limit. This pressure is related to cement strength, thickness of cement layer, host casing material mechanical properties, host casing thickness, formation type and formation strength. Ironing can cause implications that hinder the deployment of the technology. Therefore, the understanding of ironing becomes essential. A physical model is built in-house to calculate expansion forces, stresses, strains and post expansion casing dimensions under different conditions. In this study, only free casing and overlap expansion of two casings are addressed while the cement and formation will be incorporated in future study. Since the axial strain can be predicted by the physical model, the onset of ironing can be confirmed. In addition, this model helps in understanding ironing and the parameters influencing it. Finally, the physical model is validated with Finite Element (FE) simulations and small-scale experiments. The results of the study confirm that high pressure leads to ironing when the casing is expanded in tension mode.

Keywords: casing expansion, cement, formation, metal forming, plasticity, well design

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Authors: Ramona-Niculina Jurcau, Ioana-Marieta Jurcau, Dong Hun Kwak, Nicolae-Alexandru Colceriu

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Background: Academic environment led, in time, to the birth of some research subjects concluded with many publications. One of these issues is related to the learning stress. Thus far, the PubMed website displays an impressive number of papers related to the academic stress. Aims: Through this study, we aimed to evaluate the research concerning academic learning stress (ALS), by a retrospective analysis of PubMed publications. Methods: We evaluated the ALS, considering: a) different keywords as - ‘academic stress’ (AS), ‘academic stressors’ (ASs), ‘academic learning stress’ (ALS), ‘academic student stress’ (ASS), ‘academic stress college’ (ASC), ‘medical academic stress’ (MAS), ‘non-medical academic stress’ (NMAS), ‘student stress’ (SS), ‘nursing student stress’ (NS), ‘college student stress’ (CSS), ‘university student stress’ (USS), ‘medical student stress’ (MSS), ‘dental student stress’ (DSS), ‘non-medical student stress’ (NMSS), ‘learning students stress’ (LSS), ‘medical learning student stress’ (MLSS), ‘non-medical learning student stress’ (NMLSS); b) the year average for decades; c) some selection filters provided by PubMed website: Article types - Journal Article (JA), Clinical Trial (CT), Review (R); Species - Humans (H); Sex - Male (M) and Female (F); Ages - 13-18, 19-24, 19-44. Statistical evaluation was made on the basis of the Student test. Results: There were differences between keywords, referring to all filters. Nevertheless, for all keywords were noted the following: the majority of studies have indicated that subjects were humans; there were no important differences between the number of subjects M and F; the age of participants was mentioned only in some studies, predominating those with teenagers and subjects between 19-24 years. Conclusions: 1) PubMed publications document that concern for the research field of academic stress, lasts for 56 years and was materialized in more than 5.010 papers. 2) Number of publications in the field of academic stress varies depending on the selected keywords: those with a general framing (AS, ASs, ALS, ASS, SS, USS, LSS) are more numerous than those with a specific framing (ASC, MAS, NMAS, NS, CSS, MSS, DSS, NMSS, MLSS, NMLSS); those concerning the academic medical environment (MAS, NS, MSS, DSS, MLSS) prevailed compared to the non-medical environment (NMAS, NMSS, NMLSS). 3) Most of the publications are included at JA, of which a small percentage are CT and R. 4) Most of the academic stress studies were conducted with subjects both M and F, most aged under 19 years and between 19-24 years.

Keywords: academic stress, student stress, academic learning stress, medical student stress

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Authors: Petra Borilova Linhartova, Michaela Ruckova, Sabina Sevcikova, Natalie Mlcuchova, Jan Bohm, Katerina Zukalova, Monika Vlachova, Jiri Dolina, Lumir Kunovsky, Radek Kroupa, Zdenek Pavlovsky, Zdenek Danek, Tereza Deissova, Lydie Izakovicova Holla, Ondrej Slaby, Zdenek Kala

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Esophageal adenocarcinoma (EAC) is a highly aggressive malignancy that frequently develops from Barrett's esophagus (BE), a premalignant pathologic change occurring in the lower end of the esophagus. Specific microRNAs (miRNAs), small non-coding RNAs that function as posttranscriptional regulators of gene expression, were repeatedly proved to play key roles in the pathogenesis of these diseases. This pilot study aimed to analyze four selected miRNAs in esophageal tissues from healthy controls (HC) and patients with reflux esophagitis (RE)/BE/EAC, as well as to compare expression at the site of Barrett's mucosa/adenocarcinoma and healthy esophageal tissue outside the area of the main pathology in patients with BE/EAC. In this pilot study, 22 individuals (3 HC, 8 RE, 5 BE, 6 EAC) were included and endoscopically examined. RNA was isolated from the fresh-frozen esophageal tissue (stored in the RNAlater™ Stabilization Solution −70°C) using the AllPrep DNA/RNA/miRNA Universal Kit. Subsequent RT-qPCR analysis was performed using selected TaqMan MicroRNA Assays for miR-21, miR-34a, miR-196a, miR-196b, and endogenous control (RNU44). While the expression of miR-21 in the esophageal tissue with the main pathology was decreased in BE and EAC patients in comparison to the group of HC and RE patients (p=0.01), the expression of miR-196a was increased in the BE and EAC patients (p<0.01). Correlations between those miRNAs expression in tissue and severity of diagnosis were observed (p<0.05). In addition, miR-196a was significantly more expressed at the site with the main pathology than in paired adjacent esophageal tissue in BE and EAC patients (p<0.01). In conclusion, our pilot results showed that miR-196a, which regulates the proliferation, invasion, and migration (and was previously associated with esophageal squamous cell carcinoma and marked as a potential therapeutic target), could be a diagnostic tissue biomarker for BE and EAC as well.

Keywords: microRNA, barrett´s esophagus, esophageal adenocarcinoma, biomarker

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Authors: Zimu Li, Zheng Wan

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The Suez Canal plays an important role in global shipping networks and is one of the most frequently used waterways in the world. The 2021 canal obstruction by ship Ever Given in March 2021, however, completed blocked the Suez Canal for a week and caused significant disruption to world trade. Therefore, it is very important to quantitatively analyze the impact of the accident on the robustness of the global shipping network. However, the current research on maritime transportation networks is usually limited to local or small-scale networks in a certain region. Based on the complex network theory, this study establishes a global shipping complex network covering 2713 nodes and 137830 edges by using the real trajectory data of the global marine transport ship automatic identification system in 2018. At the same time, two attack modes, deliberate (Suez Canal Blocking) and random, are defined to calculate the changes in network node degree, eccentricity, clustering coefficient, network density, network isolated nodes, betweenness centrality, and closeness centrality under the two attack modes, and quantitatively analyze the actual impact of Suez Canal Blocking on the robustness of global shipping network. The results of the network robustness analysis show that Suez Canal blocking was more destructive to the shipping network than random attacks of the same scale. The network connectivity and accessibility decreased significantly, and the decline decreased with the distance between the port and the canal, showing the phenomenon of distance attenuation. This study further analyzes the impact of the blocking of the Suez Canal on Chinese ports and finds that the blocking of the Suez Canal significantly interferes withChina's shipping network and seriously affects China's normal trade activities. Finally, the impact of the global supply chain is analyzed, and it is found that blocking the canal will seriously damage the normal operation of the global supply chain.

Keywords: global shipping networks, ship AIS trajectory data, main channel, complex network, eigenvalue change

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Authors: Feridun Demir, Pelin Okdem

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Polymers are versatile materials with many unique properties, such as low density, reasonable strength, flexibility, and easy processability. However, the mechanical properties of these materials are insufficient for many engineering applications. Therefore, there is a continuous search for new polymeric materials with improved properties. Polymeric nanocomposites are an advanced class of composite materials that have attracted great attention in both academic and industrial fields. Since nano-reinforcement materials are very small in size, they provide ultra-large interfacial area per volume between the nano-element and the polymer matrix. This allows the nano-reinforcement composites to exhibit enhanced toughness without compromising hardness or optical clarity. PPy and MWCNT/PPy nanocomposites were synthesized by the chemical oxidative polymerization method and the supercapacitor properties of the obtained nanocomposites were investigated. In addition, pure MWCNT was functionalized with acid (H₂SO₄/H₂O₂) and base (NH₄OH/H₂O₂) solutions at a ratio of 3:1 and a-MWCNT/d-PPy, and b-MWCNT/d-PPy nanocomposites were obtained. The homogeneous distribution of MWCNTs in the polypyrrole matrix and shell-core type morphological structures of the nanocomposites was observed with SEM images. It was observed with SEM, FTIR and XRD analyses that the functional groups formed by the functionalization of MWCNTs caused the MWCNTs to come together and partially agglomerate. It was found that the conductivity of the nanocomposites consisting of MWCNT and d-PPy was higher than that of pure d-PPy. CV, GCD and EIS results show that the use of a-MWCNT and b-MWCNTs in nanocomposites with low particle content positively affects the supercapacitor properties of the materials but negatively at high particle content. It was revealed that the functional MWCNT particles combined in nanocomposites with high particle content cause a decrease in the conductivity and distribution of ions in the electrodes and, thus, a decrease in their energy storage capacity.

Keywords: polypyrrole, multi-walled carbon nanotube (MWCNT), conducting polymer, chemical oxidative polymerization, nanocomposite, supercapacitor

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Authors: Talal Alsulaiman, Khaldoun Khashanah

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In this paper, we provided a literature survey on the artificial stock problem (ASM). The paper began by exploring the complexity of the stock market and the needs for ASM. ASM aims to investigate the link between individual behaviors (micro level) and financial market dynamics (macro level). The variety of patterns at the macro level is a function of the AFM complexity. The financial market system is a complex system where the relationship between the micro and macro level cannot be captured analytically. Computational approaches, such as simulation, are expected to comprehend this connection. Agent-based simulation is a simulation technique commonly used to build AFMs. The paper proceeds by discussing the components of the ASM. We consider the roles of behavioral finance (BF) alongside the traditionally risk-averse assumption in the construction of agent's attributes. Also, the influence of social networks in the developing of agents’ interactions is addressed. Network topologies such as a small world, distance-based, and scale-free networks may be utilized to outline economic collaborations. In addition, the primary methods for developing agents learning and adaptive abilities have been summarized. These incorporated approach such as Genetic Algorithm, Genetic Programming, Artificial neural network and Reinforcement Learning. In addition, the most common statistical properties (the stylized facts) of stock that are used for calibration and validation of ASM are discussed. Besides, we have reviewed the major related previous studies and categorize the utilized approaches as a part of these studies. Finally, research directions and potential research questions are argued. The research directions of ASM may focus on the macro level by analyzing the market dynamic or on the micro level by investigating the wealth distributions of the agents.

Keywords: artificial stock markets, market dynamics, bounded rationality, agent based simulation, learning, interaction, social networks

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

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

Keywords: radiotherapy, veterinary oncology, chemotherapy, osteosarcoma

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Authors: Denise Schrama, Claudia Raposo, Pedro Rodrigues

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Background: Food allergies are conducted by a hypersensitive response of the immune system. These allergies are a global concern for the public health. Consumption of fish is increasing worldwide as it is a healthy meat with high nutritional value. Unfortunately, fish can cause adverse immune-mediate reactions, affecting part of the population with higher incidence in children. β-parvalbumin, a small, highly conserved stable, calcium or magnesium binding muscle protein is the main fish allergen. In fish-allergic patients, cross-reactivity between different fish species exist due to recognition of highly identical protein regions. Enolases, aldolases, or fish gelatin are other identified fish allergens in some fish species. With no available cure for fish allergies, clinical management is only based on an avoidance diet aiming at the total exclusion of offending food. Methods: Mediterranean fish (S. aurata and D. labrax) were fed specifically designed diets, enriched in components that target the expression or inactivation of parvalbumin (creatine and EDTA, respectively). After 90 days fish were sampled and biological tissues were excised. Proteomics was used to access fish allergens characterization and expression in muscle while IgE assays to confirm the lower allergenic potential are conducted in patients with history of fish allergies. Fish welfare and quality of flesh were established with biochemical, texture and sensorial analysis. Results: Fish welfare shows no major impact between diets. In case of creatine supplementation in D. labrax proteomic analysis show a slight decrease in parvalbumin expression. No accumulation of this compound was found in muscle. For EDTA supplementation in S. aurata IgE assay show a slight decrease in allergenicity when using sera of fish allergic patients. Conclusion: Supplementation with these two compounds seems to change slightly the allergenicity of the two mean Mediterranean species.

Keywords: fish allergies, fish nutrition, proteomics, aquaculture

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Authors: Yimeng Zhang

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Major depressive disorder (MDD) is a prevalent mental health condition with a substantial economic impact and limited treatment options. Acupuncture has gained attention as a promising non-pharmacological intervention for alleviating depressive symptoms. However, its mechanisms and clinical effectiveness remain incompletely understood. This meta-analysis aims to (1) synthesize existing evidence on the mechanisms and clinical effectiveness of acupuncture for depression and (2) compare these findings with pharmacological interventions, providing insights for future research. Evidence from animal models and clinical studies indicates that acupuncture may enhance hippocampal and network neuroplasticity and reduce brain inflammation, potentially alleviating depressive disorders. Clinical studies suggest that acupuncture can effectively relieve primary depression, particularly in milder cases, and is beneficial in managing post-stroke depression, pain-related depression, and postpartum depression, both as a standalone and adjunctive treatment. Notably, combining acupuncture with antidepressant pharmacotherapy appears to enhance treatment outcomes and reduce medication side effects, addressing a critical issue in conventional drug therapy's high dropout rates. This meta-analysis, encompassing 12 studies and 710 participants, draws data from eight digital databases (PubMed, EMBASE, Web of Science, EBSCOhost, CNKI, CBM, Wangfang, and CQVIP) covering the period from 2012 to 2022. Utilizing Stata software 15.0, the meta-analysis employed random-effects and fixed-effects models to assess the distribution of depression in Traditional Chinese Medicine (TCM). The results underscore the substantial evidence supporting acupuncture's beneficial effects on depression. However, the small sample sizes of many clinical trials raise concerns about the generalizability of the findings, indicating a need for further research to validate these outcomes and optimize acupuncture's role in treating depression.

Keywords: Chinese medicine, acupuncture, depression, meta-analysis

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Authors: Axel Mancebo, Ana M. Bada, Angel Casacó, Bárbara González, Avelina León, María E. Arteaga, Consuelo González, Belinda Sánchez, Adriana Carr, Nuris Ledón, Arianna Iglesias

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Despite the many preventive and therapeutic modalities aimed at curing cancer, it remains as a serious world health problem. Promising recent developments suggest that cancer immunotherapy may be the next great hope for cancer treatment. EGFRs are receptor tyrosine kinases and it is considered an important therapeutic target related with tumor progression, and several types of molecular therapies, including monoclonal antibodies, small molecules, and vaccines, have been developed to target the HER family of receptors. On the other hand, gangliosides are membrane glycosphingolipids that contain two variants of sialic acid, the N-acetylated (NeuAc) and the N-glycolylated (NeuGc) variant. The high expression of this antigen-specific molecule has been associated with malignant tumor progression and immunosuppressive mechanisms, so ganglioside could be considered as the target for cancer immunotherapy. We have been working for several years in the safety evaluation of cancer vaccines targeting these two systems, the EGF receptor and ganglioside. We presented in this work results of repeated dose toxicity studies performed in Sprague Dawley rats and Cynomolgus monkeys, including clinical observations, body weight and rectal temperature measuring, clinical pathology analysis, gross necropsy and histological examination in rodent studies, and immunological evaluation. Immunizations were capable of inducing mainly inflammatory effects at the injection site, with findings largely attributable to the adjuvants used and probably enhanced by the immunological properties of the antigens. In general, these vaccines were shown to be well tolerated, and these studies in relevant species allow treating cancer patients with tumors during long periods with relative weight safety margin.

Keywords: cancer vaccines, safety, toxicology, rats, non human primates

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Authors: Lauren C. Porter, Andrew Curtis, Eric Jefferis, Susanne Mitchell

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A wealth of research has been generated examining the variation in crime across neighborhoods. However, there is also a striking degree of crime concentration within neighborhoods. A number of studies show that a small percentage of street segments, intersections, or addresses account for a large portion of crime. Not surprisingly, a focus on these crime hot spots can be an effective strategy for reducing community level crime and related ills, such as health problems. However, research is also limited in an important respect. Studies tend to use official data to identify hot spots, such as 911 calls or calls for service. While the use of call data may be more representative of the actual level and distribution of crime than some other official measures (e.g. arrest data), call data still suffer from the 'dark figure of crime.' That is, there is most certainly a degree of error between crimes that occur versus crimes that are reported to the police. In this study, we present an alternative method of identifying crime hot spots, that does not rely on official data. In doing so, we highlight the potential utility of neighborhood-insiders to identify and understand crime dynamics within geographic spaces. Specifically, we use spatial video and geo-narratives to record the crime insights of 36 police, ex-offenders, and residents of a high crime neighborhood in northeast Ohio. Spatial mentions of crime are mapped to identify participant-identified hot spots, and these are juxtaposed with calls for service (CFS) data. While there are bound to be differences between these two sources of data, we find that one location, in particular, a corner store, emerges as a hot spot for all three groups of participants. Yet it does not emerge when we examine CFS data. A closer examination of the space around this corner store and a qualitative analysis of narrative data reveal important clues as to why this store may indeed be a hot spot, but not generate disproportionate calls to the police. In short, our results suggest that researchers who rely solely on official data to study crime hot spots may risk missing some of the most dangerous places.

Keywords: crime, narrative, video, neighborhood

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Authors: V. Pentland, S. Spilsbury, A. Biswas, M. F. Mottola, S. Paplinskie, M. S. Mitchell

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Postpartum depression (PPD) is a form of major depressive disorder that afflicts 10–22% of mothers worldwide. Rising demands for traditional PPD treatment options (e.g., psychiatry), especially in the context of the COVID-19 pandemic, are increasingly difficult to meet. More accessible treatment options (e.g., walking) are needed. The objective of this review is to determine the impact of walking on PPD severity. A structured search of seven electronic databases for randomised controlled trials published between 2000 and July 29, 2021, was completed. Studies were included if walking was the sole or primary aerobic exercise modality. A random-effects meta-analysis was conducted for studies reporting PPD symptoms measured using a clinically validated tool. A simple count of positive/null effect studies was undertaken as part of a narrative summary. Five studies involving 242 participants were included (mean age=~28.9 years; 100% with mild-to-moderate depression). Interventions were 12 (n=4) and 24 (n=1) weeks long. Each assessed PPD severity using the Edinburgh Postnatal Depression Scale (EPDS) and was included in the meta-analysis. The pooled effect estimate suggests that relative to controls, walking yielded clinically significant decreases in mean EPDS scores from baseline to intervention end (pooled MD=-4.01; 95% CI:-7.18 to -0.84, I2=86%). The narrative summary provides preliminary evidence that walking-only, supervised, and group-based interventions, including 90-120+ minutes/week of moderate-intensity walking, may produce greater EPDS reductions. While limited by a relatively small number of included studies, pooled effect estimates suggest walking may help mothers manage PPD. This is the first time walking as a treatment for PPD, an exercise modality that uniquely addresses many barriers faced by mothers has been summarized in a systematic way. Trial registration: PROSPERO (CRD42020197521) on August 16th, 2020

Keywords: postpartum, exercise, depression, walking

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Authors: Doua AlSaad, Ahmed Awaisu, Samah Elsalem, Palli Valapila Abdulrouf, Binny Thomas, Moza AlHail

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Background: It has been suggested that pyridoxine has an anti-lactogenic effect. Studies of the efficacy of pyridoxine in suppressing lactation have reported conflicting results. The aim of this review is to evaluate the effectiveness and safety of high-dose pyridoxine in postpartum lactation inhibition. Methods: This systematic review included published trials that compared the efficacy and/or safety of pyridoxine to placebo or to other pharmacological agents for the inhibition of postpartum lactation. We searched PubMed, Embase, ScienceDirect, CINAHL, AMED, the Cochrane library, and the clinical trials registry to identify relevant literature. No limit was imposed on the year of publication of the studies, and the review included studies published until 15 January 2016. Two reviewers independently extracted data and assessed the risk of bias. Results: Seven studies were included, with a total of 1155 women, of which 471 women received pyridoxine. Three studies were randomized controlled trials, while the remaining four studies were non-randomized controlled trials. All of the included studies were relatively small (n = 18 – 482). The studies compared pyridoxine with placebo, bromocriptine, and/or stilboestrol. Pyridoxine was given orally, with a total daily dose of 450 – 600 mg for 5 to 7 days. Two trials (n = 349 participants) indicated that pyridoxine was effective in inhibiting lactation in approximately 95% of the enrolled patients. All other studies failed to demonstrate pyridoxine efficacy through either clinical assessment or prolactin level measurements. Pyridoxine safety was assessed by two trials in which no serious untoward side-effects were reported. Overall, the risk of bias for most of the studies was low to moderate. Conclusion: Current evidence supporting the effectiveness of high dose pyridoxine in the inhibition of postpartum lactation is inconsistent and insufficient. Larger randomized trials are needed to confirm the efficacy of pyridoxine in postpartum lactation inhibition. Acknowledgment: This review received a grant from the Medical Research Center of Hamad Medical Corporation in Qatar (grant number: 15100/15).

Keywords: pyridoxine, safety, effectiveness, lactation inhibition

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Authors: Nahid Hassanshahi, Ayoub Karimi-Jashni, Nasser Talebbeydokhti

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Due to the economic and environmental benefits of producing less waste, the US Environmental Protection Agency (EPA) introduces source reduction as one of the most important means to deal with the problems caused by increased landfills and pollution. Waste reduction involves all waste management methods, including source reduction, recycling, and composting, which reduce waste flow to landfills or other disposal facilities. Source reduction of waste can be studied from two perspectives: avoiding waste production, or reducing per capita waste production, and waste deviation that indicates the reduction of waste transfer to landfills. The present paper has investigated home composting as a managerial solution for reduction of waste transfer to landfills. Home composting has many benefits. The use of household waste for the production of compost will result in a much smaller amount of waste being sent to landfills, which in turn will reduce the costs of waste collection, transportation and burial. Reducing the volume of waste for disposal and using them for the production of compost and plant fertilizer might help to recycle the material in a shorter time and to use them effectively in order to preserve the environment and reduce contamination. Producing compost in a home-based manner requires very small piece of land for preparation and recycling compared with other methods. The final product of home-made compost is valuable and helps to grow crops and garden plants. It is also used for modifying the soil structure and maintaining its moisture. The food that is transferred to landfills will spoil and produce leachate after a while. It will also release methane and greenhouse gases. But, composting these materials at home is the best way to manage degradable materials, use them efficiently and reduce environmental pollution. Studies have shown that the benefits of the sale of produced compost and the reduced costs of collecting, transporting, and burying waste can well be responsive to the costs of purchasing home compost machine and the cost of related trainings. Moreover, the process of producing home compost may be profitable within 4 to 5 years and as a result, it will have a major role in reducing waste management.

Keywords: compost, home compost, reducing waste, waste management

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Authors: Aida Safiera, Andika Dwi Rubyantoro, Muhammad Bagus Prakasa

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Indonesia’s needs of diesel oil each year are increasing and getting urge. However, that problems are not supported by the amount of oil production that still low and also influenced by the fact of oil reserve is reduced. Because of that, the government prefers to import from other countries than fulfill the needs of diesel. To anticipate that problem, development of fuel based on renewable diesel is started. Renewable diesel is renewable alternative fuel that is hydrocarbon derivative from decarbonylation of non-edible oil. Indonesia is rich with natural resources, including nyamplung oil (Calophyllum inophyllum oil) and zeolite. Nyamplung oil (Calophyllum inophyllum oil) has many stearic acids which are useful on renewable diesel synthesis meanwhile zeolite is cheap. Zeolite is many used on high temperature reaction and cracking process on oil industry. Zeolite also has advantages which are a high crystallization, surface area and pores. In this research, the main focus that becomes our attention is on preparation and characterization of metal nanocrystal. Active site that used in this research is Nickel Molybdenum (NiMo). The advantage of nanocrystal with nano scale is having larger surface area. The synthesis of metal nanocrystal will be done with conventional preparation modification method that is called simple heating. Simple heating method is a metal nanocrystal synthesis method using continuous media which is polymer liquid. This method is a simple method and produces a small particles size in a short time. Influence of metal nanocrystal growth on this method is the heating profile. On the synthesis of nanocrystal, the manipulated variables are temperature and calcination time. Results to achieve from this research are diameter size on nano scale (< 100 nm) and uniform size without any agglomeration. Besides that, the conversion of synthesis of renewable diesel is high and has an equal specification with petroleum diesel. Catalyst activities are tested by FT-IR and GC-TCD on decarbonylation process with a pressure 15 bar and temperature 375 °C. The highest conversion from this reaction is 35% with selectivity around 43%.

Keywords: renewable diesel, simple heating, metal nanocrystal, NiMo, zeolite

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Authors: Matthew P. Mancini, Vincent Ribiere

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Today’s workers face more numerous and complex challenges and are required to be increasingly interdependent and faster learners. Knowledge sharing activities between people have been understood as a significant element affecting organizational innovation performance. While they do have the potential to spark cognitive conflict, disagreement is important from an organizational perspective because it can stimulate the development of new ideas and perhaps pave the way for creativity, innovation, and competitive advantage. How teams cope with the cognitive conflict dimension of knowledge sharing and the associated interpersonal risk is what captures our attention. Specifically, assertive conflict management strategies have a positive influence on knowledge sharing behaviors, and team psychological safety has a positive influence on knowledge sharing intention. This paper focuses on explaining the impact that these factors have on the shaping of an individual’s decision to engage or not in knowledge sharing activities. To accomplish this, we performed an empirical analysis on the results of our questionnaire about knowledge-sharing related conflict management and team psychological safety in pharmaceutical enterprises located in North America, Europe, and Asia. First, univariate analysis is used to characterize behavior regarding conflict management strategy into two groups. Group 1 presents assertive conflict management strategies and group 2 shows unassertive ones. Then, by using SEM methodology, we evaluated the relationships between them and the team psychological safety construct with the knowledge sharing process. The results of the SEM analysis show that assertive conflict management strategies affect the knowledge sharing process the most with a small, but significant effect from team psychological safety. The findings suggest that assertive conflict management strategies are just as important as knowledge sharing intentions for encouraging knowledge sharing behavior. This paper provides clear insights into how employees manage the sharing of their knowledge in the face of conflict and interpersonal risk and the relative importance of these factors in sustaining productive knowledge sharing activities.

Keywords: cognitive dissonance, conflict management, knowledge sharing, organizational behavior, psychological safety

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Authors: Luciano Tarantino, Emanuele Balzano, Aurelio Nasto

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S.R. 53 years. January 2009: HCV-related cirrhosis, Child-Pugh A5 class, EGDS no aesophageal Varices. No important comorbidities. Treated with PEG-IFN+Ribavirin (march-november 2009) with subsequent sustained virologic response. HCVRNA absent overtime. October 2016 :CT detected small HCC nodule in the VIII segment (diam.=12 mm). Treated with US guided RF-ablation. November 2016 CT: complete necrosis. Unfortunately, the patient dropped out US and CT follow-up controls.September 2018: asthenia and weight loss. CT showed a large tumor infiltrating V-VII-VI segments and complete PVTT of right portal vein and its branches . Surgical Consultation excluded indication to Liver resection and OLT . 23 october 2018: ECT of a large peri-hilar area of the tumor including the PVTT. 1 and 3 months post-treatment CT showed complete necrosis and retraction of the thrombus and residual viable tumor in the peripheral portion of the right lobe . Therefor, the patient was reevaluated for OLT and considered eligible in waiting list . March 2019: CT showed no perihilar or portal vein recurrence and distant progression in the right lobe . March 2019 : Trans-arterial-Radio-therapy (TARE) of the right lobe. Post-treatment CT demonstrated no perihilar or portal vein recurrence and extensive necrosis of the residual tumor . December 2019: CT demonstrated several recurrences of HCC infiltrating the VI and VII segment . Howewer no recurrence was observed at hepatic hilum and in portal vessels . Therefore, on February 2020 the patient received OLT. At 44 months follow-up, no complication or recurrence or liver disfunction have been observed.

Keywords: hepatocellular carcinoma, portal vein tumor thrombosis, interventional ultrasound, liver tumor ablation, liver transplantation

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Authors: Maha Bakakri, Rachid Tadili, Fatiha Lemmini

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Morocco is one of the few countries that have kept their traditional crafts, despite the competition of modern industry and its impact on manual labor. Therefore the optimization of energy consumption becomes an obligation and this is the purpose of this document. In this work we present some characteristics of the furnace studied, its operating principle and the experimental measurements of the evolutions of the temperatures inside and outside the walls of the furnace, values which will be used later in the calculation of its thermal losses. In order to determine the major source of the thermal losses of the furnace we have established the heat balance of the furnace. The energy consumed, the useful energy and the thermal losses through the walls and the chimney of the furnace are calculated thanks to the experimental measurements which we realized for several firings. The results show that the energy consumption of this type of furnace is very high and that the main source of energy loss is mainly due to the heat losses of the combustion gases that escape from the furnace by the chimney while the losses through the walls are relatively small. it have opted for energy recovery as a solution where we can recover some of the heat lost through the use of a heat exchanger system using a double tube introduced into the flue gas exhaust stack compartment. The study on the heat recovery system is presented and the heat balance inside the exchanger is established. In this paper we also present the numerical modeling of heat transfer by conduction through the walls of the furnace. A numerical model has been established based on the finite volume method and the double scan method. It makes it possible to determine the temperature profile of the furnace and thus to calculate the thermal losses of its walls and to deduce the thermal losses due to the combustion gases. Validation of the model is done using the experimental measurements carried out on the furnace. The results obtained in this work, relating to the energy consumed during the operation of the furnace are important and are part of the energy efficiency framework that has become a key element in global energy policies. It is the fastest and cheapest way to solve energy, environmental and economic security problems.

Keywords: energy cunsumption, energy recovery, modeling, energy eficiency

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Authors: Afsaneh Mohammadnejad, Marianne Nygaard, Jan Baumbach, Shuxia Li, Weilong Li, Jesper Lund, Jacob v. B. Hjelmborg, Lene Christensen, Qihua Tan

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Cognitive impairment in the elderly is a key issue affecting the quality of life. Despite a strong genetic background in cognition, only a limited number of single nucleotide polymorphisms (SNPs) have been found. These explain a small proportion of the genetic component of cognitive function, thus leaving a large proportion unaccounted for. We hypothesize that one reason for this missing heritability is the misspecified modeling in data analysis concerning phenotype distribution as well as the relationship between SNP dosage and the phenotype of interest. In an attempt to overcome these issues, we introduced a model-free method based on the generalized correlation coefficient (GCC) in a genome-wide association study (GWAS) of cognitive function in twin samples and compared its performance with two popular linear regression models. The GCC-based GWAS identified two genome-wide significant (P-value < 5e-8) SNPs; rs2904650 near ZDHHC2 on chromosome 8 and rs111256489 near CD6 on chromosome 11. The kinship model also detected two genome-wide significant SNPs, rs112169253 on chromosome 4 and rs17417920 on chromosome 7, whereas no genome-wide significant SNPs were found by the linear mixed model (LME). Compared to the linear models, more meaningful biological pathways like GABA receptor activation, ion channel transport, neuroactive ligand-receptor interaction, and the renin-angiotensin system were found to be enriched by SNPs from GCC. The GCC model outperformed the linear regression models by identifying more genome-wide significant genetic variants and more meaningful biological pathways related to cognitive function. Moreover, GCC-based GWAS was robust in handling genetically related twin samples, which is an important feature in handling genetic confounding in association studies.

Keywords: cognition, generalized correlation coefficient, GWAS, twins

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

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

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

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Authors: Chetna Khandelwal

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This research aims to study the contentions that Farm Animal Sanctuaries pose to human-animal relationships in modernity, which have developed as a result of globalisation of the meat industry and advancements in technology. The sociological history of human-animal relationships in farming is contextualised in order to set a foundation for the follow-up examination of challenges to existing human-(farm)animal relationships by Farm Animal Sanctuaries. The methodology was influenced by relativism, and the method involved three semi-structured small-group interviews, conducted at locations of sanctuaries. The sample was chosen through purposive sampling and varied by location and size of the sanctuary. Data collected were transcribed and qualitatively coded to generate themes. Findings revealed that sanctuary contentions to established human-animal relationships by factory farming could be divided into 4 broad categories – Revealing horrors of factory farming (involving uncovering power relations in agribusiness); transforming relationships with animals (including letting them emotionally heal in accordance with their individual personalities and treating them as partial-pets); educating the public regarding welfare conditions in factory farms as well as animal sentience through practical experience or positive imagery of farm animals, and addressing retaliation made by agribusiness in the form of technologies or discursive strategies. Hence, this research concludes that The human-animal relationship in current times has been characterised by – (ideological and physical) distance from farm animals, commodification due to increased chasing of profits over welfare and exploitation using technological advancements, creating unequal power dynamics that rid animals of any agency. Challenges to this relationship can be influenced by local populations around the sanctuary but not so dependent upon the size of it. This research can benefit from further academic exploration into farm animal sanctuaries and their role in feminist animal rights activism to enrich the ongoing fight against intensive farming.

Keywords: animal rights, factory farming, farm animal sanctuaries, human-animal relationships

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Authors: Vakhtang Charaia, Mariam Lashkhi

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Foreign direct investment (FDI) plays a vital role in global business. It provides firms with new markets and advertising channels, cheaper production facilities, admission to new technology, products, skills and financing. FDI can provide a recipient country/company with a source of new technologies, capital, practice, products, management skills, and as such can be a powerful drive for economic development. It is one of the key elements of stable economic development in many countries, especially in developing ones. Therefore the size of FDI inflow is one of the most crustal factors for economic perfection in small economy countries (like, Georgia), while most of developed ones are net exporters of FDI. Since, FDI provides firms with new markets; admission to new technologies, products and management skills; marketing channels; cheaper production facilities, and financing opportunities. It plays a significant role in Georgian economic development. Increasing FDI inflows from all over the world to Georgia in last decade was achieved with the outstanding reforms managed by the Georgian government. However, such important phenomenon as world financial crisis and Georgian-Russian war put its consequence on the over amount of FDI inflow in Georgia in the last years. It is important to mention that the biggest investor region for Georgia is EU, which is interested in Georgia not only from the economic points of view but from political. The case studies from main EU investor countries show that Georgia has a big potential of investment in different areas, such as; financial sector, energy, construction, tourism industry, transport and communications. Moreover, signing of Association Agreement between Georgia and EU will further boost all the fields of economy in Georgia in both short and long terms. It will attract more investments from different countries and especially from EU. The last, but not least important issue is the calculation of annual FDI inflow to Georgia, which it is calculated differently by different organizations, based on different methodologies, but what is more important is that all of them show significant increase of FDI in last decade, which gives a positive signal to investors and underlines necessity of further improvement of investment climate in the same direction.

Keywords: foreign direct investment (FDI), Georgia, investment development path, investment climate

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Authors: Adel Alblihy, Reem Ali, Mashael Algethami, Ahmed Shoqafi, Michael S. Toss, Juliette Brownlie, Natalie J. Tatum, Ian Hickson, Paloma Ordonez Moran, Anna Grabowska, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan

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Platinum resistance is a clinical challenge in ovarian cancer. Platinating agents induce DNA damage which activate Mre11 nuclease directed DNA damage signalling and response (DDR). Upregulation of DDR may promote chemotherapy resistance. Here we have comprehensively evaluated Mre11 in epithelial ovarian cancers. In clinical cohort that received platinum- based chemotherapy (n=331), Mre11 protein overexpression was associated with aggressive phenotype and poor progression free survival (PFS) (p=0.002). In the ovarian cancer genome atlas (TCGA) cohort (n=498), Mre11 gene amplification was observed in a subset of serous tumours (5%) which correlated highly with Mre11 mRNA levels (p<0.0001). Altered Mre11 levels was linked with genome wide alterations that can influence platinum sensitivity. At the transcriptomic level (n=1259), Mre11 overexpression was associated with poor PFS (p=0.003). ROC analysis showed an area under the curve (AUC) of 0.642 for response to platinum-based chemotherapy. Pre-clinically, Mre11 depletion by gene knock down or blockade by small molecule inhibitor (Mirin) reversed platinum resistance in ovarian cancer cells and in 3D spheroid models. Importantly, Mre11 inhibition was synthetically lethal in platinum sensitive XRCC1 deficient ovarian cancer cells and 3D-spheroids. Selective cytotoxicity was associated with DNA double strand break (DSB) accumulation, S-phase cell cycle arrest and increased apoptosis. We conclude that pharmaceutical development of Mre11 inhibitors is a viable clinical strategy for platinum sensitization and synthetic lethality in ovarian cancer.

Keywords: MRE11; XRCC1, ovarian cancer, platinum sensitization, synthetic lethality

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Authors: Ali Al Orf, Khawaja Bilal Waheed

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Background and objective: Joubert syndrome (JS) is a rare, autosomal-recessive condition. Early recognition is important for management and counseling. Magnetic resonance imaging (MRI) can help in diagnosis. Therefore, we sought to evaluate clinical presentation and MRI findings in Joubert syndrome and related disorders. Method: A retrospective review of genetically proven cases of Joubert syndromes and related disorders was reviewed for their clinical presentation, demographic information, and magnetic resonance imaging findings in a period of the last 10 years. Two radiologists documented magnetic resonance imaging (MRI) findings. The presence of hypoplasia of the cerebellar vermis with hypoplasia of the superior cerebellar peduncle resembling the “Molar Tooth Sign” in the mid-brain was documented. Genetic testing results were collected to label genes linked to the diagnoses. Results: Out of 12 genetically proven JS cases, most were females (9/12), and nearly all presented with hypotonia, ataxia, developmental delay, intellectual impairment, and speech disorders. 5/12 children presented at age of 1 or below. The molar tooth sign was seen in 10/12 cases. Two cases were associated with other brain findings. Most of the cases were found associated with consanguineous marriage Conclusion and discussion: The molar tooth sign is a frequent and reliable sign of JS and related disorders. Genes related to defective cilia result in malfunctioning in the retina, renal tubule, and neural cell migration, thus producing heterogeneous syndrome complexes known as “ciliopathies.” Other ciliopathies like Senior-Loken syndrome, Bardet Biedl syndrome, and isolated nephronophthisis must be considered as the differential diagnosis of JS. The main imaging findings are the partial or complete absence of the cerebellar vermis, hypoplastic cerebellar peduncles (giving MTS), and (bat-wing appearance) fourth ventricular deformity. LimitationsSingle-center, small sample size, and retrospective nature of the study were a few of the study limitations.

Keywords: Joubart syndrome, magnetic resonance imaging, molar tooth sign, hypotonia

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Authors: A. Kachmazova, A. Shadiev, Y. Teterin, P. Yartcev

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Introduction: Biliary calculi disease (LCS) still occupies the leading position among urgent diseases of the abdominal cavity, manifesting itself from asymptomatic course to life-threatening states. Nowadays arsenal of diagnostic methods for choledocholithiasis is quite wide: ultrasound, hepatobiliscintigraphy (HBSG), magnetic resonance imaging (MRI), endoscopic retrograde cholangiography (ERCP). Among them, transabdominal ultrasound (TA ultrasound) is the most accessible and routine diagnostic method. Nowadays ERCG is the "gold" standard in diagnosis and one-stage treatment of biliary tract obstruction. However, transpapillary techniques are accompanied by serious postoperative complications (postmanipulative pancreatitis (3-5%), endoscopic papillosphincterotomy bleeding (2%), cholangitis (1%)), the lethality being 0.4%. GBSG and MRI are also quite informative methods in the diagnosis of choledocholithiasis. Small size of concrements, their localization in intrapancreatic and retroduodenal part of common bile duct significantly reduces informativity of all diagnostic methods described above, that demands additional studying of this problem. Materials and Methods: 890 patients with the diagnosis of cholelithiasis (calculous cholecystitis) were admitted to the Sklifosovsky Scientific Research Institute of Hospital Medicine in the period from August, 2020 to June, 2021. Of them 115 people with mechanical jaundice caused by concrements in bile ducts. Results: Final EUS diagnosis was made in all patients (100,0%). In all patients in whom choledocholithiasis diagnosis was revealed or confirmed after EUS, ERCP was performed urgently (within two days from the moment of its detection) as the X-ray operation room was provided; it confirmed the presence of concrements. All stones were removed by lithoextraction using Dormia basket. The postoperative period in these patients had no complications. Conclusions: EUS is the most informative and safe diagnostic method, which allows to detect choledocholithiasis in patients with discrepancies between clinical-laboratory and instrumental methods of diagnosis in shortest time, that in its turn will help to decide promptly on the further tactics of patient treatment. We consider it reasonable to include EUS in the diagnostic algorithm for choledocholithiasis. Disclosure: Nothing to disclose.

Keywords: endoscopic ultrasonography, choledocholithiasis, common bile duct, concrement, ERCP

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