Search results for: continuous damage

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

Abstract:

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: Syed Dawood Md. Taimur, Md. Hasanur Rahman, Syeda Fahmida Afrin, Farzana Islam

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The concept of myocardial injury, although first recognized from animal studies, is now recognized as a clinical phenomenon that may result in microvascular damage, no-reflow phenomenon, myocardial stunning, myocardial hibernation and ischemic preconditioning. The final consequence of this event is left ventricular (LV) systolic dysfunction leading to increased morbidity and mortality. The typical clinical case of reperfusion injury occurs in acute myocardial infarction (MI) with ST segment elevation in which an occlusion of a major epicardial coronary artery is followed by recanalization of the artery. This may occur either spontaneously or by means of thrombolysis and/or by primary percutaneous coronary intervention (PCI) with efficient platelet inhibition by aspirin (acetylsalicylic acid), clopidogrel and glycoprotein IIb/IIIa inhibitors. In recent years, percutaneous coronary intervention (PCI) has become a well-established technique for the treatment of coronary artery disease. PCI improves symptoms in patients with coronary artery disease and it has been increasing the safety of procedures. However, peri- and post-procedural myocardial injury, including angiographical slow coronary flow, microvascular embolization, and elevated levels of cardiac enzyme, such as creatine kinase and troponin-T and -I, has also been reported even in elective cases. Furthermore, myocardial reperfusion injury at the beginning of myocardial reperfusion, which causes tissue damage and cardiac dysfunction, may occur in cases of the acute coronary syndrome. Because patients with myocardial injury is related to larger myocardial infarction and have a worse long-term prognosis than those without myocardial injury, it is important to prevent myocardial injury during and/or after PCI in patients with coronary artery disease. To date, many studies have demonstrated that adjunctive pharmacological treatment suppresses myocardial injury and increases coronary blood flow during PCI procedures. In this review, we highlight the usefulness of pharmacological treatment in combination with PCI in attenuating myocardial injury in patients with coronary artery disease.

Keywords: coronary artery disease, percutaneous coronary intervention, myocardial injury, pharmacology

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Authors: Darren A. Whitaker, Dan Palmer, Jens Wesholowski, James Flaherty, John Mack, Ahmad B. Albadarin, Gavin Walker

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Traditional mechanosynthesis has been performed by either ball milling or manual grinding. However, neither of these techniques allow the easy application of process control. The temperature may change unpredictably due to friction in the process. Hence the amount of energy transferred to the reactants is intrinsically non-uniform. Recently, it has been shown that the use of Twin-Screw extrusion (TSE) can overcome these limitations. Additionally, TSE enables a platform for continuous synthesis or manufacturing as it is an open-ended process, with feedstocks at one end and product at the other. Several materials including metal-organic frameworks (MOFs), co-crystals and small organic molecules have been produced mechanochemically using TSE. The described advantages of TSE are offset by drawbacks such as increased process complexity (a large number of process parameters) and variation in feedstock flow impacting on product quality. To handle the above-mentioned drawbacks, this study utilizes UV-Vis spectrophotometry (InSpectroX, ColVisTec) as an online tool to gain real-time information about the quality of the product. Additionally, this is combined with real-time process information in an Advanced Process Control system (PharmaMV, Perceptive Engineering) allowing full supervision and control of the TSE process. Further, by characterizing the dynamic behavior of the TSE, a model predictive controller (MPC) can be employed to ensure the process remains under control when perturbed by external disturbances. Two reactions were studied; a Knoevenagel condensation reaction of barbituric acid and vanillin and, the direct amidation of hydroquinone by ammonium acetate to form N-Acetyl-para-aminophenol (APAP) commonly known as paracetamol. Both reactions could be carried out continuously using TSE, nuclear magnetic resonance (NMR) spectroscopy was used to confirm the percentage conversion of starting materials to product. This information was used to construct partial least squares (PLS) calibration models within the PharmaMV development system, which relates the percent conversion to product to the acquired UV-Vis spectrum. Once this was complete, the model was deployed within the PharmaMV Real-Time System to carry out automated optimization experiments to maximize the percentage conversion based on a set of process parameters in a design of experiments (DoE) style methodology. With the optimum set of process parameters established, a series of PRBS process response tests (i.e. Pseudo-Random Binary Sequences) around the optimum were conducted. The resultant dataset was used to build a statistical model and associated MPC. The controller maximizes product quality whilst ensuring the process remains at the optimum even as disturbances such as raw material variability are introduced into the system. To summarize, a combination of online spectral monitoring and advanced process control was used to develop a robust system for optimization and control of two TSE based mechanosynthetic processes.

Keywords: continuous synthesis, pharmaceutical, spectroscopy, advanced process control

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Authors: Xie Xiaobin, Zhang Yan, Shi Yipeng, Sun Wenying, Chen Shuang, Cai Zhipeng, Zhang Hong, Zhang Lixia, Xie Like

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Objective: The objective of this research is to compare the efficacy of the late in-situ surgical revision augmented with continuous infusion and needle revision on failed trabeculectomy blebs. Methods From December 2018 to December 2021, a prospective randomized controlled trial was performed on 44 glaucoma patients with failed bleb ≥ 6months with medically uncontrolled in Eye Hospital, China Academy of Chinese Medical Sciences. They were randomly divided into two groups. 22 eyes of 22 patients underwent the late in-situ surgical revision with continuous anterior chamber infusion in the study group, and 22 of 22 patients were treated with needle revision in the control group. Main outcome measures include preoperative and postoperative intraocular pressure (IOP), the number of anti-glaucoma medicines, the operation success rate, and the postoperative complications. Results The postoperative IOP values decreased significantly from the baseline in both groups (both P<0.05). IOP was significantly lower in the study group than in the control group at one week, 1, and 3 months postoperatively (all P<0.05). IOP reductions in the study group were substantially more prominent than in the control group at all postoperative time points (all P<0.05). The complete success rate in the study group was significantly higher than in the control group (71.4% vs. 33.3%, P<0.05), while the complete failure rate was significantly lower in the study group (0% vs. 28.5%, P<0.05). According to Cox’s proportional hazards regression analysis, high IOP at baseline was independently associated with increased risks of complete failure (adjusted hazard ratio=1.141, 95% confidence interval=1.021-1.276, P<0.05). There was no significant difference in the incidence of postoperative complications between the two groups (P>0.05). Conclusion: Both in-situ surgical and needle revision have acceptable success rates and safety for the late failed trabeculectomy blebs, while the former is likely to have a higher level of efficacy over the latter. Needle revision may be insufficient for eyes with low target IOP.

Keywords: glaucoma, trabeculectomy blebs, in-situ surgical revision, needle revision

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Authors: Anubha Kaushik, Raman Preet

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Distillery wastewater in the form of spent wash is a complex and strong industrial effluent, with high load of organic pollutants that may deplete dissolved oxygen on being discharged into aquatic systems and contaminate groundwater by leaching of pollutants, while untreated spent wash disposed on land acidifies the soil. Stringent legislative measures have therefore been framed in different countries for discharge standards of distillery effluent. Utilising the organic pollutants present in various types of wastes as food by mixed microbial populations is emerging as an eco-friendly approach in the recent years, in which complex organic matter is converted into simpler forms, and simultaneously useful gases are produced as renewable and clean energy sources. In the present study, wastewater from a rice bran based distillery has been used as the substrate in a dark fermenter, and native microbial consortium from the digester sludge has been used as the inoculum to treat the wastewater and produce hydrogen. After optimising the operational conditions in batch reactors, sequential batch mode and continuous flow stirred tank reactors were used to study the best operational conditions for enhanced and sustained hydrogen production and removal of pollutants. Since the rate of hydrogen production by the microbial consortium during dark fermentation is influenced by concentration of organic matter, pH and temperature, these operational conditions were optimised in batch mode studies. Maximum hydrogen production rate (347.87ml/L/d) was attained in 32h dark fermentation while a good proportion of COD also got removed from the wastewater. Slightly acidic initial pH seemed to favor biohydrogen production. In continuous stirred tank reactor, high H₂ production from distillery wastewater was obtained from a relatively shorter substrate retention time (SRT) of 48h and a moderate organic loading rate (OLR) of 172 g/l/d COD.

Keywords: distillery wastewater, hydrogen, microbial consortium, organic pollution, sludge

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Authors: Marinna Madrid, Nabiha Saklayen, Marinus Huber, Nicolas Vogel, Christos Boutopoulos, Michel Meunier, Eric Mazur

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Delivering material into cells is important for a diverse range of biological applications, including gene therapy, cellular engineering and imaging. We present a plasmonic substrate for delivering membrane-impermeable material into cells at high throughput and high efficiency while maintaining cell viability. The substrate fabrication is based on an affordable and fast colloidal self-assembly process. When illuminated with a femtosecond laser, the light interacts with the electrons at the surface of the metal substrate, creating localized surface plasmons that form bubbles via energy dissipation in the surrounding medium. These bubbles come into close contact with the cell membrane to form transient pores and enable entry of membrane-impermeable material via diffusion. We use fluorescence microscopy and flow cytometry to verify delivery of membrane-impermeable material into HeLa CCL-2 cells. We show delivery efficiency and cell viability data for a range of membrane-impermeable cargo, including dyes and biologically relevant material such as siRNA. We estimate the effective pore size by determining delivery efficiency for hard fluorescent spheres with diameters ranging from 20 nm to 2 um. To provide insight to the cell poration mechanism, we relate the poration data to pump-probe measurements of micro- and nano-bubble formation on the plasmonic substrate. Finally, we investigate substrate stability and reusability by using scanning electron microscopy (SEM) to inspect for damage on the substrate after laser treatment. SEM images show no visible damage. Our findings indicate that self-assembled plasmonic substrates are an affordable tool for high-throughput, high-efficiency delivery of material into mammalian cells.

Keywords: femtosecond laser, intracellular delivery, plasmonic, self-assembly

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Authors: Tuji Jemal Ahmed

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Fresh produce is an essential component of a healthy diet. However, it can also be a potential source of pathogenic microorganisms that can cause foodborne illnesses. Traditional disinfection methods, such as washing with water and chlorine, have limitations and may not effectively remove or inactivate all microorganisms. This has led to the development of alternative/new methods of fresh produce disinfection, including physical and chemical methods. In this paper, we explore the physical and chemical new methods of fresh produce disinfection, their advantages and disadvantages, and their suitability for different types of produce. Physical methods of disinfection, such as ultraviolet (UV) radiation and high-pressure processing (HPP), are crucial in ensuring the microbiological safety of fresh produce. UV radiation uses short-wavelength UV-C light to damage the DNA and RNA of microorganisms, and HPP applies high levels of pressure to fresh produce to reduce the microbial load. These physical methods are highly effective in killing a wide range of microorganisms, including bacteria, viruses, and fungi. However, they may not penetrate deep enough into the product to kill all microorganisms and can alter the sensory characteristics of the product. Chemical methods of disinfection, such as acidic electrolyzed water (AEW), ozone, and peroxyacetic acid (PAA), are also important in ensuring the microbiological safety of fresh produce. AEW uses a low concentration of hypochlorous acid and a high concentration of hydrogen ions to inactivate microorganisms, ozone uses ozone gas to damage the cell membranes and DNA of microorganisms, and PAA uses a combination of hydrogen peroxide and acetic acid to inactivate microorganisms. These chemical methods are highly effective in killing a wide range of microorganisms, but they may cause discoloration or changes in the texture and flavor of some products and may require specialized equipment and trained personnel to produce and apply. In conclusion, the selection of the most suitable method of fresh produce disinfection should take into consideration the type of product, the level of microbial contamination, the effectiveness of the method in reducing the microbial load, and any potential negative impacts on the sensory characteristics, nutritional composition, and safety of the produce.

Keywords: fresh produce, pathogenic microorganisms, foodborne illnesses, disinfection methods

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Authors: Visar Baxhuku, Halil Demolli, Alishukri Shkodra

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This paper presents the monitoring of vehicle movement, namely the developing of speed of vehicles during movement in a certain twist. The basic geometry data of twist are measured with the purpose of calculating the slide in border speed. During the research, measuring developed speed of passenger vehicles for the real conditions of the road surface, dry road with average damage, was realised. After setting values, the analysis was done in function security of movement in twist.

Keywords: critical sliding velocity, moving velocity, curve, passenger vehicles

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Authors: Yasmina Bendaali, Cristian Vaquero, Carlos Escott, Carmen González, Antonio Morata

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Consumer tendencies to healthy eating habits and request for organic beverages led to the production of new drinks from fruit juices as a source of nutrients and bioactive compounds. Grape juice is a rich source of sugars, organic acids, and phenolic compounds, which define its beneficial effect on health and the attractive sensory profile for consumers' choices (color, taste, flavor). Thus, grape juice was used as a source of sugars, avoiding the addition of sweeteners by diluting it with mineral water to obtain the sugar concentration recommended for isotonic drinks (6% to 8%) to provide energy during physical activities. In addition, phenolic compounds of grape juice are associated with many human health benefits, mainly antioxidant activity, which helps to prevent different diseases associated with oxidative stress, including cancers and cardiovascular and neurodegenerative diseases. Furthermore, physical exercise has been shown to increase the production of free radicals and other reactive oxygen species. Thus, athletes need to improve their antioxidant defense systems to prevent oxidative damage. Different studies have demonstrated the positive effect of grape juice consumption during physical activities, which improves antioxidant activity and performance, protects against oxidative damage, and reduces inflammation. Thus, the use of grape juice to develop isotonic drinks can provide isotonic drinks with antioxidant and biological activities in addition to their principal role of rehydration and replacement of minerals and carbohydrates during physical exercises. Moreover, attractive sensory characteristics, mainly color, which is provided by anthocyanin content, have a great contribution to making the drinks more natural and help to dispense the use of synthetic dyes in addition to the health benefits which will be a novel product in the field of healthy beverages responding on the demand of consumers for new, innovative, and healthy products.

Keywords: grape juice, isotonic, antioxidants, anthocyanins, natural, sport

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Authors: Lun Lou, Jintu Fan

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While personal protective equipment (PPE) prevents the healthcare personnel from exposing to harmful surroundings, it creates a barrier to the dissipation of body heat and perspiration, leading to severe heat stress during prolonged exposure, especially in hot environments. It has been found that most of the existed personal cooling strategies have limitations in achieving effective cooling performance with long duration and lightweight. This work aimed to develop a lightweight (<1.0 kg) and less expensive wearable air cooling and dehumidifying system (WCDS) that can be applied underneath the protective clothing and provide 50W mean cooling power for more than 5 hours at 35°C environmental temperature without compromising the protection of PPE. For the WCDS, blowers will be used to activate an internal air circulation inside the clothing microclimate, which doesn't interfere with the protection of PPE. An air cooling and dehumidifying chamber (ACMR) with a specific design will be developed to reduce the air temperature and humidity inside the protective clothing. Then the cooled and dried air will be supplied to upper chest and back areas through a branching tubing system for personal cooling. A detachable ice cooling unit will be applied from the outside of the PPE to extract heat from the clothing microclimate. This combination allows for convenient replacement of the cooling unit to refresh the cooling effect, which can realize a continuous cooling function without taking off the PPE or adding too much weight. A preliminary thermal manikin test showed that the WCDS was able to reduce the microclimate temperature inside the PPE averagely by about 8°C for 60 minutes when the environmental temperature was 28.0 °C and 33.5 °C, respectively. Replacing the ice cooling unit every hour can maintain this cooling effect, while the longest operation duration is determined by the battery of the blowers, which can last for about 6 hours. This unique design is especially helpful for the PPE users, such as health care workers in infectious and hot environments when continuous cooling and dehumidifying are needed, but the change of protective clothing may increase the risk of infection. The new WCDS will not only improve the thermal comfort of PPE users but can also extend their safe working duration.

Keywords: personal thermal management, heat stress, ppe, health care workers, wearable device

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Authors: Olga Kruzhkova, Irina Vorobyeva, Roman Porozov

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Vandalism is a common phenomenon, but its definition is still not clearly defined. In the public sense, vandalism is the blatant cases of pogroms in cemeteries, destruction of public places (regardless of whether these actions are authorized), damage to significant objects of culture and history (monuments, religious buildings). From a legal point of view, only such an act can be called vandalism, which is aimed at 'desecrating buildings or other structures, damaging property on public transport or in other public places'. The key here is the notion of public property that is being damaged. In addition, the principal is the semantics of messages, expressed in a kind of sign system (drawing, inscription, symbol), which initially threatens public order, the calmness of citizens, public morality. Because of this, the legal qualification of vandalism doesn’t include a sufficiently wide layer of environmental destructions that are common in modern urban space (graffiti and other damage to private property, broken shop windows, damage to entrances and elevator cabins), which in ordinary consciousness are seen as obvious facts of vandalism. At the same time, the understanding of vandalism from the position of psychology implies an appeal to the question of the limits of the activity of the subject of vandalism and his motivational basis. Also recently, the discourse on the positive meaning of some forms of vandalism (graffiti, street-art, etc.) has been activated. But there is no discussion of the role and significance of vandalism in public and individual life, although, like any socio-cultural and socio-psychological phenomenon, vandalism is not groundless and meaningless. Our aim of the study was to identify and describe the functions of vandalism as a socio-cultural and socio-psychological phenomenon of the life of the urban community, as well as personal determinants of its manifestations. The study was conducted in the spatial environment of the Russian megalopolis (Ekaterinburg) by photographing visual results of vandal acts (6217 photos) with subsequent trace-assessment and image content analysis, as well as diagnostics of personal characteristics and motivational basis of vandal activity of possible subjects of vandalism among youth. The results of the study allowed to identify the functions of vandalism at the socio-environmental and individual-subjective levels. The socio-environmental functions of vandalism include the signaling function, the function of preparing of social changes, the constructing function, and the function of managing public moods. The demonstrative-protest function, the response function, the refund function, and the self-expression function are assigned to the individual-subjective functions of vandalism. A two-dimensional model of vandal functions has been formed, where functions are distributed in the spaces 'construction reconstruction', 'emotional regulation/moral regulation'. It is noted that any function of vandal activity at the individual level becomes a kind of marker of 'points of tension' at the social and environmental level. Acknowledgment: The research was supported financially by Russian Science Foundation, (Project No. 17-18-01278).

Keywords: destruction, urban environment, vandal behavior, vandalism, vandalism functions

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Authors: Maria Angela Bedini, Fabio Bronzini

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The Italian experiences, positive and negative, of the post-earthquake are conditioned by long times and structural bureaucratic constraints, also motivated by the attempt to contain mafia infiltration and corruption. The transition from the operational phase of the emergency to the planning phase of the reconstruction project is thus hampered by a series of inefficiencies and delays, incompatible with the need for rapid recovery of the territories in crisis. In fact, intervening in areas affected by seismic events means at the same time associating the reconstruction plan with an urban and territorial rehabilitation project based on strategies and tools in which prevention and safety play a leading role in the regeneration of territories in crisis and the return of the population. On the contrary, the earthquakes that took place in Italy have instead further deprived the territories affected of the minimum requirements for habitability, in terms of accessibility and services, accentuating the depopulation process, already underway before the earthquake. The objective of this work is to address with implementing and programmatic tools the procedures and strategies to be put in place, today and in the future, in Italy and abroad, to face the challenge of the reconstruction of activities, sociality, services, risk mitigation: a protocol of operational intentions and firm points, open to a continuous updating and implementation. The methodology followed is that of the comparison in a synthetic form between the different Italian experiences of the post-earthquake, based on facts and not on intentions, to highlight elements of excellence or, on the contrary, damage. The main results obtained can be summarized in technical comparison cards on good and bad practices. With this comparison, we intend to make a concrete contribution to the reconstruction process, certainly not only related to the reconstruction of buildings but privileging the primary social and economic needs. In this context, the recent instrument applied in Italy of the strategic urban and territorial SUM (Minimal Urban Structure) and the strategic monitoring process become dynamic tools for supporting reconstruction. The conclusions establish, by points, a protocol of interventions, the priorities for integrated socio-economic strategies, multisectoral and multicultural, and highlight the innovative aspects of 'inversion' of priorities in the reconstruction process, favoring the take-off of 'accelerator' interventions social and economic and a more updated system of coexistence with risks. In this perspective, reconstruction as a necessary response to the calamitous event can and must become a unique opportunity to raise the level of protection from risks and rehabilitation and development of the most fragile places in Italy and abroad.

Keywords: an operational protocol for reconstruction, operational priorities for coexistence with seismic risk, social and economic interventions accelerators of building reconstruction, the difficult post-earthquake reconstruction in Italy

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Authors: Amelia J. McFarland, Andrew K. Davey, Shailendra Anoopkumar-Dukie

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Microglia are the resident macrophage population of the central nervous system (CNS), contributing to both innate and adaptive immune response, and brain homeostasis. Activation of microglia occurs in response to a multitude of pathogenic stimuli in their microenvironment; this induces morphological and functional changes, resulting in a state of acute neuroinflammation which facilitates injury resolution. Adequate microglial function is essential for the health of the neuroparenchyma, with microglial dysfunction implicated in numerous CNS pathologies. Given the critical role that these macrophage-derived cells play in CNS homeostasis, there is a high demand for microglial models suitable for use in neuroscience research. The isolation of primary human microglia, however, is both difficult and costly, with microglial activation an unwanted but inevitable result of the extraction process. Consequently, there is a need for the development of alternative experimental models which exhibit morphological, biochemical and functional characteristics of human microglia without the difficulties associated with primary cell lines. In this study, our aim was to evaluate whether THP-1 human peripheral blood monocytes would display microglial-like qualities following an induced differentiation, and, therefore, be suitable for use as surrogate microglia. To achieve this aim, THP-1 human peripheral blood monocytes from acute monocytic leukaemia were differentiated with a range of phorbol 12-myristate 13-acetate (PMA) concentrations (50-200 nM) using two different protocols: a 5-day continuous PMA exposure or a 3-day continuous PMA exposure followed by a 5-day rest in normal media. In each protocol and at each PMA concentration, microglial-like cell morphology was assessed through crystal violet staining and the presence of CD-14 microglial / macrophage cell surface marker. Lipopolysaccharide (LPS) from Escherichia coli (055: B5) was then added at a range of concentrations from 0-10 mcg/mL to activate the PMA-differentiated THP-1 cells. Functional microglial-like behavior was evaluated by quantifying the release of prostaglandin (PG)-E2 and pro-inflammatory cytokines interleukin (IL)-1β and tumour necrosis factor (TNF)-α using mediator-specific ELISAs. Furthermore, production of global reactive oxygen species (ROS) and nitric oxide (NO) were determined fluorometrically using dichlorodihydrofluorescein diacetate (DCFH-DA) and diaminofluorescein diacetate (DAF-2-DA) respectively. Following PMA-treatment, it was observed both differentiation protocols resulted in cells displaying distinct microglial morphology from 10 nM PMA. Activation of differentiated cells using LPS significantly augmented IL-1β, TNF-α and PGE2 release at all LPS concentrations under both differentiation protocols. Similarly, a significant increase in DCFH-DA and DAF-2-DA fluorescence was observed, indicative of increases in ROS and NO production. For all endpoints, the 5-day continuous PMA treatment protocol yielded significantly higher mediator levels than the 3-day treatment and 5-day rest protocol. Our data, therefore, suggests that the differentiation of THP-1 human monocyte cells with PMA yields a homogenous microglial-like population which, following stimulation with LPS, undergo activation to release a range of pro-inflammatory mediators associated with microglial activation. Thus, the use of PMA-differentiated THP-1 cells represents a suitable microglial model for in vitro research.

Keywords: differentiation, lipopolysaccharide, microglia, monocyte, neuroscience, THP-1

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Authors: Duane Booysen, Ashraf Kagee

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There is a high prevalence of violent crime and trauma exposure in South African society. Considering the prevalence of continuous violent crimes and traumatization in South Africa, the public mental health sector is required to combat the burgeoning effect of traumatic stress in South Africa. Trauma counselors, especially, provide important mental health services at primary health care to persons affected by traumatic events. Therefore, the evaluation and implementation of evidence-based trauma therapies is essential at a primary health care level in treating traumatic stress. A single-case design was used to evaluate the treatment effect of a Brief Trauma Treatment Programme treating persons who present with symptoms of posttraumatic stress disorder at a primary care trauma centre in Cape Town, South Africa. The sample consisted of six adult participants who presented with symptoms of posttraumatic stress and were assessed at baseline, during treatment, post-intervention and at 3-month follow. All participants received six sessions of trauma therapy. Assessment measures included the posttraumatic stress disorder symptom scale interviews for Diagnostic and Statistical Manual fifth edition (DSM5), the posttraumatic disorder checklist for DSM5, Beck Depression Inventory and Beck Anxiety Inventory. Results demonstrate that participants had noticeable reduced symptoms for traumatic stress, anxiety and depression despite living in contexts of violent crime and trauma. In conclusion, the article critically reflects on the need to evaluate and implement evidence-based treatments for the South African context, and how evidence-based treatments are used in developing socio-economic and cultural diverse contexts with continuous levels of violence and traumatization.

Keywords: psychological interventions, public mental health, traumatic stress, single-case design

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Authors: Min-Chien Su, Tzu-Hsuan Hsu, Guan-Xuan Wu, Shyh-Ming Kuo

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Lung cancer is one of the clinically challenging malignant diseases worldwide. For efficient therapeutics in cancer, combination therapy has developed to acquire a better outcome. PLK-1 was one of the major factors affecting cell mitosis in cancer cells, its inhibitor Bi6727 was proven effective in treating several different cancers namely oral cancer, colon cancer and lung cancer. Despite its low toxicity toward normal cells compared to traditional chemotherapy, it is still yet to be evaluated in detail. Livistona Chinensis (LC) is a Chinese herb that used as a traditional prescription to treat lung cancer. Due to the uncertainty of the efficacy of LC, we utilized a water extraction method to extract the Livistona Chinensis and then lyophilized into powder for further study. In this study we investigated the antiproliferation activities of Bi6727 and LC extracts (LCE) on A549 non-small lung cancer cells. The IC50 of Bi6727 and LCE on A549 are 60 nM and 0.8 mg/mL, respectively. The fluorescent staining images shown nucleolus damage in cells treated with Bi6727 and mitochondrial damage after treated with LCE. A549 cells treated with Bi6727 and LCE showed increased expression of Bax, Caspase-3 and Caspase-9 proteins from Western blot assay. LCE also inhibited A549 cells growth keeping cells at G2-M phase from cell cycle assay. Apoptosis assay results showed that LCE induced late apoptosis of A549 cells. JC-1 assay showed that the mitochondria damaged at the LCE concentration of 0.4 mg/mL. In our preliminary anti-proliferation test of combined LCE and Bi-6727 on A549 cells, we found a dramatically decrease in proliferation after treated with LCE first for 24-h and then Bi-6727 for extra 24-h. This was an important finding regarding synergistic anti-proliferation effect of these drugs, However, the usage, the application sequence of LCE and Bi-6727 on A549 cells and their related mechanisms still need to be evaluated. In summary, the drugs exerted anti-proliferation effect on A549 cells independently. We hopefully combine the usage of these two drugs will bring a different and potential outcome in treating lung cancer.

Keywords: anti-proliferation, A549, Livistona Chinensis fruit extracts, PLK-1 inhibitor

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Authors: Alan Lai, Wilson Yik

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With rapid urbanization, there has been a dramatic increase in global urban population in Asia and over half of population in Asia will live in urban regions in the near future. Facing with increasing exposure to climate-related stresses and shocks, most of the Asian cities will very likely to experience more frequent heat waves and flooding with rising sea levels, particularly the coastal cities will grapple for intense typhoons and storm surges. These climate changes have severe impacts in urban areas at the costs of infrastructure and population, for example, human health, wellbeing and high risks of dengue fever, malaria and diarrheal disease. With the increasing prominence of adaptation to climate changes, there have been changes in corresponding policies. Smaller cities have greater potentials for integrating the concept of resilience into their infrastructure as well as keeping pace with their rapid growths in population. It is therefore important to explore the potentials of Asian cities adapting to climate change and the opportunities of building climate resilience in urban planning and building design. Furthermore, previous studies have mainly attempted at exploiting the potential of resilience on a macro-level within urban planning rather than that on micro-level within the context of individual building. The resilience of individual building as a research field has not yet been much explored. Nonetheless, recent studies define that the resilience of an individual building is the one which is able to respond to physical damage and recover from such damage in a quickly and cost-effectively manner, while maintain its primary functions. There is also a need to develop an assessment tool to evaluate the resilience on building scale which is still largely uninvestigated as it should be regarded as a basic function of a building. Due to the lack of literature reporting metric for assessing building resilience with sustainability, the research will be designed as a case study to provide insight into the issue. The aim of this research project is to encourage and assist in developing neighborhood climate resilience design strategies for Hong Kong so as to bridge the gap between difference scales and that between theory and practice.

Keywords: resilience cities, building resilience, resilient buildings and infrastructure, climate resilience, hot and humid southeast area, high-density cities

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Authors: Vishvas N. Patel, Mehul Chorawala

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Currently, according to the authors best knowledge there are less effective therapeutic agents to limit intestinal mucosa damage associated with inflammatory bowel disease (IBD). Clinical studies have shown beneficial effects of several probiotics in patients of IBD. Probiotics are live organisms; confer a health benefit to the host by modulating immunoinflammation and oxidative stress. Although probiotics in murine and human improve disease severity, very little is known about the specific contribution of cell wall contents of probiotics in IBD. Herein, we investigated the ameliorative potential of cell wall contents of Lactobacillus casei (LC) in lipopolysaccharide (LPS)-induced murine colitis. Methods: Colitis was induced in LPS-sensitized rats by intracolonic instillation of LPS (50 µg/rat) for consecutive 14 days. Concurrently, cell wall contents isolated from 103, 106 and 109 CFU of LC was given subcutaneously to each rat for 21 days, considering sulfasalazine (100 mg/kg, p.o.) as standard. The severity of colitis was assessed by body weight loss, food intake, stool consistency, rectal bleeding, colon weight/length, spleen weight and histological analysis. Colonic inflammatory markers (myeloperoxidase (MPO) activity, C-reactive protein and proinflammatory cytokines) and oxidative stress markers (malondialdehyde, reduced glutathione and nitric oxide) were also assayed. Results: Cell wall contents of isolated from 106 and 109 CFU of LC significantly improved the severity of colitis by reducing body weight loss and diarrhea & bleeding incidence, improving food intake, colon weight/length, spleen weight and microscopic damage to the colonic mucosa. The treatment also reduced levels of inflammatory and oxidative stress markers and boosted antioxidant molecule. However, cell wall contents of isolated from 103 were ineffective. Conclusion: In conclusion, cell wall contents of LC attenuate LPS-induced colitis by modulating immuno-inflammation and oxidative stress.

Keywords: probiotics, Lactobacillus casei, immuno-inflammation, oxidative stress, lipopolysaccharide, colitis

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Authors: Sadaoui Djaouida

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In this paper, the predictive control method is proposed to control the synchronization of two perturbed satellites attitude motion. Based on delayed feedback control of continuous-time systems combines with the prediction-based method of discrete-time systems, this approach only needs a single controller to realize synchronization, which has considerable significance in reducing the cost and complexity for controller implementation.

Keywords: predictive control, synchronization, satellite attitude, control engineering

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Authors: Jianwen Li, Hongfang Ma, Haitao Zhang, Qiwen Sun, Weiyong Ying

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Catalytic cracking of butene to propylene was carried out in a continuous-flow fixed-bed reactor over HZSM-5 catalysts modified by nickel and phosphorus. The structure and acidity of catalysts were measured by N2 adsorption, NH3-TPD and XPS. The results revealed that surface area and strong acid sites both decreased with increasing phosphorus loadings. The increment of phosphorus loadings reduced the butene conversion but enhanced the propylene selectivity and catalyst stability.

Keywords: butene, catalytic cracking, HZSM-5, modification

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Authors: Elle Hilke Dominski

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This paper explores the impact of intersectional bullying of lesbian, gay, bisexual, transgender (LGBT) youth from a multi-layered experience perspective within bullying incidents at school. Present inclusionary measures at school may not be designed as a continuous process of finding better methods for responding to diversity, rather remain ‘fixed’ as singular solutions applied universally. This paper argues recognizing education through a lens of inclusion begins to realize most educational systems are poorly equipped to handle diversity.

Keywords: bullying, education, intersectional bullying, LGBT

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Authors: Omolola R. Ayepola, Nicole L. Brooks, Oluwafemi O. Oguntibeju

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The liver plays an important role in the regulation of blood glucose and is a target organ of hyperglycaemia. Hyperglycemia plays a crucial role in the onset of various liver diseases and may culminate into hepatopathy if untreated. Alteration in antioxidant defense and increase in oxidative stress that results in tissue injury is characteristic of diabetes. We evaluated the protective effects of kolaviron-a biflavonoid complex, on hepatic antioxidants, lipid peroxidation and apoptosis in the liver of diabetic rats. To induce type I diabetes, rats were injected with streptozotocin intraperitoneally at a single dose of 50 mg/kg. Oral treatment of diabetic rats with kolaviron (100 mg/kg) started on the 6th day after diabetes induction and continued for 6 weeks (5 times weekly). Diabetic rats exhibited a significant increase in the peroxidation of hepatic lipids as observed from the elevated level of malondialdehyde (MDA) estimated by High-Performance Liquid Chromatography. In addition, Oxygen Radical Absorbance Capacity (ORAC), ratio of reduced to oxidized glutathione (GSH/GSSG) and catalase (CAT) activity was decreased in the liver of diabetic rats. TUNEL assay revealed increased apoptotic cell death in the liver of diabetic rats. Examination of Pancreatic beta-cells by immunohistochemical methods revealed beta cell degeneration and reduction in beta cell/ islet area in the diabetic controls. Kolaviron-treatment increased the area of insulin immunoreactive beta-cells significantly. Kolaviron attenuated lipid peroxidation and apoptosis in the liver of diabetic rats, increased CAT activity GSH levels and the resultant GSH: GSSG. The ORAC of kolaviron-treated diabetic liver was restored to near-normal values. Kolaviron protects the liver against oxidative and apoptotic damage induced by hyperglycemia. The antidiabetic effect of kolaviron may also be related to its beneficial effects on beta-cell function.

Keywords: diabetes mellitus, kolaviron, oxidative stress, liver, apoptosis

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Authors: Nicole M. Martino

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Reinforced concrete bridge deck condition assessments primarily use visual inspection methods, where an inspector looks for and records locations of cracks, potholes, efflorescence and other signs of probable deterioration. Sounding is another technique used to diagnose the condition of a bridge deck, however this method listens for damage within the subsurface as the surface is struck with a hammer or chain. Even though extensive procedures are in place for using these inspection techniques, neither one provides the inspector with a comprehensive understanding of the internal condition of a bridge deck – the location where damage originates from.  In order to make accurate estimates of repair locations and quantities, in addition to allocating the necessary funding, a total understanding of the deck’s deteriorated state is key. The research presented in this paper collected infrared thermography and ground penetrating radar data from reinforced concrete bridge decks without an asphalt overlay. These decks were of various ages and their condition varied from brand new, to in need of replacement. The goals of this work were to first verify that these nondestructive evaluation methods could identify similar areas of healthy and damaged concrete, and then to see if combining the results of both methods would provide a higher confidence than if the condition assessment was completed using only one method. The results from each method were presented as plan view color contour plots. The results from one of the decks assessed as a part of this research, including these plan view plots, are presented in this paper. Furthermore, in order to answer the interest of transportation agencies throughout the United States, this research developed a step-by-step guide which demonstrates how to collect and assess a bridge deck using these nondestructive evaluation methods. This guide addresses setup procedures on the deck during the day of data collection, system setups and settings for different bridge decks, data post-processing for each method, and data visualization and quantification.

Keywords: bridge deck deterioration, ground penetrating radar, infrared thermography, NDT of bridge decks

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Authors: Zhenjie Liu

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This paper investigates the existence and uniqueness of solutions for singular higher order boundary value problems on time scales by using mixed monotone method. The theorems obtained are very general. For the different time scale, the problem may be the corresponding continuous or discrete boundary value problem.

Keywords: mixed monotone operator, boundary value problem, time scale, green's function, positive solution, singularity

Procedia PDF Downloads 244

Authors: Ali D. Omur, Betul Apaydin Yildirim, Yavuz S. Saglam, Selim Comakli, Mustafa Ozkaraca

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Twenty-eight male Sprague Dawley rats (aged 3 months) were used in the study. The animals were given feed and water as ad libitum. Sprague Dawley rats were randomly divided into 4 groups as 7 rats in each group. Aflatoxin B1 (7.5 μg/200 g), resveratrol (60 mg/kg) was administered to rats in groups other than the control group. At the end of the 16th day, blood, semen and tissue specimens were taken by decapitation under ether anesthesia. The effects of aflatoxin B1 and resveratrol on spermatological, pathological and biochemical parameters were determined in rats. When we evaluate the spermatological parameters, it is understood that resveratrol has a statistically significant difference in terms of sperm motility and viability (membrane integrity) compared to the control group and aflatoxin B1 administration groups, indicating a protective effect on spermatological parameters (groups: control, resveratrol, aflatoxin B1 and Afb1 + res; respectively, values of motility: 71,42 ± 0,52b, 72,85 ± 1, 48c , 60,71 ± 1,30a, 57,14 ± 2, 40a; values of viability: 63,85 ± 1,33b, 70,42 ± 2,61c, 55,00 ± 1,54a, 56,57 ± 0,89a. In terms of pathological parameters -histopathological examination- in the control and resveratrol groups, seminiferous tubules were observed to be in normal structure. In the group treated with aflatoxin, the regular structure of the spermatogenic cells deteriorated, and the seminiferous tubules became necrotic and degenerative. In the group treated with Afb1 + res, the decreasing of necrotic and degenerative changes were determined compared with in the group treated with aflatoxin. As immunohistochemical examination, cleaved caspase 3 expression was found to be very low in the control and resveratrol groups. Cleaved caspase 3 expression was severely exacerbated in seminiferous tubules in aflatoxin group but cleaved caspase 3 expression level decreased in Afb1 + res. In the biochemical direction, resveratrol has been shown to inhibit the adverse effects of aflatoxin on antioxidant levels (GSH-mmol/L, CAT-kU/L, GPx-U/mL, SOD-EU/mL) and to show a protective effect. For this purpose, the use of resveratrol with antioxidant activity was investigated in preventing or ameliorating damage to aflatoxin B1. It has been concluded that resveratrol effectively prevents the aflatoxin-induced testicular damage and lipid peroxidation. It has also been shown that resveratrol has protective effects on sperm motility and viability.

Keywords: Aflatoxin B1, rat, resveratrol, sperm

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Authors: Abhisek Sarkar, Abhimanyu Gaur

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In this report we have discussed the theoretical aspects of the flow transformation, occurring through a series of bifurcations. The parameters and their continuous diversion, the intermittent bursts in the transition zone, variation of velocity and pressure with time, effect of roughness in turbulent zone, and changes in friction factor and head loss coefficient as a function of Reynolds number for a transverse flow across a cylinder have been discussed. An analysis of the variation in the wake length with Reynolds number was done in FORTRAN.

Keywords: bifurcation, attractor, intermittence, energy cascade, energy spectra, vortex stretching

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Authors: Rafiqul Hasan, A. S. M. Tanim Anwar, Mohammad Azizul Hakim

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Background: Chronic kidney disease (CKD) is a major public health problem that continues to increase in prevalence globally. The prevalence of chronic kidney disease is increasing day by day in low to middle income countries (LMICs). People living in LMICs have the highest need for renal replacement therapy (RRT) despite they have lowest access to various modalities of treatment. As continuous ambulatory peritoneal dialysis (CAPD) does not require advanced technologies, very much infrastructure, dialysis staff support, it should be an ideal form of RRT in LMICs, particularly for those living in remote areas. To authors knowledge there was scarcity of data regarding CAPD performance in remote area of Bangladesh. This study was aimed to report the characteristics and outcomes of CAPD in ESRD patients lived in least developed area of Bangladesh. Methods: This prospective study was conducted in Cox’sbazar Medical College Hospital, Cox’sbazar and Parkview hospital Ltd, Chattogram, Bangladesh. Data were collected by questionnaire from the patients of any age with end-stage renal disease (ESRD) who underwent CAPD in 2018–2021. The baseline characteristics, PD-related complication as well as patient and technique survivals were analyzed. Results: Out of 31 patients who underwent CAPD, 18 (58%) were male on the age range of 15–79 years. The mean follow-up duration was 18 months. Mortality was inversely related with the EF of echocardiography. The peritonitis rate was 0.48 episodes per patient per year. The 1, 3 and 4-year patient survival rates were 64.34% (95% CI = 52.5–81.5), 23.79% (95% CI = 17.9 – 57.4) and 3.22% (95% CI = 31.2–77.5) respectively. Conclusions: In this study, CAPD performance was poorer than usual reference. Cardiac compromised patient and inappropriate dwell might be the main contributing factors behind this scenario. The peritonitis rate was nearly similar to that of developed countries. CAPD was cost effective than HD in remote area. Some accessible measures may be taken to make CAPD a more acceptable RRT modality with improved outcomes in poor socioeconomic backgrounds.

Keywords: dialysis cost, peritoneal dialysis, peritonitis, CAPD, least developed area, remote area, Bangladesh

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Authors: Maria Dora Horvath, Norbert Buzas, Zsanett Tesch

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Diabetes management poses many unique challenges for children and their parents. The use of a diabetes management device should not be one of these challenges as the purpose of these devices is to make the management more convenient. The objective of our study was to examine how demographical, psychological and diabetes-related factors determine the choices parents make regarding their child’s diabetes management technologies and how they perceive advanced devices. We conducted the study using an online questionnaire with 318 parents (mostly mothers). The questions of the survey were about demographical, diabetes-related and psychological factors (diabetes management problems, diabetes management competence). In addition, we asked the parents opinions about advanced diabetes management devices. We expanded our data with semi-structured in-depth interviews. 61 % of the participants Self-Monitored Blood Glucose (SMBG), and 39 % used a Continuous Glucose Monitoring System (CGM). Considering insulin administration, 58 % used Multiple Daily Insulin Injections (MDII) and 42 % used Continuous Subcutaneous Insulin Infusion (CSII). Parents who used diverse combinations of diabetes management devices showed significant differences in age (parents’ and child’s), the monthly cost of diabetes, the duration of diabetes, the highest level of education and average monthly household income. CGM users perceived diabetes management problems significantly more severe than SMBG users and CSII users felt significantly more competent in diabetes management than MDII users. Avoiding CGM use due to lack of financial resources was determined by diagnosis duration. While avoiding its use by the cause of the child rejecting, it was determined by the child’s age and diabetes competence. Using MDII instead of CSII because of the child’s rejection was determined by the monthly cost of diabetes and child’s age. We conducted a complex empirical study in which we examined perceptions and experiences of advanced and less advanced diabetes management technologies comprehensively. Our study highlights the factors that fundamentally influence parents’ motivations and choices about diabetes management technologies. These results could contribute to developing diabetes management technologies more suitable for children living with type 1 diabetes and their parents.

Keywords: advanced diabetes management technologies, children living with type 1 diabetes, diabetes management, motivation, parents

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Authors: Daniel Alfonso Reséndiz-García, Luis Antonio García-Villanueva

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As a result of the high industrial activity, which arises from the search to satisfy the needs of products and services for society, several chemical accidents have occurred, causing serious damage to different sectors: human, economic, infrastructure and environmental losses. Historically, with the study of this chemical accidents, it has been determined that the causes are mainly due to human errors (inexperienced personnel, negligence, lack of maintenance and deficient risk analysis). The industries have the aim to increase production and reduce costs. However, it should be kept in mind that the costs involved in risk studies, implementation of barriers and safety systems is much cheaper than paying for the possible damages that could occur in the event of an accident, without forgetting that there are things that cannot be replaced, such as human lives.Therefore, it is of utmost importance to implement risk studies in all industries, which provide information for prevention and planning. The aim of this study is to compare risk methodologies by identifying the consequences of accidents related to the storage of flammable, dangerous goods for decision making and emergency response.The methodologies considered in this study are qualitative and quantitative risk analysis and consequence analysis. The latter, by means of modeling software, which provides radius of affectation and the possible scope and magnitude of damages.By using risk analysis, possible scenarios of occurrence of chemical accidents in the storage of flammable substances are identified. Once the possible risk scenarios have been identified, the characteristics of the substances, their storage and atmospheric conditions are entered into the software.The results provide information that allows the implementation of prevention, detection, control, and combat elements for emergency response, thus having the necessary tools to avoid the occurrence of accidents and, if they do occur, to significantly reduce the magnitude of the damage.This study highlights the importance of risk studies applying tools that best suited to each case study. It also proves the importance of knowing the risk exposure of industrial activities for a better prevention, planning and emergency response.

Keywords: chemical accidents, emergency response, flammable substances, risk analysis, modeling

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Authors: A. Sopharak, B. Uyyanonvara, S. Barman

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Diabetic retinopathy is characterized by the development of retinal microaneurysms. The damage can be prevented if disease is treated in its early stages. In this paper, we are comparing Support Vector Machine (SVM) and Naïve Bayes (NB) classifiers for automatic microaneurysm detection in images acquired through non-dilated pupils. The Nearest Neighbor classifier is used as a baseline for comparison. Detected microaneurysms are validated with expert ophthalmologists’ hand-drawn ground-truths. The sensitivity, specificity, precision and accuracy of each method are also compared.

Keywords: diabetic retinopathy, microaneurysm, naive Bayes classifier, SVM classifier

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Authors: Skirmante Mozuriunaite

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Contemporary metropolitan areas and large cities are dynamic, rapidly growing and continuously changing. Thus, urban transformations and mutations are not a new phenomenon, but rather a continuous process. Basic factors of urban transformation are related to development of technologies, globalisation, lifestyle, etc., which, in combination with local factors, have generated an extremely great variety of urban development conditions. This article discusses the main urbanisation processes in Lithuania during last 50 year period and social factors affecting urban functional mutations.

Keywords: dispersion, functional mutations, urbanization, urban mutations, social factors

Procedia PDF Downloads 503