Search results for: metabolic control

Authors: Antonio Ruiz Gonzalez, Kwang-Leong Choy

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The measurement of electrolytes has a high value in the clinical routine. Ions are present in all body fluids with variable concentrations and are involved in multiple pathologies such as heart failures and chronic kidney disease. In the case of dissolved potassium, although a high concentration in the blood (hyperkalemia) is relatively uncommon in the general population, it is one of the most frequent acute electrolyte abnormalities. In recent years, the integration of thin films technologies in this field has allowed the development of highly sensitive biosensors with ultra-low limits of detection for the assessment of metals in liquid samples. However, despite the current efforts in the miniaturization of sensitive devices and their integration into portable systems, only a limited number of successful examples used commercially can be found. This fact can be attributed to a high cost involved in their production and the sustained degradation of the electrodes over time, which causes a signal drift in the measurements. Thus, there is an unmet necessity for the development of low-cost and robust sensors for the real-time monitoring of analyte concentrations in patients to allow the early detection and diagnosis of diseases. This paper reports a thin film ion-selective sensor for the evaluation of potassium ions in aqueous samples. As an alternative for this fabrication method, aerosol assisted chemical vapor deposition (AACVD), was applied due to cost-effectivity and fine control over the film deposition. Such a technique does not require vacuum and is suitable for the coating of large surface areas and structures with complex geometries. This approach allowed the fabrication of highly homogeneous surfaces with well-defined microstructures onto 50 nm thin gold layers. The degradative processes of the ubiquitously employed poly (vinyl chloride) membranes in contact with an electrolyte solution were studied, including the polymer leaching process, mechanical desorption of nanoparticles and chemical degradation over time. Rational design of a protective coating based on an organosilicon material in combination with cellulose to improve the long-term stability of the sensors was then carried out, showing an improvement in the performance after 5 weeks. The antifouling properties of such coating were assessed using a cutting-edge quartz microbalance sensor, allowing the quantification of the adsorbed proteins in the nanogram range. A correlation between the microstructural properties of the films with the surface energy and biomolecules adhesion was then found and used to optimize the protective film.

Keywords: hyperkalemia, drift, AACVD, organosilicon

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Authors: Amar Ghelani

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People with auditory verbal hallucinations (AVH) who seek support from mental health services commonly report feeling unheard and invalidated in their interactions with social workers and psychiatric professionals. Current mental health training and clinical approaches have proven to be inadequate in addressing the complex nature of voice hearing. Childhood trauma is a key factor in the development of AVH and can render people more vulnerable to hearing both supportive and/or disturbing voices. Lived experiences of racism, poverty, and immigration are also associated with development of what is broadly classified as psychosis. Despite evidence affirming the influence of environmental factors on voice hearing, the Western biomedical system typically conceptualizes this experience as a symptom of genetically-based mental illnesses which requires diagnosis and treatment. Overemphasis on psychiatric medications, referrals, and directive approaches to people’s problems has shifted clinical interventions away from assessing and addressing problems directly related to AVH. The Maastricht approach offers voice hearers and mental health workers an alternative and respectful starting point for understanding and coping with voices. The approach was developed by voice hearers in partnership with mental health professionals and entails an innovative method to assess and create meaning from voice hearing and related life stressors. The objectives of the approach are to help people who hear voices: (1) understand the problems and/or people the voices may represent in their history, and (2) cope with distress and find solutions to related problems. The Maastricht approach has also been found to help voice hearers integrate emotional conflicts, reduce avoidance or fear associated with AVH, improve therapeutic relationships, and increase a sense of control over internal experiences. The proposed oral presentation will be guided by a recovery-oriented theoretical framework which suggests healing from psychological wounds occurs through social connections and community support systems. The presentation will start with a brainstorming exercise to identify participants pre-existing knowledge of the subject matter. This will lead into a literature review on the relations between trauma, intersectionality, and AVH. An overview of the Maastricht approach and review of research related to its therapeutic risks and benefits will follow. Participants will learn trauma-informed coping skills and questions which can help voice hearers make meaning from their experiences. The presentation will conclude with a review of resources and learning opportunities where participants can expand their knowledge of the Hearing Voices Movement and Maastricht approach.

Keywords: Maastricht interview, recovery, therapeutic assessment, voice hearing

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Authors: W. S. Mohamed, A. A. Hammam

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Sandy soils under arid and semi-arid conditions are characterized by poor physical and biochemical properties such as low water retention, rapid organic matter decomposition, low nutrients use efficiency, and limited crop productivity. Addition of organic amendments is crucial to develop soil properties and consequently enhance nutrients use efficiency and lessen organic carbon decomposition. Two years field experiments were developed to investigate the feasibility of using poultry manure and its derived biochar integrated with different levels of N fertilizer as a soil amendment for newly reclaimed sandy soils in Western Desert of El-Minia Governorate, Egypt. Results of this research revealed that poultry manure and its derived biochar addition induced pronounced effects on soil moisture content at saturation point, field capacity (FC) and consequently available water. Data showed that application of poultry manure (PM) or PM-derived biochar (PMB) in combination with inorganic N levels had caused significant changes on a range of the investigated sandy soil biochemical properties including pH, EC, mineral N, dissolved organic carbon (DOC), dissolved organic N (DON) and quotient DOC/DON. Overall, the impact of PMB on soil physical properties was detected to be superior than the impact of PM, regardless the inorganic N levels. In addition, the obtained results showed that PM and PM application had the capacity to stimulate vigorous growth, nutritional status, production levels of wheat and sorghum, and to increase soil organic matter content and N uptake and recovery compared to control. By contrast, comparing between PM and PMB at different levels of inorganic N, the obtained results showed higher relative increases in both grain and straw yields of wheat in plots treated with PM than in those treated with PMB. The interesting feature of this research is that the biochar derived from PM increased treated sandy soil organic carbon (SOC) 1.75 times more than soil treated with PM itself at the end of cropping seasons albeit double-applied amount of PM. This was attributed to the higher carbon stability of biochar treated sandy soils increasing soil persistence for carbon decomposition in comparison with PM labile carbon. It could be concluded that organic manures applied to sandy soils under arid and semi-arid conditions are subjected to high decomposition and mineralization rates through crop seasons. Biochar derived from organic wastes considers as a source of stable carbon and could be very hopeful choice for substituting easily decomposable organic manures under arid conditions. Therefore, sustainable agriculture and productivity in newly reclaimed sandy soils desire one high rate addition of biochar derived from organic manures instead of frequent addition of such organic amendments.

Keywords: biochar, dissolved organic carbon, N-uptake, poultry, sandy soil

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Authors: João Pedro Zanella, Michel J. O. Fagundes

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Introduction: Drug use has been practised by humans universally for millennia, not excluding any population from these habits, however, the rampant drug use is a global concern due to the harm that affects the health of the world population. In this sense, it is observed the reduction of lasting and effective public policies for the resolution, increasing the demand for treatment services. With this comes ibogaine, an alkaloid derived from the root of an African bush (Tabernanthe Iboga), found mostly in Gabon and used widely by the native Bwiti population in rituals, and also other social groups, which demonstrates efficacy against chemical dependence, psychic and emotional disorders, opioid withdrawal was first confirmed by a study in rats done by Michailo Dzoljic and associates in 1988 and again in 1994. Methods: A brief description of the plant, its neurohumoral potential and the effects caused by ingested doses, in a simplified and objective way, will be discussed in the course of this abstract. Results: Ibogaine is not registered or passed by Anvisa, regarding safety and efficacy, and cannot be sold in Brazil. Its illegal trade reaches R$ 5 thousand for a session with the proceeds of the root, and its effect can last up to 72 hours, attributing Iboga's psychoactive effects to the alkaloid called ibogaine. The shrub where Ibogaine is located has pink and yellow flowers, and its fruit produced does not have psychoactive substances, but its root bark contains 6 to 7% indolic alkaloids. Besides extraction from the iboga plant, ibogaine hydrochloride can be semisynthesized from voacangine, another plant alkaloid that acts as a precursor. Its potential has the ability to perform multiple interactions with the neurotransmitter system, which are closely associated with addiction, including nicotinic, opioid and serotoninergic systems. Studies carried out by Edwards found that the doses administered of Iboga should be determined by a health professional when its purpose is to treat individuals for dependence on other drugs. Its use in small doses may cause an increase in sensibility, impaired vision and motor alterations; in moderate quantities, hallucinations, motor and neurological alterations and impaired vision; in high quantities it may cause hallucinations with personal events at a deeper level lasting up to 24 hours or more, followed by motor and visual alterations. Conclusion: The product extracted from the Iboga plant is of great importance in controlling addiction, reducing the need for the use of narcotics by patients, thus gaining a space of extreme importance in the treatment of users of psychoactive substances. It is remarkable the progress of the latest’s research about the usefulness of Ibogaine, and its benefits for certain treatments, even with the restriction of its sale in Brazil. Besides this, Ibogaine has an additional benefit of helping the patient to gain self-control over their destructive behaviours.

Keywords: alkaloids, dependence, Gabon, ibogaine

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Authors: Daniela Manila Bianchi, Samantha Lupi, Elisa Barcucci, Sandra Fragassi, Clara Tramuta, Lucia Decastelli

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Introduction: The undeclared allergens detection in food products plays a fundamental role in the safety of the allergic consumer. The protection of allergic consumers is guaranteed, in Europe, by Regulation (EU) No 1169/2011 of the European Parliament, which governs the consumer's right to information and identifies 14 food allergens to be mandatorily indicated on food labels: among these, an egg is included. An egg can be present as an ingredient or as contamination in raw and cooked products. The main allergen egg proteins are ovomucoid, ovalbumin, lysozyme, and ovotransferrin. This study presents the results of a survey conducted in Northern Italy aimed at detecting the presence of undeclared egg proteins in food matrices in the latest ten years (2011-2021). Method: In the period January 2011 - October 2021, a total of 1205 different types of food matrices (ready-to-eat, meats, and meat products, bakery and pastry products, baby foods, food supplements, pasta, fish and fish products, preparations for soups and broths) were delivered to Food Control Laboratory of Istituto Zooprofilattico Sperimentale of Piemonte Liguria and Valle d’Aosta to be analyzed as official samples in the frame of Regional Monitoring Plan of Food Safety or in the contest of food poisoning. The laboratory is ISO 17025 accredited, and since 2019, it has represented the National Reference Centre for the detection in foods of substances causing food allergies or intolerances (CreNaRiA). All samples were stored in the laboratory according to food business operator instructions and analyzed within the expiry date for the detection of undeclared egg proteins. Analyses were performed with RIDASCREEN®FAST Ei/Egg (R-Biopharm ® Italia srl) kit: the method was internally validated and accredited with a Limit of Detection (LOD) equal to 2 ppm (mg/Kg). It is a sandwich enzyme immunoassay for the quantitative analysis of whole egg powder in foods. Results: The results obtained through this study showed that egg proteins were found in 2% (n. 28) of food matrices, including meats and meat products (n. 16), fish and fish products (n. 4), bakery and pastry products (n. 4), pasta (n. 2), preparations for soups and broths (n.1) and ready-to-eat (n. 1). In particular, in 2011 egg proteins were detected in 5% of samples, in 2012 in 4%, in 2013, 2016 and 2018 in 2%, in 2014, 2015 and 2019 in 3%. No egg protein traces were detected in 2017, 2020, and 2021. Discussion: Food allergies occur in the Western World in 2% of adults and up to 8% of children. Allergy to eggs is one of the most common food allergies in the pediatrics context. The percentage of positivity obtained from this study is, however, low. The trend over the ten years has been slightly variable, with comparable data.

Keywords: allergens, food, egg proteins, immunoassay

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Authors: Saimir Cenameri, Arjana Tereziu, Kastriot Dallaku

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Introduction: Intra-uterine death is a common problem in obstetrical practice, and can lead to complications if left to resolve spontaneously. The cervix is unprepared, making inducing of labor difficult. Misoprostol is a synthetic prostaglandin E1 analogue, inexpensive, and is presented valid thanks to its ability to bring about changes in the cervix that lead to the induction of uterine contractions. Misoprostol is quickly absorbed when taken orally, resulting in high initial peak serum concentrations compared with the vaginal route. The vaginal misoprostol peak serum concentration is not as high and demonstrates a more gradual serum concentration decline. This is associated with many benefits for the patient; fast induction of labor; smaller doses; and fewer side effects (dose-depended). Mostly it has been used the regime of 50 μg/4 hour, with a high percentage of success and limited side effects. Objective: Evaluation of the efficiency of the use of oral and vaginal misoprostol in inducing labor, and comparing it with its use not by a previously defined protocol. Methods: Participants in this study included patients at U.H.O.G. 'Koco Gliozheni', Tirana from April 2004-July 2006, presenting with an indication for inducing labor in the third trimester for pregnancy termination. A total of 37 patients were randomly admitted for birth inducing activity, according to protocol (26), oral or vaginal protocol (10 vs. 16), and a control group (11), not subject to the protocol, was created. Oral or vaginal misoprostol was administered at a dose of 50 μg/4 h, while the fourth group participants were treated individually by the members of the medical staff. The main result of interest was the time between induction of labor to birth. Kruskal-Wallis test was used to compare the average age, parity, women weight, gestational age, Bishop's score, the size of the uterus and weight of the fetus between the four groups in the study. The Fisher exact test was used to compare day-stay and causes in the four groups. Mann-Whitney test was used to compare the time of the expulsion and the number of doses between oral and vaginal group. For all statistical tests used, the value of P ≤ 0.05 was considered statistically significant. Results: The four groups were comparable with regard to woman age and weight, parity, abortion indication, Bishop's score, fetal weight and the gestational age. There was significant difference in the percentage of deliveries within 24 hours. The average time from induction to birth per route (vaginal, oral, according to protocol and not according to the protocol) was respectively; 10.43h; 21.10h; 15.77h, 21.57h. There was no difference in maternal complications in groups. Conclusions: Use of vaginal misoprostol for inducing labor in the third trimester for termination of pregnancy appears to be more effective than the oral route, and even more to uses not according to the protocols approved before, where complications are greater and unjustified.

Keywords: inducing labor, misoprostol, pregnancy termination, third trimester

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Authors: Ayten Ekin Meşe, Selahattin Şentürk, Melike Duvanoğlu

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Petroleum refineries are a highly complex process industry with continuous production and high operating costs. Physical separation of crude oil starts with the crude oil distillation unit, continues with various conversion and purification units, and passes through many stages until obtaining the final product. To meet the desired product specification, process parameters are strictly followed. To be able to ensure the quality of distillates, routine analyses are performed in quality control laboratories based on appropriate international standards such as American Society for Testing and Materials (ASTM) standard methods and European Standard (EN) methods. The cut point of distillates in the crude distillation unit is very crucial for the efficiency of the upcoming processes. In order to maximize the process efficiency, the determination of the quality of distillates should be as fast as possible, reliable, and cost-effective. In this sense, an alternative study was carried out on the crude oil distillation unit that serves the entire refinery process. In this work, studies were conducted with three different crude oil distillates which are Light Straight Run Naphtha (LSRN), Heavy Straight Run Naphtha (HSRN), and Kerosene. These products are named after separation by the number of carbons it contains. LSRN consists of five to six carbon-containing hydrocarbons, HSRN consist of six to ten, and kerosene consists of sixteen to twenty-two carbon-containing hydrocarbons. Physical properties of three different crude distillation unit products (LSRN, HSRN, and Kerosene) were determined using Near-Infrared Spectroscopy with multivariate calibration. The absorbance spectra of the petroleum samples were obtained in the range from 10000 cm⁻¹ to 4000 cm⁻¹, employing a quartz transmittance flow through cell with a 2 mm light path and a resolution of 2 cm⁻¹. A total of 400 samples were collected for each petroleum sample for almost four years. Several different crude oil grades were processed during sample collection times. Extended Multiplicative Signal Correction (EMSC) and Savitzky-Golay (SG) preprocessing techniques were applied to FT-NIR spectra of samples to eliminate baseline shifts and suppress unwanted variation. Two different multivariate calibration approaches (Partial Least Squares Regression, PLS and Genetic Inverse Least Squares, GILS) and an ensemble model were applied to preprocessed FT-NIR spectra. Predictive performance of each multivariate calibration technique and preprocessing techniques were compared, and the best models were chosen according to the reproducibility of ASTM reference methods. This work demonstrates the developed models can be used for routine analysis instead of conventional analytical methods with over 90% accuracy.

Keywords: crude distillation unit, multivariate calibration, near infrared spectroscopy, data preprocessing, refinery

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Authors: Lopamudra D. Satpathy, Bani Chatterjee, Jitendra Mahakud

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The rapid economic growth in terms of output and investment necessitates a substantial growth of Total Factor Productivity (TFP) of firms which is an indicator of an economy’s technological change. The strong empirical relationship between financial sector development and economic growth clearly indicates that firms financing decisions do affect their levels of output via their investment decisions. Hence it establishes a linkage between the financial factors and productivity growth of the firms. To achieve the smooth and continuous economic growth over time, it is imperative to understand the financial channel that serves as one of the vital channels. The theoretical or logical argument behind this linkage is that when the internal financial capital is not sufficient enough for the investment, the firms always rely upon the external sources of finance. But due to the frictions and existence of information asymmetric behavior, it is always costlier for the firms to raise the external capital from the market, which in turn affect their investment sentiment and productivity. This kind of financial position of the firms puts heavy pressure on their productive activities. Keeping in view this theoretical background, the present study has tried to analyze the role of both external and internal financial factors (leverage, cash flow and liquidity) on the determination of total factor productivity of the firms of manufacturing industry and its sub-industries, maintaining a set of firm specific variables as control variables (size, age and disembodied technological intensity). An estimate of total factor productivity of the Indian manufacturing industry and sub-industries is computed using a semi-parametric approach, i.e., Levinsohn- Petrin method. It establishes the relationship between financial factors and productivity growth of 652 firms using a dynamic panel GMM method covering the time period between 1997-98 and 2012-13. From the econometric analyses, it has been found that the internal cash flow has a positive and significant impact on the productivity of overall manufacturing sector. The other financial factors like leverage and liquidity also play the significant role in the determination of total factor productivity of the Indian manufacturing sector. The significant role of internal cash flow on determination of firm-level productivity suggests that access to external finance is not available to Indian companies easily. Further, the negative impact of leverage on productivity could be due to the less developed bond market in India. These findings have certain implications for the policy makers to take various policy reforms to develop the external bond market and easily workout through which the financially constrained companies will be able to raise the financial capital in a cost-effective manner and would be able to influence their investments in the highly productive activities, which would help for the acceleration of economic growth.

Keywords: dynamic panel, financial factors, manufacturing sector, total factor productivity

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Authors: Durri Andriani, Irsan Tahar, Lilian Sarah Hiariey

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Every institution has to develop, implement, and control its policies to ensure the effectiveness of the institution. In doing so, all related stakeholders have to be involved to maximize the benefit of the policies and minimize the potential constraints and resistances. Open and distance education (ODE) institution is no different. As an education institution, ODE institution has to focus their attention to fulfilling academic needs of their students through open and distance measures. One of them is quality learning support system. Significant stakeholders in learning support system are tutors since they are the ones who directly communicate with students. Tutors are commonly seen as objects whose main responsibility is limited to implementing policies decided by management in ODE institutions. Nonetheless, tutors’ perceptions of tutorials are believed to influence tutors’ performances in facilitating learning support. It is therefore important to analyze tutors’ perception on various aspects of learning support. This paper presents analysis of tutors’ perceptions on policies of tutoriala in ODE institution using Policy Analysis Framework (PAF) modified by King, Nugent, Russell, and Lacy. Focus of this paper is on on-line tutors, those who provide tutorials via Internet. On-line tutors were chosen to stress the increasingly important used of Internet in ODE system. The research was conducted in Universitas Terbuka (UT), Indonesia. UT is purposely selected because of its large number (1,234) of courses offered and large area coverage (6000 inhabited islands). These posed UT in a unique position where learning support system has, to some extent, to be standardized while at the same time it has to be able to cater the needs of different courses in different places for students with different backgrounds. All 598 listed on-line tutors were sent the research questionnaires. Around 20% of the email addresses could not be reached. Tutors were asked to fill out open-ended questionnaires on their perceptions on definition of on-line tutorial, roles of tutors and students in on-line tutorials, requirement for on-line tutors, learning materials, and student evaluation in on-line tutorial. Data analyzed was gathered from 40 on-line tutors who sent back filled-out questionnaires. Data were analyzed qualitatively using content analysis from all 40 tutors. The results showed that using PAF as entry point in choosing learning support services as area of policy with delivery learning materials as the issue at UT has been able to provide new insights of aspects need to be consider in formulating policies in online tutorial and in learning support services. Involving tutors as source of information could be proven to be productive. In general, tutors had clear understanding about definition of online tutorial, roles of tutors and roles of students, and requirement of tutor. Tutors just need to be more involved in the policy formulation since they could provide data on students and problem faced in online tutorial. However, tutors need an adjustment in student evaluation which according tutors too focus on administrative aspects and subjective.

Keywords: distance education, on-line tutorial, tutorial policy, tutors’ perspectives

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Authors: Jeanne Leblond, Warren Viricel, Amira Mbarek

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Although several products have reached the market, gene therapeutics are still in their first stages and require optimization. It is possible to improve their lacking efficiency by the use of carefully engineered vectors, able to carry the genetic material through each of the biological barriers they need to cross. In particular, getting inside the cell is a major challenge, because these hydrophilic nucleic acids have to cross the lipid-rich plasmatic and/or endosomal membrane, before being degraded into lysosomes. It takes less than one hour for newly endocytosed liposomes to reach highly acidic lysosomes, meaning that the degradation of the carried gene occurs rapidly, thus limiting the transfection efficiency. We propose to use a new pH-sensitive lipid able to change its conformation upon protonation at endosomal pH values, leading to the disruption of the lipidic bilayer and thus to the fast release of the nucleic acids into the cytosol. It is expected that this new pH-sensitive mechanism promote endosomal escape of the gene, thereby its transfection efficiency. The main challenge of this work was to design a preparation presenting fast-responding lipidic bilayer destabilization properties at endosomal pH 5 while remaining stable at blood pH value and during storage. A series of pH-sensitive lipids able to perform a conformational switch upon acidification were designed and synthesized. Liposomes containing these switchable lipids, as well as co-lipids were prepared and characterized. The liposomes were stable at 4°C and pH 7.4 for several months. Incubation with siRNA led to the full entrapment of nucleic acids as soon as the positive/negative charge ratio was superior to 2. The best liposomal formulation demonstrated a silencing efficiency up to 10% on HeLa cells, very similar to a commercial agent, with a lowest toxicity than the commercial agent. Using flow cytometry and microscopy assays, we demonstrated that drop of pH was required for the transfection efficiency, since bafilomycin blocked the transfection efficiency. Additional evidence was brought by the synthesis of a negative control lipid, which was unable to switch its conformation, and consequently exhibited no transfection ability. Mechanistic studies revealed that the uptake was mediated through endocytosis, by clathrin and caveolae pathways, as reported for previous lipid nanoparticle systems. This potent system was used for the treatment of hypercholesterolemia. The switchable lipids were able to knockdown PCSK9 expression on human hepatocytes (Huh-7). Its efficiency is currently evaluated on in vivo mice model of PCSK9 KO mice. In summary, we designed and optimized a new cationic pH-sensitive lipid for gene delivery. Its transfection efficiency is similar to the best available commercial agent, without the usually associated toxicity. The promising results lead to its use for the treatment of hypercholesterolemia on a mice model. Anticancer applications and pulmonary chronic disease are also currently investigated.

Keywords: liposomes, siRNA, pH-sensitive, molecular switch

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Authors: Despina Giannadaki, Jos Lelieveld, Andrea Pozzer, John Evans

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Outdoor air pollution by fine particles ranks among the top ten global health risk factors that can lead to premature mortality. Epidemiological cohort studies, mainly conducted in United States and Europe, have shown that the long-term exposure to PM2.5 (particles with an aerodynamic diameter less than 2.5μm) is associated with increased mortality from cardiovascular, respiratory diseases and lung cancer. Fine particulates can cause health impacts even at very low concentrations. Previously, no concentration level has been defined below which health damage can be fully prevented. The World Health Organization ambient air quality guidelines suggest an annual mean PM2.5 concentration limit of 10μg/m3. Populations in large parts of the world, especially in East and Southeast Asia, and in the Middle East, are exposed to high levels of fine particulate pollution that by far exceeds the World Health Organization guidelines. The aim of this work is to evaluate the implementation of recent air quality standards for PM2.5 in the EU, the US and other countries worldwide and estimate what measures will be needed to substantially reduce premature mortality. We investigated premature mortality attributed to fine particulate matter (PM2.5) under adults ≥ 30yrs and children < 5yrs, applying a high-resolution global atmospheric chemistry model combined with epidemiological concentration-response functions. The latter are based on the methodology of the Global Burden of Disease for 2010, assuming a ‘safe’ annual mean PM2.5 threshold of 7.3μg/m3. We estimate the global premature mortality by PM2.5 at 3.15 million/year in 2010. China is the leading country with about 1.33 million, followed by India with 575 thousand and Pakistan with 105 thousand. For the European Union (EU) we estimate 173 thousand and the United States (US) 52 thousand in 2010. Based on sensitivity calculations we tested the gains from PM2.5 control by applying the air quality guidelines (AQG) and standards of the World Health Organization (WHO), the EU, the US and other countries. To estimate potential reductions in mortality rates we take into consideration the deaths that cannot be avoided after the implementation of PM2.5 upper limits, due to the contribution of natural sources to total PM2.5 and therefore to mortality (mainly airborne desert dust). The annual mean EU limit of 25μg/m3 would reduce global premature mortality by 18%, while within the EU the effect is negligible, indicating that the standard is largely met and that stricter limits are needed. The new US standard of 12μg/m3 would reduce premature mortality by 46% worldwide, 4% in the US and 20% in the EU. Implementing the AQG by the WHO of 10μg/m3 would reduce global premature mortality by 54%, 76% in China and 59% in India. In the EU and US, the mortality would be reduced by 36% and 14%, respectively. Hence, following the WHO guideline will prevent 1.7 million premature deaths per year. Sensitivity calculations indicate that even small changes at the lower PM2.5 standards can have major impacts on global mortality rates.

Keywords: air quality guidelines, outdoor air pollution, particulate matter, premature mortality

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Authors: Ali Kassem, Yhea Kishik, Ali Hassan, Mohamed Abdelwahab

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Introduction: Accelerated coronary and peripheral vascular atherosclerosis is one of the most common and chronic complications of diabetes mellitus. A recent aspect of coronary artery disease in this condition is its silent nature. The aim of the work: Detection of the prevalence of silent myocardial ischemia (SMI) in Upper Egypt type 2 diabetic males and to select male diabetic population who should be screened for SMI. Patients and methods: 100 type 2 diabetic male patients with a negative history of angina or anginal equivalent symptoms and 30 healthy control were included. Full medical history and thorough clinical examination were done for all participants. Fasting and post prandial blood glucose level, lipid profile, (HbA1c), microalbuminuria, and C-reactive protein were done for all participants Resting ECG, trans-thoracic echocardiography, treadmill exercise ECG, myocardial perfusion imaging were done for all participants and patients positive for one or more NITs were subjected for coronary angiography. Results Twenty nine patients (29%) were positive for one or more NITs in the patients group compared to only one case (3.3%) in the controls. After coronary angiography, 20 patients were positive for significant coronary artery stenosis in the patients group, while it was refused to be done by the patient in the controls. There were statistical significant difference between the two groups regarding, hypertension, dyslipidemia and obesity, family history of DM and IHD with higher levels of microalbuminuria, C-reactive protein, total lipids in patient group versus controls According to coronary angiography, patients were subdivided into two subgroups, 20 positive for SMI (positive for coronary angiography) and 80 negative for SMI (negative for coronary angiography). No statistical difference regarding family history of DM and type of diabetic therapy was found between the two subgroups. Yet, smoking, hypertension, obesity, dyslipidemia and family history of IHD were significantly higher in diabetics positive versus those negative for SMI. 90% of patients in subgroup positive for SMI had two or more cardiac risk factors while only two patients had one cardiac risk factor (10%). Uncontrolled DM was detected more in patients positive for SMI. Diabetic complications were more prevalent in patients positive for SMI versus those negative for SMI. Most of the patients positive for SMI have DM more than 5 years duration. Resting ECG and resting Echo detected only 6 and 11 cases, respectively, of the 20 positive cases in group positive for SMI compared to treadmill exercise ECG and myocardial perfusion imaging that detected 16 and 18 cases respectively, Conclusion: Type 2 diabetic male patients should be screened for detection of SMI when aged above 50 years old, diabetes duration is more than 5 years, presence of two or more cardiac risk factors and/or patients suffering from one or more of the chronic diabetic complications. CRP, is an important parameter for selection of type 2 diabetic male patients who should be screened for SMI. Non invasive cardiac tests are reliable for screening of SMI in these patients in our locality.

Keywords: C-reactive protein, Silent myocardial ischemia, Stress tests, type 2 DM

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Authors: Guntur Bagus Pamungkas

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As part of a tropical country that is normally rich in forest land areas, Indonesia has always been in the world's spotlight due to its significantly increasing process of deforestation. In one hand, it is related to the mainstay for maintaining the sustainability of the earth's ecosystem functions. On the other hand, they also cover the various potential sources of the global economy. Therefore, it can always be the target of different scale of investors to excessively exploit them. No wonder the emergence of disasters in various characteristics always comes up. In fact, the deforestation phenomenon does not only occur in various forest land areas in the main islands of Indonesia but also includes Java Island, the most densely populated areas in the world. This island only remains the forest land of about 9.8% of the total forest land in Indonesia due to its long history of it, especially in Central Java Province, the most densely populated area in Java. Again, not surprisingly, this province belongs to the area with the highest frequency of disasters because of it, landslides in particular. One of the areas that often experience it is Banjarnegara District, especially in mountainous areas that lies in the range from 1000 to 3000 meters above sea level, where the remains of land forest area can easyly still be found. Even among them still leaves less untouchable tropical rain forest whose area also covers part of a neighboring district, Pekalongan, which is considered to be the rest of the world's little paradise on Earth. The district's landscape is indeed beautiful, especially in the Dieng area, a major tourist destination in Central Java Province after Borobudur Temple. However, annually hazardous always threatens this district due to this landslide disaster. Even, there was a tragic event that was buried with its inhabitants a few decades ago. This research aims to find part of the concept of effective forest management through monitoring the presence of remaining forest areas in this area. The research implemented monitoring of deforestation rates using the Stochastic Cellular Automata-Markov Chain (SCA-MC) method, which serves to provide a spatial simulation of land use and cover changes (LULCC). This geospatial process uses the Landsat-8 OLI image product with Thermal Infra-Red Sensors (TIRS) Band 10 in 2020 and Landsat 5 TM with TIRS Band 6 in 2010. Then it is also integrated with physical and social geography issues using the QGIS 2.18.11 application with the Mollusce Plugin, which serves to clarify and calculate the area of land use and cover, especially in forest areas—using the LULCC method, which calculates the rate of forest area reduction in 2010-2020 in Banjarnegara District. Since the dependence of this area on the use of forest land is quite high, concepts and preventive actions are needed, such as rehabilitation and reforestation of critical lands through providing proper monitoring and targeted forest management to restore its ecosystem in the future.

Keywords: deforestation, populous area, LULCC method, proper control and effective forest management

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Authors: Azza A. Ali, Hebatalla I. Ahmed, Asmaa Abdelaty

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Background: Manganese (Mn) is a naturally occurring element. Exposure to high levels of Mn causes neurotoxic effects and represents an environmental risk factor. Mn neurotoxicity is poorly understood but changing of AChE activity, monoamines and oxidative stress has been established. Bisphenol A (BPA) is a synthetic compound widely used in the production of polycarbonate plastics. There is considerable debate about whether its exposure represents an environmental risk. Caffeine is one of the major contributors to the dietary antioxidants which prevent oxidative damage and may reduce the risk of chronic neurodegenerative diseases. Epigallocatechin-3-gallate is another major component of green tea and has known interactions with caffeine. It also has health-promoting effects in CNS. Objective: To evaluate the potential protective effects of Caffeine and/or EGCG against Mn-induced neurotoxicity either alone or in the presence of BPA in rats. Methods: Seven groups of rats were used and received daily for 5 weeks MnCl2.4H2O (10 mg/kg, IP) except the control group which received saline, corn oil and distilled H2O. Mn was injected either alone or in combination with each of the following: BPA (50 mg/kg, PO), caffeine (10 mg/kg, PO), EGCG (5 mg/kg, IP), caffeine + EGCG and BPA +caffeine +EGCG. All rats were examined in five behavioral tests (grid, bar, swimming, open field and Y- maze tests). Biochemical changes in monoamines, caspase-3, PGE2, GSK-3B, glutamate, acetyl cholinesterase and oxidative parameters, as well as histopathological changes in the brain, were also evaluated for all groups. Results: Mn significantly increased MDA and nitrite content as well as caspase-3, GSK-3B, PGE2 and glutamate levels while significantly decreased TAC and SOD as well as cholinesterase in the striatum. It also decreased DA, NE and 5-HT levels in the striatum and frontal cortex. BPA together with Mn enhanced oxidative stress generation induced by Mn while increased monoamine content that was decreased by Mn in rat striatum. BPA abolished neuronal degeneration induced by Mn in the hippocampus but not in the substantia nigra, striatum and cerebral cortex. Behavioral examinations showed that caffeine and EGCG co-administration had more pronounced protective effect against Mn-induced neurotoxicity than each one alone. EGCG alone or in combination with caffeine prevented neuronal degeneration in the substantia nigra, striatum, hippocampus and cerebral cortex induced by Mn while caffeine alone prevented neuronal degeneration in the substantia nigra and striatum but still showed some nuclear pyknosis in cerebral cortex and hippocampus. The marked protection of caffeine and EGCG co-administration also confirmed by the significant increase in TAC, SOD, ACHE, DA, NE and 5-HT as well as the decrease in MDA, nitrite, caspase-3, PGE2, GSK-3B, the glutamic acid in the striatum. Conclusion: Neuronal degeneration induced by Mn showed some inhibition with BPA exposure despite the enhancement in oxidative stress generation. Co-administration of EGCG and caffeine can protect against neuronal degeneration induced by Mn and improve behavioral deficits associated with its neurotoxicity. The protective effect of EGCG was more pronounced than that of caffeine even with BPA co-exposure.

Keywords: manganese, bisphenol a, caffeine, epigallocatechin-3-gallate, neurotoxicity, behavioral tests, rats

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Authors: Mohammad Ehsani, Iman Zarei, Soudabeh Moazemigoudarzi

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The aim of this study is to determine Pro-Environmental Behavioral Intention of Mountain Hikers to the Theory of Planned Behavior. According to many researchers nature-based recreation activities play a significant role in the tourism industry and have provided myriad opportunities for the protection of natural areas. It is essential to investigate individuals' behavior during such activities to avoid further damage to precious and dwindling natural resources. This study develops a robust model that provides a comprehensive understanding of the formation of pro-environmental behavioral intentions among climbers of Mount Damavand National Park in Iran. To this end, we combined the theory of planned behavior (TPB), value-belief-norm theory (VBN), and a hierarchical model of leisure constraints to predict individuals’ pro-environmental hiking behavior during outdoor recreation. It was used structural equation modeling to test the theoretical framework. A sample of 787 climbers was analyzed. Among the theory of planned behavior variables, perceived behavioral control showed the strongest association with behavioral intention (β = .57). This relationship indicates that if people feel they can have fewer negative impacts on national resources while hiking, it will result in more environmentally acceptable behavior. Subjective norms had a moderate positive impact on behavioral intention, indicating the importance of other people on the individual's behavior. Attitude had a small positive effect on intention. Ecological worldview positively influenced attitude and personal belief. Personal belief (awareness of consequences and ascribed responsibility) showed a positive association with TPB variables. Although the data showed a high average score in awareness of consequences (mean = 4.219 out of 5), evidence from Damavand Mount shows that there are many environmental issues that need addressing (e.g., vast amounts of garbage). National park managers need to make sure that their solutions result in awareness about proenvironmental behavior (PEB). Findings showed that negative relationship between constraints and all TPB predictors. Providing proper restrooms and parking spaces in campgrounds, strategies controlling limiting capacity and solutions for removing waste from high altitudes are helpful to decrease the negative impact of structural constraints. In order to address intrapersonal constraints, managers should provide opportunities to interest individuals in environmental activities, such as environmental celebrations or making documentaries about environmental issues. Moreover, promoting a culture of environmental protection in the Damavand Mount area would reduce interpersonal constraints. Overall, the proposed model improved the explanatory power of the TPB by predicting 64.7% of intention compared to the original TPB that accounted for 63.8% of the variance in intention.

Keywords: theory of planned behavior, pro-environmental behavior, national park, constraints

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Authors: Susie Pryor, Palak Sadhwani

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The purpose of this research is to provide the foundations for a broad research agenda examining the role loneliness plays in entrepreneurship. While qualitative research in entrepreneurship incidentally captures the existence of loneliness as a part of the lived reality of entrepreneurs, to the authors’ knowledge, no academic work has to date explored this construct in this context. Moreover, many individuals reporting high levels of loneliness (women, ethnic minorities, immigrants, low income, low education) reflect those who are currently driving small business growth in the United States. Loneliness is a persistent state of emotional distress which results from feelings of estrangement and rejection or develops in the absence of social relationships and interactions. Empirical work finds links between loneliness and depression, suicide and suicide ideation, anxiety, hostility and passiveness, lack of communication and adaptability, shyness, poor social skills and unrealistic social perceptions, self-doubts, fear of rejection, and negative self-evaluation. Lonely individuals have been found to exhibit lower levels of self-esteem, higher levels of introversion, lower affiliative tendencies, less assertiveness, higher sensitivity to rejection, a heightened external locus of control, intensified feelings of regret and guilt over past events and rigid and overly idealistic goals concerning the future. These characteristics are likely to impact entrepreneurs and their work. Research identifies some key dangers of loneliness. Loneliness damages human love and intimacy, can disturb and distract individuals from channeling creative and effective energies in a meaningful way, may result in the formation of premature, poorly thought out and at times even irresponsible decisions, and produce hard and desensitized individuals, with compromised health and quality of life concerns. The current study utilizes meta-analysis and text analytics to distinguish loneliness from other related constructs (e.g., social isolation) and categorize antecedents and effects of loneliness across subpopulations. This work has the potential to materially contribute to the field of entrepreneurship by cleanly defining constructs and providing foundational background for future research. It offers a richer understanding of the evolution of loneliness and related constructs over the life cycle of entrepreneurial start-up and development. Further, it suggests preliminary avenues for exploration and methods of discovery that will result in knowledge useful to the field of entrepreneurship. It is useful to both entrepreneurs and those work with them as well as academics interested in the topics of loneliness and entrepreneurship. It adopts a grounded theory approach.

Keywords: entrepreneurship, grounded theory, loneliness, meta-analysis

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Authors: Lucas Derks, Christine Beenhakker, Michiel Brandt, Gert Arts, Ruud van Langeveld

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Background: The method Depression in Awareness Space (DAS) is a psychotherapeutic intervention technique based on the principles of spatial cognition and imagination therapy with spatial components. The basic assumptions are: mental space is the primary organizing principle in the mind, and all psychological issues can be treated by first locating and by next relocating the conceptualizations involved. The most clinical experience was gathered over the last 20 years in the area of social issues (with the social panorama model). The latter work led to the conclusion that a mental object (image) gains emotional impact when it is placed more central, closer and higher in the visual field – and vice versa. Changing the locations of mental objects in space thus alters the (socio-) emotional meaning of the relationships. The experience of depression seems always associated with darkness. Psychologists tend to see the link between depression and darkness as a metaphor. However, clinical practice hints to the existence of more literal forms of darkness. Aims: The aim of the method Depression in Awareness Space is to reduce the distress of clients with depression in the clinical counseling practice, as a reliable alternative method of psychological therapy for the treatment of depression. The method Depression in Awareness Space aims at making dark areas smaller, lighter and more transparent in order to identify the problem or the cause of the depression which lies behind the darkness. It was hypothesized that the darkness is a subjective side-effect of the neurological process of repression. After reducing the dark clouds the real problem behind the depression becomes more visible, allowing the client to work on it and in that way reduce their feelings of depression. This makes repression of the issue obsolete. Results: Clients could easily get into their 'sadness' when asked to do so and finding the location of the dark zones proved pretty easy as well. In a recent pilot study with five participants with mild depressive symptoms (measured on two different scales and tested against an untreated control group with similar symptoms), the first results were also very promising. If the mental spatial approach to depression can be proven to be really effective, this would be very good news. The Society of Mental Space Psychology is now looking for sponsoring of an up scaled experiment. Conclusions: For spatial cognition and the research into spatial psychological phenomena, the discovery of dark areas can be a step forward. Beside out of pure scientific interest, it is great to know that this discovery has a clinical implication: when darkness can be connected to depression. Also, darkness seems to be more than metaphorical expression. Progress can be monitored over measurement tools that quantify the level of depressive symptoms and by reviewing the areas of darkness.

Keywords: depression, spatial cognition, spatial imagery, social panorama

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Authors: Antonio Martín-Pardo

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With regard to the context in which this paper is inserted, it is noteworthy that the current criminal policy model in which we find immersed, denominated by some doctrine sector as the citizen security model, is characterized by a marked tendency towards the discredit of expert knowledge. This type of technic knowledge has been displaced by the common sense and by the daily experience of the people at the time of legislative drafting, as well as by excessive attention to the short-term political effects of the law. Despite this criminal-political adverse scene, we still find valuable efforts in the side of experts to bring some rationality to the legislative development. This is the case of the proposal for a new cannabis regulation model in Spain carried out by the Cannabis Policy Studies Group (hereinafter referred as ‘GEPCA’). The GEPCA is a multidisciplinary group composed by authors with multiple/different orientations, trajectories and interests, but with a common minimum objective: the conviction that the current situation regarding cannabis is unsustainable and, that a rational legislative solution must be given to the growing social pressure for the regulation of their consumption and production. This paper details the main lines through which this technical proposal is developed with the purpose of its dissemination and discussion in the Congress. The basic methodology of the proposal is inductive-expository. In that way, firstly, we will offer a brief, but solid contextualization of the situation of cannabis in Spain. This contextualization will touch on issues such as the national regulatory situation and its relationship with the international context; the criminal, judicial and penitentiary impact of the offer and consumption of cannabis, or the therapeutic use of the substance, among others. In second place, we will get down to the business properly by detailing the minutia of the three main cannabis access channels that are proposed. Namely: the regulated market, the associations of cannabis users and personal self-cultivation. In each of these options, especially in the first two, special attention will be paid to both, the production and processing of the substance and the necessary administrative control of the activity. Finally, in a third block, some notes will be given on a series of subjects that surround the different access options just mentioned above and that give fullness and coherence to the proposal outlined. Among those related issues we find some such as consumption and tenure of the substance; the issue of advertising and promotion of cannabis; consumption in areas of special risk (work or driving v. g.); the tax regime; the need to articulate evaluation instruments for the entire process; etc. The main conclusion drawn from the analysis of the proposal is the unsustainability of the current repressive system, clearly unsuccessful, and the need to develop new access routes to cannabis that guarantee both public health and the rights of people who have freely chosen to consume it.

Keywords: cannabis regulation proposal, cannabis policies studies group, criminal policy, expertise participation

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Authors: Hai L. Tran

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Previous research on agenda setting effects has often focused on the top-down influence of the media at the aggregate level, while overlooking the capacity of audience members to select media and content to fit their individual dispositions. The decentralized characteristics of online communication and digital news create more choices and greater user control, thereby enabling each audience member to seek out a unique blend of media sources, issues, and elements of messages and to mix them into a coherent individual picture of the world. This study examines how audiences use media differently depending on their prior dispositions, thereby making sense of the world in ways that are congruent with their preferences and cognitions. The current undertaking is informed by theoretical frameworks from two distinct lines of scholarship. According to the ideological migration hypothesis, individuals choose to live in communities with ideologies like their own to satisfy their need to belong. One tends to move away from Zip codes that are incongruent and toward those that are more aligned with one’s ideological orientation. This geographical division along ideological lines has been documented in social psychology research. As an extension of agenda setting, the agendamelding hypothesis argues that audiences seek out information in attractive media and blend them into a coherent narrative that fits with a common agenda shared by others, who think as they do and communicate with them about issues of public. In other words, individuals, through their media use, identify themselves with a group/community that they want to join. Accordingly, the present study hypothesizes that because ideology plays a role in pushing people toward a physical community that fits their need to belong, it also leads individuals to receive an idiosyncratic blend of media and be influenced by such selective exposure in deciding what issues are more relevant. Consequently, the individualized focus of media choices impacts how audiences perceive political news coverage and what they know about political issues. The research project utilizes recent data from The American Trends Panel survey conducted by Pew Research Center to explore the nuanced nature of agenda setting at the individual level and amid heightened polarization. Hypothesis testing is performed with both nonparametric and parametric procedures, including regression and path analysis. This research attempts to explore the media-public relationship from a bottom-up approach, considering the ability of active audience members to select among media in a larger process that entails agenda setting. It helps encourage agenda-setting scholars to further examine effects at the individual, rather than aggregate, level. In addition to theoretical contributions, the study’s findings are useful for media professionals in building and maintaining relationships with the audience considering changes in market share due to the spread of digital and social media.

Keywords: agenda setting, agendamelding, audience fragmentation, ideological migration, partisanship, polarization

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Authors: Merve Uzuner Sahin, Kumru D. Atalay, Berna Dengiz

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In today’s competitive market, there are many alternative products that can be used in similar manner and purpose. Therefore, the utility of the product is an important issue for the preferability of the brand. This utility could be measured in terms of its functionality, durability, reliability. These all are affected by the system capabilities. Reliability is an important system design criteria for the manufacturers to be able to have high availability. Availability is the probability that a system (or a component) is operating properly to its function at a specific point in time or a specific period of times. System availability provides valuable input to estimate the production rate for the company to realize the production plan. When considering only the corrective maintenance downtime of the system, mean time between failure (MTBF) and mean time to repair (MTTR) are used to obtain system availability. Also, the MTBF and MTTR values are important measures to improve system performance by adopting suitable maintenance strategies for reliability engineers and practitioners working in a system. Failure and repair time probability distributions of each component in the system should be known for the conventional availability analysis. However, generally, companies do not have statistics or quality control departments to store such a large amount of data. Real events or situations are defined deterministically instead of using stochastic data for the complete description of real systems. A fuzzy set is an alternative theory which is used to analyze the uncertainty and vagueness in real systems. The aim of this study is to present a novel approach to compute system availability using representation of MTBF and MTTR in fuzzy numbers. Based on the experience in the system, it is decided to choose 3 different spread of MTBF and MTTR such as 15%, 20% and 25% to obtain lower and upper limits of the fuzzy numbers. To the best of our knowledge, the proposed method is the first application that is used fuzzy MTBF and fuzzy MTTR for fuzzy system availability estimation. This method is easy to apply in any repairable production system by practitioners working in industry. It is provided that the reliability engineers/managers/practitioners could analyze the system performance in a more consistent and logical manner based on fuzzy availability. This paper presents a real case study of a repairable multi-stage production line in lead-acid battery production factory in Turkey. The following is focusing on the considered wet-charging battery process which has a higher production level than the other types of battery. In this system, system components could exist only in two states, working or failed, and it is assumed that when a component in the system fails, it becomes as good as new after repair. Instead of classical methods, using fuzzy set theory and obtaining intervals for these measures would be very useful for system managers, practitioners to analyze system qualifications to find better results for their working conditions. Thus, much more detailed information about system characteristics is obtained.

Keywords: availability analysis, battery production system, fuzzy sets, triangular fuzzy numbers (TFNs)

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Authors: Samuele Ghignoli, Valentina de Lorenzi, Gianmarco Ferri, Stefano Luin, Francesco Cardarelli

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Insulin and glucagon are the two essential hormones for maintaining proper blood glucose homeostasis, which is disrupted in Diabetes. A constantly growing research interest has been focused on the study of the subcellular structures involved in hormone secretion, namely insulin- and glucagon-containing granules, and on the mechanisms regulating their behaviour. Yet, while several successful attempts were reported describing the dynamic properties of insulin granules, little is known about their counterparts in α cells, the glucagon-containing granules. To fill this gap, we used αTC1 clone 9 cells as a model of α cells and ZIGIR as a fluorescent Zinc chelator for granule labelling. We started by using spatiotemporal fluorescence correlation spectroscopy in the form of imaging-derived mean square displacement (iMSD) analysis. This afforded quantitative information on the average dynamical and structural properties of glucagon granules having insulin granules as a benchmark. Interestingly, the iMSD sensitivity to average granule size allowed us to confirm that glucagon granules are smaller than insulin ones (~1.4 folds, further validated by STORM imaging). To investigate possible heterogeneities in granule dynamic properties, we moved from correlation spectroscopy to single particle tracking (SPT). We developed a MATLAB script to localize and track single granules with high spatial resolution. This enabled us to classify the glucagon granules, based on their dynamic properties, as ‘blocked’ (i.e., trajectories corresponding to immobile granules), ‘confined/diffusive’ (i.e., trajectories corresponding to slowly moving granules in a defined region of the cell), or ‘drifted’ (i.e., trajectories corresponding to fast-moving granules). In cell-culturing control conditions, results show this average distribution: 32.9 ± 9.3% blocked, 59.6 ± 9.3% conf/diff, and 7.4 ± 3.2% drifted. This benchmarking provided us with a foundation for investigating selected experimental conditions of interest, such as the glucagon-granule relationship with the cytoskeleton. For instance, if Nocodazole (10 μM) is used for microtubule depolymerization, the percentage of drifted motion collapses to 3.5 ± 1.7% while immobile granules increase to 56.0 ± 10.7% (remaining 40.4 ± 10.2% of conf/diff). This result confirms the clear link between glucagon-granule motion and cytoskeleton structures, a first step towards understanding the intracellular behaviour of this subcellular compartment. The information collected might now serve to support future investigations on glucagon granules in physiology and disease. Acknowledgment: This work has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 866127, project CAPTUR3D).

Keywords: glucagon granules, single particle tracking, correlation spectroscopy, ZIGIR

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Authors: Adae Amoako, Daniel Montero, Peter Murray, George Pujalte

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We present a case of a 42-year-old, right-handed Caucasian male who presented to a medical orthopedics clinic with left wrist pain. The patient indicated that the pain started two months prior to the visit. He could only remember helping a friend move furniture prior to the onset of pain. Examination of the left wrist showed limited extension compared to the right. There was clicking with flexion and extension of the wrist on the dorsal aspect. Mild tenderness was noticed over the distal radioulnar joint. There was ulnar and radial deviation on provocation. Initial 4-view x-rays of the left wrist showed mild radiocarpal and scapho-trapezium-trapezoid (ST-T) osteoarthritis, with subchondral cysts seen in the lunate and scaphoid, with no obvious fractures. The patient was initially put in a wrist brace and diclofenac topical gel was prescribed for pain control, as a patient could not take non-steroidal anti-inflammatory drugs (NSAIDs) due to gastritis. Despite diclofenac topical gel use and bracing, symptoms remained, and a steroid injection with 1 mL of lidocaine with 10 mg of triamcinolone acetonide was performed under fluoroscopy. He obtained some relief but after 3 months, the injection had to be repeated. On 2-month follow up after the initial evaluation, symptoms persisted. Magnetic resonance imaging (MRI) was obtained which showed an abnormal T1 hypodense signal involving the proximal pole of the scaphoid and articular collapse proximally of the scaphoid, with marked irregularity of the overlying cartilage, suggesting a remote injury, findings consistent with avascular necrosis of the proximal pole of the scaphoid. A month after that, the patient had the left proximal pole of the scaphoid debrided and an intercompartmental supraretinacular artery vascularized. Pedicle bone graft reconstruction of the proximal pole of the left scaphoid was done. A non-vascularized autograft from the left radius was also applied. He was put in a thumb spica cast with the interphalangeal joint free for 6 weeks. On 6-week follow-up after surgery, the patient was healing well and could make a composite fist with his left hand. The diagnosis of Preiser’s disease is primarily based on radiological findings. Due to the fact that necrosis happens over a period of time, most AVNs are diagnosed at the late stages of the disease. There appear to be no specific guidelines on the management AVN of the scaphoid. In the past, immobilization and arthroscopic debridement had been used. Radial osteotomy has also been tried. Vascularized bone grafts have also been used to treat Preiser’s disease. In our patient, we used three of these treatment modalities, starting with conservative management with topical NSAIDS and immobilization, then debridement with vascularized bone grafts.

Keywords: wrist pain, avascular necrosis of the scaphoid, Preiser’s disease, vascularized bone grafts

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Authors: Sarika Gupta, Harshika Khanna, Ajay K Verma, Surya Kant

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Background: Drug-resistant tuberculosis (DR-TB) is a growing health challenge to global TB control efforts. Pediatric DR-TB is one of the neglected infectious diseases. In our previously published report, we have notified an increased prevalence of DR-TB in the pediatric population at a tertiary health care centre in North India which was estimated as 17.4%, 15.1%, 18.4%, and 20.3% in (%) in the year 2018, 2019, 2020, and 2021. Limited evidence exists about a pattern of drug resistance, side effect profile and programmatic outcomes of Paediatric DR-TB treatment. Therefore, this study was done to find out the pattern of resistance, side effect profile and treatment outcome. Methodology: This was a prospective cohort study conducted at the nodal drug-resistant tuberculosis centre of a tertiary care hospital in North India from January 2021 to December 2022. Subjects included children aged between 0-18 years of age with a diagnosis of DR-TB, on the basis of GeneXpert (rifampicin [RIF] resistance detected), line probe assay and drug sensitivity testing (DST) of M. tuberculosis (MTB) grown on a culture of body fluids. Children were classified as monoresistant TB, polyresistant TB (resistance to more than 1 first-line anti-TB drug, other than both INH and RIF), MDR-TB, pre-XDR-TB and XDR-TB, as per the WHO classification. All the patients were prescribed DR TB treatment as per the standard guidelines, either shorter oral DR-TB regimen or a longer all-oral MDR/XDR-TB regimen (age below five years needed modification). All the patients were followed up for side effects of treatment once per month. The patient outcomes were categorized as good outcomes if they had completed treatment and cured or were improving during the course of treatment, while bad outcomes included death or not improving during the course of treatment. Results: Of the 50 pediatric patients included in the study, 34 were females (66.7%) and 16 were male (31.4%). Around 33 patients (64.7%) were suffering from pulmonary TB, while 17 (33.3%) were suffering from extrapulmonary TB. The proportions of monoresistant TB, polyresistant TB, MDR-TB, pre-XDR-TB and XDR-TB were 2.0%, 0%, 50.0%, 30.0% and 18.0%, respectively. Good outcome was reported in 40 patients (80.0%). The 10 bad outcomes were 7 deaths (14%) and 3 (6.0%) children who were not improving. Adverse events (single or multiple) were reported in all the patients, most of which were mild in nature. The most common adverse events were metallic taste 16(31.4%), rash and allergic reaction 15(29.4%), nausea and vomiting 13(26.0%), arthralgia 11 (21.6%) and alopecia 11 (21.6%). Serious adverse event of QTc prolongation was reported in 4 cases (7.8%), but neither arrhythmias nor symptomatic cardiac side effects occurred. Vestibular toxicity was reported in 2(3.9%), and psychotic symptoms in 4(7.8%). Hepatotoxicity, hypothyroidism, peripheral neuropathy, gynaecomastia, and amenorrhea were reported in 2 (4.0%), 4 (7.8%), 2 (3.9%), 1(2.0%), and 2 (3.9%) respectively. None of the drugs needed to be withdrawn due to uncontrolled adverse events. Conclusion: Paediatric DR TB treatment achieved favorable outcomes in a large proportion of children. DR TB treatment regimen drugs were overall well tolerated in this cohort.

Keywords: pediatric, drug-resistant, tuberculosis, adverse events, treatment

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Authors: A. R. Shokoohi, E. A. M. Bulder, C. Th. van Alphen, D. F. den Hertog, E. J. Hin

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The Northern region of the Netherlands has beautiful landscapes, a nice diversity of green and blue areas, and dispersed settlements. However, some recent population changes can become threats to health and wellbeing in these areas. The rural areas in the three northern provinces -Groningen, Friesland, and Drenthe, see youngsters leave the region for which reason they are aging faster than other regions in the Netherlands. As a result, some villages have faced major population decline that is leading to loss of facilities/amenities and a decrease in accessibility and social cohesion. Those who still live in these villages are relatively old, low educated and have low-income. To develop a deeper understanding of the health status of the people living in these areas, and help them to improve their living environment, the GO!-Method is being applied in this study. This method has been developed by the National Institute for Public Health and the Environment (RIVM) of the Netherlands and is inspired by the broad definition of health by Machteld Huber: the ability to adapt and direct control, in terms of the physical, emotional and social challenges of life, while paying extra attention to vulnerable groups. A healthy living environment is defined as an environment that residents find it pleasant and encourages and supports healthy behavior. The GO!-method integrates six domains that constitute a healthy living environment: health and lifestyle, facilities and development, safety and hygiene, social cohesion and active citizens, green areas, and air and noise pollution. First of all, this method will identify opportunities for a healthier living environment using existing information and perceptions of residents and other local stakeholders in order to strengthen social participation and quality of life in these rural areas. Second, this approach will connect identified opportunities with available and effective evidence-based interventions in order to develop an action plan from the residents and local authorities perspective which will help them to design their municipalities healthier and more resilient. This method is being used for the first time in rural areas to our best knowledge, in close collaboration with the residents and local authorities of the three provinces to create a sustainable process and stimulate social participation. Our paper will present the outcomes of the first phase of this project in collaboration with the municipality of Westerkwartier, located in the northwest of the province of Groningen. And will describe the current situation, and identify local assets, opportunities, and policies relating to healthier environment; as well as needs and challenges to achieve goals. The preliminary results show that rural demographic changes in the northern Netherlands have negative impacts on service provisions and social cohesion, and there is a need to understand this complicated situation and improve the quality of life in those areas.

Keywords: population decline, rural areas, healthy environment, Netherlands

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Authors: E. Obreque-Slier, F. Orellana-Rodríguez, R. López-Solís

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Phenolic compounds are secondary metabolites present in some foods, such as wine. Polyphenols comprise two main groups: flavonoids (anthocyanins, flavanols, and flavonols) and non-flavonoids (stilbenes and phenolic acids). Phenolic acids are low molecular weight non flavonoid compounds that are usually grouped into benzoic (gallic, vanillinic and protocatechuic acids) and cinnamic acids (ferulic, p-coumaric and caffeic acids). Likewise, tannic acid is an important polyphenol constituted mainly by gallic acid. Phenolic compounds are responsible for important properties in foods and drinks, such as color, aroma, bitterness, and astringency. Astringency is a drying, roughing, and sometimes puckering sensation that is experienced on the various oral surfaces during or immediately after tasting foods. Astringency perception has been associated with interactions between flavanols present in some foods and salivary proteins. Despite the quantitative relevance of phenolic acids in food and beverages, there is no information about its effect on salivary proteins and consequently on the sensation of astringency. The objective of this study was assessed the interaction of several phenolic acids (gallic, vanillinic, protocatechuic, ferulic, p-coumaric and caffeic acids) with saliva. Tannic acid was used as control. Thus, solutions of each phenolic acids (5 mg/mL) were mixed with human saliva (1:1 v/v). After incubation for 5 min at room temperature, 15-μL aliquots of the mixtures were dotted on a cellulose membrane and allowed to diffuse. The dry membrane was fixed in 50 g/L trichloroacetic acid, rinsed in 800 mL/L ethanol and stained for protein with Coomassie blue for 20 min, destained with several rinses of 73 g/L acetic acid and dried under a heat lamp. Both diffusion area and stain intensity of the protein spots were semiqualitative estimates for protein-tannin interaction (diffusion test). The rest of the whole saliva-phenol solution mixtures of the diffusion assay were centrifuged and fifteen-μL aliquots of each supernatant were dotted on a cellulose membrane, allowed to diffuse and processed for protein staining, as indicated above. In this latter assay, reduced protein staining was taken as indicative of protein precipitation (precipitation test). The diffusion of the salivary protein was restricted by the presence of each phenolic acids (anti-diffusive effect), while tannic acid did not alter diffusion of the salivary protein. By contrast, phenolic acids did not provoke precipitation of the salivary protein, while tannic acid produced precipitation of salivary proteins. In addition, binary mixtures (mixtures of two components) of various phenolic acids with gallic acid provoked a restriction of saliva. Similar effect was observed by the corresponding individual phenolic acids. Contrary, binary mixtures of phenolic acid with tannic acid, as well tannic acid alone, did not affect the diffusion of the saliva but they provoked an evident precipitation. In summary, phenolic acids showed a relevant interaction with the salivary proteins, thus suggesting that these wine compounds can also contribute to the sensation of astringency.

Keywords: astringency, polyphenols, tannins, tannin-protein interaction

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Authors: Brady Manescau, Ilyas Sellami, Khaled Chetehouna, Charles De Izarra, Rachid Nait-Said, Fati Zidani

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During a fire in an oil and gas refinery, several thermal accidents can occur and cause serious damage to people and environment. Among these accidents, the BLEVE (Boiling Liquid Expanding Vapor Explosion) is most observed and remains a major concern for risk decision-makers. It corresponds to a violent vaporization of explosive nature following the rupture of a vessel containing a liquid at a temperature significantly higher than its normal boiling point at atmospheric pressure. Their effects on the environment generally appear in three ways: blast overpressure, radiation from the fireball if the liquid involved is flammable and fragment hazards. In order to estimate the potential damage that would be caused by such an explosion, risk decision-makers often use quantitative risk analysis (QRA). This analysis is a rigorous and advanced approach that requires a reliable data in order to obtain a good estimate and control of risks. However, in most cases, the data used in QRA are obtained from the empirical correlations. These empirical correlations generally overestimate BLEVE effects because they are based on simplifications and do not take into account real parameters like the geometry effect. Considering that these risk analyses are based on an assessment of BLEVE effects on human life and plant equipment, more precise and reliable data should be provided. From this point of view, the CFD modeling of BLEVE effects appears as a solution to the empirical law limitations. In this context, the main objective is to develop a numerical tool in order to predict BLEVE thermal effects using the CFD code FDS version 6. Simulations are carried out with a mesh size of 1 m. The fireball source is modeled as a vertical release of hot fuel in a short time. The modeling of fireball dynamics is based on a single step combustion using an EDC model coupled with the default LES turbulence model. Fireball characteristics (diameter, height, heat flux and lifetime) issued from the large scale BAM experiment are used to demonstrate the ability of FDS to simulate the various steps of the BLEVE phenomenon from ignition up to total burnout. The influence of release parameters such as the injection rate and the radiative fraction on the fireball heat flux is also presented. Predictions are very encouraging and show good agreement in comparison with BAM experiment data. In addition, a numerical study is carried out on an operational propane accumulator in an Algerian gas processing plant of SONATRACH company located in the Hassi R’Mel Gas Field (the largest gas field in Algeria).

Keywords: BLEVE effects, CFD, FDS, fireball, LES, QRA

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Authors: Shiamaa Eltantawy, Gihan Sobhy, Alif Alaam

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Wilson disease, or hepatolenticular degeneration, is an autosomal recessive disease that results in excess copper buildup in the body. It primarily affects the liver and basal ganglia of the brain, but it can affect other organ systems. Musculoskeletal abnormalities, including premature osteoarthritis, skeletal deformity, and pathological bone fractures, can occasionally be found in WD patients with a hepatic or neurologic type. The aim was to assess the prevalence of osteoporosis and osteopenia in Wilson’s disease patients. This case-control study was conducted on ninety children recruited from the inpatient ward and outpatient clinic of the Paediatric Hepatology, Gastroenterology, and Nutrition department of the National Liver Institute at Menofia University, aged from 1 to 18 years. Males were 49, and females were 41. Children were divided into three groups: (Group I) consisted of thirty patients with WD; (Group II) consisted of thirty patients with chronic liver disease other than WD; (Group III) consisted of thirty age- and sex-matched healthy The exclusion criteria were patients with hyperparathyroidism, hyperthyroidism, renal failure, Cushing's syndrome, and patients on certain drugs such as chemotherapy, anticonvulsants, or steroids. All patients were subjected to the following: 1- Full history-taking and clinical examination. 2-Laboratory investigations: (FBC,ALT,AST,serum albumin, total protein, total serum bilirubin,direct bilirubin,alkaline phosphatase, prothrombin time, serum critine,parathyroid hormone, serum calcium, serum phosphrus). 3-Bone mineral density (BMD, gm/cm2) values were measured by dual-energy X-ray absorptiometry (DEXA). The results revealed that there was a highly statistically significant difference between the three groups regarding the DEXA scan, and there was no statistically significant difference between groups I and II, but the WD group had the lowest bone mineral density. The WD group had a large number of cases of osteopenia and osteoporosis, but there was no statistically significant difference with the group II mean, while a high statistically significant difference was found when compared to group III. In the WD group, there were 20 patients with osteopenia, 4 patients with osteoporosis, and 6 patients who were normal. The percentages were 66.7%, 13.3%, and 20%, respectively. Therefore, the largest number of cases in the WD group had osteopenia. There was no statistically significant difference found between WD patients on different treatment regimens regarding DEXA scan results (Z-Score). There was no statistically significant difference found between patients in the WD group (normal, osteopenic, or osteoporotic) regarding phosphorus (mg/dL), but there was a highly statistically significant difference found between them regarding ionised Ca (mmol/L). Therefore, there was a decrease in bone mineral density when the Ca level was decreased. In summary, Wilson disease is associated with bone demineralization. The largest number of cases in the WD group in our study had osteopenia (66.7%). Different treatment regimens (zinc monotherapy, Artamin, and zinc) as well as different laboratory parameters have no effect on bone mineralization in WD cases. Decreased ionised Ca is associated with low BMD in WD patients. Children with WD should be investigated for BMD.

Keywords: wilson disease, Bone mineral density, liver disease, osteoporosis

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Authors: Alinka Molnár-Tóth, Tímea Tánczos, Regina Barna, Katalin Jakab, Péter Klivényi

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Supported by neuroscientific findings, the so-called Hub-and-Spoke model of the human semantic system is based on two subcomponents of semantic cognition, namely the semantic control process and semantic representation. Our semantic knowledge is multimodal in nature, as the knowledge system stored in relation to a conception is extensive and broad, while different aspects of the conception may be relevant depending on the purpose. The motivation of our research is to develop a new diagnostic measurement procedure based on the preservation of semantic representation, which is appropriate to the specificities of the Hungarian language and which can be used to compare the non-verbal semantic knowledge of healthy and aphasic persons. The development of the test will broaden the Hungarian clinical diagnostic toolkit, which will allow for more specific therapy planning. The sample of healthy persons (n=480) was determined by the last census data for the representativeness of the sample. Based on the concept of the Pyramids and Palm Tree Test, and according to the characteristics of the Hungarian language, we have elaborated a test based on different types of semantic information, in which the subjects are presented with three pictures: they have to choose the one that best fits the target word above from the two lower options, based on the semantic relation defined. We have measured 5 types of semantic knowledge representations: associative relations, taxonomy, motional representations, concrete as well as abstract verbs. As the first step in our data analysis, we examined the normal distribution of our results, and since it was not normally distributed (p < 0.05), we used nonparametric statistics further into the analysis. Using descriptive statistics, we could determine the frequency of the correct and incorrect responses, and with this knowledge, we could later adjust and remove the items of questionable reliability. The reliability was tested using Cronbach’s α, and it can be safely said that all the results were in an acceptable range of reliability (α = 0.6-0.8). We then tested for the potential gender differences using the Mann Whitney-U test, however, we found no difference between the two (p < 0.05). Likewise, we didn’t see that the age had any effect on the results using one-way ANOVA (p < 0.05), however, the level of education did influence the results (p > 0.05). The relationships between the subtests were observed by the nonparametric Spearman’s rho correlation matrix, showing statistically significant correlation between the subtests (p > 0.05), signifying a linear relationship between the measured semantic functions. A margin of error of 5% was used in all cases. The research will contribute to the expansion of the clinical diagnostic toolkit and will be relevant for the individualised therapeutic design of treatment procedures. The use of a non-verbal test procedure will allow an early assessment of the most severe language conditions, which is a priority in the differential diagnosis. The measurement of reaction time is expected to advance prodrome research, as the tests can be easily conducted in the subclinical phase.

Keywords: communication disorders, diagnostic toolkit, neurorehabilitation, semantic knowlegde

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Authors: Ch. Sridevi, A. Chalapathi Rao, P. Srinivasulu

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The location accuracy of data products is a critical parameter in assessing the geometric performance of satellite sensors. This study focuses on reliability analysis of onboard sensors to evaluate their performance in terms of location accuracy performance over time. The analysis utilizes field failure data and employs the weibull distribution to determine the reliability and in turn to understand the improvements or degradations over a period of time. The analysis begins by scrutinizing the location accuracy error which is the root mean square (RMS) error of differences between ground control point coordinates observed on the product and the map and identifying the failure data with reference to time. A significant challenge in this study is to thoroughly analyze the possibility of an infant mortality phase in the data. To address this, the Weibull distribution is utilized to determine if the data exhibits an infant stage or if it has transitioned into the operational phase. The shape parameter beta plays a crucial role in identifying this stage. Additionally, determining the exact start of the operational phase and the end of the infant stage poses another challenge as it is crucial to eliminate residual infant mortality or wear-out from the model, as it can significantly increase the total failure rate. To address this, an approach utilizing the well-established statistical Laplace test is applied to infer the behavior of sensors and to accurately ascertain the duration of different phases in the lifetime and the time required for stabilization. This approach also helps in understanding if the bathtub curve model, which accounts for the different phases in the lifetime of a product, is appropriate for the data and whether the thresholds for the infant period and wear-out phase are accurately estimated by validating the data in individual phases with Weibull distribution curve fitting analysis. Once the operational phase is determined, reliability is assessed using Weibull analysis. This analysis not only provides insights into the reliability of individual sensors with regards to location accuracy over the required period of time, but also establishes a model that can be applied to automate similar analyses for various sensors and parameters using field failure data. Furthermore, the identification of the best-performing sensor through this analysis serves as a benchmark for future missions and designs, ensuring continuous improvement in sensor performance and reliability. Overall, this study provides a methodology to accurately determine the duration of different phases in the life data of individual sensors. It enables an assessment of the time required for stabilization and provides insights into the reliability during the operational phase and the commencement of the wear-out phase. By employing this methodology, designers can make informed decisions regarding sensor performance with regards to location accuracy, contributing to enhanced accuracy in satellite-based applications.

Keywords: bathtub curve, geometric performance, Laplace test, location accuracy, reliability analysis, Weibull analysis

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Authors: Ilana Singer, Anastasia Lučić, Julie Leclerc

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Introduction: Tics, characterized by repetitive, sudden, non-voluntary motor movements or vocalizations, are prevalent in chronic tic disorder (CT) and Tourette Syndrome (TS). These neurodevelopmental disorders often coexist with various psychiatric conditions, leading to challenges and reduced quality of life. While medication in conjunction with behavioral interventions, such as Habit Reversal Training (HRT), Exposure Response Prevention (ERP), and Comprehensive Behavioral Intervention for Tics (CBIT), has shown efficacy, a significant proportion of patients experience persistent tics. Thus, innovative treatment approaches are necessary to improve therapeutic outcomes, such as mindfulness-based approaches. Nonetheless, the effectiveness of mindfulness-based interventions in the context of CT and TS remains understudied. Objective: The objective of this scoping review is to provide an overview of the current state of research on mindfulness-based interventions for CT and TS, identify knowledge and evidence gaps, discuss the effectiveness of mindfulness-based interventions with other treatment options, and discuss implications for clinical practice and policy development. Method: Using guidelines from Peters (2020) and the PRISMA-ScR, a scoping review was conducted. Multiple electronic databases were searched from inception until June 2023, including MEDLINE, EMBASE, PsychInfo, Global Health, PubMed, Web of Science, and Érudit. Inclusion criteria were applied to select relevant studies, and data extraction was independently performed by two reviewers. Results: Five papers were included in the study. Firstly, we found that mindfulness interventions were found to be effective in reducing anxiety and depression while enhancing overall well-being in individuals with tics. Furthermore, the review highlighted the potential role of mindfulness in enhancing functional connectivity within the Default Mode Network (DMN) as a compensatory function in TS patients. This suggests that mindfulness interventions may complement and support traditional therapeutic approaches, particularly HRT, by positively influencing brain networks associated with tic regulation and control. Conclusion: This scoping review contributes to the understanding of the effectiveness of mindfulness-based interventions in managing CT and TS. By identifying research gaps, this review can guide future investigations and interventions to improve outcomes for individuals with CT or TS. Overall, these findings emphasize the potential benefits of incorporating mindfulness-based interventions as a smaller subset within comprehensive treatment strategies. However, it is essential to acknowledge the limitations of this scoping review, such as the exclusion of a pre-established protocol and the limited number of studies available for inclusion. Further research and clinical exploration are necessary to better understand the specific mechanisms and optimal integration of mindfulness-based interventions with existing behavioral interventions for this population.

Keywords: scoping reviews, Tourette Syndrome, tics, mindfulness-based, therapy, intervention

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