Search results for: Christine Alvarez

Authors: Christine F. Boos, Fernando M. Azevedo

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Electroencephalogram (EEG) is a record of the electrical activity of the brain that has many applications, such as monitoring alertness, coma and brain death; locating damaged areas of the brain after head injury, stroke and tumor; monitoring anesthesia depth; researching physiology and sleep disorders; researching epilepsy and localizing the seizure focus. Epilepsy is a chronic condition, or a group of diseases of high prevalence, still poorly explained by science and whose diagnosis is still predominantly clinical. The EEG recording is considered an important test for epilepsy investigation and its visual analysis is very often applied for clinical confirmation of epilepsy diagnosis. Moreover, this EEG analysis can also be used to help define the types of epileptic syndrome, determine epileptiform zone, assist in the planning of drug treatment and provide additional information about the feasibility of surgical intervention. In the context of diagnosis confirmation the analysis is made using long term EEG recordings with at least 24 hours long and acquired by a minimum of 24 electrodes in which the neurophysiologists perform a thorough visual evaluation of EEG screens in search of specific electrographic patterns called epileptiform discharges. Considering that the EEG screens usually display 10 seconds of the recording, the neurophysiologist has to evaluate 360 screens per hour of EEG or a minimum of 8,640 screens per long term EEG recording. Analyzing thousands of EEG screens in search patterns that have a maximum duration of 200 ms is a very time consuming, complex and exhaustive task. Because of this, over the years several studies have proposed automated methodologies that could facilitate the neurophysiologists’ task of identifying epileptiform discharges and a large number of methodologies used neural networks for the pattern classification. One of the differences between all of these methodologies is the type of input stimuli presented to the networks, i.e., how the EEG signal is introduced in the network. Five types of input stimuli have been commonly found in literature: raw EEG signal, morphological descriptors (i.e. parameters related to the signal’s morphology), Fast Fourier Transform (FFT) spectrum, Short-Time Fourier Transform (STFT) spectrograms and Wavelet Transform features. This study evaluates the application of these five types of input stimuli and compares the classification results of neural networks that were implemented using each of these inputs. The performance of using raw signal varied between 43 and 84% efficiency. The results of FFT spectrum and STFT spectrograms were quite similar with average efficiency being 73 and 77%, respectively. The efficiency of Wavelet Transform features varied between 57 and 81% while the descriptors presented efficiency values between 62 and 93%. After simulations we could observe that the best results were achieved when either morphological descriptors or Wavelet features were used as input stimuli.

Keywords: Artificial neural network, electroencephalogram signal, pattern recognition, signal processing

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Authors: Mauro Callejas-Cuervo, Andrea C. Alarcon-Aldana, Andres F. Ruiz-Olaya, Juan C. Alvarez

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Motion capture (MC) is the construction of a precise and accurate digital representation of a real motion. Systems have been used in the last years in a wide range of applications, from films special effects and animation, interactive entertainment, medicine, to high competitive sport where a maximum performance and low injury risk during training and competition is seeking. This paper presents an inertial and magnetic sensor based technological platform, intended for particular amplitude monitoring and telerehabilitation processes considering an efficient cost/technical considerations compromise. Our platform particularities offer high social impact possibilities by making telerehabilitation accessible to large population sectors in marginal socio-economic sector, especially in underdeveloped countries that in opposition to developed countries specialist are scarce, and high technology is not available or inexistent. This platform integrates high-resolution low-cost inertial and magnetic sensors with adequate user interfaces and communication protocols to perform a web or other communication networks available diagnosis service. The amplitude information is generated by sensors then transferred to a computing device with adequate interfaces to make it accessible to inexperienced personnel, providing a high social value. Amplitude measurements of the platform virtual system presented a good fit to its respective reference system. Analyzing the robotic arm results (estimation error RMSE 1=2.12° and estimation error RMSE 2=2.28°), it can be observed that during arm motion in any sense, the estimation error is negligible; in fact, error appears only during sense inversion what can easily be explained by the nature of inertial sensors and its relation to acceleration. Inertial sensors present a time constant delay which acts as a first order filter attenuating signals at large acceleration values as is the case for a change of sense in motion. It can be seen a damped response of platform virtual in other images where error analysis show that at maximum amplitude an underestimation of amplitude is present whereas at minimum amplitude estimations an overestimation of amplitude is observed. This work presents and describes the platform virtual as a motion capture system suitable for telerehabilitation with the cost - quality and precision - accessibility relations optimized. These particular characteristics achieved by efficiently using the state of the art of accessible generic technology in sensors and hardware, and adequate software for capture, transmission analysis and visualization, provides the capacity to offer good telerehabilitation services, reaching large more or less marginal populations where technologies and specialists are not available but accessible with basic communication networks.

Keywords: inertial sensors, joint amplitude measurement, MEMS, telerehabilitation

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Authors: Eduardo Antonio Lozano Hernandez, Nancy Ramirez Alvarez, Lorena Margarita Rios Mendoza, Jose Vinicio Macias Zamora, Felix Augusto Hernandez Guzman, Jose Luis Sanchez Osorio

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Microplastics (MPs) are one of the most numerous reported wastes found in the marine ecosystem, representing one of the greatest risks for organisms that inhabit that environment due to their bioavailability. Such is the case of bivalve mollusks, since they are capable of filtering large volumes of water, which increases the risk of contamination by microplastics through the continuous exposure to these materials. This study aims to determine, quantify and characterize microplastics found in the cultured oyster Crassostrea gigas. We also analyzed if there are spatio-temporal differences in the microplastic concentration of organisms grown in two bays having quite different human population. In addition, we wanted to have an idea of the possible impact on humans via consumption of these organisms. Commercial size organisms (>6cm length; n = 15) were collected by triplicate from eight oyster farming sites in Baja California, Mexico during winter and summer. Two sites are located in Todos Santos Bay (TSB), while the other six are located in San Quintin Bay (SQB). Site selection was based on commercial concessions for oyster farming in each bay. The organisms were chemically digested with 30% KOH (w/v) and 30% H₂O₂ (v/v) to remove the organic matter and subsequently filtered using a GF/D filter. All particles considered as possible MPs were quantified according to their physical characteristics using a stereoscopic microscope. The type of synthetic polymer was determined using a FTIR-ATR microscope and using a user as well as a commercial reference library (Nicolet iN10 Thermo Scientific, Inc.) of IR spectra of plastic polymers (with a certainty ≥70% for polymers pure; ≥50% for composite polymers). Plastic microfibers were found in all the samples analyzed. However, a low incidence of MP fragments was observed in our study (approximately 9%). The synthetic polymers identified were mainly polyester and polyacrylonitrile. In addition, polyethylene, polypropylene, polystyrene, nylon, and T. elastomer. On average, the content of microplastics in organisms were higher in TSB (0.05 ± 0.01 plastic particles (pp)/g of wet weight) than found in SQB (0.02 ± 0.004 pp/g of wet weight) in the winter period. The highest concentration of MPs found in TSB coincides with the rainy season in the region, which increases the runoff from streams and wastewater discharges to the bay, as well as the larger population pressure (> 500,000 inhabitants). Otherwise, SQB is a mainly rural location, where surface runoff from streams is minimal and in addition, does not have a wastewater discharge into the bay. During the summer, no significant differences (Manne-Whitney U test; P=0.484) were observed in the concentration of MPs found in the cultured oysters of TSB and SQB, (average: 0.01 ± 0.003 pp/g and 0.01 ± 0.002 pp/g, respectively). Finally, we concluded that the consumption of oyster does not represent a risk for humans due to the low concentrations of MPs found. The concentration of MPs is influenced by the variables such as temporality, circulations dynamics of the bay and existing demographic pressure.

Keywords: FTIR-ATR, Human risk, Microplastic, Oyster

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Authors: Alvarez M., Chapela M. J., Balboa E., Rubianes D., Sinde E., Fernandez de Ana C., Rodríguez-Blanco A.

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The gut microbiota plays an important role as gut inflammation could contribute to colorectal cancer development; however, this role is still not fully understood, and tools able to prevent this progression are yet to be developed. The main objective of this study was to monitor the effects of a mushroom extracts formulation in gut microbial community composition of an Azoxymethane (AOM)/Dextran sodium sulfate (DSS) mice model of inflammation-linked carcinogenesis. For the in vivo study, 41 adult male mice of the C57BL / 6 strain were obtained. 36 of them have been induced in a state of colon carcinogenesis by a single intraperitoneal administration of AOM at a dose of 12.5 mg/kg; the control group animals received instead of the same volume of 0.9% saline. DSS is an extremely toxic polysaccharide sulfate that causes chronic inflammation of the colon mucosa, favoring the appearance of severe colitis and the production of tumors induced by AOM. Induction by AOM/DSS is an interesting platform for chemopreventive intervention studies. This time the model was used to monitor gut microbiota changes as a result of supplementation with a specific mushroom extracts formulation previously shown to have prebiotic activity. The animals have been divided into three groups: (i) Cancer + mushroom extracts formulation experimental group: to which the MicoDigest2.0 mushroom extracts formulation developed by Hifas da Terra S.L has been administered dissolved in drinking water at an estimated concentration of 100 mg / ml. (ii) Control group of animals with Cancer: to which normal water has been administered without any type of treatment. (iii) Control group of healthy animals: these are the animals that have not been induced cancer or have not received any treatment in drinking water. This treatment has been maintained for a period of 3 months, after which the animals were sacrificed to obtain tissues that were subsequently analyzed to verify the effects of the mushroom extract formulation. A microbiological analysis has been carried out to compare the microbial communities present in the intestines of the mice belonging to each of the study groups. For this, the methodology of massive sequencing by molecular analysis of the 16S gene has been used (Ion Torrent technology). Initially, DNA extraction and metagenomics libraries were prepared using the 16S Metagenomics kit, always following the manufacturer's instructions. This kit amplifies 7 of the 9 hypervariable regions of the 16S gene that will then be sequenced. Finally, the data obtained will be compared with a database that makes it possible to determine the degree of similarity of the sequences obtained with a wide range of bacterial genomes. Results obtained showed that, similarly to certain natural compounds preventing colorectal tumorigenesis, a mushroom formulation enriched the Firmicutes and Proteobacteria phyla and depleted Bacteroidetes. Therefore, it was demonstrated that the consumption of the mushroom extracts’ formulation developed could promote the recovery of the microbial balance that is disrupted in the mice model of carcinogenesis. More preclinical and clinical studies are needed to validate this promising approach.

Keywords: carcinogenesis, microbiota, mushroom extracts, inflammation

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Authors: Pierre Mintom, Armel Assiene Agamou, Leslie Toukem, William Dakam, Christine Fernande Nyangono Biyegue

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Context: Hyperuricemia, the presence of high levels of uric acid in the blood, is a known precursor to the development of gout. Recent studies have suggested a strong association between hyperuricemia and disorders of lipoprotein metabolism, specifically hypercholesterolemia. Understanding the factors associated with these conditions in gout patients is essential for effective treatment and management. Research Aim: The objective of this study was to determine the prevalence of hyperuricemia, hypercholesterolemia, and the double burden of hyperuricemia-hypercholesterolemia in the gouty population. Additionally, the study aimed to identify the factors associated with these conditions. Methodology: The study utilized a database from a survey of 150 gouty patients recruited at the Laquintinie Hospital in Douala between August 2017 and February 2018. The database contained information on anthropometric parameters, biochemical markers, and the food and drugs consumed by the patients. Hyperuricemia and hypercholesterolemia were defined based on specific serum uric acid and total cholesterol thresholds, and the double burden was defined as the co-occurrence of hyperuricemia and hypercholesterolemia. Findings: The study found that the prevalence rates for hyperuricemia, hypercholesterolemia, and the double burden were 61.3%, 76%, and 50.7% respectively. Factors associated with these conditions included hypertriglyceridemia, atherogenicity index TC/HDL ratio, atherogenicity index LDL/HDL ratio, family history, and the consumption of specific foods and drinks. Theoretical Importance: The study highlights the strong association between hyperuricemia and dyslipidemia, providing important insights for guiding treatment strategies in gout patients. Additionally, it emphasizes the significance of nutritional education in managing these metabolic disorders, suggesting the need to address eating habits in gout patients. Data Collection and Analysis Procedures: Data was collected through surveys and medical records of gouty patients. Information on anthropometric parameters, biochemical markers, and dietary habits was recorded. Prevalence rates and associated factors were determined through statistical analysis, employing odds ratios to assess the risks. Question Addressed: The study aimed to address the prevalence rates and associated factors of hyperuricemia, hypercholesterolemia, and the double burden in gouty patients. It sought to understand the relationships between these conditions and determine their implications for treatment and nutritional education. Conclusion: Findings show that it’s exists an association between hyperuricemia and hypercholesterolemia in gout patients, thus creating a double burden. The findings underscore the importance of considering family history and eating habits in addressing the double burden of hyperuricemia-hypercholesterolemia. This study provides valuable insights for guiding treatment approaches and emphasizes the need for nutritional education in gout patients. This study specifically focussed on the sick population. A case–control study between gouty and non-gouty populations would be interesting to better compare and explain the results observed.

Keywords: gout, hyperuricemia, hypercholesterolemia, double burden

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Authors: Angelica Alvarez-Lee, Sergio Martinez-Diaz, Jose Luis Garcia-Corona, Humberto Lanz-Mendoza

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World aquaculture is always looking for improvements to achieve productions with high yields avoiding the infection by pathogenic agents. The best way to achieve this is to know the biological model to create alternative treatments that could be applied in the hatcheries, which results in greater economic gains and improvements in human public health. In the last decade, immunomodulation in shrimp culture with probiotics, organic acids and different carbon sources has gained great interest, mainly in larval and juvenile stages. Immune priming is associated with a strong protective effect against a later pathogen challenge. This work provides another perspective about immunostimulation from spawning until hatching. The stimulation happens during development embryos and generates resistance to infection by pathogenic bacteria. Massive spawnings of white shrimp L. vannamei were obtained and placed in experimental units with 700 mL of sterile seawater at 30 °C, salinity of 28 ppm and continuous aeration at a density of 8 embryos.mL⁻¹. The immunostimulating effect of three death strains of non-pathogenic bacterial (Escherichia coli, Staphylococcus aureus and Bacillus subtilis) and a pathogenic strain for white shrimp (Vibrio parahaemolyticus) was evaluated. The strains killed by heat were adjusted to O.D. 0.5, at A 600 nm, and directly added to the seawater of each unit at a ratio of 1/100 (v/v). A control group of embryos without inoculum of dead bacteria was kept under the same physicochemical conditions as the rest of the treatments throughout the experiment and used as reference. The duration of the stimulus was 12 hours, then, the larvae that hatched were collected, counted and transferred to a new experimental unit (same physicochemical conditions but at a salinity of 28 ppm) to carry out a challenge of infection against the pathogen V. parahaemolyticus, adding directly to seawater an amount 1/100 (v/v) of the live strain adjusted to an OD 0.5; at A 600 nm. Subsequently, 24 hrs after infection, nauplii survival was evaluated. The results of this work shows that, after 24 hrs, the hatching rates of immunostimulated shrimp embryos with the dead strains of B. subtillis and V. parahaemolyticus are significantly higher compared to the rest of the treatments and the control. Furthermore, survival of L. vanammei after a challenge of infection of 24 hrs against the live strain of V. parahaemolyticus is greater (P < 0.05) in the larvae immunostimulated during the embryonic development with the dead strains B. subtillis and V. parahaemolyticus, followed by those that were treated with E. coli. In summary superficial antigens can stimulate the development cells to promote hatching and can have normal development in agreeing with the optical observations, plus exist a differential response effect between each treatment post-infection. This research provides evidence of the immunostimulant effect of death pathogenic and non-pathogenic bacterial strains in the rate of hatching and oversight of shrimp L. vannamei during embryonic and larval development. This research continues evaluating the effect of these death strains on the expression of genes related to the defense priming in larvae of L. vannamei that come from massive spawning in hatcheries before and after the infection challenge against V. parahaemolyticus.

Keywords: immunostimulation, L. vannamei, hatching, survival

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Authors: Laura Alvarez-Alonso, Francisco Garcia-Carro, Jorge Loredo

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Population growth and industrial development imply an increase in the energy demands and the problems caused by emissions of greenhouse effect gases, which has inspired the search for clean sources of energy. Hydrogen (H₂) is expected to play a key role in the world’s energy future by replacing fossil fuels. The properties of H₂ make it a green fuel that does not generate pollutants and supplies sufficient energy for power generation, transportation, and other applications. Supercritical Water Gasification (SCWG) represents an attractive alternative for the recovery of energy from wastes. SCWG allows conversion of a wide range of raw materials into a fuel gas with a high content of hydrogen and light hydrocarbons through their treatment at conditions higher than those that define the critical point of water (temperature of 374°C and pressure of 221 bar). Methane used as a transport fuel is another important gasification product. The number of different uses of gas and energy forms that can be produced depending on the kind of material gasified and type of technology used to process it, shows the flexibility of SCWG. This feature allows it to be integrated with several industrial processes, as well as power generation systems or waste-to-energy production systems. The final aim of this work is to study which conditions and equipment are the most efficient and advantageous to explore the possibilities to obtain streams rich in H₂ from oily wastes, which represent a major problem both for the environment and human health throughout the world. In this paper, the relative complexity of technology needed for feasible gasification process cycles is discussed with particular reference to the different feedstocks that can be used as raw material, different reactors, and energy recovery systems. For this purpose, a review of the current status of SCWG technologies has been carried out, by means of different classifications based on key features as the feed treated or the type of reactor and other apparatus. This analysis allows to improve the technology efficiency through the study of model calculations and its comparison with experimental data, the establishment of kinetics for chemical reactions, the analysis of how the main reaction parameters affect the yield and composition of products, or the determination of the most common problems and risks that can occur. The results of this work show that SCWG is a promising method for the production of both hydrogen and methane. The most significant choices of design are the reactor type and process cycle, which can be conveniently adopted according to waste characteristics. Regarding the future of the technology, the design of SCWG plants is still to be optimized to include energy recovery systems in order to reduce costs of equipment and operation derived from the high temperature and pressure conditions that are necessary to convert water to the SC state, as well as to find solutions to remove corrosion and clogging of components of the reactor.

Keywords: hydrogen production, organic wastes, supercritical water gasification, system integration, waste-to-energy

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Authors: Sonia P. Marrero Duran, Lilian Noya Dominguez, Lisandra Quintana Alvarez, Evert Martinez Perez, Ana Julia Acevedo Urquiaga

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Cuban business and economic policy are in the constant update as well as facing a client ever more knowledgeable and demanding. For that reason become fundamental for companies competitiveness through the optimization of its processes and services. One of the Cuban’s pillars, which has been sustained since the triumph of the Cuban Revolution back in 1959, is the free health service to all those who need it. This service is offered without any charge under the concept of preserving human life, but it implied costly management processes and logistics services to be able to supply the necessary medicines to all the units who provide health services. One of the key actors on the medicine supply chain is the Havana Distribution Center (HDC), which is responsible for the delivery of medicines in the province; as well as the acquisition of medicines from national and international producers and its subsequent transport to health care units and pharmacies in time, and with the required quality. This HDC also carries for all distribution centers in the country. Given the eminent need to create an actor in the supply chain that specializes in the medicines supply, the possibility of centralizing this operation in a logistics service provider is analyzed. Based on this decision, pharmacies operate as clients of the logistic service center whose main function is to centralize all logistics operations associated with the medicine supply chain. The HDC is precisely the logistic service provider in Havana and it is the center of this research. In 2017 the pharmacies had affectations in the availability of medicine due to deficiencies in the distribution routes. This is caused by the fact that they are not based on routing studies, besides the long distribution cycle. The distribution routs are fixed, attend only one type of customer and there respond to a territorial location by the municipality. Taking into consideration the above-mentioned problem, the objective of this research is to optimize the routes system in the Havana Distribution Center. To accomplish this objective, the techniques applied were document analysis, random sampling, statistical inference and tools such as Ishikawa diagram and the computerized software’s: ArcGis, Osmand y MapIfnfo. As a result, were analyzed four distribution alternatives; the actual rout, by customer type, by the municipality and the combination of the two last. It was demonstrated that the territorial location alternative does not take full advantage of the transportation capacities or the distance of the trips, which leads to elevated costs breaking whit the current ways of distribution and the currents characteristics of the clients. The principal finding of the investigation was the optimum option distribution rout is the 4th one that is formed by hospitals and the join of pharmacies, stomatology clinics, polyclinics and maternal and elderly homes. This solution breaks the territorial location by the municipality and permits different distribution cycles in dependence of medicine consumption and transport availability.

Keywords: computerized geographic software, distribution, distribution routs, vehicle problem routing (VPR)

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Authors: Renata Roma, Christine Tardif-Williams

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Engaging in daily walks with a dog (f.e. Canis lupus familiaris) during the COVID-19 pandemic may be linked to feelings of greater social-connectedness and global self-worth, and lower stress after controlling for mental health issues, lack of physical contact with others, and other stressors associated with the current pandemic. Therefore, maintaining a routine of dog walking might mitigate the effects of stressors experienced during the pandemic and promote well-being. However, many dog owners do not walk their dogs for many reasons, which are related to the owner’s and the dog’s personalities. Note that the consistency of certain personality characteristics among dogs demonstrates that it is possible to accurately measure different dimensions of personality in both dogs and their human counterparts. In addition, behavioural ratings (e.g., the dog personality questionnaire - DPQ) are reliable tools to assess the dog’s personality. Clarifying the relevance of personality factors in the context of young adult-dog relationships can shed light on interactional aspects that can potentially foster protective behaviours and promote well-being among young adults during the pandemic. This study examines if and how nine combinations of dog- and young adult-related personality characteristics (e.g., neuroticism-fearfulness) can amplify the influence of personality factors in the context of dog walking during the COVID-19 pandemic. Responses to an online large-scale survey among 440 (389 females; 47 males; 4 nonbinaries, Mage=20.7, SD= 2.13 range=17-25) young adults living with a dog in Canada were analyzed using structural equation modeling (SEM). As extraversion, conscientiousness, and neuroticism, measured through the five-factor model (FFM) inventory, are related to maintaining a routine of physical activities, these dimensions were selected for this analysis. Following an approach successfully adopted in the field of dog-human interactions, the FFM was used as the organizing framework to measure and compare the human’s and the dog’s personality in the context of dog walking. The dog-related personality dimensions activity/excitability, responsiveness to training, and fearful were correlated dimensions captured through DPQ and were added to the analysis. Two questions were used to assess dog walking. The actor-partner interdependence model (APIM) was used to check if the young adult’s responses about the dog were biased; no significant bias was observed. Activity/excitability and responsiveness to training in dogs were greatly associated with dog walking. For young adults, high scores in conscientiousness and extraversion predicted more walks with the dog. Conversely, higher scores in neuroticism predicted less engagement in dog walking. For participants high in conscientiousness, the dog’s responsiveness to training (standardized=0.14, p=0.02) and the dog’s activity/excitability (standardized=0.15, p=0.00) levels moderated dog walking behaviours by promoting more daily walks. These results suggest that some combinations in young adult and dog personality characteristics are associated with greater synergy in the young adult-dog dyad that might amplify the impact of personality factors on young adults’ dog-walking routines. These results can inform programs designed to promote the mental and physical health of young adults during the Covid-19 pandemic by highlighting the impact of synergy and reciprocity in personality characteristics between young adults and dogs.

Keywords: Covid-19 pandemic, dog walking, personality, structural equation modeling, well-being

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Authors: Suzanne Phibbs, Christine Kenney, Robyn Richardson

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The Sendai Framework for Disaster Risk Reduction called for the inclusion of indigenous people in the design and implementation of all hazard policies, plans, and standards. Ensuring that indigenous knowledge practices were included alongside scientific knowledge about disaster risk was also a key priority. Indigenous communities have specific knowledge about climate and natural hazard risk that has been developed over an extended period of time. However, research within indigenous communities can be fraught with issues such as power imbalances between the researcher and researched, the privileging of researcher agendas over community aspirations, as well as appropriation and/or inappropriate use of indigenous knowledge. This paper documents the process of working alongside a Māori community to develop a successful community-led research project. Research Design: This case study documents the development of a qualitative community-led participatory project. The community research project utilizes a kaupapa Māori research methodology which draws upon Māori research principles and concepts in order to generate knowledge about Māori resilience. The research addresses a significant gap in the disaster research literature relating to indigenous knowledge about collective hazard mitigation practices as well as resilience in rurally isolated indigenous communities. The research was designed in partnership with the Ngāti Raukawa Northern Marae Collective as well as Ngā Wairiki Ngāti Apa (a group of Māori sub-tribes who are located in the same region) and will be conducted by Māori researchers utilizing Māori values and cultural practices. The research project aims and objectives, for example, are based on themes that were identified as important to the Māori community research partners. The research methodology and methods were also negotiated with and approved by the community. Kaumātua (Māori elders) provided cultural and ethical guidance over the proposed research process and will continue to provide oversight over the conduct of the research. Purposive participant recruitment will be facilitated with support from local Māori community research partners, utilizing collective marae networks and snowballing methods. It is envisaged that Māori participants’ knowledge, experiences and views will be explored using face-to-face communication research methods such as workshops, focus groups and/or semi-structured interviews. Interviews or focus groups may be held in English and/or Te Reo (Māori language) to enhance knowledge capture. Analysis, knowledge dissemination, and co-authorship of publications will be negotiated with the Māori community research partners. Māori knowledge shared during the research will constitute participants’ intellectual property. New knowledge, theory, frameworks, and practices developed by the research will be co-owned by Māori, the researchers, and the host academic institution. Conclusion: An emphasis on indigenous knowledge systems within the Sendai Framework for Disaster Risk Reduction risks the appropriation and misuse of indigenous experiences of disaster risk identification, mitigation, and response. The research protocol underpinning this project provides an exemplar of collaborative partnership in the development and implementation of an indigenous project that has relevance to policymakers, academic researchers, other regions with indigenous communities and/or local disaster risk reduction knowledge practices.

Keywords: community resilience, indigenous disaster risk reduction, Maori, research methods

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Authors: Christine Hough, Eddie Abbott-Halpin, Tariq Mahmood, Jessica Giles

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This paper draws together the findings from two research studies, each undertaken with cohorts of South Asian Muslim respondents located in the North of England between 2017 and 2019. The first study, entitled Faith Family and Crime (FFC), investigated the extent to which a Muslim family’s social and health well-being is affected by a family member’s involvement in the Criminal Justice System (CJS). This study captured a range of data through a detailed questionnaire and structured interviews. The data from the interview transcripts were analysed using open coding and an application of aspects of the grounded theory approach. The findings provide clear evidence that the respondents were neither well-informed nor supported throughout the processes of the CJS, from arrest to post-sentencing. These experiences gave rise to mental and physical stress, potentially unfair sentencing, and a significant breakdown in communication within the respondents’ families. They serve to highlight a particular aspect of complexity in the current needs of those South Asian Muslim families who find themselves involved in the CJS and is closely connected to family structure, culture, and faith. The second study, referred to throughout this paper as #ImamsBritain (that provides the majority of content for this paper), explores how Imams, in their role as community faith leaders, can best address the complex – and changing - needs of South Asian Muslims families, such as those that emerged in the findings from FFC. The changing socio-economic and political climates of the last thirty or so years have brought about significant changes to the lives of Muslim families, and these have created more complex levels of social, cultural, and faith-based needs for families and individuals. As a consequence, Imams now have much greater demands made of them, and so their role has undergone far-reaching changes in response to this. The #ImamsBritain respondents identified a pressing need to develop a wider range of pastoral and counseling skills, which they saw as extending far beyond the traditional role of the Imam as a religious teacher and spiritual guide. The #ImamsBritain project was conducted with a cohort of British Imams in the North of England. Data was collected firstly through a questionnaire that related to the respondents’ training and development needs and then analysed in depth using the Delphi approach. Through Delphi, the data were scrutinized in depth using interpretative content analysis. The findings from this project reflect the respondents’ individual perceptions of the kind of training and development they need to fulfill their role in 21st Century Britain. They also provide a unique framework for constructing a professional guide for Imams in Great Britain. The discussions and critical analyses in this paper draw on the discourses of professionalization and pastoral care and relevant reports and reviews on Imam training in Europe and Canada.

Keywords: criminal justice system, faith and culture, Imams, Muslim community leadership, professionalization, South Asian family structure

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Authors: Fatna Benmessaoud, Mohammed Cheikh, Vencent Velay, Vanessa Vedal, Farhad Rezai-Aria, Christine Boher

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The global mechanical behavior of materials is strongly linked to their microstructure, especially their crystallographic texture and their grains morphology. These material aspects determine the mechanical fields character (heterogeneous or homogeneous), thus, they give to the global behavior a degree of anisotropy according the initial microstructure. For these reasons, the prediction of global behavior of materials in relationship with the microstructure must be performed with a multi-scale approach. Therefore, multi-scale modeling in the context of crystal plasticity is widely used. In this present contribution, a phenomenological elasto-viscoplastic model developed in the crystal plasticity context and finite element method are used to investigate the effects of crystallographic texture and grains sizes on global behavior of a polycrystalline equiaxed Ti-6Al-4V alloy. The constitutive equations of this model are written on local scale for each slip system within each grain while the strain and stress mechanical fields are investigated at the global scale via finite element scale transition. The beta phase of Ti-6Al-4V alloy modeled is negligible; its percent is less than 10%. Three families of slip systems of alpha phase are considered: basal and prismatic families with a burgers vector and pyramidal family with a burgers vector. The twinning mechanism of plastic strain is not observed in Ti-6Al-4V, therefore, it is not considered in the present modeling. Nine representative elementary volumes (REV) are generated with Voronoi tessellations. For each individual equiaxed grain, the own crystallographic orientation vis-à-vis the loading is taken into account. The meshing strategy is optimized in a way to eliminate the meshing effects and at the same time to allow calculating the individual grain size. The stress and strain fields are determined in each Gauss point of the mesh element. A post-treatment is used to calculate the local behavior (in each grain) and then by appropriate homogenization, the macroscopic behavior is calculated. The developed model is validated by comparing the numerical simulation results with an experimental data reported in the literature. It is observed that the present model is able to predict the global mechanical behavior of Ti-6Al-4V alloy and investigate the microstructural parameters' effects. According to the simulations performed on the generated volumes (REV), the macroscopic mechanical behavior of Ti-6Al-4V is strongly linked to the active slip systems family (prismatic, basal or pyramidal). The crystallographic texture determines which family of slip systems can be activated; therefore it gives to the plastic strain a heterogeneous character thus an anisotropic macroscopic mechanical behavior. The average grains size influences also the Ti-6Al-4V mechanical proprieties, especially the yield stress; by decreasing of the average grains size, the yield strength increases according to Hall-Petch relationship. The grains sizes' distribution gives to the strain fields considerable heterogeneity. By increasing grain sizes, the scattering in the localization of plastic strain is observed, thus, in certain areas the stress concentrations are stronger than other regions.

Keywords: microstructural parameters, multi-scale modeling, crystal plasticity, Ti-6Al-4V alloy

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Authors: B. R. Campomanes-Alvarez, P. Quiros, B. Fernandez

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Automatic Speech Recognition (ASR) is a machine-based process of decoding and transcribing oral speech. A typical ASR system receives acoustic input from a speaker or an audio file, analyzes it using algorithms, and produces an output in the form of a text. Some speech recognition systems use Hidden Markov Models (HMMs) to deal with the temporal variability of speech and Gaussian Mixture Models (GMMs) to determine how well each state of each HMM fits a short window of frames of coefficients that represents the acoustic input. Another way to evaluate the fit is to use a feed-forward neural network that takes several frames of coefficients as input and produces posterior probabilities over HMM states as output. Deep neural networks (DNNs) that have many hidden layers and are trained using new methods have been shown to outperform GMMs on a variety of speech recognition systems. Acoustic models for state-of-the-art ASR systems are usually training on massive amounts of data. However, audio files with their corresponding transcriptions can be difficult to obtain, especially in the Spanish language. Hence, in the case of these low-resource scenarios, building an ASR model is considered as a complex task due to the lack of labeled data, resulting in an under-trained system. Semi-supervised learning approaches arise as necessary tasks given the high cost of transcribing audio data. The main goal of this proposal is to develop a procedure based on acoustic semi-supervised learning for Spanish ASR systems by using DNNs. This semi-supervised learning approach consists of: (a) Training a seed ASR model with a DNN using a set of audios and their respective transcriptions. A DNN with a one-hidden-layer network was initialized; increasing the number of hidden layers in training, to a five. A refinement, which consisted of the weight matrix plus bias term and a Stochastic Gradient Descent (SGD) training were also performed. The objective function was the cross-entropy criterion. (b) Decoding/testing a set of unlabeled data with the obtained seed model. (c) Selecting a suitable subset of the validated data to retrain the seed model, thereby improving its performance on the target test set. To choose the most precise transcriptions, three confidence scores or metrics, regarding the lattice concept (based on the graph cost, the acoustic cost and a combination of both), was performed as selection technique. The performance of the ASR system will be calculated by means of the Word Error Rate (WER). The test dataset was renewed in order to extract the new transcriptions added to the training dataset. Some experiments were carried out in order to select the best ASR results. A comparison between a GMM-based model without retraining and the DNN proposed system was also made under the same conditions. Results showed that the semi-supervised ASR-model based on DNNs outperformed the GMM-model, in terms of WER, in all tested cases. The best result obtained an improvement of 6% relative WER. Hence, these promising results suggest that the proposed technique could be suitable for building ASR models in low-resource environments.

Keywords: automatic speech recognition, deep neural networks, machine learning, semi-supervised learning

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Authors: Christine Wiesenthal

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This paper asks how to read a particularly vexed and complicated life writing text. For over half a century, the wartime journals of Ruth Andreas Friedrich (1901-1977) circulated as among a handful of more or less authoritative and “authentic” first-hand accounts of German resistance under Hitler. A professional journalist, Andreas Friedrich is remembered today largely through her publications at the war’s end, which appeared in English as Berlin Underground (published by Henry Holt in 1947), just before their publication in Germany as Der Schattenmann “The Shadow Man” (also in 1947). A British edition by the now obscure Latimer House Limited (London) followed in 1948; it is based closely on but is not identical to, the Henry Holt American edition, which in turn differs significantly from its German counterpart. Both Berlin Underground and Der Schattenmann figure Andreas-Friedrich as a key figure in an anti-fascist cell that operated in Berlin under the code name “Uncle Emil,” and provide a riveting account of political terror, opportunism, and dissent under the Nazi regime. Recent scholars have, however, begun to raise fascinating and controversial questions about Andreas-Friedrich’s own writing/reconstruction process in compiling the journals and about her highly selective curatorial role and claims. The apparent absence of any surviving original manuscript for Andreas-Friedrich’s journals amplifies the questions around them. Crucially, so too does the role of the translator of the English editions of Berlin Underground, the enigmatic June Barrows Mussey, a subject that has thus far gone virtually unnoticed and which this paper will focus on. Mussey, a prolific American translator, simultaneously cultivated a career as a professional magician, publishing a number of books on that subject under the alias Henry Hay. While the record indicates that Mussey attempted to compartmentalize his professional life, research into the publishing and translation history of Berlin Underground suggests that the two roles converge in the fact of the translator’s invisibility, by effacing the traces of his own hand and leaving unmarked his own significant textual interventions, Mussey, in effect, edited, abridged, and altered Andreas Friedrich’s journals for the second time. In fact, it could be said that while the fictitious “Uncle Emil” is positioned as “the shadow man” of the German edition, Mussey himself also emerges as precisely that in the English rendering of the journals. The implications of Mussey’s translation of Andreas Friedrich’s journals are one of the most important un-examined gaps in the shadowy publishing history of Berlin Underground, a history full of “tricks” (Mussey’s words) and illusions of transparency. Based largely on archival research of unpublished materials and methods of close reading and comparative analysis, this study will seek to convey some preliminary insights and exploratory work and frame questions toward what is ultimately envisioned as an experimental project in poetic historiography. As this work is still in the early stages, it would be especially welcome to have the opportunity provided by this conference to connect with a community of life writing colleagues who might help think through some of the challenges and possibilities that lie ahead.

Keywords: women’s wartime diaries, translation studies, auto/biographical theory, politics of life writing

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Authors: Pablo Oteiza, Ricardo Alvarez, Mehrdad Pirnia, Fuat Can

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To effectively combat climate change, many countries around the world have committed to a decarbonisation of their electricity, along with promoting a large-scale integration of renewable energy sources (RES). While this trend represents a unique opportunity to effectively combat climate change, achieving a sound and cost-efficient energy transition towards low-carbon power systems poses significant challenges for the multi-year Transmission Network Expansion Planning (TNEP) problem. The objective of the multi-year TNEP is to determine the necessary network infrastructure to supply the projected demand in a cost-efficient way, considering the evolution of the new generation mix, including the integration of RES. The rapid integration of large-scale RES increases the variability and uncertainty in the power system operation, which in turn increases short-term flexibility requirements. To meet these requirements, flexible generating technologies such as energy storage systems must be considered within the TNEP as well, along with proper models for capturing the operational challenges of future power systems. As a consequence, TNEP formulations are becoming more complex and difficult to solve, especially for its application in realistic-sized power system models. To meet these challenges, there is an increasing need for developing efficient algorithms capable of solving the TNEP problem with reasonable computational time and resources. In this regard, a promising research area is the use of artificial intelligence (AI) techniques for solving large-scale mixed-integer optimization problems, such as the TNEP. In particular, the use of AI along with mathematical optimization strategies based on decomposition has shown great potential. In this context, this paper presents an efficient algorithm for solving the multi-year TNEP problem. The algorithm combines AI techniques with Column Generation, a traditional decomposition-based mathematical optimization method. One of the challenges of using Column Generation for solving the TNEP problem is that the subproblems are of mixed-integer nature, and therefore solving them requires significant amounts of time and resources. Hence, in this proposal we solve a linearly relaxed version of the subproblems, and trained a binary classifier that determines the value of the binary variables, based on the results obtained from the linearized version. A key feature of the proposal is that we integrate the binary classifier into the optimization algorithm in such a way that the optimality of the solution can be guaranteed. The results of a study case based on the HRP 38-bus test system shows that the binary classifier has an accuracy above 97% for estimating the value of the binary variables. Since the linearly relaxed version of the subproblems can be solved with significantly less time than the integer programming counterpart, the integration of the binary classifier into the Column Generation algorithm allowed us to reduce the computational time required for solving the problem by 50%. The final version of this paper will contain a detailed description of the proposed algorithm, the AI-based binary classifier technique and its integration into the CG algorithm. To demonstrate the capabilities of the proposal, we evaluate the algorithm in case studies with different scenarios, as well as in other power system models.

Keywords: integer optimization, machine learning, mathematical decomposition, transmission planning

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Authors: L. R. Valencia Pérez, J. M. Peña Aguilar, A. Lamadrid Álvarez, A. Pastrana Palma, H. F. Valencia Pérez, M. Vivanco Vargas

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This work proposes a Cooperation-Competitive (Coopetitive) approach that allows coordinated work among the Secretary of Public Education (SEP), the Autonomous University of Querétaro (UAQ) and government funds from National Council for Science and Technology (CONACYT) or some other international organizations. To work on an overall knowledge transfer strategy with e-learning over the Cloud, where experts in junior high and high school education, working in multidisciplinary teams, perform analysis, evaluation, design, production, validation and knowledge transfer at large scale using a Cloud Computing platform. Allowing teachers and students to have all the information required to ensure a homologated nationally knowledge of topics such as mathematics, statistics, chemistry, history, ethics, civism, etc. This work will start with a pilot test in Spanish and initially in two regional dialects Otomí and Náhuatl. Otomí has more than 285,000 speaking indigenes in Queretaro and Mexico´s central region. Náhuatl is number one indigenous dialect spoken in Mexico with more than 1,550,000 indigenes. The phase one of the project takes into account negotiations with indigenous tribes from different regions, and the Information and Communication technologies to deliver the knowledge to the indigenous schools in their native dialect. The methodology includes the following main milestones: Identification of the indigenous areas where Otomí and Náhuatl are the spoken dialects, research with the SEP the location of actual indigenous schools, analysis and inventory or current schools conditions, negotiation with tribe chiefs, analysis of the technological communication requirements to reach the indigenous communities, identification and inventory of local teachers technology knowledge, selection of a pilot topic, analysis of actual student competence with traditional education system, identification of local translators, design of the e-learning platform, design of the multimedia resources and storage strategy for “Cloud Computing”, translation of the topic to both dialects, Indigenous teachers training, pilot test, course release, project follow up, analysis of student requirements for the new technological platform, definition of a new and improved proposal with greater reach in topics and regions. Importance of phase one of the project is multiple, it includes the proposal of a working technological scheme, focusing in the cultural impact in Mexico so that indigenous tribes can improve their knowledge about new forms of crop improvement, home storage technologies, proven home remedies for common diseases, ways of preparing foods containing major nutrients, disclose strengths and weaknesses of each region, communicating through cloud computing platforms offering regional products and opening communication spaces for inter-indigenous cultural exchange.

Keywords: Mexicans indigenous tribes, education, knowledge transfer, cloud computing, otomi, Náhuatl, language

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Authors: James Brown, Stella Kortekaas, Ian Finnie, George Zhang, Christine Devine, Neil Healy

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The use of GIS as an analysis tool for engineering decision making is now best practice in the offshore industry. GIS enables multidisciplinary data integration, analysis and visualisation which allows the presentation of large and intricate datasets in a simple map-interface accessible to all project stakeholders. Presenting integrated geoscience and geotechnical data in GIS enables decision makers to be well-informed. This paper is a successful case study of how GIS spatial analysis techniques were applied to help select the most favourable pipeline route. Routing a pipeline through any natural environment has numerous obstacles, whether they be topographical, geological, engineering or financial. Where the pipeline is subjected to external hydrostatic water pressure and is carrying pressurised hydrocarbons, the requirement to safely route the pipeline through hazardous terrain becomes absolutely paramount. This study illustrates how the application of modern, GIS-based pipeline routing techniques enabled the identification of a single most-favourable pipeline route crossing of a challenging seabed terrain. Conventional approaches to pipeline route determination focus on manual avoidance of primary constraints whilst endeavouring to minimise route length. Such an approach is qualitative, subjective and is liable to bias towards the discipline and expertise that is involved in the routing process. For very short routes traversing benign seabed topography in shallow water this approach may be sufficient, but for deepwater geohazardous sites, the need for an automated, multi-criteria, and quantitative approach is essential. This study combined multiple routing constraints using modern least-cost-routing algorithms deployed in GIS, hitherto unachievable with conventional approaches. The least-cost-routing procedure begins with the assignment of geocost across the study area. Geocost is defined as a numerical penalty score representing hazard posed by each routing constraint (e.g. slope angle, rugosity, vulnerability to debris flows) to the pipeline. All geocosted routing constraints are combined to generate a composite geocost map that is used to compute the least geocost route between two defined terminals. The analyses were applied to select the most favourable pipeline route for a potential gas development in deep water. The study area is geologically complex with a series of incised, potentially active, canyons carved into a steep escarpment, with evidence of extensive debris flows. A similar debris flow in the future could cause significant damage to a poorly-placed pipeline. Protruding inter-canyon spurs offer lower-gradient options for ascending an escarpment but the vulnerability of periodic failure of these spurs is not well understood. Close collaboration between geoscientists, pipeline engineers, geotechnical engineers and of course the gas export pipeline operator guided the analyses and assignment of geocosts. Shorter route length, less severe slope angles, and geohazard avoidance were the primary drivers in identifying the most favourable route.

Keywords: geocost, geohazard, pipeline route determination, pipeline route optimisation, spatial analysis

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Authors: Jose A. Alvarez Aldegunde, Adrian Fernandez Sanchez, Matthew D. Menden, Bernardo Vila Rodriguez

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Up to five statistical pre-processings have been carried out considering the pollutant records of the stations present in Cartagena de Indias, Colombia, also taking into account the childhood asthma incidence surveys conducted in hospitals in the city by the Health Ministry of Colombia for this study. These pre-processings have consisted of different techniques such as the determination of the quality of data collection, determination of the quality of the registration network, identification and debugging of errors in data collection, completion of missing data and purified data, as well as the improvement of the time scale of records. The characterization of the quality of the data has been conducted by means of density analysis of the pollutant registration stations using ArcGis Software and through mass balance techniques, making it possible to determine inconsistencies in the records relating the registration data between stations following the linear regression. The results obtained in this process have highlighted the positive quality in the pollutant registration process. Consequently, debugging of errors has allowed us to identify certain data as statistically non-significant in the incidence and series of contamination. This data, together with certain missing records in the series recorded by the measuring stations, have been completed by statistical imputation equations. Following the application of these prior processes, the basic series of incidence data for respiratory disease and pollutant records have allowed the characterization of the influence of pollutants on respiratory diseases such as, for example, childhood asthma. This characterization has been carried out using statistical correlation methods, including visual correlation, simple linear regression correlation and spectral analysis with PAST Software which identifies maximum periodicity cycles and minimums under the formula of the Lomb periodgram. In relation to part of the results obtained, up to eleven maximums and minimums considered contemporary between the incidence records and the particles have been identified taking into account the visual comparison. The spectral analyses that have been performed on the incidence and the PM2.5 have returned a series of similar maximum periods in both registers, which are at a maximum during a period of one year and another every 25 days (0.9 and 0.07 years). The bivariate analysis has managed to characterize the variable "Daily Vehicular Flow" in the ninth position of importance of a total of 55 variables. However, the statistical correlation has not obtained a favorable result, having obtained a low value of the R2 coefficient. The series of analyses conducted has demonstrated the importance of the influence of pollutants such as PM2.5 in the development of childhood asthma in Cartagena. The quantification of the influence of the variables has been able to determine that there is a 56% probability of dependence between PM2.5 and childhood respiratory asthma in Cartagena. Considering this justification, the study could be completed through the application of the BenMap Software, throwing a series of spatial results of interpolated values of the pollutant contamination records that exceeded the established legal limits (represented by homogeneous units up to the neighborhood level) and results of the impact on the exacerbation of pediatric asthma. As a final result, an economic estimate (in Colombian Pesos) of the monthly and individual savings derived from the percentage reduction of the influence of pollutants in relation to visits to the Hospital Emergency Room due to asthma exacerbation in pediatric patients has been granted.

Keywords: Asthma Incidence, BenMap, PM2.5, Statistical Analysis

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Authors: Eduardo Cabrera-Rode, Janet Rodriguez, Aimee Alvarez, Ragmila Echevarria, Antonio D. Reyes, Ileana Cubas-Duenas, Silvia E. Turcios, Oscar Diaz-Diaz

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Obex is a nutritional supplement to help weight loss naturally. In addition, this supplement has a satiating effect that helps control the craving to eat between meals. The purpose of this study was to evaluate the effect of Obex in the metabolic syndrome (MS). This was an open label pilot study conducted in 30 patients with MS and ages between 29 and 60 years old. Participants received Obex, at a dose of one sachet before (30 to 45 minutes) the two main meals (lunch and dinner) daily (mean two sachets per day) for 3 months. The content of the sachets was dissolved in a glass of water or fruit juice. Obex ingredients: Açai (Euterpe oleracea Mart.) berry, inulin, Phaseolus vulgaris, Caralluma fimbriata, inositol, choline, arginine, ornitine, zinc sulfate, carnitine fumarate, methionine, calcium pantothenate, pyridoxine and folic acid. In addition to anthropometric measures and blood pressure, fasting plasma glucose, total cholesterol, triglycerides and HDL-cholesterol and insulin were determined. Insulin resistance was assessed by HOMA-IR index. Three indirect indexes were used to calculate insulin sensitivity [QUICKI index (Quantitative insulin sensitivity check index), Bennett index and Raynaud index]. Metabolic syndrome was defined according to the Joint Interim Statement (JIS) criteria. The JIS criteria require at least three of the following components: (1) abdominal obesity (waist circumference major or equal major or equal 94 cm for men or 80 cm for women), (2) triglycerides major or equal 1.7 mmol/L, (3) HDL cholesterol minor 1.03 mmol/L for men or minor 1.30 mmol/L for women, (4) systolic/diastolic blood pressure major or equal 130/85mmHg or use antihypertensive drugs, and (5) fasting plasma glucose major or equal 5.6 mmol/L or known treatment for diabetes. This study was approved by the Ethical and Research Committee of the National Institute of Endocrinology, Cuba and conducted according to the Declaration of Helsinki. Obex is registered as a food supplement in the National Institute of Nutrition and Food, Havana, Cuba. Written consent was obtained from all patients before the study. The clinical trial had been registered at ClinicalTrials.gov. After three months of treatment, 43.3% (13/30) of participants decreased the frequency of MS. Compared to baseline, Obex significantly reduced body weight, BMI, waist circumference, and waist/hip ratio and improved HDL-c (p<0.0001) and in addition to lowering blood pressure (p<0.05). After Obex intake, subjects also have shown a reduction in fasting plasma glucose (p<0.0001) and insulin sensitivity was enhanced (p=0.001). No adverse effects were seen in any of the participants during the study. In this pilot study, consumption of Obex decreased the prevalence of MS due to the improved selected components of the metabolic syndrome, indicating that further studies are warranted. Obex emerges as an effective and well tolerated treatment for preventing or delaying MS and therefore potential reduction of cardiovascular risk.

Keywords: nutritional supplement, metabolic syndrome, weight loss, insulin resistance

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Authors: Benjamin J. Kuo, Silvia D. Vaca, Joao Ricardo Nickenig Vissoci, Catherine A. Staton, Linda Xu, Michael Muhumuza, Hussein Ssenyonjo, John Mukasa, Joel Kiryabwire, Lydia Nanjula, Christine Muhumuza, Henry E. Rice, Gerald A. Grant, Michael M. Haglund

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Background: Traumatic Brain Injury (TBI) is disproportionally concentrated in low- and middle-income countries (LMICs), with the odds of dying from TBI in Uganda more than 4 times higher than in high income countries (HICs). The disparities in the injury incidence and outcome between LMICs and resource-rich settings have led to increased health outcomes research for TBIs and their associated risk factors in LMICs. While there have been increasing TBI studies in LMICs over the last decade, there is still a need for more robust prospective registries. In Uganda, a trauma registry implemented in 2004 at the Mulago National Referral Hospital (MNRH) showed that RTI is the major contributor (60%) of overall mortality in the casualty department. While the prior registry provides information on injury incidence and burden, it’s limited in scope and doesn’t follow patients longitudinally throughout their hospital stay nor does it focus specifically on TBIs. And although these retrospective analyses are helpful for benchmarking TBI outcomes, they make it hard to identify specific quality improvement initiatives. The relationship among epidemiology, patient risk factors, clinical care, and TBI outcomes are still relatively unknown at MNRH. Objective: The objectives of this study are to describe the processes of care and determine risk factors predictive of poor outcomes for TBI patients presenting to a single tertiary hospital in Uganda. Methods: Prospective data were collected for 563 TBI patients presenting to a tertiary hospital in Kampala from 1 June – 30 November 2016. Research Electronic Data Capture (REDCap) was used to systematically collect variables spanning 8 categories. Univariate and multivariate analysis were conducted to determine significant predictors of mortality. Results: 563 TBI patients were enrolled from 1 June – 30 November 2016. 102 patients (18%) received surgery, 29 patients (5.1%) intended for surgery failed to receive it, and 251 patients (45%) received non-operative management. Overall mortality was 9.6%, which ranged from 4.7% for mild and moderate TBI to 55% for severe TBI patients with GCS 3-5. Within each TBI severity category, mortality differed by management pathway. Variables predictive of mortality were TBI severity, more than one intracranial bleed, failure to receive surgery, high dependency unit admission, ventilator support outside of surgery, and hospital arrival delayed by more than 4 hours. Conclusions: The overall mortality rate of 9.6% in Uganda for TBI is high, and likely underestimates the true TBI mortality. Furthermore, the wide-ranging mortality (3-82%), high ICU fatality, and negative impact of care delays suggest shortcomings with the current triaging practices. Lack of surgical intervention when needed was highly predictive of mortality in TBI patients. Further research into the determinants of surgical interventions, quality of step-up care, and prolonged care delays are needed to better understand the complex interplay of variables that affect patient outcome. These insights guide the development of future interventions and resource allocation to improve patient outcomes.

Keywords: care continuum, global neurosurgery, Kampala Uganda, LMIC, Mulago, prospective registry, traumatic brain injury

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Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

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Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

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