Search results for: S. Alvarez
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 108

Search results for: S. Alvarez

18 Effect of Fermented Orange Juice Intake on Urinary 6‑Sulfatoxymelatonin in Healthy Volunteers

Authors: I. Cerrillo, A. Carrillo-Vico, M. A. Ortega, B. Escudero-López, N. Álvarez-Sánchez, F. Martín, M. S. Fernández-Pachón

Abstract:

Melatonin is a bioactive compound involved in multiple biological activities such as glucose tolerance, circadian rhythm regulation, antioxidant defense or immune system action. In elderly subjects the intake of foods and drinks rich in melatonin is very important due to its endogenous level decreases with age. Alcoholic fermentation is a process carried out in fruits, vegetables and legumes to obtain new products with improved bioactive compounds profile in relation to original substrates. Alcoholic fermentation process carried out by Saccharomycetaceae var. Pichia kluyveri induces an important synthesis of melatonin in orange juice. A novel beverage derived of fermented orange juice could be a promising source of this bioactive compound. The aim of the present study was to determine whether the acute intake of fermented orange juice increase the levels of urinary 6-sulfatoxymelatonin in healthy humans. Nine healthy volunteers (7 women and 2 men), aged between 20 and 25 years old and BMI of 21.1  2.4 kg/m2, were recruited. On the study day, participants ingested 500 mL of fermented orange juice. The first urine collection was made before fermented orange juice consumption (basal). The rest of urine collections were made in the following time intervals after fermented orange juice consumption: 0-2, 2-5, 5-10, 10- 15 and 15-24 hours. During the experimental period only the consumption of water was allowed. At lunch time a meal was provided (60 g of white bread, two slices of ham, a slice of cheese, 125 g of sweetened natural yoghurt and water). The subjects repeated the protocol with orange juice following a 2-wk washout period between both types of beverages. The levels of 6-sulfatoxymelatonin (6-SMT) were measured in urine recollected at different time points using the Melatonin-Sulfate Urine ELISA (IBL International GMBH, Hamburg, Germany). Levels of 6-SMT were corrected to those of creatinine for each sample. A significant (p < 0.05) increase in urinary 6-SMT levels was observed between 2-5 hours after fermented orange juice ingestion with respect to basal values (increase of 67,8 %). The consumption of orange juice did not induce any significant change in urinary 6-SMT levels. In addition, urinary 6-SMT levels obtained between 2-5 hours after fermented orange juice ingestion (115,6 ng/mg) were significantly different (p < 0.05) from those of orange juice (42,4 ng/mg). The enhancement of urinary 6-SMT after the ingestion of 500 mL of fermented orange juice in healthy humans compared to orange juice could be an important advantage of this novel product as an excellent source of melatonin. Fermented orange juice could be a new functional food, and its consumption could exert a potentially positive effect on health in both the maintenance of health status and the prevention of chronic diseases.

Keywords: fermented orange juice, functional beverage, healthy human, melatonin

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17 Effect of Antimony on Microorganisms in Aerobic and Anaerobic Environments

Authors: Barrera C. Monserrat, Sierra-Alvarez Reyes, Pat-Espadas Aurora, Moreno Andrade Ivan

Abstract:

Antimony is a toxic and carcinogenic metalloid considered a pollutant of priority interest by the United States Environmental Protection Agency. It is present in the environment in two oxidation states: antimonite (Sb (III)) and antimony (Sb (V)). Sb (III) is toxic to several aquatic organisms, but the potential inhibitory effect of Sb species for microorganisms has not been extensively evaluated. The fate and possible toxic impact of antimony on aerobic and anaerobic wastewater treatment systems are unknown. For this reason, the objective of this study was to evaluate the microbial toxicity of Sb (V) and Sb (III) in aerobic and anaerobic environments. Sb(V) and Sb(III) were used as potassium hexahydroxoantimonate (V) and potassium antimony tartrate, respectively (Sigma-Aldrich). The toxic effect of both Sb species in anaerobic environments was evaluated on methanogenic activity and the inhibition of hydrogen production of microorganisms from a wastewater treatment bioreactor. For the methanogenic activity, batch experiments were carried out in 160 mL serological bottles; each bottle contained basal mineral medium (100 mL), inoculum (1.5 g of VSS/L), acetate (2.56 g/L) as substrate, and variable concentrations of Sb (V) or Sb (III). Duplicate bioassays were incubated at 30 ± 2°C on an orbital shaker (105 rpm) in the dark. Methane production was monitored by gas chromatography. The hydrogen production inhibition tests were carried out in glass bottles with a working volume of 0.36 L. Glucose (50 g/L) was used as a substrate, pretreated inoculum (5 g VSS/L), mineral medium and varying concentrations of the two species of antimony. The bottles were kept under stirring and at a temperature of 35°C in an AMPTSII device that recorded hydrogen production. The toxicity of Sb on aerobic microorganisms (from a wastewater activated sludge treatment plant) was tested with a Microtox standardized toxicity test and respirometry. Results showed that Sb (III) is more toxic than Sb (V) for methanogenic microorganisms. Sb (V) caused a 50% decrease in methanogenic activity at 250 mg/L. In contrast, exposure to Sb (III) resulted in a 50% inhibition at a concentration of only 11 mg/L, and an almost complete inhibition (95%) at 25 mg/L. For hydrogen-producing microorganisms, Sb (III) and Sb (V) inhibited 50% of this production with 12.6 mg/L and 87.7 mg/L, respectively. The results for aerobic environments showed that 500 mg/L of Sb (V) do not inhibit the Allivibrio fischeri (Microtox) activity or specific oxygen uptake rate of activated sludge. In the case of Sb (III), this caused a loss of 50% of the respiration of the microorganisms at concentrations below 40 mg/L. The results obtained indicate that the toxicity of the antimony will depend on the speciation of this metalloid and that Sb (III) has a significantly higher inhibitory potential compared to Sb (V). It was shown that anaerobic microorganisms can reduce Sb (V) to Sb (III). Acknowledgments: This work was funded in part by grants from the UA-CONACYT Binational Consortium for the Regional Scientific Development and Innovation (CAZMEX), the National Institute of Health (NIH ES- 04940), and PAPIIT-DGAPA-UNAM (IN105220).

Keywords: aerobic inhibition, antimony reduction, hydrogen inhibition, methanogenic toxicity

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16 Natural Mexican Zeolite Modified with Iron to Remove Arsenic Ions from Water Sources

Authors: Maritza Estela Garay-Rodriguez, Mirella Gutierrez-Arzaluz, Miguel Torres-Rodriguez, Violeta Mugica-Alvarez

Abstract:

Arsenic is an element present in the earth's crust and is dispersed in the environment through natural processes and some anthropogenic activities. Naturally released into the environment through the weathering and erosion of sulphides mineral, some activities such as mining, the use of pesticides or wood preservatives potentially increase the concentration of arsenic in air, water, and soil. The natural arsenic release of a geological material is a threat to the world's drinking water sources. In aqueous phase is found in inorganic form, as arsenate and arsenite mainly, the contamination of groundwater by salts of this element originates what is known as endemic regional hydroarsenicism. The International Agency for Research on Cancer (IARC) categorizes the inorganic As within group I, as a substance with proven carcinogenic action for humans. It has been found the presence of As in groundwater in several countries such as Argentina, Mexico, Bangladesh, Canada and the United States. Regarding the concentration of arsenic in drinking water according to the World Health Organization (WHO) and the Environmental Protection Agency (EPA) establish maximum concentrations of 10 μg L⁻¹. In Mexico, in some states as Hidalgo, Morelos and Michoacán concentrations of arsenic have been found in bodies of water around 1000 μg L⁻¹, a concentration that is well above what is allowed by Mexican regulations with the NOM-127- SSA1-1994 that establishes a limit of 25 μg L⁻¹. Given this problem in Mexico, this research proposes the use of a natural Mexican zeolite (clinoptilolite type) native to the district of Etla in the central valley region of Oaxaca, as an adsorbent for the removal of arsenic. The zeolite was subjected to a conditioning with iron oxide by the precipitation-impregnation method with 0.5 M iron nitrate solution, in order to increase the natural adsorption capacity of this material. The removal of arsenic was carried out in a column with a fixed bed of conditioned zeolite, since it combines the advantages of a conventional filter with those of a natural adsorbent medium, providing a continuous treatment, of low cost and relatively easy to operate, for its implementation in marginalized areas. The zeolite was characterized by XRD, SEM/EDS, and FTIR before and after the arsenic adsorption tests, the results showed that the modification methods used are adequate to prepare adsorbent materials since it does not modify its structure, the results showed that with a particle size of 1.18 mm, an initial concentration of As (V) ions of 1 ppm, a pH of 7 and at room temperature, a removal of 98.7% was obtained with an adsorption capacity of 260 μg As g⁻¹ zeolite. The results obtained indicated that the conditioned zeolite is favorable for the elimination of arsenate in water containing up to 1000 μg As L⁻¹ and could be suitable for removing arsenate from pits of water.

Keywords: adsorption, arsenic, iron conditioning, natural zeolite

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15 Gender Differences in the Impact and Subjective Interpretation of Childhood Sexual Abuse Survivors

Authors: T. Borja-Alvarez, V. Jiménez-Borja, M. Jiménez Borja, C. J. Jiménez-Mosquera

Abstract:

Research on child sexual abuse has predominantly focused on female survivors. This has resulted in less research looking at the particular context in which this abuse takes place for boys and the impact this abuse may have on male survivors. The aim of this study is to examine the sex and age of the perpetrators of child sexual abuse and explore gender differences in the impact along with the subjective interpretation that survivors attribute to these experiences. The data for this study was obtained from Ecuadorian university students (M = 230, F = 293) who reported sexual abuse using the ISPCAN Child Abuse Screening Tool Retrospective version (ICAST-R). Participants completed Horowitz's Impact of Event Scale (IES) and were also requested to choose among neutral, positive, and negative adjectives to describe these experiences. The results indicate that in the case of males, perpetrators were both males (adults =27%, peers =20%, relatives =10.3%, cousins =7.4%) and young females (girlfriends or ex-girlfriends =25.6%, neighborhood =20.7%, school =16.7%, cousins =15.3%, strangers =12.8%). In contrast, almost all females reported that adult males were the perpetrators (relatives =29.6%, neighborhood =11.9%, strangers =19.9%, family friends =9.7%). Regarding the impact of these events, significant gender differences emerged. More females (50%) than males (20%) presented symptoms of post-traumatic stress disorder (PTSD). Gender differences also surfaced in the way survivors interpret their experiences. Almost half of the male participants selected the word “consensual” followed by the words “normal”, “helped me to mature”, “shameful”, “confusing”, and “traumatic”. In contrast, almost all females chose the word “non-consensual” followed by the words “shameful”, “traumatic”, “scary”, and “confusing”. In conclusion, the findings of this study suggest that young females and adult males were the most common perpetrators of sexually abused boys whereas adult males were the most common perpetrators of sexually abused girls. The impact and the subjective interpretation of these experiences were more negative for girls than for boys. The factors that account for the gender differences in the impact and the interpretation of these experiences need further exploration. It is likely that the cultural expectations of sexual behaviors for boys and girls in Latin American societies may partially explain the differential impact in the way these childhood sexual abuse experiences are interpreted in adulthood. In Ecuador, as is the case in other Latin American countries, the machismo culture not only accepts but encourages early sexual behaviors in boys and negatively judges premature sexual behavior in females. The result of these different sexual expectations may be that sexually abused boys may re-define these experiences as “consensual” and “normal” in adulthood, even though these were not consensual at the time of occurrence. Future studies are needed to more deeply understand the different contexts of sexual abuse for boys and girls in order to analyze the long-term impact of these experiences.

Keywords: abuse, child, gender differences, sexual

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14 Investigating the Key Success Factors of Supplier Collaboration Governance in the Aerospace Industry

Authors: Maria Jose Granero Paris, Ana Isabel Jimenez Zarco, Agustin Pablo Alvarez Herranz

Abstract:

In the industrial sector collaboration with suppliers is key to the development of innovations in the field of processes. Access to resources and expertise that are not available in the business, obtaining a cost advantage, or the reduction of the time needed to carry out innovation are some of the benefits associated with the process. However, the success of this collaborative process is compromised, when from the beginning not clearly rules have been established that govern the relationship. Abundant studies developed in the field of innovation emphasize the strategic importance of the concept of “Governance”. Despite this, there have been few papers that have analyzed how the governance process of the relationship must be designed and managed to ensure the success of the collaboration process. The lack of literature in this area responds to the wide diversity of contexts where collaborative processes to innovate take place. Thus, in sectors such as the car industry there is a strong collaborative tradition between manufacturers and suppliers being part of the value chain. In this case, it is common to establish mechanisms and procedures that fix formal and clear objectives to regulate the relationship, and establishes the rights and obligations of each of the parties involved. By contrast, in other sectors, collaborative relationships to innovate are not a common way of working, particularly when their aim is the development of process improvements. It is in this case, it is when the lack of mechanisms to establish and regulate the behavior of those involved, can give rise to conflicts, and the failure of the cooperative relationship. Because of this the present paper analyzes the similarities and differences in the processes of governance in collaboration with suppliers in the European aerospace industry With these ideas in mind, we present research is twofold: Understand the importance of governance as a key element of the success of the collaboration in the development of product and process innovations, Establish the mechanisms and procedures to ensure the proper management of the processes of collaboration. Following the methodology of the case study, we analyze the way in which manufacturers and suppliers cooperate in the development of new products and processes in two industries with different levels of technological intensity and collaborative tradition: the automotive and aerospace. The identification of those elements playing a key role to establish a successful governance and relationship management and the compression of the mechanisms of regulation and control in place at the automotive sector can be use to propose solutions to some of the conflicts that currently arise in aerospace industry. The paper concludes by analyzing the strategic implications for the aerospace industry entails the adoption of some of the practices traditionally used in other industrial sectors. Finally, it is important to highlight that in this paper are presented the first results of a research project currently in progress describing a model of governance that explains the way to manage outsourced services to suppliers in the European aerospace industry, through the analysis of companies in the sector located in Germany, France and Spain.

Keywords: supplier collaboration, supplier relationship governance, innovation management, product innovation, process innovation

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13 Investigating the Governance of Engineering Services in the Aerospace and Automotive Industries

Authors: Maria Jose Granero Paris, Ana Isabel Jimenez Zarco, Agustin Pablo Alvarez Herranz

Abstract:

In the industrial sector collaboration with suppliers is key to the development of innovations in the field of processes. Access to resources and expertise that are not available in the business, obtaining a cost advantage, or the reduction of the time needed to carry out innovation are some of the benefits associated with the process. However, the success of this collaborative process is compromised, when from the beginning not clearly rules have been established that govern the relationship. Abundant studies developed in the field of innovation emphasize the strategic importance of the concept of “Goverance”. Despite this, there have been few papers that have analyzed how the governance process of the relationship must be designed and managed to ensure the success of the cooperation process. The lack of literature in this area responds to the wide diversity of contexts where collaborative processes to innovate take place. Thus, in sectors such as the car industry there is a strong collaborative tradition between manufacturers and suppliers being part of the value chain. In this case, it is common to establish mechanisms and procedures that fix formal and clear objectives to regulate the relationship, and establishes the rights and obligations of each of the parties involved. By contrast, in other sectors, collaborative relationships to innovate are not a common way of working, particularly when their aim is the development of process improvements. It is in this case, it is when the lack of mechanisms to establish and regulate the behavior of those involved, can give rise to conflicts, and the failure of the cooperative relationship. Because of this the present paper analyzes the similarities and differences in the processes of governance in collaboration with service providers in engineering R & D in the European aerospace industry. With these ideas in mind, we present research is twofold: - Understand the importance of governance as a key element of the success of the cooperation in the development of process innovations, - Establish the mechanisms and procedures to ensure the proper management of the processes of cooperation. Following the methodology of the case study, we analyze the way in which manufacturers and suppliers cooperate in the development of new processes in two industries with different levels of technological intensity and collaborative tradition: the automotive and aerospace. The identification of those elements playing a key role to establish a successful governance and relationship management and the compression of the mechanisms of regulation and control in place at the automotive sector can be use to propose solutions to some of the conflicts that currently arise in aerospace industry. The paper concludes by analyzing the strategic implications for the aerospace industry entails the adoption of some of the practices traditionally used in other industrial sectors. Finally, it is important to highlight that in this paper are presented the first results of a research project currently in progress describing a model of governance that explains the way to manage outsourced engineering services to suppliers in the European aerospace industry, through the analysis of companies in the sector located in Germany, France and Spain.

Keywords: innovation management, innovation governance, managing collaborative innovation, process innovation

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12 Platform Virtual for Joint Amplitude Measurement Based in MEMS

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

Abstract:

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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11 Microplastic Concentrations in Cultured Oyster in Two Bays of Baja California, Mexico

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

Abstract:

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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10 Gut Microbial Dynamics in a Mouse Model of Inflammation-Linked Carcinogenesis as a Result of Diet Supplementation with Specific Mushroom Extracts

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

Abstract:

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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9 Defense Priming from Egg to Larvae in Litopenaeus vannamei with Non-Pathogenic and Pathogenic Bacteria Strains

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

Abstract:

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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8 Supercritical Water Gasification of Organic Wastes for Hydrogen Production and Waste Valorization

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

Abstract:

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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7 Distribution Routs Redesign through the Vehicle Problem Routing in Havana Distribution Center

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

Abstract:

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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6 Semi-Supervised Learning for Spanish Speech Recognition Using Deep Neural Networks

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

Abstract:

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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5 An Efficient Algorithm for Solving the Transmission Network Expansion Planning Problem Integrating Machine Learning with Mathematical Decomposition

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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4 Educational Knowledge Transfer in Indigenous Mexican Areas Using Cloud Computing

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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3 Influence of Atmospheric Pollutants on Child Respiratory Disease in Cartagena De Indias, Colombia

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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2 Effect of a Nutritional Supplement Containing Euterpe oleracea Mart., Inulin, Phaseolus vulgaris and Caralluma fimbriata in Persons with Metabolic Syndrome

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

Abstract:

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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1 MANIFEST-2, a Global, Phase 3, Randomized, Double-Blind, Active-Control Study of Pelabresib (CPI-0610) and Ruxolitinib vs. Placebo and Ruxolitinib in JAK Inhibitor-Naïve Myelofibrosis Patients

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

Abstract:

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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