Search results for: Jean Gray C. Achapero

Authors: Jean Ware, Susan W. Jones

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Background: The benefits of grammar instruction in the teaching of writing is contested in most English speaking countries. A majority of Anglophone countries abandoned the teaching of grammar in the 1950s based on the conclusions that it had no positive impact on learners’ development of reading, writing, and language. Although the decontextualised teaching of grammar is not helpful in improving writing, a curriculum with a focus on grammar in an embedded and meaningful way can help learners develop their understanding of the mechanisms of language. Although British learners are generally not taught grammar rules explicitly, learners in schools in France, the Netherlands, and Germany are taught explicitly about the structure of their own language. Exposing learners to grammatical analysis can help them develop their understanding of language. Indeed, if learners are taught that each part of speech has an identified role in the sentence. This means that rather than have to memorise lists of words or spelling patterns, they can focus on determining each word or phrase’s task in the sentence. These processes of categorisation and deduction are higher order thinking skills. When considering definitions of dyslexia available in Great Britain, the explicit teaching of grammar in context could help learners with persistent literacy difficulties. Indeed, learners with dyslexia often develop strengths in problem solving; the teaching of grammar could, therefore, help them develop their understanding of language by using analytical and logical thinking. Aims: This study aims at gaining a further understanding of how the explicit teaching of grammar in context can benefit learners with persistent literacy difficulties. The project is designed to identify ways of adapting existing grammar focussed teaching materials so that learners with specific learning difficulties such as dyslexia can use them to further develop their writing skills. It intends to improve educational practice through action, analysis and reflection. Research Design/Methods: The project, therefore, uses an action research design and multiple sources of evidence. The data collection tools used were standardised test data, teacher assessment data, semi-structured interviews, learners’ before and after attempts at a writing task at the beginning and end of the cycle, documentary data and lesson observation carried out by a specialist teacher. Existing teaching materials were adapted for use with five Year 9 learners who had experienced persistent literacy difficulties from primary school onwards. The initial adaptations included reducing the amount of content to be taught in each lesson, and pre teaching some of the metalanguage needed. Findings: Learners’ before and after attempts at the writing task were scored by a colleague who did not know the order of the attempts. All five learners’ scores were higher on the second writing task. Learners reported that they had enjoyed the teaching approach. They also made suggestions to be included in the second cycle, as did the colleague who carried out observations. Conclusions: Although this is a very small exploratory study, these results suggest that adapting grammar focused teaching materials shows promise for helping learners with persistent literacy difficulties develop their writing skills.

Keywords: explicit teaching of grammar in context, literacy acquisition, persistent literacy difficulties, writing skills

Procedia PDF Downloads 156

Authors: Mehdi Soula, Yosra Mani, Estelle Saras, Antoine Drapeau, Raoudha Grami, Mahjoub Aouni, Jean-Yves Madec, Marisa Haenni, Wejdene Mansour

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Multi-resistance to antibiotics in gram-negative bacilli and particularly in enterobacteriaceae, has become frequent in hospitals in Tunisia. However, data on antibiotic resistant bacteria in aquatic products are scarce. The aims of this study are to estimate the proportion of ESBL- and carbapenemase-producing Enterobacterales in seafood (clams and fish) in Tunisia and to molecularly characterize the collected isolates. Two types of seafood were sampled in unrelated markets in four different regions in Tunisia (641 pieces of farmed fish and 1075 mediterranean clams divided into 215 pools, and each pool contained 5 pieces). Once purchased, all samples were incubated in tubes containing peptone salt broth for 24 to 48h at 37°C. After incubation, overnight cultures were isolated on selective MacConkey agar plates supplemented with either imipenem or cefotaxime, identified using API20E test strips (bioMérieux, Marcy-l’Étoile, France) and confirmed by Maldi-TOF MS. Antimicrobial susceptibility was determined by the disk diffusion method on Mueller-Hinton agar plates and results were interpreted according to CA-SFM 2021. ESBL-producing Enterobacterales were detected using the Double Disc Synergy Test (DDST). Carbapenem-resistance was detected using an ertapenem disk and was respectively confirmed using the ROSCO KPC/MBL and OXA-48 Confirm Kit (ROSCO Diagnostica, Taastrup, Denmark). DNA was extracted using a NucleoSpin Microbial DNA extraction kit (Macherey-Nagel, Hoerdt, France), according to the manufacturer’s instructions. Resistance genes were determined using the CGE online tools. The replicon content and plasmid formula were identified from the WGS data using PlasmidFinder 2.0.1 and pMLST 2.0. From farmed fishes, nine ESBL-producing strains (9/641, 1.4%) were isolated, which were identified as E. coli (n=6) and K. pneumoniae (n=3). Among the 215 pools of 5 clams analyzed, 18 ESBL-producing isolates were identified, including 14 E. coli and 4 K. pneumoniae. A low isolation rate of ESBL-producing Enterobacterales was detected 1.6% (18/1075) in clam pools. In fish, the ESBL phenotype was due to the presence of the blaCTX-M-15 gene in all nine isolates, but no carbapenemase gene was identified. In clams, the predominant ESBL phenotype was blaCTX-M-1 (n=6/18). blaCPE (NDM1, OXA48) was detected only in 3 isolates ‘K. pneumoniae isolates’. Replicon typing on the strains carring the ESBL and carbapenemase gene revelead that the major type plasmid carried ESBL were IncF (42.3%) [n=11/26]. In all, our results suggest that seafood can be a reservoir of multi-drug resistant bacteria, most probably of human origin but also by the selection pressure of antibiotic. Our findings raise concerns that seafood bought for consumption may serve as potential reservoirs of AMR genes and pose serious threat to public health.

Keywords: BLSE, carbapenemase, enterobacterales, tunisian seafood

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Authors: Guillaume Soubeyran, Fabrice Micoud, Benoit Morin, Jean-Philippe Poirot-Crouvezier, Magali Reytier

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Proton Exchange Membrane Fuel Cell (PEMFC) technology is considered as a solution for the reduction of CO2 emissions. However, this technology still meets several challenges for high-scale industrialization. In this context, the increase of durability remains a critical aspect for competitiveness of this technology. Fortunately, performance degradations in nominal operating conditions is partially reversible, meaning that if specific conditions are applied, a partial recovery of fuel cell performance can be achieved, while irreversible degradations can only be mitigated. Thus, it is worth studying the optimal conditions to rejuvenate these reversible degradations and assessing the long-term impact of such procedures on the performance of the cell. Reversible degradations consist mainly of anode Pt active sites poisoning by carbon monoxide at the anode, heterogeneities in water management during use, and oxidation/deactivation of Pt active sites at the cathode. The latter is identified as a major source of reversible performance loss caused by the presence oxygen, high temperature and high cathode potential that favor platinum oxidation, especially in high efficiency operating points. Hence, we studied here a recovery procedure aiming at reducing the platinum oxides by decreasing cathode potential during operation. Indeed, the application of short air starvation phase leads to a drop of cathode potential. Cell performances are temporarily increased afterwards. Nevertheless, local temperature and current heterogeneities within the cells are favored and shall be minimized. The consumption of fuel during the recovery phase shall also be considered to evaluate the global efficiency. Consequently, the purpose of this work is to find an optimal compromise between the recovery of reversible degradations by air starvation, the increase of global cell efficiency and the mitigation of irreversible degradations effects. Different operating parameters have first been studied such as cell voltage, temperature and humidity in single cell set-up. Considering the global PEMFC system efficiency, tests showed that reducing duration of recovery phase and reducing cell voltage was the key to ensure an efficient recovery. Recovery phase frequency was a major factor as well. A specific method was established to find the optimal frequency depending on the duration and voltage of the recovery phase. Then, long-term degradations have also been studied by applying FC-DLC cycles based on NEDC cycles on a 4-cell short stack by alternating test sequences with and without recovery phases. Depending on recovery phase timing, cell efficiency during the cycle was increased up to 2% thanks to a mean voltage increase of 10 mV during test sequences with recovery phases. However, cyclic voltammetry tests results suggest that the implementation of recovery phases causes an acceleration of the decrease of platinum active areas that could be due to the high potential variations applied to the cathode electrode during operation.

Keywords: durability, PEMFC, recovery procedure, reversible degradation

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Authors: Elodie Niemiec, Philippe Champagne, Jean-Francois Blach, Philippe Moreau, Anthony Thuault, Arnaud Tricoteaux

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Hygiene of equipment in contact with users is an important issue in the railroad industry. The numerous cleanings to eliminate bacteria and dirt cost a lot. Besides, mechanical solicitations on contact parts are observed daily. It should be interesting to elaborate on a self-cleaning and antibacterial coating with sufficient adhesion and good resistance against mechanical and chemical solicitations. Thus, a Hauts-de-France and Maubeuge Val-de-Sambre conurbation authority co-financed Ph.D. thesis has been set up since October 2017 based on anterior studies carried by the Laboratory of Ceramic Materials and Processing. To accomplish this task, a soft chemical route has been implemented to bring a lotus effect on metallic substrates. It involves nanometric liquid zinc oxide synthesis under 100°C. The originality here consists in a variation of surface texturing by modification of the synthesis time of the species in solution. This helps to adjust wettability. Nanostructured zinc oxide has been chosen because of the inherent photocatalytic effect, which can activate organic substance degradation. Two methods of heating have been compared: conventional and microwave assistance. Tested subtracts are made of stainless steel to conform to transport uses. Substrate preparation was the first step of this protocol: a meticulous cleaning of the samples is applied. The main goal of the elaboration protocol is to fix enough zinc-based seeds to make them grow during the next step as desired (nanorod shaped). To improve this adhesion, a silica gel has been formulated and optimized to ensure chemical bonding between substrate and zinc seeds. The last step consists of deposing a wide carbonated organosilane to improve the superhydrophobic property of the coating. The quasi-proportionality between the reaction time and the nanorod length will be demonstrated. Water Contact (superior to 150°) and Roll-off Angle at different steps of the process will be presented. The antibacterial effect has been proved with Escherichia Coli, Staphylococcus Aureus, and Bacillus Subtilis. The mortality rate is found to be four times superior to a non-treated substrate. Photocatalytic experiences were carried out from different dyed solutions in contact with treated samples under UV irradiation. Spectroscopic measurements allow to determinate times of degradation according to the zinc quantity available on the surface. The final coating obtained is, therefore, not a monolayer but rather a set of amorphous/crystalline/amorphous layers that have been characterized by spectroscopic ellipsometry. We will show that the thickness of the nanostructured oxide layer depends essentially on the synthesis time set in the hydrothermal growth step. A green, easy-to-process and control coating with self-cleaning and antibacterial properties has been synthesized with a satisfying surface structuration.

Keywords: antibacterial, biomimetism, soft-chemistry, zinc oxide

Procedia PDF Downloads 142

Authors: Jose A. C. Venancio, Alexandrino J. M. Goncalves, Anabela Marto, Nuno C. S. Rodrigues, Rita M. T. Ascenso

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Nowadays, it is common to find people who are concerned about getting away from the everyday life routine, looking forward to outcome well-being and pleasant emotions. Trying to disconnect themselves from the usual places of work and residence, they pursue different places, such as tourist destinations, aiming to have unexpected experiences. In order to make this exploration process easier, cities and tourism agencies seek new opportunities and solutions, creating routes with diverse cultural landmarks, including natural landscapes and historic buildings. These offers frequently aspire to the preservation of the local patrimony. In nature and wildlife, birdwatching is an activity that has been increasing, both in cities and in the countryside. This activity seeks to find, observe and identify the diversity of birds that live permanently or temporarily in these places, and it is usually supported by birdwatching guides. Leiria (Portugal) is a well-known city, presenting several historical and natural landmarks, like the Lis river and the castle where King D. Dinis lived in the 13th century. Along the Lis River, a conservation process was carried out and a pedestrian route was created (Polis project). This is considered an excellent spot for birdwatching, especially for the gray heron (Ardea cinerea) and for the kingfisher (Alcedo atthis). There is also a route through the city, from the riverside to the castle, which encloses a characterized variety of species, such as the barn swallow (Hirundo rustica), known for passing through different seasons of the year. Birdwatching is sometimes a difficult task since it is not always possible to see all bird species that inhabit a given place. For this reason, a need to create a technological solution was found to ease this activity. This project aims to encourage people to learn about the various species of birds that live along the Lis River and to promote the preservation of nature in a conscious way. This work is being conducted in collaboration with Leiria Municipal Council and with the Environmental Interpretation Centre. It intends to show the majesty of the Lis River, a place visited daily by several people, such as children and families, who use it for didactic and recreational activities. We are developing a mobile multi-platform application (Guard@Lis) that allows bird species to be observed along a given route, using representative digital 3D models through the integration of augmented reality technologies. Guard@Lis displays a route with points of interest for birdwatching and a list of species for each point of interest, along with scientific information, images and sounds for every species. For some birds, to ensure their observation, the user can watch them in loco, in their real and natural environment, with their mobile device by means of augmented reality, giving the sensation of presence of these birds, even if they cannot be seen in that place at that moment. The augmented reality feature is being developed with Vuforia SDK, using a hybrid approach to recognition and tracking processes, combining marks and geolocation techniques. This application proposes routes and notifies users with alerts for the possibility of viewing models of augmented reality birds. The final Guard@Lis prototype will be tested by volunteers in-situ.

Keywords: augmented reality, birdwatching route, mobile application, nature tourism, watch birds using augmented reality

Procedia PDF Downloads 177

Authors: Julia Kapr, Andrea Rossi, Haribaskar Ramachandran, Marius Pollet, Ilka Egger, Selina Dangeleit, Katharina Koch, Jean Krutmann, Ellen Fritsche

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It is widely acknowledged that animal models do not always represent human disease. Especially human brain development is difficult to model in animals due to a variety of structural and functional species-specificities. This causes significant discrepancies between predicted and apparent drug efficacies in clinical trials and their subsequent failure. Emerging alternatives based on 3D in vitro approaches, such as human brain spheres or organoids, may in the future reduce and ultimately replace animal models. Here, we present a human induced pluripotent stem cell (hiPSC)-based 3D neural in a vitro disease model for the Cockayne Syndrome B (CSB). CSB is a rare hereditary disease and is accompanied by severe neurologic defects, such as microcephaly, ataxia and intellectual disability, with currently no treatment options. Therefore, the aim of this study is to investigate the molecular and cellular defects found in neural hiPSC-derived CSB models. Understanding the underlying pathology of CSB enables the development of treatment options. The two CSB models used in this study comprise a patient-derived hiPSC line and its isogenic control as well as a CSB-deficient cell line based on a healthy hiPSC line (IMR90-4) background thereby excluding genetic background-related effects. Neurally induced and differentiated brain sphere cultures were characterized via RNA Sequencing, western blot (WB), immunocytochemistry (ICC) and multielectrode arrays (MEAs). CSB-deficiency leads to an altered gene expression of markers for autophagy, focal adhesion and neural network formation. Cell migration was significantly reduced and electrical activity was significantly increased in the disease cell lines. These data hint that the cellular pathologies is possibly underlying CSB. By induction of autophagy, the migration phenotype could be partially rescued, suggesting a crucial role of disturbed autophagy in defective neural migration of the disease lines. Altered autophagy may also lead to inefficient mitophagy. Accordingly, disease cell lines were shown to have a lower mitochondrial base activity and a higher susceptibility to mitochondrial stress induced by rotenone. Since mitochondria play an important role in neurotransmitter cycling, we suggest that defective mitochondria may lead to altered electrical activity in the disease cell lines. Failure to clear the defective mitochondria by mitophagy and thus missing initiation cues for new mitochondrial production could potentiate this problem. With our data, we aim at establishing a disease adverse outcome pathway (AOP), thereby adding to the in-depth understanding of this multi-faced disorder and subsequently contributing to alternative drug development.

Keywords: autophagy, disease modeling, in vitro, pluripotent stem cells

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Authors: Jean Felix Tuyisingize

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Speeding or inappropriate speed is a major problem worldwide, contributing to 10-15% of road crashes and 30% of fatal injury crashes. The consequences of speeding put the driver's life at risk and the lives of other road users like motorists, cyclists, and pedestrians. To control vehicle speeds, governments, and traffic authorities enforced speed regulations through speed cameras and speed section control, which monitor all vehicle speeds and detect plate numbers to levy penalties. However, speed limit violations are prevalent, even on motorways with speed cameras. The problem with speed cameras is that they alter driver behaviors, and their effect declines with increasing distance from the speed camera location. Drivers decelerate short distances before the camera and vigorously accelerate above the speed limit just after passing by the camera. The sudden decelerating near cameras causes the drivers to try to make up for lost time after passing it, and they do this by speeding up, resulting in a phenomenon known as the "Kangaroo jump" or "V-profile" around camera/ASSC areas. This study investigated the impact of speed enforcement devices, specifically Average Speed Section Control (ASSCs) and fixed cameras, on acceleration and deceleration events within their vicinity. The research employed advanced statistical and Geographic Information System (GIS) analysis on naturalistic driving data, to uncover speeding patterns near the speed enforcement systems. The study revealed a notable concentration of events within a 600-meter radius of enforcement devices, suggesting their influence on driver behaviors within a specific range. However, most of these events are of low severity, suggesting that drivers may not significantly alter their speed upon encountering these devices. This behavior could be attributed to several reasons, such as consistently maintaining safe speeds or using real-time in-vehicle intervention systems. The complexity of driver behavior is also highlighted, indicating the potential influence of factors like traffic density, road conditions, weather, time of day, and driver characteristics. Further, the study highlighted that high-severity events often occurred outside speed enforcement zones, particularly around intersections, indicating these as potential hotspots for drastic speed changes. These findings call for a broader perspective on traffic safety interventions beyond reliance on speed enforcement devices. However, the study acknowledges certain limitations, such as its reliance on a specific geographical focus, which may impact the broad applicability of the findings. Additionally, the severity of speed modification events was categorized into low, medium, and high, which could oversimplify the continuum of speed changes and potentially mask trends within each category. This research contributes valuable insights to traffic safety and driver behavior literature, illuminating the complexity of driver behavior and the potential influence of factors beyond the presence of speed enforcement devices. Future research directions may employ various categories of event severity. They may also explore the role of in-vehicle technologies, driver characteristics, and a broader set of environmental variables in driving behavior and traffic safety.

Keywords: acceleration, deceleration, speeding, inappropriate speed, speed enforcement cameras

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Authors: Bissonnette Jean-François, Dossa Fabrice

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The project focuses on analyzing the spatial and temporal evolution of mangrove forest ecosystems near the city of Douala, Cameroon, in response to increasing human and environmental pressures. The selected study area, located in the Wouri River estuary, has a unique combination of economic importance, and ecological prominence. The study included valuable insights by conducting semi-structured interviews with resource operators and local officials. The thorough analysis of socio-economic data, farmer surveys, and satellite-derived information was carried out utilizing quantitative approaches in Excel and SPSS. Simultaneously, qualitative data was subjected to rigorous classification and correlation with other sources. The use of ArcGIS and CorelDraw facilitated the visual representation of the gradual changes seen in various land cover classifications. The research reveals complex processes that characterize mangrove ecosystems on Manoka and Cape Cameroon Islands. The lack of regulations in urbanization and the continuous growth of infrastructure have led to a significant increase in land conversion, causing negative impacts on natural landscapes and forests. The repeated instances of flooding and coastal erosion have further shaped landscape alterations, fostering the proliferation of water and mudflat areas. The unregulated use of mangrove resources is a significant factor in the degradation of these ecosystems. Activities including the use of wood for smoking and fishing, together with the coastal pollution resulting from the absence of waste collection, have had a significant influence. In addition, forest operators contribute to the degradation of vegetation, hence exacerbating the harmful impact of invasive species on the ecosystem. Strategic interventions are necessary to guarantee the sustainable management of these ecosystems. The proposals include advocating for sustainable wood exploitation techniques, using appropriate techniques, along with regeneration, and enforcing rules to prevent wood overexploitation. By implementing these measures, the ecological balance can be preserved, safeguarding the long-term viability of these precious ecosystems. On a conceptual level, this paper uses the framework developed by Elinor Ostrom and her colleagues to investigate the consequences of open access resources, where local actors have not been able to enforce measures to prevent overexploitation of mangrove wood resources. Governmental authorities have demonstrated limited capacity to enforce sustainable management of wood resources and have not been able to establish effective relationships with local fishing communities and with communities involved in the purchase of wood. As a result, wood resources in the mangrove areas remain largely accessible, while authorities do not monitor wood volumes extracted nor methods of exploitation. There have only been limited and punctual attempts at forest restoration with no significant consequence on mangrove forests dynamics.

Keywords: Mangroves, forest management, governance, open access resources, Cameroon

Procedia PDF Downloads 63

Authors: Jean Pierre Kabue, Emma Meader, Afsatou Ndama Traore, Paul R. Hunter, Natasha Potgieter

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Norovirus is now considered the most common cause of outbreaks of nonbacterial gastroenteritis. Limited data are available for Norovirus strains in Africa, especially in rural and peri-urban areas. Despite the excessive burden of diarrhea disease in developing countries, Norovirus infections have been to date mostly reported in developed countries. There is a need to investigate intensively the role of viral agents associated with diarrhea in different settings in Africa continent. To determine the prevalence and genetic diversity of Norovirus strains circulating in the rural communities in the Limpopo Province, South Africa and investigate the genetic relationship between Norovirus strains, a cross-sectional study was performed on human stools collected from rural communities. Between July 2014 and April 2015, outpatient children under 5 years of age from rural communities of Vhembe District, South Africa, were recorded for the study. A total of 303 stool specimens were collected from those with diarrhea (n=253) and without (n=50) diarrhea. NoVs were identified using real-time one-step RT-PCR. Partial Sequence analyses were performed to genotype the strains. Phylogenetic analyses were performed to compare identified NoVs genotypes to the worldwide circulating strains. Norovirus detection rate was 41.1% (104/253) in children with diarrhea. There was no significant difference (OR=1.24; 95% CI 0.66-2.33) in Norovirus detection between symptomatic and asymptomatic children. Comparison of the median CT values for NoV in children with diarrhea and without diarrhea revealed significant statistical difference of estimated GII viral load from both groups, with a much higher viral burden in children with diarrhea. To our knowledge, this is the first study reporting on the differences in estimated viral load of GII and GI NoV positive cases and controls. GII.Pe (n=9) were the predominant genotypes followed by GII.Pe/GII.4 Sydney 2012 (n=8) suspected recombinant and GII.4 Sydney 2012 variants(n=7). Two unassigned GII.4 variants and an unusual RdRp genotype GII.P15 were found. With note, the rare GIIP15 identified in this study has a common ancestor with GIIP15 strain from Japan previously reported as GII/untypeable recombinant strain implicated in a gastroenteritis outbreak. To our knowledge, this is the first report of this unusual genotype in the African continent. Though not confirmed predictive of diarrhea disease in this study, the high detection rate of NoV is an indication of subsequent exposure of children from rural communities to enteric pathogens due to poor sanitation and hygiene practices. The results reveal that the difference between asymptomatic and symptomatic children with NoV may possibly be related to the NoV genogroups involved. The findings emphasize NoV genetic diversity and predominance of GII.Pe/GII.4 Sydney 2012, indicative of increased NoV activity. An uncommon GII.P15 and two unassigned GII.4 variants were also identified from rural settings of the Vhembe District/South Africa. NoV surveillance is required to help to inform investigations into NoV evolution, and to support vaccine development programmes in Africa.

Keywords: asymptomatic, common, outpatients, norovirus genetic diversity, sporadic gastroenteritis, South African rural communities, symptomatic

Procedia PDF Downloads 195

Authors: Abdoulaye Maihatchi Ahamed, Zubin Arora, Benjamin Swobada, Jean-yves Lansot, Alexandre Chagnes

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Lithium-ion battery (LiB) is the technology of choice in the development of electric vehicles. But there are still many challenges, including the development of positive electrode materials exhibiting high cycle ability, high energy density, and low environmental impact. For this latter, LiBs must be manufactured in a circular approach by developing the appropriate strategies to reuse and recycle them. Presently, the recycling of LiBs is carried out by the pyrometallurgical route, but more and more processes implement or will implement the hydrometallurgical route or a combination of pyrometallurgical and hydrometallurgical operations. After producing the black mass by mineral processing, the hydrometallurgical process consists in leaching the black mass in order to uptake the metals contained in the cathodic material. Then, these metals are extracted selectively by liquid-liquid extraction, solid-liquid extraction, and/or precipitation stages. However, liquid-liquid extraction combined with precipitation/crystallization steps is the most implemented operation in the LiB recycling process to selectively extract copper, aluminum, cobalt, nickel, manganese, and lithium from the leaching solution and precipitate these metals as high-grade sulfate or carbonate salts. Liquid-liquid extraction consists in contacting an organic solvent and an aqueous feed solution containing several metals, including the targeted metal(s) to extract. The organic phase is non-miscible with the aqueous phase. It is composed of an extractant to extract the target metals and a diluent, which is usually aliphatic kerosene produced from the petroleum industry. Sometimes, a phase modifier is added in the formulation of the extraction solvent to avoid the third phase formation. The extraction properties of the diluent do not depend only on the chemical structure of the extractant, but it may also depend on the nature of the diluent. Indeed, the interactions between the diluent can influence more or less the interactions between extractant molecules besides the extractant-diluent interactions. Only a few studies in the literature addressed the influence of the diluent on the extraction properties, while many studies focused on the effect of the extractants. Recently, new low-carbon footprint aliphatic diluents were produced by catalytic dearomatisation and distillation of bio-based oil. This study aims at investigating the influence of the nature of the diluent on the extraction properties of three extractants towards cobalt, nickel, manganese, copper, aluminum, and lithium: Cyanex®272 for nickel-cobalt separation, DEHPA for manganese extraction, and Acorga M5640 for copper extraction. The diluents used in the formulation of the extraction solvents are (i) low-odor aliphatic kerosene produced from the petroleum industry (ELIXORE 180, ELIXORE 230, ELIXORE 205, and ISANE IP 175) and (ii) bio-sourced aliphatic diluents (DEV 2138, DEV 2139, DEV 1763, DEV 2160, DEV 2161 and DEV 2063). After discussing the effect of the diluents on the extraction properties, this conference will address the development of a low carbon footprint process based on the use of the best bio-sourced diluent for the production of high-grade cobalt sulfate, nickel sulfate, manganese sulfate, and lithium carbonate, as well as metal copper.

Keywords: diluent, hydrometallurgy, lithium-ion battery, recycling

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Authors: Maria De Los Angeles Ortega, Denis Bruneau, Patrick Sebastian, Jean-Pierre Nadeau, Alain Sommier, Saed Raji

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Phase change materials (PCM) present attractive features that made them a passive solution for thermal comfort assessment in buildings during summer time. They show a large storage capacity per volume unit in comparison with other structural materials like bricks or concrete. If their use is matched with the peak load periods, they can contribute to the reduction of the primary energy consumption related to cooling applications. Despite these promising characteristics, they present some drawbacks. Commercial PCMs, as paraffines, offer a low thermal conductivity affecting the overall performance of the system. In some cases, the material can be enhanced, adding other elements that improve the conductivity, but in general, a design of the unit that optimizes the thermal performance is sought. The material selection is the departing point during the designing stage, and it does not leave plenty of room for optimization. The PCM melting point depends highly on the atmospheric characteristics of the building location. The selection must relay within the maximum, and the minimum temperature reached during the day. The geometry of the PCM container and the geometrical distribution of these containers are designing parameters, as well. They significantly affect the heat transfer, and therefore its phenomena must be studied exhaustively. During its lifetime, an air-PCM unit in a building must cool down the place during daytime, while the melting of the PCM occurs. At night, the PCM must be regenerated to be ready for next uses. When the system is not in service, a minimal amount of thermal exchanges is desired. The aforementioned functions result in the presence of sensible and latent heat storage and release. Hence different types of mechanisms drive the heat transfer phenomena. An experimental test was designed to study the heat transfer phenomena occurring in a circular tube bundle air-PCM exchanger. An in-line arrangement was selected as the geometrical distribution of the containers. With the aim of visual identification, the containers material and a section of the test bench were transparent. Some instruments were placed on the bench for measuring temperature and velocity. The PCM properties were also available through differential scanning calorimeter (DSC) tests. An evolution of the temperature during both cycles, melting and solidification were obtained. The results showed some phenomena at a local level (tubes) and on an overall level (exchanger). Conduction and convection appeared as the main heat transfer mechanisms. From these results, two approaches to analyze the heat transfer were followed. The first approach described the phenomena in a single tube as a series of thermal resistances, where a pure conduction controlled heat transfer was assumed in the PCM. For the second approach, the temperature measurements were used to find some significant dimensionless numbers and parameters as Stefan, Fourier and Rayleigh numbers, and the melting fraction. These approaches allowed us to identify the heat transfer phenomena during both cycles. The presence of natural convection during melting might have been stated from the influence of the Rayleigh number on the correlations obtained.

Keywords: phase change materials, air-PCM exchangers, convection, conduction

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Authors: Guillaume Bélanger, Jean-Philippe Fontaine, Clémence Hauduc

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There is an undeniable thirst from organic chemists and from the pharmaceutical industry to access complex alkaloids with short syntheses. While medicinal chemists are interested in the fascinating wide range of biological properties of alkaloids, synthetic chemists are rather interested in finding new routes to access these challenging natural products of often low availability from nature. To synthesize complex polycyclic cores of natural products, reaction cascades or sequences performed one-pot offer a neat advantage over classical methods for their rapid increase in molecular complexity in a single operation. In counterpart, reaction cascades need to be run on substrates bearing all the required functional groups necessary for the key cyclizations. Chemoselectivity is thus a major issue associated with such a strategy, in addition to diastereocontrol and regiocontrol for the overall transformation. In the pursuit of synthetic efficiency, our research group developed an innovative one-pot transformation of linear substrates into bi- and tricyclic adducts applied to the construction of Aspidospermatan-type alkaloids. The latter is a rich class of indole alkaloids bearing a unique bridged azatricyclic core. Despite many efforts toward the synthesis of members of this family, efficient and versatile synthetic routes are still coveted. Indeed, very short, non-racemic approaches are rather scarce: for example, in the cases of aspidospermidine and aspidospermine, syntheses are all fifteen steps and over. We envisaged a unified approach to access several members of the Aspidospermatan alkaloids family. The key sequence features a highly chemoselective formamide activation that triggers a Vilsmeier-Haack cyclization, followed by an azomethine ylide generation and intramolecular cycloaddition. Despite the high density and variety of functional groups on the substrates (electron-rich and electron-poor alkenes, nitrile, amide, ester, enol ether), the sequence generated three new carbon-carbon bonds and three rings in a single operation with good yield and high chemoselectivity. A detailed study of amide, nucleophile, and dipolarophile variations to finally get to the successful combination required for the key transformation will be presented. To complete the indoline fragment of the natural products, we developed an original approach. Indeed, all reported routes to Aspidospermatan alkaloids introduce the indoline or indole early in the synthesis. In our work, the indoline needs to be installed on the azatricyclic core after the key cyclization sequence. As a result, typical Fischer indolization is not suited since this reaction is known to fail on such substrates. We thus envisaged a unique photocatalyzed decarboxylative radical cyclization. The development of this reaction as well as the scope and limitations of the methodology, will also be presented. The original Vilsmeier-Haack and azomethine ylide cyclization sequence as well as the new photocatalyzed decarboxylative radical cyclization will undoubtedly open access to new routes toward polycyclic indole alkaloids and derivatives of pharmaceutical interest in general.

Keywords: Aspidospermatan alkaloids, azomethine ylide cycloaddition, decarboxylative radical cyclization, indole and indoline synthesis, one-pot sequential cyclizations, photocatalysis, Vilsmeier-Haack Cyclization

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Authors: Utkarsh A. Mishra, Ankit Bansal

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At high temperature, radiative heat transfer is the dominant mode of heat transfer. It is governed by various phenomena such as photon emission, absorption, and scattering. The solution of the governing integrodifferential equation of radiative transfer is a complex process, more when the effect of participating medium and wavelength properties are taken into consideration. Although a generic formulation of such radiative transport problem can be modeled for a wide variety of problems with non-gray, non-diffusive surfaces, there is always a trade-off between simplicity and accuracy of the problem. Recently, solutions of complicated mathematical problems with statistical methods based on randomization of naturally occurring phenomena have gained significant importance. Photon bundles with discrete energy can be replicated with random numbers describing the emission, absorption, and scattering processes. Photon Monte Carlo (PMC) is a simple, yet powerful technique, to solve radiative transfer problems in complicated geometries with arbitrary participating medium. The method, on the one hand, increases the accuracy of estimation, and on the other hand, increases the computational cost. The participating media -generally a gas, such as CO₂, CO, and H₂O- present complex emission and absorption spectra. To model the emission/absorption accurately with random numbers requires a weighted sampling as different sections of the spectrum carries different importance. Importance sampling (IS) was implemented to sample random photon of arbitrary wavelength, and the sampled data provided unbiased training of MC estimators for better results. A better replacement to uniform random numbers is using deterministic, quasi-random sequences. Halton, Sobol, and Faure Low-Discrepancy Sequences are used in this study. They possess better space-filling performance than the uniform random number generator and gives rise to a low variance, stable Quasi-Monte Carlo (QMC) estimators with faster convergence. An optimal supervised learning scheme was further considered to reduce the computation costs of the PMC simulation. A one-dimensional plane-parallel slab problem with participating media was formulated. The history of some randomly sampled photon bundles is recorded to train an Artificial Neural Network (ANN), back-propagation model. The flux was calculated using the standard quasi PMC and was considered to be the training target. Results obtained with the proposed model for the one-dimensional problem are compared with the exact analytical and PMC model with the Line by Line (LBL) spectral model. The approximate variance obtained was around 3.14%. Results were analyzed with respect to time and the total flux in both cases. A significant reduction in variance as well a faster rate of convergence was observed in the case of the QMC method over the standard PMC method. However, the results obtained with the ANN method resulted in greater variance (around 25-28%) as compared to the other cases. There is a great scope of machine learning models to help in further reduction of computation cost once trained successfully. Multiple ways of selecting the input data as well as various architectures will be tried such that the concerned environment can be fully addressed to the ANN model. Better results can be achieved in this unexplored domain.

Keywords: radiative heat transfer, Monte Carlo Method, pseudo-random numbers, low discrepancy sequences, artificial neural networks

Procedia PDF Downloads 223

Authors: Jérémy Philippe, Lucien Baldas, Batoul Attar, Jean-Charles Mare

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The proposed communication deals with the research and development of a rotary direct-drive servo valve for aerospace applications. A key challenge of the project is to downsize the electromagnetic torque motor by reducing the torque required to drive the rotary spool. It is intended to optimize the spool and the sleeve geometries by combining a Computational Fluid Dynamics (CFD) approach with commercial optimization software. The present communication addresses an important phase of the project, which consists firstly of gaining confidence in the simulation results. It is well known that the force needed to pilot a sliding spool valve comes from several physical effects: hydraulic forces, friction and inertia/mass of the moving assembly. Among them, the flow force is usually a major contributor to the steady-state (or Root Mean Square) driving torque. In recent decades, CFD has gradually become a standard simulation tool for studying fluid-structure interactions. However, in the particular case of high-pressure valve design, the authors have experienced that the calculated overall hydraulic force depends on the parameterization and options used to build and run the CFD model. To solve this issue, the authors have selected the standard case of the linear spool valve, which is addressed in detail in numerous scientific references (analytical models, experiments, CFD simulations). The first CFD simulations run by the authors have shown that the evolution of the equivalent discharge coefficient vs. Reynolds number at the metering orifice corresponds well to the values that can be predicted by the classical analytical models. Oppositely, the simulated flow force was found to be quite different from the value calculated analytically. This drove the authors to investigate minutely the influence of the studied domain and the setting of the CFD simulation. It was firstly shown that the flow recirculates in the inlet and outlet channels if their length is not sufficient regarding their hydraulic diameter. The dead volume on the uncontrolled orifice side also plays a significant role. These examples highlight the influence of the geometry of the fluid domain considered. The second action was to investigate the influence of the type of mesh, the turbulence models and near-wall approaches, and the numerical solver and discretization scheme order. Two approaches were used to determine the overall hydraulic force acting on the moving spool. First, the force was deduced from the momentum balance on a control domain delimited by the valve inlet and outlet and the spool walls. Second, the overall hydraulic force was calculated from the integral of pressure and shear forces acting at the boundaries of the fluid domain. This underlined the significant contribution of the viscous forces acting on the spool between the inlet and outlet orifices, which are generally not considered in the literature. This also emphasized the influence of the choices made for the implementation of CFD calculation and results analysis. With the step-by-step process adopted to increase confidence in the CFD simulations, the authors propose a set of best practices and recommendations for the efficient use of CFD to design high-pressure spool valves.

Keywords: computational fluid dynamics, hydraulic forces, servovalve, rotary servovalve

Procedia PDF Downloads 43

Authors: Christelle Rabbat, Carole Vouebou, Sary Awad, Alan Jean-Marie

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Hydrogen has been proven to be a viable alternative to standard fuels as it is easy to produce and only generates water vapour and zero carbon emissions. However, despite the hydrogen benefits, the widespread adoption of hydrogen fuel cell vehicles and internal combustion engine vehicles is impeded by several challenges. The lack of refueling infrastructures remains one of the main hindering factors due to the high costs associated with their design, construction, and operation. Besides, the lack of hydrogen vehicles on the road diminishes the economic viability of investing in refueling infrastructure. Simultaneously, the absence of accessible refueling stations discourages consumers from adopting hydrogen vehicles, perpetuating a cycle of limited market uptake. To address these challenges, the implementation of adequate policies incentivizing the use of hydrogen vehicles and the reduction of the investment and operation costs of hydrogen refueling stations (HRS) are essential to put both investors and customers at ease. Even though the transition to hydrogen cars has been rather slow, public transportation companies have shown a keen interest in this highly promising fuel. Besides, their hydrogen demand is easier to predict and regulate than personal vehicles. Due to the reduced complexity of designing a suitable hydrogen supply chain for public vehicles, this sub-sector could be a great starting point to facilitate the adoption of hydrogen vehicles. Consequently, this study will focus on designing a chain of on-site green HRS for the public transportation network in Nantes Metropole leveraging the latest relevant technological advances aiming to reduce the costs while ensuring reliability, safety, and ease of access. To reduce the cost of HRS and encourage their widespread adoption, a network of 7 H35-T40 HRS has been designed, replacing the conventional J-T valves with turbo-expanders. Each station in the network has a daily capacity of 1,920 kg. Thus, the HRS network can produce up to 12.5 tH2 per day. The detailed cost analysis has revealed a CAPEX per station of 16.6 M euros leading to a network CAPEX of 116.2 M euros. The proposed station siting prioritized Nantes metropole’s 5 bus depots and included 2 city-centre locations. Thanks to the turbo-expander technology, the cooling capacity of the proposed HRS is 19% lower than that of a conventional station equipped with J-T valves, resulting in significant CAPEX savings estimated at 708,560 € per station, thus nearly 5 million euros for the whole HRS network. Besides, the turbo-expander power generation ranges from 7.7 to 112 kW. Thus, the power produced can be used within the station or sold as electricity to the main grid, which would, in turn, maximize the station’s profit. Despite the substantial initial investment required, the environmental benefits, cost savings, and energy efficiencies realized through the transition to hydrogen fuel cell buses and the deployment of HRS equipped with turbo-expanders offer considerable advantages for both TAN and Nantes Metropole. These initiatives underscore their enduring commitment to fostering green mobility and combatting climate change in the long term.

Keywords: green hydrogen, refueling stations, turbo-expander, heavy-duty vehicles

Procedia PDF Downloads 56

Authors: Sami El Khatib, Agnès Leroux, Jean-Louis Merlin, François Guillemin, Marie-Ange D’Hallewin

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Photodynamic therapy (PDT) is a treatment modality based on the cytotoxic effect occurring on the target tissues by interaction of a photosensitizer with light in the presence of oxygen. One of the major advances in PDT can be attributed to the use of topical aminolevulinic (ALA) to induce Protoporphyrin IX (PpIX) for the treatment of early stage cancers as well as diagnosis. ALA is a precursor of the heme synthesis pathway. Locally delivered to the target tissue ALA overcomes the negative feedback exerted by heme and promotes the transient formation of PpIX in situ to reach critical effective levels in cells and tissue. Whereas early steps of the heme pathway occur in the cytosol, PpIX synthesis is shown to be held in the mitochondrial membranes and PpIX fluorescence is expected to accumulate in close vicinity of the initial building site and to progressively diffuse to the neighboring cytoplasmic compartment or other lipophylic organelles. PpIX is known to be highly reactive and will be degraded when irradiated with light. PpIX photobleaching is believed to be governed by a singlet oxygen mediated mechanism in the presence of oxidized amino acids and proteins. PpIX photobleaching and subsequent spectral phototransformation were described widely in tumor cells incubated in vitro with ALA solution, or ex vivo in human and porcine mucosa superfused with hexylaminolevulinate (hALA). PpIX photobleaching was also studied in vivo, using animal models such as normal or tumor mice skin and orthotopic rat bladder model. Hexyl aminolevulinate a more potent lipophilic derivative of ALA was proposed as an adjunct to standard cystoscopy in the fluorescence diagnosis of bladder cancer and other malignancies. We have previously reported the effectiveness of hALA mediated PDT of rat bladder cancer. Although normal and tumor bladder epithelium exhibit similar fluorescence intensities after intravesical instillation of two hALA concentrations (8 and 16 mM), the therapeutic response at 8mM and 20J/cm2 was completely different from the one observed at 16mM irradiated with the same light dose. Where the tumor is destroyed, leaving the underlying submucosa and muscle intact after an 8 mM instillation, 16mM sensitization and subsequent illumination results in the complete destruction of the underlying bladder wall but leaves the tumor undamaged. The object of the current study is to try to unravel the underlying mechanism for this apparent contradiction. PpIX extraction showed identical amounts of photosensitizer in tumor bearing bladders at both concentrations. Photobleaching experiments revealed mono-exponential decay curves in both situations but with a two times faster decay constant in case of 16mM bladders. Fluorescence microscopy shows an identical fluorescence pattern for normal bladders at both concentrations and tumor bladders at 8mM with bright spots. Tumor bladders at 16 mM exhibit a more diffuse cytoplasmic fluorescence distribution. The different response to PDT with regard to the initial pro-drug concentration can thus be attributed to the different cellular localization.

Keywords: bladder cancer, hexyl-aminolevulinate, photobleaching, confocal fluorescence microscopy

Procedia PDF Downloads 407

Authors: Kazuhiro Tateda, Elisa Gonzalez, Shuhei Ito, Kirstin Heinrich, Kevin Sweetland, Pingping Zhang, Catia Ferreira, Michael Pride, Jennifer Moisi, Sharon Gray, Bennett Lee, Fred Angulo

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Clostridium difficile (C. difficile) is the most common cause of antibiotic-associated diarrhea and infectious diarrhea in healthcare settings. Japan has an aging population; the elderly are at increased risk of hospitalization, antibiotic use, and C. difficile infection (CDI). Little is known about the population-based incidence and disease burden of CDI in Japan although limited hospital-based studies have reported a lower incidence than the United States. To understand CDI disease burden in Japan, CLOUD (Clostridium difficile Infection Burden of Disease in Adults in Japan) was developed. CLOUD will derive population-based incidence estimates of the number of CDI cases per 100,000 population per year in Ota-ku (population 723,341), one of the districts in Tokyo, Japan. CLOUD will include approximately 14 of the 28 Ota-ku hospitals including Toho University Hospital, which is a 1,000 bed tertiary care teaching hospital. During the 12-month patient enrollment period, which is scheduled to begin in November 2018, Ota-ku residents > 50 years of age who are hospitalized at a participating hospital with diarrhea ( > 3 unformed stools (Bristol Stool Chart 5-7) in 24 hours) will be actively ascertained, consented, and enrolled by study surveillance staff. A stool specimen will be collected from enrolled patients and tested at a local reference laboratory (LSI Medience, Tokyo) using QUIK CHEK COMPLETE® (Abbott Laboratories). which simultaneously tests specimens for the presence of glutamate dehydrogenase (GDH) and C. difficile toxins A and B. A frozen stool specimen will also be sent to the Pfizer Laboratory (Pearl River, United States) for analysis using a two-step diagnostic testing algorithm that is based on detection of C. difficile strains/spores harboring toxin B gene by PCR followed by detection of free toxins (A and B) using a proprietary cell cytotoxicity neutralization assay (CCNA) developed by Pfizer. Positive specimens will be anaerobically cultured, and C. difficile isolates will be characterized by ribotyping and whole genomic sequencing. CDI patients enrolled in CLOUD will be contacted weekly for 90 days following diarrhea onset to describe clinical outcomes including recurrence, reinfection, and mortality, and patient reported economic, clinical and humanistic outcomes (e.g., health-related quality of life, worsening of comorbidities, and patient and caregiver work absenteeism). Studies will also be undertaken to fully characterize the catchment area to enable population-based estimates. The 12-month active ascertainment of CDI cases among hospitalized Ota-ku residents with diarrhea in CLOUD, and the characterization of the Ota-ku catchment area, including estimation of the proportion of all hospitalizations of Ota-ku residents that occur in the CLOUD-participating hospitals, will yield CDI population-based incidence estimates, which can be stratified by age groups, risk groups, and source (hospital-acquired or community-acquired). These incidence estimates will be extrapolated, following age standardization using national census data, to yield CDI disease burden estimates for Japan. CLOUD also serves as a model for studies in other countries that can use the CLOUD protocol to estimate CDI disease burden.

Keywords: Clostridium difficile, disease burden, epidemiology, study protocol

Procedia PDF Downloads 261

Authors: Petra Gergelova, Sofia Ioannidou, Davide Arcella, Alexandra Tard, Polly E. Boon, Oliver Lindtner, Christina Tlustos, Jean-Charles Leblanc

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Objectives: To assess chronic dietary exposure to food additives in different European countries and population groups. Method and Design: The European Food Safety Authority’s (EFSA) Panel on Food Additives and Nutrient Sources added to Food (ANS) estimates chronic dietary exposure to food additives with the purpose of re-evaluating food additives that were previously authorized in Europe. For this, EFSA uses concentration values (usage and/or analytical occurrence data) reported through regular public calls for data by food industry and European countries. These are combined, at individual level, with national food consumption data from the EFSA Comprehensive European Food Consumption Database including data from 33 dietary surveys from 19 European countries and considering six different population groups (infants, toddlers, children, adolescents, adults and the elderly). EFSA ANS Panel estimates dietary exposure for each individual in the EFSA Comprehensive Database by combining the occurrence levels per food group with their corresponding consumption amount per kg body weight. An individual average exposure per day is calculated, resulting in distributions of individual exposures per survey and population group. Based on these distributions, the average and 95th percentile of exposure is calculated per survey and per population group. Dietary exposure is assessed based on two different sets of data: (a) Maximum permitted levels (MPLs) of use set down in the EU legislation (defined as regulatory maximum level exposure assessment scenario) and (b) usage levels and/or analytical occurrence data (defined as refined exposure assessment scenario). The refined exposure assessment scenario is sub-divided into the brand-loyal consumer scenario and the non-brand-loyal consumer scenario. For the brand-loyal consumer scenario, the consumer is considered to be exposed on long-term basis to the highest reported usage/analytical level for one food group, and at the mean level for the remaining food groups. For the non-brand-loyal consumer scenario, the consumer is considered to be exposed on long-term basis to the mean reported usage/analytical level for all food groups. An additional exposure from sources other than direct addition of food additives (i.e. natural presence, contaminants, and carriers of food additives) is also estimated, as appropriate. Results: Since 2014, this methodology has been applied in about 30 food additive exposure assessments conducted as part of scientific opinions of the EFSA ANS Panel. For example, under the non-brand-loyal scenario, the highest 95th percentile of exposure to α-tocopherol (E 307) and ammonium phosphatides (E 442) was estimated in toddlers up to 5.9 and 8.7 mg/kg body weight/day, respectively. The same estimates under the brand-loyal scenario in toddlers resulted in exposures of 8.1 and 20.7 mg/kg body weight/day, respectively. For the regulatory maximum level exposure assessment scenario, the highest 95th percentile of exposure to α-tocopherol (E 307) and ammonium phosphatides (E 442) was estimated in toddlers up to 11.9 and 30.3 mg/kg body weight/day, respectively. Conclusions: Detailed and up-to-date information on food additive concentration values (usage and/or analytical occurrence data) and food consumption data enable the assessment of chronic dietary exposure to food additives to more realistic levels.

Keywords: α-tocopherol, ammonium phosphatides, dietary exposure assessment, European Food Safety Authority, food additives, food consumption data

Procedia PDF Downloads 325

Authors: Elsie M. Nolte, Annie M. Joubert, Roy Lakier, Maryke Etsebeth, Jolene M. Helena, Marcel Verwey, Laurence Lafanechere, Anne E. Theron

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Treatment regimens for breast- and lung cancers may include both radiation- and chemotherapy. Ideally, a pharmaceutical agent which selectively sensitizes cancer cells to gamma (γ)-radiation would allow administration of lower doses of each modality, yielding synergistic anti-cancer benefits and lower metastasis occurrence, in addition to decreasing the side-effect profiles. A range of 2-methoxyestradiol (2-ME) analogues, namely 2-ethyl-3-O-sulphamoyl-estra-1,3,5 (10) 15-tetraene-3-ol-17one (ESE-15-one), 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol) and 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16) were in silico-designed by our laboratory, with the aim of improving the parent compound’s bioavailability in vivo. The main effect of these compounds is the disruption of microtubule dynamics with a resultant mitotic accumulation and induction of programmed cell death in various cancer cell lines. This in vitro study aimed to determine the cellular responses involved in the radiation sensitization effects of these analogues at low doses in breast- and lung cancer cell lines. The oestrogen receptor positive MCF-7-, oestrogen receptor negative MDA-MB-231- and triple negative BT-20 breast cancer cell lines as well as the A549 lung cancer cell line were used. The minimal compound- and radiation doses able to induce apoptosis were determined using annexin-V and cell cycle progression markers. These doses (cell line dependent) were used to pre-sensitize the cancer cells 24 hours prior to 6 gray (Gy) radiation. Experiments were conducted on samples exposed to the individual- as well as the combination treatment conditions in order to determine whether the combination treatment yielded an additive cell death response. Morphological studies included light-, fluorescence- and transmission electron microscopy. Apoptosis induction was determined by flow cytometry employing annexin V, cell cycle analysis, B-cell lymphoma 2 (Bcl-2) signalling, as well as reactive oxygen species (ROS) production. Clonogenic studies were performed by allowing colony formation for 10 days post radiation. Deoxyribonucleic acid (DNA) damage was quantified via γ-H2AX foci and micronuclei quantification. Amplification of the p53 signalling pathway was determined by western blot. Results indicated that exposing breast- and lung cancer cells to nanomolar concentrations of these analogues 24 hours prior to γ-radiation induced more cell death than the compound- and radiation treatments alone. Hypercondensed chromatin, decreased cell density, a damaged cytoskeleton and an increase in apoptotic body formation were observed in cells exposed to the combination treatment condition. An increased number of cells present in the sub-G1 phase as well as increased annexin-V staining, elevation of ROS formation and decreased Bcl-2 signalling confirmed the additive effect of the combination treatment. In addition, colony formation decreased significantly. p53 signalling pathways were significantly amplified in cells exposed to the analogues 24 hours prior to radiation, as was the amount of DNA damage. In conclusion, our results indicated that pre-treatment of breast- and lung cancer cells with low doses of 2-ME analogues sensitized breast- and lung cancer cells to γ-radiation and induced apoptosis more so than the individual treatments alone. Future studies will focus on the effect of the combination treatment on non-malignant cellular counterparts.

Keywords: cancer, microtubule dynamics, radiation therapy, radiosensitization

Procedia PDF Downloads 207

Authors: Lionel Trovalet, Lisa Liu, Dimitri Bigot, Nadia Hammami, Jean-Pierre Habas, Bruno Malet-Damour

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The MCP-iBAT1 project is carried out to study the behavior of Phase Change Materials (PCM) integrated in building envelopes in a tropical environment. Through the phase transitions (melting and freezing) of the material, thermal energy can be absorbed or released. This process enables the regulation of indoor temperatures and the improvement of thermal comfort for the occupants. Most of the commercially available PCMs are more suitable to temperate climates than to tropical climates. The case of Reunion Island is noteworthy as there are multiple micro-climates. This leads to our key question: developing one or multiple bio-based PCMs that cover the thermal needs of the different locations of the island. The present paper focuses on the numerical approach to select the PCM properties relevant to tropical areas. Numerical simulations have been carried out with two softwares: EnergyPlusTM and Isolab. The latter has been developed in the laboratory, with the implicit Finite Difference Method, in order to evaluate different physical models. Both are Thermal Dynamic Simulation (TDS) softwares that predict the building’s thermal behavior with one-dimensional heat transfers. The parameters used in this study are the construction’s characteristics (dimensions and materials) and the environment’s description (meteorological data and building surroundings). The building is modeled in accordance with the experimental setup. It is divided into two rooms, cells A and B, with same dimensions. Cell A is the reference, while in cell B, a layer of commercial PCM (Thermo Confort of MCI Technologies) has been applied to the inner surface of the North wall. Sensors are installed in each room to retrieve temperatures, heat flows, and humidity rates. The collected data are used for the comparison with the numerical results. Our strategy is to implement two similar buildings at different altitudes (Saint-Pierre: 70m and Le Tampon: 520m) to measure different temperature ranges. Therefore, we are able to collect data for various seasons during a condensed time period. The following methodology is used to validate the numerical models: calibration of the thermal and PCM models in EnergyPlusTM and Isolab based on experimental measures, then numerical testing with a sensitivity analysis of the parameters to reach the targeted indoor temperatures. The calibration relies on the past ten months’ measures (from September 2020 to June 2021), with a focus on one-week study on November (beginning of summer) when the effect of PCM on inner surface temperatures is more visible. A first simulation with the PCM model of EnergyPlus gave results approaching the measurements with a mean error of 5%. The studied property in this paper is the melting temperature of the PCM. By determining the representative temperature of winter, summer and inter-seasons with past annual’s weather data, it is possible to build a numerical model of multi-layered PCM. Hence, the combined properties of the materials will provide an optimal scenario for the application on PCM in tropical areas. Future works will focus on the development of bio-based PCMs with the selected properties followed by experimental and numerical validation of the materials. 1Materiaux ´ a Changement de Phase, une innovation pour le B ` ati Tropical

Keywords: energyplus, multi-layer of PCM, phase changing materials, tropical area

Procedia PDF Downloads 95

Authors: Nikola Toshikj, Michel Ramonda, Sylvain Catrouillet, Jean-Jacques Robin, Sebastien Blanquer

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Biodegradable and biocompatible block copolymers have risen as the golden materials in both medical and environmental applications. Moreover, if their architecture is of controlled manner, higher applications can be foreseen. In the meantime, organocatalytic ROP has been promoted as more rapid and immaculate route, compared to the traditional organometallic catalysis, towards efficient synthesis of block copolymer architectures. Therefore, herein we report novel organocatalytic pathway with guanidine molecules (TBD) for supported synthesis of trimethylene carbonate initiated by poly(caprolactone) as pre-polymer. Pristine PTMC-b-PCL-b-PTMC block copolymer structure, without any residual products and clear desired block proportions, was achieved under 1.5 hours at room temperature and verified by NMR spectroscopies and size-exclusion chromatography. Besides, when elaborating block copolymer films, further stability and amelioration of mechanical properties can be achieved via additional reticulation step of precedently methacrylated block copolymers. Subsequently, stimulated by the insufficient studies on the phase-separation/crystallinity relationship in these semi-crystalline block copolymer systems, their intrinsic thermal and morphology properties were investigated by differential scanning calorimetry and atomic force microscopy. Firstly, by DSC measurements, the block copolymers with χABN values superior to 20 presented two distinct glass transition temperatures, close to the ones of the respecting homopolymers, demonstrating an initial indication of a phase-separated system. In the interim, the existence of the crystalline phase was supported by the presence of melting temperature. As expected, the crystallinity driven phase-separated morphology predominated in the AFM analysis of the block copolymers. Neither crosslinking at melted state, hence creation of a dense polymer network, disturbed the crystallinity phenomena. However, the later revealed as sensible to rapid liquid nitrogen quenching directly from the melted state. Therefore, AFM analysis of liquid nitrogen quenched and crosslinked block copolymer films demonstrated a thermodynamically driven phase-separation clearly predominating over the originally crystalline one. These AFM films remained stable with their morphology unchanged even after 4 months at room temperature. However, as demonstrated by DSC analysis once rising the temperature above the melting temperature of the PCL block, neither the crosslinking nor the liquid nitrogen quenching shattered the semi-crystalline network, while the access to thermodynamical phase-separated structures was possible for temperatures under the poly (caprolactone) melting point. Precisely this coexistence of dual crosslinked/crystalline networks in the same copolymer structure allowed us to establish, for the first time, the shape-memory properties in such materials, as verified by thermomechanical analysis. Moreover, the response temperature to the material original shape depended on the block copolymer emplacement, hence PTMC or PCL as end-block. Therefore, it has been possible to reach a block copolymer with transition temperature around 40°C thus opening potential real-life medical applications. In conclusion, the initial study of phase-separation/crystallinity relationship in PTMC-b-PCL-b-PTMC block copolymers lead to the discovery of novel shape memory materials with superior properties, widely demanded in modern-life applications.

Keywords: biodegradable block copolymers, organocatalytic ROP, self-assembly, shape-memory

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Authors: Hugo Daneluzzo, Christelle Rabbat, Alan Jean-Marie

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Water electrolysis is one of the most advanced technologies for producing hydrogen and can be easily combined with electricity from different sources. Under the influence of electric current, water molecules can be split into oxygen and hydrogen. The production of hydrogen by water electrolysis favors the integration of renewable energy sources into the energy mix by compensating for their intermittence through the storage of the energy produced when production exceeds demand and its release during off-peak production periods. Among the various electrolysis technologies, anion exchange membrane (AEM) electrolyser cells are emerging as a reliable technology for water electrolysis. Modeling and simulation are effective tools to save time, money, and effort during the optimization of operating conditions and the investigation of the design. The modeling and simulation become even more important when dealing with multiphysics dynamic systems. One of those systems is the AEM electrolysis cell involving complex physico-chemical reactions. Once developed, models may be utilized to comprehend the mechanisms to control and detect flaws in the systems. Several modeling methods have been initiated by scientists. These methods can be separated into two main approaches, namely equation-based modeling and graph-based modeling. The former approach is less user-friendly and difficult to update as it is based on ordinary or partial differential equations to represent the systems. However, the latter approach is more user-friendly and allows a clear representation of physical phenomena. In this case, the system is depicted by connecting subsystems, so-called blocks, through ports based on their physical interactions, hence being suitable for multiphysics systems. Among the graphical modelling methods, the bond graph is receiving increasing attention as being domain-independent and relying on the energy exchange between the components of the system. At present, few studies have investigated the modelling of AEM systems. A mathematical model and a bond graph model were used in previous studies to model the electrolysis cell performance. In this study, experimental data from literature were simulated using OpenModelica using bond graphs and mathematical approaches. The polarization curves at different operating conditions obtained by both approaches were compared with experimental ones. It was stated that both models predicted satisfactorily the polarization curves with error margins lower than 2% for equation-based models and lower than 5% for the bond graph model. The activation polarization of hydrogen evolution reactions (HER) and oxygen evolution reactions (OER) were behind the voltage loss in the AEM electrolyzer, whereas ion conduction through the membrane resulted in the ohmic loss. Therefore, highly active electro-catalysts are required for both HER and OER while high-conductivity AEMs are needed for effectively lowering the ohmic losses. The bond graph simulation of the polarisation curve for operating conditions at various temperatures has illustrated that voltage increases with temperature owing to the technology of the membrane. Simulation of the polarisation curve can be tested virtually, hence resulting in reduced cost and time involved due to experimental testing and improved design optimization. Further improvements can be made by implementing the bond graph model in a real power-to-gas-to-power scenario.

Keywords: hydrogen production, anion-exchange membrane, electrolyzer, mathematical modeling, multiphysics modeling

Procedia PDF Downloads 91

Authors: Pierre-Andre Mudry, Jean Decaix, Jeremy Schmid, Cesar Papilloud, Cecile Munch-Alligne

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In most of the Swiss Alpine regions, the availability of water resources is usually adequate even in times of drought, as evidenced by the 2003 and 2018 summers. Indeed, important natural stocks are for the moment available in the form of snow and ice, but the situation is likely to change in the future due to global and regional climate change. In addition, alpine mountain regions are areas where climate change will be felt very rapidly and with high intensity. For instance, the ice regime of these regions has already been affected in recent years with a modification of the monthly availability and extreme events of precipitations. The current research, focusing on the municipality of Val de Bagnes, located in the canton of Valais, Switzerland, is part of a project led by the Altis company and achieved in collaboration with WSL, BlueArk Entremont, and HES-SO Valais-Wallis. In this region, water occupies a key position notably for winter and summer tourism. Thus, multiple actors want to apprehend the future needs and availabilities of water, on both the 2050 and 2100 horizons, in order to plan the modifications to the water supply and distribution networks. For those changes to be salient and efficient, a good knowledge of the current water distribution networks is of most importance. In the current case, the water drinking network is well documented, but this is not the case for the irrigation one. Since the water consumption for irrigation is ten times higher than for drinking water, data acquisition on the irrigation network is a major point to determine future scenarios. This paper first presents the instrumentation and simulation of the irrigation network using custom-designed IoT devices, which are coupled with a digital clone simulated to reduce the number of measuring locations. The developed IoT ad-hoc devices are energy-autonomous and can measure flows and pressures using industrial sensors such as calorimetric water flow meters. Measurements are periodically transmitted using the LoRaWAN protocol over a dedicated infrastructure deployed in the municipality. The gathered values can then be visualized in real-time on a dashboard, which also provides historical data for analysis. In a second phase, a digital clone of the irrigation network was modeled using EPANET, a software for water distribution systems that performs extended-period simulations of flows and pressures in pressurized networks composed of reservoirs, pipes, junctions, and sinks. As a preliminary work, only a part of the irrigation network was modelled and validated by comparisons with the measurements. The simulations are carried out by imposing the consumption of water at several locations. The validation is performed by comparing the simulated pressures are different nodes with the measured ones. An accuracy of +/- 15% is observed on most of the nodes, which is acceptable for the operator of the network and demonstrates the validity of the approach. Future steps will focus on the deployment of the measurement devices on the whole network and the complete modelling of the network. Then, scenarios of future consumption will be investigated. Acknowledgment— The authors would like to thank the Swiss Federal Office for Environment (FOEN), the Swiss Federal Office for Agriculture (OFAG) for their financial supports, and ALTIS for the technical support, this project being part of the Swiss Pilot program 'Adaptation aux changements climatiques'.

Keywords: hydraulic digital clone, IoT water monitoring, LoRaWAN water measurements, EPANET, irrigation network

Procedia PDF Downloads 145

Authors: Aisling Gough, Ruth F. Hunter, Jianjun Tang, Sarah F. Brennan, Oliver Smith, Mark A. Tully, Chris Patterson, Alberto Longo, George Hutchinson, Lindsay Prior, David French, Jean Adams, Emma McIntosh, Frank Kee

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Background: As a large proportion of the UK workforce is employed in sedentary occupations, worksite interventions have the potential to contribute significantly to the health of the population. The UK Government is currently encouraging the use of financial incentives to promote healthier lifestyles but there is a dearth of evidence regarding the effectiveness and sustainability of incentive schemes to promote physical activity in the workplace. Methods: A large cluster RCT is currently underway, incorporating nested behavioural economic field experiments and process evaluation, to evaluate the effectiveness of a Physical Activity Loyalty Scheme. Office-based employees were recruited from large public sector organisations in Lisburn and Belfast (Northern Ireland) and randomised to an Intervention or Control group. Participants in the Intervention Group were encouraged to take part in 150 minutes of physical activity per week through provision of financial incentives (retailer vouchers) to those who met physical activity targets throughout the course of the 6 month intervention. Minutes of physical activity were monitored when participants passed by sensors (holding a keyfob) placed along main walking routes, parks and public transport stops nearby their workplace. Participants in the Control Group will complete the same outcome assessments (waiting-list control). The primary outcome is steps per day measured via pedometers (7 days). Secondary outcomes include health and wellbeing (Short Form-8, EuroQol-5D-5L, Warwick Edinburgh Mental Well Being Scale), and work absenteeism and presenteeism. Data will be collected at baseline, 6, 12 and 18 months. Information on PAL card & website usage, voucher downloads and redemption of vouchers will also be collected as part of a comprehensive process evaluation. Results: In total, 853 participants have been recruited from 9 workplaces in Lisburn, 12 buildings within the Stormont Estate, Queen’s University Belfast and Belfast City Hospital. Participants have been randomised to intervention and control groups. Baseline and 6-month data for the Physical Activity Loyalty Scheme has been collected. Findings regarding the effectiveness of the intervention from the 6-month follow-up data will be presented. Discussion: This study will address the gap in knowledge regarding the effectiveness and cost-effectiveness of a workplace-based financial incentive scheme to promote a healthier lifestyle. As the UK workforce is increasingly sedentary, workplace-based physical activity interventions have significant potential in terms of encouraging employees to partake in physical activity during the working day which could lead to substantial improvements in physical activity levels overall. Implications: If a workplace based physical activity intervention such as this proves to be both effective and cost-effective, there is great potential to contribute significantly to the health and wellbeing of the workforce in the future. Workplace-based physical activity interventions have the potential to improve the physical and mental health of employees which may in turn lead to economic benefits for the employer, such as reduction in rates of absenteeism and increased productivity.

Keywords: behaviour change, cluster randomised controlled trial, loyalty scheme, physical activity

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Authors: Danielle Slomberg, Jerome Labille, Riccardo Catalano, Jean-Claude Hubaud, Alexandra Lopes, Alice Tagliati, Teresa Fernandes

Abstract:

In the assessment and management of cosmetics and personal care products, sunscreens are of emerging concern regarding both human and environmental health. Organic UV blockers in many sunscreens have been evidenced to undergo rapid photodegradation, induce dermal allergic reactions due to skin penetration, and to cause adverse effects on marine systems. While mineral UV-blockers may offer a safer alternative, their fate and impact and resulting regulation are still under consideration, largely related to the potential influence of nanotechnology-based products on both consumers and the environment. Nanometric titanium dioxide (TiO₂) UV-blockers have many advantages in terms of sun protection and asthetics (i.e., transparency). These UV-blockers typically consist of rutile nanoparticles coated with a primary mineral layer (silica or alumina) aimed at blocking the nanomaterial photoactivity and can include a secondary organic coating (e.g., stearic acid, methicone) aimed at favouring dispersion of the nanomaterial in the sunscreen formulation. The nanomaterials contained in the sunscreen can leave the skin either through a bathing of everyday usage, with subsequent release into rivers, lakes, seashores, and/or sewage treatment plants. The nanomaterial behaviour, fate and impact in these different systems is largely determined by its surface properties, (e.g. the nanomaterial coating type) and lifetime. The present work aims to develop the eco-design of sunscreens through the minimisation of risks associated with nanomaterials incorporated into the formulation. All stages of the sunscreen’s life cycle must be considered in this aspect, from its manufacture to its end-of-life, through its use by the consumer to its impact on the exposed environment. Reducing the potential release and/or toxicity of the nanomaterial from the sunscreen is a decisive criterion for its eco-design. TiO₂ UV-blockers of varied size and surface coating (e.g., stearic acid and silica) have been selected for this study. Hydrophobic TiO₂ UV-blockers (i.e., stearic acid-coated) were incorporated into a typical water-in-oil (w/o) formulation while hydrophilic, silica-coated TiO₂ UV-blockers were dispersed into an oil-in-water (o/w) formulation. The resulting sunscreens were characterised in terms of nanomaterial localisation, sun protection factor, and photo-passivation. The risk to the direct aquatic environment was assessed by evaluating the release of nanomaterials from the sunscreen through a simulated laboratory aging procedure. The size distribution, surface charge, and degradation state of the nano-composite by-products, as well as their nanomaterial concentration and colloidal behaviour were determined in a variety of aqueous environments (e.g., seawater and freshwater). Release of the hydrophobic nanocomposites into the aqueous environment was driven by oil droplet formation while hydrophilic nano-composites were readily dispersed. Ecotoxicity of the sunscreen by-products (from both w/o and o/w formulations) and their risk to marine organisms were assessed using coral symbiotes and tropical corals, evaluating both lethal and sublethal toxicities. The data dissemination and provided risk knowledge from the present work will help guide regulation related to nanomaterials in sunscreen, provide better information for consumers, and allow for easier decision-making for manufacturers.

Keywords: alteration, environmental fate, sunscreens, titanium dioxide nanoparticles

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Authors: Yiqi Zhu, Jean Francois Trani, Rameez Ulhassan

Abstract:

Extreme weather phenomena increased by 46% between 2007 and 2017 and have become more intense with the rise in global average temperatures. This increased intensity of climate variations often induces humanitarian crises and particularly affects vulnerable populations in low- and middle-income countries (LMICs). Expectant and lactating mothers are among the most vulnerable groups. Pakistan ranks 10th among the most affected countries by climate disasters. In 2022, monsoon floods submerged a third of the country, causing the loss of 1,500 lives. Approximately 650,000 expectant and lactating mothers faced systematic stress from climatic disasters. Our study used participatory methods to investigate the systematic impact of climatic disasters on maternal health. In March 2023, we conducted six Group Model Building (GMB) workshops with healthcare workers, fathers, and mothers separately in two of the most affected areas in Pakistan. This study was approved by the Islamic Relief Research Review Board. GMB workshops consist of three sessions. In the first session, participants discussed the factors that impact maternal health. After identifying the factors, they discussed the connections among them and explored the system structures that collectively impact maternal health. Based on the discussion, a causal loop diagram (CLD) was created. Finally, participants discussed action ideas that could improve the system to enhance maternal health. Based on our discussions and the causal loop diagram, we identified interconnected factors at the family, community, and policy levels. Mothers and children are directly impacted by three interrelated factors: food insecurity, unstable housing, and lack of income. These factors create a reinforcing cycle that negatively affects both mothers and newborns. After the flood, many mothers were unable to produce sufficient breastmilk due to their health status. Without breastmilk and sufficient food for complementary feeding, babies tend to get sick in damp and unhygienic environments resulting from temporary or unstable housing. When parents take care of sick children, they miss out on income-generating opportunities. At the community level, the lack of access to clean water and sanitation (WASH) and maternal healthcare further worsens the situation. Structural failures such as a lack of safety nets and programs associated with flood preparedness make families increasingly vulnerable with each disaster. Several families reported that they had not fully recovered from a flood that occurred ten years ago, and this latest disaster destroyed their lives again. Although over twenty non-profit organizations are working in these villages, few of them provide sustainable support. Therefore, participants called for systemic changes in response to the increasing frequency of climate disasters. The study reveals the systematic vulnerabilities of mothers and children after climatic disasters. The most vulnerable populations are often affected the most by climate change. Collaborative efforts are required to improve water and forest management, strengthen public infrastructure, increase access to WASH, and gradually build climate-resilient communities. Governments, non-governmental organizations, and the community should work together to develop and implement effective strategies to prevent, mitigate, and adapt to climate change and its impacts.

Keywords: climatic disasters, maternal health, Pakistan, systematic impact, flood, disaster relief.

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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

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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Authors: Jocelyn Doucet, Jean-Philippe Laviolette, Ali Eslami

Abstract:

The end-of-life management and recycling of polymer wastes remains a key environment issue in on-going efforts to increase resource efficiency and attaining GHG emission reduction targets. Half of all the plastics ever produced were made in the last 13 years, and only about 16% of that plastic waste is collected for recycling, while 25% is incinerated, 40% is landfilled, and 19% is unmanaged and leaks in the environment and waterways. In addition to the plastic collection issue, the UN recently published a report on chemicals in plastics, which adds another layer of challenge when integrating recycled content containing toxic products into new products. To tackle these important issues, innovative solutions are required. Chemical recycling of plastics provides new complementary alternatives to the current recycled plastic market by converting waste material into a high value chemical commodity that can be reintegrated in a variety of applications, making the total market size of the output – virgin-like, high value products - larger than the market size of the input – plastic waste. Access to high-quality feedstock also remains a major obstacle, primarily due to material contamination issues. Pyrowave approaches this challenge with its innovative nano-recycling technology, which purifies polymers at the molecular level, removing undesirable contaminants and restoring the resin to its virgin state without having to depolymerise it. This breakthrough approach expands the range of plastics that can be effectively recycled, including mixed plastics with various contaminants such as lead, inorganic pigments, and flame retardants. The technology allows yields below 100ppm, and purity can be adjusted to an infinitesimal level depending on the customer's specifications. The separation of the polymer and contaminants in Pyrowave's nano-recycling process offers the unique ability to customize the solution on targeted additives and contaminants to be removed based on the difference in molecular size. This precise control enables the attainment of a final polymer purity equivalent to virgin resin. The patented process involves dissolving the contaminated material using a specially formulated solvent, purifying the mixture at the molecular level, and subsequently extracting the solvent to yield a purified polymer resin that can directly be reintegrated in new products without further treatment. Notably, this technology offers simplicity, effectiveness, and flexibility while minimizing environmental impact and preserving valuable resources in the manufacturing circuit. Pyrowave has successfully applied this nano-recycling technology to decontaminate polymers and supply purified, high-quality recycled plastics to critical industries, including food-contact compliance. The technology is low-carbon, electrified, and provides 100% traceable resins with properties identical to those of virgin resins. Additionally, the issue of low recycling rates and the limited market for traditionally hard-to-recycle plastic waste has fueled the need for new complementary alternatives. Chemical recycling, such as Pyrowave's microwave depolymerization, presents a sustainable and efficient solution by converting plastic waste into high-value commodities. By employing microwave catalytic depolymerization, Pyrowave enables a truly circular economy of plastics, particularly in treating polystyrene waste to produce virgin-like styrene monomers. This revolutionary approach boasts low energy consumption, high yields, and a reduced carbon footprint. Pyrowave offers a portfolio of sustainable, low-carbon, electric solutions to give plastic waste a second life and paves the way to the new circular economy of plastics. Here, particularly for polystyrene, we show that styrene monomer yields from Pyrowave’s polystyrene microwave depolymerization reactor is 2,2 to 1,5 times higher than that of the thermal conventional pyrolysis. In addition, we provide a detailed understanding of the microwave assisted depolymerization via analyzing the effects of microwave power, pyrolysis time, microwave receptor and temperature on the styrene product yields. Furthermore, we investigate life cycle environmental impact assessment of microwave assisted pyrolysis of polystyrene in commercial-scale production. Finally, it is worth pointing out that Pyrowave is able to treat several tons of polystyrene to produce virgin styrene monomers and manage waste/contaminated polymeric materials as well in a truly circular economy.

Keywords: nanorecycling, nanomaterials, plastic recycling, depolymerization

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