Search results for: North Western of Libya

Authors: Luc Beal

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Introduction. Among the stakeholders involved in the tourist decision-making process, the accommodation provider has the potential to play a crucial role in raising awareness, disseminating information, and thus influencing the tourists’ choice of transportation. Since the early days of tourism, the accommodation provider has consistently served as the primary point of contact with the destination, and consequently, as the primary source of information for visitors. By offering accommodation and hospitality, the accommodation provider has evolved into a trusted third party, functioning as an 'ambassador' capable of recommending the finest attractions and activities available at the destination. In contemporary times, when tourists plan their trips, they make a series of consecutive decisions, with the most important decision being to lock-in the accommodation reservation for the earliest days, so as to secure a safe arrival. Consequently, tourists place their trust in the accommodation provider not only for lodging but also for recommendations regarding restaurants, activities, and more. Thus, the latter has the opportunity to inform and influence tourists well in advance of their arrival, particularly during the booking phase, namely when it comes to selecting their mode of transportation. The pressing need to reduce greenhouse gas emissions within the tourism sector presents an opportunity to underscore the influence that accommodation providers have historically exerted on tourist decision-making . Methodology A participatory research, currently ongoing in south-western France, in collaboration with a nationwide hotel group and several destination management organizations, aims at examining the factors that determine the ability of accommodation providers to influence tourist transportation choices. Additionally, the research seeks to identify the conditions that motivate accommodation providers to assume a proactive role, such as fostering customer loyalty, reduced distribution costs, and financial compensation mechanisms. A panel of hotels participated in a series of focus group sessions with tourists, with the objective of modeling the decision-making process of tourists regarding their choice of transportation mode and to identify and quantify the types and levels of incentives liable to encourage environmentally responsible choices. Individual interviews were also conducted with hotel staff, including receptionists and guest relations officers, to develop a framework for interactions with tourists during crucial decision-making moments related to transportation choices. The primary finding of this research indicates that financial incentives significantly outweigh symbolic incentives in motivating tourists to opt for eco-friendly modes of transportation. Another noteworthy result underscores the crucial impact of organizational conditions governing interactions with tourists both before and during their stay. These conditions greatly influence the ability to raise awareness at key decision-making moments and the possibility of gathering data about the chosen transportation mode during the stay. In conclusion, this research has led to the formulation of practical recommendations for accommodation providers and Destination Marketing Organizations (DMOs). These recommendations pertain to communication protocols with tourists, the collection of evidences confirming chosen transportation modes, and the implementation of necessary incentives. Through these measures, accommodation provider can assume a central role in guiding tourists towards making responsible choices in terms of transportation.

Keywords: accommodation provider, trusted third party, environmentally-friendly transportation, green house gas, tourist decision-making process

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Authors: Olga V. Chervyakova, Elmira T. Tailakova, Vitaliy M. Strochkov, Kulyaisan T. Sultankulova, Nurlan T. Sandybayev, Lev G. Nemchinov, Rosemarie W. Hammond

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Sheep pox is a highly contagious infection that OIE regards to be one of the most dangerous animal diseases. It causes enormous economic losses because of death and slaughter of infected animals, lower productivity, cost of veterinary and sanitary as well as quarantine measures. To control spread of sheep pox infection the attenuated vaccines are widely used in the Republic of Kazakhstan and other Former Soviet Union countries. In spite of high efficiency of live vaccines, the possible presence of the residual virulence, potential genetic instability restricts their use in disease-free areas that leads to necessity to exploit new approaches in vaccine development involving recombinant DNA technology. Vaccines on the basis of recombinant proteins are the newest generation of prophylactic preparations. The main advantage of these vaccines is their low reactogenicity and this fact makes them widely used in medical and veterinary practice for vaccination of humans and farm animals. The objective of the study is to produce recombinant immunogenic proteins for development of the high-performance means for sheep pox prophylaxis. The SPV proteins were chosen for their homology with the known immunogenic vaccinia virus proteins. Assay of nucleotide and amino acid sequences of the target SPV protein genes. It has been shown that four proteins SPPV060 (ortholog L1), SPPV074 (ortholog H3), SPPV122 (ortholog A33) and SPPV141 (ortholog B5) possess transmembrane domains at N- or C-terminus while in amino acid sequences of SPPV095 (ortholog А 4) and SPPV117 (ortholog А 27) proteins these domains were absent. On the basis of these findings the primers were constructed. Target genes were amplified and subsequently cloned into the expression vector рЕТ26b(+) or рЕТ28b(+). Six constructions (pSPPV060ΔТМ, pSPPV074ΔТМ, pSPPV095, pSPPV117, pSPPV122ΔТМ and pSPPV141ΔТМ) were obtained for expression of the SPV genes under control of T7 promoter in Escherichia coli. To purify and detect recombinant proteins the amino acid sequences were modified by adding six histidine molecules at C-terminus. Induction of gene expression by IPTG was resulted in production of the proteins with molecular weights corresponding to the estimated values for SPPV060, SPPV074, SPPV095, SPPV117, SPPV122 and SPPV141, i.e. 22, 30, 20, 19, 17 and 22 kDa respectively. Optimal protocol of expression for each gene that ensures high yield of the recombinant protein was identified. Assay of cellular lysates by western blotting confirmed expression of the target proteins. Recombinant proteins bind specifically with antibodies to polyhistidine. Moreover all produced proteins are specifically recognized by the serum from experimentally SPV-infected sheep. The recombinant proteins SPPV060, SPPV074, SPPV117, SPPV122 and SPPV141 were also shown to induce formation of antibodies with virus-neutralizing activity. The results of the research will help to develop a new-generation high-performance means for specific sheep pox prophylaxis that is one of key moments in animal health protection. The research was conducted under the International project ISTC # K-1704 “Development of methods to construct recombinant prophylactic means for sheep pox with use of transgenic plants” and under the Grant Project RK MES G.2015/0115RK01983 "Recombinant vaccine for sheep pox prophylaxis".

Keywords: prophylactic preparation, recombinant protein, sheep pox virus, subunit vaccine

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Authors: Alexandra Cheira

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Cultural appropriation has been theorised as a form of colonialism in which members of a dominant culture reduce cultural elements that are deeply meaningful to a minority culture to the category of the “exotic other” since they do not experience the oppression and discriminations faced by members of the minority culture. Yet, in the particular case of literature, writers such as Lionel Shriver and Bernardine Evaristo have argued that authors from a cultural majority have a right to write in the voice of someone from a cultural minority, hence attacking the idea that this is a form of cultural appropriation. By definition, Shriver and Evaristo claim, writers are supposed to write beyond their own culture, gender, class, and/ or race. In this light, this paper discusses the limits of cultural appropriation vis-à-vis the ethics of narrative empathy by addressing the mixed critical reception of Kathryn Stockett’s The Help (2009) and Jeanine Cummins’s American Dirt (2020). In fact, both novels were acclaimed as global eye-openers regarding the struggles of respectively South American migrants and African American maids. At the same time, both novelists have been accused of cultural appropriation by telling a story that is not theirs to tell, given the fact that they are white women telling these stories in what critics have argued is really an American voice telling a story to American readers.These claims will be investigated within the framework of Edward Said’s foundational examination of Orientalism in the field of postcolonial studies as a Western style for authoritatively restructuring the Orient. This means that Orientalist stereotypes regarding Eastern cultures have implicitly validated colonial and imperial pursuits, in the specific context of literary representations of African American and Mexican cultures by white writers. At the same time, the conflicted reception of American Dirt and The Help will be examined within the critical framework of narrative empathy as theorised by Suzanne Keen. Hence, there will be a particular focus on the way a reader’s heated perception that the author’s perspective is purely dishonest can result from a friction between an author’s intention and a reader’s experience of narrative empathy, while a shared sense of empathy between authors and readers can be a rousing momentum to move beyond literary response to social action.Finally, in order to assess that “the key question should not be who can write about whom, but how the writer tells the story”, the recent controversy surrounding Dutch author Marieke Lucas Rijneveld’s decision to resign the translation of American poet Amanda Gorman’s work into Dutch will be duly investigated. In fact, Rijneveld stepped out after journalist and activist Janice Deul criticised Dutch publisher Meulenhoff for choosing a translator who was not also Black, despite the fact that 22-year-old Gorman had selected the 29-year-old Rijneveld herself, as a fellow young writer who had likewise come to fame early on in life. In this light, the critical argument that the controversial reception of The Help reveals as much about US race relations in the early twenty-first century as about the complex literary transactions between individual readers and the novel itself will also be discussed in the extended context of American Dirt and white author Marieke Rijneveld’s withdrawal from the projected translation of Black poet Amanda Gorman.

Keywords: cultural appropriation, cultural stereotypes, narrative empathy, race relations

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Authors: Caroline Seo, Jennifer Stephens, Kirstin H. Heinrich

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Background: Clostridiodes (formerly Clostridium) difficile infection (CDI) is an anaerobic, spore-forming bacterium with manifestations including diarrhea, pseudomembranous colitis and toxic megacolon. Despite general understanding that CDI may be associated with marked burden on patients’ health, there has been limited information available on the humanistic burden of CDI. The objective of this literature review was to summarize the published data on the humanistic burden of CDI globally, in order to better inform future research efforts and increase awareness of the patient perspective in this disease. Methods: A comprehensive literature review of the past 15 years (2002-2017) was conducted using MEDLINE, Embase and Cumulative Index of Nursing and Allied Health Literature. Additional searches were conducted from conference proceedings (2015-2017). Articles selected were studies specifically designed to examine the humanistic burden of illness associated with adult patients with CDI. Results: Of 3,325 articles or abstracts identified, 33 remained after screening and full text review. Sixty percent (60%) were published in 2016 or 2017. Data from the United States or Western Europe were most common. Data from Brazil, Canada, China and Spain also exist. Thirteen (13) studies used validated patient-reported outcomes instruments, mostly EQ-5D utility and SF-36 generic instruments. Three (3) studies used CDI-specific instruments (CDiff32, CDI-DaySyms). The burden of CDI impacts patients in multiple health-related quality of life (HRQOL) domains. SF-36 domains with the largest decrements compared to other GI diarrheal diseases (IBS-D and Crohn’s) were role physical, physical functioning, vitality, social functioning, and role emotional. Reported EQ-5D utilities for CDI ranged from 0.35-0.42 compared to 0.65 in Crohn’s and 0.72 in IBS-D. The majority of papers addressed physical functioning and mental health domains (67% for both). Across various studies patients reported weakness, lack of appetite, sleep disturbance, functional dependence, and decreased activities of daily lives due to the continuous diarrhea. Due to lack of control over this infection, CDI also impacts the psychological and emotional quality of life of the patients. Patients reported feelings of fear, anxiety, frustration, depression, and embarrassment. Additionally, the type of disease (primary vs. recurrent) may impact mental health. One study indicated that there is a decrement in SF-36 mental scores in patients with recurrent CDI, in comparison to patients with primary CDI. Other domains highlighted by these studies include pain (27%), social isolation (27%), vitality and fatigue (24%), self-care (9%), and caregiver burden (0%). Two studies addressed work productivity, with 1 of these studies reporting that CDI patients had the highest work productivity and activity impairment scores among the gastrointestinal diseases. No study specifically included caregiver self-report. However, 3 studies did provide mention of patients’ worry on how their diagnosis of CDI would impact family, caregivers, and/or friends. Conclusions: Despite being a serious public health issue there has been a paucity of research on the HRQOL among those with CDI. While progress is being made, gaps exist in understanding the burden on patients, caregivers, and families. Future research is warranted to aid understanding of the CDI patient perspective.

Keywords: burden, Clostridiodes, difficile, humanistic, infection

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Authors: Tatiana Rizova

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The migrant crisis, which peaked in 2015-2016, posed an unprecedented challenge to the European Union’s (EU) newest member states, including Bulgaria and Hungary. Their governments had to formulate sound migration policies with expediency and sensitivity to the needs of millions of people fleeing violent conflicts in the Middle East and failed states in North Africa. Political leaders in post-communist countries had to carefully coordinate with other EU member states on joint policies and solutions while minimizing the risk of alienating their increasingly anti-migrant domestic constituents. Post-communist member states’ governments chose distinct policy responses to the crisis, which were dictated by factors such as their governments’ partisan stances on migration, their views of the European Union, and the decision to frame the crisis as a security or a humanitarian issue. This paper explores how two Bulgarian governments (Boyko Borisov’s second and third government formed during the 43rd and 44th Bulgarian National Assembly, respectively) navigated the processes of EU migration policy making and managing the expectations of their electorates. Based on a comparative analysis of refugee policies in Bulgaria and Hungary during the height of the crisis (2015-2016) and a temporal analysis of refugee policies in Bulgaria (2015-2018), the paper advances the following conclusions. Drawing on insights of the Copenhagen school of security studies, the paper argues that cultural concerns dominated domestic debates in both Bulgaria and Hungary; both governments framed the issue predominantly as a matter of security rather than humanitarian disaster. Regardless of the similarities in issue framing, however, the two governments sought different paths of tackling the crisis. While the Bulgarian government demonstrated its willingness to comply with EU decisions (such as the proposal for mandatory quotas for refugee relocation), the Hungarian government defied EU directives and became a leading voice of dissent inside the EU. The current Bulgarian government (April 2017 - present) appears to be committed to complying with EU decisions and accepts the strategy of EU burden-sharing, while the Hungarian government has continually snubbed the EU’s appeals for cooperation despite the risk of hefty financial penalties. Hungary’s refugee policies have been influenced by the parliamentary representation of the far right-wing party Movement for a Better Hungary (Jobbik), which has encouraged the majority party (FIDESZ) to adopt harsher anti-migrant rhetoric and more hostile policies toward refugees. Bulgaria’s current government is a coalition of the center-right Citizens for a European Development of Bulgaria (GERB) and its far right-wing junior partners – the United Patriots (comprised of three nationalist political parties). The parliamentary presence of Jobbik in Hungary’s parliament has magnified the anti-migrant stance, rhetoric, and policies of Mr. Orbán’s Civic Alliance; we have yet to observe a substantial increase in the anti-migrant rhetoric and policies in Bulgaria’s case. Analyzing responses to the migrant/refugee crisis is a critical opportunity to understand how issues of cultural identity and belonging, inclusion and exclusion, regional integration and disintegration are debated and molded into policy in Europe’s youngest member states in the broader EU context.

Keywords: Copenhagen School, migrant crisis, refugees, security

Procedia PDF Downloads 98

Authors: Peregrine James Dalziel, Philip Vu Tran

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Objective / Introduction: Demand for radiology services from Emergency Departments (ED) continues to increase with greater demands placed on radiology staff providing reports for the management of complex cases. Queuing theory indicates that wide variability of process time with the random nature of request arrival increases the probability of significant queues. This can lead to delays in the time-to-availability of radiology reports (TTA-RR) and potentially impaired ED patient flow. In addition, greater “cognitive workload” of greater volume may lead to reduced productivity and increased errors. We sought to quantify the potential ED flow improvements obtainable from increased radiology providers serving 3 public hospitals in Melbourne Australia. We sought to assess the potential productivity gains, quality improvement and the cost-effectiveness of increased labor inputs. Methods & Materials: The Western Health Medical Imaging Department moved from single resident coverage on weekend days 8:30 am-10:30 pm to a limited period of 2 resident coverage 1 pm-6 pm on both weekend days. The TTA-RR for weekend CT scans was calculated from the PACs database for the 8 month period symmetrically around the date of staffing change. A multivariate linear regression model was developed to isolate the improvement in TTA-RR, between the two 4-months periods. Daily and hourly scan volume at the time of each CT scan was calculated to assess the impact of varying department workload. To assess any improvement in report quality/errors a random sample of 200 studies was assessed to compare the average number of clinically significant over-read addendums to reports between the 2 periods. Cost-effectiveness was assessed by comparing the marginal cost of additional staffing against a conservative estimate of the economic benefit of improved ED patient throughput using the Australian national insurance rebate for private ED attendance as a revenue proxy. Results: The primary resident on call and the type of scan accounted for most of the explained variability in time to report availability (R2=0.29). Increasing daily volume and hourly volume was associated with increased TTA-RR (1.5m (p<0.01) and 4.8m (p<0.01) respectively per additional scan ordered within each time frame. Reports were available 25.9 minutes sooner on average in the 4 months post-implementation of double coverage (p<0.01) with additional 23.6 minutes improvement when 2 residents were on-site concomitantly (p<0.01). The aggregate average improvement in TTA-RR was 24.8 hours per weekend day This represents the increased decision-making time available to ED physicians and potential improvement in ED bed utilisation. 5% of reports from the intervention period contained clinically significant addendums vs 7% in the single resident period but this was not statistically significant (p=0.7). The marginal cost was less than the anticipated economic benefit based assuming a 50% capture of improved TTA-RR inpatient disposition and using the lowest available national insurance rebate as a proxy for economic benefit. Conclusion: TTA-RR improved significantly during the period of increased staff availability, both during the specific period of increased staffing and throughout the day. Increased labor utilisation is cost-effective compared with the potential improved productivity for ED cases requiring CT imaging.

Keywords: workflow, quality, administration, CT, staffing

Procedia PDF Downloads 86

Authors: Rajeswari Raguraman, Sowmya Parameswaran, Krishnakumar Subramanian, Jagat Kanwar, Rupinder Kanwar

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Background: Tumor microenvironment has been implicated in several cancers to regulate cell growth, invasion and metastasis culminating in outcome of therapy. Tumor stroma consists of multiple cell types that are in constant cross-talk with the tumor cells to favour a pro-tumorigenic environment. Not much is known about the existence of tumor microenvironment in the pediatric intraocular malignancy, Retinoblastoma (RB). In the present study, we aim to understand the multiple stromal cellular subtypes and tumor stromal interactions expressed in RB tumors. Materials and Methods: Immunohistochemistry for stromal cell markers CD31, CD68, alpha-smooth muscle (α-SMA), vimentin and glial fibrillary acidic protein (GFAP) was performed on formalin fixed paraffin embedded tissues sections of RB (n=12). The differential expression of stromal target molecules; fibroblast activation protein (FAP), tenascin-C (TNC), osteopontin (SPP1), bone marrow stromal antigen 2 (BST2), stromal derived factor 2 and 4 (SDF2 and SDF4) in primary RB tumors (n=20) and normal retina (n=5) was studied by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blotting. The differential expression was correlated with the histopathological features of RB. The interaction between RB cell lines (Weri-Rb-1, NCC-RbC-51) and Bone marrow stromal cells (BMSC) was also studied using direct co-culture and indirect co-culture methods. The functional effect of the co-culture methods on the RB cells was evaluated by invasion and proliferation assays. Global gene expression was studied by using Affymetrix 3’ IVT microarray. Pathway prediction was performed using KEGG and the key molecules were validated using qRT-PCR. Results: The immunohistochemistry revealed the presence of several stromal cell types such as endothelial cells (CD31+;Vim+/-); macrophages (CD68+;Vim+/-); Fibroblasts (Vim+; CD31-;CD68- );myofibroblasts (α-SMA+/ Vim+) and invading retinal astrocytes/ differentiated retinal glia (GFAP+; Vim+). A characteristic distribution of these stromal cell types was observed in the tumor microenvironment, with endothelial cells predominantly seen in blood vessels and macrophages near actively proliferating tumor or necrotic areas. Retinal astrocytes and glia were predominant near the optic nerve regions in invasive tumors with sparse distribution in tumor foci. Fibroblasts were widely distributed with rare evidence of myofibroblasts in the tumor. Both gene and protein expression revealed statistically significant (P<0.05) up-regulation of FAP, TNC and BST2 in primary RB tumors compared to the normal retina. Co-culture of BMSC with RB cells promoted invasion and proliferation of RB cells in direct and indirect contact methods respectively. Direct co-culture of RB cell lines with BMSC resulted in gene expression changes in ECM-receptor interaction, focal adhesion, IL-8 and TGF-β signaling pathways associated with cancer. In contrast, various metabolic pathways such a glucose, fructose and amino acid metabolism were significantly altered under the indirect co-culture condition. Conclusion: The study suggests that the close interaction between RB cells and the stroma might be involved in RB tumor invasion and progression which is likely to be mediated by ECM-receptor interactions and secretory factors. Targeting the tumor stroma would be an attractive option for redesigning treatment strategies for RB.

Keywords: gene expression profiles, retinoblastoma, stromal cells, tumor microenvironment

Procedia PDF Downloads 355

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

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Introdution: Food allergies occurs, in the Western World, 2% of adults and up to 8% of children. The protection of allergic consumers is guaranted, in Eurrope, by Regulation (EU) No 1169/2011 of the European Parliament which governs the consumer's right to information and identifies 14 food allergens to be mandatory indicated on the label. Among these, mustard is a popular spice added to enhance the flavour and taste of foods. It is frequently present as an ingredient in spice blends, marinades, salad dressings, sausages, and other products. Hypersensitivity to mustard is a public health problem since the ingestion of even low amounts can trigger severe allergic reactions. In order to protect the allergic consumer, high performance methods are required for the detection of allergenic ingredients. Food safety laboratories rely on validated methods that detect hidden allergens in food to ensure the safety and health of allergic consumers. Here we present the test results for the validation and accreditation of a Real time PCR assay (RT-PCR: SPECIALfinder MC Mustard, Generon), for the detection of mustard traces in food. Materials and Methods. The method was tested on five classes of food matrices: bakery and pastry products (chocolate cookies), meats (ragù), ready-to-eat (mixed salad), dairy products (yogurt), grains, and milling products (rice and barley flour). Blank samples were spiked starting with the mustard samples (Sinapis Alba), lyophilized and stored at -18 °C, at a concentration of 1000 ppm. Serial dilutions were then prepared to a final concentration of 0.5 ppm, using the DNA extracted by ION Force FAST (Generon) from the blank samples. The Real Time PCR reaction was performed by RT-PCR SPECIALfinder MC Mustard (Generon), using CFX96 System (BioRad). Results. Real Time PCR showed a limit of detection (LOD) of 0.5 ppm in grains and milling products, ready-to-eat, meats, bakery, pastry products, and dairy products (range Ct 25-34). To determine the exclusivity parameter of the method, the ragù matrix was contaminated with Prunus dulcis (almonds), peanut (Arachis hypogaea), Glycine max (soy), Apium graveolens (celery), Allium cepa (onion), Pisum sativum (peas), Daucus carota (carrots), and Theobroma cacao (cocoa) and no cross-reactions were observed. Discussion. In terms of sensitivity, the Real Time PCR confirmed, even in complex matrix, a LOD of 0.5 ppm in five classes of food matrices tested; these values are compatible with the current regulatory situation that does not consider, at international level, to establish a quantitative criterion for the allergen considered in this study. The Real Time PCR SPECIALfinder kit for the detection of mustard proved to be easy to use and particularly appreciated for the rapid response times considering that the amplification and detection phase has a duration of less than 50 minutes. Method accuracy was rated satisfactory for sensitivity (100%) and specificity (100%) and was fully validated and accreditated. It was found adequate for the needs of the laboratory as it met the purpose for which it was applied. This study was funded in part within a project of the Italian Ministry of Health (IZS PLV 02/19 RC).

Keywords: allergens, food, mustard, real time PCR

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Authors: Abouchouaib Belahmira, Joerg W. Schneider, Hafid Saber, Sara Akboub

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The lithofacies analyzed herein were reported from the interbedded fluvial and lacustrine deposits of the Oued Issene and El Menizla formations. These formations are part of the sedimentary fill of the Carboniferous (Stephanian) submontaneous Souss basin. The latter is situated in the western High Atlas Mountains, south-central Morocco, about 50km east of Agadir. The Souss basin started as a single basin but was separated into sub-basins called Ida Ou Zal and Ida Ou Ziki by sinistral displacement along the west branch of the Tizi N'Test Fault during the end of the Mauritanid phase of the Variscan orogeny in Morocco, after the early Stephanian (Kasimovian) and before the late middle Permian (Capitanian). The studied succession is a monotonous finning-upward sequence of 1800 m thick. It consists of fine-grained sandstone, finely bedded siltstone and thinly laminated claystone, and black shale. Herein we provide a detailed characterization of lithofacies of the upper El Menizla and Oued Issène formations, with a focus on the prevailing overbank to flood plain fine-grained lithofacies. The studied facies are capping the Stephanian alluvial fan basal clast-supported conglomerates that are intercalated bedded coarse-grained sandstones of Ikhourba Formation in the Ou Zal subbasin and Tajgaline Formation in the Ida Ou Ziki subbasin, respectively. Within the fluvial elements, only two main facies have been observed. It comprises channel-fill and channel-bar deposits, mostly occur as lenticular –shape sand bodies or sheet-like sand greenish to gray fine-to medium (Fm), massive internally structureless, or very locally exhibits a medium to large scale trough-cross bedding medium to coarse sandstone (St), observable in relatively thicker bed. These facies are laterally extensive, with a thickness varying from a few to several meters. Finer-grained sediments such as mud can be present as drapes over bedforms. Whilst the fluvial association FA1, the overbank elements are represented by a relatively wide range of 5 facies. This exhibit mostly a cm scale horizontally bedded greenish fine- to medium sand and silt, and mm scale fossiliferous thinly laminated dark gray- black Corganic-rich clays to siltstone associated with black shale. Thus, FA2 includes flood plain fines (Fh, R) associated with the paleosols and back swamp coaly clay facies (C). The floodplain lake element comprises only laminated organic-rich dark gray facies of claystone, black shale, and graded siltstone. Bedsets are dm to several meters thick (typically < 1 m thick). They are intercalated between several m-thick fluvial sandstone, extend over a few meters, and are poorly bioturbated. The lacustrine facies described in this study have been divided into two sub-facies (Fl, B) based on field observations that indicate differing environmental conditions of formation. Thus, the thorough analysis of the lithofacies of the Souss basin units allows us to reconstruct the original environment that was interpreted as a typical fluvial-dominated braided to anastomosing wide distributary channel system and surrounding deep to shallow freshwater floodplain lakes and back swamps.

Keywords: Souss, carboniferous, facies, depositional setting

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Authors: Marcela Parra-Vargas, Ana Sandoval-Rodriguez, Roberto Rodriguez-Echevarria, Jose Dominguez-Rosales, Juan Armendariz-Borunda

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Non-alcoholic fatty liver disease (NAFLD) is characterized by an excess of hepatic lipids, and it is to author’s best knowledge, the most prevalent chronic liver disorder. Anthocyanin-rich food consumption is linked to health benefits in metabolic disorders associated with obesity and NAFLD, although the precise functional role of anthocyanidin delphinidin (Dp) has yet to be established. The aim of this study was to investigate the effect of the Dp in NAFLD metabolic alterations by evaluating prevention or amelioration of hepatic lipid accumulation, as well as molecular mechanisms in two experimental obesity-related models of NALFD. In vitro: HepG2 cells were incubated with sodium palmitate (PA, 1 mM) to induce lipotoxic damage, and concomitantly treated with Dp (180 uM) for 24 h. Subsequently, total lipid accumulation was measured by colorimetric staining with Oil Red O, and total intrahepatic triglycerides were determined by an enzymatic assay. To assess molecular mechanisms, cells were pre-treated with PA for 24 h and then exposed to Dp for 1 h. In vivo: four-week-old male C57BL/6Nhsd mice were allocated in two main groups. Mice were fed with standard diet (control) or high-fat and high-carbohydrate diet (45% fat, HFD) for 16 wk to induce NAFLD. Then HFD was divided into subgroups: one treated orally with Dp (15 mg/kg bw, HFD-Dp) every day for 4 wk, while HFD group treated with vehicle (DMSO). Weight and fasting glucose were recorded weekly, while dietary ingestion was measured daily. Insulin tolerance test was performed at the end of treatment. Liver histology was evaluated with H&E and Masson’s trichrome stain. RT-PCR was used to evaluate gene expression and Western Blot to determine levels of protein in both experimental models. Parametric data were analyzed with one-way ANOVA and Tukey’s post-hoc test. Kruskal-Wallis and Mann-Whitney U test for non-parametric data, and P < 0.5 were considered significant. Dp prevented hepatic lipid accumulation by PA in HepG2 hepatocytes. Furthermore, Dp down-regulated gene expression of SREBP1c, FAS, and CPT1a without modifying AMPK phosphorylation levels. In vivo, Dp oral administration did not ameliorate lipid metabolic alterations raised by HFD. Adiposity, dietary ingestion, fasting glucose, and insulin sensitivity after Dp treatment remained similar to HFD group. Histological analysis showed hepatic damage in HFD groups and no differences between HFD and HFD-Dp groups were found. Hepatic gene expression of ACC and FAS were not altered by HFD. SREBP1c was similar in both HFD and HFD-Dp groups. No significant changes were observed in SREBP1c, ACC, and FAS adipose tissue gene expression by HFD or Dp treatment. Additionally, immunoblotting analysis revealed no changes in pathway SIRT1-LKB-AMPK and PPAR alpha by both HFD groups compared to control. In conclusion, the antioxidant Dp may provoke beneficial effects in the prevention of hepatic lipid accumulation. Nevertheless, the oral dose administrated in mice that simulated the total intake of anthocyanins consumed daily by humans has no effect as a treatment on hepatic lipid metabolic alterations and histological abnormalities associated with exposure to chronic HFD. A healthy lifestyle with regular intake of antioxidants such as anthocyanins may prevent metabolic alterations in NAFLD.

Keywords: anthocyanins, antioxidants, delphinidin, non-alcoholic fatty liver disease, obesity

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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

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Authors: Giuliana Murfet, Heidi Behrens

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Chronic disease is Australia’s biggest health concern and obesity the leading risk factor for many. Obesity and chronic disease have a higher representation in rural Tasmania, where levels of socio-disadvantage are also higher. People living outside major cities have less access to health services and poorer health outcomes. To help primary healthcare professionals manage obesity, the Australian NHMRC evidence-based clinical practice guidelines for management of overweight and obesity in adults were developed. They include recommendations for practice and models for obesity management. To our knowledge there has been no research conducted that investigates translation of these guidelines into practice in rural-regional areas; where implementation can be complicated by limited financial and staffing resources. Also, the systematic review that informed the guidelines revealed a lack of evidence for chronic disease models of obesity care. The aim was to establish and evaluate a multidisciplinary model for obesity management in a group of adult people with type 2 diabetes in a dispersed rural population in Australia. Extensive stakeholder engagement was undertaken to both garner support for an obesity clinic and develop a sustainable model of care. A comprehensive nurse practitioner-led outpatient model for obesity care was designed. Multidisciplinary obesity clinics for adults with type 2 diabetes including a dietitian, psychologist, physiotherapist and nurse practitioner were set up in the north-west of Tasmania at two geographically-rural towns. Implementation was underpinned by the NHMRC guidelines and recommendations focused on: assessment approaches; promotion of health benefits of weight loss; identification of relevant programs for individualising care; medication and bariatric surgery options for obesity management; and, the importance of long-term weight management. A clinical pathway for adult weight management is delivered by the multidisciplinary team with recognition of the impact of and adjustments needed for other comorbidities. The model allowed for intensification of intervention such as bariatric surgery according to recommendations, patient desires and suitability. A randomised controlled trial is ongoing, with the aim to evaluate standard care (diabetes-focused management) compared with an obesity-related approach with additional dietetic, physiotherapy, psychology and lifestyle advice. Key barriers and enablers to guideline implementation were identified that fall under the following themes: 1) health care delivery changes and the project framework development; 2) capacity and team-building; 3) stakeholder engagement; and, 4) the research project and partnerships. Engagement of not only local hospital but also state-wide health executives and surgical services committee were paramount to the success of the project. Staff training and collective development of the framework allowed for shared understanding. Staff capacity was increased with most taking on other activities (e.g., surgery coordination). Barriers were often related to differences of opinions in focus of the project; a desire to remain evidenced based (e.g., exercise prescription) without adjusting the model to allow for consideration of comorbidities. While barriers did exist and challenges overcome; the development of critical partnerships did enable the capacity for a potential model of obesity care for rural regional areas. Importantly, the findings contribute to the evidence base for models of diabetes and obesity care that coordinate limited resources.

Keywords: diabetes, interdisciplinary, model of care, obesity, rural regional

Procedia PDF Downloads 200

Authors: Kuladip Jana

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Benzo(a)pyrene [B(a)P] is an environmental toxicant present mostly in cigarette smoke and car exhaust, is an aryl hydrocarbon receptor (AhR) ligand that exerts its toxic effects on both male and female reproductive systems. In this study, the effect of B(a)P at different doses (0.1, 0.25, 0.5, 1 and 5 mg /kg body weight) was studied on male reproductive system of rat. A significant decrease in cauda epididymal sperm count and motility along with the presence of sperm head abnormalities and altered epididymal and testicular histology were documented following B(a)P treatment. B(a)P treatment resulted apoptotic sperm cells as observed by TUNEL and Annexin V-PI assay with increased ROS, altered sperm mitochondrial membrane potential (ΔΨm) with a simultaneous decrease in the activity of antioxidant enzymes and GSH status. TUNEL positive apoptotic cells also observed in testis as well as isolated germ and Leydig cells following B(a)P exposure. Western Blot analysis revealed the activation of p38MAPK, cytosolic translocation of cytochrome-c, up-regulation of Bax and inducible nitric oxide synthase (iNOS) with cleavage of PARP and down-regulation of BCl2 in testis upon B(a)P treatment. The protein and mRNA levels of testicular key steroidogenesis regulatory proteins like StAR, cytochrome P450 IIA1 (CYPIIA1), 3β HSD, 17β HSD showed a significant decrease in a dose dependent manner while an increase in the expression of cytochrome P450 1A1 (CYP1A1), Aryl hydrocarbon Receptor (AhR), active caspase- 9 and caspase- 3 following B(a)P exposure. We conclude that exposure of benzo(a)pyrene caused testicular gamatogenic and steroidogenic disorders by induction of oxidative stress, inhibition of StAR and other steroidogenic enzymes along with activation of p38MAPK and initiated caspase-3 mediated germ and Leydig cell apoptosis.The possible protective role of naturally occurring phytochemicals against B(a)P induced testicular toxicity needs immediate consideration. Curcumin and resveratrol separately were found to protect against B(a)P induced germ cell apoptosis, and their combinatorial effect was more significant. Our present study in isolated testicular germ cell population from adult male Wistar rats, highlighted their synergistic protective effect against B(a)P induced germ cell apoptosis. Curcumin-resveratrol co-treatment decreased the expression of pro-apoptotic proteins like cleaved caspase 3,8,9, cleaved PARP, Apaf1, FasL, tBid. Curcumin-resveratrol co-treatment decreased Bax/Bcl2 ratio, mitochondria to cytosolic translocation of cytochrome c and activated the survival protein Akt. Curcumin-resveratrol decreased the expression of p53 dependent apoptotic genes like Fas, FasL, Bax, Bcl2, Apaf1.Curcumin-resveratrol co-treatment thus prevented B(a)P induced germ cell apoptosis. B(a)P induced testicular ROS generation and oxidative stress were significantly ameliorated with curcumin and resveratrol. Curcumin-resveratrol co-treatment prevented B(a)P induced nuclear translocation of AhR and CYP1A1 production. The combinatorial treatment significantly inhibited B(a)P induced ERK 1/2, p38 MAPK and JNK 1/2 activation. B(a)P treatment increased the expression of p53 and its phosphorylation (p53 ser 15). Curcumin-resveratrol co-treatment significantly decreased p53 level and its phosphorylation (p53 ser 15). The study concludes that curcumin-resveratrol synergistically modulated MAPKs and p53, prevented oxidative stress, regulated the expression of pro and anti-apoptotic proteins as well as the proteins involved in B(a)P metabolism thus protected germ cells from B(a)P induced apoptosis.

Keywords: benzo(a)pyrene, germ cell, apoptosis, oxidative stress, resveratrol, curcumin

Procedia PDF Downloads 227

Authors: Daniel Stabler, Anne-Laure Mention, Henri Hakala, Ahmad Alaassar

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In Europe, 2.2 billion tons of waste annually generate severe environmental damage and economic burdens, and negatively impact human health. A stark illustration of the problem is found within the consumer electronics industry, which reflects one of the most complex global waste streams. Of the 5.3 billion globally discarded mobile phones in 2022, only 17% were properly recycled. To address these pressing issues, Europe has made significant strides in developing waste management strategies, Circular Economy initiatives, and Right to Repair policies. These endeavors aim to make product repair and maintenance more accessible, extend product lifespans, reduce waste, and promote sustainable resource use. European countries have introduced Right to Repair policies, often in conjunction with extended producer responsibility legislation, repair subsidies, and consumer repair indices, to varying degrees of regulatory rigor. Changing societal trends emphasizing sustainability and environmental responsibility have driven consumer demand for more sustainable and repairable products, benefiting repair-focused consumer electronics businesses. In academic research, much of the literature in Management studies has examined the European Circular Economy and the Right to Repair from firm-level perspectives. These studies frequently employ a business-model lens, emphasizing innovation and strategy frameworks. However, this study takes an institutional perspective, aiming to understand the adoption of Circular Economy and repair-focused business models within the European consumer electronics market. The concepts of the Circular Economy and the Right to Repair align with institutionalism as they reflect evolving societal norms favoring sustainability and consumer empowerment. Regulatory institutions play a pivotal role in shaping and enforcing these concepts through legislation, influencing the behavior of businesses and individuals. Compliance and enforcement mechanisms are essential for their success, compelling actors to adopt sustainable practices and consider product life extension. Over time, these mechanisms create a path for more sustainable choices, underscoring the influence of institutions and societal values on behavior and decision-making. Institutionalism, particularly 'neo-institutionalism,' provides valuable insights into the factors driving the adoption of Circular and repair-focused business models. Neo-institutional pressures can manifest through coercive regulatory initiatives or normative standards shaped by socio-cultural trends. The Right to Repair movement has emerged as a prominent and influential idea within academic discourse and sustainable development initiatives. Therefore, understanding how macro-level societal shifts toward the Circular Economy and the Right to Repair trigger firm-level responses is imperative. This study aims to answer a crucial question about the impact of European Right to Repair initiatives had on the financial and environmental performance of European consumer electronics companies at the firm level. A quantitative and statistical research design will be employed. The study will encompass an extensive sample of consumer electronics firms in Northern and Western Europe, analyzing their financial and environmental performance in relation to the implementation of Right to Repair mechanisms. The study's findings are expected to provide valuable insights into the broader implications of the Right to Repair and Circular Economy initiatives on the European consumer electronics industry.

Keywords: circular economy, right to repair, institutionalism, environmental management, european union

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Authors: Teesta Dey

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Integrated Transport development with proper traffic management leads to sustainable growth of any urban sphere. Appropriate mass transport planning is essential for the populous cities in third world countries like India. The exponential growth of motor vehicles with unplanned road network is now the common feature of major urban centres in India. Kolkata, the third largest mega city in India, is not an exception of it. The imbalance between demand and supply of unplanned transport services in this city is manifested in the high economic and environmental costs borne by the associated society. With the passage of time, the growth and extent of passenger demand for rapid urban transport has outstripped proper infrastructural planning and causes severe transport problems in the overall urban realm. Hence Kolkata stands out in the world as one of the most crisis-ridden metropolises. The urban transport crisis of this city involves severe traffic congestion, the disparity in mass transport services on changing peripheral land uses, route overlapping, lowering of travel speed and faulty implementation of governmental plans as mostly induced by rapid growth of private vehicles on limited road space with huge carbon footprint. Therefore the paper will critically analyze the extant road network pattern for improving regional connectivity and accessibility, assess the degree of congestion, identify the deviation from demand and supply balance and finally evaluate the emerging alternate transport options as promoted by the government. For this purpose, linear, nodal and spatial transport network have been assessed based on certain selected indices viz. Road Degree, Traffic Volume, Shimbel Index, Direct Bus Connectivity, Average Travel and Waiting Tine Indices, Route Variety, Service Frequency, Bus Intensity, Concentration Analysis, Delay Rate, Quality of Traffic Transmission, Lane Length Duration Index and Modal Mix. Total 20 Traffic Intersection Points (TIPs) have been selected for the measurement of nodal accessibility. Critical Congestion Zones (CCZs) are delineated based on one km buffer zones of each TIP for congestion pattern analysis. A total of 480 bus routes are assessed for identifying the deficiency in network planning. Apart from bus services, the combined effects of other mass and para transit modes, containing metro rail, auto, cab and ferry services, are also analyzed. Based on systematic random sampling method, a total of 1500 daily urban passengers’ perceptions were studied for checking the ground realities. The outcome of this research identifies the spatial disparity among the 15 boroughs of the city with severe route overlapping and congestion problem. North and Central Kolkata-based mass transport services exceed the transport strength of south and peripheral Kolkata. Faulty infrastructural condition, service inadequacy, economic loss and workers’ inefficiency are the most dominant reasons behind the defective mass transport network plan. Hence there is an urgent need to revive the extant road based mass transport system of this city by implementing a holistic management approach by upgrading traffic infrastructure, designing new roads, better cooperation among different mass transport agencies, better coordination of transport and changing land use policies, large increase in funding and finally general passengers’ awareness.

Keywords: carbon footprint, critical congestion zones, direct bus connectivity, integrated transport development

Procedia PDF Downloads 249

Authors: Kuladip Jana, Bhaswati Banerjee, Parimal C. Sen

Abstract:

Benzo(a)pyrene [B(a)P] is an environmental toxicant present mostly in cigarette smoke and car exhaust, is an aryl hydrocarbon receptor (AhR) ligand that exerts its toxic effects on both male and female reproductive systems along with carcinogenesis in skin, prostate, ovary, lung and mammary glands. Our study was focused on elucidating the molecular mechanism of B(a)P induced male reproductive toxicity and its prevention with phytochemical like resveratrol. In this study, the effect of B(a)P at different doses (0.1, 0.25, 0.5, 1 and 5 mg /kg body weight) was studied on male reproductive system of Wistar rat. A significant decrease in cauda epididymal sperm count and motility along with the presence of sperm head abnormalities and altered epididymal and testicular histology were documented following B(a)P treatment. B(a)P treatment resulted apoptotic sperm cells as observed by TUNEL and Annexin V-PI assay with increased Reactive Oxygen Species (ROS), altered sperm mitochondrial membrane potential (ΔΨm) with a simultaneous decrease in the activity of antioxidant enzymes and GSH status. TUNEL positive apoptotic cells also observed in testis as well as isolated germ and Leydig cells following B(a)P exposure. Western Blot analysis revealed the activation of p38 mitogen activated protein kinase (p38MAPK), cytosolic translocation of cytochrome-c, upregulation of Bax and inducible nitric oxide synthase (iNOS) with cleavage of poly ADP ribose polymerase (PARP) and down regulation of BCl2 in testis upon B(a)P treatment. The protein and mRNA levels of testicular key steroidogenesis regulatory proteins like steroidogenic acute regulatory protein (StAR), cytochrome P450 IIA1 (CYPIIA1), 3β hydroxy steroid dehydrogenase (3β HSD), 17β hydroxy steroid dehydrogenase (17β HSD) showed a significant decrease in a dose dependent manner while an increase in the expression of cytochrome P450 1A1 (CYP1A1), Aryl hydrocarbon Receptor (AhR), active caspase- 9 and caspase- 3 following B(a)P exposure. We conclude that exposure of benzo(a)pyrene caused testicular gamatogenic and steroidogenic disorders by induction of oxidative stress, inhibition of StAR and other steroidogenic enzymes along with activation of p38MAPK and initiated caspase-3 mediated germ and Leydig cell apoptosis. Next we investigated the role of resveratrol on B(a)P induced male reproductive toxicity. Our study highlighted that resveratrol co-treatment with B(a)P maintained testicular redox potential, increased serum testosterone level and prevented steroidogenic dysfunction with enhanced expression of major testicular steroidogenic proteins (CYPIIA1, StAR, 3β HSD,17β HSD) relative to treatment with B(a)P only. Resveratrol suppressed B(a)P-induced testicular activation of p38 MAPK, ATF2, iNOS and ROS production; cytosolic translocation of Cytochome c and Caspase 3 activation thereby prevented oxidative stress of testis and inhibited apoptosis. Resveratrol co-treatment also decreased B(a)P-induced AhR protein level, its nuclear translocation and subsequent CYP1A1 promoter activation, thereby decreased protein and mRNA levels of testicular cytochrome P4501A1 (CYP1A1) and prevented BPDE-DNA adduct formation. Our findings cumulatively suggest that resveratrol prevents activation of B(a)P by modulating the transcriptional regulation of CYP1A1 and acting as an antioxidant thus prevents B(a)P-induced oxidative stress and testicular apoptosis.

Keywords: benzo(a)pyrene, resveratrol, testis, apoptosis, cytochrome P450 1A1 (CYP1A1), aryl hydrocarbon receptor (AhR), p38 MAPK/ATF2/iNOS

Procedia PDF Downloads 197

Authors: Ipsita Pujari, Abitha Thomas, Vidhu S. Babu, K. Satyamoorthy

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Orchids are esteemed as celebrities in cut flower industry globally, due to their long-lasting fragrance and freshness. Apart from splendor, the unique metabolites endowed with pharmaceutical potency have made them one of the most hunted in plant kingdom. This had led to their trafficking, resulting in habitat loss, subsequently making them occupiers of IUCN red list as RET species. Many of the orchids especially wild varieties still remain undiscovered. In view to protect and conserve the wild germplasm, researchers have been inventing novel micropropagation protocols; thereby conserving Orchids. India is overflowing with exclusive wild cultivars of Orchids, whose pharmaceutical properties remain untapped and are not marketed owing to relatively small flowers. However, their germplasm is quite pertinent to be preserved for making unusual hybrids. Dendrobium genus is the second largest among Orchids exists in India and has highest demand attributable to enduring cut flowers and significant therapeutic uses in traditional medicinal system. Though the genus is quite endemic in Western Ghat regions of the country, many species are still anonymous with their unknown curative properties. A standard breeding cycle in Orchids usually takes five to seven years (Dendrobium hybrids taking a long juvenile phase of two to five years reaching maturity and flowering stage) and this extensive life cycle has always hindered the development of Dendrobium breeding. Dendrobium is reported with essential therapeutic plant bio-chemicals and ‘Moscatilin’ is one, found exclusive to this famous Dendrobium genus. Moscatilin is reported to have anti-mutagenic and anti-cancer properties, whose positive action has very recently been demonstrated against a range of cancers. Our preliminary study here established a simple and economic small-scale propagation protocol of Dendrobium ovatum describing in vitro production of Moscatilin. Subsequently for enhancing the content of Moscatilin, an efficient experimental related to the organization of transgenic (hairy) D. ovatum root cultures through infection of Agrobacterium rhizogenes 2364 strain on MS basal medium is being reported in the present study. Hairy roots generated on almost half of the explants used (spherules, in vitro plantlets and calli) maintained through suspension cultures, after 8 weeks of co-cultivation with Agrobacterium rhizogenes. GFP assay performed with isolated hairy roots has confirmed the integrative transformation which was further positively confirmed by PCR using rolB gene specific primers. Reverse phase-high performance liquid chromatography and mass spectrometry techniques were used for quantification and accurate identification of Moscatilin respectively from transgenic systems. A noticeable ~3 fold increase in contents were observed in transformed D. ovatum root cultures as compared to the simple in vitro culture, callus culture and callus regeneration plantlets. Role of elicitors e.g., Methyl jasmonate, Salicylic acid, Yeast extract and Chitosan were tested for elevating the Moscatilin content to obtain a comprehensive optimized protocol facilitating the in vitro production of valuable Moscatilin with larger yield. This study would provide evidence towards the in vitro assembly of Moscatilin within a short time-period through not a so-expensive technology for the first time. It also serves as an appropriate basis for bioreactor scale-up resulting in commercial bioproduction of Moscatilin.

Keywords: bioproduction, Dendrobium ovatum, hairy root culture, moscatilin

Procedia PDF Downloads 204

Authors: Yogesh Dalvi, Ruby Varghese, Nibu Varghese, C. K. Krishnan Nair

Abstract:

Introduction: The Genus Phellinus, locally known as Phansomba is a well-known traditional folk medicine. Especially, in Western Ghats of India, many tribes use several species of Phellinus for various ailments related to teeth, throat, tongue, stomach and even wound healing. It is one of the few mushrooms which play a pivotal role in Ayurvedic Dravyaguna. Aim: The present study focuses on to investigate phytochemical analysis, antioxidant, and antitumor (in vitro and in vivo) potential of Phellinus robinae from South India, Kerala Material and Methods: The present study explores the following: 1. Phellinus samples were collected from Ranni, Pathanamthitta district of Kerala state, India from Artocarpus heterophyllus Lam. and species were identified using rDNA region. 2. The fruiting body was shadow dried, powdered and extracted with 50% alcohol using water bath at 60°C which was further condensed by rotary evaporator and lyophilized at minus 40°C temperature. 3. Secondary metabolites were analyzed by using various phytochemical screening assay (Hager’s Test, Wagner’s Test, Sodium hydroxide Test, Lead acetate Test, Ferric chloride Test, Folin-ciocalteu Test, Foaming Test, Benedict’s test, Fehling’s Test and Lowry’s Test). 4. Antioxidant and free radical scavenging activity were analyzed by DPPH, FRAP and Iron chelating assay. 5. The antitumor potential of Water alcohol extract of Phellinus (PAWE) is evaluated through In vitro condition by Trypan blue dye exclusion method in DLA cell line and In vivo by murine model. Result and Discussion: Preliminary phytochemical screening by various biochemical tests revealed presence of a variety of active secondary molecules like alkaloids, flavanoids, saponins, carbohydrate, protein and phenol. In DPPH and FRAP assay PAWE showed significantly higher antioxidant activity as compared to standard Ascorbic acid. While, in Iron chelating assay, PAWE exhibits similar antioxidant activity that of Butylated Hydroxytoluene (BHT) as standard. Further, in the in vitro study, PAWE showed significant inhibition on DLA cell proliferation in dose dependent manner and showed no toxicity on mice splenocytes, when compared to standard chemotherapy drug doxorubicin. In vivo study, oral administration of PAWE showed dose dependent tumor regression in mice and also raised the immunogenicity by restoring levels of antioxidant enzymes in liver and kidney tissue. In both in vitro and in vivo gene expression studies PAWE up-regulates pro-apoptotic genes (Bax, Caspases 3, 8 and 9) and down- regulates anti-apoptotic genes (Bcl2). PAWE also down regulates inflammatory gene (Cox-2) and angiogenic gene (VEGF). Conclusion: Preliminary phytochemical screening revealed that PAWE contains various secondary metabolites which contribute to its antioxidant and free radical scavenging property as evaluated by DPPH, FRAP and Iron chelating assay. PAWE exhibits anti-proliferative activity by the induction of apoptosis through a signaling cascade of death receptor-mediated extrinsic (Caspase8 and Tnf-α), as well as mitochondria-mediated intrinsic (caspase9) and caspase pathways (Caspase3, 8 and 9) and also by regressing angiogenic factor (VEGF) without any inflammation or adverse side effects. Hence, PAWE serve as a potential antioxidant and antitumor agent.

Keywords: antioxidant, antitumor, Dalton lymphoma ascites (DLA), fungi, Phellinus robinae

Procedia PDF Downloads 276

Authors: Joyjit Dey, Souvik Sen

Abstract:

Middle Permian Barakar formation is the major economic coal bearing unit of vast east-west trending Damodar Valley basin of Gondwana coalfield. Primary sedimentary structures were studied from the core holes, which represent majorly four facies groups: sandstone dominated facies, sandstone-shale heterolith facies, shale facies and coal facies. Total eight major coal seams have been identified with the bottom most seam being the thickest. Laterally, continuous coal seams were deposited in the calm and quiet environment of extensive floodplain swamps. Channel sinuosity and lateral channel migration/avulsion results in lateral facies heterogeneity and coal splitting. Geophysical well logs (Gamma-Resistivity-Density logs) have been used to establish the vertical and lateral correlation of various litho units field-wide, which reveals the predominance of repetitive fining upwards cycles. Well log data being a permanent record, offers a strong foundation for generating log based property evaluation and helps in characterization of depositional units in terms of lateral and vertical heterogeneity. Low gamma, high resistivity, low density is the typical coal seam signatures in geophysical logs. Here, we have used a density cutoff of 1.6 g/cc as a primary discriminator of coal and the same has been employed to compute various coal assay parameters, which are ash, fixed carbon, moisture, volatile content, cleat porosity, vitrinite reflectance (VRo%), which were calibrated with the laboratory based measurements. The study shows ash content and VRo% increase from west to east (towards basin margin), while fixed carbon, moisture and volatile content increase towards west, depicting increased coal quality westwards. Seam wise cleat porosity decreases from east to west, this would be an effect of overburden, as overburden pressure increases westward with the deepening of basin causing more sediment packet deposited on the western side of the study area. Coal is a porous, viscoelastic material in which velocity and strain both change nonlinearly with stress, especially for stress applied perpendicular to the bedding plane. Usually, the coal seam has a high velocity contrast relative to its neighboring layers. Despite extensive discussion of the maceral and chemical properties of coal, its elastic characteristics have received comparatively little attention. The measurement of the elastic constants of coal presents many difficulties: sample-to-sample inhomogeneity and fragility and velocity dependence on stress, orientation, humidity, and chemical content. In this study, a conclusive empirical equation VS= 0.80VP-0.86 has been used to model shear velocity from compression velocity. Also the same has been used to compute various geomechanical moduli. Geomech analyses yield a Poisson ratio of 0.348 against coals. Average bulk modulus value is 3.97 GPA, while average shear modulus and Young’s modulus values are coming out as 1.34 and 3.59 GPA respectively. These middle Permian Barakar coals show an average 23.84 MPA uniaxial compressive strength (UCS) with 4.97 MPA cohesive strength and 0.46 as friction coefficient. The output values of log based proximate parameters and geomechanical moduli suggest a medium volatile Bituminous grade for the studied coal seams, which is found in the laboratory based core study as well.

Keywords: core analysis, coal characterization, geophysical log, geo-mechanical moduli

Procedia PDF Downloads 191

Authors: Aastha Arora, Vikas Bhuria, Saurabh Singh, Uma Pathak, Shweta Mathur, Puja P. Hazari, Rajat Sandhir, Ravi Soni, Anant N. Bhatt, Bilikere S. Dwarakanath

Abstract:

Radiotherapy is an effective curative and palliative option for patients with thoracic malignancies. However, lung injury, comprising of pneumonitis and fibrosis, remains a significant clin¬ical complication of thoracic radiation, thus making it a dose-limiting factor. Also, injury to the lung is often reported as part of multi-organ failure in victims of accidental radiation exposures. Radiation induced inflammatory response in the lung, characterized by leukocyte infiltration and vascular changes, is an important contributing factor for the injury. Therefore, countermeasure agents to attenuate radiation induced inflammatory response are considered as an important approach to prevent chronic lung damage. Although Amifostine, the widely used, FDA approved radio-protector, has been found to reduce the radiation induced pneumonitis during radiation therapy of non-small cell lung carcinoma, its application during mass and field exposure is limited due to associated toxicity and ineffectiveness with the oral administration. The amifostine analogue (DRDE-30) overcomes this limitation as it is orally effective in reducing the mortality of whole body irradiated mice. The current study was undertaken to investigate the potential of DRDE-30 to ameliorate radiation induced lung damage. DRDE-30 was administered intra-peritoneally, 30 minutes prior to 13.5 Gy thoracic (60Co-gamma) radiation in C57BL/6 mice. Broncheo- alveolar lavage fluid (BALF) and lung tissues were harvested at 12 and 24 weeks post irradiation for studying inflammatory and fibrotic markers. Lactate dehydrogenase (LDH) leakage, leukocyte count and protein content in BALF were used as parameters to evaluate lung vascular permeability. Inflammatory cell signaling (p38 phosphorylation) and anti-oxidant status (MnSOD and Catalase level) was assessed by Western blot, while X-ray CT scan, H & E staining and trichrome staining were done to study the lung architecture and collagen deposition. Irradiation of the lung increased the total protein content, LDH leakage and total leukocyte count in the BALF, reflecting endothelial barrier dysfunction. These disruptive effects were significantly abolished by DRDE-30, which appear to be linked to the DRDE-30 mediated abrogation of activation of the redox-sensitive pro- inflammatory signaling cascade, the MAPK pathway. Concurrent administration of DRDE-30 with radiation inhibited radiation-induced oxidative stress by strengthening the anti-oxidant defense system and abrogated p38 mitogen-activated protein kinase activation, which was associated with reduced vascular leak and macrophage recruitment to the lungs. Histopathological examination (by H & E staining) of the lung showed radiation-induced inflammation of the lungs, characterized by cellular infiltration, interstitial oedema, alveolar wall thickening, perivascular fibrosis and obstruction of alveolar spaces, which were all reduced by pre-administration of DRDE-30. Structural analysis with X-ray CT indicated lung architecture (linked to the degree of opacity) comparable to un-irradiated mice that correlated well with the lung morphology and reduced collagen deposition. Reduction in the radiation-induced inflammation and fibrosis brought about by DRDE-30 resulted in a profound increase in animal survival (72 % in the combination vs 24% with radiation) observed at the end of 24 weeks following irradiation. These findings establish the potential of the Amifostine analogue, DRDE-30, in reducing radiation induced pulmonary injury by attenuating the inflammatory and fibrotic responses.

Keywords: amifostine, fibrosis, inflammation, lung injury radiation

Procedia PDF Downloads 484

Authors: Xu Fei (Philip) WU

Abstract:

As waste recycling concept been accepted more and more in modern societies, the organic portion of the municipal waste become a sires issue in today’s life. Depend on location and season, the organic waste can bee anywhere between 40-65% of total municipal solid waste. Also composting and anaerobic digestion technologies been applied in this field for years, however both process have difficulties been selected by economical and environmental factors. Beside environmental pollution and risk of virus spread, the compost is not a product been welcomed by people even the waste management has to give up them at no cost. The anaerobic digester has to have 70% of water and keep at 35 degree C or above; base on above conditions, the retention time only can be up to two weeks and remain solid has to be dewater and composting again. The enhancive waste water treatment has to be added after. Because these reasons, the voice of suggesting cancelling recycling program and turning all waste to mass burn incinerations have been raised-A process has already been proved has least energy efficiency and most air pollution problem associated process. A newly developed WXF Bio-energy process employs recently developed and patented pre-designed separation, multi-layer and multi-cavity successive bioreactor landfill technology. It features an improved leachate recycling technology, technologies to maximize the biogas generation rate and a reduced overall turnaround period on the land. A single properly designed and operated site can be used indefinitely. In this process, all collected biogas will be processed to eliminate H2S and other hazardous gases. The methane, carbon dioxide and hydrogen will be utilized in a proprietary process to manufacture methanol which can be sold to mitigate operating costs of the landfill. This integration of new processes offers a more advanced alternative to current sanitary landfill, incineration and compost technology. Xu Fei (Philip) Wu Xu Fei Wu is founder and Chief Scientist of W&Y Environmental International Inc. (W & Y), a Canadian environmental and sustainable energy technology company with patented landfill processes and proprietary waste to energy technologies. He has worked in environmental and sustainable energy fields over the last 25 years. Before W&Y, he worked for Conestoga-Rovers & Associates Limited, Microbe Environmental Science and Technology Inc. of Canada and The Ministry of Nuclear Industry and Ministry of Space Flight Industry of China. Xu Fei Wu holds a Master of Engineering Science degree from The University of Western Ontario. I wish present this paper as an oral presentation only Selected Conference Presentations: • “Removal of Phenolic Compounds with Algae” Presented at 25th Canadian Symposium on Water Pollution Research (CAWPRC Conference), Burlington, Ontario Canada. February, 1990 • “Removal of Phenolic Compounds with Algae” Presented at Annual Conference of Pollution Control Association of Ontario, London, Ontario, Canada. April, 1990 • “Removal of Organochlorine Compounds in a Flocculated Algae Photo-Bioreactor” Presented at International Symposium on Low Cost and Energy Saving Wastewater Treatment Technologies (IAWPRC Conference), Kiyoto, Japan, August, 1990 • “Maximizing Production and Utilization of Landfill Gas” 2009 Wuhan International Conference on Environment(CAWPRC Conference, sponsored by US EPA) Wuhan, China. October, 2009. • “WXF Bio-Energy-A Green, Sustainable Waste to Energy Process” Presented at 9Th International Conference Cooperation for Waste Issues, Kharkiv, Ukraine March, 2012 • “A Lannfill Site Can Be Recycled Indefinitely” Presented at 28th International Conference on solid Waste Technology and Management, Philadelphia, Pennsylvania, USA. March, 2013. Hosted by The Journal of Solid Waste Technology and Management.

Keywords: green fuel, waste management, bio-energy, sustainable development, methanol

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Authors: Nanine Fouche

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The Cape Flats is a low-lying sand-covered expanse of approximately 460 square kilometres, situated to the southeast of the central business district of Cape Town in the Western Cape of South Africa. The aeolian sands masking this area are often loose and compressible in the upper 1m to 1.5m of the surface, and there is a general exceedance of the maximum allowable settlement in these sands. The settlement of shallow foundations on Cape Flats sands is commonly predicted using the results of in-situ tests such as the SPT or DPSH due to the difficulty of retrieving undisturbed samples for laboratory testing. Varying degrees of accuracy and reliability are associated with these methods. More recently, shear wave velocity (Vs) profiles obtained from seismic testing, such as continuous surface wave tests (CSW), are being used for settlement prediction. Such predictions have the advantage of considering non-linear stress-strain behaviour of soil and the degradation of stiffness with increasing strain. CSW tests are rarely executed in the Cape Flats, whereas SPT’s are commonly performed. For this reason, and to facilitate better settlement predictions in Cape Flats sand, equations representing shear wave velocity (Vs) as a function of SPT blow count (N60) and vertical effective stress (v’) were generated by statistical regression of site investigation data. To reveal the most appropriate method of overburden correction, analyses were performed with a separate overburden term (Pa/σ’v) as well as using stress corrected shear wave velocity and SPT blow counts (correcting Vs. and N60 to Vs1and (N1)60respectively). Shear wave velocity profiles and SPT blow count data from three sites masked by Cape Flats sands were utilised to generate 80 Vs-SPT N data pairs for analysis. Investigated terrains included sites in the suburbs of Athlone, Muizenburg, and Atlantis, all underlain by windblown deposits comprising fine and medium sand with varying fines contents. Elastic settlement analysis was also undertaken for the Cape Flats sands, using a non-linear stepwise method based on small-strain stiffness estimates, which was obtained from the best Vs-N60 model and compared to settlement estimates using the general elastic solution with stiffness profiles determined using Stroud’s (1989) and Webb’s (1969) SPT N60-E transformation models. Stroud’s method considers strain level indirectly whereasWebb’smethod does not take account of the variation in elastic modulus with strain. The expression of Vs. in terms of N60 and Pa/σv’ derived from the Atlantis data set revealed the best fit with R2 = 0.83 and a standard error of 83.5m/s. Less accurate Vs-SPT N relations associated with the combined data set is presumably the result of inversion routines used in the analysis of the CSW results showcasing significant variation in relative density and stiffness with depth. The regression analyses revealed that the inclusion of a separate overburden term in the regression of Vs and N60, produces improved fits, as opposed to the stress corrected equations in which the R2 of the regression is notably lower. It is the correction of Vs and N60 to Vs1 and (N1)60 with empirical constants ‘n’ and ‘m’ prior to regression, that introduces bias with respect to overburden pressure. When comparing settlement prediction methods, both Stroud’s method (considering strain level indirectly) and the small strain stiffness method predict higher stiffnesses for medium dense and dense profiles than Webb’s method, which takes no account of strain level in the determination of soil stiffness. Webb’s method appears to be suitable for loose sands only. The Versak software appears to underestimate differences in settlement between square and strip footings of similar width. In conclusion, settlement analysis using small-strain stiffness data from the proposed Vs-N60 model for Cape Flats sands provides a way to take account of the non-linear stress-strain behaviour of the sands when calculating settlement.

Keywords: sands, settlement prediction, continuous surface wave test, small-strain stiffness, shear wave velocity, penetration resistance

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Authors: Rohini Das, Subhasish Das, Smruti Rekha Sahoo, Shagupta Yesmin

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The Paleoproterozoic Kolhan Group (Purana) ensemble constitutes the youngest lithostratigraphic 'outlier' in the Singhbhum Archaean craton. The Kolhan unconformably overlies both the Singhbhum granite and the Iron Ore Group (IOG). Representing a typical sandstone-shale ( +/- carbonates) sequence, the Kolhan is characterized by the development of thin and discontinuous patches of basal conglomerates draped by sandstone beds. The IOG-fault limits the western 'distal' margin of the Kolhan basin showing evidence of passive subsidence subsequent to the initial rifting stage. The basin evolved as a half-graben under the influence of an extensional stress regime. The assumption of a tectonic setting for the NE-SW trending Kolhan basin possibly relates to the basin opening to the E-W extensional stress system that prevailed during the development of the Newer Dolerite dyke. The Paleoproterozoic age of the Kolhan basin is based on the consideration of the conformable stress pattern responsible both for the basin opening and the development of the conjugate fracture system along which the Newer Dolerite dykes intruded the Singhbhum Archaean craton. The Kolhan sandstones show progressive change towards greater textural and mineralogical maturity in its upbuilding. The trend of variations in different mineralogical and textural attributes, however, exhibits inflections at different lithological levels. Petrological studies collectively indicate that the sandstones were dominantly derived from a weathered granitic crust under a humid climatic condition. Provenance-derived variations in sandstone compositions are therefore a key in unraveling regional tectonic histories. The basin axis controlled the progradation direction which was likely driven by climatically induced sediment influx, a eustatic fall, or both. In the case of the incongruent shift, increased sediment supply permitted the rivers to cross the basinal deep. Temporal association of the Kolhan with tectonic structures in the belt indicates that syn-tectonic thrust uplift, not isostatic uplift or climate, caused the influx of quartz. The sedimentation pattern in the Kolhan reflects a change from braided fluvial-ephemeral pattern to a fan-delta-lacustrine type. The channel geometries and the climate exerted a major control on the processes of sediment transfer. Repeated fault controlled uplift of the source followed by subsidence and forced regression, generated multiple sediment cyclicity that led to the fluvial-fan delta sedimentation pattern. Intermittent uplift of the faulted blocks exposed fresh bedrock to mechanical weathering that generated a large amount of detritus and resulted to forced regressions, repeatedly disrupting the cycles which may reflect a stratigraphic response of connected rift basins at the early stage of extension. The marked variations in the thickness of the fan delta succession and the stacking pattern in different measured profiles reflect the overriding tectonic controls on fan delta evolution. The accumulated fault displacement created higher accommodation and thicker delta sequences. Intermittent uplift of fault blocks exposed fresh bedrock to mechanical weathering, generated a large amount of detritus, and resulted in forced closure of the land-locked basin, repeatedly disrupting the fining upward pattern. The control of source rock lithology or climate was of secondary importance to tectonic effects. Such a retrograding fan delta could be a stratigraphic response of connected rift basins at the early stage of extension.

Keywords: Kolhan basin, petrology, sandstone, tectonics

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Authors: Stephen Verderber

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The World Health Organization (WHO) calls for research and development on ecologically sustainable, resilient structures capable of effectively responding to disaster events globally, in response to climate change, politically based diasporas, earthquakes, and other adverse events upending the rhythms of everyday life globally. By 2050, nearly 80% of the world’s population will reside in coastal zones, and this, coupled with the increasingly dire impacts of climate change, constitute a recipe for further chaos and disruption, and in light of these events, architects have yet to rise up to meet the challenge. In the arena of healthcare, rapidly deployable clinics and field hospitals can provide immediate assistance in medically underserved disaster strike zones. Transportable facilities offer multiple advantages over conventional, fixed-site hospitals, as lightweight, comparatively unencumbered alternatives. These attributes have been proven repeatedly in 20th century vehicular and tent-based structures deployed in frontline combat theaters and in prior natural disasters. Prefab transportable clinics and trauma centers recently responded adroitly to medical emergencies in the aftermath of the Haitian (2010) and Ecuadorian (2016) earthquakes, and in North American post-hurricane relief efforts (2017) while architects continue to be castigated by their engineer colleagues as chronically poor first responders. Architecturally based portable structures for healthcare currently include Redeployable Health Centers (RHCs), Redeployable Trauma Centers (RTCs), and Permanent Modular Installations (PMIs). Five tectonic variants within this typology have recently been operationalized in the field: 1. Vehicular-based Nomadics: Prefab modules installed on a truck chassis with interior compartments dropped in prior to final assembly. Alternately, a two-component apparatus is preferred, with a truck cab pulling a modular medical unit, with independent transiting component; 2. Tent and Pneumatic Systems: Tent/yurt precursors and inflatable systems lightweight and responsive to topographically challenging terrain and diverse climates; 3. Containerized Systems: The standard modular intermodal-shipping container affords structural strength, resiliency in difficult transiting conditions, and can be densely close-packed and these can be custom-built or hold flat-pack systems; 4. Flat-Packs and Pop-Up Systems: These kit-of-part assemblies are shipped in standardized or specially-designed ISO containers; and 5. Hybrid Systems: These consist of composite facilities representing a synthesis of mobile vehicular components and/or tent or shipping containers, fused with conventional or pneumatically activated tent systems. Hybrids are advantageous in many installation contexts from an aesthetic, fabrication, and transiting perspective. Advantages/disadvantages of various modular systems are comparatively examined, followed by presentation of a compendium of 80 evidence (research)-based planning and design considerations addressing site/context, transiting and commissioning, triage, decontamination/intake, diagnostic and treatment, facility tectonics, and administration/total environment. The benefits of offsite pre-manufactured fabrication are examined, as is anticipated growth in international demand for transportable healthcare facilities to meet the challenges posed by accelerating global climate change and global conflicts. This investigation into rapid response facilities for pre and post-disaster zones is drawn from a recent book by the author, the first on architecture on this topic (Innovations in Transportable Healthcare Architecture).

Keywords: disaster mitigation, rapid response healthcare architecture, offsite prefabrication

Procedia PDF Downloads 95

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

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

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

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Authors: Swaleh Aboud, Mishal Gudka, David Obura

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Background: Coral reefs are becoming increasingly vulnerable due to several threats ranging from climate change to overfishing. This has resulted in increased management and conservation efforts to protect reefs from degradation and facilitate recovery. Recruitmentof new individuals are isimportant in the recovery process and critical for the persistence of coral reef ecosystems. Local coral community structure can be influenced by successful recruit settlement, survival, and growth Understanding coral recruitment patterns can help quantify reef resilience and connectivity, establish baselines and track changes and evaluate the effectiveness of reef restoration and conservation efforts. This study will examine the abundance and spatial pattern of coral recruits and how this relates to adult community structure, including the distribution of thermal resistance and sensitive genera and their distribution in different management regimes. Methods: Coral recruit and demography surveys were conducted from 2020 to 2022, covering 35 sites in 19coral reef locations along the Kenyan coast. These included marine parks, reserves, community conservation areas (CMAs), and open access areas from the north (Marereni) to the south (Kisite) coast of Kenya and across different reef habitats. The data was collected through the underwater visual census (UVC) technique. We counted adult corals (>10 cm diameter)of23 selected genera using belt transects (25 by 1 m) and sampling of 1 m2 quadrat (at an interval of 5m) for all coloniesless than 10 cm diameter. The benthic cover was collected using photo quadrats. The surveys were only done during the northeast monsoon season. The data wereanalyzed using the R program to see the distribution patterns and the Kruskal Wallis test to see whether there was a significant difference. Spearman correlation was also applied to assess the relationship between the distribution of coral genera in recruits and adults. Results: A total of 44 different coral genera were recorded for recruits, ranging from 3at Marereni to 30at Watamu Marine Reserve. Recruit densities ranged from 1.2±1.5recruit m-2 (mean±SD) at Likoni to 10.3± 8.4 recruit m-2 at Kisite Marine Park. The overall densityof recruitssignificantly differed between reef locations, with Kisite Marine Park and Reserve and Likonihaving significantly large differences from all the other locations, while Vuma, Watamu, Malindi, and Kilifi had significantly lower differences from all the other locations. The recruit generadensity along the Kenya coastwas divided into two clusters, one of which only included sites inKisite Marine Park. Adult colonies were dominated by Porites massive, Acropora, Platygyra, and Favites, whereas recruits were dominated by Porites branching, Porites massive, Galaxea, and Acropora. However, correlation analysis revealed a statistically significant positive correlation (r=0.81, p<0.05) between recruit and adult coral densities across the 23 coral genera. Marereni, which had the lowest densityof recruits, has only thermallyresistant coral genera, while Kisite Marine Park, with the highest recruit densities, has over 90% thermal sensitive coral genera. A weak positive correlation was found between recruit density and coralline algae, dead standing corals, and turf algae, whereas a weak negative correlation was found between recruit density and bare substrate and macroalgae. Between management regimes, marine reserves were found to have more recruits than no-take zones (marine parks and CMAs) and open access areas, although the difference was not significant. Conclusion: There was a statistically significant difference in the density of recruits between different reef locations along the Kenyan coast. Although the dominating genera of adults and recruits were different, there was a strong positive correlation between their coral communities, which could indicate self-recruitment processes or consistent distance seedings (of the same recruit genera). Sites such as Kisite Marine Park, with high recruit densities but dominated by thermally sensitive genera, will, on the other hand, be adversely affected by future thermal stress. This could imply that reducing the threats to coral reefs such as overfishingcould allow for their natural regeneration and recovery.

Keywords: coral recruits, coral adult size-class, cora demography, resilience

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Authors: P. C. Kutschera, Elena C. Tesoro, Mary Grace Talamera-Sandico, Jose Maria G. Pelayo III

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Second generation military Filipino Amerasians comprise a formidable contemporary segment of the estimated 250,000-plus biracial Amerasians in the Philippines today. Overall, they are a stigmatized and socioeconomically marginalized diaspora, historically; they were abandoned or estranged by U.S. military personnel fathers assigned during the century-long Colonial, Post-World War II and Cold War Era of permanent military basing (1898-1992). Indeed, U.S. military personnel remain stationed in smaller numbers in the Philippines today. This inquiry is an outgrowth of two recent small sample studies. The first surfaced the impact of the U.S. military prostitution system on formation of the ‘Derivative Amerasian Family Construct’ on first generation Amerasians; a second, qualitative case study suggested the continued effect of the prostitution systems' destructive impetuous on second generation Amerasians. The intent of this current qualitative, multiple-case study was to actively seek out second generation sex industry toilers. The purpose was to focus further on this human phenomenon in the post-basing and post-military prostitution system eras. As background, the former military prostitution apparatus has transformed into a modern dynamic of rampant sex tourism and prostitution nationwide. This is characterized by hotel and resorts offering unrestricted carnal access, urban and provincial brothels (casas), discos, bars and pickup clubs, massage parlors, local barrio karaoke bars and street prostitution. A small case study sample (N = 4) of female and male second generation Amerasians were selected. Sample formation employed a non-probability ‘snowball’ technique drawing respondents from the notorious Angeles, Metro Manila, Olongapo City ‘AMO Amerasian Triangle’ where most former U.S. military installations were sited and modern sex tourism thrives. A six-month study and analysis of in-depth interviews of female and male sex laborers, their families and peers revealed a litany of disturbing, and troublesome experiences. Results showed profiles of debilitating human poverty, history of family disorganization, stigmatization, social marginalization and the ghost of the military prostitution system and its harmful legacy on Amerasian family units. Emerging were testimonials of wayward young people ensnared in a maelstrom of deep economic deprivation, familial dysfunction, psychological desperation and societal indifference. The paper recommends that more study is needed and implications of unstudied psychosocial and socioeconomic experiences of distressed younger generations of military Amerasians require specific research. Heretofore apathetic or disengaged U.S. institutions need to confront the issue and formulate activist and solution-oriented social welfare, human services and immigration easement policies and alternatives. These institutions specifically include academic and social science research agencies, corporate foundations, the U.S. Congress, and Departments of State, Defense and Health and Human Services, and Homeland Security (i.e. Citizen and Immigration Services) It is them who continue to endorse a laissez-faire policy of non-involvement over the entire Filipino Amerasian question. Such apathy, the paper concludes, relegates this consequential but neglected blood progeny to the status of humiliating destitution and exploitation. Amerasians; thus, remain entrapped in their former colonial, and neo-colonial habitat. Ironically, they are unwitting victims of a U.S. American homeland that fancies itself geo-politically as a strong and strategic military treaty ally of the Philippines in the Western Pacific.

Keywords: Asian Americans, diaspora, Filipino Amerasians, military prostitution, stigmatization

Procedia PDF Downloads 455