Search results for: patient reported outcomes
Commenced in January 2007
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Edition: International
Paper Count: 9273

Search results for: patient reported outcomes

33 Assessing Diagnostic and Evaluation Tools for Use in Urban Immunisation Programming: A Critical Narrative Review and Proposed Framework

Authors: Tim Crocker-Buque, Sandra Mounier-Jack, Natasha Howard

Abstract:

Background: Due to both the increasing scale and speed of urbanisation, urban areas in low and middle-income countries (LMICs) host increasingly large populations of under-immunized children, with the additional associated risks of rapid disease transmission in high-density living environments. Multiple interdependent factors are associated with these coverage disparities in urban areas and most evidence comes from relatively few countries, e.g., predominantly India, Kenya, Nigeria, and some from Pakistan, Iran, and Brazil. This study aimed to identify, describe, and assess the main tools used to measure or improve coverage of immunisation services in poor urban areas. Methods: Authors used a qualitative review design, including academic and non-academic literature, to identify tools used to improve coverage of public health interventions in urban areas. Authors selected and extracted sources that provided good examples of specific tools, or categories of tools, used in a context relevant to urban immunization. Diagnostic (e.g., for data collection, analysis, and insight generation) and programme tools (e.g., for investigating or improving ongoing programmes) and interventions (e.g., multi-component or stand-alone with evidence) were selected for inclusion to provide a range of type and availability of relevant tools. These were then prioritised using a decision-analysis framework and a tool selection guide for programme managers developed. Results: Authors reviewed tools used in urban immunisation contexts and tools designed for (i) non-immunization and/or non-health interventions in urban areas, and (ii) immunisation in rural contexts that had relevance for urban areas (e.g., Reaching every District/Child/ Zone). Many approaches combined several tools and methods, which authors categorised as diagnostic, programme, and intervention. The most common diagnostic tools were cross-sectional surveys, key informant interviews, focus group discussions, secondary analysis of routine data, and geographical mapping of outcomes, resources, and services. Programme tools involved multiple stages of data collection, analysis, insight generation, and intervention planning and included guidance documents from WHO (World Health Organisation), UNICEF (United Nations Children's Fund), USAID (United States Agency for International Development), and governments, and articles reporting on diagnostics, interventions, and/or evaluations to improve urban immunisation. Interventions involved service improvement, education, reminder/recall, incentives, outreach, mass-media, or were multi-component. The main gaps in existing tools were an assessment of macro/policy-level factors, exploration of effective immunization communication channels, and measuring in/out-migration. The proposed framework uses a problem tree approach to suggest tools to address five common challenges (i.e. identifying populations, understanding communities, issues with service access and use, improving services, improving coverage) based on context and available data. Conclusion: This study identified many tools relevant to evaluating urban LMIC immunisation programmes, including significant crossover between tools. This was encouraging in terms of supporting the identification of common areas, but problematic as data volumes, instructions, and activities could overwhelm managers and tools are not always suitably applied to suitable contexts. Further research is needed on how best to combine tools and methods to suit local contexts. Authors’ initial framework can be tested and developed further.

Keywords: health equity, immunisation, low and middle-income countries, poverty, urban health

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32 Braille Lab: A New Design Approach for Social Entrepreneurship and Innovation in Assistive Tools for the Visually Impaired

Authors: Claudio Loconsole, Daniele Leonardis, Antonio Brunetti, Gianpaolo Francesco Trotta, Nicholas Caporusso, Vitoantonio Bevilacqua

Abstract:

Unfortunately, many people still do not have access to communication, with specific regard to reading and writing. Among them, people who are blind or visually impaired, have several difficulties in getting access to the world, compared to the sighted. Indeed, despite technology advancement and cost reduction, nowadays assistive devices are still expensive such as Braille-based input/output systems which enable reading and writing texts (e.g., personal notes, documents). As a consequence, assistive technology affordability is fundamental in supporting the visually impaired in communication, learning, and social inclusion. This, in turn, has serious consequences in terms of equal access to opportunities, freedom of expression, and actual and independent participation to a society designed for the sighted. Moreover, the visually impaired experience difficulties in recognizing objects and interacting with devices in any activities of daily living. It is not a case that Braille indications are commonly reported only on medicine boxes and elevator keypads. Several software applications for the automatic translation of written text into speech (e.g., Text-To-Speech - TTS) enable reading pieces of documents. However, apart from simple tasks, in many circumstances TTS software is not suitable for understanding very complicated pieces of text requiring to dwell more on specific portions (e.g., mathematical formulas or Greek text). In addition, the experience of reading\writing text is completely different both in terms of engagement, and from an educational perspective. Statistics on the employment rate of blind people show that learning to read and write provides the visually impaired with up to 80% more opportunities of finding a job. Especially in higher educational levels, where the ability to digest very complex text is key, accessibility and availability of Braille plays a fundamental role in reducing drop-out rate of the visually impaired, thus affecting the effectiveness of the constitutional right to get access to education. In this context, the Braille Lab project aims at overcoming these social needs by including affordability in designing and developing assistive tools for visually impaired people. In detail, our awarded project focuses on a technology innovation of the operation principle of existing assistive tools for the visually impaired leaving the Human-Machine Interface unchanged. This can result in a significant reduction of the production costs and consequently of tool selling prices, thus representing an important opportunity for social entrepreneurship. The first two assistive tools designed within the Braille Lab project following the proposed approach aims to provide the possibility to personally print documents and handouts and to read texts written in Braille using refreshable Braille display, respectively. The former, named ‘Braille Cartridge’, represents an alternative solution for printing in Braille and consists in the realization of an electronic-controlled dispenser printing (cartridge) which can be integrated within traditional ink-jet printers, in order to leverage the efficiency and cost of the device mechanical structure which are already being used. The latter, named ‘Braille Cursor’, is an innovative Braille display featuring a substantial technology innovation by means of a unique cursor virtualizing Braille cells, thus limiting the number of active pins needed for Braille characters.

Keywords: Human rights, social challenges and technology innovations, visually impaired, affordability, assistive tools

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31 Phytochemical Profile and in Vitro Bioactivity Studies on Two Underutilized Vegetables in Nigeria

Authors: Borokini Funmilayo Boede

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B. alba L., commonly called ‘Amunututu’ and Solanecio biafrae called ‘Worowo’ among the Yoruba tribe in the southwest part of Nigeria are reported to be of great ethnomedicinal importance but are among many underutilized green leafy vegetables in the country. Many studies have established the nutritional values of these vegetables, utilization are very poor and indepth information on their chemical profiles is scarce. The aqueous, methanolic and ethanolic extracts of these vegetables were subjected to phytochemical screening and phenolic profiles of the alcoholic extracts were characterized by using high-performance liquid chromatography coupled with diode array detector (HPLC-DAD). Total phenol and flavonoid contents were determined, antioxidant activities were evaluated using five in vitro assays to assess DPPH, nitric oxide and hydroxyl radical-scavenging abilities, as well as reducing power with ferric reducing antioxidant assay and phosphomolybdate method. The antibacterial activities of the extracts against Staphylococcus aureus, Pseudomonas aeruginosa, and Salmonella typhi were evaluated by using agar well diffusion method and the antifungal activity evaluated against food-associated filamentous fungi by using poisoned food technique with the aim of assessing their nutraceutical potentials to encourage their production and utilization. The results revealed the presence of saponnin, steroids, tannin, terpenoid and flavonoid as well as phenolic compounds: gallic acid, chlorogenic acid, caffeic acid, coumarin, rutin, quercitrin, quercetin and kaemferol. The vegetables showed varying concentration dependent reducing and radical scavenging abilities from weak to strong compared with gallic acid, rutin, trolox and ascorbic acid used as positive controls; the aqueous extracts which gave higher concentrations of total phenol displayed higher ability to reduce Fe (lll) to Fe (ll) and stronger inhibiting power against hydroxyl radical than the alcoholic extracts and in most cases exhibited more potency than the ascorbic acids used as positive controls, at the same concentrations, whereas, methanol and / or ethanol extracts were found to be more effective in scavenging 2, 2-diphenyl-1-picryl hydrazyl radical and showed higher ability to reduce Mo (VI) to Mo (V) in total antioxidant assay than the aqueous extracts. However, the inhibition abilities of all the extracts against nitric oxide were comparable with the ascorbic acid control at the same concentrations. There were strong positive correlations with total phenol (mg GAE/g) and total flavonoid (mg RE/g) contents in the range TFC (r=0.857- 0999 and r= 0.904-1.000) and TPC (r= 0.844- 0.992 and r= 0.900 -0.999) for Basella alba and Senecio biafrae respectively. Inhibition concentration at 50 % (IC50) for each extract to scavenge DPPH, OH and NO radicals ranged from 32.73 to 1.52 compared with control (0.846 - -6.42) mg/ml. At 0.05g/ml, the vegetables were found to exhibit mild antibacterial activities against Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella typhi compared with streptomycin sulphate used as control but appreciable antifungi activities against (Trichoderma rubrum and Aspergillus fumigates) compared with bonlate antibiotic positive control. The vegetables possess appreciable antioxidant and antimicrobial properties for promoting good health, their cultivation and utilization should be encouraged especially in the face of increasing health and economic challenges and food insecurity in many parts of the world.

Keywords: antimicrobial, antioxidants, extracts, phytochemicals

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30 High Performance Lithium Ion Capacitors from Biomass Waste-Derived Activated Carbon

Authors: Makhan Maharjan, Mani Ulaganathan, Vanchiappan Aravindan, Srinivasan Madhavi, Jing-Yuan Wang, Tuti Mariana Lim

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The ever-increasing energy demand has made research to develop high performance energy storage systems that are able to fulfill energy needs. Supercapacitors have potential applications as portable energy storage devices. In recent years, there have been huge research interests to enhance the performances of supercapacitors via exploiting novel promising carbon precursors, tailoring textural properties of carbons, exploiting various electrolytes and device types. In this work, we employed orange peel (waste material) as the starting material and synthesized activated carbon by pyrolysis of KOH impregnated orange peel char at 800 °C in argon atmosphere. The resultant orange peel-derived activated carbon (OP-AC) exhibited BET surface area of 1,901 m² g-1, which is the highest surface area so far reported for the orange peel. The pore size distribution (PSD) curve exhibits the pores centered at 11.26 Å pore width, suggesting dominant microporosity. The high surface area OP-AC accommodates more ions in the electrodes and its well-developed porous structure facilitates fast diffusion of ions which subsequently enhance electrochemical performance. The OP-AC was studied as positive electrode in combination with different negative electrode materials, such as pre-lithiated graphite (LiC6) and Li4Ti5O12 for making hybrid capacitors. The lithium ion capacitor (LIC) fabricated using OP-AC with pre-lithiated graphite delivered high energy density of ~106 Wh kg–1. The energy density for OP-AC||Li4Ti5O12 capacitor was ~35 Wh kg⁻¹. For comparison purpose, configuration of OP-AC||OP-AC capacitors were studied in both aqueous (1M H2SO4) and organic (1M LiPF6 in EC-DMC) electrolytes, which delivered the energy density of 8.0 Wh kg⁻¹ and 16.3 Wh kg⁻¹, respectively. The cycling retentions obtained at current density of 1 A g⁻¹ were ~85.8, ~87.0 ~82.2 and ~58.8% after 2500 cycles for OP-AC||OP-AC (aqueous), OP-AC||OP-AC (organic), OP-AC||Li4Ti5O12 and OP-AC||LiC6 configurations, respectively. In addition, characterization studies were performed by elemental and proximate composition, thermogravimetry analysis, field emission-scanning electron microscopy, Raman spectra, X-ray diffraction (XRD) pattern, Fourier transform-infrared, X-ray photoelectron spectroscopy (XPS) and N2 sorption isotherms. The morphological features from FE-SEM exhibited well-developed porous structures. Two typical broad peaks observed in the XRD framework of the synthesized carbon implies amorphous graphitic structure. The ratio of 0.86 for ID/IG in Raman spectra infers high degree of graphitization in the sample. The band spectra of C 1s in XPS display the well resolved peaks related to carbon atoms in various chemical environments. The presence of functional groups is also corroborated from the FTIR spectroscopy. Characterization studies revealed the synthesized carbon to be promising electrode material towards the application for energy storage devices. Overall, the intriguing properties of OP-AC make it a new alternative promising electrode material for the development of high energy lithium ion capacitors from abundant, low-cost, renewable biomass waste. The authors gratefully acknowledge Agency for Science, Technology and Research (A*STAR)/ Singapore International Graduate Award (SINGA) and Nanyang Technological University (NTU), Singapore for funding support.

Keywords: energy storage, lithium-ion capacitors, orange peels, porous activated carbon

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29 Facies Analysis and Depositional Environment of the Late Carboniferous (Stephanian) Souss Basin, Morocco

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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28 Development of an Omaha System-Based Remote Intervention Program for Work-Related Musculoskeletal Disorders (WMSDs) Among Front-Line Nurses

Authors: Tianqiao Zhang, Ye Tian, Yanliang Yin, Yichao Tian, Suzhai Tian, Weige Sun, Shuhui Gong, Limei Tang, Ruoliang Tang

Abstract:

Introduction: Healthcare workers, especially the nurses all over the world, are highly vulnerable to work-related musculoskeletal disorders (WMSDs), experiencing high rates of neck, shoulder, and low back injuries, due to the unfavorable working conditions. To reduce WMSDs among nursing personnel, many workplace interventions have been developed and implemented. Unfortunately, the ongoing Covid-19 (SARS-CoV-2) pandemic has posed great challenges to the ergonomic practices and interventions in healthcare facilities, particularly the hospitals, since current Covid-19 mitigation measures, such as social distancing and working remotely, has substantially minimized in-person gatherings and trainings. On the other hand, hospitals throughout the world have been short-staffed, resulting in disturbance of shift scheduling and more importantly, the increased job demand among the available caregivers, particularly the doctors and nurses. With the latest development in communication technology, remote intervention measures have been developed as an alternative, without the necessity of in-person meetings. The Omaha System (OS) is a standardized classification system for nursing practices, including a problem classification system, an intervention system, and an outcome evaluation system. This paper describes the development of an OS-based ergonomic intervention program. Methods: First, a comprehensive literature search was performed among worldwide electronic databases, including PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), between journal inception to May 2020, resulting in a total of 1,418 scientific articles. After two independent screening processes, the final knowledge pool included eleven randomized controlled trial studies to develop the draft of the intervention program with Omaha intervention subsystem as the framework. After the determination of sample size needed for statistical power and the potential loss to follow-up, a total of 94 nurses from eight clinical departments agreed to provide written, informed consent to participate in the study, which were subsequently assigned into two random groups (i.e., intervention vs. control). A subgroup of twelve nurses were randomly selected to participate in a semi-structured interview, during which their general understanding and awareness of musculoskeletal disorders and potential interventions was assessed. Then, the first draft was modified to reflect the findings from these interviews. Meanwhile, the tentative program schedule was also assessed. Next, two rounds of consultation were conducted among experts in nursing management, occupational health, psychology, and rehabilitation, to further adjust and finalize the intervention program. The control group had access to all the information and exercise modules at baseline, while an interdisciplinary research team was formed and supervised the implementation of the on-line intervention program through multiple social media groups. Outcome measures of this comparative study included biomechanical load assessed by the Quick Exposure Check and stresses due to awkward body postures. Results and Discussion: Modification to the draft included (1) supplementing traditional Chinese medicine practices, (2) adding the use of assistive patient handling equipment, and (3) revising the on-line training method. Information module should be once a week, lasting about 20 to 30 minutes, for a total of 6 weeks, while the exercise module should be 5 times a week, each lasting about 15 to 20 minutes, for a total of 6 weeks.

Keywords: ergonomic interventions, musculoskeletal disorders (MSDs), omaha system, nurses, Covid-19

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27 Characterization of Aluminosilicates and Verification of Their Impact on Quality of Ceramic Proppants Intended for Shale Gas Output

Authors: Joanna Szymanska, Paulina Wawulska-Marek, Jaroslaw Mizera

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Nowadays, the rapid growth of global energy consumption and uncontrolled depletion of natural resources become a serious problem. Shale rocks are the largest and potential global basins containing hydrocarbons, trapped in closed pores of the shale matrix. Regardless of the shales origin, mining conditions are extremely unfavourable due to high reservoir pressure, great depths, increased clay minerals content and limited permeability (nanoDarcy) of the rocks. Taking into consideration such geomechanical barriers, effective extraction of natural gas from shales with plastic zones demands effective operations. Actually, hydraulic fracturing is the most developed technique based on the injection of pressurized fluid into a wellbore, to initiate fractures propagation. However, a rapid drop of pressure after fluid suction to the ground induces a fracture closure and conductivity reduction. In order to minimize this risk, proppants should be applied. They are solid granules transported with hydraulic fluids to locate inside the rock. Proppants act as a prop for the closing fracture, thus gas migration to a borehole is effective. Quartz sands are commonly applied proppants only at shallow deposits (USA). Whereas, ceramic proppants are designed to meet rigorous downhole conditions to intensify output. Ceramic granules predominate with higher mechanical strength, stability in strong acidic environment, spherical shape and homogeneity as well. Quality of ceramic proppants is conditioned by raw materials selection. Aim of this study was to obtain the proppants from aluminosilicates (the kaolinite subgroup) and mix of minerals with a high alumina content. These loamy minerals contain a tubular and platy morphology that improves mechanical properties and reduces their specific weight. Moreover, they are distinguished by well-developed surface area, high porosity, fine particle size, superb dispersion and nontoxic properties - very crucial for particles consolidation into spherical and crush-resistant granules in mechanical granulation process. The aluminosilicates were mixed with water and natural organic binder to improve liquid-bridges and pores formation between particles. Afterward, the green proppants were subjected to sintering at high temperatures. Evaluation of the minerals utility was based on their particle size distribution (laser diffraction study) and thermal stability (thermogravimetry). Scanning Electron Microscopy was useful for morphology and shape identification combined with specific surface area measurement (BET). Chemical composition was verified by Energy Dispersive Spectroscopy and X-ray Fluorescence. Moreover, bulk density and specific weight were measured. Such comprehensive characterization of loamy materials confirmed their favourable impact on the proppants granulation. The sintered granules were analyzed by SEM to verify the surface topography and phase transitions after sintering. Pores distribution was identified by X-Ray Tomography. This method enabled also the simulation of proppants settlement in a fracture, while measurement of bulk density was essential to predict their amount to fill a well. Roundness coefficient was also evaluated, whereas impact on mining environment was identified by turbidity and solubility in acid - to indicate risk of the material decay in a well. The obtained outcomes confirmed a positive influence of the loamy minerals on ceramic proppants properties with respect to the strict norms. This research is perspective for higher quality proppants production with costs reduction.

Keywords: aluminosilicates, ceramic proppants, mechanical granulation, shale gas

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26 Criminal Attitude vs Transparency in the Arab World

Authors: Keroles Akram Saed Ghatas

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The political violence that characterized 1992 continued into 1993, creating a major security crisis for President Hosni Mubarak's government as the death toll and human rights abuses soared. Increasingly sensitive to criticism of 's human rights activities, the government established human rights departments in key ministries, beginning with the Foreign Office in February. Similar offices have been set up in the Justice and Agriculture Ministries, and plans to set up an office in the Home Office have been announced. It turned out that the main task of the law unit was to overturn the conclusions of international human rights organizations.President Mubarak was elected in a national referendum on October 4 for a third six-year term after being appointed on July 21 by the People's Assembly, an elected parliament overwhelmingly dominated by the in-power National Democratic Party will Mr. Mubarak ran unhindered. The Interior Ministry announced that nearly 16 million people cast their votes (84% of eligible voters), of which 96.28%. voted for presidential re-election.In 1993, armed Islamic extremists escalated their attacks on Christian citizens, government officials, police officers and senior security officials, resulting in casualties among the intended victims and bystanders. Sporadic attacks on buses, boats and tourist attractions also occurred throughout the year. From March 1992 to October 28, 1993, a total of 222 people lost their lives in the riots: 36 Coptic Christians and 38 other citizens; If one is a foreigner; sixty-six members of the Security Forces; and seventy-six known or suspected activists who were killed while resisting arrest. The latter was killed in airstrikes and firefights with security forces and at the site of planned attacks. On March 9-10, a series of airstrikes in Cairo, Giza, Qalyubiya province north of the capital and Aswan killed fifteen suspected militants and five members of the security forces.One of the airstrikes in Giza, part of Greater Cairo, killed the wife and son of Khalifa Mahmoud Ramadan, a suspected militant who was himself killed. The government agency Middle East News Agency reported on March 10 that the raids were part of a "broad confrontational plan aimed at ofterrorist elements"The state of emergency declared in October 1981 after the assassination of President Anwar el-Sadat was still in force in Egypt. The law, previously in effect continuously from June 1967 to May 1980, continued to grant the executive branch unique legal powers that effectively overrode the human rights guarantees of the Egyptian constitution. These provisions included wide discretionary powers in arresting and detaining individuals, as well as the ability to try civilians in military courts. The Cairo-based Independent Organization for Human Rights said so in a document sent to the United Nations in July 1993The human rights committee said the continued imposition of the state of emergency had resulted in "another constitution for the country" and "led to widespread misconduct by the security apparatus".

Keywords: constitution, human rights, legal power, president, anwar, el-sadat, assassination, state of emergency, middle east, news, agency, confrontational, arresting, fugitive, leaders, terrorist, elements, armed islamic extremists.

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25 Al2O3-Dielectric AlGaN/GaN Enhancement-Mode MOS-HEMTs by Using Ozone Water Oxidization Technique

Authors: Ching-Sung Lee, Wei-Chou Hsu, Han-Yin Liu, Hung-Hsi Huang, Si-Fu Chen, Yun-Jung Yang, Bo-Chun Chiang, Yu-Chuang Chen, Shen-Tin Yang

Abstract:

AlGaN/GaN high electron mobility transistors (HEMTs) have been intensively studied due to their intrinsic advantages of high breakdown electric field, high electron saturation velocity, and excellent chemical stability. They are also suitable for ultra-violet (UV) photodetection due to the corresponding wavelengths of GaN bandgap. To improve the optical responsivity by decreasing the dark current due to gate leakage problems and limited Schottky barrier heights in GaN-based HEMT devices, various metal-oxide-semiconductor HEMTs (MOS-HEMTs) have been devised by using atomic layer deposition (ALD), molecular beam epitaxy (MBE), metal-organic chemical vapor deposition (MOCVD), liquid phase deposition (LPD), and RF sputtering. The gate dielectrics include MgO, HfO2, Al2O3, La2O3, and TiO2. In order to provide complementary circuit operation, enhancement-mode (E-mode) devices have been lately studied using techniques of fluorine treatment, p-type capper, piezoneutralization layer, and MOS-gate structure. This work reports an Al2O3-dielectric Al0.25Ga0.75N/GaN E-mode MOS-HEMT design by using a cost-effective ozone water oxidization technique. The present ozone oxidization method advantages of low cost processing facility, processing simplicity, compatibility to device fabrication, and room-temperature operation under atmospheric pressure. It can further reduce the gate-to-channel distance and improve the transocnductance (gm) gain for a specific oxide thickness, since the formation of the Al2O3 will consume part of the AlGaN barrier at the same time. The epitaxial structure of the studied devices was grown by using the MOCVD technique. On a Si substrate, the layer structures include a 3.9 m C-doped GaN buffer, a 300 nm GaN channel layer, and a 5 nm Al0.25Ga0.75N barrier layer. Mesa etching was performed to provide electrical isolation by using an inductively coupled-plasma reactive ion etcher (ICP-RIE). Ti/Al/Au were thermally evaporated and annealed to form the source and drain ohmic contacts. The device was immersed into the H2O2 solution pumped with ozone gas generated by using an OW-K2 ozone generator. Ni/Au were deposited as the gate electrode to complete device fabrication of MOS-HEMT. The formed Al2O3 oxide thickness 7 nm and the remained AlGaN barrier thickness is 2 nm. A reference HEMT device has also been fabricated in comparison on the same epitaxial structure. The gate dimensions are 1.2 × 100 µm 2 with a source-to-drain spacing of 5 μm for both devices. The dielectric constant (k) of Al2O3 was characterized to be 9.2 by using C-V measurement. Reduced interface state density after oxidization has been verified by the low-frequency noise spectra, Hooge coefficients, and pulse I-V measurement. Improved device characteristics at temperatures of 300 K-450 K have been achieved for the present MOS-HEMT design. Consequently, Al2O3-dielectric Al0.25Ga0.75N/GaN E-mode MOS-HEMTs by using the ozone water oxidization method are reported. In comparison with a conventional Schottky-gate HEMT, the MOS-HEMT design has demonstrated excellent enhancements of 138% (176%) in gm, max, 118% (139%) in IDS, max, 53% (62%) in BVGD, 3 (2)-order reduction in IG leakage at VGD = -60 V at 300 (450) K. This work is promising for millimeter-wave integrated circuit (MMIC) and three-terminal active UV photodetector applications.

Keywords: MOS-HEMT, enhancement mode, AlGaN/GaN, passivation, ozone water oxidation, gate leakage

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24 Pharmacophore-Based Modeling of a Series of Human Glutaminyl Cyclase Inhibitors to Identify Lead Molecules by Virtual Screening, Molecular Docking and Molecular Dynamics Simulation Study

Authors: Ankur Chaudhuri, Sibani Sen Chakraborty

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In human, glutaminyl cyclase activity is highly abundant in neuronal and secretory tissues and is preferentially restricted to hypothalamus and pituitary. The N-terminal modification of β-amyloids (Aβs) peptides by the generation of a pyro-glutamyl (pGlu) modified Aβs (pE-Aβs) is an important process in the initiation of the formation of neurotoxic plaques in Alzheimer’s disease (AD). This process is catalyzed by glutaminyl cyclase (QC). The expression of QC is characteristically up-regulated in the early stage of AD, and the hallmark of the inhibition of QC is the prevention of the formation of pE-Aβs and plaques. A computer-aided drug design (CADD) process was employed to give an idea for the designing of potentially active compounds to understand the inhibitory potency against human glutaminyl cyclase (QC). This work elaborates the ligand-based and structure-based pharmacophore exploration of glutaminyl cyclase (QC) by using the known inhibitors. Three dimensional (3D) quantitative structure-activity relationship (QSAR) methods were applied to 154 compounds with known IC50 values. All the inhibitors were divided into two sets, training-set, and test-sets. Generally, training-set was used to build the quantitative pharmacophore model based on the principle of structural diversity, whereas the test-set was employed to evaluate the predictive ability of the pharmacophore hypotheses. A chemical feature-based pharmacophore model was generated from the known 92 training-set compounds by HypoGen module implemented in Discovery Studio 2017 R2 software package. The best hypothesis was selected (Hypo1) based upon the highest correlation coefficient (0.8906), lowest total cost (463.72), and the lowest root mean square deviation (2.24Å) values. The highest correlation coefficient value indicates greater predictive activity of the hypothesis, whereas the lower root mean square deviation signifies a small deviation of experimental activity from the predicted one. The best pharmacophore model (Hypo1) of the candidate inhibitors predicted comprised four features: two hydrogen bond acceptor, one hydrogen bond donor, and one hydrophobic feature. The Hypo1 was validated by several parameters such as test set activity prediction, cost analysis, Fischer's randomization test, leave-one-out method, and heat map of ligand profiler. The predicted features were then used for virtual screening of potential compounds from NCI, ASINEX, Maybridge and Chembridge databases. More than seven million compounds were used for this purpose. The hit compounds were filtered by drug-likeness and pharmacokinetics properties. The selective hits were docked to the high-resolution three-dimensional structure of the target protein glutaminyl cyclase (PDB ID: 2AFU/2AFW) to filter these hits further. To validate the molecular docking results, the most active compound from the dataset was selected as a reference molecule. From the density functional theory (DFT) study, ten molecules were selected based on their highest HOMO (highest occupied molecular orbitals) energy and the lowest bandgap values. Molecular dynamics simulations with explicit solvation systems of the final ten hit compounds revealed that a large number of non-covalent interactions were formed with the binding site of the human glutaminyl cyclase. It was suggested that the hit compounds reported in this study could help in future designing of potent inhibitors as leads against human glutaminyl cyclase.

Keywords: glutaminyl cyclase, hit lead, pharmacophore model, simulation

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23 An Innovation Decision Process View in an Adoption of Total Laboratory Automation

Authors: Chia-Jung Chen, Yu-Chi Hsu, June-Dong Lin, Kun-Chen Chan, Chieh-Tien Wang, Li-Ching Wu, Chung-Feng Liu

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With fast advances in healthcare technology, various total laboratory automation (TLA) processes have been proposed. However, adopting TLA needs quite high funding. This study explores an early adoption experience by Taiwan’s large-scale hospital group, the Chimei Hospital Group (CMG), which owns three branch hospitals (Yongkang, Liouying and Chiali, in order by service scale), based on the five stages of Everett Rogers’ Diffusion Decision Process. 1.Knowledge stage: Over the years, two weaknesses exists in laboratory department of CMG: 1) only a few examination categories (e.g., sugar testing and HbA1c) can now be completed and reported within a day during an outpatient clinical visit; 2) the Yongkang Hospital laboratory space is dispersed across three buildings, resulting in duplicated investment in analysis instruments and inconvenient artificial specimen transportation. Thus, the senior management of the department raised a crucial question, was it time to process the redesign of the laboratory department? 2.Persuasion stage: At the end of 2013, Yongkang Hospital’s new building and restructuring project created a great opportunity for the redesign of the laboratory department. However, not all laboratory colleagues had the consensus for change. Thus, the top managers arranged a series of benchmark visits to stimulate colleagues into being aware of and accepting TLA. Later, the director of the department proposed a formal report to the top management of CMG with the results of the benchmark visits, preliminary feasibility analysis, potential benefits and so on. 3.Decision stage: This TLA suggestion was well-supported by the top management of CMG and, finally, they made a decision to carry out the project with an instrument-leasing strategy. After the announcement of a request for proposal and several vendor briefings, CMG confirmed their laboratory automation architecture and finally completed the contracts. At the same time, a cross-department project team was formed and the laboratory department assigned a section leader to the National Taiwan University Hospital for one month of relevant training. 4.Implementation stage: During the implementation, the project team called for regular meetings to review the results of the operations and to offer an immediate response to the adjustment. The main project tasks included: 1) completion of the preparatory work for beginning the automation procedures; 2) ensuring information security and privacy protection; 3) formulating automated examination process protocols; 4) evaluating the performance of new instruments and the instrument connectivity; 5)ensuring good integration with hospital information systems (HIS)/laboratory information systems (LIS); and 6) ensuring continued compliance with ISO 15189 certification. 5.Confirmation stage: In short, the core process changes include: 1) cancellation of signature seals on the specimen tubes; 2) transfer of daily examination reports to a data warehouse; 3) routine pre-admission blood drawing and formal inpatient morning blood drawing can be incorporated into an automatically-prepared tube mechanism. The study summarizes below the continuous improvement orientations: (1) Flexible reference range set-up for new instruments in LIS. (2) Restructure of the specimen category. (3) Continuous review and improvements to the examination process. (4) Whether installing the tube (specimen) delivery tracks need further evaluation.

Keywords: innovation decision process, total laboratory automation, health care

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22 Physico-Chemical Characterization of Vegetable Oils from Oleaginous Seeds (Croton megalocarpus, Ricinus communis L., and Gossypium hirsutum L.)

Authors: Patrizia Firmani, Sara Perucchini, Irene Rapone, Raffella Borrelli, Stefano Chiaberge, Manuela Grande, Rosamaria Marrazzo, Alberto Savoini, Andrea Siviero, Silvia Spera, Fabio Vago, Davide Deriu, Sergio Fanutti, Alessandro Oldani

Abstract:

According to the Renewable Energy Directive II, the use of palm oil in diesel will be gradually reduced from 2023 and should reach zero in 2030 due to the deforestation caused by its production. Eni aims at finding alternative feedstocks for its biorefineries to eliminate the use of palm oil by 2023. Therefore, the ideal vegetable oils to be used in bio-refineries are those obtainable from plants that grow in marginal lands and with low impact on food-and-feed chain; hence, Eni research is studying the possibility of using oleaginous seeds, such as castor, croton, and cotton, to extract the oils to be exploited as feedstock in bio-refineries. To verify their suitability for the upgrading processes, an analytical protocol for their characterization has been drawn up and applied. The analytical characterizations include a step of water and ashes content determination, elemental analysis (CHNS analysis, X-Ray Fluorescence, Inductively Coupled Plasma - Optical Emission Spectroscopy, ICP– Mass Spectrometry), and total acid number determination. Gas chromatography coupled to flame ionization detector (GC-FID) is used to quantify the lipid content in terms of free fatty acids, mono-, di- and triacylglycerols, and fatty acids composition. Eventually, Nuclear Magnetic Resonance and Fourier Transform-Infrared spectroscopies are exploited with GC-MS and Fourier Transform-Ion Cyclotron Resonance to study the composition of the oils. This work focuses on the GC-FID analysis of the lipid fraction of these oils, as the main constituent and of greatest interest for bio-refinery processes. Specifically, the lipid component of the extracted oil was quantified after sample silanization and transmethylation: silanization allows the elution of high-boiling compounds and is useful for determining the quantity of free acids and glycerides in oils, while transmethylation leads to a mixture of fatty acid esters and glycerol, thus allowing to evaluate the composition of glycerides in terms of Fatty Acids Methyl Esters (FAME). Cotton oil was extracted from cotton oilcake, croton oil was obtained by seeds pressing and seeds and oilcake ASE extraction, while castor oil comes from seed pressing (not performed in Eni laboratories). GC-FID analyses reported that the cotton oil is 90% constituted of triglycerides and about 6% diglycerides, while free fatty acids are about 2%. In terms of FAME, C18 acids make up 70% of the total and linoleic acid is the major constituent. Palmitic acid is present at 17.5%, while the other acids are in low concentration (<1%). Both analyzes show the presence of non-gas chromatographable compounds. Croton oils from seed pressing and extraction mainly contain triglycerides (98%). Concerning FAME, the main component is linoleic acid (approx. 80%). Oilcake croton oil shows higher abundance of diglycerides (6% vs ca 2%) and a lower content of triglycerides (38% vs 98%) compared to the previous oils. Eventually, castor oil is mostly constituted of triacylglycerols (about 69%), followed by diglycerides (about 10%). About 85.2% of total FAME is ricinoleic acid, as a constituent of triricinolein, the most abundant triglyceride of castor oil. Based on the analytical results, these oils represent feedstocks of interest for possible exploitation as advanced biofuels.

Keywords: analytical protocol, biofuels, biorefinery, gas chromatography, vegetable oil

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21 The Systematic Impact of Climatic Disasters on the Maternal Health in Pakistan

Authors: Yiqi Zhu, Jean Francois Trani, Rameez Ulhassan

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

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

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20 General Evaluation of a Three-Year Holistic Physical Activity Interventions Program in Qatar Campuses: Step into Health (SIH) in Campuses 2013- 2016

Authors: Daniela Salih Khidir, Mohamed G. Al Kuwari, Mercia V. Walt, Izzeldin J. Ibrahim

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Background: University-based physical activity interventions aim to establish durable social patterns during the transition to adulthood. This study is a comprehensive evaluation of a 3-year intervention-based program to increase the culture of physical activity (PA) routine in Qatar campuses community, using a holistic approach. Methodology: General assessment methods: formative evaluation-SIH Campuses logic model design, stakeholders’ identification; process evaluation-members’ step counts analyze and qualitative Appreciative Inquiry session (4-D model); daily steps categorized as: ≤5,000, inactive; 5,000-7,499 low active; ≥7,500, physically active; outcome evaluation - records 3 years interventions. Holistic PA interventions methods: walking interventions - pedometers distributions and walking competitions for students and staff; educational interventions - in campuses implementation of bilingual educational materials, lectures, video related to PA in prevention of non-communicable diseases (NCD); articles published online; monthly emails and sms notifications for pedometer use; mass media campaign - radio advertising, yearly pre/post press releases; community stakeholders interventions-biyearly planning/reporting/achievements rewarding/ qualitative meetings; continuous follow-up communication, biweekly steps reports. Findings: Results formative evaluation - SIH in Campuses logic model identified the need of PA awareness and education within universities, resources, activities, health benefits, program continuity. Results process evaluation: walking interventions: Phase 1: 5 universities recruited, 2352 members, 3 months competition; Phase 2: 6 new universities recruited, 1328 members in addition, 4 months competition; Phase 3: 4 new universities recruited in addition, 1210 members, 6 months competition. Results phase 1 and 2: 1,299 members eligible for analyzes: 800 females (62%), 499 males (38%); 86% non-Qataris, 14% Qatari nationals, daily step count 5,681 steps, age groups 18–24 (n=841; 68%) students, 25–64; (n=458; 35.3%) staff; 38% - low active, 37% physically active and 25% inactive. The AI main themes engaging stakeholders: awareness/education - 5 points (100%); competition, multi levels of involvement in SIH, community-based program/motivation - 4 points each (80%). The AI points represent themes’ repetition within stakeholders’ discussions. Results education interventions: 2 videos implementation, 35 000 educational materials, 3 online articles, 11 walking benefits lectures, 40 emails and sms notifications. Results community stakeholders’ interventions: 6 stakeholders meetings, 3 rewarding gatherings, 1 focus meeting, 40 individual reports, 18 overall reports. Results mass media campaign: 1 radio campaign, 7 press releases, 52 campuses newsletters. Results outcome evaluation: overall 2013-2016, the study used: 1 logic model, 3 PA holistic interventions, partnerships 15 universities, registered 4890 students and staff (aged 18-64 years), engaged 30 campuses stakeholders and 14 internal stakeholders; Total registered population: 61.5% female (2999), 38.5% male (1891), 20.2% (988) Qatari nationals, 79.8% (3902) non-Qataris, 55.5% (2710) students aged 18 – 25 years, 44.5% (2180) staff aged 26 - 64 years. Overall campaign 1,558 members eligible for analyzes: daily step count 7,923; 37% - low active, 43% physically active and 20% inactive. Conclusion: The study outcomes confirm program effectiveness and engagement of young campuses community, specifically female, in PA. The authors recommend implementations of 'holistic PA intervention program approach in Qatar' aiming to impact the community at national level for PA guidelines achievement in support of NCD prevention.

Keywords: campuses, evaluation, Qatar, step-count

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19 Towards Better Integration: Qualitative Study on Perceptions of Russian-Speaking Immigrants in Australia

Authors: Oleg Shovkovyy

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This research conducted in response to one of the most pressing questions on the agenda of many public administration offices around the world: “What could be done for better integration and assimilation of immigrants into hosting communities?” In author’s view, the answer could be suggested by immigrants themselves. They, often ‘bogged down in the past,’ snared by own idols and demons, perceive things differently, which, in turn, may result in their inability to integrate smoothly into hosting communities. Brief literature review suggests that perceptions of immigrants are completely neglected or something unsought in the current research on migrants, which, often, based on opinion polls by members of hosting communities themselves or superficial research data by various research organizations. Even those specimens that include voices of immigrants, unlikely to shed any additional light onto the problem simply because certain things are not made to speak out loud, especially to those in whose hands immigrants’ fate is (authorities). In this regard, this qualitative study, conducted by an insider to a few Russian-speaking communities, represents a unique opportunity for all stakeholders to look at the question of integration through the eyes of immigrants, from a different perspective and thus, makes research findings especially valuable for better understanding of the problem. Case study research employed ethnographic methods of gathering data where, approximately 200 Russian-speaking immigrants of first and second generations were closely observed by the Russian-speaking researcher in their usual setting, for eight months, and at different venues. The number of informal interviews with 27 key informants, with whom the researcher managed to establish a good rapport and who were keen enough to share their experiences voluntarily, were conducted. The field notes were taken at 14 locations (study sites) within the Brisbane region of Queensland, Australia. Moreover, all this time, researcher lived in dwelling of one of the immigrants and was an active participant in the social life (worship, picnics, dinners, weekend schools, concerts, cultural events, social gathering, etc.) of observed communities, whose members, to a large extent, belong to various religious lines of the Russian and Protestant Church. It was found that the majority of immigrants had experienced some discrimination in matters of hiring, employment, recognition of educational qualifications from home countries, and simply felt a sort of dislike from society in various everyday situations. Many noted complete absences or very limited state assistance in terms of employment, training, education, and housing. For instance, the Australian Government Department of Human Services not only does not stimulate job search but, on the contrary, encourages to refuse short-term works and employment. On the other hand, offered free courses on adaptation, and the English language proved to be ineffective and unpopular amongst immigrants. Many interviewees have reported overstated requirements for English proficiency and local work experience, whereas it was not critical for the given task or job. Based on the result of long-term monitoring, the researcher also had the courage to assert the negative and decelerating roles of immigrants’ communities, particularly religious communities, on processes of integration and assimilation. The findings suggest that governments should either change current immigration policies in the direction of their toughening or to take more proactive and responsible role in dealing with immigrant-related issues; for instance, increasing assistance and support to all immigrants and probably, paying more attention to and taking stake in managing and organizing lives of immigrants’ communities rather, simply leaving it all to chance.

Keywords: Australia, immigration, integration, perceptions

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18 [Keynote Talk]: Bioactive Cyclic Dipeptides of Microbial Origin in Discovery of Cytokine Inhibitors

Authors: Sajeli A. Begum, Ameer Basha, Kirti Hira, Rukaiyya Khan

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Cyclic dipeptides are simple diketopiperazine derivatives being investigated by several scientists for their biological effects which include anticancer, antimicrobial, haematological, anticonvulsant, immunomodulatory effect, etc. They are potentially active microbial metabolites having been synthesized too, for developing into drug candidates. Cultures of Pseudomonas species have earlier been reported to produce cyclic dipeptides, helping in quorum sensing signals and bacterial–host colonization phenomena during infections, causing cell anti-proliferation and immunosuppression. Fluorescing Pseudomonas species have been identified to secrete lipid derivatives, peptides, pyrroles, phenazines, indoles, aminoacids, pterines, pseudomonic acids and some antibiotics. In the present work, results of investigation on the cyclic dipeptide metabolites secreted by the culture broth of Pseudomonas species as potent pro-inflammatory cytokine inhibitors are discussed. The bacterial strain was isolated from the rhizospheric soil of groundnut crop and identified as Pseudomonas aeruginosa by 16S rDNA sequence (GenBank Accession No. KT625586). Culture broth of this strain was prepared by inoculating into King’s B broth and incubating at 30 ºC for 7 days. The ethyl acetate extract of culture broth was prepared and lyophilized to get a dry residue (EEPA). Lipopolysaccharide (LPS)-induced ELISA assay proved the inhibition of tumor necrosis factor-alpha (TNF-α) secretion in culture supernatant of RAW 264.7 cells by EEPA (IC50 38.8 μg/mL). The effect of oral administration of EEPA on plasma TNF-α level in rats was tested by ELISA kit. The LPS mediated plasma TNF-α level was reduced to 45% with 125 mg/kg dose of EEPA. Isolation of the chemical constituents of EEPA through column chromatography yielded ten cyclic dipeptides, which were characterized using nuclear magnetic resonance and mass spectroscopic techniques. These cyclic dipeptides are biosynthesized in microorganisms by multifunctional assembly of non-ribosomal peptide synthases and cyclic dipeptide synthase. Cyclo (Gly-L-Pro) was found to be more potentially (IC50 value 4.5 μg/mL) inhibiting TNF-α production followed by cyclo (trans-4-hydroxy-L-Pro-L-Phe) (IC50 value 14.2 μg/mL) and the effect was equal to that of standard immunosuppressant drug, prednisolone. Further, the effect was analyzed by determining mRNA expression of TNF-α in LPS-stimulated RAW 264.7 macrophages using quantitative real-time reverse transcription polymerase chain reaction. EEPA and isolated cyclic dipeptides demonstrated diminution of TNF-α mRNA expression levels in a dose-dependent manner under the tested conditions. Also, they were found to control the expression of other pro-inflammatory cytokines like IL-1β and IL-6, when tested through their mRNA expression levels in LPS-stimulated RAW 264.7 macrophages under LPS-stimulated conditions. In addition, significant inhibition effect was found on Nitric oxide production. Further all the compounds exhibited weak toxicity to LPS-induced RAW 264.7 cells. Thus the outcome of the study disclosed the effectiveness of EEPA and the isolated cyclic dipeptides in down-regulating key cytokines involved in pathophysiology of autoimmune diseases.In another study led by the investigators, microbial cyclic dipeptides were found to exhibit excellent antimicrobial effect against Fusarium moniliforme which is an important causative agent of Sorghum grain mold disease. Thus, cyclic dipeptides are emerging small molecular drug candidates for various autoimmune diseases.

Keywords: cyclic dipeptides, cytokines, Fusarium moniliforme, Pseudomonas, TNF-alpha

Procedia PDF Downloads 194
17 Biotech Processes to Recover Valuable Fraction from Buffalo Whey Usable in Probiotic Growth, Cosmeceutical, Nutraceutical and Food Industries

Authors: Alberto Alfano, Sergio D’ambrosio, Darshankumar Parecha, Donatella Cimini, Chiara Schiraldi.

Abstract:

The main objective of this study regards the setup of an efficient small-scale platform for the conversion of local renewable waste materials, such as whey, into added-value products, thereby reducing environmental impact and costs deriving from the disposal of processing waste products. The buffalo milk whey derived from the cheese-making process, called second cheese whey, is the main by-product of the dairy industry. Whey is the main and most polluting by-product obtained from cheese manufacturing consisting of lactose, lactic acid, proteins, and salts, making whey an added-value product. In Italy, and in particular, in the Campania region, soft cheese production needs a large volume of liquid waste, especially during late spring and summer. This project is part of a circular economy perspective focused on the conversion of potentially polluting and difficult to purify waste into a resource to be exploited, and it embodies the concept of the three “R”: reduce, recycle, and reuse. Special focus was paid to the production of health-promoting biomolecules and biopolymers, which may be exploited in different segments of the food and pharmaceutical industries. These biomolecules may be recovered through appropriate processes and reused in an attempt to obtain added value products. So, ultrafiltration and nanofiltration processes were performed to fractionate bioactive components starting from buffalo milk whey. In this direction, the present study focused on the implementation of a downstream process that converts waste generated from food and food processing industries into added value products with potential applications. Owing to innovative downstream and biotechnological processes, rather than a waste product may be considered a resource to obtain high added value products, such as food supplements (probiotics), cosmeceuticals, biopolymers, and recyclable purified water. Besides targeting gastrointestinal disorders, probiotics such as Lactobacilli have been reported to improve immunomodulation and protection of the host against infections caused by viral and bacterial pathogens. Interestingly, also inactivated microbial (probiotic) cells and their metabolic products, indicated as parabiotic and postbiotics, respectively, have a crucial role and act as mediators in the modulation of the host’s immune function. To boost the production of biomass (both viable and/or heat inactivated cells) and/or the synthesis of growth-related postbiotics, such as EPS, efficient and sustainable fermentation processes are necessary. Based on a “zero-waste” approach, wastes generated from local industries can be recovered and recycled to develop sustainable biotechnological processes to obtain probiotics as well as post and parabiotic, to be tested as bioactive compounds against gastrointestinal disorders. The results have shown it was possible to recover an ultrafiltration retentate with suitable characteristics to be used in skin dehydration, to perform films (i.e., packaging for food industries), or as a wound repair agent and a nanofiltration retentate to recover lactic acid and carbon sources (e.g., lactose, glucose..) used for microbial cultivation. On the side, the last goal is to obtain purified water that can be reused throughout the process. In fact, water reclamation and reuse provide a unique and viable opportunity to augment traditional water supplies, a key issue nowadays.

Keywords: biotech process, downstream process, probiotic growth, from waste to product, buffalo whey

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16 Recrystallization Behavior and Microstructural Evolution of Nickel Base Superalloy AD730 Billet during Hot Forging at Subsolvus Temperatures

Authors: Marcos Perez, Christian Dumont, Olivier Nodin, Sebastien Nouveau

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Nickel superalloys are used to manufacture high-temperature rotary engine parts such as high-pressure disks in gas turbine engines. High strength at high operating temperatures is required due to the levels of stress and heat the disk must withstand. Therefore it is necessary parts made from materials that can maintain mechanical strength at high temperatures whilst remain comparatively low in cost. A manufacturing process referred to as the triple melt process has made the production of cast and wrought (C&W) nickel superalloys possible. This means that the balance of cost and performance at high temperature may be optimized. AD730TM is a newly developed Ni-based superalloy for turbine disk applications, with reported superior service properties around 700°C when compared to Inconel 718 and several other alloys. The cast ingot is converted into billet during either cogging process or open die forging. The semi-finished billet is then further processed into its final geometry by forging, heat treating, and machining. Conventional ingot-to-billet conversion is an expensive and complex operation, requiring a significant amount of steps to break up the coarse as-cast structure and interdendritic regions. Due to the size of conventional ingots, it is difficult to achieve a uniformly high level of strain for recrystallization, resulting in non-recrystallized regions that retain large unrecrystallized grains. Non-uniform grain distributions will also affect the ultrasonic inspectability response, which is used to find defects in the final component. The main aim is to analyze the recrystallization behavior and microstructural evolution of AD730 at subsolvus temperatures from a semi-finished product (billet) under conditions representative of both cogging and hot forging operations. Special attention to the presence of large unrecrystallized grains was paid. Double truncated cones (DTCs) were hot forged at subsolvus temperatures in hydraulic press, followed by air cooling. SEM and EBSD analysis were conducted in the as-received (billet) and the as-forged conditions. AD730 from billet alloy presents a complex microstructure characterized by a mixture of several constituents. Large unrecrystallized grains present a substructure characterized by large misorientation gradients with the formation of medium to high angle boundaries in their interior, especially close to the grain boundaries, denoting inhomogeneous strain distribution. A fine distribution of intragranular precipitates was found in their interior, playing a key role on strain distribution and subsequent recrystallization behaviour during hot forging. Continuous dynamic recrystallization (CDRX) mechanism was found to be operating in the large unrecrystallized grains, promoting the formation intragranular DRX grains and the gradual recrystallization of these grains. Evidences that hetero-epitaxial recrystallization mechanism is operating in AD730 billet material were found. Coherent γ-shells around primary γ’ precipitates were found. However, no significant contribution to the overall recrystallization during hot forging was found. By contrast, strain presents the strongest effect on the microstructural evolution of AD730, increasing the recrystallization fraction and refining the structure. Regions with low level of deformation (ε ≤ 0.6) were translated into large fractions of unrecrystallized structures (strain accumulation). The presence of undissolved secondary γ’ precipitates (pinning effect), prior to hot forging operations, could explain these results.

Keywords: AD730 alloy, continuous dynamic recrystallization, hot forging, γ’ precipitates

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15 Modeling the Human Harbor: An Equity Project in New York City, New York USA

Authors: Lauren B. Birney

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The envisioned long-term outcome of this three-year research, and implementation plan is for 1) teachers and students to design and build their own computational models of real-world environmental-human health phenomena occurring within the context of the “Human Harbor” and 2) project researchers to evaluate the degree to which these integrated Computer Science (CS) education experiences in New York City (NYC) public school classrooms (PreK-12) impact students’ computational-technical skill development, job readiness, career motivations, and measurable abilities to understand, articulate, and solve the underlying phenomena at the center of their models. This effort builds on the partnership’s successes over the past eight years in developing a benchmark Model of restoration-based Science, Technology, Engineering, and Math (STEM) education for urban public schools and achieving relatively broad-based implementation in the nation’s largest public school system. The Billion Oyster Project Curriculum and Community Enterprise for Restoration Science (BOP-CCERS STEM + Computing) curriculum, teacher professional developments, and community engagement programs have reached more than 200 educators and 11,000 students at 124 schools, with 84 waterfront locations and Out of School of Time (OST) programs. The BOP-CCERS Partnership is poised to develop a more refined focus on integrating computer science across the STEM domains; teaching industry-aligned computational methods and tools; and explicitly preparing students from the city’s most under-resourced and underrepresented communities for upwardly mobile careers in NYC’s ever-expanding “digital economy,” in which jobs require computational thinking and an increasing percentage require discreet computer science technical skills. Project Objectives include the following: 1. Computational Thinking (CT) Integration: Integrate computational thinking core practices across existing middle/high school BOP-CCERS STEM curriculum as a means of scaffolding toward long term computer science and computational modeling outcomes. 2. Data Science and Data Analytics: Enabling Researchers to perform interviews with Teachers, students, community members, partners, stakeholders, and Science, Technology, Engineering, and Mathematics (STEM) industry Professionals. Collaborative analysis and data collection were also performed. As a centerpiece, the BOP-CCERS partnership will expand to include a dedicated computer science education partner. New York City Department of Education (NYCDOE), Computer Science for All (CS4ALL) NYC will serve as the dedicated Computer Science (CS) lead, advising the consortium on integration and curriculum development, working in tandem. The BOP-CCERS Model™ also validates that with appropriate application of technical infrastructure, intensive teacher professional developments, and curricular scaffolding, socially connected science learning can be mainstreamed in the nation’s largest urban public school system. This is evidenced and substantiated in the initial phases of BOP-CCERS™. The BOP-CCERS™ student curriculum and teacher professional development have been implemented in approximately 24% of NYC public middle schools, reaching more than 250 educators and 11,000 students directly. BOP-CCERS™ is a fully scalable and transferable educational model, adaptable to all American school districts. In all settings of the proposed Phase IV initiative, the primary beneficiary group will be underrepresented NYC public school students who live in high-poverty neighborhoods and are traditionally underrepresented in the STEM fields, including African Americans, Latinos, English language learners, and children from economically disadvantaged households. In particular, BOP-CCERS Phase IV will explicitly prepare underrepresented students for skilled positions within New York City’s expanding digital economy, computer science, computational information systems, and innovative technology sectors.

Keywords: computer science, data science, equity, diversity and inclusion, STEM education

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14 The Outcome of Early Balance Exercises and Agility Training in Sports Rehabilitation for Patients Post Anterior Cruciate Ligament (ACL) Reconstruction

Authors: S. M. A. Ismail, M. I. Ibrahim, H. Masdar, F. M. Effendi, M. F. Suhaimi, A. Suun

Abstract:

Introduction: It is generally known that the rehabilitation process is as important as the reconstruction surgery. Several literature has focused on how early the rehabilitation modalities can be initiated after the surgery to ensure a safe return of patients to sports or at least regaining the pre-injury level of function following an ACL reconstruction. Objectives: The main objective is to study and evaluate the outcome of early balance exercises and agility training in sports rehabilitation for patients post ACL reconstruction. To compare between early balance exercises and agility training as intervention and control. (material or non-material). All of them were recruited for material exercise (balance exercises and agility training with strengthening) and strengthening only rehabilitation protocol (non-material). Followed the prospective intervention trial. Materials and Methods: Post-operative ACL reconstruction patients performed in Selayang and Sg Buloh Hospitals from 2012 to 2014 were selected for this study. They were taken from Malaysian Knee Ligament Registry (MKLR) and all patients had single bundle reconstruction with autograft hamstring tendon (semitendinosus and gracilis). ACL injury from any type of sports were included. Subjects performed various type of physical activity for rehabilitation in every 18 week for a different type of rehab activity. All subject attended all 18 sessions of rehabilitation exercises and evaluation was done during the first, 9th and 18th session. Evaluation format were based on clinical assessment (anterior drawer, Lachmann, pivot shift, laxity with rolimeter, the end point and thigh circumference) and scoring (Lysholm Knee scoring and Tegner Activity Level scale). Rehabilitation protocol initiated from 24 week after the surgery. Evaluation format were based on clinical assessment (anterior drawer, Lachmann, pivot shift, laxity with rolimeter, the end point and thigh circumference) and scoring (Lysholm Knee scoring and Tegner Activity Level scale). Results and Discussion: 100 patients were selected of which 94 patients are male and 6 female. Age range is 18 to 54 year with the average of 28 years old for included 100 patients. All patients are evaluated after 24 week after the surgery. 50 of them were recruited for material exercise (balance exercises and agility training with strengthening) and 50 for strengthening only rehabilitation protocol (non-material). Demographically showed 85% suffering sports injury mainly from futsal and football. 39 % of them have abnormal BMI (26 – 38) and involving of the left knee. 100% of patient had the basic radiographic x-ray of knee and 98% had MRI. All patients had negative anterior drawer’s, Lachman test and Pivot shift test during the post ACL reconstruction after the complete rehabilitation. There was 95 subject sustained grade I injury, 5 of grade II and 0 of grade III with 90% of them had soft end-point. Overall they scored badly on presentation with 53% of Lysholm score (poor) and Tegner activity score level 3/10. After completing 9 weeks of exercises, of material group 90% had grade I laxity, 75% with firm end-point, Lysholm score 71% (fair) and Tegner activity level 5/10 comparing non-material group who had 62% of grade I laxity , 54% of firm end-point, Lyhslom score 62 % (poor) and Tegner activity level 4/10. After completed 18 weeks of exercises, of material group maintained 90% grade I laxity with 100 % with firm end-point, Lysholm score increase 91% (excellent) and Tegner activity level 7/10 comparing non-material group who had 69% of grade I laxity but maintained 54% of firm end-point, Lysholm score 76% (fair) and Tegner activity level 5/10. These showed the improvement were achieved fast on material group who have achieved satisfactory level after 9th cycle of exercises 75% (15/20) comparing non-material group who only achieved 54% (7/13) after completed 18th session. Most of them were grade I. These concepts are consolidated into our approach to prepare patients for return to play including field testing and maintenance training. Conclusions: The basic approach in ACL rehabilitation is to ensure return to sports at post-operative 6 month. Grade I and II laxity has favourable and early satisfactory outcome base on clinical assessment and Lysholm and Tegner scoring point. Reduction of laxity grading indicates satisfactory outcome. Firm end-point showed the adequacy of rehabilitation before starting previous sports game. Material exercise (balance exercises and agility training with strengthening) were beneficial and reliable in order to achieve favourable and early satisfactory outcome comparing strengthening only (non-material).We have identified that rehabilitation protocol varies between different patients. Therefore future post ACL reconstruction rehabilitation guidelines should look into focusing on rehabilitation techniques instead of time.

Keywords: post anterior cruciate ligament (ACL) reconstruction, single bundle, hamstring tendon, sports rehabilitation, balance exercises, agility balance

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13 Preparedness and Control of Mosquito-Borne Diseases: Experiences from Northwestern Italy

Authors: Federica Verna, Alessandra Pautasso, Maria Caramelli, Cristiana Maurella, Walter Mignone, Cristina Casalone

Abstract:

Mosquito-Borne Diseases (MBDs) are dangerously increasing in prevalence, geographical distribution and severity, representing an emerging threat for both humans and animals. Interaction between multiple disciplines is needed for an effective early warning, surveillance and control of MBDs, according to the One Health concept. This work reports the integrated surveillance system enforced by IZSPLV in Piedmont, Liguria and Valle d’Aosta regions (Northwestern Italy) in order to control MDBs spread. Veterinary services and local human health authority are involved in an information network, to connect the surveillance of human clinical cases with entomological surveillance and veterinary monitoring in order to implement control measures in case of outbreak. A systematic entomological surveillance is carried out during the vector season using mosquitoes traps located in sites selected according to risk factors. Collected mosquitoes are counted, identified to species level by morphological standard classification keys and pooled by collection site, date and species with a maximum of 100 individuals. Pools are analyzed, after RNA extraction, by Real Time RT-PCR distinctive for West Nile Virus (WNV) Lineage 1 and Lineage 2, Real Time RT-PCR USUTU virus (USUV) and a traditional flavivirus End-point RT-PCR. Positive pools are sequenced and the related sequences employed to perform a basic local alignment search tool (BLAST) in the GenBank library. Positive samples are sent to the National Reference Centre for Animal Exotic Diseases (CESME, Teramo) for confirmation. With particular reference to WNV, after the confirmation, as provided by national legislation, control measures involving both local veterinary and human health services are activated: equine sera are randomly sampled within a 4 km radius from the positive collection sites and tested with ELISA kit and WNV NAT screening of blood donors is introduced. This surveillance network allowed to detect since 2011 USUV circulation in this area of Italy. WNV was detected in Piedmont and Liguria for the first time in 2014 in mosquitoes. During the 2015 vector season, we observed the expansion of its activity in Piedmont. The virus was detected in almost all Provinces both in mosquitoes (6 pools) and animals (19 equine sera, 4 birds). No blood bag tested resulted infected. The first neuroinvasive human case occurred too. Competent authorities should be aware of a potentially increased risk of MBDs activity during the 2016 vector season. This work shows that this surveillance network allowed to early detect the presence of MBDs in humans and animals, and provided useful information to public authorities, in order to apply control measures. Finally, an additional value of our diagnostic protocol is the ability to detect all viruses belonging to the Flaviviridae family, considering the emergence caused by other Flaviviruses in humans such as the recent Zika virus infection in South America. Italy has climatic and environmental features conducive to Zika virus transmission, the competent vector and many travellers from Brazil reported every year.

Keywords: integrated surveillance, mosquito borne disease, West Nile virus, Zika virus

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12 Language Anxiety and Learner Achievement among University Undergraduates in Sri Lanka: A Case Study of University of Sri Jayewardenepura

Authors: Sujeeva Sebastian Pereira

Abstract:

Language Anxiety (LA) – a distinct psychological construct of self-perceptions and behaviors related to classroom language learning – is perceived as a significant variable highly correlated with Second Language Acquisition (SLA). However, the existing scholarship has inadequately explored the nuances of LA in relation to South Asia, especially in terms of Sri Lankan higher education contexts. Thus, the current study, situated within the broad areas of Psychology of SLA and Applied Linguistics, investigates the impact of competency-based LA and identity-based LA on learner achievement among undergraduates of Sri Lanka. Employing a case study approach to explore the impact of LA, 750 undergraduates of the University of Sri Jayewardenepura, Sri Lanka, thus covering 25% of the student population from all seven faculties of the university, were selected as participants using stratified proportionate sampling in terms of ethnicity, gender, and disciplines. The qualitative and quantitative research inquiry utilized for data collection include a questionnaire consisting a set of structured and unstructured questions, and semi-structured interviews as research instruments. Data analysis includes both descriptive and statistical measures. As per the quantitative measures of data analysis, the study employed Pearson Correlation Coefficient test, Chi-Square test, and Multiple Correspondence Analysis; it used LA as the dependent variable, and two types of independent variables were used: direct and indirect variables. Direct variables encompass the four main language skills- reading, writing, speaking and listening- and test anxiety. These variables were further explored through classroom activities on grammar, vocabulary and individual and group presentations. Indirect variables are identity, gender and cultural stereotypes, discipline, social background, income level, ethnicity, religion and parents’ education level. Learner achievement was measured through final scores the participants have obtained for Compulsory English- a common first-year course unit mandatory for all undergraduates. LA was measured using the FLCAS. In order to increase the validity and reliability of the study, data collected were triangulated through descriptive content analysis. Clearly evident through both the statistical analysis and the qualitative analysis of the results is the significant linear negative correlation between LA and learner achievement, and the significant negative correlation between LA and culturally-operated gender stereotypes which create identity disparities in learners. The study also found that both competency-based LA and identity-based LA are experienced primarily and inescapably due to the apprehensions regarding speaking in English. Most participants who reported high levels of LA were from an urban socio-economic background of lower income families. Findings exemplify the linguistic inequality prevalent in the socio-cultural milieu in Sri Lankan society. This inequality makes learning English a dire need, yet, very much an anxiety provoking process because of many sociolinguistic, cultural and ideological factors related to English as a Second Language (ESL) in Sri Lanka. The findings bring out the intricate interrelatedness of both the dependent variable (LA) and the independent variables stated above, emphasizing that the significant linear negative correlation between LA and learner achievement is connected to the affective, cognitive and sociolinguistic domains of SLA. Thus, the study highlights the promise in linguistic practices such as code-switching, crossing and accommodating hybrid identities as strategies in minimizing LA and maximizing the experience of ESL.

Keywords: language anxiety, identity-based anxiety, competence-based anxiety, TESL, Sri Lanka

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

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

Abstract:

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

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

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10 Design of DNA Origami Structures Using LAMP Products as a Combined System for the Detection of Extended Spectrum B-Lactamases

Authors: Kalaumari Mayoral-Peña, Ana I. Montejano-Montelongo, Josué Reyes-Muñoz, Gonzalo A. Ortiz-Mancilla, Mayrin Rodríguez-Cruz, Víctor Hernández-Villalobos, Jesús A. Guzmán-López, Santiago García-Jacobo, Iván Licona-Vázquez, Grisel Fierros-Romero, Rosario Flores-Vallejo

Abstract:

The group B-lactamic antibiotics include some of the most frequently used small drug molecules against bacterial infections. Nevertheless, an alarming decrease in their efficacy has been reported due to the emergence of antibiotic-resistant bacteria. Infections caused by bacteria expressing extended Spectrum B-lactamases (ESBLs) are difficult to treat and account for higher morbidity and mortality rates, delayed recovery, and high economic burden. According to the Global Report on Antimicrobial Resistance Surveillance, it is estimated that mortality due to resistant bacteria will ascend to 10 million cases per year worldwide. These facts highlight the importance of developing low-cost and readily accessible detection methods of drug-resistant ESBLs bacteria to prevent their spread and promote accurate and fast diagnosis. Bacterial detection is commonly done using molecular diagnostic techniques, where PCR stands out for its high performance. However, this technique requires specialized equipment not available everywhere, is time-consuming, and has a high cost. Loop-Mediated Isothermal Amplification (LAMP) is an alternative technique that works at a constant temperature, significantly decreasing the equipment cost. It yields double-stranded DNA of several lengths with repetitions of the target DNA sequence as a product. Although positive and negative results from LAMP can be discriminated by colorimetry, fluorescence, and turbidity, there is still a large room for improvement in the point-of-care implementation. DNA origami is a technique that allows the formation of 3D nanometric structures by folding a large single-stranded DNA (scaffold) into a determined shape with the help of short DNA sequences (staples), which hybridize with the scaffold. This research aimed to generate DNA origami structures using LAMP products as scaffolds to improve the sensitivity to detect ESBLs in point-of-care diagnosis. For this study, the coding sequence of the CTM-X-15 ESBL of E. coli was used to generate the LAMP products. The set of LAMP primers were designed using PrimerExplorerV5. As a result, a target sequence of 200 nucleotides from CTM-X-15 ESBL was obtained. Afterward, eight different DNA origami structures were designed using the target sequence in the SDCadnano and analyzed with CanDo to evaluate the stability of the 3D structures. The designs were constructed minimizing the total number of staples to reduce costs and complexity for point-of-care applications. After analyzing the DNA origami designs, two structures were selected. The first one was a zig-zag flat structure, while the second one was a wall-like shape. Given the sequence repetitions in the scaffold sequence, both were able to be assembled with only 6 different staples each one, ranging between 18 to 80 nucleotides. Simulations of both structures were performed using scaffolds of different sizes yielding stable structures in all the cases. The generation of the LAMP products were tested by colorimetry and electrophoresis. The formation of the DNA structures was analyzed using electrophoresis and colorimetry. The modeling of novel detection methods through bioinformatics tools allows reliable control and prediction of results. To our knowledge, this is the first study that uses LAMP products and DNA-origami in combination to delect ESBL-producing bacterial strains, which represent a promising methodology for diagnosis in the point-of-care.

Keywords: beta-lactamases, antibiotic resistance, DNA origami, isothermal amplification, LAMP technique, molecular diagnosis

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9 Highly Robust Crosslinked BIAN-based Binder to Stabilize High-Performance Silicon Anode in Lithium-Ion Secondary Battery

Authors: Agman Gupta, Rajashekar Badam, Noriyoshi Matsumi

Abstract:

Introduction: Recently, silicon has been recognized as one of the potential alternatives as anode active material in Li-ion batteries (LIBs) to replace the conventionally used graphite anodes. Silicon is abundantly present in the nature, it can alloy with lithium metal, and has a higher theoretical capacity (~4200 mAhg-1) that is approximately 10 times higher than graphite. However, because of a large volume expansion (~400%) upon repeated de-/alloying, the pulverization of Si particles causes the exfoliation of electrode laminate leading to the loss of electrical contact and adversely affecting the formation of solid-electrolyte interface (SEI).1 Functional polymers as binders have emerged as a competitive strategy to mitigate these drawbacks and failure mechanism of silicon anodes.1 A variety of aqueous/non-aqueous polymer binders like sodium carboxy-methyl cellulose (CMC-Na), styrene butadiene rubber (SBR), poly(acrylic acid), and other variants like mussel inspired binders have been investigated to overcome these drawbacks.1 However, there are only a few reports that mention the attempt of addressing all the drawbacks associated with silicon anodes effectively using a single novel functional polymer system as a binder. In this regard, here, we report a novel highly robust n-type bisiminoacenaphthenequinone (BIAN)-paraphenylene-based crosslinked polymer as a binder for Si anodes in lithium-ion batteries (Fig. 1). On its application, crosslinked-BIAN binder was evaluated to provide mechanical robustness to the large volume expansion of Si particles, maintain electrical conductivity within the electrode laminate, and facilitate in the formation of a thin SEI by restricting the extent of electrolyte decomposition on the surface of anode. The fabricated anodic half-cells were evaluated electrochemically for their rate capability, cyclability, and discharge capacity. Experimental: The polymerized BIAN (P-BIAN) copolymer was synthesized as per the procedure reported by our group.2 The synthesis of crosslinked P-BIAN: a solution of P-BIAN copolymer (1.497 g, 10 mmol) in N-methylpyrrolidone (NMP) (150 ml) was set-up to stir under reflux in nitrogen atmosphere. To this, 1,6-dibromohexane (5 mmol, 0.77 ml) was added dropwise. The resultant reaction mixture was stirred and refluxed at 150 °C for 24 hours followed by refrigeration for 3 hours at 5 °C. The product was obtained by evaporating the NMP solvent under reduced pressure and drying under vacuum at 120 °C for 12 hours. The obtained product was a black colored sticky compound. It was characterized by 1H-NMR, XPS, and FT-IR techniques. Results and Discussion: The N 1s XPS spectrum of the crosslinked BIAN polymer showed two characteristic peaks corresponding to the sp2 hybridized nitrogen (-C=N-) at 399.6 eV of the diimine backbone in the BP and quaternary nitrogen at 400.7 eV corresponding to the crosslinking of BP via dibromohexane. The DFT evaluation of the crosslinked BIAN binder showed that it has a low lying lowest unoccupied molecular orbital (LUMO) that enables it to get doped in the reducing environment and influence the formation of a thin (SEI). Therefore, due to the mechanically robust crosslinked matrices as well as its influence on the formation of a thin SEI, the crosslinked BIAN binder stabilized the Si anode-based half-cell for over 1000 cycles with a reversible capacity of ~2500 mAhg-1 and ~99% capacity retention as shown in Fig. 2. The dynamic electrochemical impedance spectroscopy (DEIS) characterization of crosslinked BIAN-based anodic half-cell confirmed that the SEI formed was thin in comparison with the conventional binder-based anodes. Acknowledgement: We are thankful to the financial support provided by JST-Mirai Program, Grant Number: JP18077239

Keywords: self-healing binder, n-type binder, thin solid-electrolyte interphase (SEI), high-capacity silicon anodes, low-LUMO

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8 Amifostine Analogue, Drde-30, Attenuates Radiation-Induced Lung Injury in Mice

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

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7 Development of Chitosan/Dextran Gelatin Methacrylate Core/Shell 3D Scaffolds and Protein/Polycaprolactone Melt Electrowriting Meshes for Tissue Regeneration Applications

Authors: J. D. Cabral, E. Murray, P. Turner, E. Hewitt, A. Ali, M. McConnell

Abstract:

Worldwide demand for organ replacement and tissue regeneration is progressively increasing. Three-dimensional (3D) bioprinting, where a physical construct is produced using computer-aided design, is a promising tool to advance the tissue engineering and regenerative medicine fields. In this paper we describe two different approaches to developing 3D bioprinted constructs for use in tissue regeneration. Bioink development is critical in achieving the 3D biofabrication of functional, regenerative tissues. Hydrogels, cross-linked macromolecules that absorb large amounts of water, have received widespread interest as bioinks due to their relevant soft tissue mechanics, biocompatibility, and tunability. In turn, not only is bioink optimisation crucial, but the creation of vascularized tissues remains a key challenge for the successful fabrication of thicker, more clinically relevant bioengineered tissues. Among the various methodologies, cell-laden hydrogels are regarded as a favorable approach; and when combined with novel core/shell 3D bioprinting technology, an innovative strategy towards creating new vessel-like structures. In this work, we investigate this cell-based approach by using human umbilical endothelial cells (HUVECs) entrapped in a viscoelastic chitosan/dextran (CD)-based core hydrogel, printed simulataneously along with a gelatin methacrylate (GelMA) shell. We have expanded beyond our previously reported FDA approved, commercialised, post-surgical CD hydrogel, Chitogel®, by functionalizing it with cell adhesion and proteolytic peptides in order to promote bone marrow-derived mesenchymal stem cell (immortalized BMSC cell line, hTERT) and HUVECs growth. The biocompatibility and biodegradability of these cell lines in a 3D bioprinted construct is demonstrated. Our studies show that particular peptide combinations crosslinked within the CD hydrogel was found to increase in vitro growth of BMSCs and HUVECs by more than two-fold. These gels were then used as a core bioink combined with the more mechanically robust, UV irradiated GelMA shell bioink, to create 3D regenerative, vessel-like scaffolds with high print fidelity. As well, microporous MEW scaffolds made from milk proteins blended with PCL were found to show promising bioactivity, exhibiting a significant increase in keratinocyte (HaCaTs) and fibroblast (normal human dermal fibroblasts, NhDFs) cell migration and proliferation when compared to PCL only scaffolds. In conclusion, our studies indicate that a peptide functionalized CD hydrogel bioink reinforced with a GelMA shell is biocompatible, biodegradable, and an appropriate cell delivery vehicle in the creation of regenerative 3D constructs. In addition, a novel 3D printing technique, melt electrowriting (MEW), which allows fabrication of micrometer fibre meshes, was used to 3D print polycaprolactone (PCL) and bioactive milk protein, lactorferrin (LF) and whey protein (WP), blended scaffolds for potential skin regeneration applications. MEW milk protein/PCL scaffolds exhibited high porosity characteristics, low overall biodegradation, and rapid protein release. Human fibroblasts and keratinocyte cells were seeded on to the scaffolds. Scaffolds containing high concentrations of LF and combined proteins (LF+WP) showed improved cell viability over time as compared to PCL only scaffolds. This research highlights two scaffolds made using two different 3D printing techniques using a combination of both natural and synthetic biomaterial components in order to create regenerative constructs as potential chronic wound treatments.

Keywords: biomaterials, hydrogels, regenerative medicine, 3D bioprinting

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6 Maternity Care Model during Natural Disaster or Humanitarian Emegerncy Setting in Rural Pakistan

Authors: Humaira Maheen, Elizabeth Hoban, Catherine Bennette

Abstract:

Background: Globally, role of Community Health Workers (CHW) as front line disaster health work force is underutilized. Developing countries which are at risk of natural disasters or humanitarian emergencies should lay down effective strategies especially to ensure adequate access to maternity care during crisis situation by using CHW as they are local, trained, and most of them possess a good relationship with the community. The Minimum Initial Service Package (MISP) is a set of universal guidelines that addresses women’s reproductive health needs during the first phase of an emergency. According to the MISP, pregnant women should have access to a skilled birth attendant and adequate transportation arrangements so they can access a maternity care facility. Pakistan is one of the few countries which has been severely affected by a number of natural disaster as well as humanitarian emergencies in last decade. Pakistan has a young and structured National Disaster Management System in place, where District Authorities play a vital role in disaster management. The District Health Department develops the contingency health plan for an emergency situation and implements it under the existing district health human resources (health workers and medical staff at the health facility) and infrastructure (health care facilities). Methods: A mixed methods study was conducted in rural villages of Sindh adjacent to the river Indus, and included in-depth interviews with 15 women who gave birth during the floods, structured interviews with 668 women who were pregnant during 2010-2014, and in-depth interviews with 25 community health workers (CHW) and 30 key informants. Results: Women said that giving birth in the relief camps during the floods was one of the most challenging times of their life. The district health department didn’t make transportation arrangement for labouring women from relief camp to the nearest health care facility. As a result 91.2% women gave birth in temporary shelters with the help of a traditional birth attendant (Dai) with no clean physical space available to birth. Of the 332 women who were pregnant at the time of the floods, 26 had adverse birth outcomes; 10 had miscarriages, 14 had stillbirths and there were four neonatal deaths. Conclusion: The district health department was not able to provide access to adequate maternity care during according to the international standard during the floods in 2011. We propose a model where CHWs will be used as frontline maternity care providers during any emergency or disaster situations in Pakistan. A separate "birthing station" should be mandatory in all district relief camps, managed by CHWs. Community midwives (CMW) would and the Lady Health Workers (LHW) would provide antenatal and postnatal care alongside, vaccination for pregnant women, neonates and children under five. There must be an ambulance facility for emergency obstetric cases and all district health facilities should have at least two medical staff identified and trained for emergency obstetric management. The District Health Department must provide clean birthing kits and regular and emergency contraceptives in the relief camps. Methods: A mixed methods study was conducted in rural villages of Sindh adjacent to the river Indus, and included in-depth interviews with 15 women who gave birth during the floods, structured interviews with 668 women who were pregnant during 2010-2014, and in-depth interviews with 25 community health workers (CHW) and 30 key informants. Results: Women said that giving birth in the relief camps during the floods was one of the most challenging times of their life. Nearly 91.2% women gave birth in temporary shelters with the help of a traditional birth attendant (Dai) with no clean physical space available to birth, and the health camp was mostly accessed by men and always overcrowded. There was no obstetric trained medical staff in the health camps or transportation provided to take women with complications to the nearest health facility. The rate of adverse outcome following disaster was 22.2% (95% CI: 8.62% – 42.2%) amongst 27 women who did not evacuate as compare to 7.91% (95% CI: 5.03% – 11.8%) among 278 women who lived in relief camp study participants. There were 27 women who evacuated on pre-flood warning and had 0% rate of adverse outcome. Conclusion: We propose a model where CHWs will be used as frontline maternity care providers during any emergency or disaster situations in Pakistan. A separate "birthing station" should be mandatory in all district relief camps, managed by CHWs. Community midwives (CMW) would and the Lady Health Workers (LHW) would provide antenatal and postnatal care alongside, vaccination for pregnant women, neonates and children under five. There must be an ambulance facility for emergency obstetric cases and all district health facilities should have at least two medical staff identified and trained for emergency obstetric management. The District Health Department must provide clean birthing kits and regular and emergency contraceptives in the relief camps.

Keywords: natural disaster, maternity care model, rural, Pakistan, community health workers

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5 Ultra-Rapid and Efficient Immunomagnetic Separation of Listeria Monocytogenes from Complex Samples in High-Gradient Magnetic Field Using Disposable Magnetic Microfluidic Device

Authors: L. Malic, X. Zhang, D. Brassard, L. Clime, J. Daoud, C. Luebbert, V. Barrere, A. Boutin, S. Bidawid, N. Corneau, J. Farber, T. Veres

Abstract:

The incidence of infections caused by foodborne pathogens such as Listeria monocytogenes (L. monocytogenes) poses a great potential threat to public health and safety. These issues are further exacerbated by legal repercussions due to “zero tolerance” food safety standards adopted in developed countries. Unfortunately, a large number of related disease outbreaks are caused by pathogens present in extremely low counts currently undetectable by available techniques. The development of highly sensitive and rapid detection of foodborne pathogens is therefore crucial, and requires robust and efficient pre-analytical sample preparation. Immunomagnetic separation is a popular approach to sample preparation. Microfluidic chips combined with external magnets have emerged as viable high throughput methods. However, external magnets alone are not suitable for the capture of nanoparticles, as very strong magnetic fields are required. Devices that incorporate externally applied magnetic field and microstructures of a soft magnetic material have thus been used for local field amplification. Unfortunately, very complex and costly fabrication processes used for integration of soft magnetic materials in the reported proof-of-concept devices would prohibit their use as disposable tools for food and water safety or diagnostic applications. We present a sample preparation magnetic microfluidic device implemented in low-cost thermoplastic polymers using fabrication techniques suitable for mass-production. The developed magnetic capture chip (M-chip) was employed for rapid capture and release of L. monocytogenes conjugated to immunomagnetic nanoparticles (IMNs) in buffer and beef filtrate. The M-chip relies on a dense array of Nickel-coated high-aspect ratio pillars for capture with controlled magnetic field distribution and a microfluidic channel network for sample delivery, waste, wash and recovery. The developed Nickel-coating process and passivation allows generation of switchable local perturbations within the uniform magnetic field generated with a pair of permanent magnets placed at the opposite edges of the chip. This leads to strong and reversible trapping force, wherein high local magnetic field gradients allow efficient capture of IMNs conjugated to L. monocytogenes flowing through the microfluidic chamber. The experimental optimization of the M-chip was performed using commercially available magnetic microparticles and fabricated silica-coated iron-oxide nanoparticles. The fabricated nanoparticles were optimized to achieve the desired magnetic moment and surface functionalization was tailored to allow efficient capture antibody immobilization. The integration, validation and further optimization of the capture and release protocol is demonstrated using both, dead and live L. monocytogenes through fluorescence microscopy and plate- culture method. The capture efficiency of the chip was found to vary as function of listeria to nanoparticle concentration ratio. The maximum capture efficiency of 30% was obtained and the 24-hour plate-culture method allowed the detection of initial sample concentration of only 16 cfu/ml. The device was also very efficient in concentrating the sample from a 10 ml initial volume. Specifically, 280% concentration efficiency was achieved in 17 minutes only, demonstrating the suitability of the system for food safety applications. In addition, flexible design and low-cost fabrication process will allow rapid sample preparation for applications beyond food and water safety, including point-of-care diagnosis.

Keywords: array of pillars, bacteria isolation, immunomagnetic sample preparation, polymer microfluidic device

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4 Microdiamond and Moissanite Inclusions in Garnets from Pohorje Mountains, Eastern Alps, Slovenia

Authors: Mirijam Vrabec, Marian Janak, Bojan Ambrozic, Angelja K. Surca, Nastja Rogan Smuc, Nina Zupancic, Saso Sturm

Abstract:

Natural microdiamonds and moissanite (SiC) can form during the orogenic events under ultrahigh-pressure metamorphic conditions (UHP), when parts of Earth’s crust are subducted to extreme depths. So far, such processes were identified only in few places on the Earth, and therefore, represent unique opportunity to study the evolution of the Earth’s deep interior. An important discovery of microdiamonds and moissanite was reported from Pohorje, (Slovenia), where they occurred as single or polyphase inclusions in garnets. Metasedimentary rocks from Pohorje are predominantly gneisses representing parts of the Austroalpine metamorphic units of the Eastern Alps. During Cretaceous orogeny, (ca. 95–92 Ma) continental crustal rocks were deeply subducted to the mantle depths (below 100 km) and metamorphosed at pressures exceeding 3.5 GPa and temperatures between 800–850 °C. Microstructural and phase analysis of the inclusions as well as detailed elemental analysis of host garnets were carried out combining several analytical techniques: optical microscope in plane polarized transmitted light, electron probe microanalysis (EPMA) with wavelength-dispersive x-ray spectrometry (WDS) and field-emission scanning microscope (FEG-SEM) with energy-dispersive x-ray spectroscopy (EDS). Micro-Raman analysis revealed sharp, first order diamond bands sometimes accompanied by graphite bands implying that transformation of diamond back to graphite occurred. To study the chemical and crystallographic relationship between microdiamonds and co-inclusions, advanced techniques of transmission electron microscopy (TEM) were applied, which included high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM), combined with EDS and electron energy-loss spectroscopy (EELS). To prepare electron transparent TEM lamellae selectively a dual-beam Focused Ion Beam/SEM (FIB/SEM) was employed. Detailed study of TEM lamellae, which was cross-sectioned from the highly faceted inclusion body located within the host garnet crystal matrix, revealed rich and rather complex internal structure. Namely, the negative crystal facets of the main inclusion body were typically decorated with up to 1 μm thick amorphous layer, reflecting the general garnet composition with slight variations in Fe/Ca content. Within these layers, ELNES analysis revealed the presence of a 28–30 nm thick layer of amorphous carbon. The very last section of this layer corresponds to composition of SiO2. Within the inclusion, besides diamond and moissanite alumosilicate mineral with pronounced layered structure, iron sulfides and chlorine were identified under TEM and CO2 and CH4 using Raman. Moissanite is found as single crystal or composed from numerous highly textured nano-crystals with the average size of 10 nm. Moissanite inclusions were found embedded inside the amorphous crust implying that moissanite crystalized well before the deposition of the amorphous layer. From the microstructural, crystallographic and chemical observations so far we can deduce, that polyphase inclusions in diamond bearing garnets from Pohorje most probably crystallized from reduced supercritical fluids. Based on layered interface structure of the host mineral multiphase process of crystallization is possible. The presence of microdiamonds and moissanite in rocks from Pohorje demonstrates that these parts of the Eastern Alps were subducted to extreme depths, and were subsequently exhumed back to the Earth's surface without complete breakdown of UHP mineral phases, allowing a rear and exceptional opportunity to study them in-situ.

Keywords: diamond, fluid inclusions, moissanite, TEM, UHP metamorphism.

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