Search results for: hybrid fault diagnosis
Commenced in January 2007
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Paper Count: 4027

Search results for: hybrid fault diagnosis

67 Quantum Dots Incorporated in Biomembrane Models for Cancer Marker

Authors: Thiago E. Goto, Carla C. Lopes, Helena B. Nader, Anielle C. A. Silva, Noelio O. Dantas, José R. Siqueira Jr., Luciano Caseli

Abstract:

Quantum dots (QD) are semiconductor nanocrystals that can be employed in biological research as a tool for fluorescence imagings, having the potential to expand in vivo and in vitro analysis as cancerous cell biomarkers. Particularly, cadmium selenide (CdSe) magic-sized quantum dots (MSQDs) exhibit stable luminescence that is feasible for biological applications, especially for imaging of tumor cells. For these facts, it is interesting to know the mechanisms of action of how such QDs mark biological cells. For that, simplified models are a suitable strategy. Among these models, Langmuir films of lipids formed at the air-water interface seem to be adequate since they can mimic half a membrane. They are monomolecular films formed at liquid-gas interfaces that can spontaneously form when organic solutions of amphiphilic compounds are spread on the liquid-gas interface. After solvent evaporation, the monomolecular film is formed, and a variety of techniques, including tensiometric, spectroscopic and optic can be applied. When the monolayer is formed by membrane lipids at the air-water interface, a model for half a membrane can be inferred where the aqueous subphase serve as a model for external or internal compartment of the cell. These films can be transferred to solid supports forming the so-called Langmuir-Blodgett (LB) films, and an ampler variety of techniques can be additionally used to characterize the film, allowing for the formation of devices and sensors. With these ideas in mind, the objective of this work was to investigate the specific interactions of CdSe MSQDs with tumorigenic and non-tumorigenic cells using Langmuir monolayers and LB films of lipids and specific cell extracts as membrane models for diagnosis of cancerous cells. Surface pressure-area isotherms and polarization modulation reflection-absorption spectroscopy (PM-IRRAS) showed an intrinsic interaction between the quantum dots, inserted in the aqueous subphase, and Langmuir monolayers, constructed either of selected lipids or of non-tumorigenic and tumorigenic cells extracts. The quantum dots expanded the monolayers and changed the PM-IRRAS spectra for the lipid monolayers. The mixed films were then compressed to high surface pressures and transferred from the floating monolayer to solid supports by using the LB technique. Images of the films were then obtained with atomic force microscopy (AFM) and confocal microscopy, which provided information about the morphology of the films. Similarities and differences between films with different composition representing cell membranes, with or without CdSe MSQDs, was analyzed. The results indicated that the interaction of quantum dots with the bioinspired films is modulated by the lipid composition. The properties of the normal cell monolayer were not significantly altered, whereas for the tumorigenic cell monolayer models, the films presented significant alteration. The images therefore exhibited a stronger effect of CdSe MSQDs on the models representing cancerous cells. As important implication of these findings, one may envisage for new bioinspired surfaces based on molecular recognition for biomedical applications.

Keywords: biomembrane, langmuir monolayers, quantum dots, surfaces

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66 Mineralized Nanoparticles as a Contrast Agent for Ultrasound and Magnetic Resonance Imaging

Authors: Jae Won Lee, Kyung Hyun Min, Hong Jae Lee, Sang Cheon Lee

Abstract:

To date, imaging techniques have attracted much attention in medicine because the detection of diseases at an early stage provides greater opportunities for successful treatment. Consequently, over the past few decades, diverse imaging modalities including magnetic resonance (MR), positron emission tomography, computed tomography, and ultrasound (US) have been developed and applied widely in the field of clinical diagnosis. However, each of the above-mentioned imaging modalities possesses unique strengths and intrinsic weaknesses, which limit their abilities to provide accurate information. Therefore, multimodal imaging systems may be a solution that can provide improved diagnostic performance. Among the current medical imaging modalities, US is a widely available real-time imaging modality. It has many advantages including safety, low cost and easy access for patients. However, its low spatial resolution precludes accurate discrimination of diseased region such as cancer sites. In contrast, MR has no tissue-penetrating limit and can provide images possessing exquisite soft tissue contrast and high spatial resolution. However, it cannot offer real-time images and needs a comparatively long imaging time. The characteristics of these imaging modalities may be considered complementary, and the modalities have been frequently combined for the clinical diagnostic process. Biominerals such as calcium carbonate (CaCO3) and calcium phosphate (CaP) exhibit pH-dependent dissolution behavior. They demonstrate pH-controlled drug release due to the dissolution of minerals in acidic pH conditions. In particular, the application of this mineralization technique to a US contrast agent has been reported recently. The CaCO3 mineral reacts with acids and decomposes to generate calcium dioxide (CO2) gas in an acidic environment. These gas-generating mineralized nanoparticles generated CO2 bubbles in the acidic environment of the tumor, thereby allowing for strong echogenic US imaging of tumor tissues. On the basis of this previous work, it was hypothesized that the loading of MR contrast agents into the CaCO3 mineralized nanoparticles may be a novel strategy in designing a contrast agent for dual imaging. Herein, CaCO3 mineralized nanoparticles that were capable of generating CO2 bubbles to trigger the release of entrapped MR contrast agents in response to tumoral acidic pH were developed for the purposes of US and MR dual-modality imaging of tumors. Gd2O3 nanoparticles were selected as an MR contrast agent. A key strategy employed in this study was to prepare Gd2O3 nanoparticle-loaded mineralized nanoparticles (Gd2O3-MNPs) using block copolymer-templated CaCO3 mineralization in the presence of calcium cations (Ca2+), carbonate anions (CO32-) and positively charged Gd2O3 nanoparticles. The CaCO3 core was considered suitable because it may effectively shield Gd2O3 nanoparticles from water molecules in the blood (pH 7.4) before decomposing to generate CO2 gas, triggering the release of Gd2O3 nanoparticles in tumor tissues (pH 6.4~7.4). The kinetics of CaCO3 dissolution and CO2 generation from the Gd2O3-MNPs were examined as a function of pH and pH-dependent in vitro magnetic relaxation; additionally, the echogenic properties were estimated to demonstrate the potential of the particles for the tumor-specific US and MR imaging.

Keywords: calcium carbonate, mineralization, ultrasound imaging, magnetic resonance imaging

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65 Benzenepropanamine Analogues as Non-detergent Microbicidal Spermicide for Effective Pre-exposure Prophylaxis

Authors: Veenu Bala, Yashpal S. Chhonker, Bhavana Kushwaha, Rabi S. Bhatta, Gopal Gupta, Vishnu L. Sharma

Abstract:

According to UNAIDS 2013 estimate nearly 52% of all individuals living with HIV are now women of reproductive age (15–44 years). Seventy-five percent cases of HIV acquisition are through heterosexual contacts and sexually transmitted infections (STIs), attributable to unsafe sexual behaviour. Each year, an estimated 500 million people acquire atleast one of four STIs: chlamydia, gonorrhoea, syphilis and trichomoniasis. Trichomonas vaginalis (TV) is exclusively sexually transmitted in adults, accounting for 30% of STI cases and associated with pelvic inflammatory disease (PID), vaginitis and pregnancy complications in women. TV infection resulted in impaired vaginal milieu, eventually favoring HIV transmission. In the absence of an effective prophylactic HIV vaccine, prevention of new infections has become a priority. It was thought worthwhile to integrate HIV prevention and reproductive health services including unintended pregnancy protection for women as both are related with unprotected sex. Initially, nonoxynol-9 (N-9) had been proposed as a spermicidal agent with microbicidal activity but on the contrary it increased HIV susceptibility due to surfactant action. Thus, to accomplish an urgent need of novel woman controlled non-detergent microbicidal spermicides benzenepropanamine analogues have been synthesized. At first, five benzenepropanamine-dithiocarbamate hybrids have been synthesized and evaluated for their spermicidal, anti-Trichomonas and anti-fungal activities along with safety profiling to cervicovaginal cells. In order to further enhance the scope of above study benzenepropanamine was hybridized with thiourea as to introduce anti-HIV potential. The synthesized hybrid molecules were evaluated for their reverse transcriptase (RT) inhibition, spermicidal, anti-Trichomonas and antimicrobial activities as well as their safety against vaginal flora and cervical cells. simulated vaginal fluid (SVF) stability and pharmacokinetics of most potent compound versus N-9 was examined in female Newzealand (NZ) rabbits to observe its absorption into systemic circulation and subsequent exposure in blood plasma through vaginal wall. The study resulted in the most promising compound N-butyl-4-(3-oxo-3-phenylpropyl) piperazin-1-carbothioamide (29) exhibiting better activity profile than N-9 as it showed RT inhibition (72.30 %), anti-Trichomonas (MIC, 46.72 µM against MTZ susceptible and MIC, 187.68 µM against resistant strain), spermicidal (MEC, 0.01%) and antifungal activity (MIC, 3.12–50 µg/mL) against four fungal strains. The high safety against vaginal epithelium (HeLa cells) and compatibility with vaginal flora (lactobacillus), SVF stability and least vaginal absorption supported its suitability for topical vaginal application. Docking study was performed to gain an insight into the binding mode and interactions of the most promising compound, N-butyl-4-(3-oxo-3-phenylpropyl) piperazin-1-carbothioamide (29) with HIV-1 Reverse Transcriptase. The docking study has revealed that compound (29) interacted with HIV-1 RT similar to standard drug Nevirapine. It may be concluded that hybridization of benzenepropanamine and thiourea moiety resulted into novel lead with multiple activities including RT inhibition. A further lead optimization may result into effective vaginal microbicides having spermicidal, anti-Trichomonas, antifungal and anti-HIV potential altogether with enhanced safety to cervico-vaginal cells in comparison to Nonoxynol-9.

Keywords: microbicidal, nonoxynol-9, reverse transcriptase, spermicide

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64 Exploitation Pattern of Atlantic Bonito in West African Waters: Case Study of the Bonito Stock in Senegalese Waters

Authors: Ousmane Sarr

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The Senegalese coasts have high productivity of fishery resources due to the frequency of intense up-welling system that occurs along its coast, caused by the maritime trade winds making its waters nutrients rich. Fishing plays a primordial role in Senegal's socioeconomic plans and food security. However, a global diagnosis of the Senegalese maritime fishing sector has highlighted the challenges this sector encounters. Among these concerns, some significant stocks, a priority target for artisanal fishing, need further assessment. If no efforts are made in this direction, most stock will be overexploited or even in decline. It is in this context that this research was initiated. This investigation aimed to apply a multi-modal approach (LBB, Catch-only-based CMSY model and its most recent version (CMSY++); JABBA, and JABBA-Select) to assess the stock of Atlantic bonito, Sarda sarda (Bloch, 1793) in the Senegalese Exclusive Economic Zone (SEEZ). Available catch, effort, and size data from Atlantic bonito over 15 years (2004-2018) were used to calculate the nominal and standardized CPUE, size-frequency distribution, and length at retentions (50 % and 95 % selectivity) of the species. These relevant results were employed as input parameters for stock assessment models mentioned above to define the stock status of this species in this region of the Atlantic Ocean. The LBB model indicated an Atlantic bonito healthy stock status with B/BMSY values ranging from 1.3 to 1.6 and B/B0 values varying from 0.47 to 0.61 of the main scenarios performed (BON_AFG_CL, BON_GN_Length, and BON_PS_Length). The results estimated by LBB are consistent with those obtained by CMSY. The CMSY model results demonstrate that the SEEZ Atlantic bonito stock is in a sound condition in the final year of the main scenarios analyzed (BON, BON-bt, BON-GN-bt, and BON-PS-bt) with sustainable relative stock biomass (B2018/BMSY = 1.13 to 1.3) and fishing pressure levels (F2018/FMSY= 0.52 to 1.43). The B/BMSY and F/FMSY results for the JABBA model ranged between 2.01 to 2.14 and 0.47 to 0.33, respectively. In contrast, The estimated B/BMSY and F/FMSY for JABBA-Select ranged from 1.91 to 1.92 and 0.52 to 0.54. The Kobe plots results of the base case scenarios ranged from 75% to 89% probability in the green area, indicating sustainable fishing pressure and an Atlantic bonito healthy stock size capable of producing high yields close to the MSY. Based on the stock assessment results, this study highlighted scientific advice for temporary management measures. This study suggests an improvement of the selectivity parameters of longlines and purse seines and a temporary prohibition of the use of sleeping nets in the fishery for the Atlantic bonito stock in the SEEZ based on the results of the length-base models. Although these actions are temporary, they can be essential to reduce or avoid intense pressure on the Atlantic bonito stock in the SEEZ. However, it is necessary to establish harvest control rules to provide coherent and solid scientific information that leads to appropriate decision-making for rational and sustainable exploitation of Atlantic bonito in the SEEZ and the Eastern Atlantic Ocean.

Keywords: multi-model approach, stock assessment, atlantic bonito, SEEZ

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63 A Single Cell Omics Experiments as Tool for Benchmarking Bioinformatics Oncology Data Analysis Tools

Authors: Maddalena Arigoni, Maria Luisa Ratto, Raffaele A. Calogero, Luca Alessandri

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The presence of tumor heterogeneity, where distinct cancer cells exhibit diverse morphological and phenotypic profiles, including gene expression, metabolism, and proliferation, poses challenges for molecular prognostic markers and patient classification for targeted therapies. Understanding the causes and progression of cancer requires research efforts aimed at characterizing heterogeneity, which can be facilitated by evolving single-cell sequencing technologies. However, analyzing single-cell data necessitates computational methods that often lack objective validation. Therefore, the establishment of benchmarking datasets is necessary to provide a controlled environment for validating bioinformatics tools in the field of single-cell oncology. Benchmarking bioinformatics tools for single-cell experiments can be costly due to the high expense involved. Therefore, datasets used for benchmarking are typically sourced from publicly available experiments, which often lack a comprehensive cell annotation. This limitation can affect the accuracy and effectiveness of such experiments as benchmarking tools. To address this issue, we introduce omics benchmark experiments designed to evaluate bioinformatics tools to depict the heterogeneity in single-cell tumor experiments. We conducted single-cell RNA sequencing on six lung cancer tumor cell lines that display resistant clones upon treatment of EGFR mutated tumors and are characterized by driver genes, namely ROS1, ALK, HER2, MET, KRAS, and BRAF. These driver genes are associated with downstream networks controlled by EGFR mutations, such as JAK-STAT, PI3K-AKT-mTOR, and MEK-ERK. The experiment also featured an EGFR-mutated cell line. Using 10XGenomics platform with cellplex technology, we analyzed the seven cell lines together with a pseudo-immunological microenvironment consisting of PBMC cells labeled with the Biolegend TotalSeq™-B Human Universal Cocktail (CITEseq). This technology allowed for independent labeling of each cell line and single-cell analysis of the pooled seven cell lines and the pseudo-microenvironment. The data generated from the aforementioned experiments are available as part of an online tool, which allows users to define cell heterogeneity and generates count tables as an output. The tool provides the cell line derivation for each cell and cell annotations for the pseudo-microenvironment based on CITEseq data by an experienced immunologist. Additionally, we created a range of pseudo-tumor tissues using different ratios of the aforementioned cells embedded in matrigel. These tissues were analyzed using 10XGenomics (FFPE samples) and Curio Bioscience (fresh frozen samples) platforms for spatial transcriptomics, further expanding the scope of our benchmark experiments. The benchmark experiments we conducted provide a unique opportunity to evaluate the performance of bioinformatics tools for detecting and characterizing tumor heterogeneity at the single-cell level. Overall, our experiments provide a controlled and standardized environment for assessing the accuracy and robustness of bioinformatics tools for studying tumor heterogeneity at the single-cell level, which can ultimately lead to more precise and effective cancer diagnosis and treatment.

Keywords: single cell omics, benchmark, spatial transcriptomics, CITEseq

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62 Severe Post Operative Gas Gangrene of the Liver: Off-Label Treatment by Percutaneous Radiofrequency Ablation

Authors: Luciano Tarantino

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Gas gangrene is a rare, severe infection with a very high mortality rate caused by Clostridium species. The infection causes a non-suppurative localized producing gas lesion from which harmful toxins that impair the inflammatory response cause vessel damage and multiple organ failure. Gas gangrene of the liver is very rare and develops suddenly, often as a complication of abdominal surgery and liver transplantation. The present paper deals with a case of gas gangrene of the liver that occurred after percutaneous MW ablation of hepatocellular carcinoma, resulting in progressive liver necrosis and multi-organ failure in spite of specific antibiotics administration. The patient was successfully treated with percutaneous Radiofrequency ablation. Case report: Female, 76 years old, Child A class cirrhosis, treated with synchronous insertion of 3 MW antennae for large HCC (5.5 cm) in the VIII segment. 24 hours after treatment, the patient was asymptomatic and left the hospital . 2 days later, she complained of fever, weakness, abdominal swelling, and pain. Abdominal US detected a 2.3 cm in size gas-containing area, eccentric within the large (7 cm) ablated area. The patient was promptly hospitalized with the diagnosis of anaerobic liver abscess and started antibiotic therapy with Imipenem/cilastatine+metronidazole+teicoplanine. On the fourth day, the patient was moved to the ICU because of dyspnea, congestive heart failure, atrial fibrillation, right pleural effusion, ascites, and renal failure. Blood tests demonstrated severe leukopenia and neutropenia, anemia, increased creatinine and blood nitrogen, high-level FDP, and high INR. Blood cultures were negative. At US, unenhanced CT, and CEUS, a progressive enlargement of the infected liver lesion was observed. Percutaneous drainage was attempted, but only drops of non-suppurative brownish material could be obtained. Pleural and peritoneal drainages gave serosanguineous muddy fluid. The Surgeon and the Anesthesiologist excluded any indication of surgical resection because of the high perioperative mortality risk. Therefore, we asked for the informed consent of the patient and her relatives to treat the gangrenous liver lesion by percutaneous Ablation. Under conscious sedation, percutaneous RFA of GG was performed by double insertion of 3 cool-tip needles (Covidien LDT, USA ) into the infected area. The procedure was well tolerated by the patient. A dramatic improvement in the patient's condition was observed in the subsequent 24 hours and thereafter. Fever and dyspnea disappeared. Normalization of blood tests, including creatinine, was observed within 4 days. Heart performance improved, 10 days after the RFA the patient left the hospital and was followed-up with weekly as an outpatient for 2 months and every two months thereafter. At 18 months follow-up, the patient is well compensated (Child-Pugh class B7), without any peritoneal or pleural effusion and without any HCC recurrence at imaging (US every 3 months, CT every 6 months). Percutaneous RFA could be a valuable therapy of focal GG of the liver in patients non-responder to antibiotics and when surgery and liver transplantation are not feasible. A fast and early indication is needed in case of rapid worsening of patient's conditions.

Keywords: liver tumor ablation, interventional ultrasound, liver infection, gas gangrene, radiofrequency ablation

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61 Holistic Urban Development: Incorporating Both Global and Local Optimization

Authors: Christoph Opperer

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The rapid urbanization of modern societies and the need for sustainable urban development demand innovative solutions that meet both individual and collective needs while addressing environmental concerns. To address these challenges, this paper presents a study that explores the potential of spatial and energetic/ecological optimization to enhance the performance of urban settlements, focusing on both architectural and urban scales. The study focuses on the application of biological principles and self-organization processes in urban planning and design, aiming to achieve a balance between ecological performance, architectural quality, and individual living conditions. The research adopts a case study approach, focusing on a 10-hectare brownfield site in the south of Vienna. The site is surrounded by a small-scale built environment as an appropriate starting point for the research and design process. However, the selected urban form is not a prerequisite for the proposed design methodology, as the findings can be applied to various urban forms and densities. The methodology used in this research involves dividing the overall building mass and program into individual small housing units. A computational model has been developed to optimize the distribution of these units, considering factors such as solar exposure/radiation, views, privacy, proximity to sources of disturbance (such as noise), and minimal internal circulation areas. The model also ensures that existing vegetation and buildings on the site are preserved and incorporated into the optimization and design process. The model allows for simultaneous optimization at two scales, architectural and urban design, which have traditionally been addressed sequentially. This holistic design approach leads to individual and collective benefits, resulting in urban environments that foster a balance between ecology and architectural quality. The results of the optimization process demonstrate a seemingly random distribution of housing units that, in fact, is a densified hybrid between traditional garden settlements and allotment settlements. This urban typology is selected due to its compatibility with the surrounding urban context, although the presented methodology can be extended to other forms of urban development and density levels. The benefits of this approach are threefold. First, it allows for the determination of ideal housing distribution that optimizes solar radiation for each building density level, essentially extending the concept of sustainable building to the urban scale. Second, the method enhances living quality by considering the orientation and positioning of individual functions within each housing unit, achieving optimal views and privacy. Third, the algorithm's flexibility and robustness facilitate the efficient implementation of urban development with various stakeholders, architects, and construction companies without compromising its performance. The core of the research is the application of global and local optimization strategies to create efficient design solutions. By considering both, the performance of individual units and the collective performance of the urban aggregation, we ensure an optimal balance between private and communal benefits. By promoting a holistic understanding of urban ecology and integrating advanced optimization strategies, our methodology offers a sustainable and efficient solution to the challenges of modern urbanization.

Keywords: sustainable development, self-organization, ecological performance, solar radiation and exposure, daylight, visibility, accessibility, spatial distribution, local and global optimization

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60 Vertebral Artery Dissection Complicating Pregnancy and Puerperium: Case Report and Review of the Literature

Authors: N. Reza Pour, S. Chuah, T. Vo

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Background: Vertebral artery dissection (VAD) is a rare complication of pregnancy. It can occur spontaneously or following a traumatic event. The pathogenesis is unclear. Predisposing factors include chronic hypertension, Marfan’s syndrome, fibromuscular dysplasia, vasculitis and cystic medial necrosis. Physiological changes of pregnancy have also been proposed as potential mechanisms of injury to the vessel wall. The clinical presentation varies and it can present as a headache, neck pain, diplopia, transient ischaemic attack, or an ischemic stroke. Isolated cases of VAD in pregnancy and puerperium have been reported in the literature. One case was found to have posterior circulation stroke as a result of bilateral VAD and labour was induced at 37 weeks gestation for preeclampsia. Another patient at 38 weeks with severe neck pain that persisted after induction for elevated blood pressure and arteriography showed right VAD postpartum. A single case of lethal VAD in pregnancy with subsequent massive subarachnoid haemorrhage has been reported which was confirmed by the autopsy. Case Presentation: We report two cases of vertebral artery dissection in pregnancy. The first patient was a 32-year-old primigravida presented at the 38th week of pregnancy with the onset of early labour and blood pressure (BP) of 130/70 on arrival. After 2 hours, the patient developed a severe headache with blurry vision and BP was 238/120. Despite treatment with an intravenous antihypertensive, she had eclamptic fit. Magnesium solfate was started and Emergency Caesarean Section was performed under the general anaesthesia. On the second day after the operation, she developed left-sided neck pain. Magnetic Resonance Imaging (MRI) angiography confirmed a short segment left vertebral artery dissection at the level of C3. The patient was treated with aspirin and remained stable without any neurological deficit. The second patient was a 33-year-old primigavida who was admitted to the hospital at 36 weeks gestation with BP of 155/105, constant headache and visual disturbances. She was medicated with an oral antihypertensive agent. On day 4, she complained of right-sided neck pain. MRI angiogram revealed a short segment dissection of the right vertebral artery at the C2-3 level. Pregnancy was terminated on the same day with emergency Caesarean Section and anticoagulation was started subsequently. Post-operative recovery was complicated by rectus sheath haematoma requiring evacuation. She was discharged home on Aspirin without any neurological sequelae. Conclusion: Because of collateral circulation, unilateral vertebral artery dissections may go unrecognized and may be more common than suspected. The outcome for most patients is benign, reflecting the adequacy of the collateral circulation in young patients. Spontaneous VAD is usually treated with anticoagulation or antiplatelet therapy for a minimum of 3-6 months to prevent future ischaemic events, allowing the dissection to heal on its own. We had two cases of VAD in the context of hypertensive disorders of pregnancy with an acceptable outcome. A high level of vigilance is required particularly with preeclamptic patients presenting with head/neck pain to allow an early diagnosis. This is as we hypothesize, early and aggressive management of vertebral artery dissection may potentially prevent further complications.

Keywords: eclampsia, preeclampsia, pregnancy, Vertebral Artery Dissection

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59 Role of Toll Like Receptor-2 in Female Genital Tuberculosis Disease Infection and Its Severity

Authors: Swati Gautam, Salman Akhtar, S. P. Jaiswar, Amita Jain

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Background: FGTB is now a major global health problem mostly in developing countries including India. In humans, Mycobacterium Tuberculosis (M.tb) is a causating agent of infection. High index of suspicion is required for early diagnosis due to asymptomatic presentation of FGTB disease. In macrophages Toll Like Receptor-2 (TLR-2) is one which mediated host’s immune response to M.tb. The expression of TLR-2 on macrophages is important to determine the fate of innate immune responses to M.tb. TLR-2 have two work. First its high expression on macrophages worsen the outer of infection and another side, it maintains M.tb to its dormant stage avoids activation of M.tb from latent phase. Single Nucleotide Polymorphism (SNP) of TLR-2 gene plays an important role in susceptibility to TB among different populations and subsequently, in the development of infertility. Methodology: This Case-Control study was done in the Department of Obs and Gynae and Department of Microbiology at King George’s Medical University, U.P, Lucknow, India. Total 300 subjects (150 Cases and 150 Controls) were enrolled in the study. All subjects were enrolled only after fulfilling the given inclusion and exclusion criteria. Inclusion criteria: Age 20-35 years, menstrual-irregularities, positive on Acid-Fast Bacilli (AFB), TB-PCR, (LJ/MGIT) culture in Endometrial Aspiration (EA). Exclusion criteria: Koch’s active, on ATT, PCOS, and Endometriosis fibroid women, positive on Gonococal and Chlamydia. Blood samples were collected in EDTA tubes from cases and healthy control women (HCW) and genomic DNA extraction was carried out by salting-out method. Genotyping of TLR2 genetic variants (Arg753Gln and Arg677Trp) were performed by using single amplification refractory mutation system (ARMS) PCR technique. PCR products were analyzed by electrophoresis on 1.2% agarose gel and visualized by gel-doc. Statistical analysis of the data was performed using the SPSS 16.3 software and computing odds ratio (OR) with 95% CI. Linkage Disequiliribium (LD) analysis was done by SNP stats online software. Results: In TLR-2 (Arg753Gln) polymorphism significant risk of FGTB observed with GG homozygous mutant genotype (OR=13, CI=0.71-237.7, p=0.05), AG heterozygous mutant genotype (OR=13.7, CI=0.76-248.06, p=0.03) however, G allele (OR=1.09, CI=0.78-1.52, p=0.67) individually was not associated with FGTB. In TLR-2 (Arg677Trp) polymorphism a significant risk of FGTB observed with TT homozygous mutant genotype (OR= 0.020, CI=0.001-0.341, p < 0.001), CT heterozygous mutant genotype (OR=0.53, CI=0.33-0.86, p=0.014) and T allele (OR=0.463, CI=0.32-0.66, p < 0.001). TT mutant genotype was only found in FGTB cases and frequency of CT heterozygous more in control group as compared to FGTB group. So, CT genotype worked as protective mutation for FGTB susceptibility group. In haplotype analysis of TLR-2 genetic variants, four possible combinations, i.e. (G-T, A-C, G-C, and A-T) were obtained. The frequency of haplotype A-C was significantly higher in FGTB cases (0.32). Control group did not show A-C haplotype and only found in FGTB cases. Conclusion: In conclusion, study showed a significant association with both genetic variants of TLR-2 of FGTB disease. Moreover, the presence of specific associated genotype/alleles suggest the possibility of disease severity and clinical approach aimed to prevent extensive damage by disease and also helpful for early detection of disease.

Keywords: ARMS, EDTA, FGTB, TLR

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58 Impact of Primary Care Telemedicine Consultations On Health Care Resource Utilisation: A Systematic Review

Authors: Anastasia Constantinou, Stephen Morris

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Background: The adoption of synchronous and asynchronous telemedicine modalities for primary care consultations has exponentially increased since the COVID-19 pandemic. However, there is limited understanding of how virtual consultations influence healthcare resource utilization and other quality measures including safety, timeliness, efficiency, patient and provider satisfaction, cost-effectiveness and environmental impact. Aim: Quantify the rate of follow-up visits, emergency department visits, hospitalizations, request for investigations and prescriptions and comment on the effect on different quality measures associated with different telemedicine modalities used for primary care services and primary care referrals to secondary care Design and setting: Systematic review in primary care Methods: A systematic search was carried out across three databases (Medline, PubMed and Scopus) between August and November 2023, using terms related to telemedicine, general practice, electronic referrals, follow-up, use and efficiency and supported by citation searching. This was followed by screening according to pre-defined criteria, data extraction and critical appraisal. Narrative synthesis and metanalysis of quantitative data was used to summarize findings. Results: The search identified 2230 studies; 50 studies are included in this review. There was a prevalence of asynchronous modalities in both primary care services (68%) and referrals from primary care to secondary care (83%), and most of the study participants were females (63.3%), with mean age of 48.2. The average follow-up for virtual consultations in primary care was 28.4% (eVisits: 36.8%, secure messages 18.7%, videoconference 23.5%) with no significant difference between them or F2F consultations. There was an average annual reduction of primary care visits by 0.09/patient, an increase in telephone visits by 0.20/patient, an increase in ED encounters by 0.011/patient, an increase in hospitalizations by 0.02/patient and an increase in out of hours visits by 0.019/patient. Laboratory testing was requested on average for 10.9% of telemedicine patients, imaging or procedures for 5.6% and prescriptions for 58.7% of patients. When looking at referrals to secondary care, on average 36.7% of virtual referrals required follow-up visit, with the average rate of follow-up for electronic referrals being higher than for videoconferencing (39.2% vs 23%, p=0.167). Technical failures were reported on average for 1.4% of virtual consultations to primary care. When using carbon footprint estimates, we calculate that the use of telemedicine in primary care services can potentially provide a net decrease in carbon footprint by 0.592kgCO2/patient/year. When follow-up rates are taken into account, we estimate that virtual consultations reduce carbon footprint for primary care services by 2.3 times, and for secondary care referrals by 2.2 times. No major concerns regarding quality of care, or patient satisfaction were identified. 5/7 studies that addressed cost-effectiveness, reported increased savings. Conclusions: Telemedicine provides quality, cost-effective, and environmentally sustainable care for patients in primary care with inconclusive evidence regarding the rates of subsequent healthcare utilization. The evidence is limited by heterogeneous, small-scale studies and lack of prospective comparative studies. Further research to identify the most appropriate telemedicine modality for different patient populations, clinical presentations, service provision (e.g. used to follow-up patients instead of initial diagnosis) as well as further education for patients and providers alike on how to make best use of this service is expected to improve outcomes and influence practice.

Keywords: telemedicine, healthcare utilisation, digital interventions, environmental impact, sustainable healthcare

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57 Optimized Electron Diffraction Detection and Data Acquisition in Diffraction Tomography: A Complete Solution by Gatan

Authors: Saleh Gorji, Sahil Gulati, Ana Pakzad

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Continuous electron diffraction tomography, also known as microcrystal electron diffraction (MicroED) or three-dimensional electron diffraction (3DED), is a powerful technique, which in combination with cryo-electron microscopy (cryo-ED), can provide atomic-scale 3D information about the crystal structure and composition of different classes of crystalline materials such as proteins, peptides, and small molecules. Unlike the well-established X-ray crystallography method, 3DED does not require large single crystals and can collect accurate electron diffraction data from crystals as small as 50 – 100 nm. This is a critical advantage as growing larger crystals, as required by X-ray crystallography methods, is often very difficult, time-consuming, and expensive. In most cases, specimens studied via 3DED method are electron beam sensitive, which means there is a limitation on the maximum amount of electron dose one can use to collect the required data for a high-resolution structure determination. Therefore, collecting data using a conventional scintillator-based fiber coupled camera brings additional challenges. This is because of the inherent noise introduced during the electron-to-photon conversion in the scintillator and transfer of light via the fibers to the sensor, which results in a poor signal-to-noise ratio and requires a relatively higher and commonly specimen-damaging electron dose rates, especially for protein crystals. As in other cryo-EM techniques, damage to the specimen can be mitigated if a direct detection camera is used which provides a high signal-to-noise ratio at low electron doses. In this work, we have used two classes of such detectors from Gatan, namely the K3® camera (a monolithic active pixel sensor) and Stela™ (that utilizes DECTRIS hybrid-pixel technology), to address this problem. The K3 is an electron counting detector optimized for low-dose applications (like structural biology cryo-EM), and Stela is also a counting electron detector but optimized for diffraction applications with high speed and high dynamic range. Lastly, data collection workflows, including crystal screening, microscope optics setup (for imaging and diffraction), stage height adjustment at each crystal position, and tomogram acquisition, can be one of the other challenges of the 3DED technique. Traditionally this has been all done manually or in a partly automated fashion using open-source software and scripting, requiring long hours on the microscope (extra cost) and extensive user interaction with the system. We have recently introduced Latitude® D in DigitalMicrograph® software, which is compatible with all pre- and post-energy-filter Gatan cameras and enables 3DED data acquisition in an automated and optimized fashion. Higher quality 3DED data enables structure determination with higher confidence, while automated workflows allow these to be completed considerably faster than before. Using multiple examples, this work will demonstrate how to direct detection electron counting cameras enhance 3DED results (3 to better than 1 Angstrom) for protein and small molecule structure determination. We will also show how Latitude D software facilitates collecting such data in an integrated and fully automated user interface.

Keywords: continuous electron diffraction tomography, direct detection, diffraction, Latitude D, Digitalmicrograph, proteins, small molecules

Procedia PDF Downloads 56
56 Differential Expression Profile Analysis of DNA Repair Genes in Mycobacterium Leprae by qPCR

Authors: Mukul Sharma, Madhusmita Das, Sundeep Chaitanya Vedithi

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Leprosy is a chronic human disease caused by Mycobacterium leprae, that cannot be cultured in vitro. Though treatable with multidrug therapy (MDT), recently, bacteria reported resistance to multiple antibiotics. Targeting DNA replication and repair pathways can serve as the foundation of developing new anti-leprosy drugs. Due to the absence of an axenic culture medium for the propagation of M. leprae, studying cellular processes, especially those belonging to DNA repair pathways, is challenging. Genomic understanding of M. Leprae harbors several protein-coding genes with no previously assigned function known as 'hypothetical proteins'. Here, we report identification and expression of known and hypothetical DNA repair genes from a human skin biopsy and mouse footpads that are involved in base excision repair, direct reversal repair, and SOS response. Initially, a bioinformatics approach was employed based on sequence similarity, identification of known protein domains to screen the hypothetical proteins in the genome of M. leprae, that are potentially related to DNA repair mechanisms. Before testing on clinical samples, pure stocks of bacterial reference DNA of M. leprae (NHDP63 strain) was used to construct standard graphs to validate and identify lower detection limit in the qPCR experiments. Primers were designed to amplify the respective transcripts, and PCR products of the predicted size were obtained. Later, excisional skin biopsies of newly diagnosed untreated, treated, and drug resistance leprosy cases from SIHR & LC hospital, Vellore, India were taken for the extraction of RNA. To determine the presence of the predicted transcripts, cDNA was generated from M. leprae mRNA isolated from clinically confirmed leprosy skin biopsy specimen across all the study groups. Melting curve analysis was performed to determine the integrity of the amplification and to rule out primer‑dimer formation. The Ct values obtained from qPCR were fitted to standard curve to determine transcript copy number. Same procedure was applied for M. leprae extracted after processing a footpad of nude mice of drug sensitive and drug resistant strains. 16S rRNA was used as positive control. Of all the 16 genes involved in BER, DR, and SOS, differential expression pattern of the genes was observed in terms of Ct values when compared to human samples; this was because of the different host and its immune response. However, no drastic variation in gene expression levels was observed in human samples except the nth gene. The higher expression of nth gene could be because of the mutations that may be associated with sequence diversity and drug resistance which suggests an important role in the repair mechanism and remains to be explored. In both human and mouse samples, SOS system – lexA and RecA, and BER genes AlkB and Ogt were expressing efficiently to deal with possible DNA damage. Together, the results of the present study suggest that DNA repair genes are constitutively expressed and may provide a reference for molecular diagnosis, therapeutic target selection, determination of treatment and prognostic judgment in M. leprae pathogenesis.

Keywords: DNA repair, human biopsy, hypothetical proteins, mouse footpads, Mycobacterium leprae, qPCR

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55 Familial Exome Sequencing to Decipher the Complex Genetic Basis of Holoprosencephaly

Authors: Artem Kim, Clara Savary, Christele Dubourg, Wilfrid Carre, Houda Hamdi-Roze, Valerie Dupé, Sylvie Odent, Marie De Tayrac, Veronique David

Abstract:

Holoprosencephaly (HPE) is a rare congenital brain malformation resulting from the incomplete separation of the two cerebral hemispheres. It is characterized by a wide phenotypic spectrum and a high degree of locus heterogeneity. Genetic defects in 16 genes have already been implicated in HPE, but account for only 30% of cases, suggesting that a large part of genetic factors remains to be discovered. HPE has been recently redefined as a complex multigenic disorder, requiring the joint effect of multiple mutational events in genes belonging to one or several developmental pathways. The onset of HPE may result from accumulation of the effects of multiple rare variants in functionally-related genes, each conferring a moderate increase in the risk of HPE onset. In order to decipher the genetic basis of HPE, unconventional patterns of inheritance involving multiple genetic factors need to be considered. The primary objective of this study was to uncover possible disease causing combinations of multiple rare variants underlying HPE by performing trio-based Whole Exome Sequencing (WES) of familial cases where no molecular diagnosis could be established. 39 families were selected with no fully-penetrant causal mutation in known HPE gene, no chromosomic aberrations/copy number variants and without any implication of environmental factors. As the main challenge was to identify disease-related variants among a large number of nonpathogenic polymorphisms detected by WES classical scheme, a novel variant prioritization approach was established. It combined WES filtering with complementary gene-level approaches: transcriptome-driven (RNA-Seq data) and clinically-driven (public clinical data) strategies. Briefly, a filtering approach was performed to select variants compatible with disease segregation, population frequency and pathogenicity prediction to identify an exhaustive list of rare deleterious variants. The exome search space was then reduced by restricting the analysis to candidate genes identified by either transcriptome-driven strategy (genes sharing highly similar expression patterns with known HPE genes during cerebral development) or clinically-driven strategy (genes associated to phenotypes of interest overlapping with HPE). Deeper analyses of candidate variants were then performed on a family-by-family basis. These included the exploration of clinical information, expression studies, variant characteristics, recurrence of mutated genes and available biological knowledge. A novel bioinformatics pipeline was designed. Applied to the 39 families, this final integrated workflow identified an average of 11 candidate variants per family. Most of candidate variants were inherited from asymptomatic parents suggesting a multigenic inheritance pattern requiring the association of multiple mutational events. The manual analysis highlighted 5 new strong HPE candidate genes showing recurrences in distinct families. Functional validations of these genes are foreseen.

Keywords: complex genetic disorder, holoprosencephaly, multiple rare variants, whole exome sequencing

Procedia PDF Downloads 173
54 Redox-labeled Electrochemical Aptasensor Array for Single-cell Detection

Authors: Shuo Li, Yannick Coffinier, Chann Lagadec, Fabrizio Cleri, Katsuhiko Nishiguchi, Akira Fujiwara, Soo Hyeon Kim, Nicolas Clément

Abstract:

The need for single cell detection and analysis techniques has increased in the past decades because of the heterogeneity of individual living cells, which increases the complexity of the pathogenesis of malignant tumors. In the search for early cancer detection, high-precision medicine and therapy, the technologies most used today for sensitive detection of target analytes and monitoring the variation of these species are mainly including two types. One is based on the identification of molecular differences at the single-cell level, such as flow cytometry, fluorescence-activated cell sorting, next generation proteomics, lipidomic studies, another is based on capturing or detecting single tumor cells from fresh or fixed primary tumors and metastatic tissues, and rare circulating tumors cells (CTCs) from blood or bone marrow, for example, dielectrophoresis technique, microfluidic based microposts chip, electrochemical (EC) approach. Compared to other methods, EC sensors have the merits of easy operation, high sensitivity, and portability. However, despite various demonstrations of low limits of detection (LOD), including aptamer sensors, arrayed EC sensors for detecting single-cell have not been demonstrated. In this work, a new technique based on 20-nm-thick nanopillars array to support cells and keep them at ideal recognition distance for redox-labeled aptamers grafted on the surface. The key advantages of this technology are not only to suppress the false positive signal arising from the pressure exerted by all (including non-target) cells pushing on the aptamers by downward force but also to stabilize the aptamer at the ideal hairpin configuration thanks to a confinement effect. With the first implementation of this technique, a LOD of 13 cells (with5.4 μL of cell suspension) was estimated. In further, the nanosupported cell technology using redox-labeled aptasensors has been pushed forward and fully integrated into a single-cell electrochemical aptasensor array. To reach this goal, the LOD has been reduced by more than one order of magnitude by suppressing parasitic capacitive electrochemical signals by minimizing the sensor area and localizing the cells. Statistical analysis at the single-cell level is demonstrated for the recognition of cancer cells. The future of this technology is discussed, and the potential for scaling over millions of electrodes, thus pushing further integration at sub-cellular level, is highlighted. Despite several demonstrations of electrochemical devices with LOD of 1 cell/mL, the implementation of single-cell bioelectrochemical sensor arrays has remained elusive due to their challenging implementation at a large scale. Here, the introduced nanopillar array technology combined with redox-labeled aptamers targeting epithelial cell adhesion molecule (EpCAM) is perfectly suited for such implementation. Combining nanopillar arrays with microwells determined for single cell trapping directly on the sensor surface, single target cells are successfully detected and analyzed. This first implementation of a single-cell electrochemical aptasensor array based on Brownian-fluctuating redox species opens new opportunities for large-scale implementation and statistical analysis of early cancer diagnosis and cancer therapy in clinical settings.

Keywords: bioelectrochemistry, aptasensors, single-cell, nanopillars

Procedia PDF Downloads 71
53 Basic Characteristics of Synchronized Stir Welding and Its Prospects

Authors: Ipei Sato, Naonori Shibata, Shoji Matsumoto, Naruhito Matsumoto

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Friction stir welding (FSW) has been widely used in the automotive, aerospace, and high-tech industries due to its superiority in mechanical properties after joining. In order to achieve a good quality joint by friction stir welding (FSW), it is necessary to secure an advanced angle (usually 3 to 5 degrees) using a dedicated FSW machine and to join on a highly rigid machine. On the other hand, although recently, a new combined machine that combines the cutting function of a conventional machining center with the FSW function has appeared on the market, its joining process window is small, so joining defects easily occur, and it lacks reproducibility, which limits its application to the automotive industry, where control accuracy is required. This has limited the use of FSW machines in the automotive industry, where control accuracy is required. FSW-only machines or hybrid equipment that combines FSW and cutting machines require high capital investment costs, which is one of the reasons why FSW itself has not penetrated the market. Synchronized stir welding, a next-generation joining technology developed by our company, requires no tilt angle and is a very cost-effective method of welding. It is a next-generation joining technology that does not require a tilt angle, does not require a complicated spindle mechanism, and minimizes the load and vibration on the spindle, temperature during joining, and shoulder diameter, thereby enabling a wide range of joining conditions and high-strength, high-speed joining with no joining defects. In synchronized stir welding, the tip of the joining tool is "driven by microwaves" in both the rotational and vertical directions of the tool. The tool is synchronized and stirred in the direction and at the speed required by the material to be stirred in response to the movement required by the material to be welded, enabling welding that exceeds conventional concepts. Conventional FSW is passively stirred by an external driving force, resulting in low joining speeds and high heat input due to the need for a large shoulder diameter. In contrast, SSW is characterized by the fact that materials are actively stirred in synchronization with the direction and speed in which they are to be stirred, resulting in a high joining speed and a small shoulder diameter, which allows joining to be completed with low heat input. The advantages of synchronized stir welding technology in terms of basic mechanical properties are described. The superiority of the basic mechanical properties of SSW over FSW was evaluated as a comparison of the strength of the joint cross section in the comparison between FSW and SSW. SSW, compared to FSW, has tensile strength; base metal 242 MPa/217 MPa after FSW 89%, base metal 242 MPa/225 MPa after SSW 93%. Vickers hardness; base metal 75.0HV/FSW; 57.5HV 76% SSW; 66.0HV 88% (weld center), showing excellent results. In the tensile test, the material used was aluminum (A5052-H112) plate 5 mm thick, and the specimen was dumbbell-shaped, 2 mm thick, 4 mm wide, and 60 mm long. Measurements were made at a loading speed of 20%/min (in accordance with Z 2241:2022). Tensile testing machine: INSTRON Japan, model: INSTRON 5982. Vickers hardness was measured on a 5 mm thick specimen of A5052 tempered H112 with a width of 15 mm at 0.3 pitch (in accordance with JIS Z 2244:2020). Vickers tester: FUTURE-TECH Model: FM-300.

Keywords: FSW, SSW, synchronized stir welding, requires no tilt angles, running peak temperature less than 100 degrees C

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52 Describing Cognitive Decline in Alzheimer's Disease via a Picture Description Writing Task

Authors: Marielle Leijten, Catherine Meulemans, Sven De Maeyer, Luuk Van Waes

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For the diagnosis of Alzheimer's disease (AD), a large variety of neuropsychological tests are available. In some of these tests, linguistic processing - both oral and written - is an important factor. Language disturbances might serve as a strong indicator for an underlying neurodegenerative disorder like AD. However, the current diagnostic instruments for language assessment mainly focus on product measures, such as text length or number of errors, ignoring the importance of the process that leads to written or spoken language production. In this study, it is our aim to describe and test differences between cognitive and impaired elderly on the basis of a selection of writing process variables (inter- and intrapersonal characteristics). These process variables are mainly related to pause times, because the number, length, and location of pauses have proven to be an important indicator of the cognitive complexity of a process. Method: Participants that were enrolled in our research were chosen on the basis of a number of basic criteria necessary to collect reliable writing process data. Furthermore, we opted to match the thirteen cognitively impaired patients (8 MCI and 5 AD) with thirteen cognitively healthy elderly. At the start of the experiment, participants were each given a number of tests, such as the Mini-Mental State Examination test (MMSE), the Geriatric Depression Scale (GDS), the forward and backward digit span and the Edinburgh Handedness Inventory (EHI). Also, a questionnaire was used to collect socio-demographic information (age, gender, eduction) of the subjects as well as more details on their level of computer literacy. The tests and questionnaire were followed by two typing tasks and two picture description tasks. For the typing tasks participants had to copy (type) characters, words and sentences from a screen, whereas the picture description tasks each consisted of an image they had to describe in a few sentences. Both the typing and the picture description tasks were logged with Inputlog, a keystroke logging tool that allows us to log and time stamp keystroke activity to reconstruct and describe text production processes. The main rationale behind keystroke logging is that writing fluency and flow reveal traces of the underlying cognitive processes. This explains the analytical focus on pause (length, number, distribution, location, etc.) and revision (number, type, operation, embeddedness, location, etc.) characteristics. As in speech, pause times are seen as indexical of cognitive effort. Results. Preliminary analysis already showed some promising results concerning pause times before, within and after words. For all variables, mixed effects models were used that included participants as a random effect and MMSE scores, GDS scores and word categories (such as determiners and nouns) as a fixed effect. For pause times before and after words cognitively impaired patients paused longer than healthy elderly. These variables did not show an interaction effect between the group participants (cognitively impaired or healthy elderly) belonged to and word categories. However, pause times within words did show an interaction effect, which indicates pause times within certain word categories differ significantly between patients and healthy elderly.

Keywords: Alzheimer's disease, keystroke logging, matching, writing process

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51 A Case Study Report on Acoustic Impact Assessment and Mitigation of the Hyprob Research Plant

Authors: D. Bianco, A. Sollazzo, M. Barbarino, G. Elia, A. Smoraldi, N. Favaloro

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The activities, described in the present paper, have been conducted in the framework of the HYPROB-New Program, carried out by the Italian Aerospace Research Centre (CIRA) promoted and funded by the Italian Ministry of University and Research (MIUR) in order to improve the National background on rocket engine systems for space applications. The Program has the strategic objective to improve National system and technology capabilities in the field of liquid rocket engines (LRE) for future Space Propulsion Systems applications, with specific regard to LOX/LCH4 technology. The main purpose of the HYPROB program is to design and build a Propulsion Test Facility (HIMP) allowing test activities on Liquid Thrusters. The development of skills in liquid rocket propulsion can only pass through extensive test campaign. Following its mission, CIRA has planned the development of new testing facilities and infrastructures for space propulsion characterized by adequate sizes and instrumentation. The IMP test cell is devoted to testing articles representative of small combustion chambers, fed with oxygen and methane, both in liquid and gaseous phase. This article describes the activities that have been carried out for the evaluation of the acoustic impact, and its consequent mitigation. The impact of the simulated acoustic disturbance has been evaluated, first, using an approximated method based on experimental data by Baumann and Coney, included in “Noise and Vibration Control Engineering” edited by Vér and Beranek. This methodology, used to evaluate the free-field radiation of jet in ideal acoustical medium, analyzes in details the jet noise and assumes sources acting at the same time. It considers as principal radiation sources the jet mixing noise, caused by the turbulent mixing of jet gas and the ambient medium. Empirical models, allowing a direct calculation of the Sound Pressure Level, are commonly used for rocket noise simulation. The model named after K. Eldred is probably one of the most exploited in this area. In this paper, an improvement of the Eldred Standard model has been used for a detailed investigation of the acoustical impact of the Hyprob facility. This new formulation contains an explicit expression for the acoustic pressure of each equivalent noise source, in terms of amplitude and phase, allowing the investigation of the sources correlation effects and their propagation through wave equations. In order to enhance the evaluation of the facility acoustic impact, including an assessment of the mitigation strategies to be set in place, a more advanced simulation campaign has been conducted using both an in-house code for noise propagation and scattering, and a commercial code for industrial noise environmental impact, CadnaA. The noise prediction obtained with the revised Eldred-based model has then been used for formulating an empirical/BEM (Boundary Element Method) hybrid approach allowing the evaluation of the barrier mitigation effect, at the design. This approach has been compared with the analogous empirical/ray-acoustics approach, implemented within CadnaA using a customized definition of sources and directivity factor. The resulting impact evaluation study is reported here, along with the design-level barrier optimization for noise mitigation.

Keywords: acoustic impact, industrial noise, mitigation, rocket noise

Procedia PDF Downloads 117
50 Fine Characterization of Glucose Modified Human Serum Albumin by Different Biophysical and Biochemical Techniques at a Range

Authors: Neelofar, Khursheed Alam, Jamal Ahmad

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Protein modification in diabetes mellitus may lead to early glycation products (EGPs) or amadori product as well as advanced glycation end products (AGEs). Early glycation involves the reaction of glucose with N-terminal and lysyl side chain amino groups to form Schiff’s base which undergoes rearrangements to form more stable early glycation product known as Amadori product. After Amadori, the reactions become more complicated leading to the formation of advanced glycation end products (AGEs) that interact with various AGE receptors, thereby playing an important role in the long-term complications of diabetes. Millard reaction or nonenzymatic glycation reaction accelerate in diabetes due to hyperglycation and alter serum protein’s structure, their normal functions that lead micro and macro vascular complications in diabetic patients. In this study, Human Serum Albumin (HSA) with a constant concentration was incubated with different concentrations of glucose at 370C for a week. At 4th day, Amadori product was formed that was confirmed by colorimetric method NBT assay and TBA assay which both are authenticate early glycation product. Conformational changes in native as well as all samples of Amadori albumin with different concentrations of glucose were investigated by various biophysical and biochemical techniques. Main biophysical techniques hyperchromacity, quenching of fluorescence intensity, FTIR, CD and SDS-PAGE were used. Further conformational changes were observed by biochemical assays mainly HMF formation, fructoseamine, reduction of fructoseamine with NaBH4, carbonyl content estimation, lysine and arginine residues estimation, ANS binding property and thiol group estimation. This study find structural and biochemical changes in Amadori modified HSA with normal to hyperchronic range of glucose with respect to native HSA. When glucose concentration was increased from normal to chronic range biochemical and structural changes also increased. Highest alteration in secondary and tertiary structure and conformation in glycated HSA was observed at the hyperchronic concentration (75mM) of glucose. Although it has been found that Amadori modified proteins is also involved in secondary complications of diabetes as AGEs but very few studies have been done to analyze the conformational changes in Amadori modified proteins due to early glycation. Most of the studies were found on the structural changes in Amadori protein at a particular glucose concentration but no study was found to compare the biophysical and biochemical changes in HSA due to early glycation with a range of glucose concentration at a constant incubation time. So this study provide the information about the biochemical and biophysical changes occur in Amadori modified albumin at a range of glucose normal to chronic in diabetes. Although many implicates currently in use i.e. glycaemic control, insulin treatment and other chemical therapies that can control many aspects of diabetes. However, even with intensive use of current antidiabetic agents more than 50 % of diabetic patient’s type 2 suffers poor glycaemic control and 18 % develop serious complications within six years of diagnosis. Experimental evidence related to diabetes suggests that preventing the nonenzymatic glycation of relevant proteins or blocking their biological effects might beneficially influence the evolution of vascular complications in diabetic patients or quantization of amadori adduct of HSA by authentic antibodies against HSA-EGPs can be used as marker for early detection of the initiation/progression of secondary complications of diabetes. So this research work may be helpful for the same.

Keywords: diabetes mellitus, glycation, albumin, amadori, biophysical and biochemical techniques

Procedia PDF Downloads 239
49 Raman Spectral Fingerprints of Healthy and Cancerous Human Colorectal Tissues

Authors: Maria Karnachoriti, Ellas Spyratou, Dimitrios Lykidis, Maria Lambropoulou, Yiannis S. Raptis, Ioannis Seimenis, Efstathios P. Efstathopoulos, Athanassios G. Kontos

Abstract:

Colorectal cancer is the third most common cancer diagnosed in Europe, according to the latest incidence data provided by the World Health Organization (WHO), and early diagnosis has proved to be the key in reducing cancer-related mortality. In cases where surgical interventions are required for cancer treatment, the accurate discrimination between healthy and cancerous tissues is critical for the postoperative care of the patient. The current study focuses on the ex vivo handling of surgically excised colorectal specimens and the acquisition of their spectral fingerprints using Raman spectroscopy. Acquired data were analyzed in an effort to discriminate, in microscopic scale, between healthy and malignant margins. Raman spectroscopy is a spectroscopic technique with high detection sensitivity and spatial resolution of few micrometers. The spectral fingerprint which is produced during laser-tissue interaction is unique and characterizes the biostructure and its inflammatory or cancer state. Numerous published studies have demonstrated the potential of the technique as a tool for the discrimination between healthy and malignant tissues/cells either ex vivo or in vivo. However, the handling of the excised human specimens and the Raman measurement conditions remain challenging, unavoidably affecting measurement reliability and repeatability, as well as the technique’s overall accuracy and sensitivity. Therefore, tissue handling has to be optimized and standardized to ensure preservation of cell integrity and hydration level. Various strategies have been implemented in the past, including the use of balanced salt solutions, small humidifiers or pump-reservoir-pipette systems. In the current study, human colorectal specimens of 10X5 mm were collected from 5 patients up to now who underwent open surgery for colorectal cancer. A novel, non-toxic zinc-based fixative (Z7) was used for tissue preservation. Z7 demonstrates excellent protein preservation and protection against tissue autolysis. Micro-Raman spectra were recorded with a Renishaw Invia spectrometer from successive random 2 micrometers spots upon excitation at 785 nm to decrease fluorescent background and secure avoidance of tissue photodegradation. A temperature-controlled approach was adopted to stabilize the tissue at 2 °C, thus minimizing dehydration effects and consequent focus drift during measurement. A broad spectral range, 500-3200 cm-1,was covered with five consecutive full scans that lasted for 20 minutes in total. The average spectra were used for least square fitting analysis of the Raman modes.Subtle Raman differences were observed between normal and cancerous colorectal tissues mainly in the intensities of the 1556 cm-1 and 1628 cm-1 Raman modes which correspond to v(C=C) vibrations in porphyrins, as well as in the range of 2800-3000 cm-1 due to CH2 stretching of lipids and CH3 stretching of proteins. Raman spectra evaluation was supported by histological findings from twin specimens. This study demonstrates that Raman spectroscopy may constitute a promising tool for real-time verification of clear margins in colorectal cancer open surgery.

Keywords: colorectal cancer, Raman spectroscopy, malignant margins, spectral fingerprints

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48 Acoustic Radiation Force Impulse Elastography of the Hepatic Tissue of Canine Brachycephalic Patients

Authors: A. C. Facin, M. C. Maronezi , M. P. Menezes, G. L. Montanhim, L. Pavan, M. A. R. Feliciano, R. P. Nociti, R. A. R. Uscategui, P. C. Moraes

Abstract:

The incidence of brachycephalic syndrome (BS) in the clinical routine of small animals has increased significantly giving the higher proportion of brachycephalic pets in the last years and has been considered as an animal welfare problem. The treatment of BS is surgical and the clinical signs related can be considerably attenuated. Nevertheless, the systemic effects of the BS are still poorly reported and little is known about these when the surgical correction is not performed early. Affected dogs are more likely to develop cardiopulmonary, gastrointestinal and sleep disorders in which the chronic hypoxemia plays a major role. This syndrome is compared with the obstructive sleep apnea (OSA) in humans, both considered as causes of systemic and metabolic dysfunction. Among the several consequences of the BS little is known if the syndrome also affects the hepatic tissue of brachycephalic patients. Elastography is a promising ultrasound technique that evaluates tissue elasticity and has been recently used with the purpose of diagnosis of liver fibrosis. In medicine, it is a growing concern regarding the hepatic injury of patients affected by OSA. This prospective study hypothesizes if there is any consequence of BS in the hepatic parenchyma of brachycephalic dogs that don’t receive any surgical treatment. This study was conducted following the approval of the Animal Ethics and Welfare Committee of the Faculdade de Ciências Agrárias e Veterinárias, UNESP, Campus Jaboticabal, Brazil (protocol no 17944/2017) and funded by Sao Paulo Research Foundation (FAPESP, process no 2017/24809-4). The methodology was based in ARFI elastography using the ACUSON S2000/SIEMENS device, with convex multifrequential transducer and specific software as well as clinical evaluation of the syndrome, in order to determine if they can be used as a prognostic non-invasive tool. On quantitative elastography, it was collected three measures of shear wave velocity (meters per second) and depth in centimeters in the left lateral, left medial, right lateral, right medial and caudate lobe of the liver. The brachycephalic patients, 16 pugs and 30 french bulldogs, were classified using a previously established 4-point functional grading system based on clinical evaluation before and after a 3-minute exercise tolerance test already established and validated. The control group was based on the same features collected in 22 beagles. The software R version 3.3.0 was used for the analysis and the significance level was set at 0.05. The data were analysed for normality of residuals and homogeneity of variances by Shapiro-Wilks test. Comparisons of parametric continuous variables between breeds were performed by using ANOVA with a post hoc test for pair wise comparison. The preliminary results show significant statistic differences between the brachycephalic groups and the control group in all lobes analysed (p ≤ 0,05), with higher values of shear wave velocities in the hepatic tissue of brachycephalic dogs. In this context, the results obtained in this study contributes to the understanding of BS as well as its consequences in our patients, reflecting in evidence that one more systemic consequence of the syndrome may occur in brachycephalic patients, which was not related in the veterinary literature yet.

Keywords: airway obstruction, brachycephalic airway obstructive syndrome, hepatic injury, obstructive sleep apnea

Procedia PDF Downloads 86
47 Enabling Wire Arc Additive Manufacturing in Aircraft Landing Gear Production and Its Benefits

Authors: Jun Wang, Chenglei Diao, Emanuele Pagone, Jialuo Ding, Stewart Williams

Abstract:

As a crucial component in aircraft, landing gear systems are responsible for supporting the plane during parking, taxiing, takeoff, and landing. Given the need for high load-bearing capacity over extended periods, 300M ultra-high strength steel (UHSS) is often the material of choice for crafting these systems due to its exceptional strength, toughness, and fatigue resistance. In the quest for cost-effective and sustainable manufacturing solutions, Wire Arc Additive Manufacturing (WAAM) emerges as a promising alternative for fabricating 300M UHSS landing gears. This is due to its advantages in near-net-shape forming of large components, cost-efficiency, and reduced lead times. Cranfield University has conducted an extensive preliminary study on WAAM 300M UHSS, covering feature deposition, interface analysis, and post-heat treatment. Both Gas Metal Arc (GMA) and Plasma Transferred Arc (PTA)-based WAAM methods were explored, revealing their feasibility for defect-free manufacturing. However, as-deposited 300M features showed lower strength but higher ductility compared to their forged counterparts. Subsequent post-heat treatments were effective in normalising the microstructure and mechanical properties, meeting qualification standards. A 300M UHSS landing gear demonstrator was successfully created using PTA-based WAAM, showcasing the method's precision and cost-effectiveness. The demonstrator, measuring Ф200mm x 700mm, was completed in 16 hours, using 7 kg of material at a deposition rate of 1.3kg/hr. This resulted in a significant reduction in the Buy-to-Fly (BTF) ratio compared to traditional manufacturing methods, further validating WAAM's potential for this application. A "cradle-to-gate" environmental impact assessment, which considers the cumulative effects from raw material extraction to customer shipment, has revealed promising outcomes. Utilising Wire Arc Additive Manufacturing (WAAM) for landing gear components significantly reduces the need for raw material extraction and refinement compared to traditional subtractive methods. This, in turn, lessens the burden on subsequent manufacturing processes, including heat treatment, machining, and transportation. Our estimates indicate that the carbon footprint of the component could be halved when switching from traditional machining to WAAM. Similar reductions are observed in embodied energy consumption and other environmental impact indicators, such as emissions to air, water, and land. Additionally, WAAM offers the unique advantage of part repair by redepositing only the necessary material, a capability not available through conventional methods. Our research shows that WAAM-based repairs can drastically reduce environmental impact, even when accounting for additional transportation for repairs. Consequently, WAAM emerges as a pivotal technology for reducing environmental impact in manufacturing, aiding the industry in its crucial and ambitious journey towards Net Zero. This study paves the way for transformative benefits across the aerospace industry, as we integrate manufacturing into a hybrid solution that offers substantial savings and access to more sustainable technologies for critical component production.

Keywords: WAAM, aircraft landing gear, microstructure, mechanical performance, life cycle assessment

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46 The Need for a More Defined Role for Psychologists in Adult Consultation Liaison Services in Hospital Settings

Authors: Ana Violante, Jodie Maccarrone, Maria Fimiani

Abstract:

In the United States, over 30 million people are hospitalized annually for conditions that require acute, 24-hour, supervised care. The experience of hospitalization can be traumatic, exposing the patient to loss of control, autonomy, and productivity. Furthermore, 40% of patients admitted to hospitals for general medical illness have a comorbid psychiatric diagnosis. Research suggests individuals admitted with psychiatric comorbidities experience poorer health outcomes, higher utilization rates and increased overall cost of care. Empirical work suggests hospital settings that include a consultation liaison (CL) service report reduced length of stay, lower costs per patient, improved medical staff and patient satisfaction and reduced readmission after 180 days. Despite the overall positive impact CL services can have on patient care, it is estimated that only 1% - 2.8% of hospital admits receive these services, and most research has been conducted by the field of psychiatry. Health psychologists could play an important role in increasing access to this valuable service, though the extent to which health psychologists participate in CL settings is not well known. Objective: Outline the preliminary findings from an empirical study to understand how many APPIC internship training programs offer adult consultation liaison rotations within inpatient hospital settings nationally, as well as describe the specific nature of these training experiences. Research Method/Design: Data was exported into Excel from the 2022-2023 APPIC Directory categorized as “health psychology” sites. It initially returned a total of 537 health training programs out 1518 total programs (35% of all APPIC programs). A full review included a quantitative and qualitative comprehensive review of the APPIC program summary, the site website, and program brochures. The quantitative review extracted the number of training positions; amount of stipend; location or state of program, patient, population, and rotation. The qualitative review examined the nature of the training experience. Results: 29 (5%) of all APPIC health psychology internship training programs (2%) respectively of all APPIC training internship programs offering internship CL training were identified. Of the 29 internship training programs, 16 were exclusively within a pediatric setting (55%), 11 were exclusively within an adult setting (38%), and two were a mix of pediatric and adult settings (7%). CL training sites were located to 19 states, offering a total of 153 positions nationally, with Florida containing the largest number of programs (4). Only six programs offered 12-month training opportunities while the rest offered CL as a major (6 month) to minor (3-4 month) rotation. The program’s stipend for CL training positions ranged from $25,000 to $62,400, with an average of $32,056. Conclusions: These preliminary findings suggest CL training and services are currently limited. Training opportunities that do exist are mostly limited to minor, short rotations and governed by psychiatry. Health psychologists are well-positioned to better define the role of psychology in consultation liaison services and enhance and formalize existing training protocols. Future research should explore in more detail empirical outcomes of CL services that employ psychology and delineate the contributions of psychology from psychiatry and other disciplines within an inpatient hospital setting.

Keywords: consultation liaison, health psychology, hospital setting, training

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45 Post Liberal Perspective on Minorities Visibility in Contemporary Visual Culture: The Case of Mizrahi Jews

Authors: Merav Alush Levron, Sivan Rajuan Shtang

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From as early as their emergence in Europe and the US, postmodern and post-colonial paradigm have formed the backbone of the visual culture field of study. The self-representation project of political minorities is studied, described and explained within the premises and perspectives drawn from these paradigms, addressing the key issues they had raised: modernism’s crisis of representation. The struggle for self-representation, agency and multicultural visibility sought to challenge the liberal pretense of universality and equality, hitting at its different blind spots, on issues such as class, gender, race, sex, and nationality. This struggle yielded subversive identity and hybrid performances, including reclaiming, mimicry and masquerading. These performances sought to defy the uniform, universal self, which forms the basis for the liberal, rational, enlightened subject. The argument of this research runs that this politics of representation itself is confined within liberal thought. Alongside post-colonialism and multiculturalism’s contribution in undermining oppressive structures of power, generating diversity in cultural visibility, and exposing the failure of liberal colorblindness, this subversion is constituted in the visual field by way of confrontation, flying in the face of the universal law and relying on its ongoing comparison and attribution to this law. Relying on Deleuze and Guattari, this research set out to draw theoretic and empiric attention to an alternative, post-liberal occurrence which has been taking place in the visual field in parallel to the contra-hegemonic phase and as a product of political reality in the aftermath of the crisis of representation. It is no longer a counter-representation; rather, it is a motion of organic minor desire, progressing in the form of flows and generating what Deleuze and Guattari termed deterritorialization of social structures. This discussion shall have its focus on current post-liberal performances of ‘Mizrahim’ (Jewish Israelis of Arab and Muslim extraction) in the visual field in Israel. In television, video art and photography, these performances challenge the issue of representation and generate concrete peripheral Mizrahiness, realized in the visual organization of the photographic frame. Mizrahiness then transforms from ‘confrontational’ representation into a 'presence', flooding the visual sphere in our plain sight, in a process of 'becoming'. The Mizrahi desire is exerted on the plains of sound, spoken language, the body and the space where they appear. It removes from these plains the coding and stratification engendered by European dominance and rational, liberal enlightenment. This stratification, adhering to the hegemonic surface, is flooded not by way of resisting false consciousness or employing hybridity, but by way of the Mizrahi identity’s own productive, material immanent yearning. The Mizrahi desire reverberates with Mizrahi peripheral 'worlds of meaning', where post-colonial interpretation almost invariably identifies a product of internalized oppression, and a recurrence thereof, rather than a source in itself - an ‘offshoot, never a wellspring’, as Nissim Mizrachi clarifies in his recent pioneering work. The peripheral Mizrahi performance ‘unhook itself’, in Deleuze and Guattari words, from the point of subjectification and interpretation and does not correspond with the partialness, absence, and split that mark post-colonial identities.

Keywords: desire, minority, Mizrahi Jews, post-colonialism, post-liberalism, visibility, Deleuze and Guattari

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44 Hydroinformatics of Smart Cities: Real-Time Water Quality Prediction Model Using a Hybrid Approach

Authors: Elisa Coraggio, Dawei Han, Weiru Liu, Theo Tryfonas

Abstract:

Water is one of the most important resources for human society. The world is currently undergoing a wave of urban growth, and pollution problems are of a great impact. Monitoring water quality is a key task for the future of the environment and human species. In recent times, researchers, using Smart Cities technologies are trying to mitigate the problems generated by the population growth in urban areas. The availability of huge amounts of data collected by a pervasive urban IoT can increase the transparency of decision making. Several services have already been implemented in Smart Cities, but more and more services will be involved in the future. Water quality monitoring can successfully be implemented in the urban IoT. The combination of water quality sensors, cloud computing, smart city infrastructure, and IoT technology can lead to a bright future for environmental monitoring. In the past decades, lots of effort has been put on monitoring and predicting water quality using traditional approaches based on manual collection and laboratory-based analysis, which are slow and laborious. The present study proposes a methodology for implementing a water quality prediction model using artificial intelligence techniques and comparing the results obtained with different algorithms. Furthermore, a 3D numerical model will be created using the software D-Water Quality, and simulation results will be used as a training dataset for the artificial intelligence algorithm. This study derives the methodology and demonstrates its implementation based on information and data collected at the floating harbour in the city of Bristol (UK). The city of Bristol is blessed with the Bristol-Is-Open infrastructure that includes Wi-Fi network and virtual machines. It was also named the UK ’s smartest city in 2017.In recent times, researchers, using Smart Cities technologies are trying to mitigate the problems generated by the population growth in urban areas. The availability of huge amounts of data collected by a pervasive urban IoT can increase the transparency of decision making. Several services have already been implemented in Smart Cities, but more and more services will be involved in the future. Water quality monitoring can successfully be implemented in the urban IoT. The combination of water quality sensors, cloud computing, smart city infrastructure, and IoT technology can lead to a bright future for the environment monitoring. In the past decades, lots of effort has been put on monitoring and predicting water quality using traditional approaches based on manual collection and laboratory-based analysis, which are slow and laborious. The present study proposes a new methodology for implementing a water quality prediction model using artificial intelligence techniques and comparing the results obtained with different algorithms. Furthermore, a 3D numerical model will be created using the software D-Water Quality, and simulation results will be used as a training dataset for the Artificial Intelligence algorithm. This study derives the methodology and demonstrate its implementation based on information and data collected at the floating harbour in the city of Bristol (UK). The city of Bristol is blessed with the Bristol-Is-Open infrastructure that includes Wi-Fi network and virtual machines. It was also named the UK ’s smartest city in 2017.

Keywords: artificial intelligence, hydroinformatics, numerical modelling, smart cities, water quality

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43 Hanta Virus Infection in a Child and Sequelae

Authors: Vijay Samuel, Tina Thekkekkara, Shoma Ganguly

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There is no reported Hanta Seoul virus infection in children in the UK so far, making it quite challenging for clinicians in diagnosing, predicting and prognosticating the outcome of the infection to patients and parents. We report a case of a ten-year-old girl who presented with pyrexia associated with headache, photophobia and abdominal pain. The family had recently acquired two pet rats six weeks ago. She appeared flushed with peri-oral pallor, coated the strawberry tongue, inflamed tonsils and bilateral cervical lymphadenopathy. Her liver and splenic edges were palpable. Investigations showed that she was thrombocytopenic with deranged renal and liver functions. An ultrasound abdomen demonstrated a mildly enlarged spleen, peripancreatic lymph node and an acalculous cholecystitis. In view of her clinical presentation, a diagnosis of leptospirosis was considered and she was commenced on intravenous benzylpenicillin. The following day she became oliguric, developed significant proteinuria and her renal function deteriorated. Following conservative management, her urine output gradually improved along with her renal function, proteinuria and thrombocytopaenia. Serology for leptospirosis and various other viruses were negative. Following discussion with the Rare and Imported Pathogens Laboratory at Porton hanta virus serology was requested and found to be strongly positive for Seoul hanta virus. Following discharge she developed palpitations, fatigue, severe headache and cognitive difficulties including memory loss and difficulties in spelling, reading and mathematics. Extensive investigations including ECG, MRI brain and CSF studies were performed and revealed no significant abnormalities. Since 2012, there have been six cases of acute kidney injury due to Hantavirus infection in the UK. Two cases were from the Humber region and were exposure to wild rats and the other four were exposed to specially bred pet fancy rats. Hanta virus infections can cause mild flu like symptoms but two clinical syndromes are associated with severe disease including haemorrhagic fever with renal syndrome, which may be associated with thrombocytopenia and Hantavirus cardiopulmonary syndrome. Neuropsychological impairments reported following hantavirus pulmonary syndrome and following Puumala virus infection have been reported. Minor white matter lesions were found in about half of the patients investigated with MRI brain. Seoul virus has a global distribution owing to the dispersal of its carrier host rats, through global trade. Several ports in the region could explain the possible establishment of Seoul virus in local populations of rats in the Yorkshire and Humber region. The risk of infection for occupationally exposed groups is 1-3% compared to 32.9% for specialist pet rat owners. The report highlight’s the importance of routinely asking about pets in the family. We hope to raise awareness of the emergence of hantavirus infection in the UK, particularly in the Yorkshire and Humber region. Clinicians should consider hantavirus infection as a potential cause of febrile illness causing renal impairment in children. Awareness of the possible neuro-cognitive sequele would help the clinicians offer appropriate information and support to children and their families. Contacting Rare and Imported Pathogens Laboratory at Porton is a useful resource for clinicians in UK when they consider unusual infections.

Keywords: Seoul hantavirus in child Porton, UK Acute kidney injury

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42 Framework to Organize Community-Led Project-Based Learning at a Massive Scale of 900 Indian Villages

Authors: Ayesha Selwyn, Annapoorni Chandrashekar, Kumar Ashwarya, Nishant Baghel

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Project-based learning (PBL) activities are typically implemented in technology-enabled schools by highly trained teachers. In rural India, students have limited access to technology and quality education. Implementing typical PBL activities is challenging. This study details how Pratham Education Foundation’s Hybrid Learning model was used to implement two PBL activities related to music in 900 remote Indian villages with 46,000 students aged 10-14. The activities were completed by 69% of groups that submitted a total of 15,000 videos (completed projects). Pratham’s H-Learning model reaches 100,000 students aged 3-14 in 900 Indian villages. The community-driven model engages students in 20,000 self-organized groups outside of school. The students are guided by 6,000 youth volunteers and 100 facilitators. The students partake in learning activities across subjects with the support of community stakeholders and offline digital content on shared Android tablets. A training and implementation toolkit for PBL activities is designed by subject experts. This toolkit is essential in ensuring efficient implementation of activities as facilitators aren’t highly skilled and have limited access to training resources. The toolkit details the activity at three levels of student engagement - enrollment, participation, and completion. The subject experts train project leaders and facilitators who train youth volunteers. Volunteers need to be trained on how to execute the activity and guide students. The training is focused on building the volunteers’ capacity to enable students to solve problems, rather than developing the volunteers’ subject-related knowledge. This structure ensures that continuous intervention of subject matter experts isn’t required, and the onus of judging creativity skills is put on community members. 46,000 students in the H-Learning program were engaged in two PBL activities related to Music from April-June 2019. For one activity, students had to conduct a “musical survey” in their village by designing a survey and shooting and editing a video. This activity aimed to develop students’ information retrieval, data gathering, teamwork, communication, project management, and creativity skills. It also aimed to identify talent and document local folk music. The second activity, “Pratham Idol”, was a singing competition. Students participated in performing, producing, and editing videos. This activity aimed to develop students’ teamwork and creative skills and give students a creative outlet. Students showcased their completed projects at village fairs wherein a panel of community members evaluated the videos. The shortlisted videos from all villages were further evaluated by experts who identified students and adults to participate in advanced music workshops. The H-Learning framework enables students in low resource settings to engage in PBL and develop relevant skills by leveraging community support and using video creation as a tool. In rural India, students do not have access to high-quality education or infrastructure. Therefore designing activities that can be implemented by community members after limited training is essential. The subject experts have minimal intervention once the activity is initiated, which significantly reduces the cost of implementation and allows the activity to be implemented at a massive scale.

Keywords: community supported learning, project-based learning, self-organized learning, education technology

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41 Discovering Causal Structure from Observations: The Relationships between Technophile Attitude, Users Value and Use Intention of Mobility Management Travel App

Authors: Aliasghar Mehdizadeh Dastjerdi, Francisco Camara Pereira

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The increasing complexity and demand of transport services strains transportation systems especially in urban areas with limited possibilities for building new infrastructure. The solution to this challenge requires changes of travel behavior. One of the proposed means to induce such change is multimodal travel apps. This paper describes a study of the intention to use a real-time multi-modal travel app aimed at motivating travel behavior change in the Greater Copenhagen Region (Denmark) toward promoting sustainable transport options. The proposed app is a multi-faceted smartphone app including both travel information and persuasive strategies such as health and environmental feedback, tailoring travel options, self-monitoring, tunneling users toward green behavior, social networking, nudging and gamification elements. The prospective for mobility management travel apps to stimulate sustainable mobility rests not only on the original and proper employment of the behavior change strategies, but also on explicitly anchoring it on established theoretical constructs from behavioral theories. The theoretical foundation is important because it positively and significantly influences the effectiveness of the system. However, there is a gap in current knowledge regarding the study of mobility-management travel app with support in behavioral theories, which should be explored further. This study addresses this gap by a social cognitive theory‐based examination. However, compare to conventional method in technology adoption research, this study adopts a reverse approach in which the associations between theoretical constructs are explored by Max-Min Hill-Climbing (MMHC) algorithm as a hybrid causal discovery method. A technology-use preference survey was designed to collect data. The survey elicited different groups of variables including (1) three groups of user’s motives for using the app including gain motives (e.g., saving travel time and cost), hedonic motives (e.g., enjoyment) and normative motives (e.g., less travel-related CO2 production), (2) technology-related self-concepts (i.e. technophile attitude) and (3) use Intention of the travel app. The questionnaire items led to the formulation of causal relationships discovery to learn the causal structure of the data. Causal relationships discovery from observational data is a critical challenge and it has applications in different research fields. The estimated causal structure shows that the two constructs of gain motives and technophilia have a causal effect on adoption intention. Likewise, there is a causal relationship from technophilia to both gain and hedonic motives. In line with the findings of the prior studies, it highlights the importance of functional value of the travel app as well as technology self-concept as two important variables for adoption intention. Furthermore, the results indicate the effect of technophile attitude on developing gain and hedonic motives. The causal structure shows hierarchical associations between the three groups of user’s motive. They can be explained by “frustration-regression” principle according to Alderfer's ERG (Existence, Relatedness and Growth) theory of needs meaning that a higher level need remains unfulfilled, a person may regress to lower level needs that appear easier to satisfy. To conclude, this study shows the capability of causal discovery methods to learn the causal structure of theoretical model, and accordingly interpret established associations.

Keywords: travel app, behavior change, persuasive technology, travel information, causality

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40 Auto Rickshaw Impacts with Pedestrians: A Computational Analysis of Post-Collision Kinematics and Injury Mechanics

Authors: A. J. Al-Graitti, G. A. Khalid, P. Berthelson, A. Mason-Jones, R. Prabhu, M. D. Jones

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Motor vehicle related pedestrian road traffic collisions are a major road safety challenge, since they are a leading cause of death and serious injury worldwide, contributing to a third of the global disease burden. The auto rickshaw, which is a common form of urban transport in many developing countries, plays a major transport role, both as a vehicle for hire and for private use. The most common auto rickshaws are quite unlike ‘typical’ four-wheel motor vehicle, being typically characterised by three wheels, a non-tilting sheet-metal body or open frame construction, a canvas roof and side curtains, a small drivers’ cabin, handlebar controls and a passenger space at the rear. Given the propensity, in developing countries, for auto rickshaws to be used in mixed cityscapes, where pedestrians and vehicles share the roadway, the potential for auto rickshaw impacts with pedestrians is relatively high. Whilst auto rickshaws are used in some Western countries, their limited number and spatial separation from pedestrian walkways, as a result of city planning, has not resulted in significant accident statistics. Thus, auto rickshaws have not been subject to the vehicle impact related pedestrian crash kinematic analyses and/or injury mechanics assessment, typically associated with motor vehicle development in Western Europe, North America and Japan. This study presents a parametric analysis of auto rickshaw related pedestrian impacts by computational simulation, using a Finite Element model of an auto rickshaw and an LS-DYNA 50th percentile male Hybrid III Anthropometric Test Device (dummy). Parametric variables include auto rickshaw impact velocity, auto rickshaw impact region (front, centre or offset) and relative pedestrian impact position (front, side and rear). The output data of each impact simulation was correlated against reported injury metrics, Head Injury Criterion (front, side and rear), Neck injury Criterion (front, side and rear), Abbreviated Injury Scale and reported risk level and adds greater understanding to the issue of auto rickshaw related pedestrian injury risk. The parametric analyses suggest that pedestrians are subject to a relatively high risk of injury during impacts with an auto rickshaw at velocities of 20 km/h or greater, which during some of the impact simulations may even risk fatalities. The present study provides valuable evidence for informing a series of recommendations and guidelines for making the auto rickshaw safer during collisions with pedestrians. Whilst it is acknowledged that the present research findings are based in the field of safety engineering and may over represent injury risk, compared to “Real World” accidents, many of the simulated interactions produced injury response values significantly greater than current threshold curves and thus, justify their inclusion in the study. To reduce the injury risk level and increase the safety of the auto rickshaw, there should be a reduction in the velocity of the auto rickshaw and, or, consideration of engineering solutions, such as retro fitting injury mitigation technologies to those auto rickshaw contact regions which are the subject of the greatest risk of producing pedestrian injury.

Keywords: auto rickshaw, finite element analysis, injury risk level, LS-DYNA, pedestrian impact

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39 Networks, Regulations and Public Action: The Emerging Experiences of Sao Paulo

Authors: Lya Porto, Giulia Giacchè, Mario Aquino Alves

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The paper aims to describe the linkage between government and civil society proposing a study on agro-ecological agriculture policy and urban action in São Paulo city underling the main achievements obtained. The negotiation processes between social movements and the government (inputs) and its results on political regulation and public action for Urban Agriculture (UA) in São Paulo city (outputs) have been investigated. The method adopted is qualitative, with techniques of semi-structured interviews, participant observation, and documental analysis. The authors conducted 30 semi-structured interviews with organic farmers, activists, governmental and non-governmental managers. Participant observation was conducted in public gardens, urban farms, public audiences, democratic councils, and social movements meetings. Finally, public plans and laws were also analyzed. São Paulo city with around 12 million inhabitants spread out in a 1522 km2 is the economic capital of Brazil, marked by spatial and socioeconomic segregation, currently aggravated by environmental crisis, characterized by water scarcity, pollution, and climate changes. In recent years, Urban Agriculture (UA) social movements gained strength and struggle for a different city with more green areas, organic food production, and public occupation. As the dynamics of UA occurs by the action of multiple actresses and institutions that struggle to build multiple senses on UA, the analysis will be based on literature about solidarity economy, governance, public action and networks. Those theories will mark out the analysis that will emphasize the approach of inter-subjectivity built between subjects, as well as the hybrid dynamics of multiple actors and spaces in the construction of policies for UA. Concerning UA we identified four main typologies based on land ownership, main function (economic or activist), form of organization of the space, and type of production (organic or not). The City Hall registers 500 productive unities of agriculture, with around 1500 producers, but researcher estimated a larger number of unities. Concerning the social movements we identified three categories that differ in goals and types of organization, but all of them work by networks of activists and/or organizations. The first category does not consider themselves as a movement, but a network. They occupy public spaces to grow organic food and to propose another type of social relations in the city. This action is similar to what became known as the green guerrillas. The second is configured as a movement that is structured to raise awareness about agro-ecological activities. The third one is a network of social movements, farmers, organizations and politicians that work focused on pressure and negotiation with executive and legislative government to approve regulations and policies on organic and agro-ecological Urban Agriculture. We conclude by highlighting how the interaction among institutions and civil society produced important achievements for recognition and implementation of UA within the city. Some results of this process are awareness for local production, legal and institutional recognition of the rural zone around the city into the planning tool, the investment on organic school public procurements, the establishment of participatory management of public squares, the inclusion of UA on Municipal Strategic Plan and Master Plan.

Keywords: public action, policies, agroecology, urban and peri-urban agriculture, Sao Paulo

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38 Electroactive Ferrocenyl Dendrimers as Transducers for Fabrication of Label-Free Electrochemical Immunosensor

Authors: Sudeshna Chandra, Christian Gäbler, Christian Schliebe, Heinrich Lang

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Highly branched dendrimers provide structural homogeneity, controlled composition, comparable size to biomolecules, internal porosity and multiple functional groups for conjugating reactions. Electro-active dendrimers containing multiple redox units have generated great interest in their use as electrode modifiers for development of biosensors. The electron transfer between the redox-active dendrimers and the biomolecules play a key role in developing a biosensor. Ferrocenes have multiple and electrochemically equivalent redox units that can act as electron “pool” in a system. The ferrocenyl-terminated polyamidoamine dendrimer is capable of transferring multiple numbers of electrons under the same applied potential. Therefore, they can be used for dual purposes: one in building a film over the electrode for immunosensors and the other for immobilizing biomolecules for sensing. Electrochemical immunosensor, thus developed, exhibit fast and sensitive analysis, inexpensive and involve no prior sample pre-treatment. Electrochemical amperometric immunosensors are even more promising because they can achieve a very low detection limit with high sensitivity. Detection of the cancer biomarkers at an early stage can provide crucial information for foundational research of life science, clinical diagnosis and prevention of disease. Elevated concentration of biomarkers in body fluid is an early indication of some type of cancerous disease and among all the biomarkers, IgG is the most common and extensively used clinical cancer biomarkers. We present an IgG (=immunoglobulin) electrochemical immunosensor using a newly synthesized redox-active ferrocenyl dendrimer of generation 2 (G2Fc) as glassy carbon electrode material for immobilizing the antibody. The electrochemical performance of the modified electrodes was assessed in both aqueous and non-aqueous media using varying scan rates to elucidate the reaction mechanism. The potential shift was found to be higher in an aqueous electrolyte due to presence of more H-bond which reduced the electrostatic attraction within the amido groups of the dendrimers. The cyclic voltammetric studies of the G2Fc-modified GCE in 0.1 M PBS solution of pH 7.2 showed a pair of well-defined redox peaks. The peak current decreased significantly with the immobilization of the anti-goat IgG. After the immunosensor is blocked with BSA, a further decrease in the peak current was observed due to the attachment of the protein BSA to the immunosensor. A significant decrease in the current signal of the BSA/anti-IgG/G2Fc/GCE was observed upon immobilizing IgG which may be due to the formation of immune-conjugates that blocks the tunneling of mass and electron transfer. The current signal was found to be directly related to the amount of IgG captured on the electrode surface. With increase in the concentration of IgG, there is a formation of an increasing amount of immune-conjugates that decreased the peak current. The incubation time and concentration of the antibody was optimized for better analytical performance of the immunosensor. The developed amperometric immunosensor is sensitive to IgG concentration as low as 2 ng/mL. Tailoring of redox-active dendrimers provides enhanced electroactivity to the system and enlarges the sensor surface for binding the antibodies. It may be assumed that both electron transfer and diffusion contribute to the signal transformation between the dendrimers and the antibody.

Keywords: ferrocenyl dendrimers, electrochemical immunosensors, immunoglobulin, amperometry

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