Search results for: Mohr-Coulomb failure criterion

Authors: Sthanu Mahadev, Wen Chan, Melanie Lim

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Anisotropy dominated continuous-fiber composite materials have garnered attention in numerous mechanical and aerospace structural applications. Tailored mechanical properties in advanced composites can exhibit superiority in terms of stiffness-to-weight ratio, strength-to-weight ratio, low-density characteristics, coupled with significant improvements in fatigue resistance as opposed to metal structure counterparts. Extensive research has demonstrated their core potential as more than just mere lightweight substitutes to conventional materials. Prior work done by Mahadev and Chan focused on formulating a modified composite shell theory based prognosis methodology for investigating the structural response of thin-walled circular cylindrical shell type composite configurations under in-plane mechanical loads respectively. The prime motivation to develop this theory stemmed from its capability to generate simple yet accurate closed-form analytical results that can efficiently characterize circular composite shell construction. It showcased the development of a novel mathematical framework to analytically identify the location of the centroid for thin-walled, open cross-section, curved composite shells that were characterized by circumferential arc angle, thickness-to-mean radius ratio, and total laminate thickness. Ply stress variations for curved cylindrical shells were analytically examined under the application of centric tensile and bending loading. This work presents a cost-effective, small-platform experimental methodology by taking advantage of the full-field measurement capability of digital image correlation (DIC) for an accurate assessment of key mechanical parameters such as in-plane mechanical stresses and strains, centroid location etc. Mechanical property measurement of advanced composite materials can become challenging due to their anisotropy and complex failure mechanisms. Full-field displacement measurements are well suited for characterizing the mechanical properties of composite materials because of the complexity of their deformation. This work encompasses the fabrication of a set of curved cylindrical shell coupons, the design and development of a novel test-fixture design and an innovative experimental methodology that demonstrates the capability to very accurately predict the location of centroid in such curved composite cylindrical strips via employing a DIC based strain measurement technique. Error percentage difference between experimental centroid measurements and previously estimated analytical centroid results are observed to be in good agreement. The developed analytical modified-shell theory provides the capability to understand the fundamental behavior of thin-walled cylindrical shells and offers the potential to generate novel avenues to understand the physics of such structures at a laminate level.

Keywords: anisotropy, composites, curved cylindrical shells, digital image correlation

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Authors: Mariyah Poonawala, Selvan Ravindran, Anuradha Vaidya

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Despite much progress in understanding the regulatory factors and cytokines that support the maturation of the various cell lineages of the hematopoietic system, factors that govern the self-renewal and proliferation of hematopoietic stem cells (HSCs) is still a grey area of research. Hematopoietic stem cell transplantation (HSCT) has evolved over the years and gained tremendous importance in the treatment of both malignant and non-malignant diseases. However, factors such as graft rejection and multiple organ failure have challenged HSCT from time to time, underscoring the urgent need for development of milder processes for successful hematopoietic transplantation. An emerging concept in the field of stem cell biology states that the interactions between the bone-marrow micro-environment and the hematopoietic stem and progenitor cells is essential for regulation, maintenance, commitment and proliferation of stem cells. Understanding the role of mesenchymal stromal cells in modulating the functionality of HSCs is, therefore, an important area of research. Trans-resveratrol has been extensively studied for its various properties to combat and prevent cancer, diabetes and cardiovascular diseases etc. The aim of the present study was to understand the effect of trans-resveratrol on HSCs using single and co-culture systems. We have used KG1a cells since it is a well accepted hematopoietic stem cell model system. Our preliminary experiments showed that low concentrations of trans-resveratrol stimulated the HSCs to undergo proliferation whereas high concentrations of trans-resveratrol did not stimulate the cells to proliferate. We used a murine fibroblast cell line, M210B4, as a stromal feeder layer. On culturing the KG1a cells with M210B4 cells, we observed that the stimulatory as well as inhibitory effects of trans-resveratrol at low and high concentrations respectively, were enhanced. Our further experiments showed that low concentration of trans-resveratrol reduced the generation of reactive oxygen species (ROS) and nitric oxide (NO) whereas high concentrations increased the oxidative stress in KG1a cells. We speculated that perhaps the oxidative stress was imposing inhibitory effects at high concentration and the same was confirmed by performing an apoptotic assay. Furthermore, cell cycle analysis and growth kinetic experiments provided evidence that low concentration of trans-resveratrol reduced the doubling time of the cells. Our hypothesis is that perhaps at low concentration of trans-resveratrol the cells get pushed into the G0/G1 phase and re-enter the cell cycle resulting in their proliferation, whereas at high concentration the cells are perhaps arrested at G2/M phase or at cytokinesis and therefore undergo apoptosis. Liquid Chromatography-Quantitative-Time of Flight–Mass Spectroscopy (LC-Q-TOF MS) analyses indicated the presence of trans-resveratrol and its metabolite(s) in the supernatant of the co-cultured cells incubated with high concentration of trans-resveratrol. We conjecture that perhaps the metabolites of trans-resveratrol are responsible for the apoptosis observed at the high concentration. Our findings may shed light on the unsolved problems in the in vitro expansion of stem cells and may have implications in the ex vivo manipulation of HSCs for therapeutic purposes.

Keywords: co-culture system, hematopoietic micro-environment, KG1a cell line, M210B4 cell line, trans-resveratrol

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Authors: Inas Raafat, Azza El Bassiouny, Waldemar L. Olszewsky, Nagui E. Mikhail, Mona Nossier, Nora E. I. El-Bassiouni, Mona Zoheiry, Houda Abou Taleb, Noha Abd El-Aal, Ali Baioumy, Shimaa Attia

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Background: Orthotopic liver transplantation is an established treatment for patients with severe acute and end-stage chronic liver disease. The shortage of donor organs continues to be the rate-limiting factor for liver transplantation throughout the world. Hepatocyte transplantation is a promising treatment for several liver diseases and can, also, be used as a "bridge" to liver transplantation in cases of liver failure. Aim of the work: This study was designed to develop a highly efficient protocol for isolation and transplantation of hepatocytes in experimental Lewis rat model to provide satisfactory guidelines for future application on humans.Materials and Methods: Hepatocytes were isolated from the liver by double perfusion technique and bone marrow cells were isolated by centrifugation of shafts of tibia and femur of donor Lewis rats. Recipient rats were subjected to sub-lethal dose of irradiation 2 days before transplantation. In a laparotomy operation the spleen was injected by freshly isolated hepatocytes and bone marrow cells were injected intravenously. The animals were sacrificed 45 day latter and splenic sections were prepared and stained with H & E, PAS AFP and Prox1. Results: The data obtained from this study showed that the double perfusion technique is successful in separation of hepatocytes regarding cell number and viability. Also the method used for bone marrow cells separation gave excellent results regarding cell number and viability. Intrasplenic engraftment of hepatocytes and live tissue formation within the splenic tissue were found in 70% of cases. Hematoxylin and eosin stained splenic sections from 7 rats showed sheets and clusters of cells among the splenic tissues. Periodic Acid Schiff stained splenic sections from 7 rats showed clusters of hepatocytes with intensely stained pink cytoplasmic granules denoting the presence of glycogen. Splenic sections from 7 rats stained with anti-α-fetoprotein antibody showed brownish cytoplasmic staining of the hepatocytes denoting positive expression of AFP. Splenic sections from 7 rats stained with anti-Prox1 showed brownish nuclear staining of the hepatocytes denoting positive expression of Prox1 gene on these cells. Also, positive expression of Prox1 gene was detected on lymphocytes aggregations in the spleens. Conclusions: Isolation of liver cells by double perfusion technique using collagenase buffer is a reliable method that has a very satisfactory yield regarding cell number and viability. The intrasplenic route of transplantation of the freshly isolated liver cells in an immunocompromised model was found to give good results regarding cell engraftment and tissue formation. Further studies are needed to assess function of engrafted hepatocytes by measuring prothrombin time, serum albumin and bilirubin levels.

Keywords: Lewis rats, hepatocytes, BMCs, transplantation, AFP, Prox1

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Authors: Eleni Karasavvidou

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Social and anthropological research, parallel to Gender Studies, highlighted the relationship between social structures and symbolic forms as an important field of interaction and recording of 'social trends.' Since the study of representations can contribute to the understanding of the social functions and power relations, they encompass. This ‘mirage,’ however, has not only to do with the representations themselves but also with the ways they are received and the film or critical narratives that are established as dominant or alternative. Cinema and the criticism of its cultural products are no exception. Even in the rapidly changing media landscape of the 21st century, movies remain an integral and widespread part of popular culture, making films an extremely powerful means of 'legitimizing' or 'delegitimizing' visions of domination and commonsensical gender stereotypes throughout society. And yet it is film criticism, the 'language per se,' that legitimizes, reinforces, rewards and reproduces (or at least ignores) the stereotypical depictions of female roles that remain common in the realm of film images. This creates the need for this issue to have emerged (also) in academic research questioning gender criteria in film reviews as part of the effort for an inclusive art and society. Qualitative content analysis is used to examine female roles in selected Oscar-nominated films against their reviews from leading websites and newspapers. This method was chosen because of the complex nature of the depictions in the films and the narratives they evoke. The films were divided into basic scenes depicting social functions, such as love and work relationships, positions of power and their function, which were analyzed by content analysis, with borrowings from structuralism (Gennette) and the local/universal images of intercultural philology (Wierlacher). In addition to the measurement of the general ‘representation-time’ by gender, other qualitative characteristics were also analyzed, such as: speaking time, sayings or key actions, overall quality of the character's action in relation to the development of the scenario and social representations in general, as well as quantitatively (insufficient number of female lead roles, fewer key supporting roles, relatively few female directors and people in the production chain and how they might affect screen representations. The quantitative analysis in this study was used to complement the qualitative content analysis. Then the focus shifted to the criteria of film criticism and to the rhetorical narratives that exclude or highlight in relation to gender identities and functions. In the criteria and language of film criticism, stereotypes are often reproduced or allegedly overturned within the framework of apolitical "identity politics," which mainly addresses the surface of a self-referential cultural-consumer product without connecting it more deeply with the material and cultural life. One of the prime examples of this failure is the Bechtel Test, which tracks whether female characters speak in a film regardless of whether women's stories are represented or not in the films analyzed. If perceived unbiased male filmmakers still fail to tell truly feminist stories, the same is the case with the criteria of criticism and the related interventions.

Keywords: representations, context analysis, reviews, sexist stereotypes

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Authors: Gokulan Vethanayakam, Daniel Aston

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Introduction: The ReSPECT process supports healthcare professionals when making patient-centered decisions in the event of an emergency. It has been widely adopted by the NHS in England and allows patients to express thoughts and wishes about treatments and outcomes that they consider acceptable. It includes (but is not limited to) cardiopulmonary resuscitation decisions. ReSPECT conversations should ideally occur prior to ICU admission and should be documented in the eight sections of the nationally-standardised ReSPECT form. This audit evaluated the use of ReSPECT on a busy cardiothoracic ICU in an NHS Trust where established policies advocating its use exist. Methods: This audit was a retrospective review of ReSPECT forms for a sample of high-risk patients admitted to ICU at the Royal Papworth Hospital between January 2021 and March 2022. Patients all received one of the following interventions: Veno-Venous Extra-Corporeal Membrane Oxygenation (VV-ECMO) for severe respiratory failure (retrieved via the national ECMO service); cardiac or pulmonary transplantation-related surgical procedures (including organ transplants and Ventricular Assist Device (VAD) implantation); or elective non-transplant cardiac surgery. The quality of documentation on ReSPECT forms was evaluated using national standards and a graded ranking tool devised by the authors which was used to assess narrative aspects of the forms. Quality was ranked as A (excellent) to D (poor). Results: Of 230 patients (74 VV-ECMO, 104 transplant, 52 elective non-transplant surgery), 43 (18.7%) had a ReSPECT form and only one (0.43%) patient had a ReSPECT form completed prior to ICU admission. Of the 43 forms completed, 38 (88.4%) were completed due to the commencement of End of Life (EoL) care. No non-transplant surgical patients included in the audit had a ReSPECT form. There was documentation of balance of care (section 4a), CPR status (section 4c), capacity assessment (section 5), and patient involvement in completing the form (section 6a) on all 43 forms. Of the 34 patients assessed as lacking capacity to make decisions, only 22 (64.7%) had reasons documented. Other sections were variably completed; 29 (67.4%) forms had relevant background information included to a good standard (section 2a). Clinical guidance for the patient (section 4b) was given in 25 (58.1%), of which 11 stated the rationale that underpinned it. Seven forms (16.3%) contained information in an inappropriate section. In a comparison of ReSPECT forms completed ahead of an EoL trigger with those completed when EoL care began, there was a higher number of entries in section 3 (considering patient’s values/fears) that were assessed at grades A-B in the former group (p = 0.014), suggesting higher quality. Similarly, forms from the transplant group contained higher quality information in section 3 than those from the VV-ECMO group (p = 0.0005). Conclusions: Utilisation of the ReSPECT process in high-risk patients is yet to be well-adopted in this trust. Teams who meet patients before hospital admission for transplant or high-risk surgery should be encouraged to engage with the ReSPECT process at this point in the patient's journey. VV-ECMO retrieval teams should consider ReSPECT conversations with patients’ relatives at the time of retrieval.

Keywords: audit, critical care, end of life, ICU, ReSPECT, resuscitation

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Authors: S. B. R. Slagmulder

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Monitoring inspiratory effort and dynamic lung stress in patients on pressure support ventilation in the ICU is important for protecting against self inflicted lung injury (P-SILI) and diaphragm dysfunction. Strategies to address the detrimental effects of respiratory drive and effort can lead to improved patient outcomes. Two non-invasive estimation methods, occlusion pressure (Pocc) and P0.1, have been proposed for achieving lung and diaphragm protective ventilation. However, their relationship and interpretation in neuro ICU patients is not well understood. P0.1 is the airway pressure measured during a 100-millisecond occlusion of the inspiratory port. It reflects the neural drive from the respiratory centers to the diaphragm and respiratory muscles, indicating the patient's respiratory drive during the initiation of each breath. Occlusion pressure, measured during a brief inspiratory pause against a closed airway, provides information about the inspiratory muscles' strength and the system's total resistance and compliance. Research Objective: Understanding the relationship between Pocc and P0.1 in brain-injured patients can provide insights into the interpretation of these values in pressure support ventilation. This knowledge can contribute to determining extubation readiness and optimizing ventilation strategies to improve patient outcomes. The central goal is to asses a study protocol for determining the relationship between Pocc and P0.1 in brain-injured patients on pressure support ventilation and their ability to predict successful extubation. Additionally, comparing these values between brain-damaged and non-brain-damaged patients may provide valuable insights. Key Areas of Inquiry: 1. How do Pocc and P0.1 values correlate within brain injury patients undergoing pressure support ventilation? 2. To what extent can Pocc and P0.1 values serve as predictive indicators for successful extubation in patients with brain injuries? 3. What differentiates the Pocc and P0.1 values between patients with brain injuries and those without? Methodology: P0.1 and occlusion pressures are standard measurements for pressure support ventilation patients, taken by attending doctors as per protocol. We utilize electronic patient records for existing data. Unpaired T-test will be conducted to compare P0.1 and Pocc values between both study groups. Associations between P0.1 and Pocc and other study variables, such as extubation, will be explored with simple regression and correlation analysis. Depending on how the data evolve, subgroup analysis will be performed for patients with and without extubation failure. Results: While it is anticipated that neuro patients may exhibit high respiratory drive, the linkage between such elevation, quantified by P0.1, and successful extubation remains unknown The analysis will focus on determining the ability of these values to predict successful extubation and their potential impact on ventilation strategies. Conclusion: Further research is pending to fully understand the potential of these indices and their impact on mechanical ventilation in different patient populations and clinical scenarios. Understanding these relationships can aid in determining extubation readiness and tailoring ventilation strategies to improve patient outcomes in this specific patient population. Additionally, it is vital to account for the influence of sedatives, neurological scores, and BMI on respiratory drive and occlusion pressures to ensure a comprehensive analysis.

Keywords: brain damage, diaphragm dysfunction, occlusion pressure, p0.1, respiratory drive

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Authors: Natalie Hoyer

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Usually, steel structures are designed for the upper region of the steel toughness-temperature curve. To address the reduced toughness properties in the temperature transition range, additional safety assessments based on fracture mechanics are necessary. These assessments enable the appropriate selection of steel materials to prevent brittle fracture. In this context, recommendations were established in 2011 to regulate the appropriate selection of steel grades for bridge bearing components. However, these recommendations are no longer fully aligned with more recent insights: Designing bridge bearings and their components in accordance with DIN EN 1337 and the relevant sections of DIN EN 1993 has led to an increasing trend of using large plate thicknesses, especially for long-span bridges. However, these plate thicknesses surpass the application limits specified in the national appendix of DIN EN 1993-2. Furthermore, compliance with the regulations outlined in DIN EN 1993-1-10 regarding material toughness and through-thickness properties requires some further modifications. Therefore, these standards cannot be directly applied to the material selection for bearings without additional information. In addition, recent findings indicate that certain bridge bearing components are subjected to high fatigue loads, necessitating consideration in structural design, material selection, and calculations. To address this issue, the German Center for Rail Traffic Research initiated a research project aimed at developing a proposal to enhance the existing standards. This proposal seeks to establish guidelines for the selection of steel materials for bridge bearings to prevent brittle fracture, particularly for thick plates and components exposed to specific fatigue loads. The results derived from theoretical analyses, including finite element simulations and analytical calculations, are verified through component testing on a large-scale. During these large-scale tests, where a brittle failure is deliberately induced in a bearing component, an artificially generated defect is introduced into the specimen at the predetermined hotspot. Subsequently, a dynamic load is imposed until the crack initiation process transpires, replicating realistic conditions akin to a sharp notch resembling a fatigue crack. To stop the action of the dynamic load in time, it is important to precisely determine the point at which the crack size transitions from stable crack growth to unstable crack growth. To achieve this, the potential drop measurement method is employed. The proposed paper informs about the choice of measurement method (alternating current potential drop (ACPD) or direct current potential drop (DCPD)), presents results from correlations with created FE models, and may proposes a new approach to introduce beach marks into the fracture surface within the framework of potential drop measurement.

Keywords: beach marking, bridge bearing design, brittle fracture, design for fatigue, potential drop

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Authors: Pamela Chia, Tay Yoong Chuan

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Introduction: Severe pulmonary hypertension (PH) patients requiring non-cardiac surgery risk have increased mortality rates ranging. These patients are plagued with cardiorespiratory failure, dysrhythmias and anticoagulation potentially with concurrent sepsis and renal insufficiency, perioperative morbidity. We present a deaf-mute patient with severe idiopathic PH emergently prepared for ruptured ectopic laparotomy. Case Report: A 20 year-old female, 62kg (BMI 25 kg/m2) with severe idiopathic PH (2DE Ejection Fraction was 41%, Pulmonary Artery Systolic Pressure (PASP) 105 mmHg, Right ventricle strain and hypertrophy) and selective mutism was rushed in for emergency laparotomy after presenting to the emergency department for abdominal pain. The patient had an NYHA Class II with room air SpO2 93-95%. While awaiting lung transplant, the patient takes warfarin, Sildanefil, Macitentan and even Selexipag for rising PASP. At presentation, vital signs: BP 95/63, HR 119 SpO2 88% (room air). Despite decreasing haemoglobin 14 to 10g/dL, INR 2.59 was reversed with prothrombin concentrate, and Vitamin K. ECG revealed Right Bundle Branch Block with right ventricular strain and x-ray showed cardiomegaly, dilated Right Ventricle, Pulmonary Arteries, basal atelectasis. Arterial blood gas showed compensated metabolic acidosis pH 7.4 pCO2 32 pO2 53 HCO3 20 BE -4 SaO2 88%. The cardiothoracic surgeon concluded no role for Extracorporeal Membrane Oxygenation (ECMO). We inserted invasive arterial and central venous lines with blood transfusion via an 18G cannula before the patient underwent a midline laparotomy, haemostasis of ruptured ovarian cyst with 2.4L of clots under general anesthesia and FloTrac cardiac output monitoring. Rapid sequence induction was done with Midazolam/Propofol, remifentanil infusion, and rocuronium. The patient was maintained on Desflurane. Blood products and colloids were transfused for further 1.5L blood loss. Postoperatively, the patient was transferred to the intensive care unit and was extubated uneventfully 7hours later. The patient went home a week later. Discussion: Emergency hemostasis laparotomy in anticoagulated WHO Class I PH patient awaiting lung transplant with no ECMO backup poses tremendous stress on the deaf-mute patient and the anesthesiologist. Balancing hemodynamics avoiding hypotension while awaiting hemostasis in the presence of pulmonary arterial dilators and anticoagulation requires close titration of volatiles, which decreases RV contractility. We review the contraindicated anesthetic agents (ketamine, N2O), choice of vasopressors in hypotension to maintain Aortic-right ventricular pressure gradients and nitric oxide use perioperatively. Conclusion: Interdisciplinary communication with a deaf-mute moribund patient and anesthesia considerations pose many rare challenges worth sharing.

Keywords: pulmonary hypertension, case report, warfarin reversal, emergency surgery

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Authors: Roberta Pecoraro, Elena Maria Scalisi

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Engineered Nanoparticles (ENPs) and Nanomaterials (ENMs) concern an active research area and a sector in full expansion. They have physical-chemical characteristics and small size that improve their performance compared to common materials. Due to the increase in their production and their subsequent release into the environment, new strategies are emerging to assess risk of nanomaterials. NPs can be released into the environment through aquatic systems by human activities and exert toxicity on living organisms. We evaluated the potential toxic effect of cerium oxide (CeO2) nanoparticles because it’s used in different fields due to its peculiar properties. In order to assess nanoparticles toxicity, Fish Embryo Toxicity (FET) test was performed. Powders of CeO2 NPs supplied by the CNR-IMM of Catania are indicated as CeO2 type 1 (as-prepared) and CeO2 type 2 (modified), while CeO2 type 3 (commercial) is supplied by Sigma-Aldrich. Starting from a stock solution (0.001g/10 ml dilution water) of each type of CeO2 NPs, the other concentration solutions were obtained adding 1 ml of the stock solution to 9 ml of dilution water, leading to three different solutions of concentration (10-4, 10-5, 10-6 g/ml). All the solutions have been sonicated to avoid natural tendency of NPs to aggregate and sediment. FET test was performed according to the OECD guidelines for testing chemicals using our internal protocol procedure. A number of eight selected fertilized eggs were placed in each becher filled with 5 ml of each concentration of the three types of CeO2 NPs; control samples were incubated only with dilution water. Replication was performed for each concentration. During the exposure period, we observed four endpoints (embryo coagulation, lack of formation of somites, failure to lift the yolk bag, no heartbeat) by a stereomicroscope every 24 hours. Immunohistochemical analysis on treated larvae was performed to evaluate the expression of metallothioneins (MTs), Heat Shock Proteins 70 (HSP70) and 7-ethoxyresorufin-O-diethylase (EROD). Our results have not shown evident alterations on embryonic development because all embryos completed the development and the hatching of the eggs, started around the 48th hour after exposure, took place within the last observation at 72 hours. A good reactivity, both in the embryos and in the newly hatched larvae, was found. The presence of heartbeat has also been observed in embryos with reduced mobility confirming their viability. A higher expression of EROD biomarker was observed in the larvae exposed to the three types of CeO2, showing a clear difference with the control. A weak positivity was found for MTs biomarker in treated larvae as well as in the control. HSP70 are expressed homogeneously in all the type of nanoparticles tested but not too much greater than control. Our results are in agreement with other studies in the literature, in which the exposure of Danio rerio larvae to other metal oxide nanoparticles does not show adverse effects on survival and hatching time. Further studies are necessary to clarify the role of these NPs and also to solve conflicting opinions.

Keywords: Danio rerio, endpoints, fish embryo toxicity test, metallic nanoparticles

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Authors: Robert Pocklington

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Most current language courses expect students to be ‘vocational’, sacrificing their free time in order to learn. However, pupils with a full-time job, or bringing up children, hardly have a spare moment. Others just need the language as a tool or a qualification, as if it were book-keeping or a driving license. Then there are children in unstructured families whose stressful life makes private study almost impossible. And the countless parents whose evenings and weekends have become a nightmare, trying to get the children to do their homework. There are many arguments against homework being a necessity (rather than an optional extra for more ambitious or dedicated students), making a clear case for teaching methods which facilitate full learning of the key content within the classroom. A methodology which could be described as Programmed Mastery Learning has been used at Fluency Language Academy (Spain) since 1992, to teach English to over 4000 pupils yearly, with a staff of around 100 teachers, barely requiring homework. The course is structured according to the tenets of Programmed Learning: small manageable teaching steps, immediate feedback, and constant successful activity. For the Mastery component (not stopping until everyone has learned), the memorisation and practice are entrusted to flashcard-based drilling in the classroom, leading all students to progress together and develop a permanently growing knowledge base. Vocabulary and expressions are memorised using flashcards as stimuli, obliging the brain to constantly recover words from the long-term memory and converting them into reflex knowledge, before they are deployed in sentence building. The use of grammar rules is practised with ‘cue’ flashcards: the brain refers consciously to the grammar rule each time it produces a phrase until it comes easily. This automation of lexicon and correct grammar use greatly facilitates all other language and conversational activities. The full B2 course consists of 48 units each of which takes a class an average of 17,5 hours to complete, allowing the vast majority of students to reach B2 level in 840 class hours, which is corroborated by an 85% pass-rate in the Cambridge University B2 exam (First Certificate). In the past, studying for qualifications was just one of many different options open to young people. Nowadays, youngsters need to stay at school and obtain qualifications in order to get any kind of job. There are many students in our classes who have little intrinsic interest in what they are studying; they just need the certificate. In these circumstances and with increasing government pressure to minimise failure, teachers can no longer think ‘If they don’t study, and fail, its their problem’. It is now becoming the teacher’s problem. Teachers are ever more in need of methods which make their pupils successful learners; this means assuring learning in the classroom. Furthermore, homework is arguably the main divider between successful middle-class schoolchildren and failing working-class children who drop out: if everything important is learned at school, the latter will have a much better chance, favouring inclusiveness in the language classroom.

Keywords: flashcard drilling, fluency method, mastery learning, programmed learning, teaching English as a foreign language

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Authors: Banafsheh Nikmehr, Mohsen Bahrami, Yueqiang Song, Anuradha Koduru, Ayse K. Vuruskan, Hongkun Lu, Mallory Pitts, Tolga B. Mesen, Tamer M. Yalcinkaya

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The number of people who receive in vitro fertilization (IVF) treatment has increased on a startling trajectory over the past two decades. Despite advances in this field, particularly the introduction of intracytoplasmic sperm injection (ICSI) and the preimplantation genetic screening (PGS), the IVF success remains low. A major factor contributing to IVF failure is embryonic aneuploidy (abnormal chromosome content), which often results in miscarriage and birth defects. Although PGS is often used as the standard diagnostic tool to identify aneuploid embryos, it is an invasive approach that could affect the embryo development, and yet inaccessible to many patients due its high costs. As such, there is a clear need for a non-invasive cost-effective approach to identify euploid embryos for single embryo transfer (SET). The reported differences between morphokinetic behaviors of aneuploid and euploid embryos has shown promise to address this need. However, current literature is inconclusive and further research is urgently needed to translate current findings into clinical diagnostics. In this ongoing study, we found significant differences between morphokinetic behaviors of euploid and aneuploid embryos that provides important insights and reaffirms the promise of such behaviors for developing non-invasive methodologies. Methodology—A total of 242 embryos (euploid: 149, aneuploid: 93) from 74 patients who underwent IVF treatment in Carolinas Fertility Clinics in Winston-Salem, NC, were analyzed. All embryos were incubated in an EmbryoScope incubator. The patients were randomly selected from January 2019 to June 2021 with most patients having both euploid and aneuploid embryos. All embryos reached the blastocyst stage and had known PGS outcomes. The ploidy assessment was done by a third-party testing laboratory on day 5-7 embryo biopsies. The morphokinetic variables of each embryo were measured by the EmbryoViewer software (Uniesense FertiliTech) on time-lapse images using 7 focal depths. We compared the time to: pronuclei fading (tPNf), division to 2,3,…,9 cells (t2, t3,…,t9), start of embryo compaction (tSC), Morula formation (tM), start of blastocyst formation (tSC), blastocyst formation (tB), and blastocyst expansion (tEB), as well as intervals between them (e.g., c23 = t3 – t2). We used a mixed regression method for our statistical analyses to account for the correlation between multiple embryos per patient. Major Findings— The average age of the patients was 35.04 yrs. The average patient age associated with euploid and aneuploid embryos was not different (P = 0.6454). We found a significant difference in c45 = t5-t4 (P = 0.0298). Our results indicated this interval on average lasts significantly longer for aneuploid embryos - c45(aneuploid) = 11.93hr vs c45(euploid) = 7.97hr. In a separate analysis limited to embryos from the same patients (patients = 47, total embryos=200, euploid=112, aneuploid=88), we obtained the same results (P = 0.0316). The statistical power for this analysis exceeded 87%. No other variable was different between the two groups. Conclusion— Our results demonstrate the importance of morphokinetic variables as potential biomarkers that could aid in non-invasively characterizing euploid and aneuploid embryos. We seek to study a larger population of embryos and incorporate the embryo quality in future studies.

Keywords: IVF, embryo, euploidy, aneuploidy, morphokinteic

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Authors: Irfan Anjum Manarvi, Fawzi Aljassir

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Human bones have been a keen area of research over a long time in the field of biomechanical engineering. Medical professionals, as well as engineering academics and researchers, have investigated various bones by using medical, mechanical, and materials approaches to discover the available body of knowledge. Their major focus has been to establish properties of these and ultimately develop processes and tools either to prevent fracture or recover its damage. Literature shows that mechanical professionals conducted a variety of tests for hardness, deformation, and strain field measurement to arrive at their findings. However, they considered these results accuracy to be insufficient due to various limitations of tools, test equipment, difficulties in the availability of human bones. They proposed the need for further studies to first overcome inaccuracies in measurement methods, testing machines, and experimental errors and then carry out experimental or theoretical studies. Finite Element analysis is a technique which was developed for the aerospace industry due to the complexity of design and materials. But over a period of time, it has found its applications in many other industries due to accuracy and flexibility in selection of materials and types of loading that could be theoretically applied to an object under study. In the past few decades, the field of biomechanical engineering has also started to see its applicability. However, the work done in the area of Tarsals, metatarsals and phalanges using this technique is very limited. Therefore, present research has been focused on using this technique for analysis of these critical bones of the human body. This technique requires a 3-dimensional geometric computer model of the object to be analyzed. In the present research, a 3d laser scanner was used for accurate geometric scans of individual tarsals, metatarsals, and phalanges from a typical human foot to make these computer geometric models. These were then imported into a Finite Element Analysis software and a length refining process was carried out prior to analysis to ensure the computer models were true representatives of actual bone. This was followed by analysis of each bone individually. A number of constraints and load conditions were applied to observe the stress and strain distributions in these bones under the conditions of compression and tensile loads or their combination. Results were collected for deformations in various axis, and stress and strain distributions were observed to identify critical locations where fracture could occur. A comparative analysis of failure properties of all the three types of bones was carried out to establish which of these could fail earlier which is presented in this research. Results of this investigation could be used for further experimental studies by the academics and researchers, as well as industrial engineers, for development of various foot protection devices or tools for surgical operations and recovery treatment of these bones. Researchers could build up on these models to carryout analysis of a complete human foot through Finite Element analysis under various loading conditions such as walking, marching, running, and landing after a jump etc.

Keywords: tarsals, metatarsals, phalanges, 3D scanning, finite element analysis

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Authors: Nautiyal Ruchira, Nautiyal Hemant, Chaudhury Devnanda, Bhargava Surbhi, Chauhan Nidhi

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Introduction: South East Asian region contributes 2.5 million cases of malaria each year to the global burden of 300 to 500 million of which 76% is reported from India. Government of India launched a national program almost half a century ago, still malaria remains a major public health challenge. Pregnant women are more susceptible to severe malaria and its fetomaternal complications. Inadequate surveillance and under-reporting underestimates the problem. Aim: Present study aimed to analyze the clinical course and pattern of malaria during pregnancy and to study the feto-maternal outcome. Methodology: This is a prospective observational study carried out at Himalayan Institute of Medical Sciences – a tertiary care center in the sub-Himalayan state of Uttarakhand, Northern India. All the pregnant women with malaria and its complications were recruited in the study during 2009 to 2014 which included referred cases from the state of western Uttar Pradesh. A thorough history and clinical examination were carried out to assess maternal and fetal condition. Relevant investigations including haemogram, platelet count, LFT, RFT, and USG was done. Blood slides and rapid diagnostic tests were done to diagnose the type of malaria.The primary outcomes measured were the type of malaria infection, maternal complications associated with malaria, outcome of pregnancy and effect on the fetus. Results: 67 antenatal cases with malaria infection were studied. 71% patients were diagnosed with plasmodium vivax infection, 25% cases were plasmodium falciparum positive and in 3% cases mixed infection was found. 38(56%) patients were primigravida and 29(43%) were multiparous. Most of the patients had already received some treatment from their local doctors and presented with severe malaria with the complications. Thrombocytopenia was the commonest manifestation seen in 35(52%) patients, jaundice in 28%, severe anemia in 18%, and severe oligohydramnios in 10% and renal failure in 6% cases. Regarding pregnancy outcome there were 44 % preterm deliveries, 22% had IUFD and abortions in 6% cases.20% of newborn were low birth weight and 6% were IUGR. There was only one maternal death which occurred due to ARDS in falciparum malaria. Although Plasmodium vivax was the main parasite considering the severity of clinical presentation, all the patients received intensive care. As most of the patients had received chloroquine therapy hence they were treated with IV artesunate followed by oral artemesinin combination therapy. Other therapies in the form of packed RBC’s and platelet transfusions, dialysis and ventilator support were provided when required. Conclusion: Even in areas with annual parasite index (API) less than 2 like ours, malaria in pregnancy could be an alarming problem. Vivax malaria cannot be considered benign in pregnancy because of high incidence of morbidity. Prompt diagnosis and aggressive treatment can reduce morbidity and mortality significantly. Increased community level research, integrating ANC checkups with the distribution of insecticide-treated nets in areas of high endemicity, imparting education and awareness will strengthen the existing control strategies.

Keywords: severe malaria, pregnancy, plasmodium vivax, plasmodium falciparum

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Authors: Jason Ceavers, Travis Thompson, Juan Torres, Ramanakumar Anam, Alan Wong, Andrei Carvalho, Shane Quo, Shawn Alonso, Moises Cintron, Ricardo C. Carrero, German Lopez, Vamsi Garimella, German Giese

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Introduction: Advance directives (AD) are essential for patients to communicate their wishes when they are not able to. Ideally, these discussions should not occur for the first time when a patient is hospitalized with an acute life-threatening illness. There is a large number of patients who do not have clearly documented ADs, resulting in the misutilization of resources and additional patient harm. This is a nationwide issue, and the Joint Commission has it as one of its national quality metrics. Presented here is a proposed protocol to increase the number of documented AD discussions in a community-based, internal medicine residency primary care clinic in South Florida. Methods: The SMART Aim for this quality improvement project is to increase documentation of AD discussions in the outpatient setting by 25% within three months in medicare patients. A survey was sent to stakeholders (clinic attendings, residents, medical assistants, front desk staff, and clinic managers), asking them for three factors they believed contributed most to the low documentation rate of AD discussions. The two most important factors were time constraints and systems issues (such as lack of a standard method to document ADs and ADs not being uploaded to the chart) which were brought up by 25% and 21.2% of the 32 survey responders, respectively. Pre-intervention data from clinic patients in 2020-2021 revealed 17.05% of patients had clear, actionable ADs documented. To address these issues, an AD pocket card was created to give to patients. One side of the card has a brief explanation of what ADs are. The other side has a column of interventions (cardiopulmonary resuscitation, mechanical ventilation, dialysis, tracheostomy, feeding tube) with boxes patients check off if they want the intervention done, do not want the intervention, do not want to discuss the topic, or need more information. These cards are to be filled out and scanned into their electronic chart to be reviewed by the resident before their appointment. The interventions that patients want more information on will be discussed by the provider. If any changes are made, the card will be re-scanned into their chart. After three months, we will chart review the patients seen in the clinic to determine how many medicare patients have a pocket card uploaded and how many have advance directives discussions documented in a progress note or annual wellness note. If there is not enough time for an AD discussion, a follow-up appointment can be scheduled for that discussion. Discussion: ADs are a crucial part of patient care, and failure to understand a patient’s wishes leads to improper utilization of resources, avoidable litigation, and patient harm. Time constraints and systems issues were identified as two major factors contributing to the lack of advance directive discussion in our community-based resident primary care clinic. Our project aims at increasing the documentation rate for ADs through a simple pocket card intervention. These are self-explanatory, easy to read and allow the patients to clearly express what interventions they desire or what they want to discuss further with their physician.

Keywords: advance directives, community-based, pocket card, primary care clinic

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Authors: T. Ghatauray, J. Ingram, P. Holborn

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The transition from a ‘carbon rich’ fossil fuel dependent to a ‘sustainable’ and ‘renewable’ hydrogen based society will see the deployment of hydrogen fuel cells (HFC) in transport applications and in the generation of heat and power for buildings, as part of a decentralised power network. Many deployments will be low power HFCs for domestic combined heat and power (CHP) and commercial ‘transportable’ HFCs for environmental situations, such as lighting and telephone towers. For broad commercialisation of small fuel cells to be achieved there needs to be significant confidence in their safety in both domestic and environmental applications. Low power HFCs are housed in protective steel enclosures. Standard enclosures have plain rectangular ventilation openings intended for thermal management of electronics and not the dispersion of a buoyant gas. Degradation of the HFC or supply pipework in use could lead to a low-level leak and a build-up of hydrogen gas in the enclosure. Hydrogen’s wide flammable range (4-75%) is a significant safety concern, with ineffective enclosure ventilation having the potential to cause flammable mixtures to develop with the risk of explosion. Mechanical ventilation is effective at managing enclosure hydrogen concentrations, but drains HFC power and is vulnerable to failure. This is undesirable in low power and remote installations and reliable passive ventilation systems are preferred. Passive ventilation depends upon buoyancy driven flow, with the size, shape and position of ventilation openings critical for producing predictable flows and maintaining low buoyant gas concentrations. With environmentally sited enclosures, ventilation openings with pressed horizontal and angled louvres are preferred to protect the HFC and electronics inside. There is an economic cost to adding louvres, but also a safety concern. A question arises over whether the use of pressed louvre vents impairs enclosure passive ventilation performance, when compared to same opening area plain vents. Comparison small enclosure (0.144m³) tests of same opening area pressed louvre and plain vents were undertaken. A displacement ventilation arrangement was incorporated into the enclosure with opposing upper and lower ventilation openings. A range of vent areas were tested. Helium (used as a safe analogue for hydrogen) was released from a 4mm nozzle at the base of the enclosure to simulate a hydrogen leak at leak rates from 1 to 10 lpm. Helium sensors were used to record concentrations at eight heights in the enclosure. The enclosure was otherwise empty. These tests determined that the use of pressed and angled louvre ventilation openings on the enclosure impaired the passive ventilation flow and increased helium concentrations in the enclosure. High-level stratified buoyant gas layers were also found to be deeper than with plain vent openings and were within the flammable range. The presence of gas within the flammable range is of concern, particularly as the addition of the fuel cell and electronics in the enclosure would further reduce the available volume and increase concentrations. The opening area of louvre vents would need to be greater than equivalent plain vents to achieve comparable ventilation flows or alternative schemes would need to be considered.

Keywords: enclosure, fuel cell, helium, hydrogen safety, louvre vent, passive ventilation

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Authors: Antonela Matana, Dubravka Brdar, Vesela Torlak, Marijana Popovic, Ivana Gunjaca, Ozren Polasek, Vesna Boraska Perica, Maja Barbalic, Ante Punda, Caroline Hayward, Tatijana Zemunik

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Parathyroid hormone (PTH) plays a critical role in the regulation of bone mineral metabolism and calcium homeostasis. Higher PTH levels are associated with heart failure, hypertension, coronary artery disease, cardiovascular mortality and poorer bone health. A twin study estimated that 60% of the variation in PTH concentrations is genetically determined. Only one GWAS of PTH concentration has been reported to date. Identified loci explained 4.5% of the variance in circulating PTH, suggesting that additional genetic variants remain undiscovered. Therefore, the aim of this study was to identify novel genetic variants associated with PTH levels in a general population. We have performed a GWAS meta-analysis on 2596 individuals originating from three Croatian cohorts: City of Split and the Islands of Korčula and Vis, within a large-scale project of “10,001 Dalmatians”. A total of 7 411 206 variants, imputed using the 1000 Genomes reference panel, with minor allele frequency ≥ 1% and Rsq ≥ 0.5 were analyzed for the association. GWAS within each data set was performed under an additive model, controlling for age, gender and relatedness. Meta-analysis was conducted using the inverse-variance fixed-effects method. Furthermore, to identify sex-specific effects, we have conducted GWAS meta-analyses analyzing males and females separately. In addition, we have performed biological pathway analysis. Four SNPs, representing one locus, reached genome-wide significance. The most significant SNP was rs11099476 on chromosome 4 (P=1.15x10-8), which explained 1.14 % of the variance in PTH. The SNP is located near the protein-coding gene RASGEF1B. Additionally, we detected suggestive association with SNPs, rs77178854 located on chromosome 2 in the DPP10 gene (P=2.46x10-7) and rs481121 located on chromosome 1 (P=3.58x10-7) near the GRIK1 gene. One of the top hits detected in the main meta-analysis, intron variant rs77178854 located within DPP10 gene, reached genome-wide significance in females (P=2.21x10-9). No single locus was identified in the meta-analysis in males. Fifteen biological pathways were functionally enriched at a P<0.01, including muscle contraction, ion homeostasis and cardiac conduction as the most significant pathways. RASGEF1B is the guanine nucleotide exchange factor, known to be associated with height, bone density, and hip. DPP10 encodes a membrane protein that is a member of the serine proteases family, which binds specific voltage-gated potassium channels and alters their expression and biophysical properties. In conclusion, we identified 2 novel loci associated with PTH levels in a general population, providing us with further insights into the genetics of this complex trait.

Keywords: general population, genome-wide association analysis, parathyroid hormone, single nucleotide polymorphisms.

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Authors: Nancy A. Delich, Stephen D. Roberts

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This case study explores using self-efficacy theory in counseling deaf and hard of hearing students in one California school district. Self-efficacy is described as the confidence a student has for performing a set of skills required to succeed at a specific task. When students need to learn a skill, self-efficacy can be a major factor in influencing behavioral change. Self-efficacy is domain specific, meaning that students can have high confidence in their abilities to accomplish a task in one domain, while at the same time having low confidence in their abilities to accomplish another task in a different domain. The communication isolation experienced by deaf and hard of hearing children and adolescents can negatively impact their belief about their ability to navigate life challenges. There is a need to address issues that impact deaf and hard of hearing students’ social-emotional development. Failure to address these needs may result in depression, suicidal ideation, and anxiety among other mental health concerns. Self-efficacy training can be used to address these socio-emotional developmental issues with this population. Four sources of experiences are applied during an intervention: (a) enactive mastery experience, (b) vicarious experience, (c) verbal persuasion, and (d) physiological and affective states. This case study describes the use of self-efficacy training with a coed group of 12 deaf and hard of hearing high school students who experienced bullying at school. Beginning with enactive mastery experience, the counselor introduced the topic of bullying to the group. The counselor educated the students about the different types of bullying while teaching them the terminology, signs and their meanings. The most effective way to increase self-efficacy is through extensive practice. To better understand these concepts, the students practiced through role-playing with the goal of developing self-advocacy skills. Vicarious experience is the perception that students have about their capabilities. Viewing other students advocating for themselves, cognitively rehearsing what actions they will and will not take, and teaching each other how to stand up against bullying can strengthen their belief in successfully overcoming bullying. The third source of self-efficacy beliefs is verbal persuasion. It occurs when others express belief in the capabilities of the student. Didactic training and pedagogic materials on bullying were employed as part of the group counseling sessions. The fourth source of self-efficacy appraisals is physiological and affective states. Students expect positive emotions to be associated with successful skilled performance. When students practice new skills, the counselor can apply several strategies to enhance self-efficacy while reducing and controlling emotional and physical states. The intervention plan incorporated all four sources of self-efficacy training during several interactive group sessions regarding bullying. There was an increased understanding around the issues of bullying, resulting in the students’ belief of their ability to perform protective behaviors and deter future occurrences. The outcome of the intervention plan resulted in a reduction of reported bullying incidents. In conclusion, self-efficacy training can be an effective counseling and teaching strategy in addressing and enhancing the social-emotional functioning with deaf and hard of hearing adolescents.

Keywords: counseling, self-efficacy, bullying, social-emotional development, mental health, deaf and hard of hearing students

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Authors: Mahsa Mousavi, Hamid Reza Pourshaghaghi, Mohammad Tahghighi, Henk Corporaal

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Recently, Statistic Random-Access Memory-based (SRAM-based) Field-Programmable Gate Arrays (FPGAs) are widely used in aeronautics and space systems where high dependability is demanded and considered as a mandatory requirement. Since design’s circuit is stored in configuration memory in SRAM-based FPGAs; they are very sensitive to Single Event Upsets (SEUs). In addition, the adverse effects of SEUs on the electronics used in space are much higher than in the Earth. Thus, developing fault tolerant techniques play crucial roles for the use of SRAM-based FPGAs in space. However, fault tolerance techniques introduce additional penalties in system parameters, e.g., area, power, performance and design time. In this paper, an accurate estimation of configuration memory vulnerability to SEUs is proposed for approximate-tolerant applications. This vulnerability estimation is highly required for compromising between the overhead introduced by fault tolerance techniques and system robustness. In this paper, we study applications in which the exact final output value is not necessarily always a concern meaning that some of the SEU-induced changes in output values are negligible. We therefore define and propose Approximate-based Configuration Memory Vulnerability Factor (ACMVF) estimation to avoid overestimating configuration memory vulnerability to SEUs. In this paper, we assess the vulnerability of configuration memory by injecting SEUs in configuration memory bits and comparing the output values of a given circuit in presence of SEUs with expected correct output. In spite of conventional vulnerability factor calculation methods, which accounts any deviations from the expected value as failures, in our proposed method a threshold margin is considered depending on user-case applications. Given the proposed threshold margin in our model, a failure occurs only when the difference between the erroneous output value and the expected output value is more than this margin. The ACMVF is subsequently calculated by acquiring the ratio of failures with respect to the total number of SEU injections. In our paper, a test-bench for emulating SEUs and calculating ACMVF is implemented on Zynq-7000 FPGA platform. This system makes use of the Single Event Mitigation (SEM) IP core to inject SEUs into configuration memory bits of the target design implemented in Zynq-7000 FPGA. Experimental results for 32-bit adder show that, when 1% to 10% deviation from correct output is considered, the counted failures number is reduced 41% to 59% compared with the failures number counted by conventional vulnerability factor calculation. It means that estimation accuracy of the configuration memory vulnerability to SEUs is improved up to 58% in the case that 10% deviation is acceptable in output results. Note that less than 10% deviation in addition result is reasonably tolerable for many applications in approximate computing domain such as Convolutional Neural Network (CNN).

Keywords: fault tolerance, FPGA, single event upset, approximate computing

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Authors: Javier E. García-Gallo, Nelson J. Fonseca-Ruiz, John F. Duitama-Munoz

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Sepsis is a syndrome that occurs with physiological and biochemical abnormalities induced by severe infection and carries a high mortality and morbidity, therefore the severity of its condition must be interpreted quickly. After patient admission in an intensive care unit (ICU), it is necessary to synthesize the large volume of information that is collected from patients in a value that represents the severity of their condition. Traditional severity of illness scores seeks to be applicable to all patient populations, and usually assess in-hospital mortality. However, the use of machine learning techniques and the data of a population that shares a common characteristic could lead to the development of customized mortality prediction scores with better performance. This study presents the development of a score for the one-year mortality prediction of the patients that are admitted to an ICU with a sepsis diagnosis. 5650 ICU admissions extracted from the MIMICIII database were evaluated, divided into two groups: 70% to develop the score and 30% to validate it. Comorbidities, demographics and clinical information of the first 24 hours after the ICU admission were used to develop a mortality prediction score. LASSO (least absolute shrinkage and selection operator) and SGB (Stochastic Gradient Boosting) variable importance methodologies were used to select the set of variables that make up the developed score; each of this variables was dichotomized and a cut-off point that divides the population into two groups with different mean mortalities was found; if the patient is in the group that presents a higher mortality a one is assigned to the particular variable, otherwise a zero is assigned. These binary variables are used in a logistic regression (LR) model, and its coefficients were rounded to the nearest integer. The resulting integers are the point values that make up the score when multiplied with each binary variables and summed. The one-year mortality probability was estimated using the score as the only variable in a LR model. Predictive power of the score, was evaluated using the 1695 admissions of the validation subset obtaining an area under the receiver operating characteristic curve of 0.7528, which outperforms the results obtained with Sequential Organ Failure Assessment (SOFA), Oxford Acute Severity of Illness Score (OASIS) and Simplified Acute Physiology Score II (SAPSII) scores on the same validation subset. Observed and predicted mortality rates within estimated probabilities deciles were compared graphically and found to be similar, indicating that the risk estimate obtained with the score is close to the observed mortality, it is also observed that the number of events (deaths) is indeed increasing as the outcome go from the decile with the lowest probabilities to the decile with the highest probabilities. Sepsis is a syndrome that carries a high mortality, 43.3% for the patients included in this study; therefore, tools that help clinicians to quickly and accurately predict a worse prognosis are needed. This work demonstrates the importance of customization of mortality prediction scores since the developed score provides better performance than traditional scoring systems.

Keywords: intensive care, logistic regression model, mortality prediction, sepsis, severity of illness, stochastic gradient boosting

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Authors: N. Naz, A. D. Domenico, M. N. Huda

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Soft Robotics is a rapidly growing multidisciplinary field where robots are fabricated using highly deformable materials motivated by bioinspired designs. The high dexterity and adaptability to the external environments during contact make soft robots ideal for applications such as gripping delicate objects, locomotion, and biomedical devices. The actuation system of soft robots mainly includes fluidic, tendon-driven, and smart material actuation. Among them, Soft Pneumatic Actuator, also known as SPA, remains the most popular choice due to its flexibility, safety, easy implementation, and cost-effectiveness. However, at present, most of the fabrication of SPA is still based on traditional molding and casting techniques where the mold is 3d printed into which silicone rubber is cast and consolidated. This conventional method is time-consuming and involves intensive manual labour with the limitation of repeatability and accuracy in design. Recent advancements in direct 3d printing of different soft materials can significantly reduce the repetitive manual task with an ability to fabricate complex geometries and multicomponent designs in a single manufacturing step. The aim of this research work is to design and analyse the Soft Pneumatic Actuator (SPA) utilizing both conventional casting and modern direct 3d printing technologies. The mold of the SPA for traditional casting is 3d printed using fused deposition modeling (FDM) with the polylactic acid (PLA) thermoplastic wire. Hyperelastic soft materials such as Ecoflex-0030/0050 are cast into the mold and consolidated using a lab oven. The bending behaviour is observed experimentally with different pressures of air compressor to ensure uniform bending without any failure. For direct 3D-printing of SPA fused deposition modeling (FDM) with thermoplastic polyurethane (TPU) and stereolithography (SLA) with an elastic resin are used. The actuator is modeled using the finite element method (FEM) to analyse the nonlinear bending behaviour, stress concentration and strain distribution of different hyperelastic materials after pressurization. FEM analysis is carried out using Ansys Workbench software with a Yeon-2nd order hyperelastic material model. FEM includes long-shape deformation, contact between surfaces, and gravity influences. For mesh generation, quadratic tetrahedron, hybrid, and constant pressure mesh are used. SPA is connected to a baseplate that is in connection with the air compressor. A fixed boundary is applied on the baseplate, and static pressure is applied orthogonally to all surfaces of the internal chambers and channels with a closed continuum model. The simulated results from FEM are compared with the experimental results. The experiments are performed in a laboratory set-up where the developed SPA is connected to a compressed air source with a pressure gauge. A comparison study based on performance analysis is done between FDM and SLA printed SPA with the molded counterparts. Furthermore, the molded and 3d printed SPA has been used to develop a three-finger soft pneumatic gripper and has been tested for handling delicate objects.

Keywords: finite element method, fused deposition modeling, hyperelastic, soft pneumatic actuator

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Authors: Mohamad F. Jamiluddin, Emeline Sarry, Ana Bejanariu, Cécile Bauche

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Introduction: Over 360 million people are chronically infected with hepatitis B virus (HBV), of whom 1 million die each year from HBV-associated liver cirrhosis or hepatocellular carcinoma. Current treatment options for chronic hepatitis B depend on interferon-α (IFNα) or nucleos(t)ide analogs, which control virus replication but rarely eliminate the virus. Treatment with PEG-IFNα leads to a sustained antiviral response in only one third of patients. After withdrawal of the drugs, the rebound of viremia is observed in the majority of patients. Furthermore, the long-term treatment is subsequently associated with the appearance of drug resistant HBV strains that is often the cause of the therapy failure. Among the new therapeutic avenues being developed, therapeutic vaccine aimed at inducing immune responses similar to those found in resolvers is of growing interest. The high prevalence of chronic hepatitis B necessitates the design of better vaccination strategies capable of eliciting broad-spectrum of cell-mediated immunity(CMI) and humoral immune response that can control chronic hepatitis B. Induction of HBV-specific T cells and B cells by therapeutic vaccination may be an innovative strategy to overcome virus persistence. Lentiviral vectors developed and optimized by THERAVECTYS, due to their ability to transduce non-dividing cells, including dendritic cells, and induce CMI response, have demonstrated their effectiveness as vaccination tools. Method: To develop a HBV therapeutic vaccine that can induce a broad but specific immune response, we generated recombinant lentiviral vector carrying IRES(Internal Ribosome Entry Site)-containing bicistronic constructs which allow the coexpression of two vaccine products, namely HBV T- cell epitope vaccine and HBV virus like particle (VLP) vaccine. HBV T-cell epitope vaccine consists of immunodominant cluster of CD4 and CD8 epitopes with spacer in between them and epitopes are derived from HBV surface protein, HBV core, HBV X and polymerase. While HBV VLP vaccine is a HBV core protein based chimeric VLP with surface protein B-cell epitopes displayed. In order to evaluate the immunogenicity, mice were immunized with lentiviral constructs by intramuscular injection. The T cell and antibody immune responses of the two vaccine products were analyzed using IFN-γ ELISpot assay and ELISA respectively to quantify the adaptive response to HBV antigens. Results: Following a single administration in mice, lentiviral construct elicited robust antigen-specific IFN-γ responses to the encoded antigens. The HBV T- cell epitope vaccine demonstrated significantly higher T cell immunogenicity than HBV VLP vaccine. Importantly, we demonstrated by ELISA that antibodies are induced against both HBV surface protein and HBV core protein when mice injected with vaccine construct (p < 0.05). Conclusion: Our results highlight that THERAVECTYS lentiviral vectors may represent a powerful platform for immunization strategy against chronic hepatitis B. Our data suggests the likely importance of Lentiviral vector based novel bicistronic construct for further study, in combination with drugs or as standalone antigens, as a therapeutic lentiviral based HBV vaccines. THERAVECTYS bicistronic HBV vaccine will be further evaluated in animal efficacy studies.

Keywords: chronic hepatitis B, lentiviral vectors, therapeutic vaccine, virus-like particle

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Authors: Changhan Ouyang, Zhonglin Xie

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In response to proatherosclerotic factors such as oxidized lipids, or to therapeutic interventions such as angioplasty, stents, or bypass surgery, vascular smooth muscle cells (VSMCs) migrate from the media to the intima, resulting in intimal hyperplasia, restenosis, graft failure, or atherosclerosis. These proatherosclerotic factors also activate autophagy in VSMCs. However, the functional role of autophagy in vascular health and disease remains poorly understood. In the present study, we determined the role of autophagy in the regulation of VSMC migration. Autophagy activity in cultured human aortic smooth muscle cells (HASMCs) and mouse carotid arteries was measured by Western blot analysis of microtubule-associated protein 1 light chain 3 B (LC3B) and P62. The VSMC migration was determined by scratch wound assay and transwell migration assay. Ex vivo smooth muscle cell migration was determined using aortic ring assay. The in vivo SMC migration was examined by staining the carotid artery sections with smooth muscle alpha actin (alpha SMA) after carotid artery ligation. To examine the relationship between autophagy and neointimal hyperplasia, C57BL/6J mice were subjected to carotid artery ligation. Seven days after injury, protein levels of Atg5, Atg7, Beclin1, and LC3B drastically increased and remained higher in the injured arteries three weeks after the injury. In parallel with the activation of autophagy, vascular injury-induced neointimal hyperplasia as estimated by increased intima/media ratio. The en face staining of carotid artery showed that vascular injury enhanced alpha SMA staining in the intimal cells as compared with the sham operation. Treatment of HASMCs with platelet-derived growth factor (PDGF), one of the major factors for vascular remodeling in response to vascular injury, increased Atg7 and LC3 II protein levels and enhanced autophagosome formation. In addition, aortic ring assay demonstrated that PDGF treated aortic rings displayed an increase in neovessel formation compared with control rings. Whole mount staining for CD31 and alpha SMA in PDGF treated neovessels revealed that the neovessel structures were stained by alpha SMA but not CD31. In contrast, pharmacological and genetic suppression of autophagy inhibits VSMC migration. Especially, gene silencing of Atg7 inhibited VSMC migration induced by PDGF. Furthermore, three weeks after ligation, markedly decreased neointimal formation was found in mice treated with chloroquine, an inhibitor of autophagy. Quantitative morphometric analysis of the injured vessels revealed a marked reduction in the intima/media ratio in the mice treated with chloroquine. Conclusion: Autophagy activation increases VSMC migration while autophagy suppression inhibits VSMC migration. These findings suggest that autophagy suppression may be an important therapeutic strategy for atherosclerosis and intimal hyperplasia.

Keywords: autophagy, vascular smooth muscle cell, migration, neointimal formation

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Authors: Mirosław Krzemieniewski, Marcin Zieliński, Marcin Dębowski

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Electrokinetic disintegration is one of the high-voltage electric methods. The design of systems is exceptionally simple. Biomass flows through a system of pipes with alongside mounted electrodes that generate an electric field. Discharges in the electric field deform cell walls and lead to their successive perforation, thereby making their contents easily available to bacteria. The spark-over occurs between electrode surface and pipe jacket which is the second pole and closes the circuit. The value of voltage ranges from 10 to 100kV. Electrodes are supplied by normal “power grid” monophase electric current (230V, 50Hz). Next, the electric current changes into direct current of 24V in modules serving for particular electrodes, and this current directly feeds the electrodes. The installation is completely safe because the value of generated current does not exceed 250mA and because conductors are grounded. Therefore, there is no risk of electric shock posed to the personnel, even in the case of failure or incorrect connection. Low values of the electric current mean small energy consumption by the electrode which is extremely low – only 35W per electrode – compared to other methods of disintegration. Pipes with electrodes with diameter of DN150 are made of acid-proof steel and connected from both sides with 90º elbows ended with flanges. The available S and U types of pipes enable very convenient fitting with system construction in the existing installations and rooms or facilitate space management in new applications. The system of pipes for electrokinetic disintegration may be installed horizontally, vertically, askew, on special stands or also directly on the wall of a room. The number of pipes and electrodes is determined by operating conditions as well as the quantity of substrate, type of biomass, content of dry matter, method of disintegration (single or circulatory), mounting site etc. The most effective method involves pre-treatment of substrate that may be pumped through the disintegration system on the way to the fermentation tank or recirculated in a buffered intermediate tank (substrate mixing tank). Biomass structure destruction in the process of electrokinetic disintegration causes shortening of substrate retention time in the tank and acceleration of biogas production. A significant intensification of the fermentation process was observed in the systems operating in the technical scale, with the greatest increase in biogas production reaching 18%. The secondary, but highly significant for the energetic balance, effect is a tangible decrease of energy input by agitators in tanks. It is due to reduced viscosity of the biomass after disintegration, and may result in energy savings reaching even 20-30% of the earlier noted consumption. Other observed phenomena include reduction in the layer of surface scum, reduced sewage capability for foaming and successive decrease in the quantity of bottom sludge banks. Considering the above, the system for electrokinetic disintegration seems a very interesting and valuable solutions meeting the offer of specialist equipment for the processing of plant biomass, including Virginia fanpetals, before the process of methane fermentation.

Keywords: electrokinetic disintegration, biomass, biogas production, fermentation, Virginia fanpetals

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Authors: Qudsiya Baig

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Empathy yields an unparalleled therapeutic value within patient physician interactions. Medical research is inundated with evidence to support that a physician’s ability to empathise with patients leads to a greater willingness to report symptoms, an improvement in diagnostic accuracy and safety, and a better adherence and satisfaction with treatment plans. Furthermore, the Institute of Medicine states that empathy leads to a more patient-centred care, which is one of the six main goals of a 21st century health system. However, there is a paradox between the theoretical significance of empathy and its presence, or lack thereof, in clinical practice. Recent studies have reported that empathy declines amongst students and physicians over time. The three most impactful contributors to this decline are: (1) disagreements over the definitions of empathy making it difficult to implement it into practice (2) poor consideration or regulation of empathy leading to burnout and thus, abandonment altogether, and (3) the lack of diversity in the curriculum and the influence of medical culture, which prioritises science over patient experience, limiting some physicians from using ‘too much’ empathy in the fear of losing clinical objectivity. These issues were investigated by conducting a fully inductive thematic narrative analysis of patient narratives in the UK to evaluate the behaviours and attitudes that patients associate with empathy. The principal enquiries underpinning this study included uncovering the factors that affected experience of empathy within provider-patient interactions and to analyse their effects on patient care. This research contributes uniquely to this discourse by examining the phenomenon of empathy directly from patients’ experiences, which were systematically extracted from a repository of online patient narratives of care titled ‘CareOpinion UK’. Narrative analysis was specifically chosen as the methodology to examine narratives from a phenomenological lens to focus on the particularity and context of each story. By enquiring beyond the superficial who-whatwhere, the study of narratives prescribed meaning to illness by highlighting the everyday reality of patients who face the exigent life circumstances created by suffering, disability, and the threat of life. The following six themes were found to be the most impactful in influencing the experience of empathy: dismissive behaviours, judgmental attitudes, undermining patients’ pain or concerns, holistic care and failures and successes of communication or language. For each theme there were overarching themes relating to either a failure to understand the patient’s perspective or a success in taking a person-centred approach. An in-depth analysis revealed that a lack of empathy was greatly associated with an emotive-cognitive imbalance, which disengaged physicians with their patients’ emotions. This study hereby concludes that competent providers require a combination of knowledge, skills, and more importantly empathic attitudes to help create a context for effective care. The crucial elements of that context involve (a) identifying empathy clues within interactions to engage with patients’ situations, (b) attributing a perspective to the patient through perspective-taking and (c) adapting behaviour and communication according to patient’s individual needs. Empathy underpins that context, as does an appreciation of narrative, and the two are interrelated.

Keywords: empathy, narratives, person-centred, perspective, perspective-taking

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Authors: Roberta Mugellesi Dow

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As the climate crisis becomes unignorable, it is imperative that new services are developed addressing not only the needs of customers but also taking into account its impact on the environment. The Telecommunication and Integrated Application (TIA) Directorate of ESA is supporting the green transition with particular attention to the sustainable mobility.“Accelerating the shift to sustainable and smart mobility” is at the core of the European Green Deal strategy, which seeks a 90% reduction in related emissions by 2050 . Transforming the way that people and goods move is essential to increasing mobility while decreasing environmental impact, and transport must be considered holistically to produce a shared vision of green intermodal mobility. The use of space technologies, integrated with terrestrial technologies, is an enabler of smarter traffic management and increased transport efficiency for automated and connected multimodal mobility. Satellite connectivity, including future 5G networks, and digital technologies such as Digital Twin, AI, Machine Learning, and cloud-based applications are key enablers of sustainable mobility.SatCom is essential to ensure that connectivity is ubiquitously available, even in remote and rural areas, or in case of a failure, by the convergence of terrestrial and SatCom connectivity networks, This is especially crucial when there are risks of network failures or cyber-attacks targeting terrestrial communication. SatCom ensures communication network robustness and resilience. The combination of terrestrial and satellite communication networks is making possible intelligent and ubiquitous V2X systems and PNT services with significantly enhanced reliability and security, hyper-fast wireless access, as well as much seamless communication coverage. SatNav is essential in providing accurate tracking and tracing capabilities for automated vehicles and in guiding them to target locations. SatNav can also enable location-based services like car sharing applications, parking assistance, and fare payment. In addition to GNSS receivers, wireless connections, radar, lidar, and other installed sensors can enable automated vehicles to monitor surroundings, to ‘talk to each other’ and with infrastructure in real-time, and to respond to changes instantaneously. SatEO can be used to provide the maps required by the traffic management, as well as evaluate the conditions on the ground, assess changes and provide key data for monitoring and forecasting air pollution and other important parameters. Earth Observation derived data are used to provide meteorological information such as wind speed and direction, humidity, and others that must be considered into models contributing to traffic management services. The paper will provide examples of services and applications that have been developed aiming to identify innovative solutions and new business models that are allowed by new digital technologies engaging space and non space ecosystem together to deliver value and providing innovative, greener solutions in the mobility sector. Examples include Connected Autonomous Vehicles, electric vehicles, green logistics, and others. For the technologies relevant are the hybrid satcom and 5G providing ubiquitous coverage, IoT integration with non space technologies, as well as navigation, PNT technology, and other space data.

Keywords: sustainability, connectivity, mobility, satellites

Procedia PDF Downloads 137

Authors: Yael Rieder, Yael Gilboa, S. O. Adva, Efrat Halevi, Ronnie Tepper

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Background: Operation of ultrasound equipment is a core skill for many clinical specialties. As part of the training program at -Simultech- a simulation center for Ob\Gyn at the Meir Medical Center, Israel, teaching how to operate ultrasound equipment requires dealing with misunderstandings of spatial and 3D orientation, failure of the operator to hold a transducer correctly, and limited ability to evaluate the data on the screen. We have developed a platform intended to endow physicians and sonographers with clinical and operational skills of obstetric ultrasound. Simultech's simulations are focused on medical knowledge, risk management, technology operations and physician-patient communication. The simulations encompass extreme work conditions. Setup: Between eight and ten of the eight hundred and fifty physicians and sonographers of the Clalit health services from seven hospitals and eight community centers across Israel, participate in individual Ob/Gyn training sessions each week. These include Ob/Gyn specialists, experts, interns, and sonographers. Innovative teaching and training methodologies: The six-hour training program includes: (1) An educational computer program that challenges trainees to deal with medical questions based upon ultrasound pictures and films. (2) Sophisticated hands-on simulators that challenge the trainees to practice correct grip of the transducer, elucidate pathology, and practice daily tasks such as biometric measurements and analysis of sonographic data. (3) Participation in a video-taped simulation which focuses on physician-patient communications. In the simulation, the physician is required to diagnose the clinical condition of a hired actress based on the data she provides and by evaluating the assigned ultrasound films accordingly. Giving ‘bad news’ to the patient may put the physician in a stressful situation that must be properly managed. (4) Feedback at the end of each phase is provided by a designated trainer, not a physician, who is specially qualified by Ob\Gyn senior specialists. (5) A group exercise in which the trainer presents a medico-legal case in order to encourage the participants to use their own experience and knowledge to conduct a productive ‘brainstorming’ session. Medical cases are presented and analyzed by the participants together with the trainer's feedback. Findings: (1) The training methods and content that Simultech provides allows trainees to review their medical and communications skills. (2) Simultech training sessions expose physicians to both basic and new, up-to-date cases, refreshing and expanding the trainee's knowledge. (3) Practicing on advanced simulators enables trainees to understand the sonographic space and to implement the basic principles of ultrasound. (4) Communications simulations were found to be beneficial for trainees who were unaware of their interpersonal skills. The trainer feedback, supported by the recorded simulation, allows the trainee to draw conclusions about his performance. Conclusion: Simultech was found to contribute to physicians at all levels of clinical expertise who deal with ultrasound. A break in daily routine together with attendance at a neutral educational center can vastly improve performance and outlook.

Keywords: medical training, simulations, ultrasound, Simultech

Procedia PDF Downloads 280

Authors: Natalie Riley, Anita Quigley, Robert M. I. Kapsa, George W. Greene

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As the fields of medicine and bionics grow rapidly in technological advancement, the future and success of it depends on the ability to effectively interface between the artificial and the biological worlds. The biggest obstacle when it comes to implantable, electronic medical devices, is maintaining a ‘clean’, low noise electrical connection that allows for efficient sharing of electrical information between the artificial and biological systems. Implant fouling occurs with the adhesion and accumulation of proteins and various cell types as a result of the immune response to protect itself from the foreign object, essentially forming an electrical insulation barrier that often leads to implant failure over time. Lubricin (LUB) functions as a major boundary lubricant in articular joints, a unique glycoprotein with impressive anti-adhesive properties that self-assembles to virtually any substrate to form a highly ordered, ‘telechelic’ polymer brush. LUB does not passivate electroactive surfaces which makes it ideal, along with its innate biocompatibility, as a coating for implantable bionic electrodes. It is the aim of the study to investigate LUB’s anti-fouling properties and its potential as a safe, bioinspired material for coating applications to enhance the performance and longevity of implantable medical devices as well as reducing the frequency of implant replacement surgeries. Native, bovine-derived LUB (N-LUB) and recombinant LUB (R-LUB) were applied to gold-coated mylar surfaces. Fibroblast, chondrocyte and neural cell types were cultured and grown on the coatings under both passive and electrically stimulated conditions to test the stability and anti-adhesive property of the LUB coating in the presence of an electric field. Lactate dehydrogenase (LDH) assays were conducted as a directly proportional cell population count on each surface along with immunofluorescent microscopy to visualize cells. One-way analysis of variance (ANOVA) with post-hoc Tukey’s test was used to test for statistical significance. Under both passive and electrically stimulated conditions, LUB significantly reduced cell attachment compared to bare gold. Comparing the two coating types, R-LUB reduced cell attachment significantly compared to its native counterpart. Immunofluorescent micrographs visually confirmed LUB’s antiadhesive property, R-LUB consistently demonstrating significantly less attached cells for both fibroblasts and chondrocytes. Preliminary results investigating neural cells have so far demonstrated that R-LUB has little effect on reducing neural cell attachment; the study is ongoing. Recombinant LUB coatings demonstrated impressive anti-adhesive properties, reducing cell attachment in fibroblasts and chondrocytes. These findings and the availability of recombinant LUB brings into question the results of previous experiments conducted using native-derived LUB, its potential not adequately represented nor realized due to unknown factors and impurities that warrant further study. R-LUB is stable and maintains its anti-fouling property under electrical stimulation, making it suitable for electroactive surfaces.

Keywords: anti-fouling, bioinspired, cell attachment, lubricin

Procedia PDF Downloads 124

Authors: Bijit Kalita, K. V. N. Surendra

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The pulley works under both compressive loading due to contacting belt in tension and central torque due to cause rotation. In a power transmission system, the belt pulley assemblies offer a contact problem in the form of two mating cylindrical parts. In this work, we modeled a pulley as a heavy two-dimensional circular disk. Stress analysis due to contact loading in the pulley mechanism is performed. Finite element analysis (FEA) is conducted for a pulley to investigate the stresses experienced on its inner and outer periphery. In most of the heavy-duty applications, most frequently used mechanisms to transmit power in applications such as automotive engines, industrial machines, etc. is Belt Drive. Usually, very heavy circular disks are used as pulleys. A pulley could be entitled as a drum and may have a groove between two flanges around the circumference. A rope, belt, cable or chain can be the driving element of a pulley system that runs over the pulley inside the groove. A pulley is experienced by normal and shear tractions on its contact region in the process of motion transmission. The region may be belt-pulley contact surface or pulley-shaft contact surface. In 1895, Hertz solved the elastic contact problem for point contact and line contact of an ideal smooth object. Afterward, this hypothesis is generally utilized for computing the actual contact zone. Detailed stress analysis in such contact region of such pulleys is quite necessary to prevent early failure. In this paper, the results of the finite element analyses carried out on the compressed disk of a belt pulley arrangement using fracture mechanics concepts are shown. Based on the literature on contact stress problem induced in the wide field of applications, generated stress distribution on the shaft-pulley and belt-pulley interfaces due to the application of high-tension and torque was evaluated in this study using FEA concepts. Finally, the results obtained from ANSYS (APDL) were compared with the Hertzian contact theory. The study is mainly focused on the fatigue life estimation of a rotating part as a component of an engine assembly using the most famous Paris equation. Digital Image Correlation (DIC) analyses have been performed using the open-source software. From the displacement computed using the images acquired at a minimum and maximum force, displacement field amplitude is computed. From these fields, the crack path is defined and stress intensity factors and crack tip position are extracted. A non-linear least-squares projection is used for the purpose of the estimation of fatigue crack growth. Further study will be extended for the various application of rotating machinery such as rotating flywheel disk, jet engine, compressor disk, roller disk cutter etc., where Stress Intensity Factor (SIF) calculation plays a significant role on the accuracy and reliability of a safe design. Additionally, this study will be progressed to predict crack propagation in the pulley using maximum tangential stress (MTS) criteria for mixed mode fracture.

Keywords: crack-tip deformations, contact stress, stress concentration, stress intensity factor

Procedia PDF Downloads 125

Authors: Dina Farran, Mark Ashworth, Fiona Gaughran

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Atrial fibrillation (AF), the most prevalent cardiac arrhythmia, is associated with an increased risk of stroke, contributing to heart failure and death. In this project, we aim to improve patient safety by screening for stroke risk among people with AF and co-morbid mental illness. To do so, we started by conducting a systematic review and meta-analysis on prevalence, management, and outcomes of AF in people with Serious Mental Illness (SMI) versus the general population. We then evaluated oral anticoagulation (OAC) prescription trends in people with AF and co-morbid SMI in King’s College Hospital. We also evaluated the association between mental illness severity and OAC prescription in eligible patients in South London and Maudsley (SLaM) NHS Foundation Trust. Next, we implemented an electronic clinical decision support system (eCDSS) consisting of a visual prompt on patient electronic Personal Health Records to screen for AF-related stroke risk in three Mental Health of Older Adults wards at SLaM. Finally, we assessed the feasibility and acceptability of the eCDSS by qualitatively investigating clinicians’ perspectives of the potential usefulness of the eCDSS (pre-intervention) and their experiences and their views regarding its impact on clinicians and patients (post-intervention). The systematic review showed that people with SMI had low reported rates of AF. AF patients with SMI were less likely to receive OAC than the general population. When receiving warfarin, people with SMI, particularly bipolar disorder, experienced poor anticoagulation control compared to the general population. Meta-analysis showed that SMI was not significantly associated with an increased risk of stroke or major bleeding when adjusting for underlying risk factors. The main findings of the first observational study were that among AF patients having a high stroke risk, those with co-morbid SMI were less likely than non-SMI to be prescribed any OAC, particularly warfarin. After 2019, there was no significant difference between the two groups. In the second observational study, patients with AF and co-morbid SMI were less likely to be prescribed any OAC compared to those with dementia, substance use disorders, or common mental disorders, adjusting for age, sex, stroke, and bleeding risk scores. Among AF patients with co-morbid SMI, warfarin was less likely to be prescribed to those having alcohol or substance dependency, serious self-injury, hallucinations or delusions, and activities of daily living impairment. In the intervention, clinicians were asked to confirm the presence of AF, clinically assess stroke and bleeding risks, record risk scores in clinical notes, and refer patients at high risk of stroke to OAC clinics. Clinicians reported many potential benefits for the eCDSS, including improving clinical effectiveness, better identification of patients at risk, safer and more comprehensive care, consistency in decision making and saving time. Identified potential risks included rigidity in decision-making, overreliance, reduced critical thinking, false positive recommendations, annoyance, and increased workload. This study presents a unique opportunity to quantify AF patients with mental illness who are at high risk of severe outcomes using electronic health records. This has the potential to improve health outcomes and, therefore patients' quality of life.

Keywords: atrial fibrillation, stroke, mental health conditions, electronic clinical decision support systems

Procedia PDF Downloads 50

Authors: Jaco Oosthuizen, Nerina C. Van Der Merwe

Abstract:

The National Health Laboratory Services in Bloemfontien has been the diagnostic testing facility for 1830 patients for familial breast cancer since 1997. From the cohort, 540 were comprehensively screened using High-Resolution Melting Analysis or Next Generation Sequencing for the presence of point mutations and/or indels. Approximately 90% of these patients stil remain undiagnosed as they are BRCA1/2 negative. Multiplex ligation-dependent probe amplification was initially added to screen for copy number variation detection, but with the introduction of next generation sequencing in 2017, was substituted and is currently used as a confirmation assay. The aim was to investigate the viability of utilizing internationally designed copy number variation detection assays based on mostly European/Caucasian genomic data for use within a South African context. The multiplex ligation-dependent probe amplification technique is based on the hybridization and subsequent ligation of multiple probes to a targeted exon. The ligated probes are amplified using conventional polymerase chain reaction, followed by fragment analysis by means of capillary electrophoresis. The experimental design of the assay was performed according to the guidelines of MRC-Holland. For BRCA1 (P002-D1) and BRCA2 (P045-B3), both multiplex assays were validated, and results were confirmed using a secondary probe set for each gene. The next generation sequencing technique is based on target amplification via multiplex polymerase chain reaction, where after the amplicons are sequenced parallel on a semiconductor chip. Amplified read counts are visualized as relative copy numbers to determine the median of the absolute values of all pairwise differences. Various experimental parameters such as DNA quality, quantity, and signal intensity or read depth were verified using positive and negative patients previously tested internationally. DNA quality and quantity proved to be the critical factors during the verification of both assays. The quantity influenced the relative copy number frequency directly whereas the quality of the DNA and its salt concentration influenced denaturation consistency in both assays. Multiplex ligation-dependent probe amplification produced false positives due to ligation failure when ligation was inhibited due to a variant present within the ligation site. Next generation sequencing produced false positives due to read dropout when primer sequences did not meet optimal multiplex binding kinetics due to population variants in the primer binding site. The analytical sensitivity and specificity for the South African population have been proven. Verification resulted in repeatable reactions with regards to the detection of relative copy number differences. Both multiplex ligation-dependent probe amplification and next generation sequencing multiplex panels need to be optimized to accommodate South African polymorphisms present within the genetically diverse ethnic groups to reduce the false copy number variation positive rate and increase performance efficiency.

Keywords: familial breast cancer, multiplex ligation-dependent probe amplification, next generation sequencing, South Africa

Procedia PDF Downloads 232