Search results for: arterial progression

Authors: M. U. Arshid, M. A. Kamal

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The engineering design process is the activities formulation, to help an engineer raising a plan with a specified goal and performance. The engineering design process is a multi-stage course of action including the conceptualization, research, feasibility studies, establishment of design parameters, preliminary and finally the detailed design. It is a progression from the abstract to the concrete; starting with probably abstract ideas about need, and thereafter elaborating detailed specifications of the object that would satisfy the needs, identified. Engineering design issues, problems, and solutions are discussed in this paper using qualitative approach from an information structure perspective. The objective is to identify the problems, to analyze them and propose solutions by integrating; innovation, practical experience, time and resource management, communications skills, isolating the problem in coordination with all stakeholders. Consequently, this would be beneficial for the engineering community to improve the Engineering design practices.

Keywords: engineering design, engineering design issues, innovation, public sector projects

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Authors: Michael Zaidman, Naum Simanovsky

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The most of brachial birth palsies are transient. Children with incomplete recovery almost always develop an internal rotation and adduction contracture. The muscle imbalance around the shoulder results in glenohumeral joint deformity and functional limitations. Natural history of glenohumeral deformity is it’s progression with worsening of function. Anteversion glenoid osteotomy with latissimus dorsi and teres major tendon transfers could be an alternative procedure of proximal humeral external rotation osteotomy for patients with severe glenohumeral dysplasia secondary to brachial plexus birth palsy. We will discuss pre-operative planning and stepped operative technique of the procedure on clinical example.

Keywords: obstetric brachial plexus palsy, glenoid anteversion osteotomy, tendon transfer, operative technique

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Authors: Mohammad Ahmadi

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Argumentative writing is a highly opinion-based form of discourse that necessitates the ability to address commonly held opinions (endoxa). To enhance the development of persuasive, argumentative essays, the incorporation of classical rhetorical theory, with a specific focus on topics related to the canon of Invention (inventio), can be advantageous. This research investigates the practical application of rhetorical theory in teaching students how to construct compelling argumentative essays. The fundamental premise of this study is the limited familiarity of rhetoric and composition students with rhetorical theory. Consequently, this paper presents an effective pedagogical approach to introduce rhetorical theory to students, beginning from a foundational level. It delineates the procedures and progression that educators should adopt to elucidate and facilitate students' comprehension of rhetorical theory while demonstrating its utilization in the writing of an argumentative essay.

Keywords: argumentative essay, rhetorical theory, pedagogy, invention

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Authors: Christine P. Gibson, Ramona Alex, Michael Farney, Johana Vallejo-Elias, Mitra Esfandiarei

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Aortic aneurysm is the leading cause of death in Marfan syndrome (MFS), a connective tissue disorder caused by mutations in fibrillin-1 gene (FBN1). MFS aneurysm is characterized by weakening of the aortic wall due to elastin fibers fragmentation and disorganization. The above-average height and distinct physical features make young adults with MFS desirable candidates for competitive sports; but little is known about the exercise limit at which they will be at risk for aortic rupture. On the other hand, aerobic cardiovascular exercise has been shown to have protective effects on the heart and aorta. We have previously reported that mild aerobic exercise can delay the formation of aortic aneurysm in a mouse model of MFS. In this study, we aimed to investigate the effects of various levels of exercise intensity on the progression of aortic aneurysm in the mouse model. Starting at 4 weeks of age, we subjected control and MFS mice to different levels of exercise intensity (8m/min, 10m/min, 15m/min, and 20m/min, corresponding to 55%, 65%, 75%, and 85% of VO2 max, respectively) on a treadmill for 30 minutes per day, five days a week for the duration of the study. At 24 weeks of age, aortic tissue were isolated and subjected to structural and functional studies using histology and wire myography in order to evaluate the effects of different exercise routines on elastin fragmentation and organization and aortic wall elasticity/stiffness. Our data shows that exercise training at the intensity levels between 55%-75% significantly reduces elastin fragmentation and disorganization, with less recovery observed in 85% MFS group. The reversibility of elasticity was also significantly restored in MFS mice subjected to 55%-75% intensity; however, the recovery was less pronounced in MFS mice subjected to 85% intensity. Furthermore, our data shows that smooth muscle cells (SMCs) contractilion in response to vasoconstrictor agent phenylephrine (100nM) is significantly reduced in MFS aorta (54.84 ± 1.63 mN/mm2) as compared to control (95.85 ± 3.04 mN/mm2). At 55% of intensity, exercise did not rescue SMCs contraction (63.45 ± 1.70 mN/mm2), while at higher intensity levels, SMCs contraction in response to phenylephrine was restored to levels similar to control aorta [65% (81.88 ± 4.57 mN/mm2), 75% (86.22 ± 3.84 mN/mm2), and 85% (83.91 ± 5.42 mN/mm2)]. This study provides the first time evidence that high intensity exercise (e.g. 85%) may not provide the most beneficial effects on aortic function (vasoconstriction) and structure (elastin fragmentation, aortic wall elasticity) during the progression of aortic aneurysm in MFS mice. On the other hand, based on our observations, medium intensity exercise (e.g. 65%) seems to provide the utmost protective effects on aortic structure and function in MFS mice. These findings provide new insights into the potential capacity, in which MFS patients could participate in various aerobic exercise routines, especially in young adults affected by cardiovascular complications particularly aortic aneurysm. This work was funded by Midwestern University Research Fund.

Keywords: aerobic exercise, aortic aneurysm, aortic wall elasticity, elastin fragmentation, Marfan syndrome

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Authors: Lokesh Bhatt, Jayesh Rathod

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Hypertension is one of the most prevalent cardiovascular disorder. It is responsible for several other cardiovascular disorders. Although many drugs are available for the treatment of hypertension, still a large population has uncontrolled blood pressure. Thus there is an unmet need for new therapeutic approaches for the same. Fruit juice of Citrus paradise contains several flavonoids with vasodilatory activity. We hypothesized that alcoholic extract of Citrus paradise, which contains flavonoids, might attenuate hypertension. The objective of the present study was to evaluate the antihypertensive activity of alcoholic extract of Citrus paradise fruit juice in rats. Hypertension was induced using one clip one kidney model in rats. The renal artery was occluded for 4 h after removal of one kidney. Once stabilized, the ganglionic blockade was performed followed by removal of the arterial clip from the kidney. Removal of clip resulted in an increase in blood pressure which is due to release of renin from the kidney. Alcoholic extract of Citrus paradise fruit juice was then administered at 50 mg/kg and 100 mg/kg dose by intravenous injection. Blood pressure was monitored continuously. Alcoholic extract of Citrus paradise fruit juice reduced hypertension in dose-dependent manner. Antihypertensive activity was found to be associated with vasodilation. The results of the present study showed antihypertensive potential of alcoholic extract of Citrus paradise fruit juice.

Keywords: citrus paradise, alcoholic extract, one clip one kidney model, vasodilation

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Authors: Nurul Nadrah

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As a result of the COVID-19 pandemic, a movement control order was implemented, leading to the adoption of online learning as a substitute for conventional classroom instruction. Thus, this study aims to determine the differences in skill performance between online learning and conventional methods among nursing students. We employed a quasi-experimental design with purposive sampling, involving a total of 59 nursing students, and used online learning as the intervention. As a result, the study found there was a significant difference in student skill performance between online learning and conventional methods. As a conclusion, in times of hardship, it is necessary to implement alternative pedagogical approaches, especially in critical fields like nursing, to ensure the uninterrupted progression of educational programs. This study suggests that online learning can be effectively employed as a means of imparting knowledge to nursing students during their training.

Keywords: nursing education, online learning, skill performance, conventional learning method

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Authors: Priyanka Patil, Logan Manikam

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Background: The first 1000 days of life are a critical window and can result in adverse health consequences due to inadequate nutrition. South-Asian (SA) communities face significant health disparities, particularly in maternal and child health. Community-based interventions, often employing Participatory-Learning and Action (PLA) approaches, have effectively addressed health inequalities in lower-income nations. The aim of this study was to assess the feasibility of implementing a PLA intervention to improve infant feeding and care practices in SA communities living in London. Methods: Comprehensive analyses were conducted to assess the feasibility/fidelity of this pilot randomized controlled trial. Summary statistics were computed to compare key metrics, including participant consent rates, attendance, retention, intervention support, and perceived effectiveness, against predefined progression rules guiding toward a definitive trial. Secondary outcomes were analyzed, drawing insights from multiple sources, such as The Children’s-Eating-Behaviour Questionnaire (CEBQ), Parental-Feeding-Style Questionnaires (PFSQ), Food-diary, and the Equality-Impact-Assessment (EIA) tool. A video analysis of children's mealtime behavior trends was conducted. Feedback interviews were collected from study participants. Results: Process-outcome measures met predefined progression rules for a definitive trial, which deemed the intervention as feasible and acceptable. The secondary outcomes analysis revealed no significant changes in children's BMI z-scores. This could be attributed to the abbreviated follow-up period of 6 months, reduced from 12 months, due to COVID-19-related delays. CEBQ analysis showed increased food responsiveness, along with decreased emotional over/undereating. A similar trend was observed in PFSQ. The EIA tool found no potential discrimination areas, and video analysis revealed a decrease in force-feeding practices. Participant feedback revealed improved awareness and knowledge sharing. Conclusion: This study demonstrates that a co-adapted PLA intervention is feasible and well-received in optimizing infant-care practices among South-Asian community members in a high-income country. These findings highlight the potential of community-based interventions to enhance health outcomes, promoting health equity.

Keywords: child health, childhood obesity, community-based, infant nutrition

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Authors: B. V. Murlimanju

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Background: Scaphoid bone is commonly fractured among all the bones of the wrist. The fracture can damage the arteries and would cause avascular necrosis of the scaphoid. In this present study, the goal was to study the topography and number of nutrient foramina in the scaphoid bones of South Indian population. Methods: We studied 46 human scaphoid bones, among them 20 were left sided and 26 belonged to the right side. The scaphoid bones were available at the department of anatomy of our institution. The scaphoid bones were macroscopically observed for the topography and number of nutrient foramina. The data was collected, tabulated and analyzed. Results: The nutrient foramina were observed in all the scaphoid bones (100%). The locations of the foramina were over the non-articular surfaces in all these scaphoids. They were distributed over the palmar and dorsal surfaces. The foramina were found proximal as well as distal to the mid waist of the scaphoid bone. Their number ranged between 9 and 54 in each scaphoid bone. The number ranged between 2-24 over the palmar surface and 7-36 over the dorsal surface. They ranged between 2-24 proximal to the waist and 3-39 distal to the waist. Conclusion: The knowledge of arterial supply, topography of nutrient foramen and their number is essential to understand the concepts of avascular necrosis of scaphoid bone. It will be enlightening to understand the non-union of the fracture of waist of the scaphoid. The morphological data is required to the operating hand surgeon. We do believe that the present study has provided additional information about the topography and number of nutrient foramina of the human scaphoid bones.

Keywords: avascular necrosis, nutrient foramen, scaphoid, vascular

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Authors: Umadevi B., Dinesh P. A., Indira. R., Vinay C. V.

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A mathematical model is developed to study the simultaneous effects of particle drag and slip parameter on the velocity as well as rate of flow in an annular cross sectional region bounded by two eccentric cylinders. In physiological flows this phenomena can be observed in an eccentric catheterized artery with inner cylinder wall is impermeable and outer cylinder wall is permeable. Blood is a heterogeneous fluid having liquid phase consisting of plasma in which a solid phase of suspended cells and proteins. Arterial wall gets damaged due to aging and lipid molecules get deposited between damaged tissue cells. Blood flow increases towards the damaged tissues in the artery. In this investigation blood is modeled as two phase fluid as one is a fluid phase and the other is particulate phase. The velocity of the fluid phase and rate of flow are obtained by transforming eccentric annulus to concentric annulus with the conformal mapping. The formulated governing equations are analytically solved for the velocity and rate of flow. The numerical investigations are carried out by varying eccentricity parameter, slip parameter and drag parameter. Enhancement of slip parameter signifies loss of fluid then the velocity and rate of flow will be decreased. As particulate drag parameter increases then the velocity as well as rate flow decreases. Eccentricity facilitates transport of more fluid then the velocity and rate of flow increases.

Keywords: catheter, slip parameter, drag parameter, eccentricity

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Authors: Mary Fargher

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This paper examines the opportunities of using a more hierarchical approach to geospatial enquiry in using GIS in school geography. A case is made that it is not just the lack of teacher technological knowledge that is stopping some teachers from using GIS in the classroom but that there is a gap in their understanding of how to link GIS use more specifically to the pedagogy of teaching geography with GIS. Using a hierarchical approach to geospatial enquiry as a theoretical framework, the analysis shows clearly how concepts of spatial distribution, interaction, relation, comparison, and temporal relationships can be used by teachers more explicitly to capitalise on the analytical power of GIS and to construct what can be interpreted as powerful geographical knowledge. An exemplar illustrating this approach on the topic of geo-hazards is then presented for critical analysis and discussion. Recommendations are then made for a model of progression for geography teacher education with GIS through hierarchical geospatial enquiry that takes into account beginner, intermediate, and more advanced users.

Keywords: digital geography, GIS, education, hierarchical geospatial enquiry, powerful geographical knowledge

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Authors: Venus Torabi

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ISIS, the terrorist organization, modified two videogames, ARMA III and Grand Theft Auto 5 (2013) as means of online recruitment and ideological propaganda. The urge to study the mechanism at work, whether it has been successful or not, derives (Digital) Humanities experts to explore how codes of terror, Islamic ideology and recruitment strategies are incorporated into the ludic mechanics of videogames. Another aspect of the significance lies in the fact that this is a latent problem that has not been fully addressed in an interdisciplinary framework prior to this study, to the best of the researcher’s knowledge. Therefore, due to the complexity of the subject, the present paper entangles with game studies, philosophical and religious poles to form the methodology of conducting the research. As a contextualized epistemology of such exploitation of videogames, the core argument is building on the notion of “Culture Industry” proposed by Theodore W. Adorno and Max Horkheimer in Dialectic of Enlightenment (2002). This article posits that the ideological underpinnings of ISIS’s cause corroborated by the action-bound mechanics of the videogames are in line with adhering to the Islamic Eschatology as a furnishing ground and an excuse in exercising terrorism. It is an account of ISIS’s modification of the videogames, a tool of technological progression to practice online radicalization. Dialectically, this practice is packed up in rhetoric for recognizing a religious myth (the advent of a savior), as a hallmark of regression. The study puts forth that ISIS’s wreaking havoc on the world, both in reality and within action videogames, is negotiating the process of self-assertion in the players of such videogames (by assuming one’s self a member of terrorists) that leads to self-annihilation. It tries to unfold how ludic Mod videogames are misused as tools of mass deception towards ethnic cleansing in reality and line with the distorted Eschatological myth. To conclude, this study posits videogames to be a new avenue of mass deception in the framework of the Culture Industry. Yet, this emerges as a two-edged sword of mass deception in ISIS’s modification of videogames. It shows that ISIS is not only trying to hijack the minds through online/ludic recruitment, it potentially deceives the Muslim communities or those prone to radicalization into believing that it's terrorist practices are preparing the world for the advent of a religious savior based on Islamic Eschatology. This is to claim that the harsh actions of the videogames are potentially breeding minds by seeds of terrorist propaganda and numbing them to violence. The real world becomes an extension of that harsh virtual environment in a ludic/actual continuum, the extension that is contributing to the mass deception mechanism of the terrorists, in a clandestine trend.

Keywords: culture industry, dialectic, ISIS, islamic eschatology, mass deception, video games

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Authors: Mariam Wagih Nagib Eskandar

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The engineering design process is the activities formulation, to help an engineer raising a plan with a specified goal and performance. The engineering design process is a multi-stage course of action including the conceptualization, research, feasibility studies, establishment of design parameters, preliminary and finally the detailed design. It is a progression from the abstract to the concrete; starting with probably abstract ideas about need, and thereafter elaborating detailed specifications of the object that would satisfy the needs, identified. Engineering design issues, problems, and solutions are discussed in this paper using qualitative approach from an information structure perspective. The objective is to identify the problems, to analyze them and propose solutions by integrating; innovation, practical experience, time and resource management, communications skills, isolating the problem in coordination with all stakeholders. Consequently, this would be beneficial for the engineering community to improve the Engineering design practices.

Keywords: education, engineering, math, performanceengineering design, architectural engineering, team-based learning, construction safetyrequirement engineering, models, practices, organizations

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Authors: Vishnu Varthan Vaithiyalingam Jagannathan, Lakshmi Karunanidhi Santhanalakshmi, Srividya Ammayappan Rajam

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Formononetin is the O-Methoxy Flavonol that has many pharmacological activities, which belongs to the flavonoid family. In the current study, activity of this molecule was evaluated in lung cancer cell lines. In general, flavonoids possess certain anticancer mechanism. Being a flavonoid subfamily, this molecule was subjected to evaluate cytotoxicity assay by MTT ((3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide)) stain, mode of cell death assay stained by acridine orange and ethidium bromide and Evaluation of Apoptosis pathway (extrinsic or intrinsic) by Caspase 3/7 stain and Rhodamine-123 stain. From the results, we could able to confirm that the investigatory molecule formononetin has anticancer activity and in future, the study will propose to evaluate the formononetin action against genetic changes occurs during lung cancer progression.

Keywords: Caspase 3/7, formononetin, lung cancer, Rhodamine-123

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Authors: Mounir Gaci, Salim Meziani, Atmane Fouathia

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The purpose of the present paper is to model the behavior of metal alloy, type TRIP steel (Transformation Induced Plasticity), during solid/solid phase transition. A two-dimensional micromechanical model is implemented in finite element software (ZEBULON) to simulate the martensitic transformation in Fe-Ni-C steel grain under mechanical tensile stress of 250 MPa. The effects of non-uniform grain boundary and the criterion of mechanical shear load on the transformation and on the TRIP value during martensitic transformation are studied. The suggested mechanical criterion is favourable to the influence of the shear phenomenon on the progression of the martensitic transformation (Magee’s mechanism). The obtained results are in satisfactory agreement with experimental ones and show the influence of the grain boundary shape and the chosen mechanical criterion (SMF) on the transformation parameters.

Keywords: martensitic transformation, non-uniform Grain Boundary, TRIP, shear Mechanical force (SMF)

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Authors: Angelis P. Barlampas

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Learning Objectives: The purpose of this study is to inform briefly the reader about the applications of AI in chest radiology. Background: Currently, there are 190 FDA-approved radiology AI applications, with 42 (22%) pertaining specifically to thoracic radiology. Imaging findings OR Procedure details Aids of AI in chest radiology1: Detects and segments pulmonary nodules. Subtracts bone to provide an unobstructed view of the underlying lung parenchyma and provides further information on nodule characteristics, such as nodule location, nodule two-dimensional size or three dimensional (3D) volume, change in nodule size over time, attenuation data (i.e., mean, minimum, and/or maximum Hounsfield units [HU]), morphological assessments, or combinations of the above. Reclassifies indeterminate pulmonary nodules into low or high risk with higher accuracy than conventional risk models. Detects pleural effusion . Differentiates tension pneumothorax from nontension pneumothorax. Detects cardiomegaly, calcification, consolidation, mediastinal widening, atelectasis, fibrosis and pneumoperitoneum. Localises automatically vertebrae segments, labels ribs and detects rib fractures. Measures the distance from the tube tip to the carina and localizes both endotracheal tubes and central vascular lines. Detects consolidation and progression of parenchymal diseases such as pulmonary fibrosis or chronic obstructive pulmonary disease (COPD).Can evaluate lobar volumes. Identifies and labels pulmonary bronchi and vasculature and quantifies air-trapping. Offers emphysema evaluation. Provides functional respiratory imaging, whereby high-resolution CT images are post-processed to quantify airflow by lung region and may be used to quantify key biomarkers such as airway resistance, air-trapping, ventilation mapping, lung and lobar volume, and blood vessel and airway volume. Assesses the lung parenchyma by way of density evaluation. Provides percentages of tissues within defined attenuation (HU) ranges besides furnishing automated lung segmentation and lung volume information. Improves image quality for noisy images with built-in denoising function. Detects emphysema, a common condition seen in patients with history of smoking and hyperdense or opacified regions, thereby aiding in the diagnosis of certain pathologies, such as COVID-19 pneumonia. It aids in cardiac segmentation and calcium detection, aorta segmentation and diameter measurements, and vertebral body segmentation and density measurements. Conclusion: The future is yet to come, but AI already is a helpful tool for the daily practice in radiology. It is assumed, that the continuing progression of the computerized systems and the improvements in software algorithms , will redder AI into the second hand of the radiologist.

Keywords: artificial intelligence, chest imaging, nodule detection, automated diagnoses

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Authors: Stefan Bradu, Daniel Siegel, Jameson Loyal, Andrea Leaf, Alana Kurtti, Usha Alapati, Jared Jagdeo

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Compared with all other variants of nodular melanoma, patients with polypoid nodular melanoma have the lowest 5-year survival rate. The pathophysiology and management of polypoid melanoma are scarcely reported in the literature. Although surgical excision is the cornerstone of melanoma management, treatment of polypoid melanoma is complicated by several negative prognostic factors, including early metastasis. This report demonstrates the successful treatment of a rapidly developing red nodular polypoid melanoma with metastasis using surgery and adjuvant nivolumab in a SARS-CoV-2-positive patient who delayed seeking care due to the COVID-19 pandemic. In addition to detailing the successful treatment approach, the immunosuppressive effects of SARS-2-CoV and its possible contribution to the rapid progression of polypoid melanoma are discussed. This case highlights the complex challenges of melanoma diagnosis and management during the COVID-19 pandemic.

Keywords: covid-19, dermatology, immunotherapy, melanoma, nivolumab

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Authors: Shruti Motiwale, Xianlin Zhou, Reuben H. Kraft

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Military and sports personnel are often required to wear heavy helmets for extended periods of time. This leads to excessive cyclic loads on the neck and an increased chance of injury. Computational models offer one approach to understand and predict the time progression of disc degeneration under severe cyclic loading. In this paper, we have applied an analytic non-linear damage evolution model to estimate damage evolution in an intervertebral disc due to cyclic loads over decade-long time periods. We have also proposed a novel strategy for inclusion of recovery in the damage model. Our results show that damage only grows 20% in the initial 75% of the life, growing exponentially in the remaining 25% life. The analysis also shows that it is crucial to include recovery in a damage model.

Keywords: cervical spine, computational biomechanics, damage evolution, intervertebral disc, continuum damage mechanics

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Authors: Shaista Suhail

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As cancer populations is increasing sharply, the incidence of oral squamous cell carcinoma (OSCC) has also been expected to increase. Oral carcinogenesis is a highly complex, multistep process which involves accumulation of genetic alterations that lead to the induction of proteins promoting cell growth (encoded by oncogenes), increased enzymatic (telomerase) activity promoting cancer cell proliferation. The global increase in frequency and mortality, as well as the poor prognosis of oral squamous cell carcinoma, has intensified current research efforts in the field of prevention and early detection of this disease. The advances in the understanding of the molecular basis of oral cancer should help in the identification of new markers. The study of the carcinogenic process of the oral cancer, including continued analysis of new genetic alterations, along with their temporal sequencing during initiation, promotion and progression, will allow us to identify new diagnostic and prognostic factors, which will provide a promising basis for the application of more rational and efficient treatments. Telomerase activity has been readily found in most cancer biopsies, in premalignant lesions or germ cells. Activity of telomerase is generally absent in normal tissues. It is known to be induced upon immortalization or malignant transformation of human cells such as in oral cancer cells. Maintenance of telomeres plays an essential role during transformation of precancer to malignant stage. Mammalian telomeres, a specialized nucleoprotein structures are composed of large conctamers of the guanine-rich sequence 5_-TTAGGG-3_. The roles of telomeres in regulating both stability of genome and replicative immortality seem to contribute in essential ways in cancer initiation and progression. It is concluded that activity of telomerase can be used as a biomarker for diagnosis of malignant oral cancer and a target for inactivation in chemotherapy or gene therapy. Its expression will also prove to be an important diagnostic tool as well as a novel target for cancer therapy. The activation of telomerase may be an important step in tumorgenesis which can be controlled by inactivating its activity during chemotherapy. The expression and activity of telomerase are indispensable for cancer development. There are no drugs which can effect extremely to treat oral cancers. There is a general call for new emerging drugs or methods that are highly effective towards cancer treatment, possess low toxicity, and have a minor environment impact. Some novel natural products also offer opportunities for innovation in drug discovery. Natural compounds isolated from medicinal plants, as rich sources of novel anticancer drugs, have been of increasing interest with some enzyme (telomerase) blockage property. The alarming reports of cancer cases increase the awareness amongst the clinicians and researchers pertaining to investigate newer drug with low toxicity.

Keywords: oral carcinoma, telomere, telomerase, blockage

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Authors: Frederick Huie, Lauren Fusfeld, William Burchenal, Scott Howell, Alyssa McVey, Thomas F. Goss

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Alzheimer’s Disease (AD) is a degenerative brain disease characterized by memory loss and cognitive decline that presents a substantial economic burden for patients and health insurers in the US. This study evaluates the payer budget impact of the DISCERN™ test in the diagnosis and management of patients with symptoms of dementia evaluated for AD. DISCERN™ comprises three assays that assess critical factors related to AD that regulate memory, formation of synaptic connections among neurons, and levels of amyloid plaques and neurofibrillary tangles in the brain and can provide a quicker, more accurate diagnosis than tests in the current diagnostic pathway (CDP). An Excel-based model with a three-year horizon was developed to assess the budget impact of DISCERN™ compared with CDP in a Medicare Advantage plan with 1M beneficiaries. Model parameters were identified through a literature review and were verified through consultation with clinicians experienced in diagnosis and management of AD. The model assesses direct medical costs/savings for patients based on the following categories: •Diagnosis: costs of diagnosis using DISCERN™ and CDP. •False Negative (FN) diagnosis: incremental cost of care avoidable with a correct AD diagnosis and appropriately directed medication. •True Positive (TP) diagnosis: AD medication costs; cost from a later TP diagnosis with the CDP versus DISCERN™ in the year of diagnosis, and savings from the delay in AD progression due to appropriate AD medication in patients who are correctly diagnosed after a FN diagnosis.•False Positive (FP) diagnosis: cost of AD medication for patients who do not have AD. A one-way sensitivity analysis was conducted to assess the effect of varying key clinical and cost parameters ±10%. An additional scenario analysis was developed to evaluate the impact of individual inputs. In the base scenario, DISCERN™ is estimated to decrease costs by $4.75M over three years, equating to approximately $63.11 saved per test per year for a cohort followed over three years. While the diagnosis cost is higher with DISCERN™ than with CDP modalities, this cost is offset by the higher overall costs associated with CDP due to the longer time needed to receive a TP diagnosis and the larger number of patients who receive a FN diagnosis and progress more rapidly than if they had received appropriate AD medication. The sensitivity analysis shows that the three parameters with the greatest impact on savings are: reduced sensitivity of DISCERN™, improved sensitivity of the CDP, and a reduction in the percentage of disease progression that is avoided with appropriate AD medication. A scenario analysis in which DISCERN™ reduces the utilization for patients of computed tomography from 21% in the base case to 16%, magnetic resonance imaging from 37% to 27% and cerebrospinal fluid biomarker testing, positive emission tomography, electroencephalograms, and polysomnography testing from 4%, 5%, 10%, and 8%, respectively, in the base case to 0%, results in an overall three-year net savings of $14.5M. DISCERN™ improves the rate of accurate, definitive diagnosis of AD earlier in the disease and may generate savings for Medicare Advantage plans.

Keywords: Alzheimer’s disease, budget, dementia, diagnosis.

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Authors: Minh Dong Le, Viet Dung Nguyen, Do Huu Viet, Nguyen Huu Tu

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In this paper, we present a new method for circumscribed masses detection in mammograms. Our method is evaluated on 23 mammographic images of circumscribed masses and 20 normal mammograms from public Mini-MIAS database. The method is quite sanguine with sensitivity (SE) of 95% with only about 1 false positive per image (FPpI). To achieve above results we carry out a progression following: Firstly, the input images are preprocessed with the aim to enhance key information of circumscribed masses; Next, we calculate and evaluate statistically basic features of abnormal regions on training database; Then, mammograms on testing database are divided into equal blocks which calculated corresponding features. Finally, using priority order of basic features to classify blocks as an abnormal or normal regions.

Keywords: mammograms, circumscribed masses, evaluated statistically, priority order of basic features

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Authors: Cheng-Cao Sun, Shu-Jun Li, De-Jia Li

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Long non-coding RNA (lncRNA) X inactivate-specific transcript (XIST) has been verified as an oncogenic gene in several human malignant tumors, and its dysregulation was closed associated with tumor initiation, development and progression. Nevertheless, whether the aberrant expression of XIST in human nasopharyngeal carcinoma (NPC) is corrected with malignancy, metastasis or prognosis has not been elaborated. Here, we discovered that XIST was up-regulated in NPC tissues and higher expression of XIST contributed to a markedly poorer survival time. In addition, multivariate analysis demonstrated XIST was an independent risk factor for prognosis. XIST over-expression enhanced, while XIST silencing hampered the cell growth in NPC. Additionally, mechanistic analysis revealed that XIST up-regulated the expression of miR-34a-5p targeted gene E2F3 through acting as a competitive ‘sponge’ of miR-34a-5p. Taking all into account, we concluded that XIST functioned as an oncogene in NPC through up-regulating E2F3 in part through ‘spongeing’ miR-34a-5p.

Keywords: X inactivate-specific transcript; hsa-miRNA-34a-5p, miR-34a-5p; E2F3, nasopharyngeal carcinoma, tumorigenesis

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Authors: Amirah Azzeri, Fatiha H. Shabaruddin, Scott A. McDonald, Rosmawati Mohamed, Maznah Dahlui

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Objective: A scaled-up treatment cascade with direct-acting antiviral (DAA) therapy is necessary to achieve global WHO targets for hepatitis C virus (HCV) elimination in Malaysia. Recently, limited access to Sofosbuvir/Daclatasvir (SOF/DAC) is available through compulsory licensing, with future access to Sofosbuvir/Velpatasvir (SOF/VEL) expected through voluntary licensing due to recent agreements. SOF/VEL has superior clinical outcomes, particularly for cirrhotic stages, but has higher drug acquisition costs compared to SOF/DAC. It has been proposed that a stratified treatment cascade might be the most cost-efficient approach for Malaysia whereby all HCV patients are treated with SOF/DAC except for patients with cirrhosis who are treated with SOF/VEL. This study aimed to conduct a five-year budget impact analysis from the provider perspective of the proposed stratified treatment cascade for HCV treatment in Malaysia. Method: A disease progression model that was developed based on model-predicted HCV epidemiology data in Malaysia was used for the analysis, where all HCV patients in scenario A were treated with SOF/DAC for all disease stages while in scenario B, SOF/DAC was used only for non-cirrhotic patients and SOF/VEL was used for the cirrhotic patients. The model projections estimated the annual numbers of patients in care and the numbers of patients to be initiated on DAA treatment nationally. Healthcare costs associated with DAA therapy and disease stage monitoring was included to estimate the downstream cost implications. For scenario B, the estimated treatment uptake of SOF/VEL for cirrhotic patients were 25%, 50%, 75%, 100% and 100% for 2018, 2019, 2020, 2021 and 2022 respectively. Healthcare costs were estimated based on standard clinical pathways for DAA treatment described in recent guidelines. All costs were reported in US dollars (conversion rate US$1=RM4.09, the price year 2018). Scenario analysis was conducted for 5% and 10% reduction of SOF/VEL acquisition cost anticipated from the competitive market pricing of generic DAA in Malaysia. Results: The stratified treatment cascade with SOF/VEL in Scenario B was found to be cost-saving compared to Scenario A. A substantial portion of the cost reduction was due to the costs associated with DAA therapy which resulted in USD 40 thousand (year 1) to USD 443 thousand (year 5) savings annually, with cumulative savings of USD 1.1 million after 5 years. Cost reductions for disease stage monitoring were seen in year three onwards which resulted in cumulative savings of USD 1.1 thousand. Scenario analysis estimated cumulative savings of USD 1.24 to USD 1.35 million when the acquisition cost of SOF/VEL was reduced. Conclusion: A stratified treatment cascade with SOF/VEL was expected to be cost-saving and can results in a budget impact reduction in overall healthcare expenditure in Malaysia compared to treatment with SOF/DAC. The better clinical efficacy with SOF/VEL is expected to halt patients’ HCV disease progression and may reduce downstream costs of treating advanced disease stages. The findings of this analysis may be useful to inform healthcare policies for HCV treatment in Malaysia.

Keywords: Malaysia, direct acting antiviral, compulsory licensing, voluntary licensing

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Authors: Laura Gleason, Sahithi Talasila, Lauren Banner, Ladan Afifi, Neda Nikbakht

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Primary cutaneous anaplastic large cell lymphoma (pcALCL) accounts for 9% of all cutaneous T-cell lymphomas. pcALCL is classically characterized as a solitary papulonodule that often enlarges, ulcerates, and can be locally destructive, but overall exhibits an indolent course with overall 5-year survival estimated to be 90%. Distinguishing pcALCL from systemic ALCL (sALCL) is essential as sALCL confers a poorer prognosis with average 5-year survival being 40-50%. Although extremely rare, there have been several cases of ALK-positive ALCL diagnosed on skin biopsy without evidence of systemic involvement, which poses several challenges in the classification, prognostication, treatment, and follow-up of these patients. Objectives: We present a case of cutaneous ALK-positive ALCL without evidence of systemic involvement, and a narrative review of the literature to further characterize that ALK-positive ALCL limited to the skin is a distinct variant with a unique presentation, history, and prognosis. A 30-year-old woman presented for evaluation of an erythematous-violaceous papule present on her right chest for two months. With the development of multifocal disease and persistent lymphadenopathy, a bone marrow biopsy and lymph node excisional biopsy were performed to assess for systemic disease. Both biopsies were unrevealing. The patient was counseled on pursuing systemic therapy consisting of Brentuximab, Cyclophosphamide, Doxorubicin, and Prednisone given the concern for sALCL. Apropos of the patient we searched for clinically evident, cutaneous ALK-positive ALCL cases, with and without systemic involvement, in the English literature. Risk factors, such as tumor location, number, size, ALK localization, ALK translocations, and recurrence, were evaluated in cases of cutaneous ALK-positive ALCL. The majority of patients with cutaneous ALK-positive ALCL did not progress to systemic disease. The majority of cases that progressed to systemic disease in adults had recurring skin lesions and cytoplasmic localization of ALK. ALK translocations did not influence disease progression. Mean time to disease progression was 16.7 months, and significant mortality (50%) was observed in those cases that progressed to systemic disease. Pediatric cases did not exhibit a trend similar to adult cases. In both the adult and pediatric cases, a subset of cutaneous-limited ALK-positive ALCL were treated with chemotherapy. All cases treated with chemotherapy did not progress to systemic disease. Apropos of an ALK-positive ALCL patient with clinical cutaneous limited disease in the histologic presence of systemic markers, we discussed the literature data, highlighting the crucial issues related to developing a clinical strategy to approach this rare subtype of ALCL. Physicians need to be aware of the overall spectrum of ALCL, including cutaneous limited disease, systemic disease, disease with NPM-ALK translocation, disease with ALK and EMA positivity, and disease with skin recurrence.

Keywords: anaplastic large cell lymphoma, systemic, cutaneous, anaplastic lymphoma kinase, ALK, ALCL, sALCL, pcALCL, cALCL

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Authors: Renato André S. Silva, Nana L. F. Sampaio, Carlos J. G. Cruz, Bruno Vianna, Flávio O. Pires

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multiple stage bicycle races require high physiological loads from professional cyclists. Such demands can lead to immunosuppression and health problems. However, in this type of competition, little is known about its physiological effects on amateur athletes, who generally receive less medical support. Thus, this study analyzes the hematological effects of a multiple stage bicycle race on amateur cyclists. Seven Brazilian national amateur cyclists (34 ± 4.21 years) underwent a laboratory test to evaluate VO2Max (69.89 ± 7.43 ml⋅kg-1⋅min-1). Six days later, these volunteers raced in the Tour of Goiás, participating in five races in four days (435 km) of competition. Arterial blood samples were collected one day before and one day after the competition. The Kolmogorov-Smirnov tests were used to evaluate the data distribution and Wilcoxon to compare the two moments (p <0.05) of data collection. The results show: Red cells ↓ 7.8% (5.1 ± 0.28 vs 4.7 ± 0.37 106 / mm 3, p = 0.01); Hemoglobin ↓ 7.9% (15.1 ± 0.31 vs 13.9 ± 0.27 g / dL, p = 0.01); Leukocytes ↑ 9.5% (4946 ± 553 versus 5416 ± 1075 / mm 3, p = 0.17); Platelets ↓ 7.0% (200.2 ± 51.5 vs 186.1 ± 39.5 / mm 3, p = 0.01); LDH ↑ 11% (164.4 ± 28.5 vs 182.5 ± 20.5 U / L, p = 0.17); CK ↑ 13.5% (290.7 ± 206.1 vs 330.1 ± 90.5 U / L, p = 0.39); CK-MB ↑ 2% (15.7 ± 3.9 vs. 20.1 ± 2.9 U / L, p = 0.06); Cortizol ↓ 13.5% (12.1 ± 2.4 vs 9.9 ± 1.9 μg / dL, p = 0.01); Total testosterone ↓ 7% (453.6 ± 120.1 vs 421.7 ± 74.3 ng / dL, p = 0.12); IGF-1 ↓ 15.1% (213.8 ± 18.8 vs 181.5 ± 34.7 ng / mL, p = 0.04). This means that there was significant reductions in O2 allocation / transport capacities, vascular injury disruption, and a fortuitous reduction of muscle skeletal anabolism along with maintenance and / or slight elevation of immune function, glucose and lipid energy and myocardial damage. Therefore, the results suggest that no abnormal health effect was identified among the athletes after participating in the Tour de Goiás.

Keywords: cycling, health effects, cycling stages races, haematology

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Authors: Ioanna Garefi, Irene Kalemaki

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Education is not solely about preparing young people for the world of work but also about equipping them with competences that will enable them to become socially proactive, empowered, responsible, and engaged citizens who will collectively contribute to and benefit from an inclusive and sustainable future. Hence, progress assessment towards competence development is an ongoing process where continuous efforts are needed. This paper abstract presents the work of the H2020 NEMESIS project that aims to investigate, experiment and co-create together with schools a model for introducing and embedding social innovation education (SIE henceforth) in European primary and secondary schools. All in all, during the 2018-2019 academic year, 8 schools from 5 European countries involving 56 teachers, 1030 students, and 80 external stakeholders, experimented with different methodologies for embedding SIE in their contexts. This paper captures briefly the impact of these efforts towards the cultivation and progression of students’ social innovation (SI henceforth) competences. As part of the model, 14 SI competences, whose progress was evaluated, have been introduced falling under 3 interrelated categories: competences for identifying opportunities for social and collective value creation, competences for developing collaborations and building meaningful relations and competences for taking action both on an individual and collective level. Methodologically wise, the evaluation strategy employed was informed by a realist approach, enabling the researchers to go beyond synthesizing 'what happened' and towards understanding 'why it happened', delving into ‘what works, for whom and in what circumstances’. The reason for choosing such an approach was because it goes beyond attempting to answer the basic yes or no question of evaluation and focus on an ‘explanatory quest’ tracing the limits of when and where intervention is effective. A rich mix of sources of evidence have been employed, from focus groups with 80 people from the 5 EU countries to an online survey to 206 students, classroom observations, students’ narratives granting them with the opportunity to freely express their opinions, short stories letting students express their feelings through their imagination and also, drawings so that younger children can express their perception of reality. All these evidences offered insights on the impact of SIE on the development of students’ competences. Research findings showed that students progressed in all 14 SI competences through their involvement in the different activities. This positive progression is attributed to the model’s three core principles: 1) the student-centered approach, rendering students active and self-determined producers of their own learning, 2) the co-creation process fostering intergenerational interactions, empowering thus students by making their voices heard and valued and also, 3) the transformative social action whereby through their projects, students are able to witness the impact they are bringing about with their actions. Concluding, these initial findings, together with the forthcoming evaluation research to a pool of 30 schools around Europe, have the potential to raise the dynamics of the under-investigated field of SIE and encourage its embeddedness in more schools around Europe.

Keywords: competence development, education, social innovation, students

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Authors: Diwei Lin, Amanda Jh. Tan

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We present a very rare case of de novo large cell neuroendocrine carcinoma of the prostate (LCNEC) in an 84-year-old male on a background of high-grade, muscle-invasive transitional cell carcinoma of the bladder. While NE tumours account for 1% to 5% of all cases of prostate cancer and scattered NE cells can be found in 10% to 100% of prostate adenocarcinomas, pure LCNEC of the prostate is extremely rare. Most LCNEC of the prostate is thought to originate by clonal progression under the selection pressure of therapy and refractory to long-term hormonal treatment for adenocarcinoma of the prostate. De novo LCNEC is only described in case reports and is thought to develop via direct malignant transformation. Limited data in the English literature makes it difficult to accurately predict the prognosis of LCNEC of the prostate. However, current evidence suggesting that increasing NE differentiation in prostate adenocarcinoma is associated with a higher stage, high-grade disease, and a worse prognosis.

Keywords: large cell neuroendocrine cancer, prostate cancer, refractory cancer, medical and health sciences

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Authors: Karissa Graham, Andrew Campbell-Lloyd

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The deep inferior epigastric artery perforator flap (DIEP) is used to reconstruct large volumes of tissue. The DIEP flap is based on the deep inferior epigastric artery (DIEA) and vein. Accurate knowledge of the anatomy of these vessels allows for efficient dissection of the flap, minimal damage to surrounding tissue, and a well vascularized flap. A 54 year old lady was assessed for bilateral delayed autologous reconstruction with DIEP free flaps. The right DIEA was consistent with the described anatomy. The left DIEA had a vessel branching shortly after leaving the external iliac artery and before entering the muscle. This independent branch entered the muscle and had a long intramuscular course to the largest perforator. The main DIEA vessel demonstrated a type II branching pattern but had perforators that were too small to have a viable DIEP flap. There were no communicating arterial branches between the independent vessel and DIEA, however, there was one venous communication between them. A muscle sparing transverse rectus abdominis muscle flap was raised using the main periumbilical perforator from the independent vessel. Our case report demonstrated an unreported anatomical variant of the DIEA. A few anatomical variants have been described in the literature, including a unilateral absent DIEA and peritoneal-cutaneous perforators that had no connection to the DIEA. Doing a pre-operative CTA helps to identify these rare anatomical variations, which leads to safer, more efficient, and effective operating.

Keywords: aberrant anatomy, CT angiography, DIEP anatomy, free flap

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Authors: Jessica Peart, Sarim Al Zubaidy

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This paper examines the main dialogic and reformative aspects that have constituted the developing implementation of an English language module in a common pre-sessional program in Oman, the General Foundation Program (GFP), at the new Military Technological College (MTC), in Oman’s capital, muscat. The MTC is the first of its kind in the country to merge military with academic training and has been running programs since September 2013 over five trimesters to date, receiving external validation and accreditation from the University of Portsmouth (UoP), UK. From this starting point, We will provide context on the parameters that necessitated delivery of this common but specially tailored pre-sessional program at the MTC and outline in detail how the English module with integrated key study skills and personal tutoring support was initially conceived before operations commenced and cooperation between all stakeholders took practical shape. This enquiry traces how stakeholders from students to faculty, college boards and collaborative university partners have considered and redefined the in part static and dynamic boundaries of their larger and smaller scale stakes. With regard to the widely held recognition that pre-sessional students require training in transferable study skills in order to succeed at university, we will chart the subsequent and ongoing adjustments made to the generic, pastoral and integrated elements of that program. Driving this concerted effort has been at base the need for a GFP concerned with three criteria for incoming MTC students cadets, namely to develop candidate’s rounded capacity for intellectual, technical and physical skill as both students and cadets, to generate linguistic proficiency and discerning use of appropriate language registers and to allow personal and collective time for adjustment to a multilayered, brand new environment, while also working within a regulated timeline for academic progression to the MTC diploma or degree levels. The English Department teaching staff’s facilitation of the initial program’s methodologies and timeframe for the GFP English module has garnered a keen and diverse sense of the holistic student cadet experience, which a range of alterations to the program demonstrate. These include alterations to the class types and overall program duration as well as greater multiplicity of exposure within learning environments. In surveying the impact of these composite maneuvers and challenges within a proactive and evolving context of teaching and learning, it is finally demonstrated how student cadet levels of productivity and self-reliance on the one hand and retention issues on the other are being gainfully steered towards progression within a framework for inclusive reciprocal dialogue, gathering thereby civilian and military backgrounds toward uniquely united ends.

Keywords: English module transferable skills, faculty dialogue, governance structure, overarching regulatory agencies

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Authors: Shalini Rankawat, Mansi Rankawat, Rahul Dubey, Mazad Zaveri

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Physiological signals such as electrocardiogram (ECG) and arterial blood pressure (ABP) in the intensive care unit (ICU) are often seriously corrupted by noise, artifacts, and missing data, which lead to errors in the estimation of heart rate (HR) and incidences of false alarm from ICU monitors. Clinical support in ICU requires most reliable heart rate estimation. Cardiac activity, because of its relatively high electrical energy, may introduce artifacts in Electroencephalogram (EEG), Electrooculogram (EOG), and Electromyogram (EMG) recordings. This paper presents a robust heart rate estimation method by detection of R-peaks of ECG artifacts in EEG, EMG & EOG signals, using energy-based function and a novel Signal Quality Index (SQI) assessment technique. SQIs of physiological signals (EEG, EMG, & EOG) were obtained by correlation of nonlinear energy operator (teager energy) of these signals with either ECG or ABP signal. HR is estimated from ECG, ABP, EEG, EMG, and EOG signals from separate Kalman filter based upon individual SQIs. Data fusion of each HR estimate was then performed by weighing each estimate by the Kalman filters’ SQI modified innovations. The fused signal HR estimate is more accurate and robust than any of the individual HR estimate. This method was evaluated on MIMIC II data base of PhysioNet from bedside monitors of ICU patients. The method provides an accurate HR estimate even in the presence of noise and artifacts.

Keywords: ECG, ABP, EEG, EMG, EOG, ECG artifacts, Teager-Kaiser energy, heart rate, signal quality index, Kalman filter, data fusion

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Authors: Khamis Al-Gharbi, Said M. Gattoufi, Ali H. Al-Badi, Ali Al-Hashmi

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The case study presents the progression of a project management of Al-Shifa, a healthcare information system in Oman. The case study describes the evolution of the implementation of a healthcare information system tailored to meet the needs of the healthcare units under the supervision of the Ministry of Health (MOH) in Oman. A focus group methodology was used for collecting the relevant information from the main project's stakeholders. In addition reports about the project made available for the researchers. The case analysis is made based on the Project Management approach developed by the Project Management Institute (PMI). The main finding that there was no formal project management approach adopted by the MOH for the development and implementation of the herewith mentioned healthcare information system project. Furthermore, the project had suffered a scope creep in terms of features, cost and time-schedule. The recommendations of the authors, for the rescue of the project from its current dilemma, consist of technological, administrative and human resources development actions.

Keywords: project management, information system, healthcare, Al-Shifa, Oman

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