Search results for: surgery results
Commenced in January 2007
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Edition: International
Paper Count: 37648

Search results for: surgery results

36628 Some Results on Cluster Synchronization

Authors: Shahed Vahedi, Mohd Salmi Md Noorani

Abstract:

This paper investigates cluster synchronization phenomena between community networks. We focus on the situation where a variety of dynamics occur in the clusters. In particular, we show that different synchronization states simultaneously occur between the networks. The controller is designed having an adaptive control gain, and theoretical results are derived via Lyapunov stability. Simulations on well-known dynamical systems are provided to elucidate our results.

Keywords: cluster synchronization, adaptive control, community network, simulation

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36627 Optimization of Perfusion Distribution in Custom Vascular Stent-Grafts Through Patient-Specific CFD Models

Authors: Scott M. Black, Craig Maclean, Pauline Hall Barrientos, Konstantinos Ritos, Asimina Kazakidi

Abstract:

Aortic aneurysms and dissections are leading causes of death in cardiovascular disease. Both inevitably lead to hemodynamic instability without surgical intervention in the form of vascular stent-graft deployment. An accurate description of the aortic geometry and blood flow in patient-specific cases is vital for treatment planning and long-term success of such grafts, as they must generate physiological branch perfusion and in-stent hemodynamics. The aim of this study was to create patient-specific computational fluid dynamics (CFD) models through a multi-modality, multi-dimensional approach with boundary condition optimization to predict branch flow rates and in-stent hemodynamics in custom stent-graft configurations. Three-dimensional (3D) thoracoabdominal aortae were reconstructed from four-dimensional flow-magnetic resonance imaging (4D Flow-MRI) and computed tomography (CT) medical images. The former employed a novel approach to generate and enhance vessel lumen contrast via through-plane velocity at discrete, user defined cardiac time steps post-hoc. To produce patient-specific boundary conditions (BCs), the aortic geometry was reduced to a one-dimensional (1D) model. Thereafter, a zero-dimensional (0D) 3-Element Windkessel model (3EWM) was coupled to each terminal branch to represent the distal vasculature. In this coupled 0D-1D model, the 3EWM parameters were optimized to yield branch flow waveforms which are representative of the 4D Flow-MRI-derived in-vivo data. Thereafter, a 0D-3D CFD model was created, utilizing the optimized 3EWM BCs and a 4D Flow-MRI-obtained inlet velocity profile. A sensitivity analysis on the effects of stent-graft configuration and BC parameters was then undertaken using multiple stent-graft configurations and a range of distal vasculature conditions. 4D Flow-MRI granted unparalleled visualization of blood flow throughout the cardiac cycle in both the pre- and postsurgical states. Segmentation and reconstruction of healthy and stented regions from retrospective 4D Flow-MRI images also generated 3D models with geometries which were successfully validated against their CT-derived counterparts. 0D-1D coupling efficiently captured branch flow and pressure waveforms, while 0D-3D models also enabled 3D flow visualization and quantification of clinically relevant hemodynamic parameters for in-stent thrombosis and graft limb occlusion. It was apparent that changes in 3EWM BC parameters had a pronounced effect on perfusion distribution and near-wall hemodynamics. Results show that the 3EWM parameters could be iteratively changed to simulate a range of graft limb diameters and distal vasculature conditions for a given stent-graft to determine the optimal configuration prior to surgery. To conclude, this study outlined a methodology to aid in the prediction post-surgical branch perfusion and in-stent hemodynamics in patient specific cases for the implementation of custom stent-grafts.

Keywords: 4D flow-MRI, computational fluid dynamics, vascular stent-grafts, windkessel

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36626 Catamenial Pneumothorax: Report of Two Cases and Review of the Local Literature

Authors: Angeli Marie P. Lagman, Nephtali M. Gorgonio

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Catamenial pneumothorax is defined as a recurrent accumulation of air in the pleural cavity, which occurs in the period of 72 hours before or after menses. In a menstruating woman presenting with the difficulty of breathing and chest pain with concomitant radiographic evidence of pneumothorax, a diagnosis of catamenial pneumothorax should be entertained. Two cases of catamenial pneumothorax were reported in our local literature. This report added two more cases. The first case is 45 years old G1P1, while the second case is 46 years old G2P2. These two patients had a history of pelvic endometriosis in the past. All other signs and symptoms were similar to the previously reported cases. All patients presented with difficulty of breathing associated with chest pain. Imaging studies showed right-sided pneumothorax in all patients. Intraoperatively, subpleural bleb, diaphragmatic fenestrations, and endometriotic implants were found. Three patients underwent video-assisted thoracosurgery (VATS), while one patient underwent open thoracotomy with pleurodesis. Histopathology revealed endometriosis in only two patients. All patients received postoperative hormonal therapy, and there were no recurrences noted in all patients. Endometriosis-related catamenial pneumothorax is a rare condition that needs early recognition of the symptoms. Several theories may be involved to explain the pathogenesis of catamenial pneumothorax. Two cases show a strong significant association between a history of pelvic endometriosis and the development of catamenial pneumothorax, while one case can be explained by the hormonal theory. The difficulty of breathing and chest pain in relation to menses may prompt early diagnosis. One case has shown that pneumothorax may occur even after menstruation. A biopsy of the endometrial implants may not always show endometrial glands and stroma, nor will immunostaining, which will not always show estrogen and progesterone receptors. Video-assisted thoracoscopic surgery is the gold standard in the diagnosis and treatment of catamenial pneumothorax. Postoperative hormonal suppression will further reduce the disease recurrence and facilitate the effectiveness of the surgical treatment.

Keywords: catamenial pneumothorax, endometriosis, menstruation, video assisted thoracosurgery

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36625 Impact on the Results of Sub-Group Analysis on Performance of Recommender Systems

Authors: Ho Yeon Park, Kyoung-Jae Kim

Abstract:

The purpose of this study is to investigate whether friendship in social media can be an important factor in recommender system through social scientific analysis of friendship in popular social media such as Facebook and Twitter. For this purpose, this study analyzes data on friendship in real social media using component analysis and clique analysis among sub-group analysis in social network analysis. In this study, we propose an algorithm to reflect the results of sub-group analysis on the recommender system. The key to this algorithm is to ensure that recommendations from users in friendships are more likely to be reflected in recommendations from users. As a result of this study, outcomes of various subgroup analyzes were derived, and it was confirmed that the results were different from the results of the existing recommender system. Therefore, it is considered that the results of the subgroup analysis affect the recommendation performance of the system. Future research will attempt to generalize the results of the research through further analysis of various social data.

Keywords: sub-group analysis, social media, social network analysis, recommender systems

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36624 Coefficients of Some Double Trigonometric Cosine and Sine Series

Authors: Jatinderdeep Kaur

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In this paper, the results of Kano from one-dimensional cosine and sine series are extended to two-dimensional cosine and sine series. To extend these results, some classes of coefficient sequences such as the class of semi convexity and class R are extended from one dimension to two dimensions. Under these extended classes, I have checked the function f(x,y) is two dimensional Fourier Cosine and Sine series or equivalently it represents an integrable function. Further, some results are obtained which are the generalization of Moricz's results.

Keywords: conjugate dirichlet kernel, conjugate fejer kernel, fourier series, semi-convexity

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36623 Using Multiomic Plasma Profiling From Liquid Biopsies to Identify Potential Signatures for Disease Diagnostics in Late-Stage Non-small Cell Lung Cancer (NSCLC) in Trinidad and Tobago

Authors: Nicole Ramlachan, Samuel Mark West

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Lung cancer is the leading cause of cancer-associated deaths in North America, with the vast majority being non-small cell lung cancer (NSCLC), with a five-year survival rate of only 24%. Non-invasive discovery of biomarkers associated with early-diagnosis of NSCLC can enable precision oncology efforts using liquid biopsy-based multiomics profiling of plasma. Although tissue biopsies are currently the gold standard for tumor profiling, this method presents many limitations since these are invasive, risky, and sometimes hard to obtain as well as only giving a limited tumor profile. Blood-based tests provides a less-invasive, more robust approach to interrogate both tumor- and non-tumor-derived signals. We intend to examine 30 stage III-IV NSCLC patients pre-surgery and collect plasma samples.Cell-free DNA (cfDNA) will be extracted from plasma, and next-generation sequencing (NGS) performed. Through the analysis of tumor-specific alterations, including single nucleotide variants (SNVs), insertions, deletions, copy number variations (CNVs), and methylation alterations, we intend to identify tumor-derived DNA—ctDNA among the total pool of cfDNA. This would generate data to be used as an accurate form of cancer genotyping for diagnostic purposes. Using liquid biopsies offer opportunities to improve the surveillance of cancer patients during treatment and would supplement current diagnosis and tumor profiling strategies previously not readily available in Trinidad and Tobago. It would be useful and advantageous to use this in diagnosis and tumour profiling as well as to monitor cancer patients, providing early information regarding disease evolution and treatment efficacy, and reorient treatment strategies in, timethereby improving clinical oncology outcomes.

Keywords: genomics, multiomics, clinical genetics, genotyping, oncology, diagnostics

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36622 Modification of Titanium Surfaces with Micro/Nanospheres for Local Antibiotic Release

Authors: Burcu Doymus, Fatma N. Kok, Sakip Onder

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Titanium and titanium-based materials are commonly used to replace or regenerate the injured or lost tissues because of accidents or illnesses. Hospital infections and strong bond formation at the implant-tissue interface are directly affecting the success of the implantation as weak bonding with the native tissue and hospital infections lead to revision surgery. The purpose of the presented study is to modify the surface of the titanium substrates with nano/microspheres for local drug delivery and to prevent hospital infections. Firstly, titanium surfaces were silanized with APTES (3-Triethoxysilylpropylamine) following the negatively charged oxide layer formation. Then characterization studies using Scanning Electron Microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) were done on the modified surfaces. Secondly, microspheres/nanospheres were prepared with chitosan that is a natural polymer and having valuable properties such as non-toxicity, high biocompatibility, low allergen city and biodegradability for biomedical applications. Antibiotic (ciprofloxacin) loaded micro/nanospheres have been fabricated using emulsion cross-linking method and have been immobilized onto the titanium surfaces with different immobilization techniques such as covalent bond and entrapment. Optimization studies on size and drug loading capacities of micro/nanospheres were conducted before the immobilization process. Light microscopy and SEM were used to visualize and measure the size of the produced micro/nanospheres. Loaded and released drug amounts were determined by using UV- spectrophotometer at 278 nm. Finally, SEM analysis and drug release studies on the micro/nanospheres coated Ti surfaces were done. As a conclusion, it was shown that micro/nanospheres were immobilized onto the surfaces successfully and drug release from these surfaces was in a controlled manner. Moreover, the density of the micro/nanospheres after the drug release studies was higher on the surfaces where the entrapment technique was used for immobilization. Acknowledgement: This work is financially supported by The Scientific and Technological Research Council Of Turkey (Project # 217M220)

Keywords: chitosan, controlled drug release, nanosphere, nosocomial infections, titanium

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36621 Investigating the Antimicrobial Activity of Essential Oil Derived from Pistacia atlantica Gum against Extensively Drug-Resistant Gram-Negative Acinetobacter baumannii

Authors: Zhala Ahmad, Zainab Lazim, Haider Hamzah

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Bacterial resistance is a pressing global health issue, with multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) strains to pose a serious threat. In this context, researchers are investigating effective, safe, and affordable metabolites to combat these pathogens. This study focuses on gum essential oil (GEO) extracted from Pistacia atlantica and its activity and the mechanism of action against XDR Gram-negative Acinetobacter baumannii. GEO was extracted by hydrodistillation and analyzed using GC-MS. Eleven A. baumannii isolates were collected from the ward environment of Burn and Plastic Surgery Hospital in Al Sulaymaniyah City, Iraq. They were identified using the VITEK 2 system, 16S rRNA gene, and confirmed with the blaₒₓₐ₋₅₁ gene; A. baumannii ATCC 19606 was used as a reference strain. The isolates were identified as resistant to twelve different antibiotics spanning six distinct antibiotic classes while showing susceptibility to tetracycline and trimethoprim. Over 40 chemical constituents were detected in the gum's essential oils, with α-pinene being the most abundant. GEO was found to inhibit the growth of A. baumannii isolates; the minimum inhibitory concentration (MIC) of GEO was 2.5 µl/ml. GEO induced protein leakage, phosphate, and potassium ion efflux, distorted cell morphology, and cell death in the tested bacteria. GEO exhibited bacterial clearance and anti-adhesion activity using Band-Aids. This study's findings suggest that GEO could be used as a potential alternative treatment for infectious diseases caused by XRD pathogens, shedding further light on the importance of GEO in biomedical applications. Future studies must focus on generating clinically feasible sources of GEO for testing in small animal models before proceeding to human trials, ensuring safe and effective translation from the laboratory to the clinic.

Keywords: antibiotic resistance, Acinetobacter baumannii, essential oils, Pistacia atlantica, alpha-pinene

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36620 Numerical Investigation of Geotextile Application in Clay Reinforcement in ABAQUS Software

Authors: Seyed Abolhasan Naeini, Eisa Aliagahei

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Today, the use of geosynthetic materials in geotechnical activities is increasing significantly. One of the main uses of these materials is to increase the compressive strength of clay reinforced by geotextile layers. In the present study, the effect of clay reinforcement by geotextile layers in increasing the compressive strength of clay has been investigated using modeling in ABAQUS 6.11.3 software. For this purpose, the modified Drager Prager model has been chosen to simulate the stress-strain behavior of soil layers and the linear elastic model for the geotextile layer. Unreinforced samples and reinforced samples are modeled by geotextile layers (1, 2 and 3 geotextile layers) by software. In order to validate the results, an article in the same field was used and the numerical modeling results were calibrated with the laboratory results. Based on the obtained results, the software has a suitable capability for modeling and the results of the numerical model overlap with the laboratory results to a very acceptable extent, by increasing the number of geotextile layers, the error between the results of the laboratory sample and the software model increases. The highest amount of error is related to the sample reinforced with three layers of geotextile and is 7.3%.

Keywords: Abaqus, cap model, clay, geotextile layer, reinforced soil

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36619 The Dual Catastrophe of Behçet’s Disease Visual Loss Followed by Acute Spinal Shock After Lumbar Drain Removal

Authors: Naim Izet Kajtazi

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Context: Increased intracranial pressure and associated symptoms such as headache, papilledema, motor or sensory deficits, seizures, and conscious disturbance are well-known in acute CVT. However, visual loss is not commonly associated with this disease, except in the case of secondary IIH associated with it. Process: We report a case of a 40-year-old male with Behçet’s disease and cerebral venous thrombosis, and other multiple comorbidities admitted with a four-day history of increasing headache and rapidly progressive visual loss bilaterally. The neurological examination was positive for bilateral papilledema of grade 3 with light perception on the left eye and counting fingers on the right eye. Brain imaging showed old findings of cerebral venous thrombosis without any intraparenchymal lesions to suggest a flare-up of Behçet’s disease. The lumbar puncture, followed by the lumbar drain insertion, gave no benefit in headache or vision. However, he completely lost sight. The right optic nerve sheath fenestration did not result in vision improvement. The acute spinal shock complicated the lumbar drain removal due to epidural hematoma. An urgent lumbar laminectomy with hematoma evacuation undertook. Intra-operatively, the neurosurgeon noted suspicious abnormal vessels at conus medullaris with the possibility of an arteriovenous malformation. Outcome: In a few days following the spinal surgery, the patient vision started to improve. Further improvement was achieved after plasma exchange sessions followed by cyclophosphamide. In the recent follow-up in the clinic, he reported better vision, drove, and completed his Ph.D. studies. Relevance: Visual loss in patients with Behçet’s disease should always be anticipated and taken reasonable care of, ensuring that they receive well-combined immunosuppression with anticoagulation and agents to reduce intracranial pressure. This patient’s story is significant for a high disease burden and complicated hospital course by acute spinal shock due to spinal lumbar drain removal with a possible underlying spinal arteriovenous malformation.

Keywords: Behcet disease, optic neuritis, IIH, CVT

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36618 Euthanasia with Reference to Defective Newborns: An Analysis

Authors: Nibedita Priyadarsini

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It is said that Ethics has a wide range of application which mainly deals with human life and human behavior. All ethical decisions are ultimately concerned with life and death. Both life and death must be considered dignified. Medical ethics with its different topics mostly deals with life and death concepts among which euthanasia is one. Various types of debates continue over Euthanasia long since. The question of putting an end to someone’s life has aroused controversial in legal sphere as well as in moral sphere. To permit or not to permit has remained an enigma the world over. Modern medicine is in the stage of transcending limits that cannot be set aside. The morality of allowing people to die without treatment has become more important as methods of treatment have become more sophisticated. Allowing someone to die states an essential recognition that there is some point in any terminal illness when further curative treatment has no purpose and the patient in such situation should allow dying a natural death in comfort, peace, and dignity, without any interference from medical science and technology. But taking a human life is in general sense is illogical in itself. It can be said that when we kill someone, we cause the death; whereas if we merely let someone die, then we will not be responsible for anyone’s death. This point is often made in connection with the euthanasia cases and which is often debatable. Euthanasia in the pediatric age group involves some important issues that are different from those of adult issues. The main distinction that occurs is that the infants and newborns and young children are not able to decide about their future as the adult does. In certain cases, where the child born with some serious deformities with no hope of recovery, in that cases doctor decide not to perform surgery in order to remove the blockage, and let the baby die. Our aim in this paper is to examine, whether it is ethically justified to withhold or to apply euthanasia on the part of the defective infant. What to do with severely defective infants from earliest time if got to know that they are not going to survive at all? Here, it will deal mostly with the ethics in deciding the relevant ethical concerns in the practice of euthanasia with the defective newborns issues. Some cases in relation to disabled infants and newborn baby will be taken in order to show what to do in a critical condition, that the patient and family members undergoes and under which condition those could be eradicated, if not all but some. The final choice must be with the benefit of the patient.

Keywords: ethics, medical ethics, euthanasia, defective newborns

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36617 The Two-Lane Rural Analysis and Comparison of Police Statistics and Results with the Help IHSDM

Authors: S. Amanpour, F. Mohamadian, S. A. Tabatabai

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With the number of accidents and fatalities in recent years can be concluded that Iran is the status of road accidents, remains in a crisis. Investigate the causes of such incidents in all countries is a necessity. By doing this research, the results of the number and type of accidents and the location of the crash will be available. It is possible to prioritize economic and rational solutions to fix the flaws in the way of short-term the results are all the more strict rules about the desire to have black spots and cursory glance at the change of but results in long-term are desired to change the system or increase the width of the path or add extra track. In general, the relationship between the analysis of the accidents and near police statistics is the number of accidents in one year. This could prove the accuracy of the analysis done.

Keywords: traffic, IHSDM, crash, modeling, Khuzestan

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36616 Development of PVA/polypyrrole Scaffolds by Supercritical CO₂ for Its Application in Biomedicine

Authors: Antonio Montes, Antonio Cozar, Clara Pereyra, Diego Valor, Enrique Martinez de la Ossa

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Tissues and organs can be damaged because of traumatism, congenital illnesses, or cancer and the traditional therapeutic alternatives, such as surgery, cannot usually completely repair the damaged tissues. Tissue engineering allows regeneration of the patient's tissues, reducing the problems caused by the traditional methods. Scaffolds, polymeric structures with interconnected porosity, can be promoted the proliferation and adhesion of the patient’s cells in the damaged area. Furthermore, by means of impregnation of the scaffold with beneficial active substances, tissue regeneration can be induced through a drug delivery process. The objective of the work is the fabrication of a PVA scaffold coated with Gallic Acid and polypyrrole through a one-step foaming and impregnation process using the SSI technique (Supercritical Solvent Impregnation). In this technique, supercritical CO₂ penetrates into the polymer chains producing the plasticization of the polymer. In the depressurization step a CO₂ cellular nucleation and growing to take place to an interconnected porous structure of the polymer. The foaming process using supercritical CO₂ as solvent and expansion agent presents advantages compared to the traditional scaffolds’ fabrication methods, such as the polymer’s high solubility in the solvent or the possibility of carrying out the process at a low temperature, avoiding the inactivation of the active substance. In this sense, the supercritical CO₂ avoids the use of organic solvents and reduces the solvent residues in the final product. Moreover, this process does not require long processing time that could cause the stratification of substance inside the scaffold reducing the therapeutic efficiency of the formulation. An experimental design has been carried out to optimize the SSI technique operating conditions, as well as a study of the morphological characteristics of the scaffold for its use in tissue engineerings, such as porosity, conductivity or the release profiles of the active substance. It has been proved that the obtained scaffolds are partially porous, conductors of electricity and are able to release Gallic Acid in the long term.

Keywords: scaffold, foaming, supercritical, PVA, polypyrrole, gallic acid

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36615 Development of Composition and Technology of Vincristine Nanoparticles Using High-Molecular Carbohydrates of Plant Origin

Authors: L. Ebralidze, A. Tsertsvadze, D. Berashvili, A. Bakuridze

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Current cancer therapy strategies are based on surgery, radiotherapy and chemotherapy. The problems associated with chemotherapy are one of the biggest challenges for clinical medicine. These include: low specificity, broad spectrum of side effects, toxicity and development of cellular resistance. Therefore, anti-cance drugs need to be develop urgently. Particularly, in order to increase efficiency of anti-cancer drugs and reduce their side effects, scientists work on formulation of nano-drugs. The objective of this study was to develop composition and technology of vincristine nanoparticles using high-molecular carbohydrates of plant origin. Plant polysacharides, particularly, soy bean seed polysaccharides, flaxseed polysaccharides, citrus pectin, gum arabic, sodium alginate were used as objects. Based on biopharmaceutical research, vincristine containing nanoparticle formulations were prepared. High-energy emulsification and solvent evaporation methods were used for preparation of nanosystems. Polysorbat 80, polysorbat 60, sodium dodecyl sulfate, glycerol, polyvinyl alcohol were used in formulation as emulsifying agent and stabilizer of the system. The ratio of API and polysacharides, also the type of the stabilizing and emulsifying agents are very effective on the particle size of the final product. The influence of preparation technology, type and concentration of stabilizing agents on the properties of nanoparticles were evaluated. For the next stage of research, nanosystems were characterized. Physiochemical characterization of nanoparticles: their size, shape, distribution was performed using Atomic force microscope and Scanning electron microscope. The present study explored the possibility of production of NPs using plant polysaccharides. Optimal ratio of active pharmaceutical ingredient and plant polysacharids, the best stabilizer and emulsifying agent was determined. The average range of nanoparticles size and shape was visualized by SEM.

Keywords: nanoparticles, target delivery, natural high molecule carbohydrates, surfactants

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36614 Modification of Hyrax Expansion Screw to Be Used as an Intro-Oral Distractor for Anterior Maxillary Distraction in a Patient with Cleft Lip and Palate: A Case Report

Authors: Ananya Hazare, Ranjit Kamble

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Introduction: Patients with Cleft lip and palate (CL/P) can present with a maxillary retrution after cleft repair. Anterior Maxillary distraction osteogenesis (AMD) is a technique that provides simultaneous skeletal advancement and expansion of the soft tissues related to an anterior segment of the maxilla. This case presented is a case of AMD. The advantage of this technique is that the occlusion in the posterior segment can be maintained, and only the segment in cross bite is advanced for correction of the midfacial deficiency. The other alternative treatment is anterior movement by a Lefort 1 osteotomy. When a Lefort 1 osteotomy is compared with the Distraction osteogenesis or AMD, the disadvantages of the Le Fort 1 include a higher risk of morbidity, requirement of fixation, relapse tendency and unexpected changes in the nasal form. These complications were eliminated by AMD technique. This was followed by placement of the implant in the bone formed after AMD. Hence complete surgical, orthodontic and prosthodontics rehabilitation of the patient was done by an interdisciplinary approach. Methods: Patient presented with repaired UCL/P of the right side with midfacial retrusion. Intro-oral examination revealed a good occlusion in the posterior arch and anterior Crossbite from canine to canine. Patient's both maxillary lateral incisors were missing. The lower arch was well aligned with all teeth present. The study models when scored according to GOSLON yardstick received a score of 4. After pre-surgical orthodontic phase was completed an intraoral distractor was fabricated by modification of HYRAX expansion screw. After surgery, low subapical osteotomy cuts were placed and the distractor was fixed. The latency period of 5 days was observed after which the distraction was started. Distraction was done at a rate of 1 mm/day with a rhythm of 0.5mm in morning and 0.5mm in the evening. The total distraction of 12 mm was done. After a consolidation period, the distractor was removed, and retention by a removable partial denture was given. Radiographic examination confirmed mature bone formation in the distracted segment. Implants were placed and allowed to osseointegrate for approximately 4 months and were then loaded with abutments. Results: Total distraction done was 12mm and after relapse it was 8mm. After consolidation phase the radiographic examination revealed a B2 quality of bone according to the Misch's classification and sufficient height from the maxillary sinus. These findings were indicative for placement of implants in the distracted bone formed in premolar region. Implants were placed and after radiographic evidence of osseointegration was seen they were loaded with abutments. Thus resulting in a complete rehabilitation of a cleft patient by an interdisciplinary approach. Conclusion: Anterior maxillary distraction can be used as an alternative method instead of complete distraction osteogenesis or Lefort 1 advancement of maxilla in cases where the advancement needed is minimum. Use of HYRAX expansion screw modified as intra-oral distractor can be used in such cases, which significantly reduces the cost of treatment, as expensive distractors are not used. This technique is very useful and efficient in countries like India where the patient cannot afford expensive treatment options.

Keywords: cleft lip and palate, distraction osteogenesis, anterior maxillary distraction, orthodontics and dentofacial orthopaedics, hyrax expansion screw modification

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36613 Periplasmic Expression of Anti-RoxP Antibody Fragments in Escherichia Coli.

Authors: Caspar S. Carson, Gabriel W. Prather, Nicholas E. Wong, Jeffery R. Anton, William H. McCoy

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Cutibacterium acnes is a commensal bacterium found on human skin that has been linked to acne. C. acnes can also be an opportunistic pathogen when it infiltrates the body during surgery. This pathogen can cause dangerous infections of medical implants, such as shoulder replacements, leading to life-threatening blood infections. Compounding this issue, C. acnes resistance to many antibiotics has become an increasing problem worldwide, creating a need for special forms of treatment. C. acnes expresses the protein RoxP, and it requires this protein to colonize human skin. Though this protein is required for C. acnes skin colonization, its function is not yet understood. Inhibition of RoxP function might be an effective treatment for C. acnes infections. To develop such reagents, the McCoy Laboratory generated four unique anti-RoxP antibodies. Preliminary studies in the McCoy Lab have established that each antibody binds a distinct site on RoxP. To assess the potential of these antibodies as therapeutics, it is necessary to specifically characterize these antibody epitopes and evaluate them in assays that assess their ability to inhibit RoxP-dependent C. acnes growth. To provide material for these studies, an antibody expression construct, Fv-clasp(v2), was adapted to encode anti-RoxP antibody sequences. The author hypothesizes that this expression strategy can produce sufficient amounts of >95% pure antibody fragments for further characterization of these antibodies. Four anti-RoxP Fv-clasp(v2) expression constructs (pET vector-based) were transformed into E. coli BL21-Gold(DE3) cells and a small-scale expression and purification trial was performed for each construct to evaluate anti-RoxP Fv-clasp(v2) yield and purity. Successful expression and purification of these antibody constructs will allow for their use in structural studies, such as protein crystallography and cryogenic electron microscopy. Such studies would help to define the antibody binding sites on RoxP, which could then be leveraged in the development of certain methods to treat C. acnes infection through RoxP inhibition.

Keywords: structural biology, protein expression, infectious disease, antibody, therapeutics, E. coli

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36612 Extensive Cerebral Venous Thrombosis after Resection of Third Ventricle Colloid Cyst

Authors: Naim Izet Kajtazi

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Context: The third ventricle colloid cyst (CC) is a benign growth usually located in the third ventricle and can cause various neurological symptoms, including sudden death. Modern surgical interventions may still result in a wide range of complications and cerebral venous thrombosis (CVT) is among them. Process: A 38-year-old female with an existing diagnosis of diabetes mellitus (DM) and hypothyroidism and a six-month history of headaches, blurred vision, and vomiting presented to our clinic three days after the headaches became excessively severe. Neurological examination on admission revealed bilateral papilledema without any associated focal neurological deficits. Brain computed tomography (CT) and magnetic resonance imaging (MRI) confirmed the presence of a third ventricle colloid cyst and associated non-communicating hydrocephalus involving the lateral ventricles. As a result, the patient underwent emergency bilateral external ventricular drainage (EVD) insertion followed by a third ventricular CC excision under neuronavigation through a right frontal craniotomy. Twelve days post-operatively, the patient developed further headaches, followed by a generalized tonic-clonic seizure that led to no postictal neurological deficits. Nonetheless, computed tomography venography of the brain revealed extensive thrombosis of the superior sagittal sinus, inferior sagittal sinus, right sigmoid sinus, and right internal jugular vein. A newly diagnosed CVT was treated with intravenous heparin. The patient was discharged with warfarin, which was discontinued after 12 months. Ten years after her illness, she remained stable and free from any neurological deficits but still suffered from mild chronic headaches. Outcome: Ten years after her illness, she remained stable and free from any neurological deficits but still suffered from mild chronic headaches. Relevance: A preoperative venous study should be performed in all cases to gain a better understanding of the venous anatomy. We advocate meticulous microsurgical techniques to protect the venous system surrounding the foramen of Monro and reduce the amount of retraction during surgery.

Keywords: CVT, seizures, third ventricle colloid cyst, MRI of brain

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36611 Anaesthetic Management of Congenitally Corrected Transposition of Great Arteries with Complete Heart Block in a Parturient for Emergency Caesarean Section

Authors: Lokvendra S. Budania, Yogesh K Gaude, Vamsidhar Chamala

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Introduction: Congenitally corrected transposition of great arteries (CCTGA) is a complex congenital heart disease where there are both atrioventricular and ventriculoarterial discordances, usually accompanied by other cardiovascular malformations. Case Report: A 24-year-old primigravida known case of CCTGA at 37 weeks of gestation was referred to our hospital for safe delivery. Her electrocardiogram showed HR-40/pm, echocardiography showed Ejection Fraction of 65% and CCTGA. Temporary pacemaker was inserted by cardiologist in catheterization laboratory, before giving trial of labour in view of complete heart block. She was planned for normal delivery, but emergency Caesarean section was planned due to non-reassuring foetal Cardiotocography Pre-op vitals showed PR-50 bpm with temporary pacemaker, Blood pressure-110/70 mmHg, SpO2-99% on room air. Nil per oral was inadequate. Patency of two peripheral IV cannula checked and left radial arterial line secured. Epidural Anaesthesia was planned, and catheter was placed at L2-L3. Test dose was given, Anaesthesia was provided with 5ml + 5ml of 2% Lignocaine with 25 mcg Fentanyl and further 2.5Ml of 0.5% Bupivacaine was given to achieve a sensory level of T6. Cesarean section was performed and baby was delivered. Cautery was avoided during this procedure. IV Oxytocin (15U) was added to 500 mL of ringer’s lactate. Hypotension was treated with phenylephrine boluses. Patient was shifted to post-operative care unit and later to high dependency unit for monitoring. Post op vitals remained stable. Temporary pacemaker was removed after 24 hours of surgery. Her post-operative period was uneventful and discharged from hospital. Conclusion: Rare congenital cardiac disorders require detail knowledge of pathophysiology and associated comorbidities with the disease. Meticulously planned and carefully titrated neuraxial techniques will be beneficial for such cases.

Keywords: congenitally corrected transposition of great arteries, complete heart block, emergency LSCS, epidural anaesthesia

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36610 Equivalent Circuit Modelling of Active Reflectarray Antenna

Authors: M. Y. Ismail, M. Inam

Abstract:

This paper presents equivalent circuit modeling of active planar reflectors which can be used for the detailed analysis and characterization of reflector performance in terms of lumped components. Equivalent circuit representation has been proposed for PIN diodes and liquid crystal based active planar reflectors designed within X-band frequency range. A very close agreement has been demonstrated between equivalent circuit results, 3D EM simulated results as well as measured scattering parameter results. In the case of measured results, a maximum discrepancy of 1.05dB was observed in the reflection loss performance, which can be attributed to the losses occurred during measurement process.

Keywords: Equivalent circuit modelling, planar reflectors, reflectarray antenna, PIN diode, liquid crystal

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36609 Hermite–Hadamard Type Integral Inequalities Involving k–Riemann–Liouville Fractional Integrals and Their Applications

Authors: Artion Kashuri, Rozana Liko

Abstract:

In this paper, some generalization integral inequalities of Hermite–Hadamard type for functions whose derivatives are s–convex in modulus are given by using k–fractional integrals. Some applications to special means are obtained as well. Some known versions are recovered as special cases from our results. We note that our inequalities can be viewed as new refinements of the previous results. Finally, our results have a deep connection with various fractional integral operators and interested readers can find new interesting results using our idea and technique as well.

Keywords: Hermite-Hadamard's inequalities, Hölder's inequality, k-Riemann-Liouville fractional integral, special means

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36608 Successful Rehabilitation of Recalcitrant Knee Pain Due to Anterior Cruciate Ligament Injury Masked by Extensive Skin Graft: A Case Report

Authors: Geum Yeon Sim, Tyler Pigott, Julio Vasquez

Abstract:

A 38-year-old obese female with no apparent past medical history presented with left knee pain. Six months ago, she sustained a left knee dislocation in a motor vehicle accident that was managed with a skin graft over the left lower extremity without any reconstructive surgery. She developed persistent pain and stiffness in her left knee that worsened with walking and stair climbing. Examination revealed healed extensive skin graft over the left lower extremity, including the left knee. Palpation showed moderate tenderness along the superior border of the patella, exquisite tenderness over MCL, and mild tenderness on the tibial tuberosity. There was normal sensation, reflexes, and strength in her lower extremities. There was limited active and passive range of motion of her left knee during flexion. There was instability noted upon the valgus stress test of the left knee. Left knee magnetic resonance imaging showed high-grade (grade 2-3) injury of the proximal superficial fibers of the MCL and diffuse thickening and signal abnormality of the cruciate ligaments, as well as edema-like subchondral marrow signal change in the anterolateral aspect of the lateral femoral condyle weight-bearing surface. There was also notable extensive scarring and edema of the skin, subcutaneous soft tissues, and musculature surrounding the knee. The patient was managed with left knee immobilization for five months, which was complicated by limited knee flexion. Physical therapy consisting of quadriceps, hamstrings, gastrocnemius stretching and strengthening, range of motion exercises, scar/soft tissue mobilization, and gait training was given with marked improvement in pain and range of motion. The patient experienced a further reduction in pain as well as an improvement in function with home exercises consisting of continued strengthening and stretching.

Keywords: ligamentous injury, trauma, rehabilitation, knee pain

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36607 Unveiling the Mystery: Median Arcuate Ligament Syndrome in a Middle-Aged Female Presenting with Abdominal Pain

Authors: Thaer Khaleel Swaid, Maryam Al Ahmad, Ishtiaq Ahmad

Abstract:

47-year-old female, known to have a liver cyst and hemangiomas, presented to the gastroenterology clinic for chronic moderate postprandial epigastric pain, which is aggravated by food, leaning forward and relieved on lying flat. The pain was associated with nausea, vomiting, heartburn and excessive burping. She opened her bowel daily, having well-formed stools without blood or mucus. The patient denied NSAID intake, smoking or alcohol. On physical examination during the episode of pain abdomen revealed a soft, lax abdomen and mild tenderness in the epigastric region without organomegaly. Bowel sounds were audible. Her routine hematological and biochemical parameters were within normal, including CBC, Celiac serology, Lipase, Metabolic profile and H pylori stool antigen. The patient underwent an Ultrasound of the abdomen which showed multiple liver cysts, hemangioma, normal GB and biliary tree. Based on the clinical picture and to narrow our differential diagnosis, an ultrasound Doppler for the abdomen was ordered, and it showed celiac artery peak systolic velocity in expiration is 270cm/s, suggestive of median arcuate ligament syndrome. She Had computerized tomography abdomen done and showed a Narrowing of the celiac artery at the origin, likely secondary to low insertion of the median arcuate ligament. Furthermore, Gastroscopy and, later on colonoscopy were done, which was unremarkable. A laparoscopic decompression of the celiac trunk was indicated, for which the patient was referred to vascular surgery. This case confirms that Median Arcuate Ligament syndrome is an unusual diagnosis and is always challenging. Usually, patients undergo extensive workups before a final diagnosis is achieved. Our case highlights the challenge of diagnosing MALS since this entity is rare. It is a good choice to perform abdominal ultrasound with Doppler imaging on a patient with symptoms such as postprandial angina.

Keywords: Unveiling the Mystery, MALS, rare entity, Rare vascular phenomenon

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36606 Cost-Conscious Treatment of Basal Cell Carcinoma

Authors: Palak V. Patel, Jessica Pixley, Steven R. Feldman

Abstract:

Introduction: Basal cell carcinoma (BCC) is the most common skin cancer worldwide and requires substantial resources to treat. When choosing between indicated therapies, providers consider their associated adverse effects, efficacy, cosmesis, and function preservation. The patient’s tumor burden, infiltrative risk, and risk of tumor recurrence are also considered. Treatment cost is often left out of these discussions. This can lead to financial toxicity, which describes the harm and quality of life reductions inflicted by high care costs. Methods: We studied the guidelines set forth by the American Academy of Dermatology for the treatment of BCC. A PubMed literature search was conducted to identify the costs of each recommended therapy. We discuss costs alongside treatment efficacy and side-effect profile. Results: Surgical treatment for BCC can be cost-effective if the appropriate treatment is selected for the presenting tumor. Curettage and electrodesiccation can be used in low-grade, low-recurrence tumors in aesthetically unimportant areas. The benefits of cost-conscious care are not likely to be outweighed by the risks of poor cosmesis or tumor return ($471 BCC of the cheek). When tumor burden is limited, MMS offers better cure rates and lower recurrence rates than surgical excision, and with comparable costs (MMS $1263; SE $949). Surgical excision with permanent sections may be indicated when tumor burden is more extensive or if molecular testing is necessary. The utility of surgical excision with frozen sections, which costs substantially more than MMS without comparable outcomes, is less clear (SE with frozen sections $2334-$3085). Less data exists on non-surgical treatments for BCC. These techniques cost less, but recurrence-risk is high. Side-effects of nonsurgical treatment are limited to local skin reactions, and cosmesis is good. Cryotherapy, 5-FU, and MAL-PDT are all more affordable than surgery, but high recurrence rates increase risk of secondary financial and psychosocial burden (recurrence rates 21-39%; cost $100-270). Radiation therapy offers better clearance rates than other nonsurgical treatments but is associated with similar recurrence rates and a significantly larger financial burden ($2591-$3460 BCC of the cheek). Treatments for advanced or metastatic BCC are extremely costly, but few patients require their use, and the societal cost burden remains low. Vismodegib and sonidegib have good response rates but substantial side effects, and therapy should be combined with multidisciplinary care and palliative measures. Expert-review has found sonidegib to be the less expensive and more efficacious option (vismodegib $128,358; sonidegib $122,579). Platinum therapy, while not FDA-approved, is also effective but expensive (~91,435). Immunotherapy offers a new line of treatment in patients intolerant of hedgehog inhibitors ($683,061). Conclusion: Dermatologists working within resource-compressed practices and with resource-limited patients must prudently manage the healthcare dollar. Surgical therapies for BCC offer the lowest risk of recurrence at the most reasonable cost. Non-surgical therapies are more affordable, but high recurrence rates increase the risk of secondary financial and psychosocial burdens. Treatments for advanced BCC are incredibly costly, but the low incidence means the overall cost to the system is low.

Keywords: nonmelanoma skin cancer, basal cell skin cancer, squamous cell skin cancer, cost of care

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36605 Data Mining Algorithms Analysis: Case Study of Price Predictions of Lands

Authors: Julio Albuja, David Zaldumbide

Abstract:

Data analysis is an important step before taking a decision about money. The aim of this work is to analyze the factors that influence the final price of the houses through data mining algorithms. To our best knowledge, previous work was researched just to compare results. Furthermore, before using the data of the data set, the Z-Transformation were used to standardize the data in the same range. Hence, the data was classified into two groups to visualize them in a readability format. A decision tree was built, and graphical data is displayed where clearly is easy to see the results and the factors' influence in these graphics. The definitions of these methods are described, as well as the descriptions of the results. Finally, conclusions and recommendations are presented related to the released results that our research showed making it easier to apply these algorithms using a customized data set.

Keywords: algorithms, data, decision tree, transformation

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36604 Consonant Harmony and the Challenges of Articulation and Perception

Authors: Froogh Shooshtaryzadeh, Pramod Pandey

Abstract:

The present study investigates place and manner harmony in typically developing (TD) children and children with phonological disorder (PD) who are acquiring Farsi as their first language. Five TD and five PD children are examined regarding their place and manner harmony patterns. Data is collected through a Picture-Naming Task using 132 pictures of different items designed to elicit the production of 132 different words. The examination of the data has indicated some similarities and differences in harmony patterns in PD and TD children. Moreover, the results of this study on the place and manner harmony have illustrated some differences with the results of the preceding studies on languages other than Farsi. The results of this study are discussed and compared with results from other studies. Optimality Theory is employed to explain some of the findings of this study.

Keywords: place harmony, manner harmony, phonological development, Farsi

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36603 Comparative Analysis of the Performance Between Public and Private Companies: Explanatory Factors

Authors: Atziri Moreno Vite, David Silva Gutiérrez

Abstract:

Oil companies have become the key player in the world energy scenario thanks to their strong control of the level of hydrocarbon reserves and production. The present research aims to identify the main factors that explain the results of these companies through an in-depth review of the specialized literature and to analyze the results of these companies by means of econometric analysis with techniques such as Data Envelopment Analysis (DEA). The results show the relevance and impact of factors such as the level of employment or investment of the company.

Keywords: oil companies, performance, determinants, productive

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36602 Comparison of the Dose Reached to the Rectum and Bladder in Two Treatment Methods by Tandem and Ovoid and Tandem and Ring in the High Dose Rate Brachytherapy of Cervical Cancer

Authors: Akbar Haghzadeh Saraskanroud, Amir Hossein Yahyavi Zanjani, Niloofar Kargar, Hanieh Ahrabi

Abstract:

Cervical cancer refers to an unusual growth of cells in the cervix. The cervix is the lower part of the uterus, which connects to the vagina. Various risk factors such as human papillomavirus (HPV), having a weakened immune system, smoking or breathing in secondhand smoke, reproductive factors, and obesity play important roles in causing most cervical cancers. When cervical cancer happens, surgery is often the first treatment option to remove it. Other treatments might include chemotherapy and targeted therapy medicines. Radiation therapy with high-energy photon beams also may be used. Sometimes combined treatment, including radiation with low-dose chemotherapy, was applied. Intracavitary brachytherapy is an integral part of radiotherapy for locally advanced gynecologic malignancies such as cervical cancer. In the treatment of cervical cancer, there are different tools for doing brachytherapy. Two combinations of different applicators for this purpose are Tandem and Ovoid and Tandem and Ring. This study evaluated the dose differences between these two methods in the organs at risk of the rectum, sigmoid, and bladder. In this study, the treatment planswere simulated by the Oncentra treatment planning system and Tandem, Ovid, and Rings of different sizes. CT scan images of 23 patients were treated with HDR_BT Elekta Flexitron system were used for this study. Contouring of HR-CTV, rectum and bladder was performed for all patients. Then, the received dose of 0.1 and 0.2cc volumes of organs at risk were obtained and compared for these two methods: T-Ovoid and T-Ring. By doing investigations and dose measurements of points A and B and the volumes specified by ICRU, it seems that when comparing ring and ovoid to tandem and ovoid, the total dose to the rectum was lower by about 11%, and the bladder was 7%. In the case of HR CTV, this comparison showed that this ratio is about 7% better. Figure 1 shows the amount of decrease in rectum dose in the T-Ring method compared to T-Ovoid. Figure 2 indicates the amount of decrease in bladder dose in the T-Ring method compared to T-Ovoid. Finally, figure 3 illustrates the amount of HR-CTV coverage in the T-Ring method compared to the T-Ovoid.

Keywords: cervical cancer, brachytherapy, rectum, tandem and ovoid, tandem and ring.

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36601 An Unusual Cause of Electrocardiographic Artefact: Patient's Warming Blanket

Authors: Sanjay Dhiraaj, Puneet Goyal, Aditya Kapoor, Gaurav Misra

Abstract:

In electrocardiography, an ECG artefact is used to indicate something that is not heart-made. Although technological advancements have produced monitors with the potential of providing accurate information and reliable heart rate alarms, despite this, interference of the displayed electrocardiogram still occurs. These interferences can be from the various electrical gadgets present in the operating room or electrical signals from other parts of the body. Artefacts may also occur due to poor electrode contact with the body or due to machine malfunction. Knowing these artefacts is of utmost importance so as to avoid unnecessary and unwarranted diagnostic as well as interventional procedures. We report a case of ECG artefacts occurring due to patient warming blanket and its consequences. A 20-year-old male with a preoperative diagnosis of exstrophy epispadias complex was posted for surgery under epidural and general anaesthesia. Just after endotracheal intubation, we observed nonspecific ECG changes on the monitor. At a first glance, the monitor strip revealed broad QRs complexes suggesting a ventricular bigeminal rhythm. Closer analysis revealed these to be artefacts because although the complexes were looking broad on the first glance there was clear presence of normal sinus complexes which were immediately followed by 'broad complexes' or artefacts produced by some device or connection. These broad complexes were labeled as artefacts as they were originating in the absolute refractory period of the previous normal sinus beat. It would be physiologically impossible for the myocardium to depolarize so rapidly as to produce a second QRS complex. A search for the possible reason for the artefacts was made and after deepening the plane of anaesthesia, ruling out any possible electrolyte abnormalities, checking of ECG leads and its connections, changing monitors, checking all other monitoring connections, checking for proper grounding of anaesthesia machine and OT table, we found that after switching off the patient’s warming apparatus the rhythm returned to a normal sinus one and the 'broad complexes' or artefacts disappeared. As misdiagnosis of ECG artefacts may subject patients to unnecessary diagnostic and therapeutic interventions so a thorough knowledge of the patient and monitors allow for a quick interpretation and resolution of the problem.

Keywords: ECG artefacts, patient warming blanket, peri-operative arrhythmias, mobile messaging services

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36600 Ectopic Mediastinal Parathyroid Adenoma: A Case Report with Diagnostic and Management Challenges

Authors: Augustina Konadu Larbi-Ampofo, Ekemini Umoinwek

Abstract:

Background: Hypercalcaemia is a common electrolyte imbalance that increases mortality if poorly controlled. Primary hyperparathyroidism often presents like this with a prevalence of 0.1-0.3%. Management due to an ectopic parathyroid adenoma in the mediastinum is challenging, especially in a patient with a pacemaker. Case Presentation: A 79-year-old woman with a history of a previous cardiac arrest, permanent pacemaker, ischaemic heart disease, bilateral renal calculi, rectal polyps, liver cirrhosis, and a family history of hyperthyroidism presented to the emergency department with acute back pain. Management and Outcome: The patient was diagnosed with primary hyperparathyroidism due to her elevated corrected calcium and parathyroid hormone levels. Parathyroid investigations consisting of an NM MIBI scan, SPECT-CT, 4D parathyroid scan, and an ultrasound scan of the neck and thorax confirmed an ectopic parathyroid adenoma in the mediastinum at the level of the aortic arch, along with benign thyroid nodules. The location of the adenoma warranted a thoracoscopic surgical approach; however, the presence of her pacemaker and other cardiovascular conditions predisposed her to a potentially poorer post-operative outcome. Discussion: Mediastinal ectopic parathyroid adenomas are rare and difficult to diagnose and treat, often needing a multimodal imaging approach for accurate localisation. Surgery is a definitive treatment; however, in this patient, long-term medical treatment with cinacalcet was the only next suitable treatment option. The difficulty with this is that cinacalcet tackles the biochemical markers of the disease entity and not the disease itself, leaving room for what happens next if there is refractory/uncontrolled hypercalcaemia in this patient with a pacemaker. Moreover, the coexistence of her multiple conditions raises the suspicion of an underlying multisystemic or multiple endocrine disorder, with multiple endocrine neoplasia coming to mind, necessitating further genetic or autoimmune investigations. Conclusion: Mediastinal ectopic parathyroid adenomas are rare, with diagnostic and management challenges.

Keywords: mediastinal ectopic parathyroid adenoma, hyperparathyroidism, SPECT/CT, nuclear medicine, multimodal imaging

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36599 The Design of a Phase I/II Trial of Neoadjuvant RT with Interdigitated Multiple Fractions of Lattice RT for Large High-grade Soft-Tissue Sarcoma

Authors: Georges F. Hatoum, Thomas H. Temple, Silvio Garcia, Xiaodong Wu

Abstract:

Soft Tissue Sarcomas (STS) represent a diverse group of malignancies with heterogeneous clinical and pathological features. The treatment of extremity STS aims to achieve optimal local tumor control, improved survival, and preservation of limb function. The National Comprehensive Cancer Network guidelines, based on the cumulated clinical data, recommend radiation therapy (RT) in conjunction with limb-sparing surgery for large, high-grade STS measuring greater than 5 cm in size. Such treatment strategy can offer a cure for patients. However, when recurrence occurs (in nearly half of patients), the prognosis is poor, with a median survival of 12 to 15 months and with only palliative treatment options available. The spatially-fractionated-radiotherapy (SFRT), with a long history of treating bulky tumors as a non-mainstream technique, has gained new attention in recent years due to its unconventional therapeutic effects, such as bystander/abscopal effects. Combining single fraction of GRID, the original form of SFRT, with conventional RT was shown to have marginally increased the rate of pathological necrosis, which has been recognized to have a positive correlation to overall survival. In an effort to consistently increase the pathological necrosis rate over 90%, multiple fractions of Lattice RT (LRT), a newer form of 3D SFRT, interdigitated with the standard RT as neoadjuvant therapy was conducted in a preliminary clinical setting. With favorable results of over 95% of necrosis rate in a small cohort of patients, a Phase I/II clinical study was proposed to exam the safety and feasibility of this new strategy. Herein the design of the clinical study is presented. In this single-arm, two-stage phase I/II clinical trial, the primary objectives are >80% of the patients achieving >90% tumor necrosis and to evaluation the toxicity; the secondary objectives are to evaluate the local control, disease free survival and overall survival (OS), as well as the correlation between clinical response and the relevant biomarkers. The study plans to accrue patients over a span of two years. All patient will be treated with the new neoadjuvant RT regimen, in which one of every five fractions of conventional RT is replaced by a LRT fraction with vertices receiving dose ≥10Gy while keeping the tumor periphery at or close to 2 Gy per fraction. Surgical removal of the tumor is planned to occur 6 to 8 weeks following the completion of radiation therapy. The study will employ a Pocock-style early stopping boundary to ensure patient safety. The patients will be followed and monitored for a period of five years. Despite much effort, the rarity of the disease has resulted in limited novel therapeutic breakthroughs. Although a higher rate of treatment-induced tumor necrosis has been associated with improved OS, with the current techniques, only 20% of patients with large, high-grade tumors achieve a tumor necrosis rate exceeding 50%. If this new neoadjuvant strategy is proven effective, an appreciable improvement in clinical outcome without added toxicity can be anticipated. Due to the rarity of the disease, it is hoped that such study could be orchestrated in a multi-institutional setting.

Keywords: lattice RT, necrosis, SFRT, soft tissue sarcoma

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