Search results for: normal load

Authors: Seyedeh Nasim Mirbahari, Taha Azad, Mehdi Totonchi

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Oncolytic viruses, which only replicate in tumor cells, are being extensively studied for their use in cancer therapy. A particular virus known as the vaccinia virus, a member of the poxvirus family, has demonstrated oncolytic abilities glioma. Treating Glioma with traditional methods such as chemotherapy and radiotherapy is quite challenging. Even though oncolytic viruses have shown immense potential in cancer treatment, their effectiveness in glioblastoma treatment is still low. Therefore, there is a need to improve and optimize immunotherapies for better results. In this study, we have designed oncoVV-TT, which can more effectively target tumor cells while minimizing replication in normal cells by replacing the thymidine kinase gene with a luc-p2a-GFP gene expression cassette. Human glioblastoma cell line U251 MG, rat glioblastoma cell line C6, and non-tumor cell line HFF were plated at 105 cells in a 12-well plates in 2 mL of DMEM-F2 medium with 10% FBS added to each well. Then incubated at 37°C. After 16 hours, the cells were treated with oncoVV-TT at an MOI of 0.01, 0.1 and left in the incubator for a further 24, 48, 72 and 96 hours. Viral replication assay, fluorescence imaging and viability tests, including trypan blue and crystal violet, were conducted to evaluate the cytotoxic effect of oncoVV-TT. The finding shows that oncoVV-TT had significantly higher cytotoxic activity and proliferation rates in tumor cells in a dose and time-dependent manner, with the strongest effect observed in U251 MG. To conclude, oncoVV-TT has the potential to be a promising oncolytic virus for cancer treatment, with a more cytotoxic effect in human glioblastoma cells versus rat glioma cells. To assess the effectiveness of vaccinia virus-mediated viral therapy, we have tested U251mg and C6 tumor cell lines taken from human and rat gliomas, respectively. The study evaluated oncoVV-TT's ability to replicate and lyse cells and analyzed the survival rates of the tested cell lines when treated with different doses of oncoVV-TT. Additionally, we compared the sensitivity of human and mouse glioma cell lines to the oncolytic vaccinia virus. All experiments regarding viruses were conducted under biosafety level 2. We engineered a Vaccinia-based oncolytic virus called oncoVV-TT to replicate specifically in tumor cells. To propagate the oncoVV-TT virus, HeLa cells (5 × 104/well) were plated in 24-well plates and incubated overnight to attach to the bottom of the wells. Subsequently, 10 MOI virus was added. After 48 h, cells were harvested by scraping, and viruses were collected by 3 sequential freezing and thawing cycles followed by removal of cell debris by centrifugation (1500 rpm, 5 min). The supernatant was stored at −80 ◦C for the following experiments. To measure the replication of the virus in Hela, cells (5 × 104/well) were plated in 24-well plates and incubated overnight to attach to the bottom of the wells. Subsequently, 5 MOI virus or equal dilution of PBS was added. At the treatment time of 0 h, 24 h, 48 h, 72 h and 96 h, the viral titers were determined under the fluorescence microscope (BZ-X700; Keyence, Osaka, Japan). Fluorescence intensity was quantified using the imagej software according to the manufacturer’s protocol. For the isolation of single-virus clones, HeLa cells seeded in six-well plates (5×105 cells/well). After 24 h (100% confluent), the cells were infected with a 10-fold dilution series of TianTan green fluorescent protein (GFP)virus and incubated for 4 h. To examine the cytotoxic effect of oncoVV-TT virus ofn U251mg and C6 cell, trypan blue and crystal violet assay was used.

Keywords: oncolytic virus, immune therapy, glioma, vaccinia virus

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Authors: Zakia Hbellaq

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The Mediterranean region is considered a hotbed for climate change. Morocco is a semi-arid Mediterranean country facing water shortages and poor water quality. Its limited water resources limit the activities of various economic sectors. Most of Morocco's territory is in arid and desert areas. The potential water resources are estimated at 22 billion m3, which is equivalent to about 700 m3/inhabitant/year, and Morocco is in a state of structural water stress. Strictly speaking, the Kingdom of Morocco is one of the “very riskiest” countries, according to the World Resources Institute (WRI), which oversees the calculation of water stress risk in 167 countries. The surprising results of the Institute (WRI) rank Morocco as one of the riskiest countries in terms of water scarcity, ranking 3.89 out of 5, thus occupying the 23rd place out of a total of 167 countries, which indicates that the demand for water exceeds the available resources. Agriculture with a score of 3.89 is most affected by water stress from irrigation and places a heavy burden on the water table. Irrigation is an unavoidable technical need and has undeniable economic and social benefits given the available resources and climatic conditions. Irrigation, and therefore the agricultural sector, currently uses 86% of its water resources, while industry uses 5.5%. Although its development has undeniable economic and social benefits, it also contributes to the overfishing of most groundwater resources and the surprising decline in levels and deterioration of water quality in some aquifers. In this context, REUSE is one of the proposed solutions to reduce the water footprint of the agricultural sector and alleviate the shortage of water resources. Indeed, wastewater reuse, also known as REUSE (reuse of treated wastewater), is a step forward not only for the circular economy but also for the future, especially in the context of climate change. In particular, water reuse provides an alternative to existing water supplies and can be used to improve water security, sustainability, and resilience. However, given the introduction of organic trace pollutants or, organic micro-pollutants, the absorption of emerging contaminants, and decreasing salinity, it is possible to tackle innovative capabilities to overcome these problems and ensure food and health safety. To this end, attention will be paid to the adoption of an integrated and attractive approach, based on the reinforcement and optimization of the treatments proposed for the elimination of the organic load with particular attention to the elimination of emerging pollutants, to achieve this goal. , membrane bioreactors (MBR) as stand-alone technologies are not able to meet the requirements of WHO guidelines. They will be combined with heterogeneous Fenton processes using persulfate or hydrogen peroxide oxidants. Similarly, adsorption and filtration are applied as tertiary treatment In addition, the evaluation of crop performance in terms of yield, productivity, quality, and safety, through the optimization of Trichoderma sp strains that will be used to increase crop resistance to abiotic stresses, as well as the use of modern omics tools such as transcriptomic analysis using RNA sequencing and methylation to identify adaptive traits and associated genetic diversity that is tolerant/resistant/resilient to biotic and abiotic stresses. Hence, ensuring this approach will undoubtedly alleviate water scarcity and, likewise, increase the negative and harmful impact of wastewater irrigation on the condition of crops and the health of their consumers.

Keywords: water scarcity, food security, irrigation, agricultural water footprint, reuse, emerging contaminants

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Authors: S. Candamano, A. Iorfida, L. Pagnotta, F. Crea

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Basalt fabric reinforced cementitious composites (FRCM) have attracted great attention because they result in being effective in structural strengthening and eco-efficient. In this study, authors investigate their mechanical behavior when an alkali-activated binder, with tuned properties and containing high amounts of industrial by-products, such as ground granulated blast furnace slag, is used. Reinforcement is made up of a balanced, coated bidirectional fabric made out of basalt fibres and stainless steel micro-wire, with a mesh size of 8x8 mm and an equivalent design thickness equal to 0.064 mm. Mortars mixes have been prepared by maintaining constant the water/(reactive powders) and sand/(reactive powders) ratios at 0.53 and 2.7 respectively. Tensile tests were carried out on composite specimens of nominal dimensions equal to 500 mm x 50 mm x 10 mm, with 6 embedded rovings in the loading direction. Direct shear tests (DST), aimed to the stress-transfer mechanism and failure modes of basalt-FRCM composites, were carried out on brickwork substrate using an externally bonded basalt-FRCM composite strip 10 mm thick, 50 mm wide and a bonded length of 300 mm. Mortars exhibit, after 28 days of curing, a compressive strength of 32 MPa and a flexural strength of 5.5 MPa. Main hydration product is a poorly crystalline CASH gel. The constitutive behavior of the composite has been identified by means of direct tensile tests, with response curves showing a tri-linear behavior. The first linear phase represents the uncracked (I) stage, the second (II) is identified by crack development and the third (III) corresponds to cracked stage, completely developed up to failure. All specimens exhibit a crack pattern throughout the gauge length and failure occurred as a result of sequential tensile failure of the fibre bundles, after reaching the ultimate tensile strength. The behavior is mainly governed by cracks development (II) and widening (III) up to failure. The main average values related to the stages are σI= 173 MPa and εI= 0.026% that are the stress and strain of the transition point between stages I and II, corresponding to the first mortar cracking; σu = 456 MPa and εu= 2.20% that are the ultimate tensile strength and strain, respectively. The tensile modulus of elasticity in stage III is EIII= 41 GPa. All single-lap shear test specimens failed due to composite debonding. It occurred at the internal fabric-to-matrix interface, and it was the result of fracture of the matrix between the fibre bundles. For all specimens, transversal cracks were visible on the external surface of the composite and involved only the external matrix layer. This cracking appears when the interfacial shear stresses increase and slippage of the fabric at the internal matrix layer interface occurs. Since the external matrix layer is bonded to the reinforcement fabric, it translates with the slipped fabric. Average peak load around 945 N, peak stress around 308 MPa, and global slip around 6 mm were measured. The preliminary test results allow affirming that Alkali Activated Binders can be considered a potentially valid alternative to traditional mortars in designing FRCM composites.

Keywords: alkali activated binders, basalt-FRCM composites, direct shear tests, structural strengthening

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Authors: S. Candamano, A. Iorfida, F. Crea, A. Macario

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Recently, basalt fabric reinforced cementitious composites (FRCM) have attracted great attention because they result to be effective in structural strengthening and cost/environment efficient. In this study, authors investigate their mechanical behavior when an inorganic matrix, belonging to the family of alkali-activated binders, is used. In particular, the matrix has been designed to contain high amounts of industrial by-products and waste, such as Ground Granulated Blast Furnace Slag (GGBFS) and Fly Ash. Fresh state properties, such as workability, mechanical properties and shrinkage behavior of the matrix have been measured, while microstructures and reaction products were analyzed by Scanning Electron Microscopy and X-Ray Diffractometry. Reinforcement is made up of a balanced, coated bidirectional fabric made out of basalt fibres and stainless steel micro-wire, with a mesh size of 8x8 mm and an equivalent design thickness equal to 0.064 mm. Mortars mixes have been prepared by maintaining constant the water/(reactive powders) and sand/(reactive powders) ratios at 0.53 and 2.7 respectively. An appropriate experimental campaign based on direct tensile tests on composite specimens and single-lap shear bond test on brickwork substrate has been thus carried out to investigate their mechanical behavior under tension, the stress-transfer mechanism and failure modes. Tensile tests were carried out on composite specimens of nominal dimensions equal to 500 mm x 50 mm x 10 mm, with 6 embedded rovings in the loading direction. Direct shear tests (DST) were carried out on brickwork substrate using an externally bonded basalt-FRCM composite strip 10 mm thick, 50 mm wide and a bonded length of 300 mm. Mortars exhibit, after 28 days of curing, an average compressive strength of 32 MPa and flexural strength of 5.5 MPa. Main hydration product is a poorly crystalline aluminium-modified calcium silicate hydrate (C-A-S-H) gel. The constitutive behavior of the composite has been identified by means of direct tensile tests, with response curves showing a tri-linear behavior. Test results indicate that the behavior is mainly governed by cracks development (II) and widening (III) up to failure. The ultimate tensile strength and strain were respectively σᵤ = 456 MPa and ɛᵤ= 2.20%. The tensile modulus of elasticity in stage III was EIII= 41 GPa. All single-lap shear test specimens failed due to composite debonding. It occurred at the internal fabric-to-matrix interface, and it was the result of a fracture of the matrix between the fibre bundles. For all specimens, transversal cracks were visible on the external surface of the composite and involved only the external matrix layer. This cracking appears when the interfacial shear stresses increase and slippage of the fabric at the internal matrix layer interface occurs. Since the external matrix layer is bonded to the reinforcement fabric, it translates with the slipped fabric. Average peak load around 945 N, peak stress around 308 MPa and global slip around 6 mm were measured. The preliminary test results allow affirming that Alkali-Activated Materials can be considered a potentially valid alternative to traditional mortars in designing FRCM composites.

Keywords: Alkali-activated binders, Basalt-FRCM composites, direct shear tests, structural strengthening

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Authors: Kaaryn Cater

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People vary in how they perceive, process, and react to internal, external, social, and emotional environmental factors; some are more sensitive than others. Compassionate people have a highly reactive nervous system and are more impacted by positive and negative environmental conditions (Differential Susceptibility). Further, some sensitive individuals are disproportionately able to benefit from positive and supportive environments without necessarily suffering negative impacts in less supportive environments (Vantage Sensitivity). Environmental sensitivity is underpinned by physiological, genetic, and personality/temperamental factors, and the phenotypic expression of high sensitivity is Sensory Processing Sensitivity. The hallmarks of Sensory Processing Sensitivity are deep cognitive processing, emotional reactivity, high levels of empathy, noticing environmental subtleties, a tendency to observe new and novel situations, and a propensity to become overwhelmed when over-stimulated. Several educational advantages associated with high sensitivity include creativity, enhanced memory, divergent thinking, giftedness, and metacognitive monitoring. High sensitivity can also lead to some educational challenges, particularly managing multiple conflicting demands and negotiating low sensory thresholds. A mixed methods study was undertaken. In the first quantitative study, participants completed the Perceived Success in Study Survey (PSISS) and the Highly Sensitive Person Scale (HSPS-12). Inclusion criteria were current or previous postsecondary education experience. The survey was presented on social media, and snowball recruitment was employed (n=365). The Excel spreadsheets were uploaded to the statistical package for the social sciences (SPSS)26, and descriptive statistics found normal distribution. T-tests and analysis of variance (ANOVA) calculations found no difference in the responses of demographic groups, and Principal Components Analysis and the posthoc Tukey calculations identified positive associations between high sensitivity and three of the five PSISS factors. Further ANOVA calculations found positive associations between the PSISS and two of the three sensitivity subscales. This study included a response field to register interest in further research. Respondents who scored in the 70th percentile on the HSPS-12 were invited to participate in a semi-structured interview. Thirteen interviews were conducted remotely (12 female). Reflexive inductive thematic analysis was employed to analyse data, and a descriptive approach was employed to present data reflective of participant experience. The results of this study found that compassionate students prioritize work-life balance; employ a range of practical metacognitive study and self-care strategies; value independent learning; connect with learning that is meaningful; and are bothered by aspects of the physical learning environment, including lighting, noise, and indoor environmental pollutants. There is a dearth of research investigating sensitivity in the educational context, and these studies highlight the need to promote widespread education sector awareness of environmental sensitivity, and the need to include sensitivity in sector and institutional diversity and inclusion initiatives.

Keywords: differential susceptibility, highly sensitive person, learning, neurosensitivity, sensory processing sensitivity, vantage sensitivity

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Authors: Muna Mitchell, Akshay Parchure, Krishna Singaraju

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There is an increasing need for medium- to long-span steel bridges with complex geometry due to site restrictions in developed areas. One of the solutions to grade separations in congested areas is to use longer spans on skewed supports that avoid at-grade obstructions limiting impacts to the foundation. Where vertical clearances are also a constraint, continuous steel girders can be used to reduce superstructure depths. Combining continuous long steel spans on severe skews can resolve the constraints at a cost. The behavior of skewed girders is challenging to analyze and design with subsequent complexity during fabrication and construction. As a part of a corridor improvement project, Walter P Moore designed two 1700-foot side-by-side bridges carrying four lanes of traffic in each direction over a railroad track. The bridges consist of prestressed concrete girder approach spans and three-span continuous steel plate girder units. The roadway design added complex geometry to the bridge with horizontal and vertical curves combined with superelevation transitions within the plate girder units. The substructure at the steel units was skewed approximately 56 degrees to satisfy the existing railroad right-of-way requirements. A horizontal point of curvature (PC) near the end of the steel units required the use flared girders and chorded slab edges. Due to the flared girder geometry, the cross-frame spacing in each bay is unique. Staggered cross frames were provided based on AASHTO LRFD and NCHRP guidelines for high skew steel bridges. Skewed steel bridges develop significant forces in the cross frames and rotation in the girder websdue to differential displacements along the girders under dead and live loads. In addition, under thermal loads, skewed steel bridges expand and contract not along the alignment parallel to the girders but along the diagonal connecting the acute corners, resulting in horizontal displacement both along and perpendicular to the girders. AASHTO LRFD recommends a 95 degree Fahrenheit temperature differential for the design of joints and bearings. The live load and the thermal loads resulted in significant horizontal forces and rotations in the bearings that necessitated the use of HLMR bearings. A unique bearing layout was selected to minimize the effect of thermal forces. The span length, width, skew, and roadway geometry at the bridges also required modular bridge joint systems (MBJS) with inverted-T bent caps to accommodate movement in the steel units. 2D and 3D finite element analysis models were developed to accurately determine the forces and rotations in the girders, cross frames, and bearings and to estimate thermal displacements at the joints. This paper covers the decision-making process for developing the framing plan, bearing configurations, joint type, and analysis models involved in the design of the high-skew three-span continuous steel plate girder bridges.

Keywords: complex geometry, continuous steel plate girders, finite element structural analysis, high skew, HLMR bearings, modular joint

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Authors: V. Saccà, A. Sarica, F. Novellino, S. Barone, T. Tallarico, E. Filippelli, A. Granata, P. Valentino, A. Quattrone

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The work aim was to evaluate how well Random Forest (RF) and Support Vector Machine (SVM) algorithms could support the early diagnosis of Multiple Sclerosis (MS) from resting-state functional connectivity data. In particular, we wanted to explore the ability in distinguishing between controls and patients of mean signals extracted from ICA components corresponding to 15 well-known networks. Eighteen patients with early-MS (mean-age 37.42±8.11, 9 females) were recruited according to McDonald and Polman, and matched for demographic variables with 19 healthy controls (mean-age 37.55±14.76, 10 females). MRI was acquired by a 3T scanner with 8-channel head coil: (a)whole-brain T1-weighted; (b)conventional T2-weighted; (c)resting-state functional MRI (rsFMRI), 200 volumes. Estimated total lesion load (ml) and number of lesions were calculated using LST-toolbox from the corrected T1 and FLAIR. All rsFMRIs were pre-processed using tools from the FMRIB's Software Library as follows: (1) discarding of the first 5 volumes to remove T1 equilibrium effects, (2) skull-stripping of images, (3) motion and slice-time correction, (4) denoising with high-pass temporal filter (128s), (5) spatial smoothing with a Gaussian kernel of FWHM 8mm. No statistical significant differences (t-test, p < 0.05) were found between the two groups in the mean Euclidian distance and the mean Euler angle. WM and CSF signal together with 6 motion parameters were regressed out from the time series. We applied an independent component analysis (ICA) with the GIFT-toolbox using the Infomax approach with number of components=21. Fifteen mean components were visually identified by two experts. The resulting z-score maps were thresholded and binarized to extract the mean signal of the 15 networks for each subject. Statistical and machine learning analysis were then conducted on this dataset composed of 37 rows (subjects) and 15 features (mean signal in the network) with R language. The dataset was randomly splitted into training (75%) and test sets and two different classifiers were trained: RF and RBF-SVM. We used the intrinsic feature selection of RF, based on the Gini index, and recursive feature elimination (rfe) for the SVM, to obtain a rank of the most predictive variables. Thus, we built two new classifiers only on the most important features and we evaluated the accuracies (with and without feature selection) on test-set. The classifiers, trained on all the features, showed very poor accuracies on training (RF:58.62%, SVM:65.52%) and test sets (RF:62.5%, SVM:50%). Interestingly, when feature selection by RF and rfe-SVM were performed, the most important variable was the sensori-motor network I in both cases. Indeed, with only this network, RF and SVM classifiers reached an accuracy of 87.5% on test-set. More interestingly, the only misclassified patient resulted to have the lowest value of lesion volume. We showed that, with two different classification algorithms and feature selection approaches, the best discriminant network between controls and early MS, was the sensori-motor I. Similar importance values were obtained for the sensori-motor II, cerebellum and working memory networks. These findings, in according to the early manifestation of motor/sensorial deficits in MS, could represent an encouraging step toward the translation to the clinical diagnosis and prognosis.

Keywords: feature selection, machine learning, multiple sclerosis, random forest, support vector machine

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Authors: Monika Dmitrzak-Weglarz, Aleksandra Rajewska-Rager, Maria Skibinska, Natalia Lepczynska, Piotr Sibilski, Joanna Pawlak, Pawel Kapelski, Joanna Hauser

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Epidermal growth factor (EGF) is a well-known neurotrophic factor that involves in neuronal growth and synaptic plasticity. The proteomic research provided in order to identify novel candidate biological markers for mood disorders focused on elevated EGF serum level in patients during depression episode. However, the EGF association with mood disorder spectrum among adolescents and young adults has not been studied extensively. In this study, we aim to investigate the serum levels of EGF in adolescents and young adults during hypo/manic, depressive episodes and in remission compared to healthy control group. In our study, we involved 80 patients aged 12-24 years in 2-year follow-up study with a primary diagnosis of mood disorder spectrum, and 35 healthy volunteers matched by age and gender. Diagnoses were established according to DSM-IV-TR criteria using structured clinical interviews: K-SADS for child and adolescents, and SCID for young adults. Clinical and biological evaluations were made at baseline and euthymic mood (at 3th or 6th month of treatment and after 1 and 2 years). The Young Mania Rating Scale and Hamilton Rating Scale for Depression were used for assessment. The study protocols were approved by the relevant ethics committee. Serum protein concentration was determined by Enzyme-Linked Immunosorbent Assays (ELISA) method. Human EGF (cat. no DY 236) DuoSet ELISA kit was used (R&D Systems). Serum EGF levels were analysed with following variables: age, age under 18 and above 18 years old, sex, family history of affective disorders, drug-free vs. medicated. Shapiro-Wilk test was used to test the normality of the data. The homogeneity of variance was calculated with Levene’s test. EGF levels showed non-normal distribution and the homogeneity of variance was violated. Non-parametric tests: Mann-Whitney U test, Kruskall-Wallis ANOVA, Friedman’s ANOVA, Wilcoxon signed rank test, Spearman correlation coefficient was applied in the analyses The statistical significance level was set at p<0.05. Elevated EGF level at baseline (p=0.001) and at month 24 (p=0.02) was detected in study subjects compared with controls. Increased EGF level in women at month 12 (p=0.02) compared to men in study group have been observed. Using Wilcoxon signed rank test differences in EGF levels were detected: decrease from baseline to month 3 (p=0.014) and increase comparing: month 3 vs. 24 (p=0.013); month 6 vs. 12 (p=0.021) and vs. 24 (p=0.008). EGF level at baseline was negatively correlated with depression and mania occurrence at 24 months. EGF level at 24 months was positively correlated with depression and mania occurrence at 12 months. No other correlations of EGF levels with clinical and demographical variables have been detected. The findings of the present study indicate that EGF serum level is significantly elevated in the study group of patients compared to the controls. We also observed fluctuations in EGF levels during two years of disease observation. EGF seems to be useful as an early marker for prediction of diagnosis, course of illness and treatment response in young patients during first episode od mood disorders, which requires further investigation. Grant was founded by National Science Center in Poland no 2011/03/D/NZ5/06146.

Keywords: biological marker, epidermal growth factor, mood disorders, prediction

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Authors: Gabrielle Robertson, Matthew Downs, Joseph Dagher

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Iron deposition in the brain has been linked with a host of neurological disorders such as Alzheimer’s, Parkinson’s, and Multiple Sclerosis. While some treatment options exist, there are no objective measurement tools that allow for the monitoring of iron levels in the brain in vivo. An emerging Magnetic Resonance Imaging (MRI) method has been recently proposed to deduce iron concentration through quantitative measurement of magnetic susceptibility. This is a multi-step process that involves repeated modeling of physical processes via approximate numerical solutions. For example, the last two steps of this Quantitative Susceptibility Mapping (QSM) method involve I) mapping magnetic field into magnetic susceptibility and II) mapping magnetic susceptibility into iron concentration. Process I involves solving an ill-posed inverse problem by using regularization via injection of prior belief. The end result from Process II highly depends on the model used to describe the molecular content of each voxel (type of iron, water fraction, etc.) Due to these factors, the accuracy and repeatability of QSM have been an active area of research in the MRI and medical imaging community. This work aims to estimate iron concentration in the brain via a single step. A synthetic numerical model of the human head was created by automatically and manually segmenting the human head on a high-resolution grid (640x640x640, 0.4mm³) yielding detailed structures such as microvasculature and subcortical regions as well as bone, soft tissue, Cerebral Spinal Fluid, sinuses, arteries, and eyes. Each segmented region was then assigned tissue properties such as relaxation rates, proton density, electromagnetic tissue properties and iron concentration. These tissue property values were randomly selected from a Probability Distribution Function derived from a thorough literature review. In addition to having unique tissue property values, different synthetic head realizations also possess unique structural geometry created by morphing the boundary regions of different areas within normal physical constraints. This model of the human brain is then used to create synthetic MRI measurements. This is repeated thousands of times, for different head shapes, volume, tissue properties and noise realizations. Collectively, this constitutes a training-set that is similar to in vivo data, but larger than datasets available from clinical measurements. This 3D convolutional U-Net neural network architecture was used to train data-driven Deep Learning models to solve for iron concentrations from raw MRI measurements. The performance was then tested on both synthetic data not used in training as well as real in vivo data. Results showed that the model trained on synthetic MRI measurements is able to directly learn iron concentrations in areas of interest more effectively than other existing QSM reconstruction methods. For comparison, models trained on random geometric shapes (as proposed in the Deep QSM method) are less effective than models trained on realistic synthetic head models. Such an accurate method for the quantitative measurement of iron deposits in the brain would be of important value in clinical studies aiming to understand the role of iron in neurological disease.

Keywords: magnetic resonance imaging, MRI, iron deposition, machine learning, quantitative susceptibility mapping

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Authors: Samia A. El-Fiky, Fouad A. Abou-Zaid, Ibrahim M. Farag, Naira M. El-Fiky

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Clomipramine hydrochloride is one of the most used tricyclic antidepressant drug in Egypt. This drug contains in its chemical structure on two benzene rings. Benzene is considered to be toxic and clastogenic agent. So, the present study was designed to assess the genotoxic effect of Clomipramine hydrochloride on somatic and germ cells in mice. Three dose levels 0.195 (Low), 0.26 (Medium), and 0.65 (High) mg/kg.b.wt. were used. Seven groups of male mice were utilized in this work. The first group was employed as a control. In the remaining six groups, each of the above doses was orally administrated for two groups, one of them was treated for 5 days and the other group was given the same dose for 30 days. At the end of experiments, the animals were sacrificed for cytogenetic and sperm examination as well as histopathological investigations by using hematoxylin and eosin stains (H and E stains) and electron microscope. Concerning the sperm studies, these studies were confined to 5 days treatment with different dose levels. Moreover, the ultrastructural investigation by electron microscope was restricted to 30 days treatment with drug doses. The results of the dose dependent effect of Clomipramine showed that the treatment with three different doses induced increases of frequencies of chromosome aberrations in bone marrow and spermatocyte cells as compared to control. In addition, mitotic and meiotic activities of somatic and germ cells were declined. The treatments with medium or high doses were more effective for inducing significant increases of chromosome aberrations and significant decreases of cell divisions than treatment with low dose. The effect of high dose was more pronounced for causing such genetic deleterious in respect to effect of medium dose. Moreover, the results of the time dependent effect of Clomipramine observed that the treatment with different dose levels for 30 days led to significant increases of genetic aberrations than treatment for 5 days. Sperm examinations revealed that the treatment with Clomipramine at different dose levels caused significant increase of sperm shape abnormalities and significant decrease in sperm count as compared to control. The adverse effects on sperm shape and count were more obviousness by using the treatments with medium or high doses than those found in treatment with low dose. The group of mice treated with high dose had the highest rate of sperm shape abnormalities and the lowest proportion of sperm count as compared to mice received medium dose. In histopathological investigation, hematoxylin and eosin stains showed that, the using of low dose of Clomipramine for 5 or 30 days caused a little pathological changes in liver tissue. However, using medium and high doses for 5 or 30 days induced severe damages than that observed in mice treated with low dose. The treatment with high dose for 30 days gave the worst results of pathological changes in hepatic cells. Moreover, ultrastructure examination revealed, the mice treated with low dose of Clomipramine had little differences in liver histological architecture as compared to control group. These differences were confined to cytoplasmic inclusions. Whereas, prominent pathological changes in nuclei as well as dilated of rough Endoplasmic Reticulum (rER) were observed in mice treated with medium or high doses of Clomipramine drug. In conclusion, the present study adds evidence that treatments with medium or high doses of Clomipramine have genotoxic effects on somatic and germ cells of mice, as unwanted side effects. However, the using of low dose (especially for short time, 5 days) can be utilized as a therapeutic dose, where it caused relatively similar proportions of genetic, sperm, and histopathological changes as those found in normal control.

Keywords: chromosome aberrations, clomipramine, mice, histopathology, sperm abnormalities

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Authors: Ikele Chika Bright, Mgbenka Bernard Obialo, Ikele Chioma Faith

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Icthyophthiriasis is a prevalent protozoan (ectoparasite) mostly affecting cultured and aquarium fishes. The majority of the chemotherapeutants lack efficacy for completely eliminating Ich parasite without affecting the environment and they are not safe for human health. The present work is focused on the evaluating different immersion treatments of African catfish (Clarias gariepinus) infected with ichthyophthiriasis and treated with a non-chemical and environmental friendly parasiticides Moringa oleifera. A total number of 800 apparently healthy parasites free (examined) post juvenile catfish were obtained from a reputable farm, disinfected with potassium permanganate in a quarantine tank to remove any possible external parasites. The fish were further challenged with approximately 44,000 infective stages of theronts which were obtained through serial passages by cohabitation. Seven groups (A-G) of post Juvenile were used for the experiment which was carried out into three stages; Dips (60minutes), short term treatment (24-96h) and prolong bath treatment (0-15 days). The concentrations selected were dependent on the outcome of the LC50 of the plant material from which dose-dependent factors were used to select various concentrations of the treatment. In Dips treatment, group D-G were treated with 1,500mg/L, 2500mg/L., 3500mg/L and 4500mg/L, short-term treatment was treated with 150mg/L, 250mg/L, 350mg/L and 450mg/L and prolong bath was treated with 15mg/L, 25mg/L, 35mg/L and 45mg/L of the plant extract whereas group A, B and C were normal control, Ich- infested not treated and Ich- infested treated with standard drug (Acriflavin), respectively. The various types of treatment applied with corresponding concentrations showed almost complete elimination of the adult parasites (trophonts) both in the gills and the body smear, thereby making M. oleifera a potential parasiticides. There were serious pathological alterations in the skin and gills which are usually the main point for Ich parasites invasion but no significant morphological characteristics was noted among the treated groups subjected to different immersion treatment patterns. Epitheliocystis, aneurysm, oedema, hemorrhage, and localization of the adult parasite in the gills were the overall common observations made in the gills whereas degeneration of muscle fibre, dermatitis, hemorrhage, oedema, abscess formation and keratinisation were observed in the skin. However, there are no pathological changes in the control group. Moreover, biochemical parameters such as urea, creatinine, albumin., globulin, total protein, ALT, AST), blood chemistry (sodium, chloride, potassium, bicarbonate), antioxidants (CAT, SOD, GPx, LPO), enzymatic activities (myeloperoxidase, thioreadoxin reductase), Inflammatory response (C-reactive protein), Stress markers (lactate dehydrogenase), heamatological parameters (RBC, PCV, WBC, HB and differential count), lipid profile (total cholesterol, tryglycerides , high density lipoprotein and low density lipoprotein) all showed various significant (P<0.05) and no significant (P>0.05) responses among the Ich-infested fish treated under three immersion treatments. It is suggested that M. oleifera may serve as an alternatives to chemotherapeutants for control of Ichthyophthiriasis in African catfish Clarias gariepinus.

Keywords: Icthyophthirius multifilis, immersion treatment, pathophysiology, African catfish

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Authors: Nitika Sharma, Yogesh Jain

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Introduction: An efficient Information System helps in improving the service delivery as well provides the foundation for policy and regulation of other building blocks of Health System. Health care organizations require an integrated working of its various sub-systems. An efficient EMR software boosts the teamwork amongst the various sub-systems thereby resulting in improved service delivery. Although there has been a huge impetus to EMR under the Digital India initiative, it has still not been mandated in India. It is generally implemented in huge funded public or private healthcare organizations only. Objective: The study was conducted to understand the factors that lead to the successful adoption of an affordable EMR in the low level healthcare organization. It intended to understand the design of the EMR and address the solutions to the challenges faced in adoption of the EMR. Methodology: The study was conducted in a non-profit registered Healthcare organization that has been providing healthcare facilities to more than 2500 villages including certain areas that are difficult to access. The data was collected with help of field notes, in-depth interviews and participant observation. A total of 16 participants using the EMR from different departments were enrolled via purposive sampling technique. The participants included in the study were working in the organization before the implementation of the EMR system. The study was conducted in one month period from 25 June-20 July 2018. The Ethical approval was taken from the institute along with prior approval of the participants. Data analysis: A word document of more than 4000 words was obtained after transcribing and translating the answers of respondents. It was further analyzed by focused coding, a line by line review of the transcripts, underlining words, phrases or sentences that might suggest themes to do thematic narrative analysis. Results: Based on the answers the results were thematically grouped under four headings: 1. governance of organization, 2. architecture and design of the software, 3. features of the software, 4. challenges faced in adoption and the solutions to address them. It was inferred that the successful implementation was attributed to the easy and comprehensive design of the system which has facilitated not only easy data storage and retrieval but contributes in constructing a decision support system for the staff. Portability has lead to increased acceptance by physicians. The proper division of labor, increased efficiency of staff, incorporation of auto-correction features and facilitation of task shifting has lead to increased acceptance amongst the users of various departments. Geographical inhibitions, low computer literacy and high patient load were the major challenges faced during its implementation. Despite of dual efforts made both by the architects and administrators to combat these challenges, there are still certain ongoing challenges faced by organization. Conclusion: Whenever any new technology is adopted there are certain innovators, early adopters, late adopters and laggards. The same pattern was followed in adoption of this software. He challenges were overcome with joint efforts of organization administrators and users as well. Thereby this case study provides a framework of implementing similar systems in public sector of countries that are struggling for digitizing the healthcare in presence of crunch of human and financial resources.

Keywords: EMR, healthcare technology, e-health, EHR

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Authors: Kakali Roy, Sahana P. Raju, Subhra Dhar, Sandipan Dhar

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Introduction: Xeroderma pigmentosa (XP) is a rare inherited (autosomal recessive) disease resulting from impairment in DNA repair that involves recognition and repair of ultraviolet radiation (UVR) induced DNA damage in the nucleotide excision repair pathway. Which results in increased photosensitivity, UVR induced damage to skin and eye, increased susceptibility of skin and ocular cancer, and progressive neurodegeneration in some patients. XP is present worldwide, with higher incidence in areas having frequent consanguinity. Being extremely rare, there is limited literature on XP and associated complications. Here, the clinico-pathological experience (spectrum of clinical presentation, histopathological findings of malignant skin lesions, and progression) of managing 8 cases of XP is presented. Methodology: A retrospective study was conducted in a pediatric tertiary care hospital in eastern India during a ten-year period from 2013 to 2022. A clinical diagnosis was made based on severe sun burn or premature photo-aging and/or onset of cutaneous malignancies at early age (1st decade) in background of consanguinity and autosomal recessive inheritance pattern in family. Results: The mean age of presentation was 1.2 years (range of 7month-3years), while three children presented during their infancy. Male to female ratio was 5:3, and all were born of consanguineous marriage. They presented with dermatological manifestations (100%) followed by ophthalmic (75%) and/or neurological symptoms (25%). Patients had normal skin at birth but soon developed extreme sensitivity to UVR in the form of exaggerated sun tanning, burning, and blistering on minimal sun exposure, followed by abnormal skin pigmentation like freckles and lentiginosis. Subsequently, over time there was progressive xerosis, atrophy, wrinkling, and poikiloderma. Six patients had varied degree of ocular involvement, while three of them had severe manifestation, including madarosis, tylosis, ectropion, Lagopthalmos, Pthysis bulbi, clouding and scarring of the cornea with complete or partial loss of vision, and ophthalmic malignancies. 50% (n=4) cases had skin and ocular pre-malignant (actinic keratosis) and malignant lesions, including melanoma and non melanoma skin cancer (NMSC) like squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in their early childhood. One patient had simultaneous occurrence of multiple malignancies together (SCC, BCC, and melanoma). Subnormal intelligence was noticed as neurological feature, and none had sensory neural hearing loss, microcephaly, neuroregression, or neurdeficit. All the patients had been being managed by a multidisciplinary team of pediatricians, dermatologists, ophthalmologists, neurologists and psychiatrists. Conclusion: Although till date there is no complete cure for XP and the disease is ultimately fatal. But increased awareness, early diagnosis followed by persistent vigorous protection from UVR, and regular screening for early detection of malignancies along with psychological support can drastically improve patients’ quality of life and life expectancy. Further research is required on formulating optimal management of XP, specifically the role and possibilities of gene therapy in XP.

Keywords: childhood malignancies, dermato-pathological findings, eastern India, Xeroderma pigmentosa

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Authors: Sebastian Kehne, Alexander Epple, Werner Herfs

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A new method for optimal selection of components for multi-axes forward-feed drive systems is proposed in which the choice of motors, gear boxes and ball screw drives is optimized. Essential is here the synchronization of electrical and mechanical frequency behavior of all axes because even advanced controls (like H∞-controls) can only control a small part of the mechanical modes – namely only those of observable and controllable states whose value can be derived from the positions of extern linear length measurement systems and/or rotary encoders on the motor or gear box shafts. Further problems are the unknown processing forces like cutting forces in machine tools during normal operation which make the estimation and control via an observer even more difficult. To start with, the open source Modelica Feed Drive Library which was developed at the Laboratory for Machine Tools, and Production Engineering (WZL) is extended from one axis design to the multi axes design. It is capable to simulate the mechanical, electrical and thermal behavior of permanent magnet synchronous machines with inverters, different gear boxes and ball screw drives in a mechanical system. To keep the calculation time down analytical equations are used for field and torque producing equivalent circuit, heat dissipation and mechanical torque at the shaft. As a first step, a small machine tool with a working area of 635 x 315 x 420 mm is taken apart, and the mechanical transfer behavior is measured with an impulse hammer and acceleration sensors. With the frequency transfer functions, a mechanical finite element model is built up which is reduced with substructure coupling to a mass-damper system which models the most important modes of the axes. The model is modelled with Modelica Feed Drive Library and validated by further relative measurements between machine table and spindle holder with a piezo actor and acceleration sensors. In a next step, the choice of possible components in motor catalogues is limited by derived analytical formulas which are based on well-known metrics to gain effective power and torque of the components. The simulation in Modelica is run with different permanent magnet synchronous motors, gear boxes and ball screw drives from different suppliers. To speed up the optimization different black-box optimization methods (Surrogate-based, gradient-based and evolutionary) are tested on the case. The objective that was chosen is to minimize the integral of the deviations if a step is given on the position controls of the different axes. Small values are good measures for a high dynamic axes. In each iteration (evaluation of one set of components) the control variables are adjusted automatically to have an overshoot less than 1%. It is obtained that the order of the components in optimization problem has a deep impact on the speed of the black-box optimization. An approach to do efficient black-box optimization for multi-axes design is presented in the last part. The authors would like to thank the German Research Foundation DFG for financial support of the project “Optimierung des mechatronischen Entwurfs von mehrachsigen Antriebssystemen (HE 5386/14-1 | 6954/4-1)” (English: Optimization of the Mechatronic Design of Multi-Axes Drive Systems).

Keywords: ball screw drive design, discrete optimization, forward feed drives, gear box design, linear drives, machine tools, motor design, multi-axes design

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Authors: Marit D. Murry, Amy K. Marks

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The transition to college is a critical period that affords abundant opportunities for growth in conjunction with novel challenges for emerging adults. During this time, emerging adults are garnering experiences and acquiring hosts of new information that they are required to synthesize and use to inform life-shaping decisions. This stage is characterized by instability and exploration, which necessitates a diverse set of coping skills to successfully navigate and positively adapt to their evolving environment. However, important sociocultural factors result in differences that occur developmentally for minority emerging adults (i.e., emerging adults with an identity that has been or is marginalized). While the transition to college holds vast potential, not all are afforded the same chances, and many individuals enter into this stage at varying degrees of readiness. Understanding the nuance and diversity of student preparedness for college and contextualizing these factors will better equip systems to support incoming students. Emerging adulthood for ethnic, racial minority students presents itself as an opportunity for growth and resiliency in the face of systemic adversity. Ethnic, racial identity (ERI) is defined as an identity that develops as a function of one’s ethnic-racial group membership. Research continues to demonstrate ERI as a resilience factor that promotes positive adjustment in young adulthood. Adaptive coping responses (e.g., engaging in help-seeking behavior, drawing on personal and community resources) have been identified as possible mechanisms through which ERI buffers youth against stressful life events, including discrimination. Additionally, trait mindfulness has been identified as a significant predictor of general psychological health, and mindfulness practice has been shown to be a self-regulatory strategy that promotes healthy stress responses and adaptive coping strategy selection. The current study employed a person-centered approach to explore emerging patterns across ethnic identity development and psychological well-being criterion variables among college freshmen. Data from 283 incoming college freshmen at Northeastern University were analyzed. The Brief COPE Acceptance and Emotional Support scales, the Five Factor Mindfulness Questionnaire, and MIEM Exploration and Affirmation measures were used to inform the cluster profiles. The TwoStep auto-clustering algorithm revealed an optimal three-cluster solution (BIC = 848.49), which classified 92.6% (n = 262) of participants in the sample into one of the three clusters. The clusters were characterized as ‘Mixed Adjustment’, ‘Lowest Adjustment’, and ‘Moderate Adjustment.’ Cluster composition varied significantly by ethnicity X² (2, N = 262) = 7.74 (p = .021) and gender X² (2, N = 259) = 10.40 (p = .034). The ‘Lowest Adjustment’ cluster contained the highest proportion of students of color, 41% (n = 32), and male-identifying students, 44.2% (n = 34). Follow-up analyses showed higher ERI exploration in ‘Moderate Adjustment’ cluster members, also reported higher levels of psychological distress, with significantly elevated depression scores (p = .011), psychological diagnoses of depression (p = .013), anxiety (p = .005) and psychiatric disorders (p = .025). Supporting prior research, students engaging with identity exploration processes often endure more psychological distress. These results indicate that students undergoing identity development may require more socialization and different services beyond normal strategies.

Keywords: adjustment, coping, college, emerging adulthood, ethnic-racial identity, psychological well-being, resilience

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Authors: Hyojung Shin, Munhee Kweon

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Non-suicide Self Injuri (NSSI) can be defined as the act of an individual who does not intend to die directly and intentionally damaging his or her body tissues. According to a study conducted by the Korean Ministry of Education in 2018, the NSSI is widely spreading among teenagers, with 7.9 percent of all middle school students and 6.4 percent of high school students reporting experience in NSSI. As such, it is understood that the first time of the NSSI is in adolescence. However, the NSSI may not start and stop at a certain time, but may last longer. However, despite the widespread prevalence of NSSI among teenagers, little is known about the process and maintenance of NSSI college students on a continuous development basis. Korea's NSSI research trends are mainly focused on individual internal vulnerabilities (high levels of painful emotions/awareness, lack of pain tolerance) and interpersonal vulnerabilities (poor communication skills and social problem solving), and little studies have been done on individuals' unique characteristics and environmental factors such as substrate or environmental vulnerability factors. In particular, environmental factors are associated with the occurrence of NSSI by acting as a vulnerability factor that can interfere with the emotional control of individuals, whereas individual factors play a more direct role by contributing to the maintenance of NSSI, so it is more important to consider this for personal environmental involvement in NSSI. This study focused on the Fight-Flight-Freeze System as a factor in the defensive avoidance system of Reward Sensitivity in individual factors. Also, Environmental factors include the level of expressed emotion in family. Wedig and Nock (2007) said that if parents with a self-critical cognitive style take the form of criticizing their children, the experience of NSSI increases. The high level of parental criticism is related to the increasing frequency of NSSI acts as well as to serious levels of NSSI. If the normal coping mechanism fails to control emotions, people want to overcome emotional difficulties even through NSSI, and emotional disturbances experienced by individuals within an unsupported social relationship increase vulnerability to NSSI. Based on these theories, this study is to find ways to prevent NSSI and intervene in counseling effectively by verifying the differences between the characteristics experienced NSSI persons and non-experienced NSSI persons. Therefore, the purpose of this research was to examine the relationship of Fight-Flight-Freeze System (FFFS), level of expressed emotion in family and emotion regulation difficulties, comparing those who experienced Non-Suicidal Self-Injury (NSSI) with those who did not experienced Non-Suicidal Self-Injury (NSSI). The data were collected from university students in Seoul Korea and Gyeonggi-do province. 99 subjects were experienced student of NSSI, while 375 were non- experienced student of NSSI. The results of this study are as follows. First, the result of t-test indicated that NSSI attempters showed a significant difference in fight-flight-freeze system, level of expressed emotion and emotion regulation difficulties, compared with non-attempters. Second, fight-flight-freeze system, level of expressed emotion in family and emotion regulation difficulties of NSSI attempters showed a significant difference in correlation. The correlation was significant only freeze system of fight-flight-freeze system, Level of expressed emotion in family and emotion regulation difficulties. Third, freeze system and level of expressed emotion in family predicted emotion regulation difficulties of NSSI attempters. Fight-freeze system and level of expressed emotion in family predicted emotion regulation difficulties of non-NSSI attempters. Lastly, Practical implications for counselors and limitations of this study are discussed.

Keywords: fight-flight-freeze system, level of expressed emotion in family, emotion regulation difficulty, non-suicidal self injury

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Authors: Fossarello Maurizio, Mattana Giorgio, Tatti Filippo.

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The most widely performed surgical procedure in Open-Angle Glaucoma (OAG) is trabeculectomy. Although this filtering procedure is extremely effective, surgical failure and postoperative complications are reported. Due to the its invasive nature and possible complications, trabeculectomy is usually reserved, in practice, for patients who are refractory to medical and laser therapy. Recently, a number of micro-invasive surgical techniques (MIGS: Micro-Invasive Glaucoma Surgery), have been introduced in clinical practice. They meet the criteria of micro-incisional approach, minimal tissue damage, short surgical time, reliable IOP reduction, extremely high safety profile and rapid post-operative recovery. Xen45 Gel Implant (Allergan, Dublin, Ireland) is one of the MIGS alternatives, and consists in a porcine gelatin tube designed to create an aqueous flow from the anterior chamber to the subconjunctival space, bypassing the resistance of the trabecular meshwork. In this study we report the results of this technique as a favorable option in the treatment of OAG for its benefits in term of efficacy and safety, either alone or in combination with cataract surgery. This is a retrospective, single-center study conducted in consecutive OAG patients, who underwent Xen45 Gel Stent implantation alone or in combination with phacoemulsification, from October 2018 to June 2019. The primary endpoint of the study was to evaluate the reduction of both IOP and number of antiglaucoma medications at 12 months. The secondary endpoint was to correlate filtering bleb morphology evaluated by means of anterior segment OCT with efficacy in IOP lowering and eventual further procedures requirement. Data were recorded on Microsoft Excel and study analysis was performed using Microsoft Excel and SPSS (IBM). Mean values with standard deviations were calculated for IOPs and number of antiglaucoma medications at all points. Kolmogorov-Smirnov test showed that IOP followed a normal distribution at all time, therefore the paired Student’s T test was used to compare baseline and postoperative mean IOP. Correlation between postoperative Day 1 IOP and Month 12 IOP was evaluated using Pearson coefficient. Thirty-six eyes of 36 patients were evaluated. As compared to baseline, mean IOP and the mean number of antiglaucoma medications significantly decreased from 27,33 ± 7,67 mmHg to 16,3 ± 2,89 mmHg (38,8% reduction) and from 2,64 ± 1,39 to 0,42 ± 0,8 (84% reduction), respectively, at 12 months after surgery (both p < 0,001). According to bleb morphology, eyes were divided in uniform group (n=8, 22,2%), subconjunctival separation group (n=5, 13,9%), microcystic multiform group (n=9, 25%) and multiple internal layer group (n=14, 38,9%). Comparing to baseline, there was no significative difference in IOP between the 4 groups at month 12 follow-up visit. Adverse events included bleb function decrease (n=14, 38,9%), hypotony (n=8, 22,2%) and choroidal detachment (n=2, 5,6%). All eyes presenting bleb flattening underwent needling and MMC injection. The higher percentage of patients that required secondary needling was in the uniform group (75%), with a significant difference between the groups (p=0,03). Xen45 gel stent, either alone or in combination with phacoemulsification, provided a significant lowering in both IOP and medical antiglaucoma treatment and an elevated safety profile.

Keywords: anterior segment OCT, bleb morphology, micro-invasive glaucoma surgery, open angle glaucoma, Xen45 gel implant

Procedia PDF Downloads 101

Authors: Chandranath Chatterjee, Amina Khatun, Bhabagrahi Sahoo

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With the changing climate, precipitation events are intensified in the tropical river basins. Since these river basins are significantly influenced by the monsoonal rainfall pattern, critical impacts are observed on the agricultural practices in the downstream river reaches. This study analyses the crop damage and associated flood risk in terms of net benefit in the paddy-dominated tropical Indian delta of the Mahanadi River. The Mahanadi River basin lies in eastern part of the Indian sub-continent and is greatly affected by the southwest monsoon rainfall extending from the month of June to September. This river delta is highly flood-prone and has suffered from recurring high floods, especially after the 2000s. In this study, the lumped conceptual model, Nedbør Afstrømnings Model (NAM) from the suite of MIKE models, is used for rainfall-runoff modeling. The NAM model is laterally integrated with the MIKE11-Hydrodynamic (HD) model to route the runoffs up to the head of the delta region. To obtain the precipitation-derived future projected discharges at the head of the delta, nine Global Climate Models (GCMs), namely, BCC-CSM1.1(m), GFDL-CM3, GFDL-ESM2G, HadGEM2-AO, IPSL-CM5A-LR, IPSL-CM5A-MR, MIROC5, MIROC-ESM-CHEM and NorESM1-M, available in the Coupled Model Intercomparison Project-Phase 5 (CMIP5) archive are considered. These nine GCMs are previously found to best-capture the Indian Summer Monsoon rainfall. Based on the performance of the nine GCMs in reproducing the historical discharge pattern, three GCMs (HadGEM2-AO, IPSL-CM5A-MR and MIROC-ESM-CHEM) are selected. A higher Taylor Skill Score is considered as the GCM selection criteria. Thereafter, the 10-year return period design flood is estimated using L-moments based flood frequency analysis for the historical and three future projected periods (2010-2039, 2040-2069 and 2070-2099) under Representative Concentration Pathways (RCP) 4.5 and 8.5. A non-dimensional hydrograph analysis is performed to obtain the hydrographs for the historical/projected 10-year return period design floods. These hydrographs are forced into the calibrated and validated coupled 1D-2D hydrodynamic model, MIKE FLOOD, to simulate the flood inundation in the delta region. Historical and projected flood risk is defined based on the information about the flood inundation simulated by the MIKE FLOOD model and the inundation depth-damage-duration relationship of a normal rice variety cultivated in the river delta. In general, flood risk is expected to increase in all the future projected time periods as compared to the historical episode. Further, in comparison to the 2010s (2010-2039), an increased flood risk in the 2040s (2040-2069) is shown by all the three selected GCMs. However, the flood risk then declines in the 2070s as we move towards the end of the century (2070-2099). The methodology adopted herein for flood risk assessment is one of its kind and may be implemented in any world-river basin. The results obtained from this study can help in future flood preparedness by implementing suitable flood adaptation strategies.

Keywords: flood frequency analysis, flood risk, global climate models (GCMs), paddy cultivation

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Authors: Ahmad Saad, Shuja Abbas, Breanna Marine

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Introduction: This study explores the potential applications of autologous pedal fat pad grafting as a minimally invasive therapeutic strategy for addressing pedal fat pad loss. Without adequate shock absorbing tissue, a patient can experience functional deficits, ulcerations, loss of quality of life, and significant limitations with ambulation. This study details a novel technique involving autologous adipose grafting from the abdomen to enhance plantar fat pad thickness in a patient involved in a severe motor vehicle accident which resulted in total fat pad loss of the heel. Autologous adipose grafting (AAG) was used following adipose allografting in an effort to recreate a normal shock absorbing surface to allow return to activities of daily living and painless ambulation. Methods: A 46-year-old male sustained multiple open pedal fractures and necrosis to the heel fat pad after a motorcycle accident, which resulted in complete loss of the calcaneal fat pad. The patient underwent serial debridement’s, utilization of wound vac therapy and split thickness skin grafting to accomplish complete closure, despite complete loss of adipose to area. Patient presented with complaints of pain on ambulation, inability to bear weight on the heel, recurrent ulcerations, admitted had not been ambulating for two years. Clinical exam demonstrated complete loss of the plantar fat pad with a thin layer of epithelial tissue overlying the calcaneal bone, allowing visibility of the osseous contour of the calcaneus. Scar tissue had formed in place of the fat pad, with thickened epithelial tissue extending from the midfoot to the calcaneus. After conservative measures were exhausted, the patient opted for initial management by adipose allograft matrix (AAM) injections. Post operative X-ray imaging revealed noticeable improvement in calcaneal fat pad thickness. At 1 year follow up, the patient was able to ambulate without assistive devices. The fat pad at this point was significantly thicker than it was pre-operatively, but the thickness did not restore to pre-accident thickness. In order to compare the take of allograft versus autografting of adipose tissue, the decision to use adipose autograft through abdominal liposuction harvesting was deemed suitable. A general surgeon completed harvesting of adipose cells from the patient’s abdomen via liposuction, and a podiatric surgeon performed the AAG injection into the heel. Total of 15 cc’s of autologous adipose tissue injected to the calcaneus. Results: There was a visual increase in the calcaneal fat pad thickness both clinically and radiographically. At the 6-week follow up, imaging revealed retention of the calcaneal fat pad thickness. Three months postop, patient returned to activities of daily living and increased quality of life due to their increased ability to ambulate. Discussion: AAG is a novel treatment for pedal fat pad loss. These treatments may be viable and reproducible therapeutic choices for patients suffering from fat pad atrophy, fat pad loss, and/or plantar ulcerations. Both treatments of AAM and AAG exhibited similar therapeutic results by providing pain relief for ambulation and allowing for patients to return to their quality of life.

Keywords: podiatry, wound, adipose, allograft, autograft, wound care, limb reconstruction, injection, limb salvage

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Authors: Martyna Ekiert, Natalia Grzechnik, Joanna Karbowniczek, Urszula Stachewicz, Andrzej Mlyniec

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Tendon grafting is a common procedure performed to treat tendon rupture. Before the surgical procedure, tissues intended for grafts (i.e., Achilles tendon) are stored in ultra-low temperatures for a long time and also may be subjected to unfavorable conditions, such as repetitive freezing (F) and thawing (T). Such storage protocols may highly influence the graft mechanical properties, decrease its functionality and thus increase the risk of complications during the transplant procedure. The literature reports on the influence of multiple F/T cycles on internal structure and mechanical properties of tendons stay inconclusive, confirming and denying the negative influence of multiple F/T at the same time. An inconsistent research methodology and lack of clear limit of F/T cycles, which disqualifies tissue for surgical graft purposes, encouraged us to investigate the issue of multiple F/T cycles by the mean of biomechanical tensile tests supported with Scanning Electron Microscope (SEM) imaging. The study was conducted on male bovine Achilles tendon-derived from the local abattoir. Fresh tendons were cleaned of excessive membranes and then sectioned to obtained fascicle bundles. Collected samples were randomly assigned to 6 groups subjected to 1, 2, 4, 6, 8 and 12 cycles of freezing-thawing (F/T), respectively. Each F/T cycle included deep freezing at -80°C temperature, followed by thawing at room temperature. After final thawing, thin slices of the side part of samples subjected to 1, 4, 8 and 12 F/T cycles were collected for SEM imaging. Then, the width and thickness of all samples were measured to calculate the cross-sectional area. Biomechanical tests were performed using the universal testing machine (model Instron 8872, INSTRON®, Norwood, Massachusetts, USA) using a load cell with a maximum capacity of 250 kN and standard atmospheric conditions. Both ends of each fascicle bundle were manually clamped in grasping clamps using abrasive paper and wet cellulose wadding swabs to prevent tissue slipping while clamping and testing. Samples were subjected to the testing procedure including pre-loading, pre-cycling, loading, holding and unloading steps to obtain stress-strain curves for representing tendon stretching and relaxation. The stiffness of AT fascicles bundle samples was evaluated in terms of modulus of elasticity (Young’s modulus), calculated from the slope of the linear region of stress-strain curves. SEM imaging was preceded by chemical sample preparation including 24hr fixation in 3% glutaraldehyde buffered with 0.1 M phosphate buffer, washing with 0.1 M phosphate buffer solution and dehydration in a graded ethanol solution. SEM images (Merlin Gemini II microscope, ZEISS®) were taken using 30 000x mag, which allowed measuring a diameter of collagen fibrils. The results confirm a decrease in fascicle bundles Young’s modulus as well as a decrease in the diameter of collagen fibrils. These results confirm the negative influence of multiple F/T cycles on the mechanical properties of tendon tissue.

Keywords: biomechanics, collagen, fascicle bundles, soft tissue

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Authors: Amberly Brigden, Ali Heawood, Emma C. Anderson, Richard Morris, Esther Crawley

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Background: Paediatric chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) is characterised by persistent, disabling fatigue. Health services see patients below the age of 12. This age group experience high levels of disability, with low levels of school attendance, high levels of fatigue, anxiety, functional disability and pain. CFS/ME interventions have been developed for adolescents, but the developmental needs of younger children suggest treatment should be tailored to this age group. Little is known about how intervention should be delivered to this age group, and further work is needed to explore this. Qualitative research aids patient-centered design of health intervention. Methods: Five to 11-year-olds and their parents were recruited from a specialist CFS/ME service. Semi-structured interviews explored the families’ experience of the condition and perspectives on treatment. Interactive and arts-based methods were used. Interviews were audio-recorded, transcribed and analysed thematically. Qualitative Results: 14 parents and 7 children were interviewed. Early analysis of the interviews revealed the importance of the social-ecological setting of the child, which led to themes being developed in the context of Systems Theory. Theme one relates to the level of the child, theme two the family system, theme three the organisational and societal systems, and theme four cuts-across all levels. Theme1: The child’s capacity to describe, understand and manage their condition. Younger children struggled to describe their internal experiences, such as physical symptoms. Parents felt younger children did not understand some concepts of CFS/ME and did not have the capabilities to monitor and self-regulate their behaviour, as required by treatment. A spectrum of abilities was described; older children (10-11-year-olds) were more involved in clinical sessions and had more responsibility for self-management. Theme2: Parents’ responsibility for managing their child’s condition. Parents took responsibility for regulating their child’s behaviour in accordance with the treatment programme. They structured their child’s environment, gave direct instructions to their child, and communicated the needs of their child to others involved in care. Parents wanted their child to experience a 'normal' childhood and took steps to shield their child from medicalization, including diagnostic labels and clinical discussions. Theme3: Parental isolation and the role of organisational and societal systems. Parents felt unsupported in their role of managing the condition and felt negative responses from primary care health services and schools were underpinned by a lack of awareness and knowledge about CFS/ME in younger children. This sometimes led to a protracted time to diagnosis. Parents felt that schools have the potential important role in managing the child’s condition. Theme4: Complexity and uncertainty. Many parents valued specialist treatment (which included activity management, physiotherapy, sleep management, dietary advice, medical management and psychological support), but felt it needed to account for the complexity of the condition in younger children. Some parents expressed uncertainty about the diagnosis and the treatment programme. Conclusions: Interventions for younger children need to consider the 'systems' (family, organisational and societal) involved in the child’s care. Future research will include interviews with clinicians and schools supporting younger children with CFS/ME.

Keywords: chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME), pediatric, qualitative, treatment

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Authors: Dilek Ozturk, Narin Ozturk, Zeliha Pala Kara, Engin Kaptan, Serap Sancar Bas, Nurten Ozsoy, Alper Okyar

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Most physiological processes oscillate in a rhythmic manner in mammals including metabolism and energy homeostasis, locomotor activity, hormone secretion, immune and endocrine system functions. Endocrine body rhythms are tightly regulated by the circadian timing system. The hypothalamic-pituitary-thyroid (HPT) axis is under circadian control at multiple levels from hypothalamus to thyroid gland. Since circadian timing system controls a variety of biological functions in mammals, circadian rhythms of biological functions may modify the drug tolerability/toxicity depending on the dosing time. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer agent that is active against many cancers. It was also found to be active in medullary thyroid cancer. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus on the thyroid gland and hormones in mice. Healthy C57BL/6J mice were synchronized with 12h:12h Light-Dark cycle (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding to Light onset). Everolimus was administered to male (5 mg/kg/day) and female mice (15 mg/kg/day) orally at ZT1-rest period- and ZT13-activity period- for 4 weeks; body weight loss, clinical signs and possible changes in serum thyroid hormone levels (TSH and free T4) were examined. Histological alterations in the thyroid gland were evaluated according to the following criteria: follicular size, colloid density and viscidity, height of the follicular epithelium and the presence of necrotic cells. The statistical significance between differences was analyzed with ANOVA. Study findings included everolimus-related diarrhea, decreased activity, decreased body weight gains, alterations in serum TSH levels, and histopathological changes in thyroid gland. Decreases in mean body weight gains were more evident in mice treated at ZT1 as compared to ZT13 (p < 0.001, for both sexes). Control tissue sections of thyroid glands exhibited well-organized histoarchitecture when compared to everolimus-treated groups. Everolimus caused histopathological alterations in thyroid glands in male (5 mg/kg, slightly) and female mice (15 mg/kg; p < 0.01 for both ZT as compared to their controls) irrespective of dosing-time. TSH levels were slightly decreased upon everolimus treatment at ZT13 in both males and females. Conversely, increases in TSH levels were observed when everolimus treated at ZT1 in both males (5 mg/kg; p < 0.05) and females (15 mg/kg; slightly). No statistically significant alterations in serum free T4 levels were observed. TSH and free T4 is clinically important thyroid hormones since a number of disease states have been linked to alterations in these hormones. Serum free T4 levels within the normal ranges in the presence of abnormal serum TSH levels in everolimus treated mice may suggest subclinical thyroid disease which may have repercussions on the cardiovascular system, as well as on other organs and systems. Our study has revealed the histological damage on thyroid gland induced by subacute everolimus administration, this effect was irrespective of dosing time. However, based on the body weight changes and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13 in both male and females. Yet, effects of everolimus on thyroid functions may deserve further studies regarding their clinical importance and chronotoxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, thyroid gland, thyroid hormones

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Authors: Wonil Nam, Xiang Ren, Inyoung Kim, Masoud Agah, Wei Zhou

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Despite its ultrasensitive detection capability, surface-enhanced Raman spectroscopy (SERS) faces challenges as a quantitative biochemical analysis tool due to the significant dependence of local field intensity in hotspots on nanoscale geometric variations of plasmonic nanostructures. Therefore, despite enormous progress in plasmonic nanoengineering of high-performance SERS devices, it is still challenging to quantitatively correlate the measured SERS signals with the actual molecule concentrations at hotspots. A significant effort has been devoted to developing SERS calibration methods by introducing internal standards. It has been achieved by placing Raman tags at plasmonic hotspots. Raman tags undergo similar SERS enhancement at the same hotspots, and ratiometric SERS signals for analytes of interest can be generated with reduced dependence on geometrical variations. However, using Raman tags still faces challenges for real-world applications, including spatial competition between the analyte and tags in hotspots, spectral interference, laser-induced degradation/desorption due to plasmon-enhanced photochemical/photothermal effects. We show that electronic Raman scattering (ERS) signals from metallic nanostructures at hotspots can serve as the internal calibration standard to enable quantitative SERS analysis and improve biostatistical analysis. We perform SERS with Au-SiO₂ multilayered metal-insulator-metal nano laminated plasmonic nanostructures. Since the ERS signal is proportional to the volume density of electron-hole occupation in hotspots, the ERS signals exponentially increase when the wavenumber is approaching the zero value. By a long-pass filter, generally used in backscattered SERS configurations, to chop the ERS background continuum, we can observe an ERS pseudo-peak, IERS. Both ERS and SERS processes experience the |E|⁴ local enhancements during the excitation and inelastic scattering transitions. We calibrated IMRS of 10 μM Rhodamine 6G in solution by IERS. The results show that ERS calibration generates a new analytical value, ISERS/IERS, insensitive to variations from different hotspots and thus can quantitatively reflect the molecular concentration information. Given the calibration capability of ERS signals, we performed label-free SERS analysis of living biological systems using four different breast normal and cancer cell lines cultured on nano-laminated SERS devices. 2D Raman mapping over 100 μm × 100 μm, containing several cells, was conducted. The SERS spectra were subsequently analyzed by multivariate analysis using partial least square discriminant analysis. Remarkably, after ERS calibration, MCF-10A and MCF-7 cells are further separated while the two triple-negative breast cancer cells (MDA-MB-231 and HCC-1806) are more overlapped, in good agreement with the well-known cancer categorization regarding the degree of malignancy. To assess the strength of ERS calibration, we further carried out a drug efficacy study using MDA-MB-231 and different concentrations of anti-cancer drug paclitaxel (PTX). After ERS calibration, we can more clearly segregate the control/low-dosage groups (0 and 1.5 nM), the middle-dosage group (5 nM), and the group treated with half-maximal inhibitory concentration (IC50, 15 nM). Therefore, we envision that ERS calibrated SERS can find crucial opportunities in label-free molecular profiling of complicated biological systems.

Keywords: cancer cell drug efficacy, plasmonics, surface-enhanced Raman spectroscopy (SERS), SERS calibration

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Authors: Dadash Huseynov, Elmira Aliyeva, Robert Hoogendoorn, Salomon Kroonenberg

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The study of organic material in bottom sediments together with lithologic and biostratigraphic data improves our understanding of the evolution of fluvial and deltaic systems. The modern Kura River delta is located in the Southwest Caspian Sea and is fluvial-dominated. The river distributes its sediment load through three channels oriented North-East, South-East, and South-West. The offshore modern delta consists of thinly bedded or laminated silty clays and dark grey clays. Locally sand and shell-rich horizons occur. Onshore delta is composed of channel-levee sands and floodplain silts and clays. Overall sedimentation rates in the delta determined by the 210Pb method range between 1.5-3.0 cm/yr. We investigated the distribution of organic material in the deltaic sediments in 300 samples selected from 3m deep piston cores. The studies of transparent sections demonstrate that deltaic sediments are enriched in terrestrial debris. It is non-transparent and has an irregular, isometric, or elongated shape, angular edges, black or dark-brown colour, and a clearly expressed fabric. Partially it is dissolved at the edges and is replaced by iron sulphides. Fragments of marine algae have more smooth edges, brown colour. They are transparent; the fabric is rarely preserved. The evidences of dissolution and gelification are well observed. Iron sulphides are common. The recorded third type of organic material has a round, drop-like, or oval shape and belongs to planktonic organisms. Their initial organic material is strongly transformed or replaced by dark organic compounds, probably, neoplasms. The particles are red-brown and transparent. The iron sulphides are not observed. The amount of Corg in the uppermost portion of sediments accumulated in the offshore Kura River delta varies from 0.2 to 1.22%, with median values of 0.6-0.8%. In poorly sorted sediments Corg content changes from 0.24 to 0.97% (average 0.69%), silty-sandy clay - 0.45 to 1.22% (average 0.77%), sandy-silty clay - 0.5 to 0.97% (average 0.67%), silty clay - 0.52 to 0.95% (average 0.70%). The data demonstrate that in sediments deposited during Caspian Sea high stand in 1929, the minimum of Corg content is localised near the mouth of the main south-eastern distributary channel and coincides with the minimum of the clay fraction. At the same time, the maximum of organic matter content locates near the mouth of the eastern channel, which was inactive at that time. In sediments accumulated during the last Caspian Sea low stand in 1977, the area of Corg minimum is attached to the north-eastern distributary’s mouth. It indicates the high activity of this distributary during the Caspian Sea fall. The area of Corg minimum is also recorded around the mouth of the main channel and eastern part of the delta. Maximums of Corg and clay fraction shift towards the basin. During the Caspian high stand in 1995, the minimum of Corg content is again observed in the mouth of the main south-eastern channel. The distribution of organic matter in the modern sediments of the Kura river delta displays the strong time dependence and reflects progradational-retrogradational cycles of evolution of this fluvial-deltaic system.

Keywords: high and low stands, Kura River delta, South Caspian Sea, organic matter

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

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

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

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Authors: Gagandeep Singh Digra, Pawan Kumar, Mandeep Kaur Sidhu

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INTRODUCTION: Chronic Progressive External Ophthalmoplegia (CPEO), also known as Progressive External Ophthalmoplegia (PEO), is a type of eye disorder characterized by a loss of the muscle functions involved in eye and eyelid movement. CPEO can be caused by mutations in mitochondrial DNA. It typically manifests in young adults with bilateral and progressive ptosis as the most common presentation but can also present with difficulty swallowing (dysphagia) and general weakness of the skeletal muscles (myopathy), particularly in the neck, arms, or legs. CASE PRESENTATION: This is a case discussion of 3 cousins who presented to our clinic. A 23-year-old male with past surgical history (PSH) of ptosis repair 2 years ago presented with a chief complaint of nasal intonation for 1.5 years associated with difficulty swallowing. The patient also complained of nasal regurgitation of liquids. He denied any headaches, fever, seizures, weakness of arms or legs, urinary complaints or changes in bowel habits. Physical Examination was positive for facial muscle weakness, including an inability to lift eyebrows (Frontalis), inability to close eyes tightly (Orbicularis Oculi), corneal reflex absent bilaterally, difficulty clenching jaw (Masseter muscle), difficulty smiling (Zygomaticus major), inability to elevate upper lip (Zygomaticus minor). Another cousin of the first patient, a 25-year-old male with no past medical history, presented with complaints of nasal intonation for 2 years associated with difficulty swallowing. He denied a history of nasal regurgitation, headaches, fever, seizures, weakness, urinary complaints or changes in bowel habits. Physical Examination showed facial muscle weakness of the Frontalis muscle, Orbicularis Oculi muscle, Masseter Muscle, Zygomaticus Major, Zygomaticus Minor and absent corneal reflexes. A 28-year-old male, a cousin of the first two patients, presented with chief complaints of ptosis and nasal intonation for the last 8 years. He also complained of difficulty swallowing and nasal regurgitation of liquids. His physical examination showed facial muscle weakness, including frontalis muscle (inability to lift eyebrows), Orbicularis Oculi (inability to close eyes tightly), absent corneal reflexes bilaterally, Zygomaticus Major (difficulty smiling), and Zygomaticus Minor (inability to elevate upper lip). MRI brain and visual field of all the patients were normal. Differential diagnoses, including Grave’s disease, Myasthenia Gravis and Glioma, were ruled out. Due to financial reasons, muscle biopsy could not be pursued. Pedigree analysis revealed only males were affected, likely due to maternal inheritance, so the clinical diagnosis of CPEO was made. The patients underwent symptomatic management, including ptosis surgical correction for the third patient. CONCLUSION: Chronic Progressive External Ophthalmoplegia (CPEO), a rare case entity, occurs in young adults as a manifestation of mitochondrial myopathy. There are three modes of transmission- maternal transmission associated with mitochondrial point mutations, autosomal recessive, and autosomal dominant. CPEO can sometimes be difficult to diagnose, especially in asymmetric presentation. Therefore, it is crucial to keep it in differential diagnosis to avoid delay in diagnosis.

Keywords: neurology, chronic, progressive, ophthalmoplegia

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Authors: Hyohun Kim, Dongwha Shin, Yeonseok Kim, Ji-Su Ahn, Kensuke Nakamura, Dongeun Choi, Byung-Woo Hong

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Artefacts are commonly encountered in the imaging process of clinical computed tomography (CT) where the artefact refers to any systematic discrepancy between the reconstructed observation and the true attenuation coefficient of the object. It is known that CT images are inherently more prone to artefacts due to its image formation process where a large number of independent detectors are involved, and they are assumed to yield consistent measurements. There are a number of different artefact types including noise, beam hardening, scatter, pseudo-enhancement, motion, helical, ring, and metal artefacts, which cause serious difficulties in reading images. Thus, it is desired to remove nuisance factors from the degraded image leaving the fundamental intrinsic information that can provide better interpretation of the anatomical and pathological characteristics. However, it is considered as a difficult task due to the high dimensionality and variability of data to be recovered, which naturally motivates the use of machine learning techniques. We propose an image restoration algorithm based on the deep neural network framework where the denoising auto-encoders are stacked building multiple layers. The denoising auto-encoder is a variant of a classical auto-encoder that takes an input data and maps it to a hidden representation through a deterministic mapping using a non-linear activation function. The latent representation is then mapped back into a reconstruction the size of which is the same as the size of the input data. The reconstruction error can be measured by the traditional squared error assuming the residual follows a normal distribution. In addition to the designed loss function, an effective regularization scheme using residual-driven dropout determined based on the gradient at each layer. The optimal weights are computed by the classical stochastic gradient descent algorithm combined with the back-propagation algorithm. In our algorithm, we initially decompose an input image into its intrinsic representation and the nuisance factors including artefacts based on the classical Total Variation problem that can be efficiently optimized by the convex optimization algorithm such as primal-dual method. The intrinsic forms of the input images are provided to the deep denosing auto-encoders with their original forms in the training phase. In the testing phase, a given image is first decomposed into the intrinsic form and then provided to the trained network to obtain its reconstruction. We apply our algorithm to the restoration of the corrupted CT images by the artefacts. It is shown that our algorithm improves the readability and enhances the anatomical and pathological properties of the object. The quantitative evaluation is performed in terms of the PSNR, and the qualitative evaluation provides significant improvement in reading images despite degrading artefacts. The experimental results indicate the potential of our algorithm as a prior solution to the image interpretation tasks in a variety of medical imaging applications. This work was supported by the MISP(Ministry of Science and ICT), Korea, under the National Program for Excellence in SW (20170001000011001) supervised by the IITP(Institute for Information and Communications Technology Promotion).

Keywords: auto-encoder neural network, CT image artefact, deep learning, intrinsic image representation, noise reduction, total variation

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Authors: Nikhilesh Singh, Shishir Gaur, Anitha K. Sharma

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Climate change and anthropogenic stress have severely affected ecosystems all over the globe. Indian rivers are under immense pressure, facing challenges like pollution, encroachment, extreme fluctuation in the flow regime, local ignorance and lack of coordination between stakeholders. To counter all these issues a holistic river rejuvenation plan is needed that tests, innovates and implements sustainable solutions in the river space for sustainable river management. Smart Laboratory for Clean Rivers (SLCR) an Indo-Danish collaboration project, provides a living lab setup that brings all the stakeholders (government agencies, academic and industrial partners and locals) together to engage, learn, co-creating and experiment for a clean and sustainable river that last for ages. Just like every mega project requires piloting, SLCR has opted for a small catchment of the Varuna River, located in the Middle Ganga Basin in India. Considering the integrated approach of river rejuvenation, SLCR embraces various techniques and upgrades for rejuvenation. Likely, maintaining flow in the channel in the lean period, Managed Aquifer Recharge (MAR) is a proven technology. In SLCR, Floa-TEM high-resolution lithological data is used in MAR models to have better decision-making for MAR structures nearby of the river to enhance the river aquifer exchanges. Furthermore, the concerns of quality in the river are a big issue. A city like Varanasi which is located in the last stretch of the river, generates almost 260 MLD of domestic waste in the catchment. The existing STP system is working at full efficiency. Instead of installing a new STP for the future, SLCR is upgrading those STPs with an IoT-based system that optimizes according to the nutrient load and energy consumption. SLCR also advocate nature-based solutions like a reed bed for the drains having less flow. In search of micropollutants, SLCR uses fingerprint analysis involves employing advanced techniques like chromatography and mass spectrometry to create unique chemical profiles. However, rejuvenation attempts cannot be possible without involving the entire catchment. A holistic water management plan that includes storm management, water harvesting structure to efficiently manage the flow of water in the catchment and installation of several buffer zones to restrict pollutants entering into the river. Similarly, carbon (emission and sequestration) is also an important parameter for the catchment. By adopting eco-friendly practices, a ripple effect positively influences the catchment's water dynamics and aids in the revival of river systems. SLCR has adopted 4 villages to make them carbon-neutral and water-positive. Moreover, for the 24×7 monitoring of the river and the catchment, robust IoT devices are going to be installed to observe, river and groundwater quality, groundwater level, river discharge and carbon emission in the catchment and ultimately provide fuel for the data analytics. In its completion, SLCR will provide a river restoration manual, which will strategise the detailed plan and way of implementation for stakeholders. Lastly, the entire process is planned in such a way that will be managed by local administrations and stakeholders equipped with capacity-building activity. This holistic approach makes SLCR unique in the field of river rejuvenation.

Keywords: sustainable management, holistic approach, living lab, integrated river management

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

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

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

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Authors: Mohsen Abdelrazek Khorshid Ali Selim

Abstract:

Disadvantages and errors of current concrete reinforcement methodsL: Current concrete reinforcement methods are adopted in most parts of the world in their various doctrines and names. They adopt the so-called concrete slab system, where these slabs are semi-independent and isolated from each other and from the surrounding environment of concrete columns or beams, so that the reinforcing steel does not cross from one slab to another or from one slab to adjacent columns. It or the beams surrounding it and vice versa are only a few centimeters and no more. The same applies exactly to the concrete columns that support the building, where the reinforcing steel does not extend from the slabs or beams to the inside of the columns or vice versa except for a few centimeters and no more, just as the reinforcing steel does not extend from inside the column at the top. The ceiling is only a few centimetres, and the same thing is literally repeated in the concrete beams that connect the columns and separate the slabs, where the reinforcing steel does not cross from one beam to another or from one beam to the slabs or columns adjacent to it and vice versa, except for a few centimeters, which makes the basic building elements of columns, slabs and beams They all work in isolation from each other and from the environment surrounding them from all sides. This traditional method of reinforcement may be valid and lasting in geographical areas that are not exposed to earthquakes and earthquakes, where all the loads and tensile forces in the building are constantly directed vertically downward due to gravity and are borne directly by the vertical reinforcement of the building. However, in the case of earthquakes and earthquakes, the loads and tensile forces in the building shift from the vertical direction to the horizontal direction at an angle of inclination that depends on the strength of the earthquake, and most of them are borne by the horizontal reinforcement extending between the basic elements of the building, such as columns, slabs and beams, and since the crossing of the reinforcement between each of the columns, slabs and beams between them And each other, and vice versa, does not exceed several centimeters. In any case, the tensile strength, cohesion and bonding between the various parts of the building are very weak, which causes the buildings to disintegrate and collapse in the horrific manner that we saw in the earthquake in Turkey and Syria in February 2023, which caused the collapse of tens of thousands of buildings in A few seconds later, it left more than 50,000 dead, hundreds of thousands injured, and millions displaced. Description of the new earthquake-resistant model: The idea of the new model in the reinforcement of concrete buildings and constructions is based on the theory that we have formulated as follows: [The tensile strength, cohesion and bonding between the basic parts of the concrete building (columns, beams and slabs) increases as the lengths of the reinforcing steel bars increase and they extend and branch and the different parts of the building share them with each other.] . In other words, the strength, solidity, and cohesion of concrete buildings increase and they become resistant to earthquakes as the lengths of the reinforcing steel bars increase, extend, branch, and share with the various parts of the building, such as columns, beams, and slabs. That is, the reinforcing skewers of the columns must extend in their lengths without cutting to cross from one floor to another until their end. Likewise, the reinforcing skewers of the beams must extend in their lengths without cutting to cross from one beam to another. The ends of these skewers must rest at the bottom of the columns adjacent to the beams. The same thing applies to the reinforcing skewers of the slabs where they must These skewers should be extended in their lengths without cutting to cross from one tile to another, and the ends of these skewers should rest either under the adjacent columns or inside the beams adjacent to the slabs as follows: First, reinforce the columns: The columns have the lion's share of the reinforcing steel in this model in terms of type and quantity, as the columns contain two types of reinforcing bars. The first type is large-diameter bars that emerge from the base of the building, which are the nerves of the column. These bars must extend over their normal length of 12 meters or more and extend to a height of three floors, if desired. In raising other floors, bars with the same diameter and the same length are added to the top after the second floor. The second type is bars with a smaller diameter, and they are the same ones that are used to reinforce beams and slabs, so that the bars that reinforce the beams and slabs facing each column are bent down inside this column and along the entire length of the column. This requires an order. Most engineers do not prefer it, which is to pour the entire columns and pour the roof at once, but we prefer this method because it enables us to extend the reinforcing bars of both the beams and slabs to the bottom of the columns so that the entire building becomes one concrete block that is cohesive and resistant to earthquakes. Secondly, arming the cameras: The beams' reinforcing skewers must also extend to a full length of 12 meters or more without cutting. The ends of the skewers are bent and dropped inside the column at the beginning of the beam to its bottom. Then the skewers are extended inside the beam so that their other end falls under the facing column at the end of the beam. The skewers may cross over the head of a column. Another passes through another adjacent beam and rests at the bottom of a third column, according to the lengths of each of the skewers and beams. Third, reinforcement of slabs: The slab reinforcing skewers must also extend their entire length, 12 meters or more, without cutting, distinguishing between two cases. The first case is the skewers opposite the columns, and their ends are dropped inside one of the columns. Then the skewers cross inside the adjacent slab and their other end falls below the opposite column. The skewers may cross over The head of the adjacent column passes through another adjacent slab and rests at the bottom of a third column, according to the dimensions of the slabs and the lengths of the skewers. The second case is the skewers opposite the beams, and their ends must be bent in the form of a square or rectangle according to the dimensions of the beam’s width and height, and this square or rectangle is dropped inside the beam at the beginning of the slab, and it serves as The skewers are for the beams, then the skewers are extended along the length of the slab, and at the end of the slab, the skewers are bent down to the bottom of the adjacent beam in the shape of the letter U, after which the skewers are extended inside the adjacent slab, and this is repeated in the same way inside the other adjacent beams until the end of the skewer, then it is bent downward in the form of a square or rectangle inside the beam, as happened. In its beginning.

Keywords: earthquake resistant buildings, earthquake resistant concrete constructions, new technology for reinforcement of concrete buildings, new technology in concrete reinforcement

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