Search results for: multiple cranial nerve impairment
5112 Muscle Relaxant Dantrolene Repurposed to Treat Alzheimer's Disease
Authors: Huafeng Wei
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Failures of developing new drugs primarily based on the amyloid pathology hypothesis after decades of efforts internationally lead to changes of focus targeting alternative pathways of pathology in Alzheimer’s disease (AD). Disruption of intracellular Ca2+ homeostasis, especially the pathological and excessive Ca2+ release from the endoplasmic reticulum (ER) via ryanodine receptor (RyRs) Ca2+ channels, has been considered an upstream pathology resulting in major AD pathologies, such as amyloid and Tau pathology, mitochondria damage and inflammation, etc. Therefore, dantrolene, an inhibitor of RyRs that reduces the pathological Ca2+ release from ER and a clinically available drug for the treatment of malignant hyperthermia and muscle spasm, is expected to ameliorate AD multiple pathologies synapse and cognitive dysfunction. Our own studies indicated that dantrolene ameliorated impairment of neurogenesis and synaptogenesis in neurons developed from induced pluripotent stem cells (iPSCs) originated from skin fibroblasts of either familiar (FAD) or sporadic (SAD) AD by restoring intracellular Ca2+ homeostasis. Intranasal administration of dantrolene significantly increased its passage across the blood-brain barrier (BBB) and, therefore its brain concentrations and durations. This can render dantrolene a more effective therapeutic drug with fewer side effects for chronic AD treatment. This review summarizes the potential therapeutic and side effects of dantrolene and repurposes intranasal dantrolene as a disease-modifying drug for future AD treatment.Keywords: Alzheimer's disease, calcium, drug development, dementia, neurodegeneration, neurogenesis
Procedia PDF Downloads 2095111 2D Numerical Modeling of Ultrasonic Measurements in Concrete: Wave Propagation in a Multiple-Scattering Medium
Authors: T. Yu, L. Audibert, J. F. Chaix, D. Komatitsch, V. Garnier, J. M. Henault
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Linear Ultrasonic Techniques play a major role in Non-Destructive Evaluation (NDE) for civil engineering structures in concrete since they can meet operational requirements. Interpretation of ultrasonic measurements could be improved by a better understanding of ultrasonic wave propagation in a multiple scattering medium. This work aims to develop a 2D numerical model of ultrasonic wave propagation in a heterogeneous medium, like concrete, integrating the multiple scattering phenomena in SPECFEM software. The coherent field of multiple scattering is obtained by averaging numerical wave fields, and it is used to determine the effective phase velocity and attenuation corresponding to an equivalent homogeneous medium. First, this model is applied to one scattering element (a cylinder) in a homogenous medium in a linear-elastic system, and its validation is completed thanks to the comparison with analytical solution. Then, some cases of multiple scattering by a set of randomly located cylinders or polygons are simulated to perform parametric studies on the influence of frequency and scatterer size, concentration, and shape. Also, the effective properties are compared with the predictions of Waterman-Truell model to verify its validity. Finally, the mortar viscoelastic behavior is introduced in the simulation in order to considerer the dispersion and the attenuation due to porosity included in the cement paste. In the future, different steps will be developed: The comparisons with experimental results, the interpretation of NDE measurements, and the optimization of NDE parameters before an auscultation.Keywords: attenuation, multiple-scattering medium, numerical modeling, phase velocity, ultrasonic measurements
Procedia PDF Downloads 2765110 Specific Language Impirment in Kannada: Evidence Form a Morphologically Complex Language
Authors: Shivani Tiwari, Prathibha Karanth, B. Rajashekhar
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Impairments of syntactic morphology are often considered central in children with Specific Language Impairment (SLI). In English and related languages, deficits of tense-related grammatical morphology could serve as a clinical marker of SLI. Yet, cross-linguistic studies on SLI in the recent past suggest that the nature and severity of morphosyntactic deficits in children with SLI varies with the language being investigated. Therefore, in the present study we investigated the morphosyntactic deficits in a group of children with SLI who speak Kannada, a morphologically complex Dravidian language spoken in Indian subcontinent. A group of 15 children with SLI participated in this study. Two more groups of typical developing children (15 each) matched for language and age to children with SLI, were included as control participants. All participants were assessed for morphosyntactic comprehension and expression using standardized language test and a spontaneous speech task. Results of the study showed that children with SLI differed significantly from age-matched but not language-matched control group, on tasks of both comprehension and expression of morphosyntax. This finding is, however, in contrast with the reports of English-speaking children with SLI who are reported to be poorer than younger MLU-matched children on tasks of morphosyntax. The observed difference in impairments of morphosyntax in Kannada-speaking children with SLI from English-speaking children with SLI is explained based on the morphological richness theory. The theory predicts that children with SLI perform relatively better in morphologically rich language due to occurrence of their frequent and consistent features that mark the morphological markers. The authors, therefore, conclude that language-specific features do influence manifestation of the disorder in children with SLI.Keywords: specific language impairment, morphosyntax, Kannada, manifestation
Procedia PDF Downloads 2445109 Correlation Between Diastolic Function and Lower GLS in Hypertensive Patients
Authors: A. Kherraf, S. Ouarrak, L. Azzouzi, R. Habbal
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Introduction: Preserved LVEF heart failure is an important cause of mortality and morbidity in hypertensive patients. A strong correlation between impaired diastolic function and longitudinal systolic dysfunction. could have several explanations, first, the diastole is an energy dependent process, especially during its first phase, it also includes active systolic components during the phase of iso volumetric relaxation, in addition, the impairment of the intrinsic myocytic function is part of hypertensive pathology as evidenced by recent studies. METHODS AND MATERIALS: This work consists of performing in a series of 333 hypertensive patients (aged 25 to 75 years) a complete echocardiographic study, including LVEF by Simpson biplane method, the calculation of the indexed left ventricular mass, the analysis of the diastolic function, and finally, the study of the longitudinal deformation of the LV by the technique of speckletracking (calculation of the GLS). Patients with secondary hypertension, leaky or stenosing valve disease, arrhythmia, and a history of coronary insufficiency were excluded from this study. RESULTS: Of the 333 hypertensive patients, 225 patients (67.5%) had impaired diastolic function, of which 60 patients (18%) had high filling pressures. 49.39% had echocardigraphic HVG, Almost all of these patients (60 patients) had low GLS. There is a statistically very significant relationship between lower GLS and increased left ventricular filling pressures in hypertensive patients. These results suggest that increased filling pressures are closely associated with atrioventricular interaction in patients with hypertension, with a strong correlation with impairment of longitudinal systolic function and diastolic function CONCLUSION: Overall, a linear relationship is established between increased left ventricular mass, diastolic dysfunction, and longitudinal LV systolic dysfunctionKeywords: hypertension, diastolic function, left ventricle, heart failure
Procedia PDF Downloads 1275108 Study on a Family of Optimal Fourth-Order Multiple-Root Solver
Authors: Young Hee Geum
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In this paper,we develop the complex dynamics of a family of optimal fourth-order multiple-root solvers and plot their basins of attraction. Mobius conjugacy maps and extraneous fixed points applied to a prototype quadratic polynomial raised to the power of the known integer multiplicity m are investigated. A 300 x 300 uniform grid centered at the origin covering 3 x 3 square region is chosen to visualize the initial values on each basin of attraction in accordance with a coloring scheme based on their dynamical behavior. The illustrative basins of attractions applied to various test polynomials and the corresponding statistical data for convergence are shown to confirm the theoretical convergence.Keywords: basin of attraction, conjugacy, fourth-order, multiple-root finder
Procedia PDF Downloads 2945107 External Validation of Established Pre-Operative Scoring Systems in Predicting Response to Microvascular Decompression for Trigeminal Neuralgia
Authors: Kantha Siddhanth Gujjari, Shaani Singhal, Robert Andrew Danks, Adrian Praeger
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Background: Trigeminal neuralgia (TN) is a heterogenous pain syndrome characterised by short paroxysms of lancinating facial pain in the distribution of the trigeminal nerve, often triggered by usually innocuous stimuli. TN has a low prevalence of less than 0.1%, of which 80% to 90% is caused by compression of the trigeminal nerve from an adjacent artery or vein. The root entry zone of the trigeminal nerve is most sensitive to neurovascular conflict (NVC), causing dysmyelination. Whilst microvascular decompression (MVD) is an effective treatment for TN with NVC, all patients do not achieve long-term pain relief. Pre-operative scoring systems by Panczykowski and Hardaway have been proposed but have not been externally validated. These pre-operative scoring systems are composite scores calculated according to a subtype of TN, presence and degree of neurovascular conflict, and response to medical treatments. There is discordance in the assessment of NVC identified on pre-operative magnetic resonance imaging (MRI) between neurosurgeons and radiologists. To our best knowledge, the prognostic impact for MVD of this difference of interpretation has not previously been investigated in the form of a composite scoring system such as those suggested by Panczykowski and Hardaway. Aims: This study aims to identify prognostic factors and externally validate the proposed scoring systems by Panczykowski and Hardaway for TN. A secondary aim is to investigate the prognostic difference between a neurosurgeon's interpretation of NVC on MRI compared with a radiologist’s. Methods: This retrospective cohort study included 95 patients who underwent de novo MVD in a single neurosurgical unit in Melbourne. Data was recorded from patients’ hospital records and neurosurgeon’s correspondence from perioperative clinic reviews. Patient demographics, type of TN, distribution of TN, response to carbamazepine, neurosurgeon, and radiologist interpretation of NVC on MRI, were clearly described prospectively and preoperatively in the correspondence. Scoring systems published by Panczykowski et al. and Hardaway et al. were used to determine composite scores, which were compared with the recurrence of TN recorded during follow-up over 1-year. Categorical data analysed using Pearson chi-square testing. Independent numerical and nominal data analysed with logistical regression. Results: Logistical regression showed that a Panczykowski composite score of greater than 3 points was associated with a higher likelihood of pain-free outcome 1-year post-MVD with an OR 1.81 (95%CI 1.41-2.61, p=0.032). The composite score using neurosurgeon’s impression of NVC had an OR 2.96 (95%CI 2.28-3.31, p=0.048). A Hardaway composite score of greater than 2 points was associated with a higher likelihood of pain-free outcome 1 year post-MVD with an OR 3.41 (95%CI 2.58-4.37, p=0.028). The composite score using neurosurgeon’s impression of NVC had an OR 3.96 (95%CI 3.01-4.65, p=0.042). Conclusion: Composite scores developed by Panczykowski and Hardaway were validated for the prediction of response to MVD in TN. A composite score based on the neurosurgeon’s interpretation of NVC on MRI, when compared with the radiologist’s had a greater correlation with pain-free outcomes 1 year post-MVD.Keywords: de novo microvascular decompression, neurovascular conflict, prognosis, trigeminal neuralgia
Procedia PDF Downloads 745106 Efficacy and Safety of Computerized Cognitive Training Combined with SSRIs for Treating Cognitive Impairment Among Patients with Late-Life Depression: A 12-Week, Randomized Controlled Study
Authors: Xiao Wang, Qinge Zhang
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Background: This randomized, open-label study examined the therapeutic effects of computerized cognitive training (CCT) combined with selective serotonin reuptake inhibitors (SSRIs) on cognitive impairment among patients with late-life depression (LLD). Method: Study data were collected from May 5, 2021, to April 21, 2023. Outpatients who met diagnostic criteria for major depressive disorder according to the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria (i.e., a total score on the 17-item Hamilton Depression Rating Scale (HAMD-17) ≥ 18 and a total score on the Montreal Cognitive Assessment scale (MOCA) <26) were randomly assigned to receive up to 12 weeks of CCT and SSRIs treatment (n=57) or SSRIs and Control treatment (n=61). The primary outcome was the change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores from baseline to week 12 between the two groups. The secondary outcomes included changes in the HAMD-17 score, Hamilton Anxiety Scale (HAMA) score and Neuropsychiatric Inventory (NPI) score. Mixed model repeated measures (MMRM) analysis was performed on modified intention-to-treat (mITT) and completer populations. Results: The full analysis set (FAS) included 118 patients (CCT and SSRIs group, n=57; SSRIs and Control group, n =61). Over the 12-week study period, the reduction in the ADAS-cog total score was significant (P < 0.001) in both groups, while MMRM analysis revealed a significantly greater reduction in cognitive function (ADAS-cog total scores) from baseline to posttreatment in the CCT and SSRIs group than in the SSRI and Control group [(F (1,115) =13.65, least-squares mean difference [95% CI]: −2.77 [−3.73, −1.81], p<0.001)]. There were significantly greater improvements in depression symptoms (measured by the HAMD-17) in the CCT and SSRIs group than in the control group [MMRM, estimated mean difference (SE) between groups −3.59 [−5.02, −2.15], p < 0.001]. The least-squares mean changes in the HAMA scores and NPI scores between baseline and week 8 were greater in the CCT and SSRIs group than in the control group (all P < 0.05). There was no significant difference between groups on response rates and remission rates by using the last-observation-carried-forward (LOCF) method (all P > 0.05). The most frequent adverse events (AEs) in both groups were dry mouth, somnolence, and constipation. There was no significant difference in the incidence of adverse events between the two groups. Conclusions: CCT combined with SSRIs was efficacious and well tolerated in LLD patients with cognitive impairment.Keywords: late-life depression, cognitive function, computerized cognitive training, SSRIs
Procedia PDF Downloads 555105 Causes of Blindness and Low Vision among Visually Impaired Population Supported by Welfare Organization in Ardabil Province in Iran
Authors: Mohammad Maeiyat, Ali Maeiyat Ivatlou, Rasul Fani Khiavi, Abouzar Maeiyat Ivatlou, Parya Maeiyat
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Purpose: Considering the fact that visual impairment is still one of the countries health problem, this study was conducted to determine the causes of blindness and low vision in visually impaired membership of Ardabil Province welfare organization. Methods: The present study which was based on descriptive and national-census, that carried out in visually impaired population supported by welfare organization in all urban and rural areas of Ardabil Province in 2013 and Collection of samples lasted for 7 months. The subjects were inspected by optometrist to determine their visual status (blindness or low vision) and then referred to ophthalmologist in order to discover the main causes of visual impairment based on the international classification of diseases version 10. Statistical analysis of collected data was performed using SPSS software version 18. Results: Overall, 403 subjects with mean age of years participated in this study. 73.2% were blind, 26.8 % were low vision and according gender grouping 60.50 % of them were male, 39.50 % were female that divided into three groups with the age level of lower than 15 (11.2%) 15 to 49 (76.7%), and 50 and higher (12.1%). The age range was 1 to 78 years. The causes of blindness and low vision were in descending order: optic atrophy (18.4%), retinitis pigmentosa (16.8%), corneal diseases (12.4%), chorioretinal diseases (9.4%), cataract (8.9%), glaucoma (8.2%), phthisis bulbi (7.2%), degenerative myopia (6.9%), microphtalmos ( 4%), amblyopia (3.2%), albinism (2.5%) and nistagmus (2%). Conclusion: in this study the main causes of visual impairments were optic atrophy and retinitis pigmentosa, thus specific prevention plans can be effective in reducing the incidence of visual disabilities.Keywords: blindness, low vision, welfare, ardabil
Procedia PDF Downloads 4405104 Identification of Outliers in Flood Frequency Analysis: Comparison of Original and Multiple Grubbs-Beck Test
Authors: Ayesha S. Rahman, Khaled Haddad, Ataur Rahman
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At-site flood frequency analysis is used to estimate flood quantiles when at-site record length is reasonably long. In Australia, FLIKE software has been introduced for at-site flood frequency analysis. The advantage of FLIKE is that, for a given application, the user can compare a number of most commonly adopted probability distributions and parameter estimation methods relatively quickly using a windows interface. The new version of FLIKE has been incorporated with the multiple Grubbs and Beck test which can identify multiple numbers of potentially influential low flows. This paper presents a case study considering six catchments in eastern Australia which compares two outlier identification tests (original Grubbs and Beck test and multiple Grubbs and Beck test) and two commonly applied probability distributions (Generalized Extreme Value (GEV) and Log Pearson type 3 (LP3)) using FLIKE software. It has been found that the multiple Grubbs and Beck test when used with LP3 distribution provides more accurate flood quantile estimates than when LP3 distribution is used with the original Grubbs and Beck test. Between these two methods, the differences in flood quantile estimates have been found to be up to 61% for the six study catchments. It has also been found that GEV distribution (with L moments) and LP3 distribution with the multiple Grubbs and Beck test provide quite similar results in most of the cases; however, a difference up to 38% has been noted for flood quantiles for annual exceedance probability (AEP) of 1 in 100 for one catchment. These findings need to be confirmed with a greater number of stations across other Australian states.Keywords: floods, FLIKE, probability distributions, flood frequency, outlier
Procedia PDF Downloads 4525103 Student Performance and Confidence Analysis on Education Virtual Environments through Different Assessment Strategies
Authors: Rubén Manrique, Delio Balcázar, José Parrado, Sebastián Rodríguez
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Hand in hand with the evolution of technology, education systems have moved to virtual environments to provide increased coverage and facilitate the access to education. However, measuring student performance in virtual environments presents significant challenges to ensure students are acquiring the expected skills. In this study, the confidence and performance of engineering students in virtual environments is analyzed through different evaluation strategies. The effect of the assessment strategy in student confidence is identified using educational data mining techniques. Four assessment strategies were used. First, a conventional multiple choice test; second, a multiple choice test with feedback; third, a multiple choice test with a second chance; and fourth; a multiple choice test with feedback and second chance. Our results show that applying testing with online feedback strategies can influence positively student confidence.Keywords: assessment strategies, educational data mining, student performance, student confidence
Procedia PDF Downloads 3545102 Cooperative CDD Scheme Based On Hierarchical Modulation in OFDM System
Authors: Seung-Jun Yu, Yeong-Seop Ahn, Young-Min Ko, Hyoung-Kyu Song
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In order to achieve high data rate and increase the spectral efficiency, multiple input multiple output (MIMO) system has been proposed. However, multiple antennas are limited by size and cost. Therefore, recently developed cooperative diversity scheme, which profits the transmit diversity only with the existing hardware by constituting a virtual antenna array, can be a solution. However, most of the introduced cooperative techniques have a common fault of decreased transmission rate because the destination should receive the decodable compositions of symbols from the source and the relay. In this paper, we propose a cooperative cyclic delay diversity (CDD) scheme that uses hierarchical modulation. This scheme is free from the rate loss and allows seamless cooperative communication.Keywords: MIMO, cooperative communication, CDD, hierarchical modulation
Procedia PDF Downloads 5505101 Design and Performance Improvement of Three-Dimensional Optical Code Division Multiple Access Networks with NAND Detection Technique
Authors: Satyasen Panda, Urmila Bhanja
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In this paper, we have presented and analyzed three-dimensional (3-D) matrices of wavelength/time/space code for optical code division multiple access (OCDMA) networks with NAND subtraction detection technique. The 3-D codes are constructed by integrating a two-dimensional modified quadratic congruence (MQC) code with one-dimensional modified prime (MP) code. The respective encoders and decoders were designed using fiber Bragg gratings and optical delay lines to minimize the bit error rate (BER). The performance analysis of the 3D-OCDMA system is based on measurement of signal to noise ratio (SNR), BER and eye diagram for a different number of simultaneous users. Also, in the analysis, various types of noises and multiple access interference (MAI) effects were considered. The results obtained with NAND detection technique were compared with those obtained with OR and AND subtraction techniques. The comparison results proved that the NAND detection technique with 3-D MQC\MP code can accommodate more number of simultaneous users for longer distances of fiber with minimum BER as compared to OR and AND subtraction techniques. The received optical power is also measured at various levels of BER to analyze the effect of attenuation.Keywords: Cross Correlation (CC), Three dimensional Optical Code Division Multiple Access (3-D OCDMA), Spectral Amplitude Coding Optical Code Division Multiple Access (SAC-OCDMA), Multiple Access Interference (MAI), Phase Induced Intensity Noise (PIIN), Three Dimensional Modified Quadratic Congruence/Modified Prime (3-D MQC/MP) code
Procedia PDF Downloads 4135100 The Predictive Utility of Subjective Cognitive Decline Using Item Level Data from the Everyday Cognition (ECog) Scales
Authors: J. Fox, J. Randhawa, M. Chan, L. Campbell, A. Weakely, D. J. Harvey, S. Tomaszewski Farias
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Early identification of individuals at risk for conversion to dementia provides an opportunity for preventative treatment. Many older adults (30-60%) report specific subjective cognitive decline (SCD); however, previous research is inconsistent in terms of what types of complaints predict future cognitive decline. The purpose of this study is to identify which specific complaints from the Everyday Cognition Scales (ECog) scales, a measure of self-reported concerns for everyday abilities across six cognitive domains, are associated with: 1) conversion from a clinical diagnosis of normal to either MCI or dementia (categorical variable) and 2) progressive cognitive decline in memory and executive function (continuous variables). 415 cognitively normal older adults were monitored annually for an average of 5 years. Cox proportional hazards models were used to assess associations between self-reported ECog items and progression to impairment (MCI or dementia). A total of 114 individuals progressed to impairment; the mean time to progression was 4.9 years (SD=3.4 years, range=0.8-13.8). Follow-up models were run controlling for depression. A subset of individuals (n=352) underwent repeat cognitive assessments for an average of 5.3 years. For those individuals, mixed effects models with random intercepts and slopes were used to assess associations between ECog items and change in neuropsychological measures of episodic memory or executive function. Prior to controlling for depression, subjective concerns on five of the eight Everyday Memory items, three of the nine Everyday Language items, one of the seven Everyday Visuospatial items, two of the five Everyday Planning items, and one of the six Everyday Organization items were associated with subsequent diagnostic conversion (HR=1.25 to 1.59, p=0.003 to 0.03). However, after controlling for depression, only two specific complaints of remembering appointments, meetings, and engagements and understanding spoken directions and instructions were associated with subsequent diagnostic conversion. Episodic memory in individuals reporting no concern on ECog items did not significantly change over time (p>0.4). More complaints on seven of the eight Everyday Memory items, three of the nine Everyday Language items, and three of the seven Everyday Visuospatial items were associated with a decline in episodic memory (Interaction estimate=-0.055 to 0.001, p=0.003 to 0.04). Executive function in those reporting no concern on ECog items declined slightly (p <0.001 to 0.06). More complaints on three of the eight Everyday Memory items and three of the nine Everyday Language items were associated with a decline in executive function (Interaction estimate=-0.021 to -0.012, p=0.002 to 0.04). These findings suggest that specific complaints across several cognitive domains are associated with diagnostic conversion. Specific complaints in the domains of Everyday Memory and Language are associated with a decline in both episodic memory and executive function. Increased monitoring and treatment of individuals with these specific SCD may be warranted.Keywords: alzheimer’s disease, dementia, memory complaints, mild cognitive impairment, risk factors, subjective cognitive decline
Procedia PDF Downloads 805099 Central Nervous System Lesion Differentiation in the Emergency Radiology Department
Authors: Angelis P. Barlampas
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An 89 years old woman came to the emergency department complaining of long-lasting headaches and nausea. A CT examination was performed, and a homogeneous midline anterior cranial fossa lesion was revealed, which was situated near the base and measured 2,4 cm in diameter. The patient was allergic, and an i.v.c injection could not be done on the spot, and neither could an MRI exam because of metallic implants. How could someone narrow down the differential diagnosis? The interhemispheric meningioma is usually a silent midline lesion with no edema, and most often presents as a homogeneous, solid type, isodense, or slightly hyperdense mass ( usually the smallest lesions as this one ). Of them, 20-30% have some calcifications. Hyperostosis is typical for meningiomas that abut the base of the skull but is absent in the current case, presumably of a more cephalad location that is borderline away from the bone. Because further investigation could not be done, as the patient was allergic to the contrast media, some other differential options should be considered. Regarding the site of the lesion, the most common other entities to keep in mind are the following: Metastasis, tumor of skull base, abscess, primary brain tumors, meningioma, giant aneurysm of the anterior cerebral artery, olfactory neuroblastoma, interhemispheric meningioma, giant aneurysm of the anterior cerebral artery, midline lesion. Appearance will depend on whether the aneurysm is non-thrombosed, or partially, or completely thrombosed. Non-contrast: slightly hyperdense, well-defined round extra-axial mass, may demonstrate a peripheral calcified rim, olfactory neuroblastoma, midline lesion. The mass is of soft tissue attenuation and is relatively homogeneous. Focal calcifications are occasionally present. When an intracranial extension is present, peritumoral cysts between it and the overlying brain are often present. Final diagnosis interhemispheric meningioma (Known from the previous patient’s history). Meningiomas come from the meningocytes or the arachnoid cells of the meninges. They are usually found incidentally, have an indolent course, and their most common location is extra-axial, parasagittal, and supratentorial. Other locations include the sphenoid ridge, olfactory groove, juxtasellar, infratentorial, intraventricular, pineal gland area, and optic nerve meningioma. They are clinically silent entities, except for large ones, which can present with headaches, changes in personality status, paresis, or symptomatology according to their specific site and may cause edema of the surrounding brain tissue. Imaging findings include the presence of calcifications, the CSF cleft sign, hyperostosis of adjacent bone, dural tail, and white matter buckling sign. After i.v.c. injection, they enhance brightly and homogenously, except for large ones, which may exhibit necrotic areas or may be heavily calcified. Malignant or cystic variants demonstrate more heterogeneity and less intense enhancement. Sometimes, it is inevitable that the needed CT protocol cannot be performed, especially in the emergency department. In these cases, the radiologist must focus on the characteristic imaging features of the unenhanced lesion, as well as in previous examinations or a known lesion history, in order to come to the right report conclusion.Keywords: computed tomography, emergency radiology, metastasis, tumor of skull base, abscess, primary brain tumors, meningioma, giant aneurysm of the anterior cerebral artery, olfactory neuroblastoma, interhemispheric meningioma
Procedia PDF Downloads 695098 Impact of Transgenic Adipose Derived Stem Cells in the Healing of Spinal Cord Injury of Dogs
Authors: Imdad Ullah Khan, Yongseok Yoon, Kyeung Uk Choi, Kwang Rae Jo, Namyul Kim, Eunbee Lee, Wan Hee Kim, Oh-Kyeong Kweon
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The primary spinal cord injury (SCI) causes mechanical damage to the neurons and blood vessels. It leads to secondary SCI, which activates multiple pathological pathways, which expand neuronal damage at the injury site. It is characterized by vascular disruption, ischemia, excitotoxicity, oxidation, inflammation, and apoptotic cell death. It causes nerve demyelination and disruption of axons, which perpetuate a loss of impulse conduction through the injured spinal cord. It also leads to the production of myelin inhibitory molecules, which with a concomitant formation of an astroglial scar, impede axonal regeneration. The pivotal role regarding the neuronal necrosis is played by oxidation and inflammation. During an early stage of spinal cord injury, there occurs an abundant expression of reactive oxygen species (ROS) due to defective mitochondrial metabolism and abundant migration of phagocytes (macrophages, neutrophils). ROS cause lipid peroxidation of the cell membrane, and cell death. Abundant migration of neutrophils, macrophages, and lymphocytes collectively produce pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1beta (IL-1β), matrix metalloproteinase, superoxide dismutase, and myeloperoxidases which synergize neuronal apoptosis. Therefore, it is crucial to control inflammation and oxidation injury to minimize the nerve cell death during secondary spinal cord injury. Therefore, in response to oxidation and inflammation, heme oxygenase-1 (HO-1) is induced by the resident cells to ameliorate the milieu. In the meanwhile, neurotrophic factors are induced to promote neuroregeneration. However, it seems that anti-stress enzyme (HO-1) and neurotrophic factor (BDNF) do not significantly combat the pathological events during secondary spinal cord injury. Therefore, optimum healing can be induced if anti-inflammatory and neurotrophic factors are administered in a higher amount through an exogenous source. During the first experiment, the inflammation and neuroregeneration were selectively targeted. HO-1 expressing MSCs (HO-1 MSCs) and BDNF expressing MSCs (BDNF MSC) were co-transplanted in one group (combination group) of dogs with subacute spinal cord injury to selectively control the expression of inflammatory cytokines by HO-1 and induce neuroregeneration by BDNF. We compared the combination group with the HO-1 MSCs group, BDNF MSCs group, and GFP MSCs group. We found that the combination group showed significant improvement in functional recovery. It showed increased expression of neural markers and growth-associated proteins (GAP-43) than in other groups, which depicts enhanced neuroregeneration/neural sparing due to reduced expression of pro-inflammatory cytokines such as TNF-alpha, IL-6 and COX-2; and increased expression of anti-inflammatory markers such as IL-10 and HO-1. Histopathological study revealed reduced intra-parenchymal fibrosis in the injured spinal cord segment in the combination group than in other groups. Thus it was concluded that selectively targeting the inflammation and neuronal growth with the combined use of HO-1 MSCs and BDNF MSCs more favorably promote healing of the SCI. HO-1 MSCs play a role in controlling the inflammation, which favors the BDNF induced neuroregeneration at the injured spinal cord segment of dogs.Keywords: HO-1 MSCs, BDNF MSCs, neuroregeneration, inflammation, anti-inflammation, spinal cord injury, dogs
Procedia PDF Downloads 1195097 The Effect of Penalizing Wrong Answers in the Computerized Modified Multiple Choice Testing System
Authors: Min Hae Song, Jooyong Park
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Even though assessment using information and communication technology will most likely lead the future of educational assessment, there is little research on this topic. Computerized assessment will not only cut costs but also measure students' performance in ways not possible before. In this context, this study introduces a tool which can overcome the problems of multiple choice tests. Multiple-choice tests (MC) are efficient in automatic grading, however structural problems of multiple-choice tests allow students to find the correct answer from options even though they do not know the answer. A computerized modified multiple-choice testing system (CMMT) was developed using the interactivity of computers, that presents questions first, and options later for a short time when the student requests for them. This study was conducted to find out whether penalizing for wrong answers in CMMT could lower random guessing. In this study, we checked whether students knew the answers by having them respond to the short-answer tests before choosing the given options in CMMT or MC format. Ninety-four students were tested with the directions that they will be penalized for wrong answers, but not for no response. There were 4 experimental conditions: two conditions of high or low percentage of penalizing, each in traditional multiple-choice or CMMT format. In the low penalty condition, the penalty rate was the probability of getting the correct answer by random guessing. In the high penalty condition, students were penalized at twice the percentage of the low penalty condition. The results showed that the number of no response was significantly higher for the CMMT format and the number of random guesses was significantly lower for the CMMT format. There were no significant between the two penalty conditions. This result may be due to the fact that the actual score difference between the two conditions was too small. In the discussion, the possibility of applying CMMT format tests while penalizing wrong answers in actual testing settings was addressed.Keywords: computerized modified multiple choice test format, multiple-choice test format, penalizing, test format
Procedia PDF Downloads 1685096 Generalized Mean-Field Theory of Phase Unwrapping via Multiple Interferograms
Authors: Yohei Saika
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On the basis of Bayesian inference using the maximizer of the posterior marginal estimate, we carry out phase unwrapping using multiple interferograms via generalized mean-field theory. Numerical calculations for a typical wave-front in remote sensing using the synthetic aperture radar interferometry, phase diagram in hyper-parameter space clarifies that the present method succeeds in phase unwrapping perfectly under the constraint of surface- consistency condition, if the interferograms are not corrupted by any noises. Also, we find that prior is useful for extending a phase in which phase unwrapping under the constraint of the surface-consistency condition. These results are quantitatively confirmed by the Monte Carlo simulation.Keywords: Bayesian inference, generalized mean-field theory, phase unwrapping, multiple interferograms, statistical mechanics
Procedia PDF Downloads 4795095 Students Competencies in the Use of Computer Assistive Technology at Akropong School for the Blind in the Eastern of Ghana
Authors: Joseph Ampratwum, Yaw Nyadu Offei, Afua Ntoaduro, Frank Twum
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The use of computer assistive technology has captured the attention of individuals with visual impairment. Children with visual impairments who are tactual learners have one unique need which is quite different from all other disability groups. They depend on the use of computer assistive technology for reading, writing, receiving information and sending information as well. The objective of the study was to assess students’ competencies in the use of computer assistive technology at Akropong School for the Blind in Ghana. This became necessary because little research has been conducted to document the competencies and challenges in the use of computer among students with visual impairments in Africa. A case study design with a mixed research strategy was adopted for the study. A purposive sampling technique was used to sample 35 students from Akropong School for the Blind in the eastern region of Ghana. The researcher gathered both quantitative and qualitative data to measure students’ competencies in keyboarding skills and Job Access with Speech (JAWS), as well as the other challenges. The findings indicated that comparatively students’ competency in keyboard skills was higher than JAWS application use. Thus students had reached higher stages in the conscious competencies matrix in the former than the latter. It was generally noted that challenges limiting effective use of students’ competencies in computer assistive technology in the School were more personal than external influences. This was because most of the challenges were due to the individual response to the training and familiarity in developing their competencies in using computer assistive technology. Base on this it was recommended that efforts should be made to stock up the laboratory with additional computers. Directly in line with the first recommendation, it was further suggested that more practice time should be created for the students to maximize computer use. Also Licensed JAWS must be acquired by the school to advance students’ competence in using computer assistive technology.Keywords: computer assistive technology, job access with speech, keyboard, visual impairment
Procedia PDF Downloads 3455094 The Strengths and Limitations of the Statistical Modeling of Complex Social Phenomenon: Focusing on SEM, Path Analysis, or Multiple Regression Models
Authors: Jihye Jeon
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This paper analyzes the conceptual framework of three statistical methods, multiple regression, path analysis, and structural equation models. When establishing research model of the statistical modeling of complex social phenomenon, it is important to know the strengths and limitations of three statistical models. This study explored the character, strength, and limitation of each modeling and suggested some strategies for accurate explaining or predicting the causal relationships among variables. Especially, on the studying of depression or mental health, the common mistakes of research modeling were discussed.Keywords: multiple regression, path analysis, structural equation models, statistical modeling, social and psychological phenomenon
Procedia PDF Downloads 6585093 Integration Program Through Physical Education Lessons for The Influence of Some Physical Fitness Health-Related Components in Visual Handicapped Children
Authors: Said S. Almaiuof
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Integration Program Through Physical Education Lessons for The Influence of Some Physical Fitness Health-Related Components in Visual Handicapped Children. Propose of the study: The aim of this study is to design and evaluate a program for the physical education lesson to improve the cardio-respiratory endurance, considering the lesson of physical education as one of the educational means to achieve the society aims toward health and fitness, concerning the importance of the cardio-respiratory endurance as an essential one of the physical fitness health-related components. And this program tried to give them hand of help as a part of the society having the same rights as the rest of the society. Methodology: The researcher used the experimental method as a suitable method for this study and tested its hypothesis. The subject of the research selected randomly of the two classes from primary education in TRIPOLI-LIBYA, it was 28 boys (14-15) years old, then divided into groups, experimental group, n=13, which practiced the special exercises program and control group, n=15, which only practiced the normal school program. The selected child subjected to a medical examination in order to make sure that they are healthy, and the Vo2max measured by cycle ergometry and test some physical fitness makers before and after the program. Results: The study cleared that the experimental group developed in all physical variation in comparison with the control group which has a little development in a general balance only. Results are following: 1. The experimental group was successful more than the control group in all the research variation. 2. There were some improvements in time of keeping Balance in control group only. Discussion /conclusion: According to statistical analysis of data related to the values of the variables in this study; the suggested exercise program according to development the cardio respiratory endurance (CRE), and some physical fitness more than the program which already implemented in the school was less effective, just there is developing on keep balancing. It’s statistically significant (p<0.05) after applying this program. Improving the experimental group on (CRE), balance, running, sit and reach, from the suggested exercise program of what indicate the partaking program positive in improve those physical variables, and the selected exercises may contributed in improving the (CRE) for visual impairment and its pivotal in visual impairment children’s life. A health-related physical education curriculum can provide students with substantially more physical activity during physical education classes. The results show that the physical rehabilitation program for visual impairment children helped them in developing their defects due to the injury which means that this program should be in every organization having this part of people to increase their production and give them hand of help as a part of the society having the same rights as the rest of the society and to establish the idea of sport for all.Keywords: visual handicapped, cardio-respiratory endurance, health, ergometry, education
Procedia PDF Downloads 4355092 Melatonin Rescue Fungicide Induced Behavioral and Reproductive Abnormalities through Changes of Dopaminergic Activity in the Brain of Catfish, Mystus cavasisu
Authors: Muhammad Badruzzaman, Alif Hasan, Md. Shahjahan
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Propiconazole is a triazole fungicide extensively used in agriculture which can harm to non-target organisms in aquatic environment through runoff. Chronic exposure to environmental pesticides turn to behavioral impairment in vertebrates including teleosts. However, the potential effect of this fungicide on neurobehavioral impairment and release from it in vertebrates has not been fully explored. In this work, we examined the role of melatonin to rescue fungicide induced neurobehavioral and reproductive alternation and its connection with changes in dopaminergic activity in the brain of Mystus cavasius. After fish were exposed to water containing propiconazole at 0, 0.1, 5, and 250 µg/L for 3 days, significant increases of DA, 3,4-dihydroxyphenylacetic acid (DOPAC; a DA metabolite), and their ratio (DOPAC/DA) were observed in whole brain at 250 µg/L concentration. When fish were treated with propiconazole at 250 µg/L for 3 days, there was a significant elevation of DA, DOPAC and DOPAC/DA in diencephalon and pituitary, and only DA in the telencephalon, compared with control fish. Besides, it induced a reduction in extracellular serotonin and had an anxiolytic-like effect, supported by a decrease in cortisol production. Increased locomotor activity, anxiety and aggressiveness, decreased gonadosomatic index with few vitellogenic oocytes in ovaries after propiconazole treatment. When fish were treated with melatonin, D1 (SCH-23390) or D2 (Haloperidol) dopamine receptor antagonists and combined of melatonin and D1/D2 receptor antagonist and was observed melatonin + D2 receptor antagonist rescued fungicide induced all behavioral changes in fish. These results indicate that propiconazole increases locomotor activity, anxiety and aggressiveness and decreases reproductive activity, which was rescued by combined treatment of melatonin and dopamine receptor antagonist.Keywords: behavior, catfish, dopamine, fungicide, melatonin
Procedia PDF Downloads 1155091 An Analysis of Pick Travel Distances for Non-Traditional Unit Load Warehouses with Multiple P/D Points
Authors: Subir S. Rao
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Existing warehouse configurations use non-traditional aisle designs with a central P/D point in their models, which is mathematically simple but less practical. Many warehouses use multiple P/D points to avoid congestion for pickers, and different warehouses have different flow policies and infrastructure for using the P/D points. Many warehouses use multiple P/D points with non-traditional aisle designs in their analytical models. Standard warehouse models introduce one-sided multiple P/D points in a flying-V warehouse and minimize pick distance for a one-way travel between an active P/D point and a pick location with P/D points, assuming uniform flow rates. A simulation of the mathematical model generally uses four fixed configurations of P/D points which are on two different sides of the warehouse. It can be easily proved that if the source and destination P/D points are both chosen randomly, in a uniform way, then minimizing the one-way travel is the same as minimizing the two-way travel. Another warehouse configuration analytically models the warehouse for multiple one-sided P/D points while keeping the angle of the cross-aisles and picking aisles as a decision variable. The minimization of the one-way pick travel distance from the P/D point to the pick location by finding the optimal position/angle of the cross-aisle and picking aisle for warehouses having different numbers of multiple P/D points with variable flow rates is also one of the objectives. Most models of warehouses with multiple P/D points are one-way travel models and we extend these analytical models to minimize the two-way pick travel distance wherein the destination P/D is chosen optimally for the return route, which is not similar to minimizing the one-way travel. In most warehouse models, the return P/D is chosen randomly, but in our research, the return route P/D point is chosen optimally. Such warehouses are common in practice, where the flow rates at the P/D points are flexible and depend totally on the position of the picks. A good warehouse management system is efficient in consolidating orders over multiple P/D points in warehouses where the P/D is flexible in function. In the latter arrangement, pickers and shrink-wrap processes are not assigned to particular P/D points, which ultimately makes the P/D points more flexible and easy to use interchangeably for picking and deposits. The number of P/D points considered in this research uniformly increases from a single-central one to a maximum of each aisle symmetrically having a P/D point below it.Keywords: non-traditional warehouse, V cross-aisle, multiple P/D point, pick travel distance
Procedia PDF Downloads 435090 A Handheld Light Meter Device for Methamphetamine Detection in Oral Fluid
Authors: Anindita Sen
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Oral fluid is a promising diagnostic matrix for drugs of abuse compared to urine and serum. Detection of methamphetamine in oral fluid would pave way for the easy evaluation of impairment in drivers during roadside drug testing as well as ensure safe working environments by facilitating evaluation of impairment in employees at workplaces. A membrane-based point-of-care (POC) friendly pre-treatment technique has been developed which aided elimination of interferences caused by salivary proteins and facilitated the demonstration of methamphetamine detection in saliva using a gold nanoparticle based colorimetric aptasensor platform. It was found that the colorimetric response in saliva was always suppressed owing to the matrix effects. By navigating the challenging interfering issues in saliva, we were successfully able to detect methamphetamine at nanomolar levels in saliva offering immense promise for the translation of these platforms for on-site diagnostic systems. This subsequently motivated the development of a handheld portable light meter device that can reliably transduce the aptasensors colorimetric response into absorbance, facilitating quantitative detection of analyte concentrations on-site. This is crucial due to the prevalent unreliability and sensitivity problems of the conventional drug testing kits. The fabricated light meter device response was validated against a standard UV-Vis spectrometer to confirm reliability. The portable and cost-effective handheld detector device features sensitivity comparable to the well-established UV-Vis benchtop instrument and the easy-to-use device could potentially serve as a prototype for a commercial device in the future.Keywords: aptasensors, colorimetric gold nanoparticle assay, point-of-care, oral fluid
Procedia PDF Downloads 625089 Effects of Breed and Number of Embryos Transferred on the Efficacy of MOET in Sheep
Authors: Ayman A. Swelum, Abdullah N. Al-Owaimer, Mohamed A. Abouheif
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This study aimed to evaluate the effects of sheep breed and the number of embryos transferred on the success of multiple ovulation and embryo transfer (MOET). Sixteen Najdi and Naeimi ewes were used as donors. Multiple ovulation was achieved using equine chorionic gonadotropin (eCG). Thirty-five recipient ewes were divided into four groups: Najdi or Naeimi ewes that received either one or two embryos. After lambing, the gestation length, litter size, and sex of the lambs were recorded. The rates of pregnancy, lambing, and embryo survival were lower in the recipient Najdi than Naeimi ewes when two embryos were transferred. In contrast, the Naeimi ewes that received one embryo had a significantly lower embryo transfer success. In conclusion, the response of ewes to multiple ovulation stimulation using eCG was significantly high in Naeimi ewes (9.8±1.17). Moreover, transferring one embryo resulted in a significantly high pregnancy rate in the Najdi sheep (60%).Keywords: embryo transfer, multiple ovulation, Najdi, Naeimi, sheep
Procedia PDF Downloads 7305088 Basins of Attraction for Quartic-Order Methods
Authors: Young Hee Geum
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We compare optimal quartic order method for the multiple zeros of nonlinear equations illustrating the basins of attraction. To construct basins of attraction effectively, we take a 600×600 uniform grid points at the origin of the complex plane and paint the initial values on the basins of attraction with different colors according to the iteration number required for convergence.Keywords: basins of attraction, convergence, multiple-root, nonlinear equation
Procedia PDF Downloads 2525087 A Systematic Approach for Analyzing Multiple Cyber-Physical Attacks on the Smart Grid
Authors: Yatin Wadhawan, Clifford Neuman, Anas Al Majali
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In this paper, we evaluate the resilience of the smart grid system in the presence of multiple cyber-physical attacks on its distinct functional components. We discuss attack-defense scenarios and their effect on smart grid resilience. Through contingency simulations in the Network and PowerWorld Simulator, we analyze multiple cyber-physical attacks that propagate from the cyber domain to power systems and discuss how such attacks destabilize the underlying power grid. The analysis of such simulations helps system administrators develop more resilient systems and improves the response of the system in the presence of cyber-physical attacks.Keywords: smart grid, gas pipeline, cyber- physical attack, security, resilience
Procedia PDF Downloads 3155086 Detection of Change Points in Earthquakes Data: A Bayesian Approach
Authors: F. A. Al-Awadhi, D. Al-Hulail
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In this study, we applied the Bayesian hierarchical model to detect single and multiple change points for daily earthquake body wave magnitude. The change point analysis is used in both backward (off-line) and forward (on-line) statistical research. In this study, it is used with the backward approach. Different types of change parameters are considered (mean, variance or both). The posterior model and the conditional distributions for single and multiple change points are derived and implemented using BUGS software. The model is applicable for any set of data. The sensitivity of the model is tested using different prior and likelihood functions. Using Mb data, we concluded that during January 2002 and December 2003, three changes occurred in the mean magnitude of Mb in Kuwait and its vicinity.Keywords: multiple change points, Markov Chain Monte Carlo, earthquake magnitude, hierarchical Bayesian mode
Procedia PDF Downloads 4585085 The Risk of Post-stroke Pneumonia and Its One-Year Disability in Taiwan
Authors: Hui-Chi Huang, Su-Ju Yang, Ching-Wei Lin, Jui-Yao Tsai, Liang-Yiang
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Background: Evidence exists that pneumonia is a frequently encountered complication after stroke which is associated with a higher rate of mortality and increased long-term disability Purpose: To determine the predictors associated with the risk of one-year disability in acute stroke. Methods: Data for this longitudinal follow-up study were extracted from a tertiary referral medical center’s stroke registry database in Northern Taipei. Eligible patients with acute stroke admitted to the hospital and completed a one-year follow up were recruited for analysis. Favorable outcome was defined as a modified Rankin Scale score ≤ 2. SAS version 9.2 was used for the multivariable regression analyses to examine the factors correlated with the one-year disability in stroke patients. Results: From January 2012 to December 2013, a total of 1373 (mean age: 70.49±15.4 years, 913(66.5%) males) consecutively administered acute stroke patients were recruited. Overall, the rate of one-year disability was 37.20%(404/1086) in those without post-stroke pneumonia. It increased to 82.93 %(238/287) in patients developed post-stroke pneumonia. Factors associated with increased risk of disability were age ≧ 75(OR= 4.845, p<.0001), female /gender (OR=1.568, p =.0062), previous stroke (OR= 1.868, p = <. 0001) ,dementia (OR= 2.872, p =.0047), ventilator use (OR= 4.653, p <. 0001),age ≧ 75 /pneumonia (OR=1.236, p <. 0001) , ICU admission (OR=3.314, p <.0001) , nasogastric tube insertion (OR= 4.28, p <.0001), speech therapy (OR= 1.79, p =.0142), urinary tract infection (OR= 1.865, p =.0018), estimated glomerular filtration rate (eGFR > 60 )(OR= 0.525, p= .0029), Admission NIHSS >11 (OR= 2.101, p = .0099), Length of hospitalization > 30(d) (OR= 5.182, p <.0001). Conclusion: Older age, severe neurological deficit, complications, rehabilitation intervention, length of hospitalization >30(d), and cognitive impairment were significantly associated with Post-stroke functional impairment, especially those with post-stroke pneumonia. These findings could open new avenues in the management of stroke patients.Keywords: stroke, risk, pneumonia, disability
Procedia PDF Downloads 2335084 Big Classes, Bigger Ambitions: A Participatory Approach to the Multiple-Choice Exam
Authors: Melanie Adrian, Elspeth McCulloch, Emily-Jean Gallant
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Resources -financial, physical, and human- are increasingly constrained in higher education. University classes are getting bigger, and the concomitant grading burden on faculty is growing rapidly. Multiple-choice exams are seen by some as one solution to these changes. How much students retain, however, and what their testing experience is, continues to be debated. Are multiple-choice exams serving students well, or are they bearing the burden of these developments? Is there a way to address both the resource constraints and make these types of exams more meaningful? In short, how do we engender evaluation methods for large-scale classes that provide opportunities for heightened student learning and enrichment? The following article lays out a testing approach we have employed in four iterations of the same third-year law class. We base our comments in this paper on our initial observations as well as data gathered from an ethics-approved study looking at student experiences. This testing approach provides students with multiple opportunities for revision (thus increasing chances for long term retention), is both individually and collaboratively driven (thus reflecting the individual effort and group effort) and is automatically graded (thus draining limited institutional resources). We found that overall students appreciated the approach and found it more ‘humane’, that it notably reduced pre-exam and intra-exam stress levels, increased ease, and lowered nervousness.Keywords: exam, higher education, multiple-choice, law
Procedia PDF Downloads 1285083 Pathology of Explanted Transvaginal Meshes
Authors: Vladimir V. Iakovlev, Erin T. Carey, John Steege
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The use of polypropylene mesh devices for Pelvic Organ Prolapse (POP) spread rapidly during the last decade, yet our knowledge of the mesh-tissue interaction is far from complete. We aimed to perform a thorough pathological examination of explanted POP meshes and describe findings that may explain mechanisms of complications resulting in product excision. We report a spectrum of important findings, including nerve ingrowth, mesh deformation, involvement of detrusor muscle with neural ganglia, and polypropylene degradation. Analysis of these findings may improve and guide future treatment strategies.Keywords: transvaginal, mesh, nerves, polypropylene degradation
Procedia PDF Downloads 403