Search results for: Alaa A. Ghanem
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 143

Search results for: Alaa A. Ghanem

23 Tri/Tetra-Block Copolymeric Nanocarriers as a Potential Ocular Delivery System of Lornoxicam: Experimental Design-Based Preparation, in-vitro Characterization and in-vivo Estimation of Transcorneal Permeation

Authors: Alaa Hamed Salama, Rehab Nabil Shamma

Abstract:

Introduction: Polymeric micelles that can deliver drug to intended sites of the eye have attracted much scientific attention recently. The aim of this study was to review the aqueous-based formulation of drug-loaded polymeric micelles that hold significant promise for ophthalmic drug delivery. This study investigated the synergistic performance of mixed polymeric micelles made of linear and branched poly (ethylene oxide)-poly (propylene oxide) for the more effective encapsulation of Lornoxicam (LX) as a hydrophobic model drug. Methods: The co-micellization process of 10% binary systems combining different weight ratios of the highly hydrophilic poloxamers; Synperonic® PE/P84, and Synperonic® PE/F127 and the hydrophobic poloxamine counterpart (Tetronic® T701) was investigated by means of photon correlation spectroscopy and cloud point. The drug-loaded micelles were tested for their solubilizing capacity towards LX. Results: Results showed a sharp solubility increase from 0.46 mg/ml up to more than 4.34 mg/ml, representing about 136-fold increase. Optimized formulation was selected to achieve maximum drug solubilizing power and clarity with lowest possible particle size. The optimized formulation was characterized by 1HNMR analysis which revealed complete encapsulation of the drug within the micelles. Further investigations by histopathological and confocal laser studies revealed the non-irritant nature and good corneal penetrating power of the proposed nano-formulation. Conclusion: LX-loaded polymeric nanomicellar formulation was fabricated allowing easy application of the drug in the form of clear eye drops that do not cause blurred vision or discomfort, thus achieving high patient compliance.

Keywords: confocal laser scanning microscopy, Histopathological studies, Lornoxicam, micellar solubilization

Procedia PDF Downloads 449
22 Hip Strategy in Dynamic Postural Control in Recurrent Ankle Sprain

Authors: Radwa Elshorbagy, Alaa Elden Balbaa, Khaled Ayad, Waleed Reda

Abstract:

Introduction: Ankle sprain is a common lower limb injury that is complicated by high recurrence rate. The cause of recurrence is not clear; however, changes in motor control have been postulated. Objective: to determine the contribution of proximal hip strategy to dynamic postural control in patients with recurrent ankle sprain. Methods: Fifteen subjects with recurrent ankle sprain (group A) and fifteen healthy control subjects (group B) participated in this study. Abductor-adductors as well as flexor-extensor hip musculatures control was abolished by fatigue using the Biodex Isokinetic System. Dynamic postural control was measured before and after fatigue by the Biodex Balance System. Results: Repeated measures MANOVA was used to compare between and within group differences, in group A fatiguing of hip muscles (flexors-extensors and abductors-adductors) increased overall stability index (OASI), anteroposterior stability index (APSI) and mediolateral stability index (MLSI) significantly (p=0.00) whereas; in group B fatiguing of hip flexors-extensors increased significantly OASI and APSI only (p= 0.017, 0.010; respectively) while fatiguing of hip abductors-adductors has no significant effect on these variables. Moreover, patients with ankle sprain had significantly lower dynamic balance after hip muscles fatigue compared to the control group. Specifically, after hip flexor-extensor fatigue, the OASI, APSI and MLSI were increased significantly than those of the control values (p= 0.002, 0.011, and 0.003, respectively) whereas fatiguing of hip abductors-adductors increased significantly in OASI and APSI only (p=0.012, 0.026, respectively). Conclusion: To maintain dynamic balance, patients with recurrent ankle sprain seem to rely more on the hip strategy. This means that those patients depend on a top to down instead of down to top strategy clinical relevance: patients with recurrent ankle sprain less efficient in maintaining the dynamic postural control due to the change in motor strategies. Indicating that health care providers and rehabilitation specialists should treat CAI as a global/central and not just as a simple local or peripheral injury.

Keywords: hip strategy, ankle strategy, postural control, dynamic balance

Procedia PDF Downloads 338
21 The Contribution of Hip Strategy in Dynamic Postural Control in Recurrent Ankle Sprain

Authors: Radwa El Shorbagy, Alaa El Din Balbaa, Khaled Ayad, Waleed Reda

Abstract:

Introduction: Ankle sprain is a common lower limb injury that is complicated by high recurrence rate. The cause of recurrence is not clear; however, changes in motor control have been postulated. Objective: to determine the contribution of proximal hip strategy to dynamic postural control in patients with recurrent ankle sprain. Methods: Fifteen subjects with recurrent ankle sprain (group A) and fifteen healthy control subjects (group B) participated in this study. Abductor-adductors as well as flexor-extensor hip musculatures control was abolished by fatigue using the Biodex Isokinetic System. Dynamic postural control was measured before and after fatigue by the Biodex Balance System Results: Repeated measures MANOVA was used to compare between and within group differences, In group A fatiguing of hip muscles (flexors-extensors and abductors-adductors) increased overall stability index (OASI), anteroposterior stability index (APSI) and mediolateral stability index (MLSI) significantly (p= 0.00) whereas; in group B fatiguing of hip flexors-extensors increased significantly OASI and APSI only (p= 0.017, 0.010; respectively) while fatiguing of hip abductors-adductors has no significant effect on these variables. Moreover, patients with ankle sprain had significantly lower dynamic balance after hip muscles fatigue compared to the control group. Specifically, after hip flexor-extensor fatigue, the OASI, APSI and MLSI were increased significantly than those of the control values (p= 0.002, 0.011, and 0.003, respectively) whereas fatiguing of hip abductors-adductors increased significantly in OASI and APSI only (p=0.012, 0.026, respectively). Conclusion: To maintain dynamic balance, patients with recurrent ankle sprain seem to relay more on the hip strategy. This means that those patients depend on a top to down instead of down to top strategy clinical relevance: patients with recurrent ankle sprain less efficient in maintaining the dynamic postural control due to the change in motor strategies. Indicating that health care providers and rehabilitation specialists should treat CAI as a global/central and not just as a simple local or peripheral injury.

Keywords: ankle sprain, fatigue hip muscles, dynamic balance

Procedia PDF Downloads 300
20 Correlation Study between Clinical and Radiological Findings in Knee Osteoarthritis

Authors: Nabil A. A. Mohamed, Alaa A. A. Balbaa, Khaled E. Ayad

Abstract:

Osteoarthritis (OA) of the knee is the most common form of arthritis and leads to more activity limitations (e.g., disability in walking and stair climbing) than any other disease, especially in the elderly. Recently, impaired proprioceptive accuracy of the knee has been proposed as a local factor in the onset and progression of radiographic knee OA (ROA). Purpose: To compare the clinical and radiological findings in healthy with that of knee OA. Also, to determine if there is a correlation between the clinical and radiological findings in patients with knee OA. Subjects: Fifty one patients diagnosed as unilateral or bilateral knee OA with age ranged between 35-70 years, from both gender without any previous history of knee trauma or surgery, and twenty one normal subjects with age ranged from 35 - 68 years. METHODS: peak torque/body weight (PT/BW) was recorded from knee extensors at isokinetic isometric mode at angle of 45 degree. Also, the Absolute Angular Error was recorded at 45O and 30O to measure joint position sense (JPS). They made anteroposterior (AP) plain X-rays from standing semiflexed knee position and their average score of Timed Up and Go test(TUG) and WOMAC were recorded as a measure of knee pain, stiffness and function. Comparison between the mean values of different variables in the two groups was performed using unpaired student t test. The P value less or equal to 0.05 was considered significant. Results: There were significant differences between the studied variables between the experimental and control groups except the values of AAE at 30O. Also, there were no significant correlation between the clinical findings (pain, function, muscle strength and proprioception) and the severity of arthritic changes in X-rays. CONCLUSION: From the finding of the current study we can conclude that there were a significant difference between the both groups in all studied parameters (the WOMAC, functional level, quadriceps muscle strength and the joint proprioception). Also this study did not support the dependency on radiological findings in management of knee OA as the radiological features did not necessarily indicate the level of structural damage of patients with knee OA and we should consider the clinical features in our treatment plan.

Keywords: joint position sense, peak torque, proprioception, radiological knee osteoarthritis

Procedia PDF Downloads 302
19 Risk-Sharing Financing of Islamic Banks: Better Shielded against Interest Rate Risk

Authors: Mirzet SeHo, Alaa Alaabed, Mansur Masih

Abstract:

In theory, risk-sharing-based financing (RSF) is considered a corner stone of Islamic finance. It is argued to render Islamic banks more resilient to shocks. In practice, however, this feature of Islamic financial products is almost negligible. Instead, debt-based instruments, with conventional like features, have overwhelmed the nascent industry. In addition, the framework of present-day economic, regulatory and financial reality inevitably exposes Islamic banks in dual banking systems to problems of conventional banks. This includes, but is not limited to, interest rate risk. Empirical evidence has, thus far, confirmed such exposures, despite Islamic banks’ interest-free operations. This study applies system GMM in modeling the determinants of RSF, and finds that RSF is insensitive to changes in interest rates. Hence, our results provide support to the “stability” view of risk-sharing-based financing. This suggests RSF as the way forward for risk management at Islamic banks, in the absence of widely acceptable Shariah compliant hedging instruments. Further support to the stability view is given by evidence of counter-cyclicality. Unlike debt-based lending that inflates artificial asset bubbles through credit expansion during the upswing of business cycles, RSF is negatively related to GDP growth. Our results also imply a significantly strong relationship between risk-sharing deposits and RSF. However, the pass-through of these deposits to RSF is economically low. Only about 40% of risk-sharing deposits are channeled to risk-sharing financing. This raises questions on the validity of the industry’s claim that depositors accustomed to conventional banking shun away from risk sharing and signals potential for better balance sheet management at Islamic banks. Overall, our findings suggest that, on the one hand, Islamic banks can gain ‘independence’ from conventional banks and interest rates through risk-sharing products, the potential for which is enormous. On the other hand, RSF could enable policy makers to improve systemic stability and restrain excessive credit expansion through its countercyclical features.

Keywords: Islamic banks, risk-sharing, financing, interest rate, dynamic system GMM

Procedia PDF Downloads 316
18 Prevalence and Clinical Significance of Antiphospholipid Antibodies in COVID-19 Patients Admitted to Intensive Care Units

Authors: Mostafa Najim, Alaa Rahhal, Fadi Khir, Safae Abu Yousef, Amer Aljundi, Feryal Ibrahim, Aliaa Amer, Ahmed Soliman Mohamed, Samira Saleh, Dekra Alfaridi, Ahmed Mahfouz, Sumaya Al-Yafei, Faraj Howady, Mohamad Yahya Khatib, Samar Alemadi

Abstract:

Background: Coronavirus disease 2019 (COVID-19) increases the risk of coagulopathy among critically ill patients. Although the presence of antiphospholipid antibodies (aPLs) has been proposed as a possible mechanism of COVID-19 induced coagulopathy, their clinical significance among critically ill patients with COVID-19 remains uncertain. Methods: This prospective observational study included patients with COVID-19 admitted to intensive care units (ICU) to evaluate the prevalence and clinical significance of aPLs, including anticardiolipin IgG/IgM, anti-β2-glycoprotein IgG/IgM, and lupus anticoagulant. The study outcomes included the prevalence of aPLs, a primary composite outcome of all-cause mortality, and arterial or venous thrombosis among aPLs positive patients versus aPLs negative patients during their ICU stay. Multiple logistic regression was used to assess the influence of aPLs on the primary composite outcome of mortality and thrombosis. Results: A total of 60 critically ill patients were enrolled. Of whom, 57 (95%) were male, with a mean age of 52.8 ± 12.2 years, and the majority were from Asia (68%). Twenty-two patients (37%) were found to have positive aPLs; of whom 21 patients were positive for lupus anticoagulant, whereas one patient was positive for anti-β2-glycoprotein IgG/IgM. The composite outcome of mortality and thrombosis during ICU did not differ among patients with positive aPLs compared to those with negative aPLs (4 (18%) vs. 6 (16%), aOR= 0.98, 95% CI 0.1-6.7; p-value= 0.986). Likewise, the secondary outcomes, including all-cause mortality, venous thrombosis, arterial thrombosis, discharge from ICU, time to mortality, and time to discharge from ICU, did not differ between those with positive aPLs upon ICU admission in comparison to patients with negative aPLs. Conclusion: The presence of aPLs does not seem to affect the outcomes of critically ill patients with COVID-19 in terms of all-cause mortality and thrombosis. Therefore, clinicians may not screen critically ill patients with COVID-19 for aPLs unless deemed clinically appropriate.

Keywords: antiphospholipid antibodies, critically ill patients, coagulopathy, coronavirus

Procedia PDF Downloads 166
17 Performance of Reinforced Concrete Wall with Opening Using Analytical Model

Authors: Alaa Morsy, Youssef Ibrahim

Abstract:

Earthquake is one of the most catastrophic events, which makes enormous harm to properties and human lives. As a piece of a safe building configuration, reinforced concrete walls are given in structures to decrease horizontal displacements under seismic load. Shear walls are additionally used to oppose the horizontal loads that might be incited by the impact of wind. Reinforced concrete walls in residential buildings might have openings that are required for windows in outside walls or for doors in inside walls or different states of openings due to architectural purposes. The size, position, and area of openings may fluctuate from an engineering perspective. Shear walls can encounter harm around corners of entryways and windows because of advancement of stress concentration under the impact of vertical or horizontal loads. The openings cause a diminishing in shear wall capacity. It might have an unfavorable impact on the stiffness of reinforced concrete wall and on the seismic reaction of structures. Finite Element Method using software package ‘ANSYS ver. 12’ becomes an essential approach in analyzing civil engineering problems numerically. Now we can make various models with different parameters in short time by using ANSYS instead of doing it experimentally, which consumes a lot of time and money. Finite element modeling approach has been conducted to study the effect of opening shape, size and position in RC wall with different thicknesses under axial and lateral static loads. The proposed finite element approach has been verified with experimental programme conducted by the researchers and validated by their variables. A very good correlation has been observed between the model and experimental results including load capacity, failure mode, and lateral displacement. A parametric study is applied to investigate the effect of opening size, shape, position on different reinforced concrete wall thicknesses. The results may be useful for improving existing design models and to be applied in practice, as it satisfies both the architectural and the structural requirements.

Keywords: Ansys, concrete walls, openings, out of plane behavior, seismic, shear wall

Procedia PDF Downloads 167
16 Toxicological and Histopathological Studies on the Effect of Tartrazine in Male Albino Rats

Authors: F. Alaa Ali, S. A. Sherein Abdelgayed, S. Osama. EL-Tawil, M. Adel Bakeer

Abstract:

Tartrazine is an organic azo dyes food additive widely used in foods, drugs, and cosmetics. The present study aimed to investigate the toxic effects of tartrazine on kidneys and liver biomarkers in addition to the investigation of oxidative stress and change of histopathological structure of liver and kidneys in 30 male rats. Tartrazine was orally administrated daily at dose 200 mg/ kg bw (1/ 10 LD50) for sixty days. Serum and tissue samples were collected at the end of the experiment to investigate the underlying mechanism of tartrazine through assessment oxidative stress (Glutathione (GSH), Superoxide dismutase (SOD) and malondialdehyde (MDA) and biochemical markers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), Total protein and Urea). Liver and kidneys tissue were collected and preserved in 10% formalin for histopathological examination. The obtained values were statistically analyzed by one way analysis of variance (ANOVA) followed by multiple comparison test. Biochemical analysis revealed that tartrazine induced significant increase in serum ALT, AST, total protein, urea level compared to control group. Tartrazine showed significant decrease in liver GSH and SOD where their values when compared to control group. Tartrazine induced increase in liver MDA compared to control group. Histopathology of the liver showed diffuse vacuolar degeneration in hepatic parenchyma, the portal area showed sever changes sever in hepatoportal blood vessels and in the bile ducts. The kidneys showed degenerated tubules at the cortex together with mononuclear leucocytes inflammatory cells infiltration. There is perivascular edema with inflammatory cell infiltration surrounding the congested and hyalinized vascular wall of blood vessel. The present study indicates that the subchronic effects of tartrazine have a toxic effect on the liver and kidneys together with induction of oxidative stress by formation of free radicals. Therefore, people should avoid the hazards of consuming tartrazine.

Keywords: albino rats, tartrazine, toxicity, pathology

Procedia PDF Downloads 357
15 Self-Inflating Soft Tissue Expander Outcome for Alveolar Ridge Augmentation a Randomized Controlled Clinical and Histological Study

Authors: Alaa T. Ali, Nevine H. Kheir El Din, Ehab S. Abdelhamid, Ahmed E. Amr

Abstract:

Objective: Severe alveolar bone resorption is usually associated with a deficient amount of soft tissues. soft tissue expansion is introduced to provide an adequate amount of soft tissue over the grafted area. This study aimed to assess the efficacy of sub-periosteal self-inflating osmotic tissue expanders used as preparatory surgery before horizontal alveolar ridge augmentation using autogenous onlay block bone graft. Methods: A prospective randomized controlled clinical trial was performed. Sixteen partially edentulous patients demanding horizontal bone augmentation in the anterior maxilla were randomly assigned to horizontal ridge augmentation with autogenous bone block grafts harvested from the mandibular symphysis. For the test group, soft tissue expanders were placed sub-periosteally before horizontal ridge augmentation. Impressions were taken before and after STE, and the cast models were optically scanned and superimposed to be used for volumetric analysis. Horizontal ridge augmentation was carried out after STE completion. For the control group, a periosteal releasing incision was performed during bone augmentation procedures. Implants were placed in both groups at re-entry surgery after six months period. A core biopsy was taken. Histomorphometric assessment for newly formed bone surface area, mature collagen area fraction, the osteoblasts count, and blood vessel count were performed. The change in alveolar ridge width was evaluated through bone caliper and CBCT. Results: Soft tissue expander successfully provides a Surplus amount of soft tissues in 5 out of 8 patients in the test group. Complications during the expansion period were perforation through oral mucosa occurred in two patients. Infection occurred in one patient. The mean soft tissue volume gain was 393.9 ± 322mm. After 6 months. The mean horizontal bone gains for the test and control groups were 3.14 mm and 3.69 mm, respectively. Conclusion: STE with a sub-periosteal approach is an applicable method to achieve an additional soft tissue and to reduce bone block graft exposure and wound dehiscence.

Keywords: soft tissue expander, ridge augmentation, block graft, symphysis bone block

Procedia PDF Downloads 125
14 The Yield of Neuroimaging in Patients Presenting to the Emergency Department with Isolated Neuro-Ophthalmological Conditions

Authors: Dalia El Hadi, Alaa Bou Ghannam, Hala Mostafa, Hana Mansour, Ibrahim Hashim, Soubhi Tahhan, Tharwat El Zahran

Abstract:

Introduction: Neuro-ophthalmological emergencies require prompt assessment and management to avoid vision or life-threatening sequelae. Some would require neuroimaging. Most commonly used are the CT and MRI of the Brain. They can be over-used when not indicated. Their yield remains dependent on multiple factors relating to the clinical scenario. Methods: A retrospective cross-sectional study was conducted by reviewing the electronic medical records of patients presenting to the Emergency Department (ED) with isolated neuro-ophthalmologic complaints. For each patient, data were collected on the clinical presentation, whether neuroimaging was performed (and which type), and the result of neuroimaging. Analysis of the performed neuroimaging was made, and its yield was determined. Results: A total of 211 patients were reviewed. The complaints or symptoms at presentation were: blurry vision, change in the visual field, transient vision loss, floaters, double vision, eye pain, eyelid droop, headache, dizziness and others such as nausea or vomiting. In the ED, a total of 126 neuroimaging procedures were performed. Ninety-four imagings (74.6%) were normal, while 32 (25.4%) had relevant abnormal findings. Only 2 symptoms were significant for abnormal imaging: blurry vision (p-value= 0.038) and visual field change (p-value= 0.014). While 4 physical exam findings had significant abnormal imaging: visual field defect (p-value= 0.016), abnormal pupil reactivity (p-value= 0.028), afferent pupillary defect (p-value= 0.018), and abnormal optic disc exam (p-value= 0.009). Conclusion: Risk indicators for abnormal neuroimaging in the setting of neuro-ophthalmological emergencies are blurred vision or changes in the visual field on history taking. While visual field irregularities, abnormal pupil reactivity with or without afferent pupillary defect, or abnormal optic discs, are risk factors related to physical testing. These findings, when present, should sway the ED physician towards neuroimaging but still individualizing each case is of utmost importance to prevent time-consuming, resource-draining, and sometimes unnecessary workup. In the end, it suggests a well-structured patient-centered algorithm to be followed by ED physicians.

Keywords: emergency department, neuro-ophthalmology, neuroimaging, risk indicators

Procedia PDF Downloads 179
13 Comparative Effect of Microbial Phytase Supplementation on Layer Chickens Fed Diets with Required or Low Phosphorous Level

Authors: Hamada Ahmed, Mervat A. Abdel-Latif, Alaa. A. Ghoraba, Samah A. Ganna

Abstract:

An experiment was conducted to determine the effect of microbial phytase (Quantum Blue®) supplementation on layer chickens fed diets with required or low phosphorous level in corn-soybean based diets. One hundred and sixteen 23-week-old Lohman brown laying hens were used in 8-week feeding trial. Hens were randomly allotted into four treatments where the group (1) (control group) was fed basal diet without phytase, group (2) fed basal diet supplemented with phytase, group (3) fed diet supplemented with phytase as a replacement of 25% of monocalcium phosphate and group (4) fed diet supplemented with phytase as a replacement of 50% of monocalcium phosphate. Records on daily egg production, egg mass, egg weight and body weight of hens at the end of experimental period were recorded. Results revealed no significant (p ≥ 0.05) differences were observed among the other dietary treatments in BW, egg production, egg mass, feed intake or feed conversion when these parameters were evaluated over the duration of the experiment while egg weight showed significant (p < 0.05) increase in all phytase supplemented groups. There was no significant (p ≥ 0.05) differences in egg quality including egg length, egg width, egg shape index, yolk height, yolk width, yolk index, yolk weight and yolk albumin ratio while egg albumin was significantly increased (p < 0.05) in group (2) and group (3). Egg shell weight increased significantly (p < 0.05) in all phytase supplemented groups when compared with the control group also shell thickness increased significantly (p < 0.05) in both group (2 &3). No significant (P ≥ 0.05) difference was observed in serum Ca, P level while alkaline phosphatase was significantly (P ˂ 0.05) increased in group (3). Egg shell analysis showed increase in egg shell ash% in all phytase supplemented groups when compared with the control group, egg shell calcium % was higher in group (3) and group (4) than the control group while group (2) showed lower egg shell calcium% than the other experimental groups, egg shell phosphorous% was higher in all phytase supplemented groups than the control group. Phosphorous digestability was significantly (P ˂ 0.05) increased in all phytase supplemented groups than the control group and the highest p digestability was in group (4). Calcium digestability showed significant (P ˂ 0.05) increase in all phytase supplemented groups when compared with the control group and the highest digetability was in group (4).

Keywords: layers, microbial phytase, Ca and P availability, egg production, egg characteristics

Procedia PDF Downloads 187
12 Pyrazolylpyrazolines: Design, Synthesis and Biological Evaluation as Dual Acting Antimalarial-Antileishmanial Agents

Authors: Adnan Bekhit, Eskedar Lodebo, Ariaya Hymete, Hanan Ragab, Alaa El-Din Bekhit

Abstract:

Malaria and leishmaniasis have emerged as serious universal health problems throughout history of mankind. According to the WHO 2008 malarial report, half of the world population is at risk of malarial infection with an estimate of 1 million deaths occurring annually mainly in the African region. Furthermore, 12-15 million people are infected with Leishmaniasis worldwide. Despite the continuous introduction of a large number of agents for the treatment of malaria, there is still unmet medical needs due to the emergence of resistance. Resistance has occurred for almost all therapeutic agents approved for the treatment of malaria. Accordingly, it was the aim of this work to design and synthesis a group of antimalarial-antileshmanial agents that would show inhibitory activity against chloroquine-resistant strain of Plasmodium falciparum. The synthesized compounds were designed to contain a pyrazolylpyrazoline moiety having an aromatic group (p-tolyl or p-chlorophenyl) at N1-position of one pyrazoline ring due to the reports of promising activities of such compounds. A formyl or acyl substituent was introduced at the N1-position of the other pyrazoline ring, to investigate the effect of bulkiness of acyl substituents at this position. The synthesized compounds were evaluated for their in-vivo antimalarial activity against Plasmodium berghei infected mice at dose levels of 20 and 30 mg/Kg. the two most active compounds were evaluated for their antimalarial activity against chloroquin-resistant strain (RKL9) of Plasmodium falciparum. In addition, the synthesized compounds were tested for their in-vitro antileshmanial activity against Leishmania aethiopica promastigotes and amastigotes. For both antimalarial and antileishmanial activities, compounds having an N1-p-tolyl group at the first pyrazoline ring did not require bulkiness at the second pyrazoline ring nitrogen where the compound bearing an acetyl group proved to be the most active of the whole series. On the other hand, bulkiness at the N1-position of the second pyazoline ring was necessary in case of compounds carrying the p-chlorophenyl group, where the two derivatives having an N1-butanoyl and an N1-benzoyl moieties at the second pyrazoline showed the best activity. Furthermore, the toxicity of the active compounds were tested and were proved to be non-toxic at 125, 250 and 500 mg/Kg. In addition, docking of the most active compound (having a p-tolyl group at the first pyrazoline-N and an acetyl moiety on the other pyrazoline-N) was performed against dihydrofolate reductase enzyme.

Keywords: pyrazoline derivatives, in-vivo antimalarial activity, docking, dihydrofolate reductase

Procedia PDF Downloads 341
11 The Effect of Nanotechnology Structured Water on Lower Urinary Tract Symptoms in Men with Benign Prostatic Hyperplasia: A Double-Blinded Randomized Study

Authors: Ali Kamal M. Sami, Safa Almukhtar, Alaa Al-Krush, Ismael Hama-Amin Akha Weas, Ruqaya Ahmed Alqais

Abstract:

Introduction and Objectives Lower urinary tract symptoms (LUTS) are common among men with benign prostatic hyperplasia (BPH). The combination of 5 alpha-reductase inhibitors and alpha-blockers has been used as a conservative treatment of male LUTS secondary to BPH. Nanotechnology structured water magnalife is a type of water that is produced by modulators and specific frequency and energy fields that transform ordinary water into this Nanowater. In this study, we evaluated the use of Nano-water with the conservative treatment and to see if it improves the outcome and gives better results in those patients with LUTS/BPH. Material and methods For a period of 3 months, 200 men with International Prostate Symptom Score (IPSS)≥13, maximum flow rate (Qmax)≤ 15ml/s, and prostate volume > 30 and <80 ccs were randomly divided into two groups. Group A 100 men were given Nano-water with the (tamsulosindutasteride) and group B 100 men were given ordinary bottled water with the (tamsulosindutasteride). The water bottles were unlabeled and were given in a daily dose of 20ml/kg body weight. Dutasteride 0.5mg and tamsulosin 0.4 mg daily doses. Both groups were evaluated for the IPSS, Qmax, Residual Urine (RU), International Index of Erectile Function–Erectile Function (IIEF-EF) domain at the beginning (baseline data), and at the end of the 3 months. Results Of the 200 men with LUTS who were included in this study, 193 men were followed, and 7 men dropped out of the study for different reasons. In group A which included 97 men with LUTS, IPSS decreased by 16.82 (from 20.47 to 6.65) (P<0.00001) and Qmax increased by 5.73 ml/s (from 11.71 to 17.44) (P<0.00001) and RU <50 ml in 88% of patients (P<0.00001) and IIEF-EF increased to 26.65 (from 16.85) (P<0.00001). While in group B, 96 men with LUTS, IPSS decreased by 8.74(from 19.59 to 10.85)(P<0.00001) and Qmax increased by 4.67 ml/s(from 10.74 to 15.41)(P<0.00001), RU<50 ml in 75% of patients (P<0.00001), and IIEF-EF increased to 21(from 15.87)(P<0.00001). Group A had better results than group B. IPSS in group A decreased to 6.65 vs 10.85 in group B(P<0.00001), also Qmax increased to 17.44 in group A vs 15.41 in group B(P<0.00001), group A had RU <50 ml in 88% of patients vs 75% of patients in group B(P<0.00001).Group A had better IIEF-EF which increased to 26.65 vs 21 in group B(P<0.00001). While the differences between the baseline data of both groups were statistically not significant. Conclusion The use of nanotechnology structured water magnalife gives a better result in terms of LUTS and scores in patients with BPH. This combination is showing improvements in IPSS and even in erectile function in those men after 3 months.

Keywords: nano water, lower urinary tract symptoms, benign prostatic hypertrophy, erectile dysfunction

Procedia PDF Downloads 71
10 The Supply Chain Operation Reference Model Adaptation in the Developing Countries: An Empirical Study on the Egyptian Automotive Sector

Authors: Alaa Osman, Sara Elgazzar, Breksal Elmiligy

Abstract:

The Supply Chain Operation Reference (SCOR) model is considered one of the most widely implemented supply chain performance measurement systems (SCPMSs). Several studies have been proposed on the SCOR model adaptation in developed countries context; while there is a limited availability of previous work on the SCPMSs application generally and the SCOR model specifically in developing nations. This paper presents a research agenda on the SCOR model adaptation in the developing countries. It aims at investigating the challenges of adapting the SCOR model to manage and measure supply chain performance in developing countries. The research will exemplify the system in the Egyptian automotive sector to gain a comprehensive understanding of how the application of the SCOR model can affect the performance of automotive companies in Egypt, with a necessary understanding of challenges and obstacles faced the adaptation of the model in the Egyptian supply chain context. An empirical study was conducted on the Egyptian automotive sector in three companies considering three different classes: BMW, Hyundai and Brilliance. First, in-depth interviews were carried out to gain an insight into the implementation and the relevance of the concepts of supply chain management and performance measurement in the Egyptian automotive industry. Then, a formal survey was designed based on the SCOR model five main processes (plan, source, make, deliver and return) and best practices to investigate the challenges and obstacles faced the adaptation of the SCOR model in the Egyptian automotive supply chain. Finally, based on the survey results, the appropriate best practices for each process were identified in order to overcome the SCOR model adaptation challenges. The results showed that the implementation of the SCOR model faced different challenges and unavailability of the required enablers. The survey highlighted the low integration of end-to-end supply chain, lacks commitment for the innovative ideas and technologies, financial constraints and lack of practical training and support as the main challenges faced the adaptation of the SCOR model in the Egyptian automotive supply chain. The research provides an original contribution to knowledge by proposing a procedure to identify challenges encountered during the process of SCOR model adoption which can pave a way for further research in the area of SCPMSs adaptation, particularly in the developing countries. The research can help managers and organizations to identify obstacles and difficulties of the SCOR model adaptation, subsequently this can facilitate measuring the improved performance or changes in the organizational performance.

Keywords: automotive sector, developing countries, SCOR model, supply chain performance

Procedia PDF Downloads 374
9 Reproductive Behaviour of the Red Sea Immigrant Lagocephalus sceleratus (Gmelin, 1789) from the Mediterranean Coast, Egypt

Authors: Mahmoud Farrag, Alaa Elhaweet, El-Sayed Akel, Mohsen Moustafa

Abstract:

The present work aimed to study the reproductive strategy of the common lesspsian puffer fish Lagocephalus sceleratus (Gmeln, 1879) from the Egyptian Mediterranean Waters. It is a famous migratory species plays an important role in the field of fisheries and ecology of aquatic ecosystem. The obtained results illustrated seven maturity stages of gonads as; I- Thread like stage: II- Immature stage (Virgin stage), III- Maturing stage (Developing Virgin and recovering spent), IV - Nearly ripe stage, V- Fully ripe; VI-Spawning stage, VII- Spent stage. Sex ratio, exhibited males had higher number than females representing 52.44 % of the total fishes with sex ratio 1: 0.91. Fish length corresponding to 50% maturation was 38.5 cm for males and 41 cm for females. The corresponding ages (age at first maturity) are equal to 2.14 and 2.27 years for male and female respectively. The gonado somatic index (GSI) increased from April for both sexes with peak in June (8.567±4.729) for males and May (6.769±4.662) for females, then the sharp decrease was observed in October showing prolong spawning season from April to September for both sexes. The hepato somatic indices (HSI) for males were lower values than those of females, it were high from December to early spawning (April & May), with the peak in April (5.217 ± 2.167) for males, and in March (5.453± 1.792) for females, then these values started to decrease towards the end of spawning period. The ova diameter ranged from 0.02 to 0.85mm, the mature ova ranged from 0.16 to 0.85mm and showed progressive increase from April towards September during spawning period introducing one peak of mature and ripe eggs. The absolute fecundity increased as the fish grew in weight and length; it was ranged from 260288 to 2372931 for fish weight and ranged from 698 to 3285 cm for length with an average of 1449522±720975. The relative fecundity ranged from 373 to 722 for fish weight with an average of 776±231, while it range from 5784 to 32957 for fish length groups ranged from 43-45 to 70-72 cm with an average of 24478 ±10011 eggs. Histological characters of gonads during the year of study indicating this fish species has prolonged spawning season from April to September where ripe oocytes were observed during this period. This species is considered totally or uni spawner with synchronous group as it contained one to two developmental stages at the same gonad and releases its ripe ova in one batch during the spawning season. These results illustrated more adaptation of this species in new habitat.

Keywords: reproductive biology, histology, Lagocephalus sceleratus, Mediterranean Sea, Egypt

Procedia PDF Downloads 433
8 Challenges of Strategies for Improving Sustainability in Urban Historical Context in Developing Countries: The Case of Shiraz Bein Al-Haramein

Authors: Amir Hossein Ashari, Sedighe Erfan Manesh

Abstract:

One of the problems in developing countries is renovating the historical context and inducing behaviors appropriate to modern life to such a context. This study was conducted using field and library methods in 2012. Similar cases carried out in Iran and developing countries were compared to unveil the strengths and weaknesses of these projects. At present, in the historical context of Shiraz, the distance between two religious shrines of Shahcheragh (Ahmad ibn Musa) and Astaneh (Sayed Alaa al-Din Hossein), which are significant places in religious, cultural, social, and economic terms, is an area full of historic places called Bein Al-Haramein. Unfortunately, some of these places have been worn out and are not appropriate for common uses. The basic strategy of Bein Al-Haramein was to improve social development of Shiraz, to enhance the vitality and dynamism of the historical context of Bein Al-Haramein and to create tourist attractions in order to boost the city's economic and social stability. To this end, the project includes the huge Bein Al-Haramein Commercial Complex which is under construction now. To construct the complex, officials have decided to demolish places of historical value which can lead to irreparable consequences. Iranian urban design has always been based on three elements of bazaars, mosques and government facilities with bazaars being the organic connector of the other elements. Therefore, the best strategy in the above case is to provide for a commercial connection between the two poles. Although this strategy is included in the project, lack of attention to renovation principles in this area and complete destruction of the context will lead to its irreversible damage and will destroy its cultural and historical identity. In urban planning of this project, some important issues have been neglected including: preserving valuable buildings and special old features of the city, rebuilding worn buildings and context to attract trust and confidence of the people, developing new models according to changes, improving the structural position of old context with minimal degradation, attracting partnerships of residents and protecting their rights and finally using potential facilities of the old context. The best strategy for achieving sustainability in Bein Al-Haramein can be the one used in the distance between Santa Maria Novella and Santa Maria Del Fiore churches in historical context where while protecting the historic context and constructions, old buildings were renovated and given different commercial and service uses making them sustainable and dynamic places. Similarly, in Bein Al-Haramein, renovating old constructions and monuments and giving different commercial and other uses to them can help improve the economic and social sustainability of the area.

Keywords: Bein Al-Haramein, sustainability, historical context, historical context

Procedia PDF Downloads 442
7 Reproductive Behavior of the Red Sea Immigrant Lagocephalus sceleratus (Gmelin, 1789) from the Mediterranean Coast, Egypt

Authors: Mahmoud M. S. Farrag, Alaa A. K. Elhaweet, El-Sayed Kh. A. Akel, Mohsen A. Moustafa

Abstract:

The present work aimed to study the reproductive strategy of the common lessepsian puffer fish Lagocephalus sceleratus (Gmelin, 1879) from the Egyptian Mediterranean Waters. It is a famous migratory species plays an important role in the field of fisheries and ecology of aquatic ecosystem. The specimens were collected monthly from the landing centers along the Egyptian Mediterranean coast during 2012. Six maturity stages were recorded: (I) Thread like stage, (II) Immature stage (Virgin stage), (III) Maturing stage (Developing Virgin and recovering spent), (IV) Nearly ripe stage, (V) Fully ripe, (VI) Spawning stage, (VII) Spent stage. According to sex ratio, males exhibited higher number than females representing 52.44 % of the total fishes with sex ratio 1: 0.91. Fish length corresponding to 50% maturation was 38.5 cm for males and 41 cm for females. The corresponding ages (age at first maturity) are equal to 2.14 and 2.27 years for male and female respectively. The ova diameter ranged from 0.02mm to 0.85mm, the mature ova ranged from 0.16mm to 0.85mm and showed progressive increase from April towards September. Also, the presences of ova diameter in one peak of mature and ripe eggs in the ovaries were observed during spawning period. The relationship between gutted weight and absolute fecundity indicated that that fecundity increased as the fish grew in weight. The absolute fecundity ranged from 260288 to 2372931 for fish weight ranged from 698 to 3285 cm with an average of 1449522±720975. The relative fecundity ranged from 373 to 722 for fish weight ranged from 698 to 3285 cm with an average of 776±231. The spawning season of L. sceleratus was investigated from the data of gonado-somatic index and monthly distribution of maturity stages along the year as well as sequence of ova diameter for mature stages and exhibited a relatively prolong spawning season extending from April for both sexes and ends in August for male while ends in September for female. Fish releases its ripe ova in one batch during the spawning season. Histologically, the ovarian cycle of L. sceleratus was classified into six stages and the testicular cycle into five stages. Histological characters of gonads of L. sceleratus during the year of study had confirmed the previous results of distribution of maturity stages, gonado-somatic index and ova diameter, indicating this fish species has prolonged spawning season from April to September. This species is considered totally or uni spawner with synchronous group as it contained one to two developmental stages at the same gonad.

Keywords: Lagocephalus sceleratus, reproductive biology, oogenesis, histology

Procedia PDF Downloads 304
6 The Effect of Positional Release Technique versus Kinesio Tape on Iliocostalis lumborum in Back Myofascial Pain Syndrome

Authors: Shams Khaled Abdelrahman Abdallah Elbaz, Alaa Aldeen Abd Al Hakeem Balbaa

Abstract:

Purpose: The purpose of this study was to compare the effects of Positional Release Technique versus Kinesio Tape on pain level, pressure pain threshold level and functional disability in patients with back myofascial pain syndrome at iliocostalis lumborum. Backgrounds/significance: Myofascial Pain Syndrome is a common muscular pain syndrome that arises from trigger points which are hyperirritable, painful and tender points within a taut band of skeletal muscle. In more recent literature, about 75% of patients with musculoskeletal pain presenting to a community medical centres suffer from myofascial pain syndrome.Iliocostalis lumborum are most likely to develop active trigger points. Subjects: Thirty patients diagnosed as back myofascial pain syndrome with active trigger points in iliocostalis lumborum muscle bilaterally had participated in this study. Methods and materials: Patients were randomly distributed into two groups. The first group consisted of 15 patients (8 males and 7 females) with mean age 30.6 (±3.08) years, they received positional release technique which was applied 3 times per session, 3/week every other day for 2 weeks. The second group consisted of 15 patients(5 males, 10 females) with a mean age 30.4 (±3.35) years, they received kinesio tape which was applied and changed every 3 days with one day off for a total 3 times in 2 weeks. Both techniques were applied over trigger points of the iliocostalis lumborum bilaterally. Patients were evaluated pretreatment and posttreatment program for Pain intensity (Visual analogue scale), pressure pain threshold (digital pressure algometry), and functional disability (The Oswestry Disability Index). Analyses: Repeated measures MANOVA was used to detect differences within and between groups pre and post treatment. Then the univariate ANOVA test was conducted for the analysis of each dependant variable within and between groups. All statistical analyses were done using SPSS. with significance level set at p<0.05 throughout all analyses. Results: The results revealed that there was no significant difference between positional release technique and kinesio tape technique on pain level, pressure pain threshold and functional activities (p > 0.05). Both groups of patients showed significant improvement in all the measured variables (p < 0.05) evident by significant reduction of both pain intensity and functional disability as well as significant increase of pressure pain threshold Conclusions : Both positional release technique and kinesio taping technique are effective in reducing pain level, improving pressure pain threshold and improving function in treating patients who suffering from back myofascial pain syndrome at iliocostalis lumborum. As there was no statistically significant difference was proven between both of them.

Keywords: positional release technique, kinesio tape, myofascial pain syndrome, Iliocostalis lumborum

Procedia PDF Downloads 231
5 Counteract Heat Stress on Broiler Chicks by Adding Anti-Heat Stress Vitamins (Vitamin C and E) with Organic Zinc

Authors: Omnia Y. Shawky, Asmaa M. Megahed, Alaa E. ElKomy, A. E. Abd-El-Hamid, Y. A. Attia

Abstract:

This study was carried out to elevate the broilers physiological response against heat stress and reduce this impact by adding vitamin C (VC), vitamin E (VE) alone/or with organic zinc (Zn) to chicks’ rations. A total of 192, 26-day-old Arbor Acers male chicks were randomly divided into equal 8 groups (4 replicates for each). All experimental groups were treated as follow: Group 2 was served as a heat stress control that reared at 37ºC with relative humidity 53 ± 8% for 6 hours/day for three successive days/week and fed the basal diet only. Groups 3-8 were heat stressed in a like manner to group 2 and fed basal diet inclusion 200mg VC (group 3), 200mg VE (group 4), 200mg VC+200mg VE (group 5), 200mg VC+30mg Zn (group 6), 200mg VE+30mg Zn (group 7) and 200mg VC+200mg VE+30mg Zn (group 8) /kg feed, while Group 1 was served as a positive control that reared on a neutral temperature (NT) (approximately 21ºC) and fed the basal diet only. Respiration rate and rectal temperature were boosted of HS chicks (80.8 breath/min and 41.97ºC) compared to NT group (60.12 breath/min and 40.9ºC), while, adding VC alone and with VE or Zn resulted in decrease these measurements. Heat stress had a significantly negative effect on chicks body weight gain, feed consumption and feed conversion ratio compared to the NT group, this harmful effect could be overcome by adding VC and VE individually or with Zn. Chicks exposed to heat stress showed slightly increase hemoglobin concentration compared to NT group, while, adding VC, VE individually or with Zn alleviated this effect. Plasma glucose concentration was significantly increased in HS group than the NT group, but adding VC, VE individually or with Zn resulted in a reduction plasma glucose level, which it was still higher than the NT group. Heat stress caused an increase in plasma total lipids and cholesterol concentration compared to the NT group and inclusion VC or VE alone or with Zn was not able to reduce this effect. The increased liver enzymes activities (AST and ALT) that observed in HS group compared to NT group were removed by adding VC and VE individually or with Zn. As well, exposure of broiler chicks to heat stress resulted in a slightly decrease in plasma total antioxidant capacity level (TAC) superoxide dismutase and catalase enzymes activities, while inclusion VC and VE individually or with Zn in chicks rations caused an increased in these measurements. Broiler chicks that exposed to HS revealed a significant increase in heat shock protein (Hsp 70) compared to the NT group, while, adding VC or VE individually or with Zn resulted in a significant decrease in Hsp70 than the HS group and VE alone or with VC had the greatest effect. In conclusion, it could be overcome the harmful and the negative effect of heat stress on broiler chicks’ productive performance and physiological status by inclusion VC (200mg) or VE (200mg) individual or in a combination with organic zinc (30 mg) in chicks’ rations.

Keywords: heat stress, broiler, vitamin C, vitamin E, organic zinc

Procedia PDF Downloads 203
4 Slope Stability and Landslides Hazard Analysis, Limitations of Existing Approaches, and a New Direction

Authors: Alisawi Alaa T., Collins P. E. F.

Abstract:

The analysis and evaluation of slope stability and landslide hazards are landslide hazards are critically important in civil engineering projects and broader considerations of safety. The level of slope stability risk should be identified due to its significant and direct financial and safety effects. Slope stability hazard analysis is performed considering static and/or dynamic loading circumstances. To reduce and/or prevent the failure hazard caused by landslides, a sophisticated and practical hazard analysis method using advanced constitutive modeling should be developed and linked to an effective solution that corresponds to the specific type of slope stability and landslides failure risk. Previous studies on slope stability analysis methods identify the failure mechanism and its corresponding solution. The commonly used approaches include used approaches include limit equilibrium methods, empirical approaches for rock slopes (e.g., slope mass rating and Q-slope), finite element or finite difference methods, and district element codes. This study presents an overview and evaluation of these analysis techniques. Contemporary source materials are used to examine these various methods on the basis of hypotheses, the factor of safety estimation, soil types, load conditions, and analysis conditions and limitations. Limit equilibrium methods play a key role in assessing the level of slope stability hazard. The slope stability safety level can be defined by identifying the equilibrium of the shear stress and shear strength. The slope is considered stable when the movement resistance forces are greater than those that drive the movement with a factor of safety (ratio of the resistance of the resistance of the driving forces) that is greater than 1.00. However, popular and practical methods, including limit equilibrium approaches, are not effective when the slope experiences complex failure mechanisms, such as progressive failure, liquefaction, internal deformation, or creep. The present study represents the first episode of an ongoing project that involves the identification of the types of landslides hazards, assessment of the level of slope stability hazard, development of a sophisticated and practical hazard analysis method, linkage of the failure type of specific landslides conditions to the appropriate solution and application of an advanced computational method for mapping the slope stability properties in the United Kingdom, and elsewhere through geographical information system (GIS) and inverse distance weighted spatial interpolation(IDW) technique. This study investigates and assesses the different assesses the different analysis and solution techniques to enhance the knowledge on the mechanism of slope stability and landslides hazard analysis and determine the available solutions for each potential landslide failure risk.

Keywords: slope stability, finite element analysis, hazard analysis, landslides hazard

Procedia PDF Downloads 100
3 Assessment of Water Pollution in the River Nile (Egypt) by Applying Blood Biomarkers in Two Excellent Model Species Oreochromis niloticus niloticus and Clarias gariepinus

Authors: Alaa G. M. Osman, Abd-El –Baset M. Abd El Reheem, Khaled Y. Abouelfadl, Usama M. Mahmoud, Mohsen A. Moustafa

Abstract:

This study aimed to explore new sites of biomarker research and to establish the use of blood parameters in wild fish populations. Four hundred and twenty fish samples were collected from six sites along the whole course of the river Nile, Egypt. The mean values of erythrocytes, thrombocytes, hemoglobin concentration, hematocrit value, and mean corpuscular volume were significantly lower in the blood of Nile tilapia and African catfish collected from downstream (contaminated) compared to upstream sites. In contrast, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration in the peripheral blood of both fish species significantly increased from upstream to downstream river Nile. The leukocytes count was significantly decreased in contaminated sites compared to upstream area. Hematological variables in the peripheral blood of Oreochromis niloticus niloticus and Clarias gariepinus exhibited significant (p<0.05) correlation with nearly all the detected chemical and physical parameters along the Nile course. In the present study, lower cellular and nuclear areas and cellular and nuclear shape factor were recorded in the erythrocytes of fish collected from downstream compared to those caught from upstream sites. This was confirmed by higher immature ratios of red cells in the blood of fish sampled from downstream river Nile. Karyorrhetic and enucleated erythrocytes were significantly correlated with physiochemical parameters in water samples collected from the same sites is being higher in the blood of fish collected from downstream sites. To see if there was any correlation between fish altered physiological fitness and environmental stress, we measured serum biochemical variables namely; total protein, cholesterol, triglycerides, calcium, chlorides, alkaline phosphatase activity (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), uric acid activity, creatinine, and serum glucose. The level of all the selected biochemical variables in the blood of O. niloticus niloticus and C. gariepinus were recorded to be significantly higher (p<0.05) in downstream sites. According to the present results, nearly all the detected haematological and blood biochemical variables are suitable indicators of contaminant exposure in O. niloticus niloticus and C. gariepinus. Also the detected erythrocytes malformations in blood collected from Nile tilapia and African catfish were proven to be suitable for bio-monitoring aquatic pollution. The results revealed species-specific differences in sensitivities, suggesting that Nile tilapia may serve as a more sensitive test species compared to African catfish.

Keywords: biomarkers, water pollution, blood parameters, river nile, african catfish, nile tilapia

Procedia PDF Downloads 291
2 Scientific and Regulatory Challenges of Advanced Therapy Medicinal Products

Authors: Alaa Abdellatif, Gabrièle Breda

Abstract:

Background. Advanced therapy medicinal products (ATMPs) are innovative therapies that mainly target orphan diseases and high unmet medical needs. ATMP includes gene therapy medicinal products (GTMP), somatic cell therapy medicinal products (CTMP), and tissue-engineered therapies (TEP). Since legislation opened the way in 2007, 25 ATMPs have been approved in the EU, which is about the same amount as the U.S. Food and Drug Administration. However, not all of the ATMPs that have been approved have successfully reached the market and retained their approval. Objectives. We aim to understand all the factors limiting the market access to very promising therapies in a systemic approach, to be able to overcome these problems, in the future, with scientific, regulatory and commercial innovations. Further to recent reviews that focus either on specific countries, products, or dimensions, we will address all the challenges faced by ATMP development today. Methodology. We used mixed methods and a multi-level approach for data collection. First, we performed an updated academic literature review on ATMP development and their scientific and market access challenges (papers published between 2018 and April 2023). Second, we analyzed industry feedback from cell and gene therapy webinars and white papers published by providers and pharmaceutical industries. Finally, we established a comparative analysis of the regulatory guidelines published by EMA and the FDA for ATMP approval. Results: The main challenges in bringing these therapies to market are the high development costs. Developing ATMPs is expensive due to the need for specialized manufacturing processes. Furthermore, the regulatory pathways for ATMPs are often complex and can vary between countries, making it challenging to obtain approval and ensure compliance with different regulations. As a result of the high costs associated with ATMPs, challenges in obtaining reimbursement from healthcare payers lead to limited patient access to these treatments. ATMPs are often developed for orphan diseases, which means that the patient population is limited for clinical trials which can make it challenging to demonstrate their safety and efficacy. In addition, the complex manufacturing processes required for ATMPs can make it challenging to scale up production to meet demand, which can limit their availability and increase costs. Finally, ATMPs face safety and efficacy challenges: dangerous adverse events of these therapies like toxicity related to the use of viral vectors or cell therapy, starting material and donor-related aspects. Conclusion. As a result of our mixed method analysis, we found that ATMPs face a number of challenges in their development, regulatory approval, and commercialization and that addressing these challenges requires collaboration between industry, regulators, healthcare providers, and patient groups. This first analysis will help us to address, for each challenge, proper and innovative solution(s) in order to increase the number of ATMPs approved and reach the patients

Keywords: advanced therapy medicinal products (ATMPs), product development, market access, innovation

Procedia PDF Downloads 76
1 Experimental-Numerical Inverse Approaches in the Characterization and Damage Detection of Soft Viscoelastic Layers from Vibration Test Data

Authors: Alaa Fezai, Anuj Sharma, Wolfgang Mueller-Hirsch, André Zimmermann

Abstract:

Viscoelastic materials have been widely used in the automotive industry over the last few decades with different functionalities. Besides their main application as a simple and efficient surface damping treatment, they may ensure optimal operating conditions for on-board electronics as thermal interface or sealing layers. The dynamic behavior of viscoelastic materials is generally dependent on many environmental factors, the most important being temperature and strain rate or frequency. Prior to the reliability analysis of systems including viscoelastic layers, it is, therefore, crucial to accurately predict the dynamic and lifetime behavior of these materials. This includes the identification of the dynamic material parameters under critical temperature and frequency conditions along with a precise damage localization and identification methodology. The goal of this work is twofold. The first part aims at applying an inverse viscoelastic material-characterization approach for a wide frequency range and under different temperature conditions. For this sake, dynamic measurements are carried on a single lap joint specimen using an electrodynamic shaker and an environmental chamber. The specimen consists of aluminum beams assembled to adapter plates through a viscoelastic adhesive layer. The experimental setup is reproduced in finite element (FE) simulations, and frequency response functions (FRF) are calculated. The parameters of both the generalized Maxwell model and the fractional derivatives model are identified through an optimization algorithm minimizing the difference between the simulated and the measured FRFs. The second goal of the current work is to guarantee an on-line detection of the damage, i.e., delamination in the viscoelastic bonding of the described specimen during frequency monitored end-of-life testing. For this purpose, an inverse technique, which determines the damage location and size based on the modal frequency shift and on the change of the mode shapes, is presented. This includes a preliminary FE model-based study correlating the delamination location and size to the change in the modal parameters and a subsequent experimental validation achieved through dynamic measurements of specimen with different, pre-generated crack scenarios and comparing it to the virgin specimen. The main advantage of the inverse characterization approach presented in the first part resides in the ability of adequately identifying the material damping and stiffness behavior of soft viscoelastic materials over a wide frequency range and under critical temperature conditions. Classic forward characterization techniques such as dynamic mechanical analysis are usually linked to limitations under critical temperature and frequency conditions due to the material behavior of soft viscoelastic materials. Furthermore, the inverse damage detection described in the second part guarantees an accurate prediction of not only the damage size but also its location using a simple test setup and outlines; therefore, the significance of inverse numerical-experimental approaches in predicting the dynamic behavior of soft bonding layers applied in automotive electronics.

Keywords: damage detection, dynamic characterization, inverse approaches, vibration testing, viscoelastic layers

Procedia PDF Downloads 205