193 research outputs found
Paraplégies spastiques héréditaires : exploration clinique au Soudan, études des origines moléculaires des formes autosomiques récessives et identification de nouveaux gènes en cause
No full textHereditary spastic paraplegias (HSP), a heterogeneous group of spastic neurodegenerative disorders which impose diagnostic challenges. I explored the clinical varieties and genetic pathways of spastic neurodegeneration in a familial Sudanese cohort. We recruited 41 Sudanese families [337 individuals/106 HSP patients]. I have established a genomic DNA bank and when necessary, skin biopsies and fibroblasts were also obtained. A phenotype-based candidate gene approach was followed in 4 families. A targeted next generation sequencing (NGS) for 74 HSP-related genes was the main screening strategy in all-remaining 37 families. Whole exome sequencing (WES) was done in search for novel mutations in new genes in families with negative screening results. Occasionally, functional studies were conducted when feasible and relevant. I identified the genetic cause in 17/41 families. In 12 families, the mutated genes were known HSP genes. In 3 families, novel genes were identified mutated. 5 candidate genes segregated with disease in 2 other families with more experiments needed to conclude. Analysis of the NGS screening panel and of WES data imposed certain challenges as multiple genetic disorders were sometimes found running in parallel in the same/different branches of highly inbred families. We could expand the phenotypic heterogeneity of these disorders due to clinical differences observed between Sudanese patients and patients of other origins even when caused by mutations by the same gene/variant. This is the first genetic screening in a large set of HSP families in Sudan. It describes new causative genes, paving the way for further deciphering of the underlying mechanisms.Les paraplégies spastiques héréditaires (PSH) font partie d’un groupe plus large de pathologies neurodégénératives associant une spasticité. J’ai exploré la variabilité clinique et moléculaire de ces pathologies à l’aide d’une cohorte de familles soudanaises. Nous avons recruté 41 familles soudanaises [337 individus/106 atteints de PSH]. J’ai extrait l’ADN génomique et constitué une banque. Le criblage de gènes candidats a été réalisé dans 4 familles en fonction du phénotype des patients. La technologie de séquençage de nouvelle génération (SNG) appliquée à 74 gènes de PSH a ensuite été appliquée aux 37 cas restants. Enfin, le séquençage de l’exome a permis de rechercher les gènes en cause dans les cas négatifs. Dans certains cas, des études fonctionnelles ont été utilisées afin de valider l’effet biologique des mutations. J’ai pu identifier la cause génétique dans 17 familles. Dans 12 familles, la mutation concernait un gène de PSH connu. Dans 3 familles, un nouveau gène a été identifié. 5 gènes candidats restent à départager dans 2 familles. Il est à noter que parfois, de multiple mutations ou maladies génétiques ségrégaient dans nos familles, dans la même branche ou dans des branches séparées. La complexité de ces familles fortement consanguines a rendu l’analyse des données du SNG difficile. Une autre particularité a été l’hétérogénéité clinique associée à des mutations du même gène entre patients de la même famille ou en comparaison avec la littérature. Ce travail est la première étude à grande échelle de patients soudanais avec PSH et rapporte de nouveaux gènes en cause, prérequis pour mieux comprendre dans le futur les mécanismes sous-jacents
Identifier les gènes candidats prédisposant à la dégénérescence spinocérébelleuse héréditaire dans une cohorte de familles soudanaises
No full textLes dégénérescences spinocérébelleuses héréditaires forme un groupe de troubles monogéniques qui partagent des mécanismes pathogènes communs et comprennent les paraplégies spastiques, l'ataxie cérébelleuse et l'ataxie spinocérébelleuse. Elles peuvent être pures ou complexe associant une neuropathie axonale ou des troubles cognitifs. Plus de 200 gènes et locus hérités via tous les modes de transmission mendéliens sont connus. L'hérédité autosomique récessive prédomine dans les communautés consanguines; cependant, une transmission autosomique dominante, de novo, et liée au chromosome X est parfois retrouvée. Le Soudan est composé de populations génétiquement diverses, mais il possède un des taux les plus élevés de consanguinité. Nous avons utilisé une combinaison de séquençage de nouvelle génération, de génotypage, d’analyse bioinformatique, et d'expérimentation fonctionnelle pour étudier 87 patients de 38 familles Soudanaises présentant ces maladies. Nous avons obtenu un diagnostic génétique dans 71-92% de ces familles, y compris sept familles dans lesquelles se transmettent des variants dans de nouveaux gènes candidats et trois familles associée à de nouveaux phénotypes dans des gènes connus. Ces résultats montrent l’hétérogénéité génétique de ces maladies et viennent compléter un peu plus leur nosologie avec des conséquences en diagnostic génétique en pratique médicale.Hereditary spinocerebellar degenerations are group of monogenic disorders that share common pathogenic mechanisms and include spastic paraplegia, cerebellar ataxia, and spinocerebellar ataxia. They can be pure or complicated with axonal neuropathy or mental impairment. More than 200 genes and loci inherited through all modes of Mendelian inheritance are known. Autosomal recessive inheritance predominates in consanguineous communities; however, autosomal dominant, de novo, and X-linked inheritance can also occur. Sudan is inhabited by genetically diverse populations, yet it has high rates of consanguinity. We used next-generation sequencing, genotyping, bioinformatics analysis, and functional experimentation to study 87 patients from 38 Sudanese families segregating multiple forms of these diseases. We reached a genetic diagnosis in 71-92% of these families, including seven families harboring variants in seven novel candidate genes and three families with novel phenotypes associated to known genes. These results highlight the heterogeneity of these diseases and add novel findings to their nosology which should have consequences in genetic diagnosis in clinical practice
Correction: Guidelines for the prevention, detection and management of the renal complications of COVID-19 in Africa
No full textThe authors of the article ‘Guidelines for the prevention, detection and management of the renal complications of COVID-19 in Africa’ [1] wish to acknowledge the contribution of Professor Hussein El Fishawy. Our guidelines drew on various sources, including the Egyptian Ministry of Health guidelines, portions of which were adapted and reproduced with permission from the Egyptian Ministry of Health. Two of the authors of those guidelines, Professors Elsayed and Zaki, are also coauthors of our paper. Professor El Fishawy was the third author of the Egyptian guidelines and we would like to acknowledge his contribution to our review through this source, especially with respect to the treatment algorithms for patients with kidney transplants and those with acute kidney injury. Reference1. Elsayed HM, Wadee S, Zaki MS, Were AJO, Ashuntantang GE, Bamgboye EL, et al. Guidelines for the prevention, detection and management of the renal complications of COVID-19 in Africa. Afr J Nephrol. 2020; 23(1):109-126
Représentations littéraires du sacré dans le roman maghrébin de langue française
No full textThis interdisciplinary study explores how Driss Chraïbi’s L’Homme du Livre (1995), Assia Djebar’s Loin de Médine (1991), and Anissa Boumediène’s La fin d’un monde (1991) present accounts of particular historical moments in early Islam. This study explores the role of the imagination as well as freedom of invention when reconstructing historical events. It engages the novels through a study of the interplay between the literary text and the sources and traditions that impact and shape the text narrative. Gaining direct access to the original sources in Arabic serves to analyze how religious and early historical materials are considered in and reflected by the fictional texts. Because the sources tend to differ in both content and approach, this study examines their preoccupations in order to determine the criteria of selection applied by each novelist.Ph.D.Includes bibliographical referencesIncludes vitaby Hanan Elsaye
Insights into Clinical, Genetic, and Pathological Aspects of Hereditary Spastic Paraplegias: A Comprehensive Overview
No full textInternational audienceHereditary spastic paraplegias (HSP) are a heterogeneous group of motor neurodegenerative disorders that have the core clinical presentation of pyramidal syndrome which starts typically in the lower limbs. They can present as pure or complex forms with all classical modes of monogenic inheritance reported. To date, there are more than 100 loci/88 spastic paraplegia genes (SPG) involved in the pathogenesis of HSP. New patterns of inheritance are being increasingly identified in this era of huge advances in genetic and functional studies. A wide range of clinical symptoms and signs are now reported to complicate HSP with increasing overall complexity of the clinical presentations considered as HSP. This is especially true with the emergence of multiple HSP phenotypes that are situated in the borderline zone with other neurogenetic disorders. The genetic diagnostic approaches and the utilized techniques leave a diagnostic gap of 25% in the best studies. In this review, we summarize the known types of HSP with special focus on those in which spasticity is the principal clinical phenotype ("SPGn" designation). We discuss their modes of inheritance, clinical phenotypes, underlying genetics, and molecular pathways, providing some observations about therapeutic opportunities gained from animal models and functional studies. This review may pave the way for more analytic approaches that take into consideration the overall picture of HSP. It will shed light on subtle associations that can explain the occurrence of the disease and allow a better understanding of its observed variations. This should help in the identification of future biomarkers, predictors of disease onset and progression, and treatments for both better functional outcomes and quality of life
Intrathecal Drug Delivery Systems Survey: Trends in Utilization in Pain Practice [Corrigendum]
No full textAbd-Sayed A, Fiala K, Weisbein J, et al. J Pain Res. 2022;15:1305–1314.
The authors have advised there is an error in the author list on page 1305. The author name “Alaa Abd-Sayed” should read “Alaa Abd-Elsayed”.
The authors apologize for this error
Clinical and Genetic Characteristics of Leukodystrophies in Africa
No full textABSTRACTRecent understanding of the genetic basis of neurological disorders in Africa has grown rapidly in the last two decades. Africa harbors the largest genetic repertoire in the world which gives unique opportunity to discover novel variant, genes, and molecular pathways associated with various neurological diseases. Despite that, large-scale genomic and exome studies are severely lacking especially for neglected diseases such as leukodystrophies. This review aims to shed light on the currently developed research in leukodystrophies in Africa. We reviewed all research articles related to “Leukodystrophy in Africa” published in Medline/PubMed and Google Scholar databases up to date. We found very few studies in leukodystrophy from Africa, especially from the Sub-Saharan regions. Metachromatic leukodystrophy was the most studied type of leukodystrophy. Published studies from North Africa (Tunisia, Morocco, and Egypt) were very limited in either sample size (case studies or single/few family studies) or molecular methods (targeted sequencing or polymerase chain reaction-restriction fragment length polymorphisms). More studies (GWAS or large family studies) with advanced techniques such as exome or whole genome sequencing are needed to unveil the genetic basis of leukodystrophy in Africa. Unmasking novel genes and molecular pathways of leukodystrophies invariably lead to better detection and treatment for both Africans and worldwide populations.</jats:p
Degradation modeling of ink fading and diffusion of printed images
No full textColor printing plays an important role in the modern society. It is known that the color of printed images degrades gradually due to the fading and diffusion of the inks. Color degradation leads to a distortion or loss of the original information in printed images. Therefore, it is desirable to understand how the color of printed images changes over time. In this dissertation, we present degradation models to predict the characteristics of the ink fading and diffusion of printed images.
We begin by modeling the ink degradation from a physics-based perspective. Color images are printed by projecting small ink dots on medium, usually paper. This technique is called halftone printing. Halftone printing of color images results in a variety of ink mixtures and subsequently their potential catalytic fading. For the most commonly used Cyan-Magenta-Yellow-Black (CMYK) ink set, sixteen possible ink mixtures are generated during printing. A state transition diagram is then proposed for the ink fading in this multi-ink printing scenario. The ink area coverage is used as the performance indicator. Assuming constant fading and diffusion rates, we develop an ink fading model based on the differential equations according to the state transition diagram and an autoregressive ink diffusion model by discretizing the two-dimensional diffusion equation. The two models are then integrated into a single degradation model.
Further examination of the developed degradation models reveals that the fading or diffusion rate is equivalent to the hazard rate in reliability engineering. It is known that the hazard rate of the exponential failure time distribution is constant. Hence, the developed degradation model with constant fading and diffusion rates is equivalent to the multistate Markov process model with exponential transition time distribution. By using non-exponential transition time distributions, the fading and diffusion rates become time-varying and a more general semi-Markov process degradation model is developed accordingly.
Moreover, stochastic process models are investigated to provide stochastic area coverage prediction for the ink degradation. We first model the ink fading using the Hull-White/Vasicek (HWV) stochastic process. The HWV ink fading model considers that the variance of the ink area coverage shrinks as it approaches zero. Besides, spatial convolution is used to model ink diffusion. The two models are integrated into a spatio-temporal stochastic degradation model for the ink fading and diffusion of printed images. The cases of recurrent and non-recurrent time-varying fading and diffusion rates are investigated.
Inks on the paper degrade, so does the paper. The degradation of paper condition may in turn affect the degradation of the inks. Therefore, the investigation of the degradation modeling of ink fading and ink diffusion with ink-paper interactions is needed. Two aspects of the ink-paper interactions are considered, i.e., the effect of paper aging such as depolymerization and yellowing, and the fiber orientation of the paper.
The degradation process of printed images usually takes a very long time. An accelerated degradation model and the optimal design of accelerated degradation test planning is developed for accurate degradation prediction of printed images. The effects of three constant environmental stresses: temperature, humidity, and illumination (intensity), are investigated, and experimental data are used to validate the proposed model. The results show strong agreements between the proposed ink fading and ink diffusion prediction model and the actual experimental data.Ph.D.Includes bibliographical reference
Reliability estimation of balanced systems with multi-dimensional distributed units
No full textBalanced systems with multi-dimensional distributed units are emerging in a diverse range of industries. This includes Unmanned Aerial Vehicles (UAV) with multi-level of rotary wings, Spherical Unmanned Vehicles (SUV), Spherical Phased Array Antenna (SPAA), etc. In this dissertation, we present the reliability estimation for such systems. In particular, we consider two configurations: 1) balanced systems with units distributed circularly on multi-level and 2) balanced systems with units distributed spherically.
First, balanced systems with units distributed circularly on multi-level are generalized as (k₁, k₂)-out-of-(n, m) pairs: G balanced systems. We consider two scenarios: 1) all units perform the same function and 2) adjacent pairs perform complementary functions. For both scenarios, unbalanced system is considered as failed. When units fail and cause the system imbalance, we explore two approaches to rebalance the system: 1) forcing down units on other locations and 2) resuming units that are previously forced down (if any). When units in a system perform the same function, operational states are defined as balanced states with at least k₁ operating pairs and each operating pair has at least k₂ units on each side. The system reliability is obtained by enumerating all of the operational states and summing the probabilities of those states. For (k₁, k₂)-out-of-(n, m) pairs: G balanced systems with adjacent pairs performing complementary functions, in addition to maintaining system balance, the adjacent operating pairs are required to perform complementary functions. Thus, if a pair fails, one of the adjacent pairs is forced down. Similarly, the system reliability is obtained by enumerating all of the operational states. It becomes computational expensive when the number of units in each pair and/or the number of pairs are large. In that case, efficient algorithms are developed to obtain the reliability for such systems.
The balanced system with units distributed spherically is generalized as a spherical k-n-i: G balanced system. We consider two balancing requirements: 1) rotational balance is maintained so that the system is not rotating w.r.t. roll, yaw and pitch axes and 2) symmetrical balance is essential in improving the systems’ stability. We present mathematical approaches to determine the balance status of a system. Similarly, the unbalanced system is rebalanced by 1) forcing down units on other locations and 2) resuming previously forced-down units. The system reliability is obtained by the enumeration of operational states and calculation of operational states’ probabilities. We develop an efficient algorithm for reliability estimation when the number of units in the system is large.
Degradation models are developed for the (k₁, k₂)-out-of-(n, m) pairs: G balanced systems to further investigate the system reliability when degradation data are available. The degradation processes of units in the system are either stationary (inverse Gaussian process) or non-stationary (improved inverse Gaussian process). We propose a degradation balance mechanism in which the ‘most’ degraded units are forced down temporarily during the degradation process so that the system is less possible to fail due to imbalance. A closed-form lower bound reliability is presented when the balance mechanism is not applied. When it is applied, reliability is obtained by Monte Carlo simulation.
From the reliability study of the both configurations, it is observed that the reliability of a balanced system with multi-dimensional distributed units depends not only on the system’s total number of units and the least number of operating units, but also on the system configurations and balance requirements. Systems with more units do not necessarily provide a higher reliability since they are more likely to fail due to imbalance. Thus, optimal system design is key to maximize the system reliability which is investigated through numerical examples in this dissertation.Ph.D.Includes bibliographical reference
Quantifying secondary particle dose contributions in proton therapy
No full textIn order to create radiotherapy treatment plans for cancer patients, dose calculations need to be done as quickly as possible to get accurate results. However, current dose calculation algorithms take too much time to be deployed effectively. The current in house algorithm of the Medical Physics and Technology Section at the TU Delft, attempts to solve this problem by utilising a deterministic algorithm that has a significant time advantage over Monte Carlo algorithms. However, this comes with the cost of inaccuracy, one of which is that it assumesall dose is deposited locally along the beam path. This is inaccurate as secondary particles created from non-elastic nuclear interactions can deposit their dose far from the beam path due to retaining significant kinetic energy. This thesis attempts to reduce this inaccuracy by mapping and quantifying the secondary particles to assess their contribution in non-local dose deposition. And analysing the relevant particle’s energy and angle distributions to gain insight into the development of the particle's characteristics with depth. Thereafter the relevantparticle’s are then utilised as a source to emulate their production in a primary proton beam at different depths to obtain the relevant 3D dose distributions. The analysis concluded that secondary protons are the most relevant secondary particle as they contribute to 88% of the secondary dose and have a significant range to deposit their dose non locally. By utilising the secondary protons as a source, it was found that the relative error between the integrated depth dose (IDD) of the scored protons and the IDD obtained directly from Monte Carlo simulations is equal to 5.1% in the z-direction and 3.4% in the x and y-direction. The absolute difference was found to be 1.54 × 10−5 Gy which is equal to 0.096% of the total dose and 2.75% of the dose contributed by all secondary particles. The results show that the methodology can produce accurate 3D dose matrices for secondary protons at different depths, which can then be used to improve the accuracy of the in house algorithm by adding the precalculated 3D dose matrices to the algorithmApplied Physic
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