Navigating through the COVID-19 pandemic. Unfinished learning in primary and secondary education in Tunisia

During the outbreak of the global SARS-CoV-2 (COVID-19) pandemic, Tunisia, like many countries, prepared an emergency plan to shift to distance learning to salvage the academic year and ensure continuous learning. However, a shortage of digital materials coupled with the fact that many households did not have adequate Internet bandwidth made it virtually impossible to secure adequate digital learning. When in-person schooling was restarted in 2020/21, primary, pre-secondary, and secondary school pupils attended school on alternate days to avoid overcrowding. As a result of the pandemic, the curriculum has been lightened, and the fundamentals have been prioritized. Based on a content analysis of the Ministry of Education documents and a survey conducted by the Ministry on remote learning, we shed light on the different measures taken to curb learning loss during the spread of the pandemic as well as the challenges facing Tunisian students and the government. The consequences of these measures are discussed along with future recommendations. (DIPF/Orig.

L’endocardite à Bartonella en Tunisie: Particularités lésionnelles et évolutives

L'endocardite à Bartonalla est une infection ubiquitaire, son diagnostic est difficile vu qu'il s'agit souvent d'endocardite à hémoculture négative. Lebut de cette étude est d'analyser les particularités lésionnelles et  évolutives de cette entité dans un pays du nord d'Afrique, la Tunisie et dedémontrer la gravité de cette infection. Nous avons étudié  rétrospectivement les dossiers médicaux de 20 patients atteints  d'endocardite à Bartonella, confirmée selon les critères de Dukes modifiés. L'âge moyen de nos patients était 37 ans avec une prédominance  masculine (SR=3). Tous nos malades avaient un niveau socio-économique bas. Le motif essentiel de consultation était la dyspnée, 6 patients étaient admis dans un tableau d'insuffisance cardiaque congestive. Une  prédilection des lésions au niveau de la valve aortique a été notée (14 cas). Quatorze patients avaient des végétations endocarditiques avec une taille qui dépasse 10 mm chez 8 malades. La majorité des patients (18 patients) présentaient une régurgitation valvulaire massive en rapport principalement avec des mutilations importantes (6 cas de ruptures de cordages mitraux, 2 cas de déchirures des sigmoïdes aortiques, un cas de perforation valvulaire aortique, un cas de désinsertion de prothèse  mitrale). Quinze malades (3/4) avaient nécessité une chirurgie à la phase active de la maladie, l'indication majeure était l'insuffisance cardiaque. Une complication neurologique était notée chez 2 malades et une  complication rénale chez 3 malades. Treize patients étaient guéris, 5 malades étaient décédés et 2 malades opérés ont présenté une  réinfection à staphylococcus aureus et à candida albicans en  postopératoire. L'endocardite à Bartonella est une infection grave. Cette Bactérie possède un potentiel destructif important. Le recours à la chirurgie est quasi constant. La morbi-mortalité est élevée. La recherche de cette bactérie devrait être alors systématique chez nos malades suspects d'endocardite d'autant plus que la bartonellose est endémique sur nos terres

A multi-biometric iris recognition system based on a deep learning approach

YesMultimodal biometric systems have been widely applied in many real-world applications due to its ability to deal with a number of significant limitations of unimodal biometric systems, including sensitivity to noise, population coverage, intra-class variability, non-universality, and vulnerability to spoofing. In this paper, an efficient and real-time multimodal biometric system is proposed based on building deep learning representations for images of both the right and left irises of a person, and fusing the results obtained using a ranking-level fusion method. The trained deep learning system proposed is called IrisConvNet whose architecture is based on a combination of Convolutional Neural Network (CNN) and Softmax classifier to extract discriminative features from the input image without any domain knowledge where the input image represents the localized iris region and then classify it into one of N classes. In this work, a discriminative CNN training scheme based on a combination of back-propagation algorithm and mini-batch AdaGrad optimization method is proposed for weights updating and learning rate adaptation, respectively. In addition, other training strategies (e.g., dropout method, data augmentation) are also proposed in order to evaluate different CNN architectures. The performance of the proposed system is tested on three public datasets collected under different conditions: SDUMLA-HMT, CASIA-Iris- V3 Interval and IITD iris databases. The results obtained from the proposed system outperform other state-of-the-art of approaches (e.g., Wavelet transform, Scattering transform, Local Binary Pattern and PCA) by achieving a Rank-1 identification rate of 100% on all the employed databases and a recognition time less than one second per person

RAB32 Ser71Arg in autosomal dominant Parkinson's disease: linkage, association, and functional analyses

Background: Parkinson's disease is a progressive neurodegenerative disorder with multifactorial causes, among which genetic risk factors play a part. The RAB GTPases are regulators and substrates of LRRK2, and variants in the LRRK2 gene are important risk factors for Parkinson's disease. We aimed to explore genetic variability in RAB GTPases within cases of familial Parkinson's disease. // Methods: We did whole-exome sequencing in probands from families in Canada and Tunisia with Parkinson's disease without a genetic cause, who were recruited from the Centre for Applied Neurogenetics (Vancouver, BC, Canada), an international consortium that includes people with Parkinson's disease from 36 sites in 24 countries. 61 RAB GTPases were genetically screened, and candidate variants were genotyped in relatives of the probands to assess disease segregation by linkage analysis. Genotyping was also done to assess variant frequencies in individuals with idiopathic Parkinson's disease and controls, matched for age and sex, who were also from the Centre for Applied Neurogenetics but unrelated to the probands or each other. All participants were aged 18 years or older. The sequencing and genotyping findings were validated by case–control association analyses using bioinformatic data obtained from publicly available clinicogenomic databases (AMP-PD, GP2, and 100 000 Genomes Project) and a private German clinical diagnostic database (University of Tübingen). Clinical and pathological findings were summarised and haplotypes were determined. In-vitro studies were done to investigate protein interactions and enzyme activities. // Findings: Between June 1, 2010, and May 31, 2017, 130 probands from Canada and Tunisia (47 [36%] female and 83 [64%] male; mean age 72·7 years [SD 11·7; range 38–96]; 109 White European ancestry, 18 north African, two east Asian, and one Hispanic] underwent whole-exome sequencing. 15 variants in RAB GTPase genes were identified, of which the RAB32 variant c.213C>G (Ser71Arg) cosegregated with autosomal dominant Parkinson's disease in three families (nine affected individuals; non-parametric linkage Z score=1·95; p=0·03). 2604 unrelated individuals with Parkinson's disease and 344 matched controls were additionally genotyped, and five more people originating from five countries (Canada, Italy, Poland, Turkey, and Tunisia) were identified with the RAB32 variant. From the database searches, in which 6043 individuals with Parkinson's disease and 62 549 controls were included, another eight individuals were identified with the RAB32 variant from four countries (Canada, Germany, UK, and USA). Overall, the association of RAB32 c.213C>G (Ser71Arg) with Parkinson's disease was significant (odds ratio [OR] 13·17, 95% CI 2·15–87·23; p=0·0055; I2=99·96%). In the people who had the variant, Parkinson's disease presented at age 54·6 years (SD 12·75, range 31–81, n=16), and two-thirds had a family history of parkinsonism. RAB32 Ser71Arg heterozygotes shared a common haplotype, although penetrance was incomplete. Findings in one individual at autopsy showed sparse neurofibrillary tangle pathology in the midbrain and thalamus, without Lewy body pathology. In functional studies, RAB32 Arg71 activated LRRK2 kinase to a level greater than RAB32 Ser71. // Interpretation: RAB32 Ser71Arg is a novel genetic risk factor for Parkinson's disease, with reduced penetrance. The variant was found in individuals with Parkinson's disease from multiple ethnic groups, with the same haplotype. In-vitro assays show that RAB32 Arg71 activates LRRK2 kinase, which indicates that genetically distinct causes of familial parkinsonism share the same mechanism. The discovery of RAB32 Ser71Arg also suggests several genetically inherited causes of Parkinson's disease originated to control intracellular immunity. This shared aetiology should be considered in future translational research, while the global epidemiology of RAB32 Ser71Arg needs to be assessed to inform genetic counselling. // Funding: National Institutes of Health, the Canada Excellence Research Chairs program, Aligning Science Across Parkinson's, the Michael J Fox Foundation for Parkinson's Research, and the UK Medical Research Council

RAB32 Ser71Arg in autosomal dominant Parkinson's disease:linkage, association, and functional analyses

BACKGROUND: Parkinson's disease is a progressive neurodegenerative disorder with multifactorial causes, among which genetic risk factors play a part. The RAB GTPases are regulators and substrates of LRRK2, and variants in the LRRK2 gene are important risk factors for Parkinson's disease. We aimed to explore genetic variability in RAB GTPases within cases of familial Parkinson's disease.METHODS: We did whole-exome sequencing in probands from families in Canada and Tunisia with Parkinson's disease without a genetic cause, who were recruited from the Centre for Applied Neurogenetics (Vancouver, BC, Canada), an international consortium that includes people with Parkinson's disease from 36 sites in 24 countries. 61 RAB GTPases were genetically screened, and candidate variants were genotyped in relatives of the probands to assess disease segregation by linkage analysis. Genotyping was also done to assess variant frequencies in individuals with idiopathic Parkinson's disease and controls, matched for age and sex, who were also from the Centre for Applied Neurogenetics but unrelated to the probands or each other. All participants were aged 18 years or older. The sequencing and genotyping findings were validated by case-control association analyses using bioinformatic data obtained from publicly available clinicogenomic databases (AMP-PD, GP2, and 100 000 Genomes Project) and a private German clinical diagnostic database (University of Tübingen). Clinical and pathological findings were summarised and haplotypes were determined. In-vitro studies were done to investigate protein interactions and enzyme activities.FINDINGS: Between June 1, 2010, and May 31, 2017, 130 probands from Canada and Tunisia (47 [36%] female and 83 [64%] male; mean age 72·7 years [SD 11·7; range 38-96]; 109 White European ancestry, 18 north African, two east Asian, and one Hispanic] underwent whole-exome sequencing. 15 variants in RAB GTPase genes were identified, of which the RAB32 variant c.213C&gt;G (Ser71Arg) cosegregated with autosomal dominant Parkinson's disease in three families (nine affected individuals; non-parametric linkage Z score=1·95; p=0·03). 2604 unrelated individuals with Parkinson's disease and 344 matched controls were additionally genotyped, and five more people originating from five countries (Canada, Italy, Poland, Turkey, and Tunisia) were identified with the RAB32 variant. From the database searches, in which 6043 individuals with Parkinson's disease and 62 549 controls were included, another eight individuals were identified with the RAB32 variant from four countries (Canada, Germany, UK, and USA). Overall, the association of RAB32 c.213C&gt;G (Ser71Arg) with Parkinson's disease was significant (odds ratio [OR] 13·17, 95% CI 2·15-87·23; p=0·0055; I2=99·96%). In the people who had the variant, Parkinson's disease presented at age 54·6 years (SD 12·75, range 31-81, n=16), and two-thirds had a family history of parkinsonism. RAB32 Ser71Arg heterozygotes shared a common haplotype, although penetrance was incomplete. Findings in one individual at autopsy showed sparse neurofibrillary tangle pathology in the midbrain and thalamus, without Lewy body pathology. In functional studies, RAB32 Arg71 activated LRRK2 kinase to a level greater than RAB32 Ser71.INTERPRETATION: RAB32 Ser71Arg is a novel genetic risk factor for Parkinson's disease, with reduced penetrance. The variant was found in individuals with Parkinson's disease from multiple ethnic groups, with the same haplotype. In-vitro assays show that RAB32 Arg71 activates LRRK2 kinase, which indicates that genetically distinct causes of familial parkinsonism share the same mechanism. The discovery of RAB32 Ser71Arg also suggests several genetically inherited causes of Parkinson's disease originated to control intracellular immunity. This shared aetiology should be considered in future translational research, while the global epidemiology of RAB32 Ser71Arg needs to be assessed to inform genetic counselling.FUNDING: National Institutes of Health, the Canada Excellence Research Chairs program, Aligning Science Across Parkinson's, the Michael J Fox Foundation for Parkinson's Research, and the UK Medical Research Council.</p

Stability of domain structures in multi-domain proteins

Multi-domain proteins have many advantages with respect to stability and folding inside cells. Here we attempt to understand the intricate relationship between the domain-domain interactions and the stability of domains in isolation. We provide quantitative treatment and proof for prevailing intuitive ideas on the strategies employed by nature to stabilize otherwise unstable domains. We find that domains incapable of independent stability are stabilized by favourable interactions with tethered domains in the multi-domain context. Stability of such folds to exist independently is optimized by evolution. Specific residue mutations in the sites equivalent to inter-domain interface enhance the overall solvation, thereby stabilizing these domain folds independently. A few naturally occurring variants at these sites alter communication between domains and affect stability leading to disease manifestation. Our analysis provides safe guidelines for mutagenesis which have attractive applications in obtaining stable fragments and domain constructs essential for structural studies by crystallography and NMR

Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort

Background: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited. Objective: The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD. Methods: We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype–phenotype relationships were analyzed. Results: We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published. Conclusions: Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Effects of poling and crystallinity on the dielectric properties of Pb(In1/2Nb1/2)O3-Pb(Mg1/3Nb2/3)O3-PbTiO3 at cryogenic temperatures

The mechanisms underlying the anomalously large, room temperature piezoelectric activity of relaxor-PbTiO3 type single crystals have previously been linked to low temperature relaxations in the piezoelectric and dielectric properties. We investigate the properties of Pb(In1/2Nb1/2)O3-Pb(Mg1/3Nb2/3)O3-PbTiO3 between 10 and 300 K using dielectric permittivity measurements. We compare results on single crystal plates measured in the [001] and [111] directions with a polycrystalline ceramic of the same composition. Poled crystals have very different behaviour to unpoled crystals, whereas the dielectric spectrum of the polycrystalline ceramic changes very little on poling. A large, frequency dependent dielectric relaxation is seen in the poled [001] crystal around 100 K. The relaxation is much less prominent in the [111] cut crystal, and is not present in the polycrystalline ceramic. The unique presence of the large relaxation in poled, [001] oriented crystals indicates that the phenomenon is not due their relaxor nature alone. We propose that heterophase dynamics such as the motion of phase domain boundaries are responsible for both the anomalous electromechanical and dielectric behaviour

Using global team science to identify genetic parkinson's disease worldwide.

No abstract available