621 research outputs found

    La diversificazione intraclonale nei geni IGHV nella leucemia linfatica cronica: da un approccio bioinformatico alla clinica.

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    In dependence of the identity of the variable region of the heavy chain of the immunoglobulin (IGHV) gene respect to the germline, chronic lymphocytic leukemia (CLL) may be subdivided into U-CLL and M-CLL. The evaluation of the IGHV is a hallmark in CLL due to the stability during time and its prognostic and predictive value. Despite this, IGHV intraclonal diversification (ID) has been described in the Sanger era. However, in the Next Generation Sequencing era, no author developed a solid and reliable workflow for ID identification and quantification. It follows that ID characterization is still lacking. Moreover, nobody evaluated the clinical impact of ID in CLL yet. Using the NGS technologies we exploited the immunoglobulin repertoire of 1091 CLL samplesto generate a tailored approach for ID evaluation. Using these data, we developed an innovative methodology to identify systematic sequencing errors (SE) on sequencing data of immunological repertoire (RepSeq), correct them and evaluate ID through the calculation of the inverse Simpson Index (iSI). With focused experiments, we demonstrated the robustness of our approach and the full superimposition of corrected data with the gold standard for RepSeq, namely unique molecular identifiers-based amplification protocol. Moreover, we validate our approach by analyzing other B cell malignancies with documented ID producing a classification coherent with the literature. A validated cutoff of 1.2 of iSI was generated to discriminate CLL samples with ID features (I) and samples without (nI). Among 983 CLL patients with iSI score available, only 15% of samples displayed ID according to 8 the iSI 1.2 cutoff. Both M-CLL and U-CLL have sample with ID, despite a significant ID skewing toward M-CLL was found. No variation in IGHV family or gene usage according to the presence/absence of ID was reported. Analyzing the RepSeq data for the identification of molecular signatures compatible with canonical somatic hypermutation (SHM) processes we observed a significant higher presence of mutations based on Activation induced cytidine deaminase (AICDA) in the context of I-CLL. Indeed, a significant higher AICDA mRNA levels was observed in I-M- CLL. Lastly, taking advantage of 685 CLL patients with time to first treatment (TTFT) available, we observed a significantly longer TTFT of I-M-CLL respect to nI-M-CLL, whereas no differences were observed in U-CLL. In conclusion, we succeeded to quantitative characterize the CLL intraclonal diversification phenomenon and to demonstrate its possible clinical correlation.In dependence of the identity of the variable region of the heavy chain of the immunoglobulin (IGHV) gene respect to the germline, chronic lymphocytic leukemia (CLL) may be subdivided into U-CLL and M-CLL. The evaluation of the IGHV is a hallmark in CLL due to the stability during time and its prognostic and predictive value. Despite this, IGHV intraclonal diversification (ID) has been described in the Sanger era. However, in the Next Generation Sequencing era, no author developed a solid and reliable workflow for ID identification and quantification. It follows that ID characterization is still lacking. Moreover, nobody evaluated the clinical impact of ID in CLL yet. Using the NGS technologies we exploited the immunoglobulin repertoire of 1091 CLL samplesto generate a tailored approach for ID evaluation. Using these data, we developed an innovative methodology to identify systematic sequencing errors (SE) on sequencing data of immunological repertoire (RepSeq), correct them and evaluate ID through the calculation of the inverse Simpson Index (iSI). With focused experiments, we demonstrated the robustness of our approach and the full superimposition of corrected data with the gold standard for RepSeq, namely unique molecular identifiers-based amplification protocol. Moreover, we validate our approach by analyzing other B cell malignancies with documented ID producing a classification coherent with the literature. A validated cutoff of 1.2 of iSI was generated to discriminate CLL samples with ID features (I) and samples without (nI). Among 983 CLL patients with iSI score available, only 15% of samples displayed ID according to 8 the iSI 1.2 cutoff. Both M-CLL and U-CLL have sample with ID, despite a significant ID skewing toward M-CLL was found. No variation in IGHV family or gene usage according to the presence/absence of ID was reported. Analyzing the RepSeq data for the identification of molecular signatures compatible with canonical somatic hypermutation (SHM) processes we observed a significant higher presence of mutations based on Activation induced cytidine deaminase (AICDA) in the context of I-CLL. Indeed, a significant higher AICDA mRNA levels was observed in I-M- CLL. Lastly, taking advantage of 685 CLL patients with time to first treatment (TTFT) available, we observed a significantly longer TTFT of I-M-CLL respect to nI-M-CLL, whereas no differences were observed in U-CLL. In conclusion, we succeeded to quantitative characterize the CLL intraclonal diversification phenomenon and to demonstrate its possible clinical correlation

    Klasifikasi Citra MRI Tumor Otak Menggunakan Metode Hibrida CNN-ViT

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    A tumor is an abnormal cell that can grow in any part of the human body. This also includes the brain which is the most important organ for humans. Brain tumors can arise because a cell that should grow and die within a certain period of time remains alive and multiplies abnormally. Brain tumors require fast and accurate medical diagnosis because a patient needs to get immediate treatment. The Convolutional Neural Network (CNN) algorithm is one of the most popular algorithms for image data processing and analysis and has been incorporated into medical image classification. In addition, there is also a Vision Transformer algorithm that divides the image into several patches and tokenizes each pixel of the image. Based on this explanation, the author classifies brain tumor MRI images using the CNN-ViT hybrid method. The result of this research is the accuracy and performance of CNN-ViT hybrid compared to CNN and ViT in classifying brain tumors. The best accuracy results were obtained by CNN-ViT with an average test accuracy of 93%, CNN with an average test accuracy of 90.80% and ViT with an average test accuracy of 84.80%. In addition, the classification report results of the best scenario CNN-ViT obtained with data division 80:10:10, Adam optimization and learning rate 0.0001% are accuracy of 94%, precision of 95%, recall of 94% and f1 score of 94%

    Metabolic Syndrome Associated with Subclinical Hypothyroidism and Vit D Insufficiency - A Case Report and Discussion

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    Metabolic syndrome (MetS) associated with hypothyroidism, was reported in literature. Like-wise association between hypothyroidism and Vit. D deficiency was reported. Hypothyroidism, Vit. D deficiency in DM2 patients was also reported, in the literature. But the occurrence of MetS, hypothyroidism and Vit. D deficiency, together occurring in a case was unreported. The author presented such triple association in a male patient aged 54 years. While Met S itself was a risk factor for CVD (cardiovascular vascular disease) and so were independently, the hypothyroidism and hypovitaminosis D, the triple association would have cumulative risk for CVD. So, it would be  profitable  to screen all MetS cases with hypothyroidism, for Vit. D deficiency also, in view of the possible cumulative risk. Literature was reviewed as to the relationship of MetS to hypothyroidism and Vit D deficiency, as well as the changing diagnostic criteria of MetS and it’s pathogenesis

    Half a century of development economics : a review based on the"Handbook of Development Economics"

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    Development economics has made remarkable progress in 50 years, says the author, summarizing changes in the field since Nehru's first proposals for an independent India. Synthesizing insights about changes in the field from the many contributors to the"Handbook of Development Economics,"the author observes (among other things): 1) Different schools of thought may dominate, but the range of research has broadened. Economics has"hardened"as its practitioners have learned to use data more carefully and to reason more rigorously. 2) The policy message has been turned upside down. Gone is the idea that development is industrialization and that the main policy problem is to manage the interface between country and city. Today urbanization and industrialization are viewed as mere components of an integrated transformation, in which the expansion of foreign trade is central. Traditional institutions are viewed with far more understanding, because overhasty modernization has often proved counterproductive. 3) More than ever, development is seen as a"whole replacement"process, the key to which is mastery of Northern technology--now understood to be both simpler and more complex than previously thought. Simpler, because much technology is uncomplicated, and complex because even simple technology requires ingenuity and a costly investment in adaptations. 4) There has been a radical change in economists'view of market agents and policymakers. Gone are the days when economists thought their advice should be aimed mainly at planners. Policymakers are utility maximizers, too. Employees of state enterprises coalesce into powerful interest groups that block efforts to raise productivity. The new thinking is sometimes modified by evoking the vague concept of"governance,"under which the economist's view is to help design a system of interacting state and private institutions that, led by the state, cooperate in achieving social goals. Whether something useful will come from this line of thinking remains to be seen. The author detects major gaps in economists'undrstanding of development, suggesting a particular need for further study of collective action (a far more pervasive component of human action than is realized) and the selection of roles by individuals and the costly investment this entails (a concept that may shed light on Schumpeter's well-known but little-studied entrepreneur).Labor Policies,Economic Theory&Research,Health Economics&Finance,Environmental Economics&Policies,Decentralization,Health Economics&Finance,Poverty Assessment,Achieving Shared Growth,Economic Theory&Research,Environmental Economics&Policies

    Ta voix vit/Nous vivons : la genèse d’un poème d’Habib Tengour à l’aune de ses avant-textes

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    Cet article entend proposer quelques pistes de réflexion sur le processus de genèse d’un poème de Habib Tengour, auteur algérien. L’analyse de différents avant-textes du poème « Ta voix vit/Nous vivons », à paraître dans la revue Po&sie, permet de mettre en valeur un certain nombre de spécificités de cette écriture.This article intends to propose some reflection tracks on the genetic process of a poem by Algerian author Habib Tengour. The analysis of various foretexts of the poem « Ta voix vit/Nous vivons », about to appear in the review Po&sie, allows to bring out a number Tengour’s writing characteristics

    Towards a Practical Emergent Knowledge Exploitation

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    Provided by the author(s) and NUI Galway in accordance with publisher policies. Please cite the publishe

    Mycobacteria in Water Used for Personal Hygiene in Heavy Industry and Collieries: A Potential Risk for Employees

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    Environmental mycobacteria (EM) constitute a health risk, particularly for immunocompromised people. Workers in heavy industry and in collieries represent an at-risk group of people as their immunity is often weakened by long-term employment in dusty environments, frequent smoking and an increased occurrence of pulmonary diseases. This study was concerned with the presence of EM in non-drinking water used for the hygiene of employees in six large industrial companies and collieries. Over a period of ten years, 1096 samples of surface water treated for hygiene purposes (treated surface water) and treated surface water diluted with mining water were examined. EM were detected in 63.4 and 41.5% samples of treated surface water and treated surface water diluted with mining water, respectively. Mycobacterium gordonae, M. avium-intracellulare and M. kansasii were the most frequently detected species. Adoption of suitable precautions should be enforced to reduce the incidence of mycobacteria in shower water and to decrease the infectious pressure on employees belonging to an at-risk group of people

    Clinical Relevance and Environmental Prevalence of <i>Mycobacterium fortuitum</i> Group Members. Comment on Mugetti et al. Gene Sequencing and Phylogenetic Analysis: Powerful Tools for an Improved Diagnosis of Fish Mycobacteriosis Caused by <i>Mycobacterium fortuitum</i> Group Members. <i>Microorganisms</i> 2021, <i>9</i>, 797

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    Mycobacterium fortuitum group (MFG) members are able to cause clinical mycobacteriosis in fish and other animals including humans. M. alvei, M. arceuilense, M. brisbanense, M. conceptionense, M. fortuitum, M. peregrinum, M. porcinum, M. senegalense, M. septicum, and M. setense were isolated from fish with mycobacteriosis. In other animals only three MFG species have been isolated: M. arceuilense from camels’ milk, M. farcinogenes from cutaneous infections often described as “farcy”, and M. fortuitum from different domestic and wild mammals’ species. Out of 17, only 3 MFG species (M. arceuilense, M. lutetiense and M. montmartrense) have never been reported in humans. A total of eight MFG members (M. alvei, M. brisbanense, M. conceptionense, M. fortuitum subsp. acetamidolyticum, M. houstonense, M. peregrinum, M. porcinum, and M. septicum) have been isolated from both pulmonary and extrathoracic locations. In extrathoracic tissues five MFG species (M. boenickei, M. farcinogenes, M. neworleansense, M. senegalense, and M. setense) have been diagnosed and only one MFG member (M. fortuitum subsp. acetamidolyticum) has been isolated from pulmonary infection

    La vie ne vit pas. Penser l'enfermement par le montage et l'écriture filmique

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    Ce mémoire part du film La vie ne vit pas (réalisé par l'autrice), qui met en scène une femme hospitalisée en psychiatrie après une dépression liée à l’aliénation du travail. L’autrice montre que l’hôpital n’est pas un dehors de la société, mais reproduit les mêmes logiques de contrôle et de normalisation. Le travail du film s’appuie sur le montage comme procédé critique : l’interruption (arrêt, rupture) permet de révéler les tensions invisibles du quotidien. Inspirée par Walter Benjamin, Bertolt Brecht et Sergei Eisenstein, la recherche défend une approche fragmentaire qui refuse une narration linéaire et univoque. Le montage devient ainsi un outil pour questionner la réalité sociale et les rapports de domination. La lenteur, les pauses et les ruptures sont pensées comme des gestes de résistance à la productivité et au rythme marchand. Le mémoire propose l’interruption comme une force de transformation, autant dans la création artistique que dans la vie.This Masterthesis is based on the film La vie ne vit pas (directed by the author), which depicts a woman hospitalized in a psychiatric ward after suffering from depression linked to alienation at work. The author shows that the hospital is not outside society, but reproduces the same logic of control and normalization. The film uses editing as a critical process: interruption (stopping, breaking) reveals the invisible tensions of everyday life. Inspired by Walter Benjamin, Bertolt Brecht, and Sergei Eisenstein, the research advocates a fragmentary approach that rejects linear and univocal narration. Editing thus becomes a tool for questioning social reality and relationships of domination. Slowness, pauses, and breaks are conceived as acts of resistance to productivity and commercial rhythms. The thesis proposes interruption as a force for transformation, both in artistic creation and in life

    Nontuberculous Mycobacteria as Sapronoses: A Review

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    Mycobacteria are a unique group of microorganisms. They are characterised by exceptional adaptability and durability. They are capable of colonisation and survival even in very unfavourable conditions. In addition to the well-known obligate human pathogens, Mycobacterium tuberculosis and M. leprae, more than 200 other species have been described. Most of them form a natural part of the microflora of the external environment and thrive in aquatic and soil environments especially. For many of the mycobacterial species associated with human disease, their natural source has not yet been identified. From an ecological point of view, mycobacteria are saprophytes, and their application in human and animal diseases is opportunistic. Most cases of human disease from saprophytic mycobacteria occur in immunocompromised individuals. This adaptability and resilience to environmental pressures makes treatment of mycobacterial diseases (most often sapronoses and less often zoonoses) and permanent eradication of mycobacteria from the environment very difficult. Saprophytic mycobacterial diseases (sapronoses) are chronic and recurrent due to the fact of repeated endogenous or exogenous re-exposure. Therefore, knowledge regarding their occurrence in soil and dust would aid in the prevention of saprophytic mycobacterioses. In conjunction, their presence and ecological significance in the environment can be revealed
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