Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy

Background: Progressive multifocal leukoencephalopathy (PML) was reported to have developed in three patients treated with natalizumab. We conducted an evaluation to determine whether PML had developed in any other treated patients. Methods: We invited patients who had participated in clinical trials in which they received recent or long-term treatment with natalizumab for multiple sclerosis, Crohn's disease, or rheumatoid arthritis to participate. The clinical history, physical examination, brain magnetic resonance imaging (MRI), and testing of cerebrospinal fluid for JC virus DNA were used by an expert panel to evaluate patients for PML. We estimated the risk of PML in patients who completed at least a clinical examination for PML or had an MRI. Results: Of 3417 patients who had recently received natalizumab while participating in clinical trials, 3116 (91 percent) who were exposed to a mean of 17.9 monthly doses underwent evaluation for PML. Of these, 44 patients were referred to the expert panel because of clinical findings of possible PML, abnormalities on MRI, or a high plasma viral load of JC virus. No patient had detectable JC virus DNA in the cerebrospinal fluid. PML was ruled out in 43 of the 44 patients, but it could not be ruled out in one patient who had multiple sclerosis and progression of neurologic disease because data on cerebrospinal fluid testing and follow-up MRI were not available. Only the three previously reported cases of PML were confirmed (1.0 per 1000 treated patients; 95 percent confidence interval, 0.2 to 2.8 per 1000). Conclusions: A detailed review of possible cases of PML in patients exposed to natalizumab found no new cases and suggested a risk of PML of roughly 1 in 1000 patients treated with natalizumab for a mean of 17.9 months. The risk associated with longer treatment is not known

Leitfaden Saatgutgesundheit im Ökologischen Landbau - Ackerkulturen

Im "Leitfaden Saatgutgesundheit im Ökologischen Landbau – Ackerkulturen" werden ausgewählte saatgutbürtige Krankheiten von ackerbaulichen Kulturen samt vorbeugenden und direkten Regulierungsmöglichkeiten vorgestellt

Saberes na graduação em administração : um estudo nas universidades federais do estado de Minas Gerais

Conforme censo da educação superior no Brasil de 2015, o curso de administração é um dos mais procurados no país. Esta pesquisa teve como objetivo investigar como surgem e são legitimados os saberes na graduação em administração das universidades federais mineiras. Na tentativa de responder a este objetivo, foi realizada uma caracterização do curso, investigados os saberes veiculados na matriz curricular e analisada a produção de verdades na graduação. A abordagem metodológica escolhida para este estudo foi a da pesquisa qualitativa por meio da técnica de análise de conteúdo. A produção dos dados foi feita mediante a análise de um conjunto de 13 (treze) projetos pedagógicos. Como resultados foram identificados os objetivos do pensamento crítico e reflexivo, do campo de atuação e da qualificação técnica, os perfis responsável e generalista e os métodos da transmissão, da prática e da construção do saber. Em relação aos saberes veiculados na matriz curricular, foram investigados os saberes de formação básica, nas funções organizacionais, das especificidades regionais e organizacionais, formação social, ambiental e ética e em pesquisa. Assim, com a análise das características do curso com os saberes veiculados nas matrizes curriculares foi possível analisar a produção de verdades na graduação. Os objetivos do campo de atuação, da qualificação técnica e o perfil generalista são as características que se relacionam com os saberes mais presentes na graduação, de modo que os objetivos econômicos ainda estão ocupando uma posição hegemônica na formação dos bacharéis em administração entre as universidades pesquisadas.According to a census of higher education in Brazil in 2015, the administration course is one of the most sought after in the country. This research had as objective to investigate how the knowledge and the knowledge in the administration graduation of the federal universities of Minas Gerais arise and are legitimized. In an attempt to respond to this objective, a course characterization was carried out, the knowledge conveyed in the curricular matrix was investigated and the production of truths at the undergraduate level was analyzed. The methodological approach chosen for this study was that of the qualitative research through the technique of content analysis. The data were produced through the analysis of a set of 13 (thirteen) pedagogical projects. As results, the objectives of critical and reflexive thinking, the field of performance and technical qualification, the responsible and generalist profiles and the methods of transmission, practice and knowledge construction were identified. In relation to the knowledge conveyed in the curricular matrix, the basic training knowledge in organizational functions, regional and organizational specificities, social, environmental and ethical training and research were investigated. Thus, with the analysis of the characteristics of the course with the knowledge conveyed in the curricular matrices, it was possible to analyze the production of truths in the undergraduate course. The objectives of the field of activity, the technical qualification and the generalist profile are the characteristics that are related to the most present knowledge in the undergraduate, so that the economic objectives are still occupying a hegemonic position in the formation of the bachelors in administration among the researched universities

Progress and Recent Trends in the Application of Nanoparticles as Low Carbon Fuel Additives—A State of the Art Review

The first part of the current review highlights the evolutionary nuances and research hotspots in the field of nanoparticles in low carbon fuels. Our findings reveal that contribution to the field is largely driven by researchers from Asia, mainly India. Of the three biofuels under review, biodiesel seems to be well studied and developed, whereas studies regarding vegetable oils and alcohols remain relatively scarce. The second part also reviews the application of nanoparticles in biodiesel/vegetable oil/alcohol-based fuels holistically, emphasizing fuel properties and engine characteristics. The current review reveals that the overall characteristics of the low carbon fuel–diesel blends improve under the influence of nanoparticles during combustion in diesel engines. The most important aspect of nanoparticles is that they act as an oxygen buffer that provides additional oxygen molecules in the combustion chamber, promoting complete combustion and lowering unburnt emissions. Moreover, the nanoparticles used for these purposes exhibit excellent catalytic behaviour as a result of their high surface area-to-volume ratio—this leads to a reduction in exhaust pollutants and ensures an efficient and complete combustion. Beyond energy-based indicators, the exergy, economic, environmental, and sustainability aspects of the blends in diesel engines are discussed. It is observed that the performance of the diesel engine fuelled with low carbon fuels according to the second law of efficiency improves under the influence of the nano-additives. Our final part shows that despite the benefits of nanoparticles, humans and animals are under serious threats from the highly toxic nature of nanoparticles. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.20JCJQJC00160; Cardiff University; Universiti Tenaga Nasional: IC6-BOLDREFRESH2025This research was funded by Tianjin Science Fund for Distinguished Young Scholars, grant number 20JCJQJC00160, and the Universiti Tenaga Nasional grant no. IC6-BOLDREFRESH2025 (HCR) under the BOLD2025 Program. The APC was funded by Cardiff University

Genetic correlations and genome-wide associations of cortical structure in general population samples of 22824 adults

Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging

Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning

Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.Peer reviewe

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele