101 research outputs found

    Remote Prophylaxis of Social and Educational Adaptation of University International Entrants in Total Pandemic

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    The relevance of the study is due to the trends of the global pandemic, which provoked an extremal transition of all areas of higher education to distance learning, as the only possible way to work with domestic and international entrants and students. In addition, the trends of the pandemic in the current educational environment also determine the special need to develop remote mechanisms for a prophylaxis approach to solving the problems of social and educational adaptation of international entrants – future University students. In this regard, this article is aimed at identifying the features of remote prophylaxis of social and educational adaptation of entrants. The article reveals the transformation of social and educational adaptation of international entrants in the global pandemic; defines the structure and content of remote prophylaxis of social and educational adaptation of international University entrants in the global pandemic. Based on the results of the research, the authors of the article substantiate the prophylaxis model of the educational and software complex for remote prophylaxis of social and educational adaptation of University international entrants. The effectiveness of the model is proved by the results of its use in the process of remote social and educational adaptation of University international entrants in the context of a global pandemic. The materials of the article have practical application and can be useful in the development and implementation of various methods and practices of social and educational adaptation of international entrants – future University students in the context of a global pandemic. It is recommended for University teachers and students, methodologists, curators, Tutors

    Follow-up of breast cancer in primary care vs specialist care: results of an economic evaluation

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    A randomized controlled trial (RCT) comparing primary-care-centred follow-up of breast cancer patients with the current standard practice of specialist-centred follow-up showed no increase in delay in diagnosing recurrence, and no increase in anxiety or deterioration in health-related quality of life. An economic evaluation of the two schemes of follow-up was conducted concurrent with the RCT. Because the RCT found no difference in the primary clinical outcomes, a cost minimization analysis was conducted. Process measures of the quality of care such as frequency and length of visits were superior in primary care. Costs to patients and to the health service were lower in primary care. There was no difference in total costs of diagnostic tests, with particular tests being performed more frequently in primary care than in specialist care. Data are provided on the average frequency and length of visits, and frequency of diagnostic testing for breast cancer patients during the follow-up period. © 1999 Cancer Research Campaig

    Clinical significance of genetic aberrations in secondary acute myeloid leukemia

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    The study aimed to identify genetic lesions associated with secondary acute myeloid leukemia (sAML) in comparison with AML arising de novo (dnAML) and assess their impact on patients' overall survival (OS). High-resolution genotyping and loss of heterozygosity mapping was performed on DNA samples from 86 sAML and 117 dnAML patients, using Affymetrix Genome-Wide Human SNP 6.0 arrays. Genes TP53, RUNX1, CBL, IDH1/2, NRAS, NPM1, and FLT3 were analyzed for mutations in all patients. We identified 36 recurrent cytogenetic aberrations (more than five events). Mutations in TP53, 9pUPD, and del7q (targeting CUX1 locus) were significantly associated with sAML, while NPM1 and FLT3 mutations associated with dnAML. Patients with sAML carrying TP53 mutations demonstrated lower 1-year OS rate than those with wild-type TP53 (14.3% +/- 9.4% vs. 35.4% +/- 7.2%; P = 0.002), while complex karyotype, del7q (CUX1) and del7p (IKZF1) showed no significant effect on OS. Multivariate analysis confirmed that mutant TP53 was the only independent adverse prognostic factor for OS in sAML (hazard ratio 2.67; 95% CI: 1.335.37; P = 0.006). Patients with dnAML and complex karyotype carried sAML-associated defects (TP53 defects in 54.5%, deletions targeting FOXP1 and ETV6 loci in 45.4% of the cases). We identified several co-occurring lesions associated with either sAML or dnAML diagnosis. Our data suggest that distinct genetic lesions drive leukemogenesis in sAML. High karyotype complexity of sAML patients does not influence OS. Somatic mutations in TP53 are the only independent adverse prognostic factor in sAML. Patients with dnAML and complex karyotype show genetic features associated with sAML and myeloproliferative neoplasms. Am. J. Hematol., 2012

    Evolutionary paths to macrolide resistance in a Neisseria commensal converge on ribosomal genes through short sequence duplications

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    Neisseria commensals are an indisputable source of resistance for their pathogenic relatives. However, the evolutionary paths commensal species take to reduced susceptibility in this genus have been relatively underexplored. Here, we leverage in vitro selection as a powerful screen to identify the genetic adaptations that produce azithromycin resistance (� 2 μg/mL) in the Neisseria commensal, N. elongata. Across multiple lineages (n = 7/16), we find mutations that reduce susceptibility to azithromycin converge on the locus encoding the 50S ribosomal L34 protein (rpmH) and the intergenic region proximal to the 30S ribosomal S3 protein (rpsC) through short tandem duplication events. Interestingly, one of the laboratory evolved mutations in rpmH is identical (7LKRTYQ12), and two nearly identical, to those recently reported to contribute to high-level azithromycin resistance in N. gonorrhoeae. Transformations into the ancestral N. elongata lineage confirmed the causality of both rpmH and rpsC mutations. Though most lineages inheriting duplications suffered in vitro fitness costs, one variant showed no growth defect, suggesting the possibility that it may be sustained in natural populations. Ultimately, studies like this will be critical for predicting commensal alleles that could rapidly disseminate into pathogen populations via allelic exchange across recombinogenic microbial genera

    Fibulin-3 is necessary to prevent cardiac rupture following myocardial infarction

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    Published online: 11 September 2023Despite the high prevalence of heart failure in the western world, there are few effective treatments. Fibulin-3 is a protein involved in extracellular matrix (ECM) structural integrity, however its role in the heart is unknown. We have demonstrated, using single cell RNA-seq, that fibulin-3 was highly expressed in quiescent murine cardiac fibroblasts, with expression highest prior to injury and late post-infarct (from ~ day-28 to week-8). In humans, fibulin-3 was upregulated in left ventricular tissue and plasma of heart failure patients. Fibulin-3 knockout (Efemp1-/-) and wildtype mice were subjected to experimental myocardial infarction. Fibulin-3 deletion resulted in significantly higher rate of cardiac rupture days 3-6 post-infarct, indicating a weak and poorly formed scar, with severe ventricular remodelling in surviving mice at day-28 post-infarct. Fibulin-3 knockout mice demonstrated less collagen deposition at day-3 post-infarct, with abnormal collagen fibre-alignment. RNA-seq on day-3 infarct tissue revealed upregulation of ECM degradation and inflammatory genes, but downregulation of ECM assembly/structure/organisation genes in fibulin-3 knockout mice. GSEA pathway analysis showed enrichment of inflammatory pathways and a depletion of ECM organisation pathways. Fibulin-3 originates from cardiac fibroblasts, is upregulated in human heart failure, and is necessary for correct ECM organisation/structural integrity of fibrotic tissue to prevent cardiac rupture post-infarct.Lucy A. Murtha, Sean A. Hardy, Nishani S. Mabotuwana, Mark J. Bigland, Taleah Bailey, Kalyan Raguram, Saifei Liu, Doan T. Ngo, Aaron L. Sverdlov, Tamara Tomin, Ruth Birner, Gruenberger, Robert D. Hume, Siiri E. Iismaa, David T. Humphreys, Ralph Patrick, James J. H. Chong, Randall J. Lee, Richard P. Harvey, Robert M. Graham, Peter P. Rainer and Andrew J. Boyl

    Germany Takes Action on Corporate Due Diligence in Supply Chains: What the United States Can Learn From International Supply Chain Regulations

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    This comment addresses the United States\u27 failure to pass comprehensive federal supply chain due diligence legislation. The United States presents itself as a global leader, but its failure to pass comprehensive supply chain due diligence legislation creates a gap in human rights due diligence that can lead to corporate human rights abuses. Although the United States has passed several human rights due diligence laws, a comprehensive federal law would be more effective at preventing corporate human rights abuses in the supply chains of business organizations that operate in the United States. This comment argues that American lawmakers should look to Germany\u27s recently passed Act on Corporate Due Diligence in Supply Chains as a model for comprehensive human rights supply chain due diligence legislation. First, the comment reviews the history of business and human rights, previous attempts at supply chain due diligence legislation in the United States, and current European due diligence legislation. Next, the comment analyzes the strengths and weaknesses of Germany\u27s Act on Corporate Due Diligence in Supply Chains and analyzes the recently enacted Uyghur Forced Labor Prevention Act. Finally, the comment argues that the United States should borrow the positive provisions from Germany\u27s Act on Corporate Due Diligence in Supply Chains, improve upon its weaknesses, and pass comprehensive federal legislation to reaffirm its position as a global leader in the elimination of corporate human rights abuses
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