Screening for Incidental Sars-Cov-2 Infection in a Neurocritical Care Unit: A Longitudinal Diagnostic Prediction Model

Background: Rapid diagnosis of SARS-CoV-2 infection in patients not primarily assigned with the diagnosis of COVID-19 is highly relevant to effectively rule out virus transmission among patients and medical staff. The purpose is to develop a model for the prediction of the actual presence of a SARS-CoV-2 infection before a valid test result is available and to avoid unnecessary testing in Critical Care Units. Methods: Datasets of laboratory and blood gas analysis tests were collected retrospectively for the development and subsequent validation of machine learning (ML) based models. The data set was composed of 1. 254 SARS-CoV-2 positive cases, collected in an ICU dedicated to patients with COVID-19 pneumonia, 2a. 914 SARS-CoV-2 negative patients treated in a Neurocritical Care Unit and 2b. 32 patients treated for severe influenza pneumonia in a Medical ICU at the same hospital. The models were subsequently validated on a dataset collected from the Neurocritical Care Unit that consisted of data from 7 positive and 42 negative patients. Models were adapted to newly available laboratory values throughout their ICU stay. Extremely Randomized Trees (ERT) and Random Forest (RF) models were evaluated. A baseline model comprising fully grown trees, an optimized model including optimal values for the maximum depth, and a simplified model that only uses the 6 most important features were trained. Results: The overall best model, evaluated via crossvalidation on the development set, is an optimized ERT model with a ROC AUC value of 0.946. The model performance on the validation set is best for the simplified RF model achieving a ROC AUC value of 0.701. Gini feature and permutation importance for the simplified RF model revealed hemoglobin, procalcitonin, C-reactive protein, glomerular filtration rate based on CKD-EPI equation, creatinine, and urea as the most important input features. Using the simplified RF model and a threshold of 0.012 for the probability, a sensitivity above 80% with a specificity of 43% is achieved. Compared to a hypothetical daily testing regimen, using a threshold of 0.145, the simplified RF model detects all positive cases, and, with a false positive rate of 35%, daily tests might be reduced by two thirds. Conclusions: The model developed may support the medical staff in the ICUs by enabling faster and more reliable recognition of COVID-19. Unnecessary serial test sampling might be reduced. To ensure the quality of the model before clinical use, it should be further validated in prospective patient cohorts

Технология проведения гидравлических испытаний промысловых нефтепроводов в условиях Западной Сибири

Объектом исследования является методика и технология проведения гидравлических испытаний нефтепровода. Целью данной работы является исследование актуальной научно-технической проблемы обеспечения требуемых условий и средств для проведения гидравлических испытаний промысловых нефтепроводов. В соответствии с поставленной целью были выдвинуты следующие задачи: 1. Определить необходимую номенклатуру и объем подготовительных работ для проведения испытаний промыслового нефтепровода; 2. Исследовать основные факторы и их влияние на процесс гидравлических испытаний нефтепровода в промысловых условиях; 3. Выбор средств и методов, исключающих влияние внешних факторов на достоверность результатов испытаний.The object of study is the methodology and technology for conducting hydraulic tests of the oil pipeline. The aim of this work is to study the urgent scientific and technical problems of providing the required conditions and means for conducting hydraulic tests of field pipelines. In accordance with the goal, the following tasks were put forward: 1. To determine the necessary nomenclature and scope of preparatory work for testing the oil field pipeline; 2. Investigate the main factors and their influence on the process of hydraulic testing of the pipeline in the field; 3. The choice of tools and methods that exclude the influence of external factors on the reliability of the test results

Demonstration of ``regulatory`` process controls on the TSTA cryogenic distillation system

Due to the nature of its fusion reaction, most of the DT used to fuel the International Thermonuclear Experimental Reactor (ITER) will exit unreacted. This effluent will be purified by the fuel cleanup system so that the isotope separation system (ISS) will be fed only hydrogen isotopes and possibly some helium. The ISS will separate this feed into streams nominally composed of He/H2/HD, D2, DT, and T2. These products will be recycled through appropriate fueling systems back to the fusion reactor or returned to storage. The ISS will have to respond properly to feed conditions which change rapidly. Feed changes will propagate quickly through the entire cascade. It is apparent that an automatic control system will be required to respond to these changes and maintain product quality. It is convenient to divide such a distillation control system into `regulatory` controls and composition controls. The `regulatory` controls include liquid levels, flowrates, reboiler heats, and pressure. A system of regulatory controls has been devised and installed on the four-column cascade of cryogenic columns at the Tritium Systems Test Assembly (TSTA) at Los Alamos National Laboratory. This tritium-compatible ISS is designed for approximately 1/10 the ITER flowrate and is dedicated to fusion fuel studies. Details of the TSTA ISS have been published previously

Применение информационных технологий и этические нюансы в управлении массовым сознанием

This paper discusses the current value of information technology in our lives, as well as their application to control the mass consciousness

Acidic microenvironment plays a key role in human melanoma progression through a sustained exosome mediated transfer of clinically relevant metastatic molecules

Background: Microenvironment cues involved in melanoma progression are largely unknown. Melanoma is highly influenced in its aggressive phenotype by the changes it determinates in its microenvironment, such as pH decrease, in turn influencing cancer cell invasiveness, progression and tissue remodelling through an abundant secretion of exosomes, dictating cancer strategy to the whole host. A role of exosomes in driving melanoma progression under microenvironmental acidity was never described. Methods: We studied four differently staged human melanoma lines, reflecting melanoma progression, under microenvironmental acidic pHs pressure ranging between pH 6.0-6.7. To estimate exosome secretion as a function of tumor stage and environmental pH, we applied a technique to generate native fluorescent exosomes characterized by vesicles integrity, size, density, markers expression, and quantifiable by direct FACS analysis. Functional roles of exosomes were tested in migration and invasion tests. Then we performed a comparative proteomic analysis of acid versus control exosomes to elucidate a specific signature involved in melanoma progression. Results: We found that metastatic melanoma secretes a higher exosome amount than primary melanoma, and that acidic pH increases exosome secretion when melanoma is in an intermediate stage, i.e. metastatic non-invasive. We were thus able to show that acidic pH influences the intercellular cross-talk mediated by exosomes. In fact when exposed to exosomes produced in an acidic medium, pH naïve melanoma cells acquire migratory and invasive capacities likely due to transfer of metastatic exosomal proteins, favoring cell motility and angiogenesis. A Prognoscan-based meta-analysis study of proteins enriched in acidic exosomes, identified 11 genes (HRAS, GANAB, CFL2, HSP90B1, HSP90AB1, GSN, HSPA1L, NRAS, HSPA5, TIMP3, HYOU1), significantly correlating with poor prognosis, whose high expression was in part confirmed in bioptic samples of lymph node metastases. Conclusions: A crucial step of melanoma progression does occur at melanoma intermediate -stage, when extracellular acidic pH induces an abundant release and intra-tumoral uptake of exosomes. Such exosomes are endowed with pro-invasive molecules of clinical relevance, which may provide a signature of melanoma advancement

Attitudes and behaviors of Japanese physicians concerning withholding and withdrawal of life-sustaining treatment for end-of-life patients: results from an Internet survey

<p>Abstract</p> <p>Background</p> <p>Evidence concerning how Japanese physicians think and behave in specific clinical situations that involve withholding or withdrawal of medical interventions for end-of-life or frail elderly patients is yet insufficient.</p> <p>Methods</p> <p>To analyze decisions and actions concerning the withholding/withdrawal of life-support care by Japanese physicians, we conducted cross-sectional web-based internet survey presenting three scenarios involving an elderly comatose patient following a severe stroke. Volunteer physicians were recruited for the survey through mailing lists and medical journals. The respondents answered questions concerning attitudes and behaviors regarding decision-making for the withholding/withdrawal of life-support care, namely, the initiation/withdrawal of tube feeding and respirator attachment.</p> <p>Results</p> <p>Of the 304 responses analyzed, a majority felt that tube feeding should be initiated in these scenarios. Only 18% felt that a respirator should be attached when the patient had severe pneumonia and respiratory failure. Over half the respondents felt that tube feeding should not be withdrawn when the coma extended beyond 6 months. Only 11% responded that they actually withdrew tube feeding. Half the respondents perceived tube feeding in such a patient as a "life-sustaining treatment," whereas the other half disagreed. Physicians seeking clinical ethics consultation supported the withdrawal of tube feeding (OR, 6.4; 95% CI, 2.5–16.3; P < 0.001).</p> <p>Conclusion</p> <p>Physicians tend to harbor greater negative attitudes toward the withdrawal of life-support care than its withholding. On the other hand, they favor withholding invasive life-sustaining treatments such as the attachment of a respirator over less invasive and long-term treatments such as tube feeding. Discrepancies were demonstrated between attitudes and actual behaviors. Physicians may need systematic support for appropriate decision-making for end-of-life care.</p

Minimal state models for ionic channels involved in glucagon secretion

Pancreatic alpha cells synthesize and release glucagon. This hormone along with insulin, preserves blood glucose levels within a physiological range. During low glucose levels, alpha cells exhibit electrical activity related to glucagon secretion. In this paper, we introduce minimal state models for those ionic channels involved in this electrical activity in mice alpha cells. For estimation of model parameters, we use Monte Carlo algorithms to fit steadystate channel currents. Then, we simulate dynamic ionic currents following experimental protocols. Our aims are 1) To understand the individual ionic channel functioning and modulation that could affect glucagon secretion, and 2) To simulate ionic currents actually measured in voltage-clamp alpha-cell experiments in mice. Our estimations indicate that alpha cells are highly permeable to sodium and potassium which mainly manage action potentials. We have also found that our estimated N-type calcium channel population and density in alpha cells is in good agreement to those reported for L-type calcium channels in beta cells. This finding is strongly relevant since both, L-type and N-type calcium channels, play a main role in insulin and glucagon secretion, respectively

Evaluation of job satisfaction of practice staff and general practitioners: an exploratory study

Contains fulltext : 95875.pdf (publisher's version ) (Open Access

Pathogenesis of Scleroderma

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65784/1/j.1365-4362.1984.tb05678.x.pd

Visualization and 3D Reconstruction of Flame Cells of Taenia solium (Cestoda)

BACKGROUND: Flame cells are the terminal cells of protonephridial systems, which are part of the excretory systems of invertebrates. Although the knowledge of their biological role is incomplete, there is a consensus that these cells perform excretion/secretion activities. It has been suggested that the flame cells participate in the maintenance of the osmotic environment that the cestodes require to live inside their hosts. In live Platyhelminthes, by light microscopy, the cells appear beating their flames rapidly and, at the ultrastructural, the cells have a large body enclosing a tuft of cilia. Few studies have been performed to define the localization of the cytoskeletal proteins of these cells, and it is unclear how these proteins are involved in cell function. METHODOLOGY/PRINCIPAL FINDINGS: Parasites of two different developmental stages of T. solium were used: cysticerci recovered from naturally infected pigs and intestinal adults obtained from immunosuppressed and experimentally infected golden hamsters. Hamsters were fed viable cysticerci to recover adult parasites after one month of infection. In the present studies focusing on flame cells of cysticerci tissues was performed. Using several methods such as video, confocal and electron microscopy, in addition to computational analysis for reconstruction and modeling, we have provided a 3D visual rendition of the cytoskeletal architecture of Taenia solium flame cells. CONCLUSIONS/SIGNIFICANCE: We consider that visual representations of cells open a new way for understanding the role of these cells in the excretory systems of Platyhelminths. After reconstruction, the observation of high resolution 3D images allowed for virtual observation of the interior composition of cells. A combination of microscopic images, computational reconstructions and 3D modeling of cells appears to be useful for inferring the cellular dynamics of the flame cell cytoskeleton