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Abstract Carbon Capture, Utilization, and Storage (CCUS) offers a viable solution to reduce the carbon footprint in the petroleum industry, and foam injection presents a promising method to achieve this while simultaneously increasing oil recovery. In this work, we studied the feasibility of CO2 foam for co-optimizing enhanced oil recovery and CO2 storage in a high-salinity carbonate formation. The simulated hydrodynamic model is a depleted formation containing 30% residual oil, with three mechanisms for CO2 storage: solubility, residual, and mineralization trapping mechanisms. The results showed that after 20 years, oil recovery during foam injection was 2.7 times higher than CO2 injection, and the CO2 stored during foam flooding was 38% higher than CO2 injection. Notably, foam injection also increased CO2 storage capacity by 2.6 times, indicating the potential to store around 2 gigatons of CO2 in the simulated model. This was attributed to the ability of foam to significantly reduce gas mobility and thus form isolated bubbles through its Jamin effect. Residual trapping was the dominant trapping mechanism, contributing to over 70% of the total CO2 trapped, attributed to the reduction in the dissolution of CO2 in brine due to the high salinity of the aqueous medium. CO2 mineralization was also studied, showing the least trapping efficiency and the dissolution trend of all the carbonate minerals. This study illustrates a novel CO2 utilization and storage technique in which CO2 is concurrently sequestered while enhancing oil recovery in a depleted oil reservoir by injecting CO2 as foam. The relevance of this study lies in its potential to provide a dual benefit of reducing greenhouse gas emissions and boosting oil production, offering a sustainable approach for the petroleum industry.

Abstract A key factor affecting foam stability is the interaction of foam with oil in the reservoir. This work investigates how different types of oil influence the stability of foams generated with binary surfactant systems under a high salinity condition. Foam was generated with binary surfactant systems, one composed of a zwitterionic and a nonionic surfactant, and the other composed of an anionic and a nonionic surfactant. Our results showed that the binary surfactant foams investigated are more tolerant under high salinity conditions and in the presence of oil. This was visually observed in our microscopic analysis and was further attributed to an increase in apparent viscosity achieved with binary surfactant systems, compared to single surfactant foams. To understand the influence of oil on foam stability, we performed a mechanistic study to investigate how these oils interact with foams generated with binary surfactants, focusing on their applicability under high salinity conditions. The generation and stability of foam are linked to the ability of the surfactant system to solubilize oil molecules. Oil droplets that solubilize in the micelles appear to destabilize the foam. However, oils with higher molecular weights are too large to be solubilized in the micelles, hence the molecules will have less ability to be transported out of the foam, so oil seems to stabilize the foam. Finally, we conducted a multivariate analysis to identify the parameters that influenced foam stability in different oil types, using the experimental data from our work. The results showed that the oil molecular weight, interfacial tension between the foaming liquid and the oil, and the spreading coefficient are the most important variables for explaining the variation in the data. By performing a partial least square regression, a linear model was developed based on these most important variables, which can be used to predict foam stability for subsequent experiments under the same conditions as our work.

The introduction of Category Management in operational resources purchasing helps to improve logistics service levels and increase the profitability of industrial enterprises. There are two main purposes of the provided article. The first purpose is to develop a methodological framework for category management of operational resources supply for large industrial enterprises. Secondly, it aims to offer a mechanism for inter-organizational collaboration with suppliers and contractors in supply chains. This study is based on the methods of forecasting of the uncertain stock demand. Time-series and correlation-regression models are used for forecasting. The first finding of the research is the systematization and classification of the operational resources purchased by industrial enterprises. Modified models of operational resources inventory management and a methodology for assessing tied-up losses are offered in this article and, they are based on category management. A developed methodology allows one to make strategic decisions in the field of procurement. According to the preliminary estimates, implementation of the proposed approaches increases net profit in large industrial companies by 4–5 % in relative periods.

Once a patient has been diagnosed with severe COVID-19 pneumonia, treatment options have limited effectiveness. Opaganib is an oral treatment under investigation being evaluated for treatment of hospitalized patients with severe COVID-19 pneumonia. A randomized, placebo-controlled, double-blind phase 2/3 trial was conducted in 57 sites worldwide from August 2020 to July 2021. Patients received either opaganib (n = 230; 500 mg twice daily) or matching placebo (n = 233) for 14 days. The primary outcome was the proportion of patients no longer requiring supplemental oxygen by day 14. Secondary outcomes included changes in the World Health Organization Ordinal Scale for Clinical Improvement, viral clearance, intubation, and mortality at 28 and 42 days. Pre-specified primary and secondary outcome analyses did not demonstrate statistically significant benefit (except nominally for time to viral clearance). Post-hoc analysis revealed the fraction of inspired oxygen (FIO2) at baseline was prognostic for opaganib treatment responsiveness and corresponded to disease severity markers. Patients with FIO2 levels at or below the median value (≤60%) had better outcomes after opaganib treatment (n = 117) compared to placebo (n = 134). The proportion of patients with ≤60% FIO2 at baseline that no longer required supplemental oxygen (≥24 h) by day 14 of opaganib treatment increased (76.9% vs. 63.4%; nominal p-value = 0.033). There was a 62.6% reduction in intubation/mechanical ventilation (6.84% vs. 17.91%; nominal p-value = 0.012) and a clinically meaningful 62% reduction in mortality (5.98% vs. 16.7%; nominal p-value = 0.019) by day 42. No new safety concerns were observed. While the primary analyses were not statistically significant, post-hoc analysis suggests opaganib benefit for patients with severe COVID-19 requiring supplemental oxygen with an FIO2 of ≤60%. Further studies are warranted to prospectively confirm opaganib benefit in this subpopulation.

Oil reservoirs are nearing maturation, necessitating novel enhanced oil recovery (EOR) techniques to meet escalating global energy demands. This demand has spurred interest in reservoir production analysis and forecasting tools to enhance economic and technical efficiency. Accurate validation of these tools, known as simulators, using laboratory or field data is pivotal for precise reservoir productivity estimation. This study delves into the application of nanoparticles in foam flooding for mobility control to improve sweep efficiency. Foam generation can occur in-situ by simultaneous injection of surfactants and gas or through pre-generated foam injection into the reservoir. In this work, a series of systematic simulations were run to investigate how much injected fluids can reduce gas breakthrough while also increasing oil recovery. Subsequently, we analyzed the most effective optimization strategies, considering their economic limits. Our primary objective is to numerically model nanofoam flooding as an innovative EOR approach, synergizing foam flooding mechanisms with nanotechnology benefits. In this work, modeling of nanoparticles in foam liquid was represented by the interfacial properties provided to the injection fluid. Additionally, we simulated Water-Alternating-Gas (WAG) injection schemes across various cycles, comparing their outcomes. Our results showed that nanofoam injection achieved a higher recovery factor of at least 38% and 95% more than WAG and gas injections, respectively. The superior efficiency and productivity of foam injection compared to WAG and gas injection suggest an optimal EOR approach within the scope of our model. These simulated optimization techniques contribute to the future development of processes in this field.

ABSTRACTClinical trials of combined IDO/PD1 blockade in metastatic melanoma (MM) failed to show additional clinical benefit compared to PD1-alone inhibition. We reasoned that a tryptophan-metabolizing pathway other than the kynurenine one is essential. We immunohistochemically stained tissues along the nevus-to-MM progression pathway for tryptophan-metabolizing enzymes (TMEs; TPH1, TPH2, TDO2, IDO1) and the tryptophan transporter, LAT1. We assessed tryptophan and glucose metabolism by performing baseline C11-labeled α-methyl tryptophan (C11-AMT) and fluorodeoxyglucose (FDG) PET imaging of tumor lesions in a prospective clinical trial of pembrolizumab in MM (clinicaltrials.gov, NCT03089606). We found higher protein expression of all TMEs and LAT1 in melanoma cells than tumor-infiltrating lymphocytes (TILs) within MM tumors (n = 68). Melanoma cell-specific TPH1 and LAT1 expressions were significantly anti-correlated with TIL presence in MM. High melanoma cell-specific LAT1 and low IDO1 expression were associated with worse overall survival (OS) in MM. Exploratory optimal cutpoint survival analysis of pretreatment ‘high’ vs. ‘low’ C11-AMT SUVmax of the hottest tumor lesion per patient revealed that the ‘low’ C11-AMT SUVmax was associated with longer progression-free survival in our clinical trial (n = 26). We saw no such trends with pretreatment FDG PET SUVmax. Treatment of melanoma cell lines with telotristat, a TPH1 inhibitor, increased IDO expression and kynurenine production in addition to suppression of serotonin production. High melanoma tryptophan metabolism is a poor predictor of pembrolizumab response and an adverse prognostic factor. Serotoninergic but not kynurenine pathway activation may be significant. Melanoma cells outcompete adjacent TILs, eventually depriving the latter of an essential amino acid.

Introduction: Postoperative drain loss can exceed intraoperative blood loss and affect the severity of the patient’s condition. Aim: The objective of the study was to find significant predictors of postoperative blood loss in surgery for idiopathic scoliosis.Materials and methods: We analyzed the data of 140 patients with idiopathic scoliosis. One hundred three patients (group 1) un-derwent Smith-Petersen osteotomy as part of the multilevel pedicle screw fixation; 37 patients (group 2) required no spinal osteotomy. Correlation and regression analysis of the data was performed.Results: There were significant differences between the groups in the number of fixed segments (p

Abstract Curcumin inhibits UDP‐glucuronyltransferases, a primary metabolic pathway for cancer chemotherapeutic agents like irinotecan. Concurrent administration of both agents may exacerbate irinotecan toxicity. We conducted this phase I study to determine the safety of concurrent curcumin and irinotecan administration. Ten participants with advanced solid tumors received one of four doses (1, 2, 3, and 4 g) of a curcumin phosphatidylcholine complex (PC) orally daily, and 200 mg/m2 of i.v. infusion irinotecan on days 1 and 15 of a 28‐day cycle, to determine the maximum tolerated dose (MTD) of PC. Thirteen participants received 4 g of PC (MTD) to assess the effect on the pharmacokinetic (PK) properties of irinotecan and its metabolites, SN‐38 and SN‐38G. Irinotecan, SN‐38, and SN‐38G exposure equivalence with and without curcumin was assessed using area under the plasma concentration‐time curves from 0 to 6 h (AUC0‐6h). Safety assessments and disease responses were also evaluated. The combination of irinotecan and PC was well‐tolerated. Because there was no dose limiting toxicity, the maximum dose administered (4 g) was defined as the recommended phase II dose of PC. PC did not significantly alter the plasma exposure and other PK properties of irinotecan and its metabolites. There was no apparent increase in the incidence of irinotecan‐associated toxicities. The objective response rate was 3/19 (22%, 95% confidence interval [CI]: 5–39%), median progression free survival and overall survival (n = 23) were 4 months (95% CI: 2.9–8.9 months) and 8.4 months (95% CI: 3.7 – not evaluable [NE]), respectively. Future studies are required to evaluate the efficacy of this combination.

Foams have been successfully implemented to overcome the challenges associated with gas-enhanced oil recovery (EOR) over time. Generally, the foam helps to increase the viscosity of the injected gas, which in turn improves the effectiveness of EOR. However, this technology has rarely been applied in the oilfield due to technological and economical limitations. It is widely considered that nanoparticles may be added to foam to enhance its performance in harsh reservoir conditions to overcome some of these limitations. In this study, we employed high-pressure microscopy (HPM) as an advanced technique to examine the stability of N2 and CO2 foams at reservoir conditions, both with and without nanoparticles. The experiments were conducted under vapour and supercritical conditions. Our results indicated that foams produced at 80% quality were more stable than foams produced at 50% quality because the bubble size was significantly smaller and the bubble count was higher. Additionally, foams under supercritical conditions (sc) exhibited greater stability than foams under vapour conditions. This is because at supercritical conditions, the high density of gases helps to strengthen the foam lamella by enhancing the intermolecular contacts between the gas and the hydrophobic part of the liquid phase. Furthermore, core flooding studies were performed to investigate their effect on oil displacement and mobility control in both real and artificial core samples. Rather than focusing on precise quantitative results, our objective was to assess the effect of foams on oil recovery qualitatively. The results indicated that foam injection could significantly increase displacement efficiency, as foam injection raised total displacement efficiency from an initial 48.9% to 89.7% in the artificial core sample. Similarly, in the real core model, CO2 foam injection was implemented as a tertiary recovery method, and a recovery factor of 28.91% was obtained. These findings highlight the potential benefits of foams for EOR purposes and their ability to mitigate early gas breakthrough, which was observed after injecting approximately 0.14 PV during scCO2 injection.

Introduction: Surgical correction of adolescent idiopathic scoliosis is inevitably accompanied by blood loss. About 37–85% of patients undergo allogeneic transfusions associated with a risk of serious complications. Prediction of the expected blood loss volume remains a topical problem. In this regard, there is a need to clarify predictors of increased blood loss.Aim: To assess the effect of vertebrectomy on the intraoperative blood loss volume during surgical correction of adolescent idiopathic scoliosis.Materials and methods: A retrospective study included 511 adolescents who underwent posterior correction of spinal deformity. Two groups were allocated: Group I consisted of 303 patients who underwent multilevel transpedicular fixation; Group II included 208 patients who underwent multilevel transpedicular fixation combined with Smith-Peterson osteotomy.Results: Intergroup comparisons revealed significant differences in the number of transpedicular fixation levels and the volume of blood loss, which were higher in Group II. After aligning the groups by the number of transpedicular fixation levels using the Propensity Score Matching method, no statistically significant difference was observed. We derived formulas for calculating the expected blood loss volume in Groups I and II. Comparison of the formulas revealed that the formula for Group II predicted a significantly lower volume of blood loss, by 2.51%, while the formula for Group I predicted a significantly higher volume of blood loss, by 3.27%. In our opinion, application of the formula that overestimates expected intraoperative blood loss is most reasonable due to a possibility of the worst case scenario during surgery; therefore, the formula for Group I approaches a universal model for use.Conclusion: Smith-Peterson osteotomy did not affect the amount of blood loss during surgical correction of adolescent idiopathic scoliosis, considering the number of transpedicular fixation levels.

Hypertension is a major risk factor for cardiovascular diseases, such as strokes and myocardial infarctions. Nearly 70% of hypertension onsets in adults can be attributed to obesity, primarily due to sympathetic overdrive and the dysregulated renin-angiotensin system. Sympathetic overdrive increases vasoconstriction via α1-adrenoceptor activation on vascular cells. Despite the fact that a sympathetic outflow increases in individuals with obesity, as a rule, there is a cohort of patients with obesity who do not develop hypertension. In this study, we investigated how adrenoceptors’ expression and functioning in adipose tissue are affected by obesity-driven hypertension. Here, we demonstrated that α1A is a predominant isoform of α1-adrenoceptors expressed in the adipose tissue of patients with obesity, specifically by multipotent mesenchymal stromal cells (MSCs). These cells respond to prolonged exposure to noradrenaline in the model of sympathetic overdrive through the elevation of α1A-adrenoceptor expression and signaling. The extent of MSCs’ response to noradrenaline correlates with a patient’s arterial hypertension. scRNAseq analysis revealed that in the model of sympathetic overdrive, the subpopulation of MSCs with contractile phenotype expanded significantly. Elevated α1A-adrenoceptor expression is triggered specifically by beta3-adrenoceptors. These data define a novel pathophysiological mechanism of obesity-driven hypertension by which noradrenaline targets MSCs to increase microvessel constrictor responsivity.

By trapping CO2 and storing it in matured and depleted geological formations, atmospheric CO2 release can be reduced. Carbon capture and storage on a large scale can help to stabilize atmospheric greenhouse gas emissions. This can be achieved by using anthropogenic CO2 for enhanced oil recovery (EOR), which encourages advances in secure CO2 storage while enhancing the oil production process. This interaction is expected to hasten the development of CO2 storage technology and lower emissions from oil producing operations. Reducing CO2 mobility in the reservoir is crucial to achieving this goal as effectively as possible, and in situ foam generation offers a viable solution. It has been shown that implementing a blend of CO2 and foaming solution considerably reduces CO2 mobility and front propagation. Although there have been a few reviews of carbon capture, utilization, and storage (CCUS), none of these have concentrated on the role of foam EOR in achieving carbon neutrality. Therefore, in this brief review, methods for achieving carbon neutrality with foam EOR are comprehensively reviewed. In order to store CO2, the utilisation of atmospheric CO2 to generate foam is the main topic of this review. This approach can boost financial incentives for the energy sector, help to lower carbon emissions, and make it possible to produce oil from depleted reservoirs in a more sustainable way. Thus, identifying and examining the governing mechanisms that affect CO2 storage during foam flooding as well as reviewing the various techniques for estimating CO2 storage under actual reservoir circumstances are among the goals of this work.

Low-salinity surfactant nanofluids have recently shown promising results in the wettability alteration of reservoir rocks from oil-wet state towards more water-wet state. However, the investigation of pore-level interactions of nanofluids injection in real oil carbonate rocks at reservoir conditions, which determines the overall fluid dynamics, is lacking. Therefore, in this work, we studied the effect of nanoparticles augmented low-salinity surfactant flooding on the wettability alteration of hydrophobic carbonate rocks with harsh reservoir conditions via X-ray micro-tomography. The designed experiment scheme involved core flooding with an X-ray transparent core-holder developed for studying the flow properties of fluids at the micro level (pore scale). The wettability was quantified by measuring the differences in contact angles after the injection of low salinity, low-salinity surfactant, and low-salinity surfactant nanofluid. The findings illustrate that surfactant flooding with silica nanoparticles had a more pronounced influence on the contact angle among other injected fluids. The contact angle of the rock fell from 144° to 49°, corresponding to the water-wet conditions of carbonate rocks. The results show that the addition of a low concentration (0.005 wt.%) of SiO2 nanoparticles was enough for wettability changes in oil carbonate rocks. This study illustrates that a combination of surfactant, low-salinity, and nanoparticle features has a more pronounced effect on the three-phase contact angle than if applied separately.

Foam-enhanced oil recovery (EOR) is poised to become one of the most promising tertiary recovery techniques to keep up with the continuously increasing global energy demands. Due to their low sensitivity to gravity and permeability heterogeneities that improve sweep efficiency, foams are the preferred injection fluids over water or gas. Although foam injection has been used in the field to improve oil recovery and control gas mobility, its success is still hindered by several conceptual and operational challenges with regard to its stability and foamability under reservoir conditions. This can be attributed to the insufficient attention given to the mechanisms underlying foam generation and stability at the microscopic level in many studies. For a deeper understanding, this study reviews the most pertinent published works on foam-EOR. The major objective is to provide a broad basis for subsequent laboratory and field applications of foam-EOR. In this work, we highlighted foam classification and characterization, as well as the crucial factors impacting foam formation, stability, and oil recovery. Additionally, the principal mechanisms of foam generation are thoroughly explained. Finally, the most recent developments in foam generation and stability improvement are discussed. Foam-EOR is comprehensively reviewed in this work, with an emphasis on both theoretical and practical applications.

Over the past decades, the achievements in astronomical instrumentation have given rise to a number of novel advanced studies related to the analysis of large arrays of observational data. One of the most famous of these studies is a study of transient events in the near and far space and a search for exoplanets. The main requirements for such kinds of projects are a simultaneous coverage of the largest possible field of view with the highest possible detection limits and temporal resolution. In this study, we present a similar project aimed at creating an extensive, continuously updated survey of transient events and exoplanets. To date, the core of the project incorporates several 0.07–2.5 m optical telescopes and the 6-m BTA telescope of the Special Astrophysical Observatory of RAS (Russia), a number of other Russian observatories and the Bonhyunsan observatory of the Korea Astronomy and Space Science Institute (South Korea). Our attention is mainly focused on the description of two groups of small, wide-angle optical telescopes for primary detection. All the telescopes are originally designed for the goals of the project and may be of interest to the scientific community. A description is also given for a new, high-precision optical spectrograph for the Doppler studies of transient and exoplanet events detected within the project. We present here the philosophy, expectations and first results obtained during the first year of running the project.

The aim of the article is to investigate the impact of the new coronavirus infection on the Russian labor market and to suppose the actions to be taken to minimize negative economic consequences. The distinctiveness of this study is the differentiation of the impact of the physical and informational spread of COVID-19. The informational spread of coronavirus is measured through the dynamics of news messages related to the topic of “coronavirus” in the largest Russian media. The analysis of the average level of wages by type of economic activity, as well as the demand of employers and the number of vacancies, allow testing the hypothesis that the physical and informational spread of coronavirus caused an increase in the number of unemployed, a decrease in average wages in the studied range of economic activities, an increase in supply on the labor market, and a decrease in demand for employees. Another task of the study is to assess the dynamics of related search queries in Yandex (Russian biggest search engine), which can help to reveal the logic in the behavior of the Russian people during the pandemic as well as to understand if the Russian economy, the labor market, and society were prepared for the changes caused by the pandemic. Using a regression modeling methodology, it was found that the influence of the information environment, namely the informational spread of coronavirus, had an even greater impact on studied parameters than the physical spread. A “delay effect of physical consequences” was discovered. The conclusions obtained showed that in the conditions of wide informatization of society, it is necessary to systematically influence the physical and informational spread of coronavirus to minimize the negative consequences of the pandemic on the labor market.

Objective: Antimicrobial prophylaxis for children with vesicoureteral reflux (VUR) reduces recurrences of urinary tract infection (UTI) but requires daily antimicrobials for extended periods. We used a cost-utility model to evaluate whether the benefits of antimicrobial prophylaxis outweigh its risks and, if so, to investigate whether the benefits and risks vary according to grade of VUR.Methods: We compared the cost per quality-adjusted life-year (QALY) gained in four treatment strategies in children aged

In the medieval Indian mythology, based on the texts of the Pali canon of Ttipitaka and the Puranas, there are images there are images depicting eschatological religious and philosophical ideas. One of the main images is Kalki - the tenth avatar of Vishnu, the Hindu Messiah, whose coming, according to the Puranas, must put an end to the moral and religious decay in the last days of Kali-yuga. The myth of the bodhisattva Maitreya, whose worship is widespread among the various schools of Buddhism, is connected with the prophecy about the future rebirth of Maitreya, who awaits his time in Tushita Heaven. This article presents the eschatological content of myths about Maitreya and Kalki and how it realized in the sequence of the mythological plot, associated with the ultimate destiny of the world at the time of completion of the next time cycle. Comparing the myths of Maitreya and Kalki, shows the certain similarity between the images of Maitreya and Kalki, which raises the question of which of the mythological plots was primary Proceeding from the earlier origin of the myth about Maitreya, it should be noted that the image of Kalki in the literature of the Puranas was formed by the influence of the inclusivist strategies of the Vishnu tradition.Despite the unity of mythological functions and active interaction, the images of Kalki and Maitreya are contrasted in relation to each other, since they show two different scenarios of cyclic eschatology : the Kalki court and his cruel retribution, and the preaching of Maitreya, that bring salvation for all beings.

Abstract: Most patients who could be cured of sickle cell disease (SCD) with stem cell transplantation do not have a matched sibling donor. Successful use of alternative donors, including mismatched family members, could provide a donor for almost all patients with SCD. The use of a reduced-intensity conditioning regimen may decrease late adverse effects. Ten patients with symptomatic SCD underwent CD34+ cell-selected, T-cell–depleted peripheral blood stem cell transplantation from a mismatched family member or unrelated donor. A reduced-intensity conditioning regimen including melphalan, thiotepa, fludarabine, and rabbit anti-thymocyte globulin was used. Patients were screened for a companion study for immune reconstitution that included a donor lymphocyte infusion given 30-42 days after transplant with intravenous methotrexate as graft-versus-host disease (GVHD) prophylaxis. Seven eligible patients were treated on the companion study. Nine of 10 patients are alive with a median follow-up of 49 months (range, 14-60 months). Surviving patients have stable donor hematopoietic engraftment (mean donor chimerism, 99.1% ± 0.7%). There were no sickle cell complications after transplant. Two patients had grade II-IV acute GVHD. One patient had chronic GVHD. Epstein-Barr virus–related posttransplant lymphoproliferative disorder (PTLD) occurred in 3 patients, and 1 patient died as a consequence of treatment of PTLD. Two-year overall survival was 90%, and event-free survival was 80%. A reduced-intensity conditioning regimen followed by CD34+ cell-selected, T-cell–depleted alternative donor peripheral blood stem cell transplantation achieved primary engraftment in all patients with a low incidence of GVHD, although PTLD was problematic. This trial was registered at clinicaltrials.gov as #NCT00968864.

Background: Little is known about the prognostic significance of somatically mutated genes in metastatic melanoma (MM). We have employed a combined clinical and bioinformatics approach on tumor samples from cutaneous melanoma (SKCM) as part of The Cancer Genome Atlas project (TCGA) to identify mutated genes with potential clinical relevance.Methods: After limiting our DNA sequencing analysis to MM samples (n = 356) and to the CANCER CENSUS gene list, we filtered out mutations with low functional significance (snpEFF). We performed Cox analysis on 53 genes that were mutated in ≥3% of samples, and had ≥50% difference in incidence of mutations in deceased subjects versus alive subjects.Results: Four genes were potentially prognostic [RAC1, FGFR1, CARD11, CIITA; false discovery rate (FDR) < 0.2]. We identified 18 additional genes (e.g., SPEN, PDGFRB, GNAS, MAP2K1, EGFR, TSC2) that were less likely to have prognostic value (FDR < 0.4). Most somatic mutations in these 22 genes were infrequent (< 10%), associated with high somatic mutation burden, and were evenly distributed across all exons, except for RAC1 and MAP2K1. Mutations in only 9 of these 22 genes were also identified by RNA sequencing in >75% of the samples that exhibited corresponding DNA mutations. The low frequency, UV signature type and RNA expression of the 22 genes in MM samples were confirmed in a separate multi-institution validation cohort (n = 413). An underpowered analysis within a subset of this validation cohort with available patient follow-up (n = 224) showed that somatic mutations in SPEN and RAC1 reached borderline prognostic significance [log-rank favorable (p = 0.09) and adverse (p = 0.07), respectively]. Somatic mutations in SPEN, and to a lesser extent RAC1, were not associated with definite gene copy number or RNA expression alterations. High (>2+) nuclear plus cytoplasmic expression intensity for SPEN was associated with longer melanoma-specific overall survival (OS) compared to lower (≤ 2+) nuclear intensity (p = 0.048). We conclude that expressed somatic mutations in infrequently mutated genes beyond the well-characterized ones (e.g., BRAF, RAS, CDKN2A, PTEN, TP53), such as RAC1 and SPEN, may have prognostic significance in MM.

Целью представленного исследования является выявление особенностей воспитания наркозависимых детей родителями, страдающими межличностной зависимостью, а также разработка и апробирование программы преодоления родителями межличностной зависимости.PARTICULARITIES OF EDUCATION OF DRUG DEPENDENT CHILDREN BY PARENTS WITH INTERPERSONAL DEPENDENCE The scope of the study is to determine the particularities of educating the drug addicted children by parents with interpersonal dependence and elaborating and approving a program to overcome interpersonal addiction to parents.

The perspective combination of laser micromilling technology and jet (aerosol) printing technologies for ceramic MEMS producing of microhotplate in the surface mounted device (SMD) package for the metal oxide (MOX) sensor is describing. There are discusses technological and economic aspects of small-scale production of gas MOX sensors. Experiments with laser micromilling of Al2O3 ceramics confirmed possibility to produce MEMS microhotplate for MOX gas sensor in SMD package with form-factor SOT-23. Developed technology process is close to 3D prototype philosophy—rapid, simple and cheap.

Constraints arise naturally in many scientific experiments/studies such as in, epidemiology, biology, toxicology, etc. and often researchers ignore such information when analyzing their data and use standard methods such as the analysis of variance (ANOVA). Such methods may not only result in a loss of power and efficiency in costs of experimentation but also may result poor interpretation of the data. In this paper we discuss constrained statistical inference in the context of linear mixed effects models that arise naturally in many applications, such as in repeated measurements designs, familial studies and others. We introduce a novel methodology that is broadly applicable for a variety of constraints on the parameters. Since in many applications sample sizes are small and/or the data are not necessarily normally distributed and furthermore error variances need not be homoscedastic (i.e. heterogeneity in the data) we use an empirical best linear unbiased predictor (EBLUP) type residual based bootstrap methodology for deriving critical values of the proposed test. Our simulation studies suggest that the proposed procedure maintains the desired nominal Type I error while competing well with other tests in terms of power. We illustrate the proposed methodology by re-analyzing a clinical trial data on blood mercury level. The methodology introduced in this paper can be easily extended to other settings such as nonlinear and generalized regression models.

Calcium supplements are widely used among older adults for osteoporosis prevention and treatment. However, their effect on creatinine levels and kidney function has not been well studied.We investigated the effect of calcium supplementation on blood creatinine concentration in a randomized controlled trial of colorectal adenoma chemoprevention conducted between 2004-2013 at 11 clinical centers in the United States. Healthy participants (N = 1,675) aged 45-75 with a history of colorectal adenoma were assigned to daily supplementation with calcium (1200 mg, as carbonate), vitamin D3 (1000 IU), both, or placebo for three or five years. Changes in blood creatinine and total calcium concentration were measured after one year of treatment and multiple linear regression was used to estimate effects on creatinine concentrations.After one year of treatment, blood creatinine was 0.013±0.006 mg/dL higher on average among participants randomized to calcium compared to placebo after adjustment for other determinants of creatinine (P = 0.03). However, the effect of calcium treatment appeared to be larger among participants who consumed the most alcohol (2-6 drinks/day) or whose estimated glomerular filtration rate (eGFR) was less than 60 ml/min/1.73 m2 at baseline. The effect of calcium treatment on creatinine was only partially mediated by a concomitant increase in blood total calcium concentration and was independent of randomized vitamin D treatment. There did not appear to be further increases in creatinine after the first year of calcium treatment.Among healthy adults participating in a randomized clinical trial, daily supplementation with 1200 mg of elemental calcium caused a small increase in blood creatinine. If confirmed, this finding may have implications for clinical and public health recommendations for calcium supplementation.ClinicalTrials.gov NCT00153816.