This paper provides a kinetics model for thermal cracking of various oils over time frames which correspond to the long term storage at temperatures up to those experienced in an in situ combustion ...process. The model describes detailed kinetic mechanisms and concentration changes of individual species during the thermal cracking reactions. Also the modeling results are compared with the experimental data to verify their validity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Hallmarks of primary hyperoxaluria type 3 are nephrolithiasis and hyperoxaluria. However, little is known about factors influencing stone formation in this disease. We characterized stone events and ...examined associations with urine parameters and kidney function in a primary hyperoxaluria type 3 population.
We retrospectively analyzed clinical, and laboratory data of 70 primary hyperoxaluria type 3 patients enrolled in the Rare Kidney Stone Consortium Primary Hyperoxaluria Registry.
Kidney stones occurred in 65/70 primary hyperoxaluria type 3 patients (93%). Among the 49 patients with imaging available, the median (IQR) number of stones was 4 (2, 5), with largest stone 7 mm (4, 10) at first imaging. Clinical stone events occurred in 62/70 (89%) with median number of events per patient 3 (2, 6; range 1-49). Age at first stone event was 3 years (0.99, 8.7). Lifetime stone event rate was 0.19 events/year (0.12, 0.38) during follow-up of 10.7 (4.2, 26.3) years. Among 326 total clinical stone events, 139 (42.6%) required surgical intervention. High stone event rates persisted for most patients through the sixth decade of life. Analysis was available for 55 stones: pure calcium oxalate accounted for 69%, with mixed calcium oxalate and phosphate in 22%. Higher calcium oxalate supersaturation was associated with increased lifetime stone event rate after adjusting for age at first event (IRR 95%CI 1.23 1.16, 1.32;
< .001). By the fourth decade, estimated glomerular filtration rate was lower in primary hyperoxaluria type 3 patients than the general population.
Stones impose a lifelong burden on primary hyperoxaluria type 3 patients. Reducing urinary calcium oxalate supersaturation may reduce event frequency and surgical intervention.
A conical combustion cell was conceived and utilized in dry, wet and super wet combustion experiments at the In Situ Combustion Research Group at the University of Calgary to investigate the effect ...of continuous in situ air flux drop on the dynamics of the combustion process and to identify the characteristics of the process most importantly the extinction air flux. Minimum injected air flux at the termination of the experiments was calculated; gas phase combustion parameters were analyzed. Some of the features specific to combustion experiments in conical cells were investigated. Combustion performance analysis using oil recover/volume burned calculations for dry conical tests and oil recovered vs. volume steamed and oxygen oil ratio vs. volume burned as the crucial economical parameters of the design of wet combustion processes were calculated. This study greatly enhances the understanding of the complexity of the combustion process and illustrates its characteristic behavior at or close to its exhaustion.
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A conical combustion cell was built and utilized in combustion experiments at the In Situ Combustion Research Group at the University of Calgary to investigate the effect of continuous in situ air flux drop on the dynamics of the combustion process and to identify the characteristics of the process most importantly the extinction air flux. Nine set of top-down (gravity stable) dry, wet and superwet combustion experiments were conducted at different injection rates in sand packs representing typical Athabasca heavy oil reservoirs. The temperature profiles, the produced combustion gases and liquids as well as the unpacked core were examined. Minimum injected air flux at the termination of the experiments was calculated; gas phase combustion parameters were analyzed. Some of the features specific to combustion experiments in conical cells were investigated.
It is believed that the formation of fuel rich condition especially in presence of water at the location of the combustion front at certain locations of the core at certain circumstances tends to prevent energy generation at the combustion front even at high air injection rates. Also, it was shown that the counter current convection/diffusion of fuel gases from the combustion front to upstream locations of the core also known as the roll cell effect adversely influences the advancement of the high temperature combustion front which in turn impacts the oil mobilization and recovery.
Combustion performance analysis using oil recovered/volume burned calculations for dry conical tests and oil recovered vs. volume steamed and oxygen oil ratio vs. volume burned as the crucial economical parameters of the design of wet combustion processes were calculated. This study greatly enhances the understanding of the complexity of the in situ combustion process and illustrates its characteristic behavior at or close to its exhaustion.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
494.
Single-Molecule Biomechanics with Optical Methods Mehta, Amit D.; Rief, Matthias; Spudich, James A. ...
Science (American Association for the Advancement of Science),
03/1999, Volume:
283, Issue:
5408
Journal Article
Peer reviewed
Single-molecule observation and manipulation have come of age. With the advent of optical tweezers and other methods for probing and imaging single molecules, investigators have circumvented the ...model-dependent extrapolation from ensemble assays that has been the hallmark of classical biochemistry and biophysics. In recent years, there have been important advances in the understanding of how motor proteins work. The range of these technologies has also started to expand into areas such as DNA transcription and protein folding. Here, recent experiments with rotary motors, linear motors, RNA polymerase, and titin are described.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Abstract
Background
Limited data exist on high-sensitivity cardiac troponin (hs-cTn) for risk-stratification in COVID-19.
Methods
We conducted a multicenter, retrospective, observational, US-based ...study of COVID-19 patients undergoing hs-cTnT. Outcomes included short-term mortality (in-hospital and 30-days post-discharge) and a composite of major adverse events, including respiratory failure requiring mechanical ventilation, cardiac arrest, and shock within the index presentation and/or mortality during the index hospitalization or within 30-days post-discharge.
Results
Among 367 COVID-19 patients undergoing hs-cTnT, myocardial injury was identified in 46%. They had a higher risk for mortality (20% vs 12%, P < 0.0001; unadjusted HR 4.44, 95% CI 2.13–9.25, P < 0.001) and major adverse events (35% vs. 11%, P < 0.0001; unadjusted OR 4.29, 95% CI 2.50–7.40, P < 0.0001). Myocardial injury was associated with major adverse events (adjusted OR 3.84, 95% CI 2.00–7.36, P < 0.0001) but not mortality. Baseline (adjusted OR 1.003, 95% CI 1.00–1.007, P = 0.047) and maximum (adjusted OR 1.005, 95% CI 1.001–1.009, P = 0.0012) hs-cTnT were independent predictors of major adverse events. Most (95%) increases were due to myocardial injury, with 5% (n = 8) classified as type 1 or 2 myocardial infarction. A single hs-cTnT <6 ng/L identified 26% of patients without mortality, with a 94.9% (95% CI 87.5–98.6) negative predictive value and 93.1% sensitivity (95% CI 83.3–98.1) for major adverse events in those presenting to the ED.
Conclusions
Myocardial injury is frequent and prognostic in COVID-19. While most hs-cTnT increases are modest and due to myocardial injury, they have important prognostic implications. A single hs-cTnT <6 ng/L at presentation may facilitate the identification of patients with a favorable prognosis.
BACKGROUND.This study was undertaken to determine the incidence, pathogens and risk factors associated with development of sternal wound and other infections in children undergoing cardiac surgery.
...METHODS.Retrospective chart review was performed for all cardiac surgeries performed on children <18 years of age at Upstate Medical University at Syracuse between January, 1996, and June, 1998. For evaluation of risk factors for sternal wound infection, only patients undergoing sternotomy are included in the analysisthose with infection are compared with those without for preoperative, intraoperative and postoperative risk factors.
RESULTS.Sternal wound infection developed in 10 of 202 (5%) children after median sternotomy. Superficial sternal wound infection developed in 6 (3%) children, and 4 (2%) had deep infection. Children with sternal wound infection had lower age, higher American Society of Anesthesiologist score, longer preoperative stay, longer period of ventilation and inotropic support, longer intensive care unit and total postoperative hospital stays and increased leukocyte band cell counts preoperatively and on Postoperative Day 1 than those without sternal infection. Causative agents for sternal wound infection were Staphylococcus aureus (6), Pseudomonas aeruginosa (1) and Haemophilus influenzae non-type b (1). In addition 32 bacterial infections occurred at nonsurgical sites after 28 procedures. Infections included pneumonia, urinary tract infection and bacteremia. Longer bypass time and longer operation time were two additional risk factors for nonwound infection.
CONCLUSION.Infections continue to be a significant cause of morbidity in cardiac surgery patients. Knowledge of risk factors for infection could be useful in preventive and treatment strategies for these high-risk groups.
XIAP (X-linked inhibitor of apoptosis) deficiency is a rare inborn error of immunity. XIAP deficiency causes hyperinflammatory disease manifestations due to dysregulated TNF (tumor necrosis ...factor)-receptor signaling and NLRP3 (NOD- nucleotide-binding oligomerization domain, LRR- leucine-rich repeat and pyrin domain-containing protein 3) inflammasome function. Safe and effective long-term treatments are needed and are especially important to help prevent the need for high-risk allogeneic hematopoietic cell transplantation. Here we evaluated inflammasome inhibitors as potential therapeutics with a focus on the natural flavonoid antioxidant quercetin. Bone marrow (BM)-derived macrophages were derived from XIAP-deficient or wild-type (WT) mice. Human monocytes were obtained from control or XIAP-deficient patients. Cells were stimulated with TLR (Toll-like receptor) agonists or TNF-α ± inhibitors or quercetin. For in vivo lipopolysaccharide (LPS) challenge experiments, XIAP-deficient or WT mice were fed mouse chow ± supplemental quercetin (50 mg/kg per day exposure) for 7 days followed by a challenge with 10 ng/kg LPS. IL-1β (interleukin-1β) and IL-18 were measured by ELISA (enzyme-linked immunosorbent assay). In murine studies, quercetin prevented IL-1β secretion from XIAP knockout cells following TLR agonists or TNF-α stimulation (P < .05) and strongly reduced constitutive production of IL-18 by both WT and XIAP-deficient cells (P < .05). At 4 hours after in vivo LPS challenge, blood levels of IL-1β and IL-18 were significantly decreased in mice that had received quercetin-supplemented chow (P < .05). In experiments using human cells, quercetin greatly reduced IL-1β secretion by monocytes following TNF-α stimulation (P < .05). Our data suggest that quercetin may be an effective natural therapeutic for the prevention of XIAP deficiency-associated hyperinflammation. Clinical trials, including careful pharmacokinetic and pharmacodynamic studies to ensure that effective levels of quercetin can be obtained, are warranted.
•Quercetin inhibits XIAP deficiency-associated NLRP3 inflammasome dysfunction.•Quercetin may be an effective natural therapeutic for the prevention of XIAP deficiency-associated hyperinflammation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Rationale
Working memory deficits and associated neurofunctional abnormalities are frequently reported in attention-deficit/hyperactivity disorder (ADHD). Methylphenidate and atomoxetine improve ...working memory performance and increase activation of regions under-functioning in ADHD. Additionally, methylphenidate has been observed to modulate functional networks involved in working memory. No research, however, has examined the effects of atomoxetine or compared the two drugs.
Objectives
This study aimed to test methylphenidate and atomoxetine effects on functional connectivity during working memory in boys with ADHD.
Methods
We tested comparative effects of methylphenidate and atomoxetine on functional connectivity during the n-back task in 19 medication-naïve boys with ADHD (10–15 years old) relative to placebo and assessed potential normalisation effects of brain dysfunctions under placebo relative to 20 age-matched neurotypical boys. Patients were scanned in a randomised, double-blind, cross-over design under single doses of methylphenidate, atomoxetine, and placebo. Controls were scanned once, unmedicated.
Results
Patients under placebo showed abnormally increased connectivity between right superior parietal gyrus (rSPG) and left central operculum/insula. This hyperconnectivity was not observed when patients were under methylphenidate or atomoxetine. Furthermore, under methylphenidate, patients showed increased connectivity relative to controls between right middle frontal gyrus (rMFG) and cingulo-temporo-parietal and striato-thalamic regions, and between rSPG and cingulo-parietal areas. Interrogating these networks within patients revealed increased connectivity between both rMFG and rSPG and right supramarginal gyrus under methylphenidate relative to placebo. Nonetheless, no differences across drug conditions were observed within patients at whole brain level. No drug effects on performance were observed.
Conclusions
This study shows shared modulating effects of methylphenidate and atomoxetine on parieto-insular connectivity but exclusive effects of methylphenidate on connectivity increases in fronto-temporo-parietal and fronto-striato-thalamic networks in ADHD.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Mutations of the gene (GLA) encoding alpha-galactosidase A are implicated in Fabry disease, a progressive, X-chromosomal inherited lysosomal storage disorder. FOS--the Fabry Outcome Survey - was ...established as a long-term surveillance study to describe the natural course of Fabry disease and its response to enzyme replacement therapy in a large cohort of European patients. Clinical phenotype, age of onset and course of Fabry disease are very variable, even within the same family, which makes it difficult to define a genotype-phenotype relationship by analysing individual patients. The FOS database contains detailed medical information on a large cohort of patients and thus has the potential to provide important information to address this question.
At the time of analysis, information on 545 patients belonging to 157 families from nine European countries had been entered into the FOS database. A GLA mutation has been reported in 365 individuals (65% and 68% of all males and females, respectively) in FOS. These data were used to analyse the relationship between genotype and phenotype in Fabry disease.
A highly significant positive correlation was found between the age at entry into FOS and the FOS Severity Index in male patients with GLA missense mutations (p < 0.001) as well as in those carrying other types of mutations (p < 0.001). A positive correlation was also found between the age at entry into FOS and the number of affected organs in male patients with missense mutations, irrespective of whether the change in the amino acid side chain predicted in the alpha-galactosidase A protein was classified as a conservative or non-conservative change.
The data presented here suggest that there is a correlation between genotype and clinical severity.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UL, UM, UPUK
Polymorphisms of DNA repair genes RAD51 and XRCC3 increase susceptibility to acute myeloid leukemia (AML) in adults, an effect enhanced by deletion of the glutathione-S-transferase M1 (GSTM1) gene. ...In this study, we genotyped 452 children with de novo AML treated on CCG protocols 2941 and 2961 and compared genotype frequencies with those of normal blood donors, and analyzed the impact of genotype on outcome of therapy. XRCC3 Thr241Met, RAD51 G135C and GSTM1 genotypes did not increase susceptibility to AML when assessed singly. In contrast, when XRCC3 and RAD51 genotypes were examined together a significant increase in susceptibility to AML was seen in children with variant alleles. Analysis of outcome of therapy showed that patients heterozygous for the XRCC3 Thr241Met allele had improved post-induction disease-free survival compared to children homozygous for the major or minor allele, each of whom had similar outcomes. Improved survival was due to reduced relapse in the heterozygous children, and this effect was most marked in children randomized to therapy likely to generate DNA double-strand breaks (etoposide, daunomycin), compared with anti-metabolite (fludarabine, cytarabine) based therapy. In contrast, RAD51 G135C and the GSTM1 deletion polymorphism did not influence outcome of AML therapy in our study population.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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