Changes In Absolute Concentrations Research Articles

Advancing Low-Cost Flow Battery Chemistries

Pumped-hydroelectric presently dominates U.S. grid electricity storage capacity resources, but the past decade has brought increasing levels of electrochemical energy storage (EES) installations.1 Policymakers have recognized the need for longer-duration systems as more EES gets added to the grid and sought systems that can provide durations of 8+ hours.2 , 3 Although Li-ion presently dominates EES deployments, the average duration of U.S. utility-based-systems are relatively short at 3 hours.4 Redox flow batteries (RFBs) have an advantage over Li-ion systems at long durations due to their system architecture. The marginal cost of another hour of RFB duration asymptotes to the cost of additional active materials and their storage containers, as opposed to the cost of additional Li-ion cells, packs, and modules.Leading vanadium RFBs have made cost reductions by improving the power density of their energy conversion stacks,5 , 6 but eventually are limited by the relatively high cost of their vanadium active materials. Vanadium RFB suppliers are actively seeking to reduce this cost through business innovations. Yet, from a technical perspective, switching to lower cost active materials can also permit economically feasible long duration RFB systems.7 RTX Technology Research Center has previously reported on the low cost active material chemistries including the sulfur/manganese (S-Mn) chemistry and ligand-coordinate metals (LCM, e.g. chromium/iron).8 , 9 S/Mn uses active materials based on low-cost sulfur, a waste product of fossil fuel production, and inexpensive manganese, an element presently used commercially in disposable primary cells. LCM chemistries use mass-produced organic ligands and inexpensive metal centers like iron, chromium, and titanium, and can rely on more neutral, and benign, electrolyte pH conditions that offer wider electrochemical stability windows. Along with these benefits, LCM chemistries bring new challenges such as managing pH in an environment where small absolute concentration changes have outsized effects. This abstract will focus on the progress made advancing low-cost chemistries toward industrial relevance via thousands of hours of operation and in full-sized cell/stack form-factors. Acknowledgements: The work presented herein was funded by the Advanced Research Projects Agency-Energy (ARPA-E), U.S. Department of Energy, under Award Number DE-AR000994. The views and opinions of authors expressed herein do not necessarily state or reflect those of the United States Government or any agency thereof. References Chalamala, B., DOE Global Energy Storage Database. Sandia National Laboratories: 2020.Padilla, M., Joint Long Duration Storage Request for Offers. Energy, S. V. C., Ed. Silicon Valley Clean Energy: 2020.Albertus, P.; Manser, J. S.; Litzelman, S., Long-Duration Electricity Storage Applications, Economics, and Technologies. Joule 2020, 4 (1), 21-32.Linga, V. Duration of utility-scale batteries depend on how they're used; EIA: U.S. EIA 'Today in Energy', March 25, 2022, 2022.Sun, C. N.; Mench, M. M.; Zawodzinski, T. A., High Performance Redox Flow Batteries: An Analysis of the Upper Performance Limits of Flow Batteries Using Non-aqueous Solvents. Electrochimica Acta 2017, 237, 199-206.Perry, M. L.; Darling, R. M.; Zaffou, R., High Power Density Redox Flow Battery Cells. ECS Transactions 2013, 53 (7), 7-16.Wadia, C.; Albertus, P.; Srinivasan, V., Resource constraints on the battery energy storage potential for grid and transportation applications. Journal of Power Sources 2011, 196 (3), 1593-1598.Yang, Z.; Gerhardt, M. R.; Fortin, M.; Shovlin, C.; Weber, A. Z.; Perry, M. L.; Darling, R. M.; Saraidaridis, J. D., Polysulfide-Permanganate Flow Battery Using Abundant Active Materials. Journal of The Electrochemical Society 2021, 168 (7), 070516.Saraidaridis, J.; Yang, Z., Electrolyte Takeover Strategy for Performance Recovery in Polysulfide-Permanganate Flow Batteries. Journal of The Electrochemical Society 2021, 168 (11), 110556.

Real-Time Evaluation of Absolute, Cytosolic, Free Ca2+ and Corresponding Contractility in Isolated, Pressurized Lymph Vessels.

The lymphatic vasculature, now often referred to as "the third circulation," is located in many vital organ systems. A principal mechanical function of the lymphatic vasculature is to return fluid from extracellular spaces back to the central venous ducts. Lymph transport is mediated by spontaneous rhythmic contractions of lymph vessels (LVs). LV contractions are largely regulated by the cyclic rise and fall of cytosolic, free calcium ([Ca2+]i). This paper presents a method to concurrently calculate changes in absolute concentrations of [Ca2+]i and vessel contractility/rhythmicity in real time in isolated, pressurized LVs. Using isolated rat mesenteric LVs, we studied changes in [Ca2+]i and contractility/rhythmicity in response to drug addition. Isolated LVs were loaded with the ratiometric Ca2+-sensing indicator Fura-2AM, and video microscopy coupled with edge-detection software was used to capture [Ca2+]iand diameter measurements continuously in real time. The Fura-2AM signal from each LV was calibrated to the minimum and maximum signal for each vessel and used to calculate absolute [Ca2+]i. Diameter measurements were used to calculate contractile parameters (amplitude, end diastolic diameter, end systolic diameter, calculated flow) and rhythmicity (frequency, contraction time, relaxation time) and correlated with absolute [Ca2+]i measurements.

Changes in Cerebral Oxygenation and Systemic Physiology During a Verbal Fluency Task: Differences Between Men and Women.

Sex differences in behavioural performance of a cognitive task have been repeatedly reported in the literature. Whether such differences are also relevant for evoked cerebral haemodynamic and oxygenation responses as well as systemic physiological changes is a topic of ongoing investigations. We investigated whether changes in cerebral oxygenation and systemic physiological activity are sex-dependent during a verbal fluency task (VFT). VFT performance and changes in cerebral oxygenation and systemic physiology were investigated in 32healthy right-handed adults (17females, 15males, age: 25.5±4.3 years). The total duration of the VFT was 9 min. During this phase, subjects were also exposed to blue light (peak wavelength: 450nm, illuminance: 120lux). Before and after the VFT, subjects were in darkness. In this study, we used the systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS) approach. Absolute concentration changes of oxyhaemoglobin ([O2Hb]), deoxyhaemoglobin ([HHb]), total haemoglobin ([tHb]), as well as tissue oxygen saturation (StO2) were measured bilaterally over the prefrontal cortex (PFC) and visual cortex (VC). Systemic physiological parameters were also recorded in parallel (e.g., end-tidal CO2, heart rate, respiration rate, skin conductance). We found that: (i) Females were better VFT performers in comparison to males. (ii) Changes in [O2Hb] and [HHb] in the VC were higher for males compared to females during the VFT under blue light exposure. (iii) Lower and higher StO2 changes were detected for males compared to females in the PFC and VC, respectively. (iv) Sex-dependent changes were also evident for end-tidal CO2, heart rate, respiration rate, and pulse-respiration quotient. Our study showed that sex differences are not only observed in task performance but also in the magnitudes of changes in cerebral and physiological parameters. The findings of the current study emphasise that sex differences in brain activation and systemic physiological activity need to be considered when interpreting functional neuroimaging data. These findings offer a broad range of implications for educational purposes and facilitate a better understanding of the effects of sex on behavioural performance as well as human physiology.

Diagnostic Performance of Serial High-Sensitivity Cardiac Troponin Measurements in the Emergency Setting.

Serial high-sensitivity cardiac troponin (hsTn) testing in the emergency department (ED) and the intensive cardiac care unit may assist physicians in ruling out or ruling in acute myocardial infarction (MI). There are three major algorithms proposed for high-sensitivity cardiac troponin I (hsTnI) using serial measurements while incorporating absolute concentration changes for MI or death following ED presentation. We sought to determine the diagnostic estimates of these three algorithms and if one was superior in two different Canadian ED patient cohorts with serial hsTnI measurements. An undifferentiated ED population (Cohort-1) and an ED population with symptoms suggestive of acute coronary syndrome (ACS; Cohort-2) were clinically managed with non-hsTn testing with the hsTnI testing performed in real-time with physicians blinded to these results (i.e., hsTnI not reported). The three algorithms evaluated were the European Society of Cardiology (ESC), the High-STEACS pathway, and the COMPASS-MI algorithm. The diagnostic estimates were derived for each algorithm for the 30-day MI/death outcome for the rule-out and rule-in arm in each cohort and compared to proposed diagnostic benchmarks (i.e., sensitivity ≥ 99.0% and specificity ≥ 90.0%) with 95% confidence intervals (CI). In Cohort-1 (n = 2966 patients, 15.3% had outcome) and Cohort-2 (n = 935 patients, 15.6% had outcome), the algorithm that obtained the highest sensitivity (97.8%; 95% CI: 96.0–98.9 and 98.6%; 95% CI: 95.1–99.8, respectively) in both cohorts was COMPASS-MI. Only Cohort-2 with both the ESC and COMPASS-MI algorithms exceeded the specificity benchmark (97.0%; 95% CI: 95.5–98.0 and 96.7%; 95% CI: 95.2–97.8, respectively). Patient selection for serial hsTnI testing will affect specificity estimates, with no algorithm achieving a sensitivity ≥ 99% for 30-day MI or death.

Low-Cost Flow Battery Active Materials for Long Duration Storage

Energy storage capacity is presently dominated by pumped-hydroelectric storage, but the past decade has brought increasing levels of electrochemical energy storage (EES) installations.1 As more EES gets added to the grid, policymakers have recognized the need for longer-duration systems and sought systems that can provide durations of 8+ hours.2 , 3 At these longer durations, redox flow batteries (RFBs) have an advantage over Li-ion systems since the marginal cost of another hour duration asymptotes to the cost of additional active materials and their storage containers, rather than additional cells, packs and modules.Leading vanadium RFBs have made cost reductions by improving the power density of their energy conversion stacks,4 , 5 but eventually are limited by the relatively high, incremental cost of their vanadium active materials. Switching to lower cost active materials can permit economically feasible long duration RFB systems.6 Raytheon Technologies Research Center has previously reported on the proposed sulfur-manganese (S-Mn) chemistry, which uses active materials based on low-cost sulfur, a waste product of fossil fuel production, and inexpensive manganese, an element presently used commercially in disposable primary cells. The team has implemented electrolyte takeover RFB technology, which has made low-cost S-Mn systems feasible despite crossover-induced precipitation that hampers performance levels.7 This technology implementation has allowed S-Mn sub-scale (20+ cm2) cell operation for 1000+ hours.Additionally, development of another low-cost chemistry, relying on ligand-coordinated metal centers,8 has showed promising early results. This chemistry, which relies on a more neutral solution pH, brings new challenges, such as managing pH in an environment where small absolute concentration changes have outsized effect, but comes with benefits such as wide electrochemical stability windows.Techno-economic analysis suggests that these two chemistries present an opportunity to deliver competitively priced long duration EES systems. This abstract will focus on the progress made advancing these two chemistries toward industrial relevance. Acknowledgements: The work presented herein was funded by the Advanced Research Projects Agency-Energy (ARPA-E), U.S. Department of Energy, under Award Number DE-AR000994. The views and opinions of authors expressed herein do not necessarily state or reflect those of the United States Government or any agency thereof. References Chalamala, B., DOE Global Energy Storage Database. Sandia National Laboratories: 2020.Padilla, M., Joint Long Duration Storage Request for Offers. Energy, S. V. C., Ed. Silicon Valley Clean Energy: 2020.Albertus, P.; Manser, J. S.; Litzelman, S., Long-Duration Electricity Storage Applications, Economics, and Technologies. Joule 2020, 4 (1), 21-32.Sun, C. N.; Mench, M. M.; Zawodzinski, T. A., High Performance Redox Flow Batteries: An Analysis of the Upper Performance Limits of Flow Batteries Using Non-aqueous Solvents. Electrochimica Acta 2017, 237, 199-206.Perry, M. L.; Darling, R. M.; Zaffou, R., High Power Density Redox Flow Battery Cells. ECS Transactions 2013, 53 (7), 7-16.Wadia, C.; Albertus, P.; Srinivasan, V., Resource constraints on the battery energy storage potential for grid and transportation applications. Journal of Power Sources 2011, 196 (3), 1593-1598.Saraidaridis, J. D.; Yang, Z.; Darling, R. M.; Perry, M. L., Recovering from Precipitation Events in Redox Flow Batteries. ECS Meeting s 2020, MA2020-01 (3), 472-472.Robb, B. H.; Farrell, J. M.; Marshak, M. P., Chelated Chromium Electrolyte Enabling High-Voltage Aqueous Flow Batteries. Joule 2019, 3 (10), 2503-2512.

GEWEX Water Vapor Assessment: Validation of AIRS Tropospheric Humidity Profiles With Characterized Radiosonde Soundings

AbstractThe tropospheric water vapor profile record from the Atmospheric Infrared Sounder (AIRS) now spans over a decade, making it a valuable resource for climate studies. To be considered as a Climate Data Record, it is key that the ultimate performance of these observations are understood. The Global Energy and Water cycle Exchanges (GEWEX) water vapor assessment has been tasked with characterizing the current state of the art in water vapor products currently available for climate analysis. Within the scope of this exercise, water vapor profiles from AIRS have been assessed using collocated characterized in situ measurements of tropospheric water vapor between 2007 and 2012. We first show how previously published methods for correcting radiosondes can be applied to global records, which show high correlations to Global Climate Observing System Reference Upper‐Air Network (GRUAN) performance at pressures between the surface and 250 hPa. We go further and show the first comparison of uncertainties from both the newly created Characterized Radiosonde Measurement (CRM) and GRUAN data sets. Global estimates of AIRS water vapor profile (wet/dry) biases relative to GRUAN and CRM are within 6 ± 0.3% ppmv and 15 ± 0.1% ppmv below 300 hPa, respectively. The CRM record allows latitudinal analysis for the first time, which when examined shows sensitivity to changes in absolute concentration due to large‐scale circulation in the International Tropical Convergence Zone. This paper advances the use of state‐of‐the‐art in situ records for characterizing absolute performance, recognizing that long‐term stability needs further research.

Neuro-Metabolite Changes in a Single Season of University Ice Hockey Using Magnetic Resonance Spectroscopy

Background: Previous research has shown evidence for transient neuronal loss after repetitive head impacts (RHI) as demonstrated by a decrease in N-acetylaspartate (NAA). However, few studies have investigated other neuro-metabolites that may be altered in the presence of RHI; furthermore, the relationship of neuro-metabolite changes to neurocognitive outcome and potential sex differences remain largely unknown.Objective: The aim of this study was to identify alterations in brain metabolites and their potential association with neurocognitive performance over time as well as to characterize sex-specific differences in response to RHI.Methods: 33 collegiate ice hockey players (17 males and 16 females) underwent 3T magnetic resonance spectroscopy (MRS) and neurocognitive evaluation before and after the Canadian Interuniversity Sports (CIS) ice hockey season 2011–2012. The MRS voxel was placed in the corpus callosum. Pre- and postseason neurocognitive performances were assessed using the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT). Absolute neuro-metabolite concentrations were then compared between pre- and postseason MRS were (level of statistical significance after correction for multiple comparisons: p < 0.007) and correlated to ImPACT scores for both sexes.Results: A significant decrease in NAA was observed from preseason to postseason (p = 0.001). Furthermore, a trend toward a decrease in total choline (Cho) was observed (p = 0.044). Although no overall effect was observed for glutamate (Glu) over the season, a difference was observed with females showing a decrease in Glu and males showing an increase in Glu, though this was not statistically significant (p = 0.039). In both males and females, a negative correlation was observed between changes in Glu and changes in verbal memory (p = 0.008).Conclusion: The results of this study demonstrate changes in absolute concentrations of neuro-metabolites following exposure to RHI. Results suggest that changes in Glu are correlated with changes in verbal memory. Future studies need to investigate further the association between brain metabolites and clinical outcome as well as sex-specific differences in the brain's response to RHI.

Detection and Alterations of Acetylcarnitine in Human Skeletal Muscles by 1H MRS at 7 T.

ObjectivesThe aims of this study were to detect the acetylcarnitine resonance line at 2.13 ppm in the human vastus lateralis and soleus muscles, assess T1 and T2 relaxation times, and investigate the diurnal and exercise-related changes in absolute concentration noninvasively, using proton magnetic resonance spectroscopy at 7 T.Materials and MethodsAll measurements were performed on a 7 T whole-body Magnetom MR system with a 28-channel knee coil. Five healthy, moderately trained volunteers participated in the assessment of the detectability, repeatability, and relaxation times of acetylcarnitine. For the evaluation of the effect of training status, another 5 healthy, normally active volunteers were examined. In addition, normally active volunteers underwent a day-long protocol to estimate diurnal changes and response to the exercise.ResultsUsing a long echo time of 350 milliseconds, we were able to detect the acetylcarnitine resonance line at 2.13 ppm in both muscle groups without significant lipid contamination. The T1 of acetylcarnitine in the vastus lateralis muscle was found to be 1807.2 ± 513.1 milliseconds and T2 was found to be 129.9 ± 44.9 milliseconds. Concentrations of acetylcarnitine from the vastus lateralis muscle in moderately trained volunteers were higher than concentrations from normally active volunteers. Acetylcarnitine concentrations changed during the day, tending to be higher in the morning after an overnight fast than after lunch. After 10 minutes of high-intensity exercise, the concentration significantly increased, and 15 minutes after cessation of exercise, a decrease could be observed.ConclusionsOur results demonstrate an effective detection of acetylcarnitine using a long TE of 350 milliseconds at 7 T in the vastus lateralis and soleus muscles with high repeatability and reliability on a 7 T scanner. Our data emphasize the need for strict standardization, physical activity, and dietary conditions for the measurement of the acetylcarnitine.

Changes in relative and absolute concentrations of plasma phospholipid fatty acids observed in a randomized trial of Omega-3 fatty acids supplementation in Uganda

Expressing circulating phospholipid fatty acids (PLFAs) in relative concentrations has some limitations: the total of all fatty acids are summed to 100%; therefore, the values of individual fatty acid are not independent. In this study we examined if both relative and absolute metrics could effectively measure changes in circulating PLFA concentrations in an intervention trial. 66 HIV and HHV8 infected patients in Uganda were randomized to take 3g/d of either long-chain omega-3 fatty acids (1856mg EPA and 1232mg DHA) or high—oleic safflower oil in a 12-week double-blind trial. Plasma samples were collected at baseline and end of trial. Relative weight percentage and absolute concentrations of 41 plasma PLFAs were measured using gas chromatography. Total cholesterol was also measured. Intervention-effect changes in concentrations were calculated as differences between end of 12-week trial and baseline. Pearson correlations of relative and absolute concentration changes in individual PLFAs were high (>0.6) for 37 of the 41 PLFAs analyzed. In the intervention arm, 17 PLFAs changed significantly in relative concentration and 16 in absolute concentration, 15 of which were identical. Absolute concentration of total PLFAs decreased 95.1mg/L (95% CI: 26.0, 164.2; P=0.0085), but total cholesterol did not change significantly in the intervention arm. No significant change was observed in any of the measurements in the placebo arm. Both relative weight percentage and absolute concentrations could effectively measure changes in plasma PLFA concentrations. EPA and DHA supplementation changes the concentrations of multiple plasma PLFAs besides EPA and DHA.Both relative weight percentage and absolute concentrations could effectively measure changes in plasma phospholipid fatty acid (PLFA) concentrations.

Importance of Multiple Methylation Sites in Escherichia coli Chemotaxis.

Bacteria navigate within inhomogeneous environments by temporally comparing concentrations of chemoeffectors over the course of a few seconds and biasing their rate of reorientations accordingly, thereby drifting towards more favorable conditions. This navigation requires a short-term memory achieved through the sequential methylations and demethylations of several specific glutamate residues on the chemotaxis receptors, which progressively adjusts the receptors’ activity to track the levels of stimulation encountered by the cell with a delay. Such adaptation also tunes the receptors’ sensitivity according to the background ligand concentration, enabling the cells to respond to fractional rather than absolute concentration changes, i.e. to perform logarithmic sensing. Despite the adaptation system being principally well understood, the need for a specific number of methylation sites remains relatively unclear. Here we systematically substituted the four glutamate residues of the Tar receptor of Escherichia coli by non-methylated alanine, creating a set of 16 modified receptors with a varying number of available methylation sites and explored the effect of these substitutions on the performance of the chemotaxis system. Alanine substitutions were found to desensitize the receptors, similarly but to a lesser extent than glutamate methylation, and to affect the methylation and demethylation rates of the remaining sites in a site-specific manner. Each substitution reduces the dynamic range of chemotaxis, by one order of magnitude on average. The substitution of up to two sites could be partly compensated by the adaptation system, but the full set of methylation sites was necessary to achieve efficient logarithmic sensing.

Evaluating Stress Hormones’ Responses to Exercise in Lean versus Obese Children using Different Methodologies

Previous studies have evaluated the role of obesity on stress hormones’ responses to exercise. Responses were typically evaluated by analyzing the; 1) change in absolute concentration of the hormone over time; 2) calculated area under the curve (AUC); and 3) calculated percent change from baseline (PRE) to various time points. It was hypothesized that depending on the method used to assess changes from PRE, results and conclusions may differ in groups that present PRE differences. PURPOSE: This study determined whether three different methods to assess changes in hormonal concentrations over time yielded results leading to similar conclusions. METHODS: Eleven lean (LN: 8M/3F; age = 9.3 ± 1.2 y; body fat = 17.3 ± 4.8 %) and 11 obese (OB: 7M/4F; age = 9.0 ± 1.1 y; body fat = 39.0 ± 6.4 %) children completed a 30-min discontinuous submaximal bike test. Blood samples were collected at PRE, immediately post-exercise (IP), and 15, 30 and 60 min into recovery. Epinephrine (EPI), norepinephrine (NE) and growth hormone (GH) were analyzed using ELISA. Data were analyzed by: M1 = 2 (group) x 5 (time) repeated measures ANOVA for absolute concentrations; M2 = ANOVA for AUC; and M3 = 2 (group) x 4 (time) ANOVA for percent changes from PRE. RESULTS: M1 and M3 detected an interaction for EPI as IP > all times in LN only (p < 0.01 for both methods). For NE, M1 found a time effect (IP > all times; p < 0.01 for all) and M3 found group (LN > OB; p = 0.04) and time effects (PRE to IP > all times; p < 0.01 for all). M1 showed an interaction for GH with IP > all times in LN and OB (p < 0.01 for both) though at IP, LN > OB (p < 0.01). In contrast, M3 found a time effect (PRE to IP > PRE to 30 and 60 min; p < 0.01 for both). M2 supported M1’s findings, but not M3, for all hormones. CONCLUSION: Findings indicate that evaluating hormonal concentration changes over time using calculated percent change from PRE resulted in different conclusions compared to absolute changes over time or AUC. This difference was specific for GH, as M3 may have accounted for differences at PRE between groups. Therefore, researchers are encouraged to decide a priori the method for analysis based on whether the objective is to compare possible absolute concentration exposure of hormones to tissues, integrated responses or relative changes from PRE as interpretation of results may differ when PRE differences exist between groups.

Impact of leading presenting symptoms on the diagnostic performance of high-sensitivity cardiac troponin T and on outcomes in patients with suspected acute coronary syndrome.

Diagnostic performance of high-sensitivity cardiac troponin T (hs-cTnT) varies depending on presenting symptoms in patients with suspected acute coronary syndrome (ACS). We compared performance measures of hs-cTnT among patients admitted to the emergency department with typical chest pain (angina), dyspnea, and atypical symptoms and assessed outcomes by leading presenting symptoms. A total of 658 patients suspected of ACS and presenting with typical chest pain (n = 241, 36.6%), dyspnea (n = 142, 21.6%), or atypical symptoms (n = 275, 41.8%) were included. Diagnostic accuracy of hs-cTnT on admission was higher among patients with typical chest pain compared to those with atypical symptoms [area under the curve (AUC) 0.823 vs AUC 0.776 vs AUC 0.705, P > 0.05 and P = 0.04]. Absolute concentration changes within 6 h improved accuracy among all subgroups, with the smallest added benefit in typical chest pain and dyspnea (ΔAUC, 0.078; P = 0.02 and 0.05, P > 0.05). During 1-year follow-up, dyspnea was associated with a higher risk of death (hazard ratio, 2.36; 95% CI, 1.26-4.43, P = 0.008) and death/AMI (hazard ratio, 2.23; 95% CI, 1.21-4.11, P = 0.01) compared to typical chest pain. Optimal discriminating values for hs-cTnT were higher among patients presenting with dyspnea compared to those with typical chest pain (91.2 vs 14.1 ng/L, P < 0.001). The diagnostic performance of hs-cTnT in patients with suspected ACS depends on the leading presenting symptom. Patients admitted with dyspnea represent a high-risk cohort in which the diagnosis of ACS is less frequent and with inferior performance of serial hs-cTnT measurements. Higher hs-cTnT cutoffs at baseline and absolute changes after 6 h help to identify non-STEMI (ST segment elevation myocardial infarction) in this population.

Quantifying intracellular hydrogen peroxide perturbations in terms of concentration

Molecular level, mechanistic understanding of the roles of reactive oxygen species (ROS) in a variety of pathological conditions is hindered by the difficulties associated with determining the concentration of various ROS species. Here, we present an approach that converts fold-change in the signal from an intracellular sensor of hydrogen peroxide into changes in absolute concentration. The method uses extracellular additions of peroxide and an improved biochemical measurement of the gradient between extracellular and intracellular peroxide concentrations to calibrate the intracellular sensor. By measuring peroxiredoxin activity, we found that this gradient is 650-fold rather than the 7–10-fold that is widely cited. The resulting calibration is important for understanding the mass-action kinetics of complex networks of redox reactions, and it enables meaningful characterization and comparison of outputs from endogenous peroxide generating tools and therapeutics across studies.

The distribution and origin of dimethyldibenzothiophenes in sediment extracts from the Liaohe Basin, East China

The distributions of dimethyldibenzothiophenes (DMDBTs), the relationship between DMDBTs and dimethylbiphenyls (DMBPs), and the applications of DMDBTs as maturity indicators in source rocks have been investigated in a set of 21 lacustrine shales from the Eocene Shahejie Formation (Well SG1) in the Western Depression, Liaohe Basin, China. All source rock samples are characterized by total organic carbon contents of 1.37–3.27% and Type II (with minor Type III) kerogen. They were deposited in suboxic and brackish lacustrine environments and have maturities ranging from immature to mid-mature. The 3,3′-DMBP isomer can potentially react to yield 4,6-DMDBT; 2,6-DMDBT and 2,8-DMDBT by incorporating sulfur into biphenyl, which may be supported by a strong positive correlation between the absolute concentration changes of 3,3′-DMBP and those of 4,6-DMDBT, 2,6-DMDBT plus 2,8-DMDBT. The relative abundance of DMDBT isomers may be explained by the sulfur radical mechanism and are also controlled by steric hindrance and thermodynamic stability. The 4,6-/(1,4-+1,6)-DMDBT ratio shows no regular trend with increasing maturity at the low stage, and it should be used with caution as a maturity indicator for immature sediments. However, within the oil generation window, the relative concentration of 4,6-DMDBT progressively increases with increasing maturity, which can be explained by its higher thermodynamic stability relative to the 1,4-DMDBT isomer. The 4,6-/(1,4-+1,6)-DMDBT ratio exhibits a linear increase with increasing thermal maturity of the sediments. Thus, this ratio can be applied as an effective maturity indicator for source rocks within oil generation window.

Altered fatty acid concentrations in prefrontal cortex of schizophrenic patients

BackgroundDisturbances in prefrontal cortex phospholipid and fatty acid composition have been reported in patients with schizophrenia (SCZ), often as an incomplete lipid profile or a percent of total lipid concentration. In this study, we quantified absolute concentrations (nmol/g wet weight) and fractional concentrations (i.e. percent of total fatty acids) of several lipid classes and their constituent fatty acids in postmortem prefrontal cortex of SCZ patients (n = 10) and age-matched controls (n = 10). MethodsLipids were extracted, fractionated with thin layer chromatography and assayed. ResultsMean total lipid, phospholipid, individual phospholipids, plasmalogen, triglyceride and cholesteryl ester concentrations did not differ significantly between the groups. Compared to controls, SCZ brains showed significant increases in several monounsaturated and polyunsaturated fatty acid absolute concentrations in cholesteryl ester. Significant increases or decreases occurred in palmitoleic, linoleic, γ-linolenic and n-3 docosapentaenoic acid absolute concentrations in total lipids, triglycerides or phospholipids. Changes in fractional concentrations did not consistently reflect absolute concentration changes. ConclusionThese findings suggest disturbed prefrontal cortex fatty acid absolute concentrations, particularly within cholesteryl esters, as a pathological aspect of schizophrenia.

Comparison of a 3-hour versus a 6-hour sampling-protocol using high-sensitivity cardiac troponin T for rule-out and rule-in of non-STEMI in an unselected emergency department population

BackgroundCurrent European guidelines recommend the use of sensitive or high-sensitivity cardiac troponin assays to reduce the minimal sampling interval from 6 to 3h. MethodsWe compared a 3-hour versus a 6-hour protocol for diagnosis of non-STEMI and used the 99th percentile for rule-out, and relative and absolute concentration changes for rule-in of non-STEMI. Results459 patients with either an NSTE-ACS or elevated hs-cTnT not due to MI and hs-cTnT measurements at 0, 3 and 6h were enrolled. Among the 404 patients excluded due to an incomplete sampling protocol performance was comparable to the 459 patients with a complete sampling protocol (AUC 0.79 vs 0.80, p=ns). In the study group, non-STEMI was diagnosed in 111 cases (24.2%) and elevated hs-cTnT not due to MI was observed in 215 cases (46.8%). For rule-out of non-STEMI, NPVs were 94.9%, 98.7% and 100% on admission, at 3 and 6h with comparable performance at 3 and 6h (AUC 0.782 vs 0.790, p=ns). For rule-in a 3-hour protocol performed as well as a 6-hour protocol, with a significantly (p<0.0001) better performance of absolute (AUC 0.851 vs. 0.845, p=0.740) as compared to relative concentration changes (AUC 0.771 vs. 0.739, p=0.169). ConclusionsRule-in and rule-out of non-STEMI may be accomplished comparably effective at 3 or 6h. For rule-in, absolute kinetic changes perform better than relative changes at all time points. ROC-optimal absolute δ-change was 6.95ng/L at 3h and 8.9ng/L at 6h.

Variation of Cardiac Troponin I and T Measured with Sensitive Assays in Emergency Department Patients with Noncardiac Chest Pain

New-generation high-sensitivity assays for cardiac troponin have lower detection limits and less imprecision than earlier assays. Reference 99th-percentile cutoff values for these new assays are also lower, leading to higher frequencies of positive test results. When cardiac troponin concentrations are minimally increased, serial testing allows discrimination of myocardial infarction from other causes of increased cardiac troponin. We assessed various measures of short-term variation, including absolute concentration changes, reference change values (RCVs), and indices of individuality (II) for 2 cardiac troponin assays in emergency department (ED) patients. We collected blood from patients presenting with cardiac chest pain upon arrival in the ED and 2, 6, and 12 h later. Cardiac troponin was measured with the high-sensitivity cardiac troponin T (hs-cTnT) assay (Roche Diagnostics) and a sensitive cTnI assay (Siemens Diagnostics). Cardiac troponin results from 67 patients without acute coronary syndrome or stable angina were used in calculating absolute changes in cardiac troponin, RCVs, and II. The 95th percentiles for absolute change in cardiac troponin were 8.3 ng/L for hs-cTnT and 28 ng/L for cTnI. Within-individual and total CVs were 11% and 14% for hs-cTnT and 18% and 21% for cTnI, respectively. RCVs were 38% (hs-cTnT) and 57% (cTnI). The corresponding log-normal RCVs were +46%/-32% for hs-cTnT and +76%/-43% for cTnI. II values were 0.31 (cTnI) and 0.12 (hs-cTnT). The short-term variations and IIs of cardiac troponin were low in ED patients free of ischemic myocardial necrosis. The detection of cardiac troponin variation exceeding reference thresholds can help to identify ED patients with acute myocardial necrosis whereas variation within these limits renders acute coronary syndrome unlikely.

Findings and Recommendations From the Joint NIST-AGA Workshop on Odor Masking.

Since the days of the alchemist, the observation that some substances have a smell while other substances do not has been a source of fascination. The sense of smell, or olfaction, is our least understood sense, however it is important for many human functions, including digestion, food selection and hazard avoidance. The detailed explanation of why individual chemicals (called odorants) might have a particular smell is still elusive. The situation with mixtures of odorants is even more complex and interesting. A number of distinct odorant mixture phenomena have been documented. Odorant suppression (sometimes called masking), conjugation (as described first by Zwaadermaker) and cross-adaptation are among a collection of such phenomena. They are related to the differential effects that one odorant species will have when mixed with another. Masking is a term that describes situations in which one odorant can overpower the sensation of another. There may be profound technological implications in a number of industrial sectors, most prominently in the fuel gas sector. Here, masking is suspected when the odorant that is added to natural gas can be detected by analytical instrumentation, but cannot be properly detected by an observer with a normal sense of smell. Note that this phenomenon is distinct from odor fade, which more properly describes a decrease in the concentration of an odorant rather than a decrease, disappearance or qualitative change in the perception of the odor in the absence of a change in absolute concentration. Anecdotal descriptions of masking events in the natural gas industry have persisted for over a decade, with the frequency of such events on the rise. Pursuant to the philosophy that the technological problem cannot be addressed until the basic science is understood, NIST, in collaboration with the American Gas Association (AGA), sponsored a workshop that brought together olfactory scientists and natural gas operations personnel in an effort to achieve a common understanding and identify critical research questions. This document is a summary of that workshop, and most importantly, a compendium of the findings and recommendations that resulted from the meeting.

Baseline cholesterol absorption and the response to ezetimibe/simvastatin therapy: a post-hoc analysis of the ENHANCE trial

Subjects with increased cholesterol absorption might benefit more from statin therapy combined with a cholesterol absorption inhibitor. We assessed whether baseline cholesterol absorption markers were associated with response to ezetimibe/simvastatin therapy, in terms of LDL-cholesterol (LDL-C) lowering and cholesterol absorption inhibition, in patients with familial hypercholesterolemia (FH). In a posthoc analysis of the two-year ENHANCE trial, we assessed baseline cholesterol-adjusted campesterol (campesterol/TC) and sitosterol/TC ratios in 591 FH patients. Associations with LDL-C changes and changes in cholesterol absorption markers were evaluated by multiple regression analysis. No association was observed between baseline markers of cholesterol absorption and the extent of LDL-C response to ezetimibe/simvastatin therapy (beta = 0.020, P = 0.587 for campesterol/TC and beta<0.001, P = 0.992 for sitosterol/TC). Ezetimibe/simvastatin treatment reduced campesterol levels by 68% and sitosterol levels by 62%; reductions were most pronounced in subjects with the highest cholesterol absorption markers at baseline, the so-called high absorbers (P < 0.001). Baseline cholesterol absorption status does not determine LDL-C lowering response to ezetimibe/simvastatin therapy in FH, despite more pronounced cholesterol absorption inhibition in high absorbers. Hence, these data do not support the use of baseline absorption markers as a tool to determine optimal cholesterol lowering strategy in FH patients. However, due to the exploratory nature of any posthoc analysis, these results warrant further prospective evaluation in different populations.

Effects of cholesteryl ester transfer protein inhibition on apolipoprotein A-II-containing HDL subspecies and apolipoprotein A-II metabolism

This study was designed to establish the mechanism responsible for the increased apolipoprotein (apo) A-II levels caused by the cholesteryl ester transfer protein inhibitor torcetrapib. Nineteen subjects with low HDL cholesterol (<40 mg/dl), nine of whom were also treated with 20 mg of atorvastatin daily, received placebo for 4 weeks, followed by 120 mg of torcetrapib daily for the next 4 weeks. Six subjects in the nonatorvastatin cohort participated in a third phase, in which they received 120 mg of torcetrapib twice daily for 4 weeks. At the end of each phase, subjects underwent a primed-constant infusion of [5,5,5-(2)H(3)]L-leucine to determine the kinetics of HDL apoA-II. Relative to placebo, torcetrapib significantly increased apoA-II concentrations by reducing HDL apoA-II catabolism in the atorvastatin (-9.4%, P < 0.003) and nonatorvastatin once- (-9.9%, P = 0.02) and twice- (-13.2%, P = 0.02) daily cohorts. Torcetrapib significantly increased the amount of apoA-II in the alpha-2-migrating subpopulation of HDL when given as monotherapy (27%, P < 0.02; 57%, P < 0.003) or on a background of atorvastatin (28%, P < 0.01). In contrast, torcetrapib reduced concentrations of apoA-II in alpha-3-migrating HDL, with mean reductions of -14% (P = 0.23), -18% (P < 0.02), and -18% (P < 0.01) noted during the atorvastatin and nonatorvastatin 120 mg once- and twice-daily phases, respectively. Our findings indicate that CETP inhibition increases plasma concentrations of apoA-II by delaying HDL apoA-II catabolism and significantly alters the remodeling of apoA-II-containing HDL subpopulations.