Shorter Lag Time Research Articles

Physiological Significance of Discrimination on Stress Markers, Obesity, and LDL Oxidation among a European American and African American Cohort of Females

Factors underlying physiological reactions from perceived discrimination and its relation to adverse health outcomes are not completely understood. The main purpose of this study was to test the hypothesis that experiences of discrimination (recent and lifetime) correlate with biomarkers of stress, oxidative stress, and obesity among adult females. Data on 62 females who self-identify as African American (AA; n = 31) or European American (EA; n = 31) aged 21-45years were included. Discrimination experiences (recent and lifetime) were evaluated based on a validated instrument. Stress was assessed based on hair cortisol (HC) and salivary cortisol (SC), hsC-reactive protein (hsCRP), cardiovascular markers, and LDL-cholesterol oxidation. Obesity was measured based on BMI, waist circumference, and body fat percent. Multiple linear regression analyses were performed to evaluate the influence of experiences of discrimination. Significant differences in experiences of discrimination were observed by race (p < 0.05) and were higher in AA females. Results for the multiple regression models assessing the contribution of discrimination indicate that hsCRP and pulse were significantly associated with recent experiences of discrimination, and SC, HC, hsCRP, diastolic blood pressure (DBP), and pulse were significantly associated with lifetime experiences of discrimination when adjusted for BMI and race (p < 0.05). Finally, oxidation of LDL-cholesterol was significantly associated with salivary cortisol (p =0.0420) when adjusted by lifetime experiences of discrimination (p = 0.0366) but not for BMI (p = 0.6252). In this cross-sectional study, AA females experienced more discrimination compared to EA females. Levels of recent and lifetime experiences of discrimination were associated with some stress biomarkers. Salivary cortisol was associated with oxidation of LDL-cholesterol with shorter lag times and increased risk for cardiovascular disease.

Rapid exhumation since at least 13 Ma in the Himalaya recorded by detrital apatite fission-track dating of Bengal fan (IODP Expedition 354) and modern Himalayan river sediments

Apatite fission-track analysis of middle Bengal fan sediments (IODP expedition 354) and modern Himalayan river sediments shows that most of the detrital apatites are very young compared to their depositional ages, independent of their uranium content. Bengal fan apatites display an average central age lag time as short as 2.26±1.6 Myr since at least ∼13 Ma. Such lag times reflect a mean exhumation rate on the order of at least 1-3 km/Myr. The occurrence of detrital apatites with relatively short AFT lag times since at least 13 Ma indicates that there have always been areas of rapid erosional exhumation, supplying detrital apatites to the fluvial system and delivering them to the paleo-Ganges and/or –Brahmaputra plains and finally to the Bengal fan. It also supports that temporary storage of detrital apatites in the floodplains or delta has always been negligible since at least 13 Ma. Comparison of the AFT data of the Bengal fan with those of the Central and Eastern proximal Neogene Himalayan foreland basin shows that both paleo-Ganga and –Brahmaputra catchments provided apatites with similar short lag time to the distal Bengal Fan basin.In the modern drainage system of the Bengal fan, the apatites with young fission-track cooling ages are principally derived from areas where the topography has a sharp relief controlled by threshold hillslope processes and stream power resulting in landslide erosion as a coupled response to tectonic and fluvial forcing. By analogy with the modern erosion processes in the Himalayan range, we suggest that over the past 13 Ma, apatites were mainly derived from areas of sharp relief, where river stream power was high and hill slopes close to the threshold angle. As the exhumation signal is rather consistent since the late Miocene the detrital apatite fission-track data are either not sensitive enough to detect rapid climatically controlled changes in exhumation rates, or overall long-term erosion rates on the orogen scale are not strongly affected by climatic variations such as the variability of the Indian Summer Monsoon. Given the already rapid exhumation rates controlled by tectonics, the impact of climate variability on surface erosion rates cannot be detected with our data, especially in the case of erosion processes dominated by threshold hillslope model.

Assessment of GPM IMERG and radar quantitative precipitation estimation (QPE) products using dense rain gauge observations in the Guangdong-Hong Kong-Macao Greater Bay Area, China

The recent intensification of extreme rainfall events has the potential to aggravate the frequency and intensity of floods in urban areas and signals the urgent need for accurate and high spatiotemporal resolution precipitation data for flood monitoring and warning to alleviate the associated damages. In this context, this paper aims to statistically assess the latest Integrated Multisatellite Retrievals from Global Precipitation Measurement (IMERG) multisatellite constellation and radar quantitative precipitation estimation (QPE) products against dense rain gauge network observations under multiple temporal scales (hourly and 3-hourly) and three spatial scales (grid cumulative, regional, and grid) over the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) in China. The results indicate that (1) at the grid cumulative scale, QPE significantly outperforms IMERG products. The correlation coefficients of QPE (0.83 ≤ CORR ≤ 0.85) are much higher than those of IMERG products (0.35 ≤ CORR ≤ 0.56), the estimation of QPE is generally significantly underestimated (−0.23 ≤ BIAS ≤ -0.16), and the BIAS of IMERG products is larger than that of QPE (−0.24 ≤ BIAS ≤ 0.23). (2) At the regional scale, the accuracy of IMERG products has been significantly improved, with relatively high correlation coefficients (CORR≥0.8) and decreased root mean squared error (RMSE) values (1.18 mm ≤ RMSE ≤ 0.22 mm), and Taylor diagrams visually show that QPE is closer to the gauge observations than are IMERG products. (3) The evaluation results at the grid scale show that both IMERG products and QPE can accurately reflect the spatial distribution of precipitation. Among these results, the spatial distribution of QPE is the most consistent with the actual rainfall, although an obvious underestimation of rainfall occurs in areas with strong rainfall. (4) In terms of detection indicators, the three IMERG products are superior to QPE at capturing rainfall events and have more advantages over QPE in the estimation of instantaneous precipitation, especially for light rain events. However, QPE has better detection effects for rainfall events under rainstorm and heavy rainstorm events, indicating the hydrologic utility of this product. Among the three IMERG products, the IMERG Early Run (ER) product has the advantages of a short lag time and high accuracy, and it has the potential to be applied in flood forecasting. Future studies should improve IMERG algorithms and promote the application of QPE in urban rainstorm and flood research.

How old are the towns and villages in Central Europe? Archaeological data reveal the size of bias in dating obtained from traditional historical sources

In various research fields, from archaeology to landscape history and ecology, it is important to know the date of the origin of historical settlements (i.e. towns, villages, hamlets, isolated farms) as precisely as possible. In Central Europe, there are two primary ways to obtain the date when a settlement was founded: “historical dating” (based on historical written sources) and “archaeological dating” (based on archaeological findings). Historical dating usually does not reflect the real time of origin, since the first reference to a settlement in written sources can be recorded many years after the real origin of the settlement. However, the time lag is unknown. Until now, no study has attempted to show exactly how the time lag differs in different centuries, or whether the time lag has been affected by any geographical factors.This paper compares the dates of origin from archaeological data and from written sources of medieval and early modern settlements (n = 527, AD 850–1600) in the present-day Czech Republic. We also tested the influence of local environmental conditions on the time lag. Our comparison shows that the time lag has been decreasing with the passing of calendar years (from a time lag of 250 years for AD 1000 to approx. 80 years for AD 1400). Towns and places close to major towns also have a shorter time lag in their historical dating (the difference is almost 100 years).These results make an interpretation of the historical dating of medieval towns and villages more complicated. The length of the time lag and its dispersion means that, for the purposes of settlement dating, historical dating needs to be combined with other dating methods (especially in the medieval period). Our results also identify a possible bias in the chronology of landscape transformation.

V. M. Glushkov’s nationwide automated system: accounting aspect

Introduction. Ukrainian (Soviet) scientific and technical research was at the forefront of innovation processes in the twentieth century. Scientists paid considerable attention to the development of dual-use military technologies that were implemented in economic activity with a short time lag. One of the largest innovative projects was nationwide communications systems, such as the Internet in the US and the NWAS in the USSR. The advantage of the Soviet communications network was its focus on optimization and automation of economic processes during the pre-project research phase. Most of the scientific and technical developments were conducted in the USSR by Ukrainian scientists under the leadership of V. M. Glushkov. Based on the name of the communication network - «National Automated Information Collection and Processing System for Accounting, Planning and Management of the National Economy» refinement requires the place and role of accounting in the automated processing and transmission of information for management purposes.Purpose. The purpose of the article is to summarize the historical data about NWAS to investigate the experience and prospects of automated processing and transfer of accounting information in global (nationwide) electronic communications.Methods. General scientific empirical, logical and historical methods of knowledge of reality were used in the process of researching the place and role of accounting in the NWAS. The research is based on science general methods of economic processes, facts and phenomena of accounting and business management in the conditions of use of computer and communication technologies. The information base of the research was the historical documents about the NWAS, scientific works of domestic and foreign scientists in the accounting automation field.Results. The place and role of accounting in the nationwide communication network is determined on the basis of research of historical sources and contemporary literature on scientific and practical work of V. M. Glushkov. The methods of accounting functions realization in the NWAS and use of computer and communication technologies are investigated. Scientifically substantiated functional parallels between researches of V. M. Glushkov and modern technologies of processing and transfer of accounting information are provided. It is proved that the most innovative developments in the global dimension regarding the implementation of the principles of economic cybernetics in accounting have been implemented by Ukrainian (Soviet) scientists.Discussion. The implementation areas of V. M. Glushkov’s research in the information society and digital economy have been identified. The reasons for innovative researches stopping on formation of nationwide communication environments are found out. The questions remain: the possibility of information exchange between the Internet and the NWAS, the order of electronic communications of engineers and researchers on scientific and technical cooperation, the possibilities of using the NWAS for Soviet cyber-war (hybrid war), mechanisms of adaptation of the Soviet economy to the decrease in oil prices, realignment with the use of computer and communication technologies.

Does cell-free DNA promote coagulation and inhibit fibrinolysis in patients with unprovoked venous thromboembolism?

IntroductionCell-free DNA (CFDNA) is the major structural component of neutrophil extracellular traps (NETs). CFDNA contributes to the prothrombotic potential of NETs by promoting thrombin generation and inhibiting fibrinolysis. Patients with venous thromboembolism (VTE) have elevated circulating nucleosomes (i.e. DNA-histone complexes). In this study, we investigated if CFDNA contributes to a procoagulant and an antifibrinolytic state in patients with unprovoked VTE. Materials and methodsPlasma samples from patients with a first episode of unprovoked VTE were obtained from the D-Dimer Optimal Duration Study (DODS). We measured CFDNA plasma levels in 263 patients while on warfarin and 1-month after stopping. Thrombin generation assays and clot lysis assays were measured in patients after stopping warfarin. Comparisons were made with healthy controls. ResultsCFDNA levels in VTE patients who stopped warfarin (5.53 μg/mL; 95%CI: 5.34–5.72) were higher than during warfarin therapy (3.11 μg/mL; 95%CI: 2.98–3.25; p < .001), and higher than in healthy controls (2.77 μg/mL; 95%CI: 2.42–3.11; p < .001). VTE patients had a procoagulant state as evidenced by a shorter lag time (30.8 min; 95%CI: 29.2–32.4) compared to controls (48.2 min; 95%CI :41.0–55.5; p < .001) and a greater endogenous thrombin potential (2656 nM∗min; 95%CI: 2479–2836) compared to healthy controls (1198 nM ∗ min; 95%CI: 793–1603). There was a higher proportion of clots generated from patient plasma that were resistant to lysis (43.7%) compared to healthy controls (46.3%; p < .05). CFDNA levels were not associated with enhanced thrombin generation or impaired fibrinolysis in VTE patients. ConclusionCFDNA levels are elevated in patients with unprovoked VTE but do not correlate with the procoagulant or anti-fibrinolytic properties of patient plasma. This study suggests that additional factors in addition to CFDNA may contribute to the pathogenesis of VTE.

Multiple constrained minimum variance beamformer (MCMV) performance in connectivity analyses

Functional brain connectivity is increasingly being seen as critical for cognition, perception and motor control. Magnetoencephalography and electroencephalography are modalities that offer noninvasive mapping of electrophysiological interactions among brain regions, yet suffer from signal leakage and signal cancellation when estimating brain activity. This leads to biased connectivity values which complicate interpretation. In this study, we test the hypothesis that a Multiple Constrained Minimum Variance beamformer (MCMV) outperforms the more traditional Linearly Constrained Minimum Variance beamformer (LCMV) for estimation of electrophysiological connectivity. To this end, MCMV and LCMV performance is compared in task related analyses with both simulated data and human MEG recordings of visual steady state signals, and in resting state analyses with simulated data and human MEG data of 89 subjects. In task related scenarios connectivity was estimated using coherence and phase locking values, whereas envelope correlations were used for the resting state data. We also introduce a novel Augmented Pairwise MCMV (APW-MCMV) approach for signal leakage suppression in resting state analyses and assess its performance against LCMV and more conventional MCMV approaches. We demonstrate that with MCMV effects of signal mixing and coherent source cancellation are greatly reduced in both task related and resting state conditions, while in contrast to other approaches 0- and short time lag interactions are preserved. In addition, we demonstrate that in resting state analyses, APW-MCMV strongly reduces spurious connections while better controlling for false negatives compared to more conservative measures such as symmetrical orthogonalization.

Characterization of a Novel Human Factor VIIa Chimera with Increased Tissue Factor-Independent Activity for Emergency Hemostasis

While prophylactic treatment with emicizumab has shown remarkable efficacy in patients with hemophilia A, the treatment options for traumatic, perioperative, and breakthrough bleeding in hemophilia A or B patients with inhibitors remain extremely limited. Recombinant Factor VIIa (rFVIIa) is routinely used to promote hemostasis in hemophilia patients with inhibitors and is recommended as first line therapy for acute bleeding, especially for patients on emicizumab. In addition, rFVIIa has extensive off-label use for hemostasis in cardiovascular surgery, trauma, and intracranial hemorrhage. The hemostatic efficacy of rFVIIa depends on its ability to bind activated platelets and promote thrombin generation by activating Factor X (FX) in a tissue factor (TF)-independent manner. However, the use of rFVIIa requires frequent high doses at significant cost, and is limited by an inconsistent response. Therefore, there is a critical need for new strategies to treat acute bleeding in hemophilia patients with inhibitors and others requiring emergency hemostasis. We have previously shown that human platelets express endothelial cell protein C receptor which contributes to the platelet binding and activity of rFVIIa. Based on this work, we designed a novel FVIIa chimera (PC-FVIIa) with the potential for increased hemostatic efficacy and an enhanced safety profile compared to rFVIIa. The purpose of the current study was to characterize the in vitro activity of this chimera. A cDNA construct encoding the Gla and EGF1 domains of human Protein C along with the EGF2 and catalytic domains of human FVIIa was synthesized and cloned into HEK293 cells. Stable transfectants were selected and PC-FVIIa was purified from the media. Protein electrophoresis of eluates confirmed bands consistent with the expected molecular weight. Similar to rFVIIa, we found that autoactivation of PC-FVIIa readily occurs in the presence of calcium and phospholipid (15% PS/41% PC/44% PE). Autoactivation is rapidly accelerated by the addition of Factor Xa (FXa) and significantly impaired in the absence of either calcium or phospholipid. There was no significant difference between activated PC-FVIIa and rFVIIa in their ability to cleave a synthetic FVIIa substrate. As the Gla and EGF1 domains of rFVIIa are primarily responsible for binding TF, we hypothesized that PC-FVIIa would have little to no affinity for TF. Indeed, we found that the interaction between PC-FVIIa and TF is too weak to be measured in an assay designed to detect weak TF binding. We therefore determined the TF-independent activity of PC-FVIIa using FXa and thrombin generation assays. For some experiments, phospholipid vesicles were incubated with rFVIIa or PC-FVIIa. Plasma levels of FX were added and FXa generation was assessed using a chromogenic substrate. In these assays, the rate of FX activation by PC-FVIIa was significantly higher than that of rFVIIa (Figure 1). To determine the ability of PC-FVIIa to promote thrombin generation, we performed a modified calibrated automated thrombography assay in the absence of TF. Hemophilia A plasma was incubated with PC-FVIIa or rFVIIa in the presence of phospholipid. Subsequent thrombin generation was assessed by monitoring cleavage of a fluorogenic substrate. No appreciable thrombin generation was seen in plasma alone. Adding rFVIIa resulted in a shorter lag time than PC-FVIIa. However, PC-FVIIa led to significantly higher peak thrombin concentration and endogenous thrombin potential compared to rFVIIa. Finally, we used a prothrombinase detection system to determine the activity of PC-FVIIa on the surface of platelets activated with thrombin plus a collagen receptor agonist to generate highly procoagulant platelets. Once again, the rate of thrombin generation was significantly higher with PC-FVIIa as compared to rFVIIa, consistent with a higher rate of FX activation on the platelet surface. Taken together, these data suggest that the PC-FVIIa chimera has the potential for increased hemostatic efficacy compared to rFVIIa. Additional studies will characterize the in vivo activity of PC-FVIIa. However, the lack of affinity for TF represents a potential advantage for PC-FVIIa since long-term exposure to high levels of rFVIIa can lead to thrombosis in TF-rich tissues. As such, PC-FVIIa warrants further study as a potential therapeutic agent with unique characteristics compared to rFVIIa. Disclosures Fager: Otello Medical Inc.: Research Funding. Hoffman:Novo Nordisk A/S: Honoraria, Research Funding. Monroe:Novo Nordisk: Honoraria, Research Funding.

The pharmacokinetics of 3-fluoroamphetamine following delivery using clinically relevant routes of administration.

3-Fluoroamphetamine (also called PAL-353) is a synthetic amphetamine analog that has been investigated for cocaine use disorder (CUD), yet no studies have characterized its pharmacokinetics (PK). In the present study, we determined the PK of PAL-353 in male Sprague Dawley rats following intravenous bolus injection (5 mg/kg). Plasma samples were analyzed using a novel bioanalytical method that coupled liquid-liquid extraction and LC-MS/MS. The primary PK parameters determined by WinNonlin were a C0 (ng/mL) of 1412.09 ± 196.12 and a plasma half-life of 2.27 ± 0.67 h. As transdermal delivery may be an optimal approach to delivering PAL-353 for CUD, we assessed its PK profile following application of 50 mg of transdermal gel (10% w/w drug over 5 cm2). The 10% w/w gel resulted in a short lag time, sustained delivery, and a rapid clearance in plasma immediately after removal. The rodent PK data were verified by examining in vitro permeation through human epidermis mounted on Franz diffusion cells. An in vitro-in vivo correlation (IVIVC) analysis was performed using the Phoenix IVIVC toolkit to assess the predictive relationship between rodent and human skin absorption/permeation. The in vitro permeation study revealed a dose-proportional cumulative and steady-state flux with ~ 70% of drug permeated. The fraction absorbed in vivo and fraction permeated in vitro showed a linear relationship. In conclusion, we have characterized the PK profile of PAL-353, demonstrated that it has favorable PK properties for transdermal administration for CUD, and provided preliminary evidence of the capacity of rodent data to predict human skin flux.

River-ice and water velocities using the Planet optical cubesat constellation

Abstract. The PlanetScope constellation consists of ∼150 optical cubesats that are evenly distributed like strings of pearls on two orbital planes, scanning the Earth's land surface once per day with an approximate spatial image resolution of 3 m. Subsequent cubesats on each of the orbital planes image the Earth surface with a nominal time lag of approximately 90 s between them, which produces near-simultaneous image pairs over the across-track overlaps of the cubesat swaths. We exploit this short time lag between subsequent Planet cubesat images to track river ice floes on northern rivers as indicators of water surface velocities. The method is demonstrated for a 60 km long reach of the Amur River in Siberia, and a 200 km long reach of the Yukon River in Alaska. The accuracy of the estimated horizontal surface velocities is of the order of ±0.01 m s−1. The application of our approach is complicated by cloud cover and low sun angles at high latitudes during the periods where rivers typically carry ice floes, and by the fact that the near-simultaneous swath overlaps, by design, do not cover the complete Earth surface. Still, the approach enables direct remote sensing of river surface velocities for numerous cold-region rivers at a number of locations and occasionally several times per year – which is much more frequent and over much larger areas than currently feasible. We find that freeze-up conditions seem to offer ice floes that are generally more suitable for tracking, and over longer time periods, compared with typical ice break-up conditions. The coverage of river velocities obtained could be particularly useful in combination with satellite measurements of river area, and river surface height and slope.

The logging recognition of solid bitumen and its effect on physical properties, AC, resistivity and NMR parameters

Abstract Solid bitumen not only strongly damages the reservoir properties, but it is easily confused with oil and gas in the conventional classification logging interpretation, which seriously affects the effective recognition of oil and gas. Thus, it leads to a deceptive estimation of the reserve. Focusing on the above problems, this study takes Jurassic solid bitumen-containing reservoirs from the Santai-Northern Santai area in the Junggar Basin as an example, and aims to quantitatively evaluate the impact of solid bitumen on the porosity, permeability, resistivity, AC (Acoustic) and NMR (Nuclear Magnetic Resonance), with a comparison between the values of these parameters before and after core bitumen dissolution, as well as to establish an NMR identification method for solid bitumen. The results show that solid bitumen can damage the pore structure of the reservoir and cause a reduction of porosity and permeability. The content of solid bitumen is linearly correlated with the change of porosity and permeability. After solid bitumen dissolved, the resistivity decreased, the longitudinal wave time difference (Vp) and shear wave time difference (Vs) increased, and the shear wave time difference changed noticeably. The content of solid bitumen is exponentially correlated with the change of resistivity, and linearly correlated with the change of longitudinal wave time difference and shear wave time difference. Solid bitumen had a short transverse relaxation time and a response range of 10–1000 μs (Peak 1) on the T2 map. Bitumen-containing sandstone had 3 peaks on the T2 map. Peak 1 decreased, while Peaks 2 and 3 increased after the solid bitumen dissolved. Solid bitumen can be characterized by a typical short time lag of the transverse wave, a bigger density porosity than the NMR porosity and small values of T1LM and T2LM, which led to an effective recognition of the layers of solid bitumen. The results are significant for the exploration and development of oilfields.

X-ray properties of reverberation-mapped AGNs with super-Eddington accreting massive black holes

AbstractActive Galactic Nuclei (AGN) exhibit multi-wavelength properties that are representative of the underlying physical processes taking place in the vicinity of the accreting supermassive black hole. The black hole mass and the accretion rate are fundamental for understanding the growth of black holes, their evolution, and the impact on the host galaxies. Recent results on reverberation-mapped AGNs show that the highest accretion rate objects have systematic shorter time-lags. These super-Eddington accreting massive black holes (SEAMBHs) show BLR size 3-8 times smaller than predicted by the Radius-Luminosity (R-L) relationship. Hence, the single-epoch virial black hole mass estimates of highly accreting AGNs have an overestimation of a factor of 3-8 times. SEAMBHs likely have a slim accretion disk rather than a thin disk that is diagnostic in X-ray. I will present the extreme X-ray properties of a sample of dozen of SEAMBHs. They indeed have a steep hard X-ray photon index, Γ, and demonstrate a steeper power-law slope, ασx.

Thrombin and plasmin generation in patients with plasminogen or plasminogen activator inhibitor type 1 deficiency.

IntroductionDeficiencies of plasminogen and plasminogen activator inhibitor type 1 (PAI‐1) are rare disorders of fibrinolysis. Current laboratory assays for analysis of activity of plasminogen and PAI‐1 do not provide an accurate correlation with clinical phenotype.MethodsThe Nijmegen Hemostasis Assay (NHA) was used to simultaneously measure thrombin and plasmin generation in 5 patients with plasminogen deficiency (PLGD) and 10 patients with complete PAI‐1 deficiency. Parameters analysed included: lag time ratio, thrombin peak time ratio, thrombin peak height, thrombin potential (AUC), fibrin lysis time, plasmin peak height and plasmin potential. Parameters were expressed as a percentage compared to a reference value of 53 healthy normal controls.ResultsPatients with PLGD demonstrated a short lag time and thrombin peak time, with normal thrombin peak height but an increased AUC. Plasmin generation was able to be detected in only one (23% plasminogen activity) of the five PLGD patients. All ten PAI‐1 deficient patients demonstrated a short lag and thrombin peak time, low thrombin peak height with normal AUC. Plasmin generation revealed an increased plasmin peak and plasmin potential; interestingly, there was a large variation between individual patients despite all patients having the same homozygous defect.ConclusionPatients with either PLGD or PAI‐1 deficiency show distinct abnormalities in plasmin and thrombin generation in the NHA. The differences observed in the propagation phase of thrombin generation may be explained by plasmin generation. These results suggest that disorders of fibrinolysis also influence coagulation and a global assay measuring both activities may better correlate with clinical outcome.

Response to Comment on "Legacy nitrogen may prevent achievement of water quality goals in the Gulf of Mexico".

Ballard et al argue that our prediction of a 30-year or longer recovery time for Gulf of Mexico water quality is highly uncertain, and that much shorter time lags are equally likely. We demonstrate that their argument, based on the use of a two-component regression model, does not sufficiently consider fundamental watershed processes or multiple lines of evidence suggesting the existence of decadal-scale lags.

Measuring underlying energy efficiency in the GCC countries using a newly constructed dataset

Energy consumption accounts for most of global anthropogenic greenhouse gas emissions. Managing the growth in energy demand is therefore a key part of climate change mitigation. In the Gulf Cooperation Council (GCC) countries, energy consumption has been growing rapidly. Between 2004 and 2014, final energy consumption grew at an average annual rate of 6.8% compared to a global average of 1.8%. Energy efficiency can help GCC countries manage their energy demand growth, but it is difficult to measure energy efficiency, so analysts often rely on indirect indicators such as energy intensity. Frontier analysis can be used to measure energy efficiency, but is data intensive. To undertake frontier analysis for the GCC countries it was therefore necessary to construct a new dataset, which was used for corrected ordinary least squares to estimate underlying energy efficiency between 2004 and 2014 for two key sectors in the GCC countries: residential electricity and road transport gasoline. The results suggest that underlying energy efficiency generally improved in the GCC region, in contrast to the trend of rising energy intensity that the region has been witnessing. The energy efficiency improvements may have been driven by global technical progress and tighter global fuel economy standards, of which the GCC countries were beneficiaries. With the provision of high quality, recent data with shorter lag times, frontier analysis could be used to provide prompt feedback on the impact of energy efficiency policies and programmes, leading to better outcomes.

GluNet: A Deep Learning Framework for Accurate Glucose Forecasting.

For people with Type 1 diabetes (T1D), forecasting of blood glucose (BG) can be used to effectively avoid hyperglycemia, hypoglycemia and associated complications. The latest continuous glucose monitoring (CGM) technology allows people to observe glucose in real-time. However, an accurate glucose forecast remains a challenge. In this work, we introduce GluNet, a framework that leverages on a personalized deep neural network to predict the probabilistic distribution of short-term (30-60 minutes) future CGM measurements for subjects with T1D based on their historical data including glucose measurements, meal information, insulin doses, and other factors. It adopts the latest deep learning techniques consisting of four components: data pre-processing, label transform/recover, multi-layers of dilated convolution neural network (CNN), and post-processing. The method is evaluated in-silico for both adult and adolescent subjects. The results show significant improvements over existing methods in the literature through a comprehensive comparison in terms of root mean square error (RMSE) ([Formula: see text] mg/dL) with short time lag ([Formula: see text] minutes) for prediction horizons (PH) = 30 mins (minutes), and RMSE ([Formula: see text] mg/dL) with time lag ([Formula: see text] mins) for PH = 60 mins for virtual adult subjects. In addition, GluNet is also tested on two clinical data sets. Results show that it achieves an RMSE ([Formula: see text]mg/dL) with time lag ([Formula: see text] mins) for PH = 30 mins and an RMSE ([Formula: see text] mg/dL) with time lag ([Formula: see text]mins) for PH = 60 mins. These are the best reported results for glucose forecasting when compared with other methods including the neural network for predicting glucose (NNPG), the support vector regression (SVR), the latent variable with exogenous input (LVX), and the auto regression with exogenous input (ARX) algorithm.

Graph-Based Prediction of Meeting Participation

Given a meeting participant’s turn-taking dynamics during one segment of a meeting, and their contribution to the group discussion up to that point, our aim is to automatically predict their activity level at a later point of the meeting. The predictive models use verbal and nonverbal features derived from social network representations of each small group interaction. The best automatic prediction models consistently outperform two baseline models at multiple time-lags. We analyze which interaction features are most predictive of later meeting activity levels, and investigate the efficacy of the verbal vs. nonverbal feature classes for this prediction task. At long time-lags, linguistic features become more crucial, but performance degrades compared with prediction at short time-lags.

Pharmacokinetics and pharmacodynamics of intranasal and intravenous naloxone hydrochloride administration in healthy dogs

To evaluate the pharmacokinetics and pharmacodynamics of naloxone hydrochloride in dogs following intranasal (IN) and IV administration. 6 healthy adult mixed-breed dogs. In a blinded crossover design involving 2 experimental periods separated by a washout period (minimum of 7 days), dogs were randomly assigned to receive naloxone IN (4 mg via a commercially available fixed-dose naloxone atomizer; mean ± SD dose, 0.17 ± 0.02 mg/kg) or IV (0.04 mg/kg) in the first period and then the opposite treatment in the second period. Plasma naloxone concentrations, dog behavior, heart rate, and respiratory rate were evaluated for 24 hours/period. Naloxone administered IN was well absorbed after a short lag time (mean ± SD, 2.3 ± 1.4 minutes). Mean maximum plasma concentration following IN and IV administration was 9.3 ± 2.5 ng/mL and 18.8 ± 3.9 ng/mL, respectively. Mean time to maximum concentration following IN administration was 22.5 ± 8.2 minutes. Mean terminal half-life after IN and IV administration was 47.4 ± 6.7 minutes and 37.0 ± 6.7 minutes, respectively. Mean bioavailability of naloxone administered IN was 32 ± 13%. There were no notable changes in dog behavior, heart rate, or respiratory rate following naloxone administration by either route. Use of a naloxone atomizer for IN naloxone administration in dogs may represent an effective alternative to IV administration in emergency situations involving opioid exposure. Future studies are needed to evaluate the efficacy of IN naloxone administration in dogs with opioid intoxication, including a determination of effective doses.

Aβ42 fibril formation from predominantly oligomeric samples suggests a link between oligomer heterogeneity and fibril polymorphism.

Amyloid-β (Aβ) oligomers play a central role in the pathogenesis of Alzheimer's disease. Oligomers of different sizes, morphology and structures have been reported in both in vivo and in vitro studies, but there is a general lack of understanding about where to place these oligomers in the overall process of Aβ aggregation and fibrillization. Here, we show that Aβ42 spontaneously forms oligomers with a wide range of sizes in the same sample. These Aβ42 samples contain predominantly oligomers, and they quickly form fibrils upon incubation at 37°C. When fractionated using ultrafiltration filters, the samples enriched with smaller oligomers form fibrils at a faster rate than the samples enriched with larger oligomers, with both a shorter lag time and faster fibril growth rate. This observation is independent of Aβ42 batches and hexafluoroisopropanol treatment. Furthermore, the fibrils formed by the samples enriched with larger oligomers are more readily solubilized by epigallocatechin gallate, a main catechin component of green tea. These results suggest that the fibrils formed by larger oligomers may adopt a different structure from fibrils formed by smaller oligomers, pointing to a link between oligomer heterogeneity and fibril polymorphism.

Cis Donor Influence on O-O Bond Lability in Iron(III) Hydroperoxo Complexes: Oxidation Catalysis and Ligand Transformation.

The FeIII/FeII redox potentials for [Fe(tpen)]2+/3+, [Fe(tpena)]+/2+, and [Fe(tpenO)]+/2+ (N-R-N,N',N'-tris(2-pyridylmethyl)ethane-1,2-diamine, where R = CH2C6H4N, CH2COO-, CH2CH2O-, respectively) span 470 mV with the oxidation potentials following the order [FeII(tpenO)]+ (MeOH) < [FeII(tpena)]+ (MeCN) < [FeII(tpen)]2+ (MeCN). In their +3 oxidation states the complexes react with 1 equiv of H2O2 to give the purple [FeIII(OOH)(HL)]n+ (n = 2 for L = tpena, tpenO; n = 3 for L = tpen). A pyridine arm is decoordinated in these complexes, furnishing a second coordination sphere base which is protonated at ambient pH. The lifetimes of these transient species depend on how readily the substrate (sometimes the solvent) is oxidized and reflect the trend in both the O-O bond lability and oxidizing potency of the putative iron-based oxidant derived from the iron(III) peroxides. In methanol solution, [FeIII(tpenO)]2+ and [FeIII(tpena)]2+ exist in their Fe(III) states and hence the formation of [FeIII(OOH)(Htpena)]2+ and [FeIII(OOH)(HtpenO)]2+ is instantaneous. This is in contrast to the short lag time that occurs before adduct formation between [FeII(tpen)]2+ and H2O2 due to the requisite prior oxidation of the solution-state iron(II) complex to its iron(III) state. Stabilization of the +3 iron oxidation state in the resting state catalysts affords complexes that activate H2O2 more readily with the consequence of higher yields in the oxidation of the C-H bonds using H2O2 as terminal oxidant. The presence of a cis monodentate carboxylato donor increases the rate of oxidation by hydrogen atom transfer in comparison to the systems with an alkoxo or pyridine in this position. Competing with substrate oxidation is the oxidative modification of the alkoxido group in [FeIII(tpenO)]2+, converting it to a carboxylato group in the presence of H2O2: in effect, transforming tpenO to tpena.