Fentanyl-induced reward seeking is sex and dose dependent and is prevented by D-cysteine ethylester

Introduction: Despite their inclination to induce tolerance, addictive states, and respiratory depression, synthetic opioids are among the most effective clinically administered drugs to treat severe acute/chronic pain and induce surgical anesthesia. Current medical interventions for opioid-induced respiratory depression (OIRD), wooden chest syndrome, and opioid use disorder (OUD) show limited efficacy and are marked by low success in the face of highly potent synthetic opioids such as fentanyl. D-Cysteine ethylester (D-CYSee) prevents OIRD and post-treatment withdrawal in male/female rats and mice with minimal effect on analgesic status. However, the potential aversive or rewarding effects of D-CYSee have yet to be fully characterized and its efficacy could be compromised by interactions with opioid-reward pathology.Methods: Using a model of fentanyl-induced conditioned place preference (CPP), this study evaluated 1) the dose and sex dependent effects of fentanyl to induce rewarding states, and 2) the extent to which D-CYSee alters affective state and the acquisition of fentanyl-induced seeking behaviors.Results: Fentanyl reward-related effects were found to be dose and sex dependent. Male rats exhibited a range-bound dose response centered at 5 µg/kg. Female rats exhibited a CPP only at 50 µg/kg. This dose was effective in 25% of females with the remaining 75% showing no significant CPP at any dose. Pretreatment with 100 mg/kg, but not 10 mg/kg, D-CYSee prevented acquisition of fentanyl seeking in males while both doses were effective at preventing acquisition in females.Discussion: These findings suggest that D-CYSee is an effective co-treatment with prescribed opioids to reduce the development of OUD

Agile in the Era of Digitalization : A Finnish Survey Study

This paper was a Candidate for the Best Full Paper.Peer reviewe

Can current moisture responses predict soil CO2 efflux under altered precipitation regimes? A synthesis of manipulation experiments.

As a key component of the carbon cycle, soil CO2 efflux (SCE) is being increasingly studied to improve our mechanistic understanding of this important carbon flux. Predicting ecosystem responses to climate change often depends on extrapolation of current relationships between ecosystem processes and their climatic drivers to conditions not yet experienced by the ecosystem. This raises the question of to what extent these relationships remain unaltered beyond the current climatic window for which observations are available to constrain the relationships. Here, we evaluate whether current responses of SCE to fluctuations in soil temperature and soil water content can be used to predict SCE under altered rainfall patterns. Of the 58 experiments for which we gathered SCE data, 20 were discarded because either too few data were available or inconsistencies precluded their incorporation in the analyses. The 38 remaining experiments were used to test the hypothesis that a model parameterized with data from the control plots (using soil temperature and water content as predictor variables) could adequately predict SCE measured in the manipulated treatment. Only for 7 of these 38 experiments was this hypothesis rejected. Importantly, these were the experiments with the most reliable data sets, i.e., those providing high-frequency measurements of SCE. Regression tree analysis demonstrated that our hypothesis could be rejected only for experiments with measurement intervals of less than 11 days, and was not rejected for any of the 24 experiments with larger measurement intervals. This highlights the importance of high-frequency measurements when studying effects of altered precipitation on SCE, probably because infrequent measurement schemes have insufficient capacity to detect shifts in the climate dependencies of SCE. Hence, the most justified answer to the question of whether current moisture responses of SCE can be extrapolated to predict SCE under altered precipitation regimes is ?no? ? as based on the most reliable data sets available. We strongly recommend that future experiments focus more strongly on establishing response functions across a broader range of precipitation regimes and soil moisture conditions. Such experiments should make accurate measurements of water availability, should conduct high-frequency SCE measurements, and should consider both instantaneous responses and the potential legacy effects of climate extremes. This is important, because with the novel approach presented here, we demonstrated that, at least for some ecosystems, current moisture responses could not be extrapolated to predict SCE under altered rainfall conditions

Recent advances in pulsed-laser deposition of complex-oxides

Pulsed-laser deposition (PLD) is one of the most promising techniques for the formation of complex-oxide heterostructures, superlattices, and well-controlled interfaces. The first part of this paper presents a review of several useful modifications of the process, including methods inspired by combinatorial approaches. We then discuss detailed growth kinetics results, which illustrate that 'true' layer-by-layer (LBL) growth can only be approached, but not fully met, even though many characterization techniques reveal interfaces with unexpected sharpness. Time-resolved surface x-ray diffraction measurements show that crystallization and the majority of interlayer mass transport occur on time scales that are comparable to those of the plume/substrate interaction, providing direct experimental evidence that a growth regime exists in which non-thermal processes dominate PLD. This understanding shows how kinetic growth manipulation can bring PLD closer to ideal LBL than any other growth method available today.Comment: 37 pages, 9 figures. Revie

Contribution of Energetically Reactive Surface Features to the Dissolution of CeO2 and ThO2 Analogues for Spent Nuclear Fuel Microstructures

In the safety case for the geological disposal of nuclear waste, the release of radioactivity from the repository is controlled by the dissolution of the spent fuel in groundwater. There remain several uncertainties associated with understanding spent fuel dissolution, including the contribution of energetically reactive surface sites to the dissolution rate. In this study, we investigate how surface features influence the dissolution rate of synthetic CeO2 and ThO2, spent nuclear fuel analogues that approximate as closely as possible the microstructure characteristics of fuel-grade UO2 but are not sensitive to changes in oxidation state of the cation. The morphology of grain boundaries (natural features) and surface facets (specimen preparation-induced features) was investigated during dissolution. The effects of surface polishing on dissolution rate were also investigated. We show that preferential dissolution occurs at grain boundaries, resulting in grain boundary decohesion and enhanced dissolution rates. A strong crystallographic control was exerted, with high misorientation angle grain boundaries retreating more rapidly than those with low misorientation angles, which may be due to the accommodation of defects in the grain boundary structure. The data from these simplified analogue systems support the hypothesis that grain boundaries play a role in the so-called “instant release fraction” of spent fuel, and should be carefully considered, in conjunction with other chemical effects, in safety performance assessements for the geological disposal of spent fuel. Surface facets formed during the sample annealing process also exhibited a strong crystallographic control and were found to dissolve rapidly on initial contact with dissolution medium. Defects and strain induced during sample polishing caused an overestimation of the dissolution rate, by up to 3 orders of magnitude

Can Current Moisture Responses Predict Soil CO2 Efflux Under Altered Precipitation Regimes? A Synthesis of Manipulation Experiments

As a key component of the carbon cycle, soil CO2 efflux (SCE) is being increasingly studied to improve our mechanistic understanding of this important carbon flux. Predicting ecosystem responses to climate change often depends on extrapolation of current relationships between ecosystem processes and their climatic drivers to conditions not yet experienced by the ecosystem. This raises the question to what extent these relationships remain unaltered beyond the current climatic window for which observations are available to constrain the relationships. Here, we evaluate whether current responses of SCE to fluctuations in soil temperature and soil water content can be used to predict SCE under altered rainfall patterns. Of the 58 experiments for which we gathered SCE data, 20 were discarded because either too few data were available, or inconsistencies precluded their incorporation in the analyses. The 38 remaining experiments were used to test the hypothesis that a model parameterized with data from the control plots (using soil temperature and water content as predictor variables) could adequately predict SCE measured in the manipulated treatment. Only for seven of these 38 experiments, this hypothesis was rejected. Importantly, these were the experiments with the most reliable datasets, i.e., those providing high-frequency measurements of SCE. Accordingly, regression tree analysis demonstrated that measurement frequency was crucial; our hypothesis could be rejected only for experiments with measurement intervals of less than 11 days, and was not rejected for any of the 24 experiments with larger measurement intervals. This highlights the importance of high-frequency measurements when studying effects of altered precipitation on SCE, probably because infrequent measurement schemes have insufficient capacity to detect shifts in the climate-dependencies of SCE. We strongly recommend that future experiments focus more strongly on establishing response functions across a broader range of precipitation regimes and soil moisture conditions. Such experiments should make accurate measurements of water availability, they require high-frequency SCE measurements and they should consider both instantaneous responses and the potential legacy effects of climate extremes. This is important, because we demonstrated that at least for some ecosystems, current moisture responses cannot be extrapolated to predict SCE under altered rainfall

Can current moisture responses predict soil CO2 efflux under altered precipitation regimes? A synthesis of manipulation experiments

As a key component of the carbon cycle, soil CO2 efflux (SCE) is being increasingly studied to improve our mechanistic understanding of this important carbon flux. Predicting ecosystem responses to climate change often depends on extrapolation of current relationships between ecosystem processes and their climatic drivers to conditions not yet experienced by the ecosystem. This raises the question of to what extent these relationships remain unaltered beyond the current climatic window for which observations are available to constrain the relationships. Here, we evaluate whether current responses of SCE to fluctuations in soil temperature and soil water content can be used to predict SCE under altered rainfall patterns. Of the 58 experiments for which we gathered SCE data, 20 were discarded because either too few data were available or inconsistencies precluded their incorporation in the analyses. The 38 remaining experiments were used to test the hypothesis that a model parameterized with data from the control plots (using soil temperature and water content as predictor variables) could adequately predict SCE measured in the manipulated treatment. Only for 7 of these 38 experiments was this hypothesis rejected. Importantly, these were the experiments with the most reliable data sets, i.e., those providing high-frequency measurements of SCE. Regression tree analysis demonstrated that our hypothesis could be rejected only for experiments with measurement intervals of less than 11 days, and was not rejected for any of the 24 experiments with larger measurement intervals. This highlights the importance of high-frequency measurements when studying effects of altered precipitation on SCE, probably because infrequent measurement schemes have insufficient capacity to detect shifts in the climate dependencies of SCE. Hence, the most justified answer to the question of whether current moisture responses of SCE can be extrapolated to predict SCE under altered precipitation regimes is 'no' - as based on the most reliable data sets available. We strongly recommend that future experiments focus more strongly on establishing response functions across a broader range of precipitation regimes and soil moisture conditions. Such experiments should make accurate measurements of water availability, should conduct high-frequency SCE measurements, and should consider both instantaneous responses and the potential legacy effects of climate extremes. This is important, because with the novel approach presented here, we demonstrated that, at least for some ecosystems, current moisture responses could not be extrapolated to predict SCE under altered rainfall conditions

Speciation and fate of trace metals in estuarine sediments under reduced and oxidized conditions, Seaplane Lagoon, Alameda Naval Air Station (USA)

We have identified important chemical reactions that control the fate of metal-contaminated estuarine sediments if they are left undisturbed (in situ) or if they are dredged. We combined information on the molecular bonding of metals in solids from X-ray absorption spectroscopy (XAS) with thermodynamic and kinetic driving forces obtained from dissolved metal concentrations to deduce the dominant reactions under reduced and oxidized conditions. We evaluated the in situ geochemistry of metals (cadmium, chromium, iron, lead, manganese and zinc) as a function of sediment depth (to 100 cm) from a 60 year record of contamination at the Alameda Naval Air Station, California. Results from XAS and thermodynamic modeling of porewaters show that cadmium and most of the zinc form stable sulfide phases, and that lead and chromium are associated with stable carbonate, phosphate, phyllosilicate, or oxide minerals. Therefore, there is minimal risk associated with the release of these trace metals from the deeper sediments contaminated prior to the Clean Water Act (1975) as long as reducing conditions are maintained. Increased concentrations of dissolved metals with depth were indicative of the formation of metal HS(- )complexes. The sediments also contain zinc, chromium, and manganese associated with detrital iron-rich phyllosilicates and/or oxides. These phases are recalcitrant at near-neutral pH and do not undergo reductive dissolution within the 60 year depositional history of sediments at this site. The fate of these metals during dredging was evaluated by comparing in situ geochemistry with that of sediments oxidized by seawater in laboratory experiments. Cadmium and zinc pose the greatest hazard from dredging because their sulfides were highly reactive in seawater. However, their dissolved concentrations under oxic conditions were limited eventually by sorption to or co-precipitation with an iron (oxy)hydroxide. About 50% of the reacted CdS and 80% of the reacted ZnS were bonded to an oxide-substrate at the end of the 90-day oxidation experiment. Lead and chromium pose a minimal hazard from dredging because they are bonded to relatively insoluble carbonate, phosphate, phyllosilicate, or oxide minerals that are stable in seawater. These results point out the specific chemical behavior of individual metals in estuarine sediments, and the need for direct confirmation of metal speciation in order to constrain predictive models that realistically assess the fate of metals in urban harbors and coastal sediments