Causes and Consequences of Past and Projected Scandinavian Summer Temperatures, 500–2100 AD

Tree rings dominate millennium-long temperature reconstructions and many records originate from Scandinavia, an area for which the relative roles of external forcing and internal variation on climatic changes are, however, not yet fully understood. Here we compile 1,179 series of maximum latewood density measurements from 25 conifer sites in northern Scandinavia, establish a suite of 36 subset chronologies, and analyse their climate signal. A new reconstruction for the 1483–2006 period correlates at 0.80 with June–August temperatures back to 1860. Summer cooling during the early 17th century and peak warming in the 1930s translate into a decadal amplitude of 2.9°C, which agrees with existing Scandinavian tree-ring proxies. Climate model simulations reveal similar amounts of mid to low frequency variability, suggesting that internal ocean-atmosphere feedbacks likely influenced Scandinavian temperatures more than external forcing. Projected 21st century warming under the SRES A2 scenario would, however, exceed the reconstructed temperature envelope of the past 1,500 years

Tree-Ring-Reconstructed Summer Temperatures from Northwestern North America during the Last Nine Centuries*

Northwestern North America has one of the highest rates of recent temperature increase in the world, but the putative “divergence problem” in dendroclimatology potentially limits the ability of tree-ring proxy data at high latitudes to provide long-term context for current anthropogenic change. Here, summer temperatures are reconstructed from a Picea glauca maximum latewood density (MXD) chronology that shows a stable relationship to regional temperatures and spans most of the last millennium at the Firth River in northeastern Alaska. The warmest epoch in the last nine centuries is estimated to have occurred during the late twentieth century, with average temperatures over the last 30 yr of the reconstruction developed for this study [1973–2002 in the Common Era (CE)] approximately 1.3° ± 0.4°C warmer than the long-term preindustrial mean (1100–1850 CE), a change associated with rapid increases in greenhouse gases. Prior to the late twentieth century, multidecadal temperature fluctuations covary broadly with changes in natural radiative forcing. The findings presented here emphasize that tree-ring proxies can provide reliable indicators of temperature variability even in a rapidly warming climate

Hanford Site National Environmental Policy Act (NEPA) Characterization

This document describes the U.S. Department of Energy's (DOE) Hanford Site environment. It is updated each year and is intended to provide a consistent description of the Hanford Site environment for the many National Environmental Policy Act (NEPA) documents being prepared by DOE contractors. No statements of significance or environmental consequences are provided. This year's report is the thirteenth revision of the original document published in 1988 and is (until replaced by the fourteenth revision) the only version that is relevant for use in the preparation of Hanford NEPA, State Environmental Policy Act (SEPA), and Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) documents. The two chapters included in this document (Chapters 4 and 6) are numbered to correspond to the chapters where such information is typically presented in environmental impact statements (Weiss) and other Hanford Site NEPA or CERCLA documentation. Chapter 4.0 (Affected Environment) describes Hanford Site climate and meteorology, geology, hydrology, ecology, cultural, archaeological, and historical resources, socioeconomics, occupational safety, and noise. Chapter 6.0 (Statutory and Regulatory Requirements) describes federal and state laws and regulations, DOE directives and permits, and presidential executive orders that are applicable to the NEPA documents prepared for Hanford Site activities

Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice

IMPORTANCE: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes. OBJECTIVE: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals. EXPOSURES: Genetic test results. MAIN OUTCOMES AND MEASURES: Clinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms. RESULTS: Among 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical information available (mean [SD] time, 584 [365] days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of seizures, 37 (22.2%) had decreases in the severity of other clinical signs, and 11 (6.6%) had reduced medication adverse effects. A few patients reported worsening of outcomes, including a decline in their condition (20 [12.0%]), increased seizure frequency (6 [3.6%]), and adverse medication effects (3 [1.8%]). No clinical management changes were reported for 178 patients (42.6%). CONCLUSIONS AND RELEVANCE: Results of this cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes

Metabolites of Cannabigerol Generated by Human Cytochrome P450s Are Bioactive

The phytocannabinoid cannabigerol (CBG) is the central biosynthetic precursor to many cannabinoids, including Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Though the use of CBG has recently witnessed a widespread surge because of its beneficial health effects and lack of psychoactivity, its metabolism by human cytochrome P450s is largely unknown. Herein, we describe comprehensive in vitro and in vivo cytochrome P450 (CYP)-mediated metabolic studies of CBG, ranging from liquid chromatography tandem mass spectrometry-based primary metabolic site determination, synthetic validation, and kinetic behavior using targeted mass spectrometry. These investigations revealed that cyclo-CBG, a recently isolated phytocannabinoid, is the major metabolite that is rapidly formed by selected human cytochrome P450s (CYP2J2, CYP3A4, CYP2D6, CYP2C8, and CYP2C9). Additionally, in vivo studies with mice administered with CBG supported these studies, where cyclo-CBG is the major metabolite as well. Spectroscopic binding studies along with docking and modeling of the CBG molecule near the heme in the active site of P450s confirmed these observations, pointing at the preferred site selectivity of CBG metabolism at the prenyl chain over other positions. Importantly, we found out that CBG and its oxidized CBG metabolites reduced inflammation in BV2 microglial cells stimulated with LPS. Overall, combining enzymological studies, mass spectrometry, and chemical synthesis, we showcase that CBG is rapidly metabolized by human P450s to form oxidized metabolites that are bioactive

Metabolites of Cannabigerol (CBG) Generated by Human Cytochrome P450s are Bioactive

The phytocannabinoid cannabigerol (CBG) is the central biosynthetic precursor to many cannabinoids, including Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Though the use of CBG has recently witnessed a widespread surge because of its beneficial health effects and lack of psychoactivity, its metabolism by human cytochrome P450s is largely unknown. Herein, we describe comprehensive in vitro and in vivo cytochrome P450 (CYP)-mediated metabolic studies of CBG, ranging from LC-MS/MS-based primary metabolic site determination, synthetic validation, and kinetic behavior using targeted mass spectrometry. These investigations revealed that cyclo-CBG, a recently isolated phytocannabinoid, is the major metabolite that is rapidly formed by selected human cytochrome P450s (CYP2J2, CYP3A4, CYP2D6, CYP2C8, and CYP2C9). Additionally, in vivo studies with mice administered with CBG, supported these studies, where cyclo-CBG is the major metabolite as well. Spectroscopic binding studies along with docking and modeling of CBG molecule near the heme in the active site of P450s confirmed these observations, pointing at the preferred site-selectivity of CBG metabolism at the prenyl chain over other positions. Importantly, we found out that CBG and its oxidized CBG metabolites reduced inflammation in BV2 microglial cells stimulated with LPS. Overall, combining enzymological studies, mass spectrometry, and chemical synthesis, we showcase that CBG is rapidly metabolized by human P450s to form oxidized metabolites that are bioactive. The study reveals the structure-activity relationship of CBG metabolites and analogs to their anti-inflammatory activity

Thermal-infrared remote sensing of surface water-groundwater exchanges in a restored anastomosing channel (Upper Rhine River, France)

Ecohydrological processes are a key element to consider in functional river restorations. In the framework of a LIFE+ European restoration program, we have investigated the potential for airborne thermal‐infrared remote sensing to map surface water–groundwater exchanges and to identify their driving factors. We focused our attention on anastomosing channels on an artificial island of the Upper Rhine River (Rohrschollen), where a new channel was excavated from the floodplain to reconnect an older channel in its upstream part. These hydraulic engineering works led to an increased inflow from the Rhine Canal. Here, we propose an original data treatment chain to (a) georeference the thermal‐infrared images in geographic information system based on visible images, (b) detect and correct data errors, and (c) identify and locate thermal anomalies attributed to groundwater inputs and hyporheic upwellings. Our results, which have been compared to morpho‐sedimentary data, show that groundwater upwelling in the new channel is controlled by riffle–pool sequences and bars. This channel is characterized by large bedload transport and morphodynamic activity, forming riffles and bars. In the old channel, where riffle–pool sequences no longer exist, due to impacts of engineering works and insufficient morphodynamic effects of the restoration, thermal anomalies appeared to be less pronounced. Groundwater inputs seem to be controlled by former gravel bars outcropping on the banks, as well as by local thinning of the low‐permeability clogging layer on the channel bed

Hanford Site National Environmental Policy Act (NEPA) Characterization

This document describes the U.S. Department of Energy's (DOE) Hanford Site environment. It is updated each year and is intended to provide a consistent description of the Hanford Site environment for the many National Environmental Policy Act (NEPA) documents being prepared by DOE contractors. No statements of significance or environmental consequences are provided. This year's report is the thirteenth revision of the original document published in 1988 and is (until replaced by the fourteenth revision) the only version that is relevant for use in the preparation of Hanford NEPA, State Environmental Policy Act (SEPA), and Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) documents. The two chapters included in this document (Chapters 4 and 6) are numbered to correspond to the chapters where such information is typically presented in environmental impact statements (Weiss) and other Hanford Site NEPA or CERCLA documentation. Chapter 4.0 (Affected Environment) describes Hanford Site climate and meteorology, geology, hydrology, ecology, cultural, archaeological, and historical resources, socioeconomics, occupational safety, and noise. Chapter 6.0 (Statutory and Regulatory Requirements) describes federal and state laws and regulations, DOE directives and permits, and presidential executive orders that are applicable to the NEPA documents prepared for Hanford Site activities