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BackgroundNeonatal stroke is common and causes life-long motor and cognitive sequelae. Because neonates with stroke are not diagnosed until days-months after the injury, chronic targets for repair are needed. We evaluated oligodendrocyte maturity and myelination and assessed oligodendrocyte gene expression changes using single cell RNA sequencing (scRNA seq) at chronic timepoints in a mouse model of neonatal arterial ischemic stroke.MethodsMice underwent sixty minutes of transient right middle cerebral artery occlusion (MCAO) on postnatal day 10 (p10) and received 5-ethynyl-2’-deoxyuridine (EdU) on post-MCAO days 3-7 to label dividing cells. Animals were sacrificed 14 and 28-30 days post-MCAO for immunohistochemistry and electron microscopy. Oligodendrocytes were isolated from striatum 14 days post-MCAO for scRNA seq and differential gene expression analysis.ResultsThe density of Olig2+EdU+cells was significantly increased in ipsilateral striatum 14 days post-MCAO and the majority of oligodendrocytes were immature. Density of Olig2+EdU+cells declined significantly between 14 and 28 days post-MCAO without a concurrent increase in mature Olig2+EdU+cells. By 28 days post-MCAO there were significantly fewer myelinated axons in ipsilateral striatum. scRNA seq identified a cluster of “disease associated oligodendrocytes (DOLs)” specific to the ischemic striatum, with increased expression of MHC class I genes. Gene ontology analysis suggested decreased enrichment of pathways involved in myelin production in the reactive cluster.ConclusionsOligodendrocytes proliferate 3-7 days post-MCAO and persist at 14 days, but fail to mature by 28 days. MCAO induces a subset of oligodendrocytes with reactive phenotype, which may be a therapeutic target to promote white matter repair.

Earth's thermo-tectonic evolution determines the way the planet's interior and surface interact and shows temporal changes in both trends and periodic rhythms. By sampling the subcontinental lithospheric mantle that represents the interface between the convecting mantle and the crust, carbonatite and kimberlite should be ideal rock types for documenting this evolution. The first-order secular rise of kimberlites over time has been noted by researchers, but there is much debate over how to interpret this trend, and their second-order variability has received less attention. We compiled a comprehensive global carbonatite database and compared it with an existing kimberlite one. We find that the numbers of carbonatites and kimberlites have similar increasing secular trends, with accelerated growth after ca. 1 Ga, and show the same periodic rhythms that have been synchronized to the supercontinent cycle since ca. 2.1 Ga. We link these trends and rhythms to the long-term change of Earth and the supercontinent cycle, both of which have altered the temperature of, and the subduction-recycled volatile flux into, the subcontinental lithosphere. Such consistent records in carbonatite and kimberlite behavior provide critical evidence for the synchronous thermo-tectonic evolution of the entire subcontinental lithosphere.

The aim is to pilot a low-touch program for reducing benzodiazepine receptor agonist (BZRA; benzodiazepines, z-drugs) prescriptions among older veterans.Pilot randomized controlled trial consists of 2,009 veterans aged ≥ 65 years who received BZRA prescriptions from a Veterans Health Administration pharmacy (Colorado or Montana) during the prior 18 months. Active: Arm 1 was a mailed brochure about BZRA risks that also included information about a free, online cognitive behavioral therapy for the insomnia (CBTI) program. Arm 2 was a mailed brochure (same as arm 1) and telephone reinforcement call. Control: Arm 3 was a mailed brochure without insomnia treatment information. Active BZRA prescriptions at follow-up (6 and 12 months) were measured.In logistic regression analyses, the odds of BZRA prescription at 6- and 12-month follow-ups were not significantly different for arm 1 or 2 (active) versus arm 3 (control), including models adjusted for demographics and prescription characteristics (Although we observed no differences in active BZRA prescriptions, this pilot study provides guidance for conducting a future study, indicating a need for a more potent intervention. A full-scale trial testing an optimized program would provide conclusive results.Mailing information about BZRA risks and CBTI did not affect BZRA prescriptions.

Insects, unlike vertebrates, are widely believed to lack male-biased sex steroid hormones1. In the malaria mosquito Anopheles gambiae, the ecdysteroid 20-hydroxyecdysone (20E) appears to have evolved to both control egg development when synthesized by females2 and to induce mating refractoriness when sexually transferred by males3. Because egg development and mating are essential reproductive traits, understanding how Anopheles females integrate these hormonal signals can spur the design of new malaria control programs. Here we reveal that these reproductive functions are regulated by distinct sex steroids through a sophisticated network of ecdysteroid-activating/inactivating enzymes. We identify a male-specific oxidized ecdysteroid, 3-dehydro-20E (3D20E), which safeguards paternity by turning off female sexual receptivity following its sexual transfer and activation by dephosphorylation. Notably, 3D20E transfer also induces expression of a reproductive gene that preserves egg development during Plasmodium infection, ensuring fitness of infected females. Female-derived 20E does not trigger sexual refractoriness but instead licenses oviposition in mated individuals once a 20E-inhibiting kinase is repressed. Identifying this male-specific insect steroid hormone and its roles in regulating female sexual receptivity, fertility and interactions with Plasmodium parasites suggests the possibility for reducing the reproductive success of malaria-transmitting mosquitoes.

Plume magmatism and continental breakup led to the opening of the northeast Atlantic Ocean during the globally warm early Cenozoic. This warmth culminated in a transient (170 thousand year, kyr) hyperthermal event associated with a large, if poorly constrained, emission of carbon called the Palaeocene–Eocene Thermal Maximum (PETM) 56 million years ago (Ma). Methane from hydrothermal vents in the coeval North Atlantic Igneous Province (NAIP) has been proposed as the trigger, though isotopic constraints from deep sea sediments have instead implicated direct volcanic carbon dioxide (CO2) emissions. Here we calculate that background levels of volcanic outgassing from mid-ocean ridges and large igneous provinces yield only one-fifth of the carbon required to trigger the hyperthermal. However, geochemical analyses of volcanic sequences spanning the rift-to-drift phase of the NAIP indicate a sudden ~220 kyr-long intensification of magmatic activity coincident with the PETM. This was likely driven by thinning and enhanced decompression melting of the sub-continental lithospheric mantle, which critically contained a high proportion of carbon-rich metasomatic carbonates. Melting models and coupled tectonic–geochemical simulations indicate that >104 gigatons of subcrustal carbon was mobilized into the ocean and atmosphere sufficiently rapidly to explain the scale and pace of the PETM.

We evaluated whether reducing irrigation frequency and volume alters the ability of Phytophthora plurivora and P. cinnamomi to cause root rot on rhododendron grown in a noninfested potting medium or media infested with 1 or 100 propagules per gram (ppg) of pathogen. Plants were irrigated to maintain a substrate moisture of >70% container capacity (1.0X), one-half volume of 1.0X (0.5X), or two times the volume of 1.0X at each irrigation event for one week, followed by no irrigation, until soil moisture reached Species used in this study: Phytophthora species (Phytophthora cinnamomi Rands; Phytophthora plurivora T. Jung and T.I. Burgess); rhododendron, Rhododendron catawbiense Michx. ‘Album', ‘Roseum Elegans', and ‘Roseum Pink'.

The Devonian position of the South China Block (SCB) remains debated because apparently contradictory Devonian paleopoles have been documented. Here we report two characteristic remanent magnetization components from the mildly deformed Guanyang Devonian successions (Lochkovian-Famennian) within the cratonic interior of the SCB. Both components pass reversal tests and occur in different samples across the successions. Component A and associated paleopole DA (228.9°E, 37.7°N, A95 = 3.7°) are comparable with published Devonian data and were likely acquired before Permian-Triassic folding and likely reflect syn-depositional magnetization. Component B and its associated paleopole DB (204.6°E, 4.5°N, A95 = 5.5°) are distinct from published results and were probably acquired during minor tilting associated with the Late Devonian Liujiang orogeny. If paleopole DA was acquired prior to the Late Devonian Liujiang orogeny, the paleolatitude of the Guanyang successions varied little throughout the Devonian, but the azimuthal orientation of recorded declinations exhibits a 40° difference. The distinct positions of the two paleopoles are broadly consistent with existing enigmatic Devonian field records. Alternatively, given the uncertainty in the acquisition ages of both components in the Guanyang successions, a case can be made for component A being a secondary magnetization acquired during the Permian-Triassic Indosinian orogeny. Nonetheless, the similar distribution of Devonian paleopoles from Gondwana to those of cratonic interior of the SCB suggests a Devonian connection between the two continents, and adds further support for a non-uniformitarian geomagnetic field during this enigmatic time interval.

Interpretation of Earth's oldest preserved crustal archive, the Jack Hills zircon of Western Australia, has been controversial in terms of the onset of plate tectonics. We conduct time-series analysis on hafnium isotopes of the Jack Hills zircon and reveal an array of statistically significant cycles that are reminiscent of plate-tectonic subduction. At face value, such cycles may suggest early Earth conditions similar to those of today—the uniformitarian hypothesis that plate tectonics was essentially operational since “day one”. On the other hand, in the context of expected secular changes due to planetary evolution and geological observations, the cycles could instead imply that modern plate-tectonic subduction inherited mantle convective harmonics already facilitated by an early phase of stagnant-lid delamination—the “lid-to-plates” hypothesis. Either way, any model for the nature of plate tectonics must incorporate conditions operating during Hadean time, either by initiation of plate tectonics then or by later inheritance of preexisting cycles of mantle convection.

Since the Jurassic, there has been a clear spatiotemporal correlation between different types of metamorphism and active convergent plate margins. However, the extent to which this relationship extends into the past is poorly understood. We compared paleogeographic reconstructions and inferred plate kinematics with the age and thermobaric ratio (temperature/pressure [T/P]) of metamorphism over the past 2 b.y. The null hypothesis—that there is no spatiotemporal link between inferred plate margins and metamorphism—can be rejected. Low-T/P metamorphism is almost exclusively located near plate margins, whereas intermediate- and high-T/P metamorphism skews toward increasingly greater distances from these margins, consistent with three different tectonic settings: the subduction zone, the mountain belt, and the orogenic hinterland, respectively. However, paleogeographic reconstructions suggest that so-called “paired metamorphic belts” are rare and that high- and low-T/P localities more commonly occur along strike from each other. The observation that bimodal metamorphism is largely a function of distance from the trench and that end-member T/P types rarely occur in the same place can be explained if the style of orogenesis has evolved from hotter to colder, consistent with the abrupt emergence of low-T/P metamorphism in the Cryogenian. The widespread development of high-T/P rocks in orogenic hinterlands in the Proterozoic was followed by the production and efficient exhumation of low-T/P rocks in subduction channels in the Phanerozoic.

ObjectiveThis study compared the benefits of cognitive-behavioral therapy for insomnia for sleep, mental health symptoms, and quality of life (QoL) in a sample of women veterans with and without probable post-traumatic stress disorder (PTSD) comorbid with insomnia disorder.MethodsSeventy-three women veterans (30 with probable PTSD) received a manual-based 5-week cognitive-behavioral therapy for insomnia treatment as part of a behavioral sleep intervention study. Measures were completed at baseline, post-treatment, and 3-month follow-up. Sleep measures included the Insomnia Severity Index, Pittsburgh Sleep Quality Index, sleep efficiency measured by actigraphy, and sleep efficiency and total sleep time measured by sleep diary. Mental health measures included the PTSD Checklist-5, nightmares per week, Patient Health Questionnaire-9, and Generalized Anxiety Disorder-7 scale. QoL was measured with the Short Form-12. Linear mixed models compared changes over time across groups. Independent t tests examined PTSD symptom changes in women veterans with probable PTSD.ResultsBoth groups demonstrated improvements across sleep (ps&nbsp

Granulites represent high-grade metamorphic rocks of the deep continental crust. The metamorphism and exhumation of granulites from Archean terranes provide insights into the crustal evolution of Archean cratons and shed light on the formation and reactivation of cratons. We present petrology, U–Pb geochronology (zircon, rutile, and titanite), and pressure-temperature (P–T) paths for metadiabase dikes in an Archean granulite terrane of the North China Craton. Garnet (Grt) coronae in the metadiabase dikes are developed between plagioclase (Pl) and clinopyroxene (Cpx) via the reaction Pligneous + Cpx → Pl1 + Grt ± quartz. The reaction proceeds inward within the plagioclase, progressively consuming Pligneous (XAn = 0.65–0.69) and leaving Ca-poor Pl1 (XAn = 0.46–0.53) as the residue. Geothermobarometry and P–T pseudosections suggest peak conditions for garnet formation at ~800 °C and 10–13 kbar. During retrograde metamorphism, Grt broke down to Ca-rich Pl2 (XAn = 0.73–0.74), and ilmenite replaced rutile. Geothermobarometry and Zr-in-titanite temperatures constrain the P–T conditions of retrograde metamorphism at 700–750 °C and 4.5–7.5 kbar. Zircon and titanite U–Pb geochronology shows that the protolith of the metadiabase dike was formed at 2.4 Ga and underwent granulite-facies metamorphism at 1.86 Ga. The intrusion of mafic dikes into the Archean granulite terrane indicates that the Archean basement was also heated and buried in the Paleoproterozoic. The metadiabase dikes and the hosting Archean basement underwent Paleoproterozoic granulite-facies metamorphism at a depth of ~40 km, followed by near-isothermal decompression and subsequent near-isobaric cooling (cooling rate of 1–3 °C Myr-1) at depths of 15–25 km. Crustal shortening and thickening may have been caused by the underplating of the Khondalite series beneath the Archean basement during the amalgamation of supercontinent Columbia. The Paleoproterozoic orogeny induced a second generation of metamorphism of the Archean basement along the margin of the craton and drove the exhumation of the Archean granulite terranes to the middle crust (~15 km).

The emergence of the Ediacara biota soon after the Gaskiers glaciation ca. 580 million years ago (Ma) implies a possible glacial fuse for the evolution of animals. However, the timing of Ediacaran glaciation remains controversial because of poor age constraints on the ∼30 Ediacaran glacial deposits known worldwide. In addition, paleomagnetic constraints and a lack of convincing Snowball-like cap carbonates indicate that Ediacaran glaciations likely did not occur at low latitudes. Thus, reconciling the global occurrences without global glaciation remains a paradox. Here, we report that the large amplitude, globally synchronous ca. 571–562 Ma Shuram carbon isotope excursion occurs below the Ediacaran Hankalchough glacial deposit in Tarim, confirming a post-Shuram glaciation. Leveraging paleomagnetic evidence for a ∼90° reorientation of all continents due to true polar wander, and a non-Snowball condition that rules out low-latitude glaciations, we use paleogeographic reconstructions to further constrain glacial ages. Our results depict a ‘Great Ediacaran Glaciation’ occurring diachronously but continuously from ca. 580–560 Ma as different continents migrated through polar–temperate latitudes. The succession of radiation, turnover and extinction of the Ediacara biota strongly reflects glacial–deglacial dynamics.

Scientific research has been changing medical practice at an increasing pace. To keep up with this change, physicians of the future will need to be lifelong learners with the skills to engage with emerging science and translate it into clinical care. How medical schools can best prepare students for ongoing scientific change remains unclear. Adding to the challenge is reduced time allocated to basic science in curricula and rapid expansion of relevant scientific fields. A return to science with greater depth after clinical clerkships has been suggested, although few schools have adopted such curricula and implementation can present challenges. The authors describe an innovation at Harvard Medical School, the Advanced Integrated Science Courses (AISCs), which are taken after core clerkships. Students are required to take 2 such courses, which are offered in a variety of topics. Rather than factual content, the learning objectives are a set of generalizable skills to enable students to critically evaluate emerging research and its relationship to medical practice. Making these generalizable skills the defining principle of the courses has several important advantages: it allows standardization of acquired skills to be combined with diverse course topics ranging from basic to translational and population sciences; students can choose courses and projects aligned with their interests, thereby enhancing engagement, curiosity, and career relevance; schools can tailor course offerings to the interests of local faculty; and the generalizable skills delineate a unique purpose of these courses within the overall medical school curriculum. For the 3 years AISCs have been offered, students rated the courses highly and reported learning the intended skill set effectively. The AISC concept addresses the challenge of preparing students for this era of rapidly expanding science and should be readily adaptable to other medical schools.

Travel demand models (TDMs) with freight forecasts estimate performance metrics for competing infrastructure investments and potential policy changes. Unfortunately, freight TDMs fail to represent non-truck modes with levels of detail adequate for multi-modal infrastructure and policy evaluation. Recent expansions in the availability of maritime movement data, i.e. Automatic Identification System (AIS), make it possible to expand and improve representation of maritime modes within freight TDMs. AIS may be used to track vessel locations as timestamped latitude–longitude points. For estimation, calibration and validation of freight TDMs, this work identifies vessel trips by applying network mapping (map-matching) heuristics to AIS data. The automated methods are evaluated on a 747-mile inland waterway network, with AIS data representing 88% of vessel activity. Inspection of 3820 AIS trajectories was used to train the heuristic parameters including stop time, duration and location. Validation shows 84⋅0% accuracy in detecting stops at ports and 83⋅5% accuracy in identifying trips crossing locks. The resulting map-matched vessel trips may be applied to generate origin–destination matrices, calculate time impedances, etc. The proposed methods are transferable to waterways or maritime port systems, as AIS continues to grow.

With millions of dogs housed in shelters each year, it is important to consider how the shelter environment impacts welfare. Social isolation and a lack of control over the environment can negatively impact wellbeing. However, providing social opportunities requires costly resources and can raise concerns about increased barking. In this study, 17 dogs were observed before, during, and after a visual barrier was partially removed to increase the ability to see to other dogs and the surrounding room. Stress behaviors, crate position, and resting behaviors did not differ significantly across phases; however, vocalizations were lower in the visual access and post phases (Friedman's test

STUDY OBJECTIVES: To evaluate the clinical utility of actigraphy as compared with sleep questionnaires prior to the Multiple Sleep Latency Test (MSLT) in a sleep disorders clinic population. METHODS: Twenty-eight clinically referred participants (mean age: 42.3 ± 18.8 years) completed the study protocol. On day 1, participants completed the following questionnaires: Epworth Sleepiness Scale (ESS), Insomnia Severity Index, Pittsburgh Sleep Quality Index (PSQI), Visual Analog Scale (affect, vigor), Patient Health Questionnaire, and Multidimensional Fatigue Symptom Inventory–Short Form. On days 1–8, participants wore an actigraph and completed a sleep diary to assess mean nighttime and mean daytime total sleep time and sleep efficiency or sleep percentage. On day 9, participants repeated the ESS and completed an MSLT. Correlations assessed mean MSLT sleep-onset latency (MSLT-SOL) vs actigraphy, sleep diary, and questionnaires. Chi-square analyses assessed abnormal MSLT-SOL (≤ 8 minutes) or daytime sleepiness (ESS ≥ 10) and referral question (ie, sleep-disordered breathing vs hypersomnolence disorder). RESULTS: Mean MSLT-SOL was correlated with nighttime total sleep time assessed via both actigraphy and diary, but not with questionnaires. Significant correlations emerged for ESS score on day 1 vs 9, actigraphy vs sleep diary mean nighttime total sleep time, and PSQI vs mean sleep diary sleep efficiency. There was no significant relationship between mean MSLT-SOL and referral question. CONCLUSIONS: Our finding that total sleep time measured by actigraphy was associated with MSLT-SOL suggests it is useful in informing the interpretation of MSLT findings; however, it does not appear to be a viable substitute for MSLT for the measurement of objective sleepiness in clinical settings. CITATION: Kelly MR, Zeidler MR, DeCruz S, et al. Actigraphy prior to Multiple Sleep Latency Test: nighttime total sleep time predicts sleep-onset latency. J Clin Sleep Med. 2022;18(1):161–170.

The mechanism and timing of crustal growth and differentiation on early Earth are debated. Evidence of crustal differentiation is detectable as deviations from Earth’s assumed chondritic uniform reservoir (CHUR) as crust is extracted from the mantle leading to a melt-depleted reservoir. For the long-lived zircon Lu-Hf system, no incontrovertible evidence of significant mantle depletion >3.8 Ga exists. We conduct combined U-Pb and Lu-Hf isotopic analyses for the detrital zircon from the Caozhuang supracrustal sequence in North China. The zircon Hf isotopic compositions are broadly scattered along the CHUR evolution line. However, given the possibility of potential systematic biases in zircon petrogenesis and the unique tectonic setting of early Earth, we posit that magmatism controlled by the nascent forms of plate tectonics during the Eoarchean could have likely hidden the degree of ancient crust-mantle differentiation. The non-depleted zircon Hf isotopes observed in North China and globally during early Earth may in verity imply the existence of ubiquitous depleted mantle domains at that time.

Earth’s earliest continental crust is dominated by tonalite–trondhjemite–granodiorite (TTG) suites, making these rocks key to unlocking the global geodynamic regime operating during the Archaean (4.0–2.5 billion years ago [Ga]). The tectonic setting of TTG magmatism is controversial, with hypotheses arguing both for and against subduction. Here we conduct petrological modeling over a range of pressure–temperature conditions relevant to the Archaean geothermal gradient. Using an average enriched Archaean basaltic source composition, we predict Ba concentrations in TTG suites, which is difficult to increase after magma generated in the source. The results indicate only low geothermal gradients corresponding to hot subduction zones produce Ba-rich TTG, thus Ba represents a proxy for the onset of subduction. We then identify statistically significant increases in the Ba contents of TTG suites worldwide as recording the diachronous onset of subduction from regional at 4 Ga to globally complete sometime after 2.7 Ga.

Developing vascular networks that integrate with the host circulation and support cells engrafted within engineered tissues remains a key challenge in tissue engineering. Most previous work in this field has focused on developing new methods to build human vascular networks within engineered tissues prior to their implant in vivo, with substantively less attention paid to the role of the host in tissue vascularization and engraftment. Here, we assessed the role that different host animal models and anatomic implant locations play in vascularization and cardiomyocyte survival within engineered tissues. We found major differences in the formation of graft-derived blood vessels and survival of cardiomyocytes after implantation of identical tissues in immunodeficient athymic nude mice versus rats. Athymic mice supported robust guided vascularization of human microvessels carrying host blood but relatively sparse cardiac grafts within engineered tissues, regardless of implant site. Conversely, athymic rats produced substantive inflammatory changes that degraded grafts (abdomen) or disrupted vascular patterning (heart). Despite disrupted vascular patterning, athymic rats supported > 3-fold larger human cardiomyocyte grafts compared to athymic mice. This work demonstrates the critical importance of the host for vascularization and engraftment of engineered tissues, which has broad translational implications across regenerative medicine.

The Ordovician–Silurian transition experienced severe, but enigmatic, glaciation, as well as a paradoxical combination of mass extinction and species origination. Here we report a large and fast true polar wander (TPW) event that occurred 450–440 million years ago based on palaeomagnetic data from South China and compiled reliable palaeopoles from all major continents. Collectively, a ~50˚ wholesale rotation with maximum continental speeds of ~55 cm yr−1 is demonstrated. Multiple isolated continents moving rapidly, synchronously, and unidirectionally is less consistent with and plausible for relative plate motions than TPW. Palaeogeographic reconstructions constrained by TPW controlling for palaeolongitude explain the timing and migration of glacial centers across Gondwana, as well as the protracted end-Ordovician mass extinction. The global quadrature pattern of latitude change during TPW further explains why the extinction was accompanied by elevated levels of origination as some continents migrated into or remained in the amenable tropics.

The Paleo-Tethys and Panthalassa are two major oceans that witnessed the end-Permian mass extinction, and they have been suggested to have distinct compositions, with the Paleo-Tethys Ocean euxinic, and the much larger Panthalassa Ocean being largely ventilated. Distinctions of these two once-connected oceans imply that interactions between them must have been restricted shortly before the end-Permian extinction. However, detailed geological processes for the disconnection between them along the eastern Paleo-Tethys Ocean due to the collision of North and South China, are still unclear. Previous geochronological studies on eclogite facies rocks in the Dabie–Sulu orogenic belt, which are the metamorphic products of the collision between North and South China, have yielded mainly Triassic metamorphic ages. Nonetheless, new Permian metamorphic ages are identified from southeastern North China, northern Dabie, and the Permo–Triassic intracontinental orogen of South China, which may collectively closely associate this major tectonic event with the end-Permian extinction. New age dating results, as well as a synthesis of recent studies on metamorphic rocks, show that the onset of the collisional orogenesis dates back to the Middle Permian (270–252 Ma). We thereby provide a new tectonic model for the major continents of East Asia, in which the initial collision between North and South China during the Middle Permian critically isolated the Paleo-Tethys Ocean from the Panthalassa Ocean, facilitating the oceanographic transition of the once fossiliferous Paleo-Tethys from a life-giving nutrient-rich ocean into a euxinic death trap, thereby serving as prelude to the end-Permian extinction.

The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.

Dermatology for the pediatric skin of color population is the application of dermatology to the genetically diverse and distinctive segment of the pediatric population that includes children of non-White racial and ethnic groups with increased pigmentation including individuals of Asian, LatinX, African, Native American, Pacific Island descent, Indigenous Peoples, among others, with overlap in particular individuals, and mixtures thereof. Treating children of color is a unique skill set within the field of pediatric dermatology, requiring knowledge and sensitivity. The discipline of pediatric skin of color can be challenging. Difficulty in diagnosis of common conditions stems from underlying pigmentation, variations in common hairstyling practices, and differences in demographics of cutaneous disease, whereas some conditions are more common in children of color, other conditions have nuances in clinical appearance and/or therapeutics with regard to skin color. This article is the first in a series of two articles looking at recently published skin-related issues of high concern in children of color. Conditions reviewed in Part 1 include (1) hairstyling hair-related concerns (traction alopecia, central centrifugal cicatricial alopecia, endocrine disruption), (2) autoimmune concerns (cutaneous lupus, vitiligo), and (3) infections (tinea capitis, progressive macular hypomelanosis).

Ground-based remote sensing of atmospheric parameters is often limited to single station observations by vertical profiles at a certain geographic location. This is a limiting factor for investigating gravity wave dynamics as the spatial information is often missing, e.g., horizontal wavelength, propagation direction or intrinsic frequency. In this study, we present a new retrieval algorithm for multistatic meteor radar networks to obtain tomographic 3-D wind fields within a pre-defined domain area. The algorithm is part of the Agile Software for Gravity wAve Regional Dynamics (ASGARD) and called 3D-Var, and based on the optimal estimation technique and Bayesian statistics. The performance of the 3D-Var retrieval is demonstrated using two meteor radar networks: the Nordic Meteor Radar Cluster and the Chilean Observation Network De Meteor Radars (CONDOR). The optimal estimation implementation provide statistically sound solutions and diagnostics from the averaging kernels and measurement response. We present initial scientific results such as body forces of breaking gravity waves leading to two counter-rotating vortices and horizontal wavelength spectra indicating a transition between the rotational k−3 and divergent k-5/3 mode at scales of 80–120 km. In addition, we performed a keogram analysis over extended periods to reflect the latitudinal and temporal impact of a minor sudden stratospheric warming in December 2019. Finally, we demonstrate the applicability of the 3D-Var algorithm to perform large-scale retrievals to derive meteorological wind maps covering a latitude region from Svalbard, north of the European Arctic mainland, to central Norway.

Long-term and continuous observations of mesospheric–lower thermospheric winds are rare, but they are important to investigate climatological changes at these altitudes on timescales of several years, covering a solar cycle and longer. Such long time series are a natural heritage of the mesosphere–lower thermosphere climate, and they are valuable to compare climate models or long-term runs of general circulation models (GCMs). Here we present a climatological comparison of wind observations from six meteor radars at two conjugate latitudes to validate the corresponding mean winds and atmospheric diurnal and semidiurnal tides from three GCMs, namely the Ground-to-Topside Model of Atmosphere and Ionosphere for Aeronomy (GAIA), the Whole Atmosphere Community Climate Model Extension (Specified Dynamics) (WACCM-X(SD)), and the Upper Atmosphere ICOsahedral Non-hydrostatic (UA-ICON) model. Our results indicate that there are interhemispheric differences in the seasonal characteristics of the diurnal and semidiurnal tide. There are also some differences in the mean wind climatologies of the models and the observations. Our results indicate that GAIA shows reasonable agreement with the meteor radar observations during the winter season, whereas WACCM-X(SD) shows better agreement with the radars for the hemispheric zonal summer wind reversal, which is more consistent with the meteor radar observations. The free-running UA-ICON tends to show similar winds and tides compared to WACCM-X(SD).

In Global Navigation Satellite (GNSS)-based positioning, a user within a region covered by a network of reference stations can take advantage of the network-estimated parameters. The use of State Space Representation (SSR) parameters as GNSS-augmentation is valuable for Network-Real Time Kinematic (N-RTK) positioning and enables the ambiguity resolution for Precise Point Positioning (PPP) in the so-called PPP-RTK. SSR atmospheric corrections, i.e. tropospheric and ionospheric delays, are commonly estimated for the approximate user position by interpolation from values estimated for the reference stations. Widely used techniques are Inverse Distance Weighted, Ordinary Kriging and Weighted Least Squares (WLS). In this work, we analyze the interpolation quality of such techniques during severe weather events and Traveling Ionospheric Disturbances (TID). Furthermore, we propose modified WLS methods taking advantage of the physical atmospheric behavior during such events. Here, we exploit the use of Numerical Weather Models for tropospheric horizontal gradients information, and estimated TID parameters like wavelength and direction of propagation. Firstly, the interpolation is assessed using simulations considering artificial and real network geometries. Secondly, the proposed techniques are evaluated in post-processing using real SSR parameters generated by network computation of GNSS measurements. As examples, two severe weather events in North Europe in 2017, and one TID event over Japan in 2019 have been analyzed. The interpolation of SSR tropospheric and ionospheric parameters is evaluated. Considering the reference station positions as rover locations, the application of the modified WLS approach reduces the root mean square error in up to 80 % of the cases during sharp weather fluctuations. Also, the average error can be decreased in 64 % of the cases during the TID event investigated. Improvements up to factors larger than two are observed. Furthermore, specific cases are isolated showing particular tropospheric variations where significant errors (e.g. larger than 1 cm) can be reduced up to 20 % of the total amount. Finally, tropospheric and ionospheric messages are proposed to transmit to the user the information needed to implement the suggested interpolation properly.

The Chang’E-5 (CE5) mission has demonstrated that lunar volcanism was still active until two billion years ago, much younger than the previous isotopically dated lunar basalts. How the small Moon retained enough heat to drive such late volcanism is unknown, particularly as the CE5 mantle source was anhydrous and depleted in heat-producing elements. We conduct fractional crystallization and mantle melting simulations that show that mantle melting point depression by the presence of fusible, easily melted components could trigger young volcanism. Enriched in calcium oxide and titanium dioxide compared to older Apollo magmas, the young CE5 magma was, thus, sourced from the overturn of the late-stage fusible cumulates of the lunar magma ocean. Mantle melting point depression is the first mechanism to account for young volcanism on the Moon that is consistent with the newly returned CE5 basalts.

Mantle xenoliths from the Middle-Late Jurassic Obnazhennaya kimberlite are often compared with those from the Udachnaya kimberlite (ca. 367 Ma) to inform the evolution of the Siberia craton. Howeve...

The Neoproterozoic Era (1000–541 Ma) is characterized by the largest negative carbon isotope excursions in Earth history. Younger Neoproterozoic excursions are well-documented on multiple continental margins and associated with major events including snowball Earth glaciations, ocean-atmosphere oxygenation, and the evolution of animal multicellularity. However, due to a large gap in carbon isotopes before 900 Ma, the onset of early Neoproterozoic carbon cycle volatility has heretofore been obscure. Here, we present a mid-amplitude, negative carbon isotope excursion with δ13C values reaching a nadir of ~ − 6‰ from the Majiatun Formation in the Dalian Basin of the North China Craton dated between 950 and 920 Ma. The whole-rock 87Sr/86Sr ratios of limestone and dolostone are as low as ~0.7055, which is compatible with the Tonian age of the global carbonate curve. Identification of the Majiatun anomaly thus fills the critical gap in carbon isotopes and implies the onset of Neoproterozoic carbon cycle volatility ~130 m.y. earlier than previously thought. Now 5 negative carbon isotope excursions occur with increasing amplitude throughout Neoproterozoic time, implying deeper roots for the biogeochemical processes that may have causally led to late Neoproterozoic snowball glaciation, oxygenation, and biological innovation.