We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
The First Large Absorption Survey in H i (FLASH) is a large-area radio survey for neutral hydrogen in and around galaxies in the intermediate redshift range $0.4\lt z\lt1.0$, using the 21-cm H i absorption line as a probe of cold neutral gas. The survey uses the ASKAP radio telescope and will cover 24,000 deg$^2$ of sky over the next five years. FLASH breaks new ground in two ways – it is the first large H i absorption survey to be carried out without any optical preselection of targets, and we use an automated Bayesian line-finding tool to search through large datasets and assign a statistical significance to potential line detections. Two Pilot Surveys, covering around 3000 deg$^2$ of sky, were carried out in 2019-22 to test and verify the strategy for the full FLASH survey. The processed data products from these Pilot Surveys (spectral-line cubes, continuum images, and catalogues) are public and available online. In this paper, we describe the FLASH spectral-line and continuum data products and discuss the quality of the H i spectra and the completeness of our automated line search. Finally, we present a set of 30 new H i absorption lines that were robustly detected in the Pilot Surveys, almost doubling the number of known H i absorption systems at $0.4\lt z\lt1$. The detected lines span a wide range in H i optical depth, including three lines with a peak optical depth $\tau\gt1$, and appear to be a mixture of intervening and associated systems. Interestingly, around two-thirds of the lines found in this untargeted sample are detected against sources with a peaked-spectrum radio continuum, which are only a minor (5–20%) fraction of the overall radio-source population. The detection rate for H i absorption lines in the Pilot Surveys (0.3 to 0.5 lines per 40 deg$^2$ ASKAP field) is a factor of two below the expected value. One possible reason for this is the presence of a range of spectral-line artefacts in the Pilot Survey data that have now been mitigated and are not expected to recur in the full FLASH survey. A future paper in this series will discuss the host galaxies of the H i absorption systems identified here.
With the rapid expansion of the Infection Prevention Control/Healthcare Epidemiology (IPC/HE) fields over recent decades, the pivotal roles of IPC/HE in hospital regulation, quality improvement, patient safety, and healthcare finances have become increasingly apparent. Consequently, the demand for effective IPC/HE leaders has surged.1,2 Training in IPC/HE is essential for all infectious diseases (ID) fellows (both adult and pediatric), including those planning a career in hospital epidemiology as well as those planning to focus on general ID, transplant, HIV, etc. ID fellows, however, have historically felt ill-prepared in IPC/HE. Joiner et al’s survey highlighted this gap, revealing that only half of respondents felt adequately trained in infection control, despite half of them participating in infection control in their practice.3 IPC/HE fellow education is not currently standardized, and most IPC/HE training is led by individual mentors and healthcare facilities.
The stars of the Milky Way carry the chemical history of our Galaxy in their atmospheres as they journey through its vast expanse. Like barcodes, we can extract the chemical fingerprints of stars from high-resolution spectroscopy. The fourth data release (DR4) of the Galactic Archaeology with HERMES (GALAH) Survey, based on a decade of observations, provides the chemical abundances of up to 32 elements for 917 588 stars that also have exquisite astrometric data from the Gaia satellite. For the first time, these elements include life-essential nitrogen to complement carbon, and oxygen as well as more measurements of rare-earth elements critical to modern-life electronics, offering unparalleled insights into the chemical composition of the Milky Way. For this release, we use neural networks to simultaneously fit stellar parameters and abundances across the whole wavelength range, leveraging synthetic grids computed with Spectroscopy Made Easy. These grids account for atomic line formation in non-local thermodynamic equilibrium for 14 elements. In a two-iteration process, we first fit stellar labels to all 1 085 520 spectra, then co-add repeated observations and refine these labels using astrometric data from Gaia and 2MASS photometry, improving the accuracy and precision of stellar parameters and abundances. Our validation thoroughly assesses the reliability of spectroscopic measurements and highlights key caveats. GALAH DR4 represents yet another milestone in Galactic archaeology, combining detailed chemical compositions from multiple nucleosynthetic channels with kinematic information and age estimates. The resulting dataset, covering nearly a million stars, opens new avenues for understanding not only the chemical and dynamical history of the Milky Way but also the broader questions of the origin of elements and the evolution of planets, stars, and galaxies.
The description and delineation of trematode species is a major ongoing task. Across the field there has been, and currently still is, great variation in the standard of this work and in the sophistication of the proposal of taxonomic hypotheses. Although most species are relatively unambiguously distinct from their congeners, many are either morphologically very similar, including the major and rapidly growing component of cryptic species, or are highly variable morphologically despite little to no molecular variation for standard DNA markers. Here we review challenges in species delineation in the context provided to us by the historical literature, and the use of morphological, geographical, host, and molecular data. We observe that there are potential challenges associated with all these information sources. As a result, we encourage careful proposal of taxonomic hypotheses with consideration for underlying species concepts and frank acknowledgement of weaknesses or conflict in the data. It seems clear that there is no single source of data that provides a wholly reliable answer to our taxonomic challenges but that nuanced consideration of information from multiple sources (the ‘integrated approach’) provides the best possibility of developing hypotheses that will stand the test of time.
Objectives/Goals: The never in mitosis kinase (NEK) family regulates vital processes, namely cell cycle progression, but their potential as therapeutic targets in TNBC has not been fully explored. Our studies aim to develop a toolkit to investigate the functional roles of NEKs in pathologies including carcinogenesis. Methods/Study Population: To assess differential NEK expression in normal and tumor tissues and correlation of gene expression with patient survival, we used Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan–Meier Plotter (KMPlot) pan-cancer analysis, respectively. Basal NEK protein levels were determined by immunoblot across a panel of cell lines, including breast cancer, osteosarcoma, hepatocellular carcinoma, and non-cancerous cells, to identify appropriate systems for evaluation of NEK function. Doxycycline-inducible cell lines were generated by transduction with lentiviral stocks of NEK shRNA and overexpression constructs and antibiotic selection. Expression was analyzed by qPCR and immunoblot. Results/Anticipated Results: Expression of NEK2, 4, 5, 6, 8, and 11 was higher in breast tumors compared to normal tissue by GEPIA analysis. Further examination using KMPlot showed a correlation between elevated NEK6 expression and decreased overall survival in patients with aggressive cancers. As an initial proof-of-concept study, we analyzed NEK6 protein expression in breast cancer cells. Levels of NEK6 were elevated in TNBC cells (MDA-MB-231) compared to hormone receptor positive (HR+) breast cancer cells (MCF7). Using complementary approaches to investigate the functional role of NEK6 in breast cancer, we depleted NEK6 expression using shRNAs in TNBC cells and expressed NEK6 in HR+ cells Discussion/Significance of Impact: Because kinase dysregulation promotes oncogenesis and metastasis, targeting kinases is a key strategy in therapeutic development. A NEK-specific molecular toolkit allows researchers to elucidate NEK functions and contributions to carcinogenesis, promoting advancement of novel therapies.
This study is the first to attempt to isolate a relationship between cognitive activity and equilibration to a Nash Equilibrium. Subjects, while undergoing fMRI scans of brain activity, participated in second price auctions against a single competitor following predetermined strategy that was unknown to the subject. For this auction there is a unique strategy that will maximize the subjects’ earnings, which is also a Nash equilibrium of the associated game theoretic model of the auction. As is the case with all games, the bidding strategies of subjects participating in second price auctions most often do not reflect the equilibrium bidding strategy at first but with experience, typically exhibit a process of equilibration, or convergence toward the equilibrium. This research is focused on the process of convergence.
In the data reported here subjects participated in sixteen auctions, after which all subjects were told the strategy that will maximize their revenues, the theoretical equilibrium. Following that announcement, sixteen more auctions were performed. The question posed by the research concerns the mental activity that might accompany equilibration as it is observed in the bidding behavior. Does brain activation differ between being equilibrated and non-equilibrated in the sense of a bidding strategy? If so, are their differences in the location of activation during and after equilibration? We found significant activation in the frontal pole especially in Brodmann's area 10, the anterior cingulate cortex, the amygdala and the basal forebrain. There was significantly more activation in the basal forebrain and the anterior cingulate cortex during the first sixteen auctions than in the second sixteen. The activity in the amygdala shifted from the right side to the left after the solution was given.
Increasing daylight exposure might be a simple way to improve mental health. However, little is known about daylight-symptom associations in depressive disorders.
Methods
In a subset of the Australian Genetics of Depression Study (N = 13,480; 75% female), we explored associations between self-reported number of hours spent in daylight on a typical workday and free day and seven symptom dimensions: depressive (overall, somatic, psychological); hypo-manic-like; psychotic-like; insomnia; and daytime sleepiness. Polygenic scores for major depressive disorder (MDD); bipolar disorder (BD); and schizophrenia (SCZ) were calculated. Models were adjusted for age, sex, shift work status, employment status, season, and educational attainment. Exploratory analyses examined age-stratified associations (18–24 years; 25–34 years; 35–64 years; 65 and older). Bonferroni-corrected associations (p < 0.004) are discussed.
Results
Adults with depression reported spending a median of one hour in daylight on workdays and three hours on free days. More daylight exposure on workdays and free days was associated with lower depressive (overall, psychological, somatic) and insomnia symptoms (p’s<0.001), but higher hypo-manic-like symptoms (p’s<0.002). Genetic loading for MDD and SCZ were associated with less daylight exposure in unadjusted correlational analyses (effect sizes were not meaningful). Exploratory analyses revealed age-related heterogeneity. Among 18–24-year-olds, no symptom dimensions were associated with daylight. By contrast, for the older age groups, there was a pattern of more daylight exposure and lower insomnia symptoms (p < 0.003) (except for 25–34-year-olds on free days, p = 0.019); and lower depressive symptoms with more daylight on free days, and to some extent workdays (depending on the age-group).
Conclusions
Exploration of the causal status of daylight in depression is warranted.
Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
The opportunity to increase soybean yield has prompted Illinois farmers to plant soybean earlier than historical norms. Extending the growing season with an earlier planting date might alter the relationship between soybean growth and weed emergence timings, potentially altering the optimal herbicide application timings to minimize crop yield loss due to weed interference and ensure minimal weed seed production. The objective of this research was to examine various herbicide treatments applied at different timings and rates to assess the effect on weed control and yield in early-planted soybean. Field experiments were conducted in 2021 at three locations across central Illinois to determine effective chemical strategies for weed management in early-planted soybean. PRE treatments consisted of a S-metolachlor + metribuzin premix applied at planting or just prior to soybean emergence at 0.5X (883 + 210 g ai ha−1) or 1X (1,766 + 420 g ai ha−1) label-recommended rates. POST treatments were applied when weeds reached 10 cm tall and consisted of 1X rates of glufosinate (655 g ai ha−1) + glyphosate (1,260 g ae ha−1) + ammonium sulfate, without or with pyroxasulfone at a 0.5X (63 g ai ha−1) or 1X (126 g ai ha−1) rate. Treatments comprising both a full rate of PRE followed by a POST resulted in the greatest and most consistent weed control at the final evaluation timing. The addition of pyroxasulfone to POST treatments did not consistently reduce late-season weed emergence. The lack of a consistent effect by pyroxasulfone could be attributed to suppression of weeds by soybean canopy closure due to earlier soybean development. The full rate of PRE extended the timing of POST application 2 to 3 wk for all treatments at all locations except Urbana. Full-rate PRE treatments also reduced the time between the POST application and soybean canopy closure. Overall, a full-rate PRE reduced early-season weed interference and minimized soybean yield loss due to weed interference.
Past hydrogeological processes and human impacts may exert substantial memory effects on today’s groundwater systems. Thorough characterization of such long-term processes is required for scientists and policymakers to predict the hydrogeological impacts of land management options. Especially in data-scarce areas, historical data are essential to unravel long-term hydrogeological processes, which could not be identified by short-term fieldwork or model simulations alone. However, historical data are often overlooked or only used as background information in most hydrogeological studies. We show that the combination of historical reports and quantitative data yields major insights in the hydrogeological system of Curaçao, a small semi-arid Caribbean island. Reconstructing the island’s groundwater conditions over the past 500 years revealed that deforestation and excessive abstraction has had a detrimental effect on the island’s groundwater reserves. Historical notes and data revealed major signs of seawater intrusion, especially during abstraction peaks in the island’s industrial era. Intrusion effects are still observed locally on the island today, but additional groundwater recharge by waste water has caused freshening elsewhere. We hypothesize that the observed aquifer replenishment locally enhances submarine groundwater discharge, flushing accumulated nutrients and pollutants towards Curaçao’s fringing coral reefs. We expect that this study’s insights motivate more hydrogeologists to use historical reports and data in future studies.
Childhood sexual abuse (CSA) and emotional maltreatment are salient risk factors for the development of major depressive disorder (MDD) in women. However, the type- and timing-specific effects of emotional maltreatment experienced during adolescence on future depressive symptomatology in women with CSA have not been explored. The goal of this study was to fill this gap.
Methods
In total, 203 women (ages 20–32) with current depressive symptoms and CSA (MDD/CSA), remitted depressive symptoms and CSA (rMDD/CSA), and current depressive symptoms without CSA (MDD/no CSA) were recruited from the community and completed self-report measures. Depressive symptoms were assessed using the Beck Depression Inventory (BDI-II) and a detailed maltreatment history was collected using the Maltreatment and Abuse Chronology of Exposure (MACE). Differences in maltreatment exposure characteristics, including multiplicity and severity of maltreatment, as well as the chronologies of emotional maltreatment subtypes were compared among groups. A random forest machine-learning algorithm was utilized to assess the impact of exposure to emotional maltreatment subtypes at specific ages on current depressive symptoms.
Results
MDD/CSA women reported greater prevalence and severity of emotional maltreatment relative to rMDD/CSA and MDD/no CSA women [F(2,196) = 9.33, p < 0.001], specifically from ages 12 to 18. The strongest predictor of current depressive symptoms was parental verbal abuse at age 18 for both MDD/CSA women (variable importance [VI] = 1.08, p = 0.006) and MDD/no CSA women (VI = 0.68, p = 0.004).
Conclusions
Targeting emotional maltreatment during late adolescence might prove beneficial for future intervention efforts for MDD following CSA.
Objectives: To evaluate the effect and safety of Cannabidiol (CBD) on behavioral and psychological symptoms in elderly with Vascular dementia (VD).
Methods: Double- blind, randomized, placebo-controlled clinical trial involving elderly patients with VD at the psychogeriatrics and vascular dementia outpatient clinic at Hospital das Clínicas de Ribeirão Preto. The intervention evaluated was the use of CBD 300mg/day compared to placebo. The instruments used are: Neuropsychiatric Inventory, Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression Scale, Side Effects Scale, Mini- Mental State Examination, Brief Cognitive Screening Battery, Katz Index of Independence in Activities of Daily Living, Lawton Instrumental Activities of Daily Living Scale, Informant Questionnaire on Cognitive Decline in the Elderly, Zarit Burden Inventory. The included participants were assessed at the beginning of the study (baseline assessment), in the first, second and fourth weeks after the start of the clinicaltrial.
Results: 30 participants were included. The mixed ANOVA with repeated measures showed that there is an effect of the interaction time and group (F (2.12; 59.43) = 4.02; p < 0.05; ηp2 = 0.13) on the total score of the brief scale psychiatric assessment and neuropsychiatric inventory (F (1.58; 44.31) = 3.61; p =0.05; ηp2 = 0.11). The mixed ANOVA of repeated measures showed no effect of the interaction of time and group for the mini-mental state examination, brief cognitive screening battery. Adverse effects were mild and transient, and similar to the placebo group.
Conclusions: In this study, cannabidiol reduced psychological and behavioral symptoms in patients with vascular dementia. Future studies with larger samples are needed to confirm the findings. (F(1.58;44.31) = 3.61; p =0.05; ηp2 = 0.11). The mixed ANOVA of repeated measures showed no effect of the interaction of time and group for the mini-mental state examination, brief cognitive screening battery. Adverse effects were mild and transient, and similar to the placebo group.
In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.
Methods:
A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.
Results:
We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.
Conclusion:
The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.
Dioctophyme renale, the giant kidney worm, is a nematode related to Trichuris sp and is distributed worldwide. These parasites locate in the kidney of their definitive hosts (mainly belonging to the order Carnivora) and have an indirect life cycle with an annelid as the main intermediate host. Humans are rarely affected, but in those that are, 1 or both kidneys are destroyed. In South America, D. renale is widespread in riparian regions where changing climatic conditions, environmental degradation, and compromised sanitation are increasing the risk of distribution of this parasite, including humans. Here, we provide the descriptions of the genetic diversity of the parasite in the region by analysing 73 adult D. renale samples collected from domestic and wild carnivores. The most common hosts were (Canis lupus familiaris) and maned wolf (Chrysocyon brachyurus Fam. Canidae) among domestic and wild carnivores, respectively. This work shows the descriptions of the genetic diversity of this parasite complementing molecular methods and classical and probabilistic phylogeography. Our results strongly suggest that this parasite has been present on the continent long enough to develop local genetic variants. Also, the phylogenies show transmission between localities and bidirectional transmission between domestic and wild species. We now have new tools to understand the ecological dynamics of this parasite such as molecular markers to study its genetic diversity as well as for identification and reporting in cryptic cases.
Selenium (Se) deficiency among populations in Ethiopia is consistent with low concentrations of Se in soil and crops that could be addressed partly by Se-enriched fertilisers. This study examines the disease burden of Se deficiency in Ethiopia and evaluates the cost-effectiveness of Se agronomic biofortification. A disability-adjusted life years (DALY) framework was used, considering goiter, anaemia, and cognitive dysfunction among children and women. The potential efficiency of Se agronomic biofortification was calculated from baseline crop composition and response to Se fertilisers based on an application of 10 g/ha Se fertiliser under optimistic and pessimistic scenarios. The calculated cost per DALY was compared against gross domestic product (GDP; below 1–3 times national GDP) to consider as a cost-effective intervention. The existing national food basket supplies a total of 28·2 µg of Se for adults and 11·3 µg of Se for children, where the risk of inadequate dietary Se reaches 99·1 %–100 %. Cereals account for 61 % of the dietary Se supply. Human Se deficiency contributes to 0·164 million DALYs among children and women. Hence, 52 %, 43 %, and 5 % of the DALYs lost are attributed to anaemia, goiter, and cognitive dysfunction, respectively. Application of Se fertilisers to soils could avert an estimated 21·2–67·1 %, 26·6–67·5 % and 19·9–66·1 % of DALY via maize, teff and wheat at a cost of US$129·6–226·0, US$149·6–209·1 and US$99·3–181·6, respectively. Soil Se fertilisation of cereals could therefore be a cost-effective strategy to help alleviate Se deficiency in Ethiopia, with precedents in Finland.
Clostridioides difficile infection (CDI) may be misdiagnosed if testing is performed in the absence of signs or symptoms of disease. This study sought to support appropriate testing by estimating the impact of signs, symptoms, and healthcare exposures on pre-test likelihood of CDI.
Methods:
A panel of fifteen experts in infectious diseases participated in a modified UCLA/RAND Delphi study to estimate likelihood of CDI. Consensus, defined as agreement by >70% of panelists, was assessed via a REDCap survey. Items without consensus were discussed in a virtual meeting followed by a second survey.
Results:
All fifteen panelists completed both surveys (100% response rate). In the initial survey, consensus was present on 6 of 15 (40%) items related to risk of CDI. After panel discussion and clarification of questions, consensus (>70% agreement) was reached on all remaining items in the second survey. Antibiotics were identified as the primary risk factor for CDI and grouped into three categories: high-risk (likelihood ratio [LR] 7, 93% agreement among panelists in first survey), low-risk (LR 3, 87% agreement in first survey), and minimal-risk (LR 1, 71% agreement in first survey). Other major factors included new or unexplained severe diarrhea (e.g., ≥ 10 liquid bowel movements per day; LR 5, 100% agreement in second survey) and severe immunosuppression (LR 5, 87% agreement in second survey).
Conclusion:
Infectious disease experts concurred on the importance of signs, symptoms, and healthcare exposures for diagnosing CDI. The resulting risk estimates can be used by clinicians to optimize CDI testing and treatment.
Diagnostic criteria for major depressive disorder allow for heterogeneous symptom profiles but genetic analysis of major depressive symptoms has the potential to identify clinical and etiological subtypes. There are several challenges to integrating symptom data from genetically informative cohorts, such as sample size differences between clinical and community cohorts and various patterns of missing data.
Methods
We conducted genome-wide association studies of major depressive symptoms in three cohorts that were enriched for participants with a diagnosis of depression (Psychiatric Genomics Consortium, Australian Genetics of Depression Study, Generation Scotland) and three community cohorts who were not recruited on the basis of diagnosis (Avon Longitudinal Study of Parents and Children, Estonian Biobank, and UK Biobank). We fit a series of confirmatory factor models with factors that accounted for how symptom data was sampled and then compared alternative models with different symptom factors.
Results
The best fitting model had a distinct factor for Appetite/Weight symptoms and an additional measurement factor that accounted for the skip-structure in community cohorts (use of Depression and Anhedonia as gating symptoms).
Conclusion
The results show the importance of assessing the directionality of symptoms (such as hypersomnia versus insomnia) and of accounting for study and measurement design when meta-analyzing genetic association data.
GX is a code designed to solve the nonlinear gyrokinetic system for low-frequency turbulence in magnetized plasmas, particularly tokamaks and stellarators. In GX, our primary motivation and target is a fast gyrokinetic solver that can be used for fusion reactor design and optimization along with wide-ranging physics exploration. This has led to several code and algorithm design decisions, specifically chosen to prioritize time to solution. First, we have used a discretization algorithm that is pseudospectral in the entire phase space, including a Laguerre–Hermite pseudospectral formulation of velocity space, which allows for smooth interpolation between coarse gyrofluid-like resolutions and finer conventional gyrokinetic resolutions and efficient evaluation of a model collision operator. Additionally, we have built GX to natively target graphics processors (GPUs), which are among the fastest computational platforms available today. Finally, we have taken advantage of the reactor-relevant limit of small $\rho _*$ by using the radially local flux-tube approach. In this paper we present details about the gyrokinetic system and the numerical algorithms used in GX to solve the system. We then present several numerical benchmarks against established gyrokinetic codes in both tokamak and stellarator magnetic geometries to verify that GX correctly simulates gyrokinetic turbulence in the small $\rho _*$ limit. Moreover, we show that the convergence properties of the Laguerre–Hermite spectral velocity formulation are quite favourable for nonlinear problems of interest. Coupled with GPU acceleration, which we also investigate with scaling studies, this enables GX to be able to produce useful turbulence simulations in minutes on one (or a few) GPUs and higher fidelity results in a few hours using several GPUs. GX is open-source software that is ready for fusion reactor design studies.