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Background: Bipolar disorder (BD) is a clinical risk factor for Alzheimer’s disease (AD). Apolipoprotein E ε4 ( APOE ε4), a genetic risk factor for AD, has been associated with brain structure and neurocognition in healthy youth. Aims: We evaluated whether there was an association between APOE ε4 with neurostructure and neurocognition in youth with BD. Methods: Participants included 150 youth (78 BD:19 ε4-carriers, 72 controls:17 ε4-carriers). 3T-magnetic resonance imaging yielded measures of cortical thickness, surface area, and volume. Regions-of-interest (ROI) and vertex-wise analyses of the cortex were conducted. Neurocognitive tests of attention and working memory were examined. Results: Vertex-wise analyses revealed clusters with a diagnosis-by- APOE ε4 interaction effect for surface area ( p = 0.002) and volume ( p = 0.046) in pars triangularis (BD ε4 -carriers > BD noncarriers), and surface area ( p = 0.03) in superior frontal gyrus (controls ε4 -carriers > other groups). ROI analyses were not significant. A significant interaction effect for working memory ( p = 0.001) appeared to be driven by nominally poorer performance in BD ε4 -carriers but not control ε4 -carriers; however, post hoc contrasts were not significant. Conclusions: APOE ε4 was associated with larger neurostructural metrics in BD and controls, however, the regional association of APOE ε4 with neurostructure differed between groups. The role of APOE ε4 on neurodevelopmental processes is a plausible explanation for the observed differences. Future studies should evaluate the association of APOE ε4 with pars triangularis and its neurofunctional implications among youth with BD.

Ribosomes are macromolecular machines that are globally required for the translation of all proteins in all cells. Ribosome biogenesis, which is essential for cell growth, proliferation and survival, commences with transcription of a variety of RNAs by RNA Polymerases I and III. RNA Polymerase I (Pol I) transcribes ribosomal RNA (rRNA), while RNA Polymerase III (Pol III) transcribes 5S ribosomal RNA and transfer RNAs (tRNA) in addition to a wide variety of small non-coding RNAs. Interestingly, despite their global importance, disruptions in Pol I and Pol III function result in tissue-specific developmental disorders, with craniofacial anomalies and leukodystrophy/neurodegenerative disease being among the most prevalent. Furthermore, pathogenic variants in genes encoding subunits shared between Pol I and Pol III give rise to distinct syndromes depending on whether Pol I or Pol III function is disrupted. In this review, we discuss the global roles of Pol I and III transcription, the consequences of disruptions in Pol I and III transcription, disorders arising from pathogenic variants in Pol I and Pol III subunits, and mechanisms underpinning their tissue-specific phenotypes.

Background: Metabolic and vascular risk factors (MVRF) are associated with neurodegeneration and poor cognition. There is a need to better understand the impact of these risk factors on brain health in the decades that precede cognitive impairment. Longitudinal assessments can provide new insight regarding changes in MVRFs that are related to brain imaging features. Objective: To investigate whether longitudinal changes in MVRF spanning up to 25 years would be associated with midlife brain volume and cognition. Methods: Participants were from the CARDIA study (N = 467, age at year 25 = 50.6±3.4, female/male = 232/235, black/white = 161/306). Three models were developed, each designed to capture change over time; however, we were primarily interested in the average real variability (ARV) as a means of quantifying MVRF variability across all available assessments. Results: Multivariate partial least squares that used ARV metrics identified two significant latent variables (partial correlations ranged between 0.1 and 0.26, p

Compared with their 3D counterparts, 2D hybrid organic-inorganic halide perovskites (HOIPs) exhibit enhanced chemical stabilities and superior optoelectronic properties, which can be further tuned by the application of external pressure. Here, we report the first high-pressure study on CMA

The connection between vascular and brain metrics is well-studied in older adults, but neglected in youth and in psychiatric populations at increased cardiovascular risk. We therefore examined the association of retinal vascular caliber with cerebral blood flow (CBF) in adolescents with and without bipolar disorder (BD).Ninety-four adolescents (n = 48 BD, n = 46 controls) completed retinal fundus imaging, yielding estimates of arteriolar and venular diameter. Arterial spin labelling MRI was performed to measure CBF. We tested for associations between retinal vascular caliber and CBF in regions of interest; anterior cingulate cortex (ACC), middle frontal gyrus, and hippocampus in BD and controls separately. Complementary voxel-wise analyses were also performed.In the BD group, higher arteriovenous ratio (AVR) was associated with greater ACC CBF (β = 0.34, pLimited sample size; young, medically healthy sample limits signal detection; cross-sectional design.This study reveals that higher AVR is associated with higher regional CBF in adolescents with BD. Present findings advance understanding of potential neurofunctional mechanisms linking retinal vascular caliber with psychiatric diagnoses. This proof-of-concept study was designed to generate initial insights to guide future studies focusing on the vascular-brain connection in youth and in psychiatry.

OBJECTIVE Type 2 diabetes (T2D) increases dementia risk, but clear evidence to recommend interventions that can mitigate that risk remains lacking. This population-based retrospective cohort study aimed to determine whether new use of sodium–glucose cotransporter 2 (SGLT2) inhibitors compared with dipeptidyl peptidase 4 (DPP-4) inhibitors was associated with lower dementia risk. RESEARCH DESIGN AND METHODS Ontario residents aged ≥66 years who were new users of an SGLT2 inhibitor or a DPP-4 inhibitor from 1 July 2016 to 31 March 2021 entered the cohort. Incident dementia was identified using a validated algorithm for Alzheimer’s disease and related dementias. Propensity score–weighted Cox proportional hazards models were used to obtain adjusted hazard ratios (aHR) and CIs for time to incident dementia. To address reverse causality and disease latency, the observation window started at 1-year lag time from cohort entry. The primary analysis followed intention-to-treat exposure definition, and a secondary as-treated analysis was performed. RESULTS Among 106,903 individuals, SGLT2 inhibitors compared with DPP-4 inhibitors were associated with lower risk of dementia (14.2/1,000 person-years; aHR 0.80 [95% CI 0.71–0.89]) over a mean follow-up of 2.80 years from cohort entry. When stratified by different SGLT2 inhibitors, dapagliflozin exhibited the lowest risk (aHR 0.67 [95% CI 0.53–0.84]), followed by empagliflozin (aHR 0.78 [95% CI 0.69–0.89]), whereas canagliflozin showed no association (aHR 0.96 [95% CI 0.80–1.16]). The as-treated analysis observed a larger association (aHR 0.66 [95% CI 0.57–0.76]) than the intention-to-treat analysis. CONCLUSIONS SGLT2 inhibitors showed an association with lower dementia risk in older people with T2D. Randomized controlled trials are warranted.

Pasture-based and grass-fed branding are often associated with consumer perceptions of improved human health, environmental performance and animal welfare. Here, to examine the impacts of dairy production in detail, we contrasted global observational (n = 156) data for nitrogen and phosphorus losses from land by the duration of outdoor livestock grazing in confined, grazed and hybrid systems. Observational nitrogen losses for confined systems were lowest on a productivity—but not area—basis. No differences were noted for phosphorus losses between the systems. Modelling of the three dairy systems in New Zealand, the United States and the Netherlands yielded similar results. We found insufficient evidence that grazed dairy systems have lower nutrient losses than confined ones, but trade-offs exist between systems at farm scale. The use of a hybrid system may allow for uniform distribution of stored excreta, controlled dietary intake, high productivity and mitigation of animal welfare issues arising from climatic extremes.

MRI‐derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta‐Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis‐driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large‐scale meta‐ and mega‐analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large‐scale, collaborative studies of mental illness., This review discusses the major challenges facing neuroimaging research of bipolar disorder and highlights the major accomplishments, ongoing challenges and future goals of the ENIGMA Bipolar Disorder Working Group.

We present the highest fidelity spectrum to date of a planetary-mass object. VHS 1256 b is a M Jup widely separated (∼8″, a = 150 au), young, planetary-mass companion that shares photometric colors and spectroscopic features with the directly imaged exoplanets HR 8799c, d, and e. As an L-to-T transition object, VHS 1256 b exists along the region of the color–magnitude diagram where substellar atmospheres transition from cloudy to clear. We observed VHS 1256 b with JWST's NIRSpec IFU and MIRI MRS modes for coverage from 1 to 20 μm at resolutions of ∼1000–3700. Water, methane, carbon monoxide, carbon dioxide, sodium, and potassium are observed in several portions of the JWST spectrum based on comparisons from template brown dwarf spectra, molecular opacities, and atmospheric models. The spectral shape of VHS 1256 b is influenced by disequilibrium chemistry and clouds. We directly detect silicate clouds, the first such detection reported for a planetary-mass companion.

The current timeline for expected forcing datasets to be updated for the Coupled Model Intercomparison Project (CMIP). Includes updates expected during the CMIP6Plus project, and those for CMIP7. Datasets included are: Anthropogenic short-lived climate forcings (including CO2and CH4) Open biomass burning emissions Land use Greenhouse gas historical concentrations Stratospheric volcanic SO2 emissions and aerosol properties Ozone Nitrogen deposition Solar AMIP boundary forcing Aerosol optical properties/MACv2-SP&nbsp

It is important to understanding the mechanism behind multidecadal changes in North Atlantic ocean heat storage as these directly impact the climate of the surrounding continents. We construct a multidecadal upper ocean heat budget for the North Atlantic for the period 1950 to 2020 based on multiple observational datasets and a state of the art forced global ocean model. On multidecadal timescales ocean heat transport convergence is the dominant term in all regions of the North Atlantic. In the subpolar region (north of 45N) the heat transport convergence is largely explained by anomalous geostrophic currents acting on the mean temperature gradient. The timescale and spatial distribution of the anomalous geostrophic currents are consistent with basin scale ‘thermal’ Rossby waves propagating westwards/northwestwards in the subpolar gyre. Using a forced ocean model we link the ocean heat transport convergence with variations in the Atlantic Meridional Overturning Circulation., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

While radial velocity surveys have demonstrated that the population of gas giants peaks around $3~\text{au}$, the most recent high-contrast imaging surveys have only been sensitive to planets beyond $\sim~10~\text{au}$. Sensitivity at small angular separations from stars is currently limited by the variability of the point spread function. We demonstrate how moderate-resolution integral field spectrographs can detect planets at smaller separations ($\lesssim~0.3$ arcseconds) by detecting the distinct spectral signature of planets compared to the host star. Using OSIRIS ($R$ $\approx$ 4000) at the W. M. Keck Observatory, we present the results of a planet search via this methodology around 20 young targets in the Ophiuchus and Taurus star-forming regions. We show that OSIRIS can outperform high-contrast coronagraphic instruments equipped with extreme adaptive optics and non-redundant masking in the $0.05-0.3$ arcsecond regime. As a proof of concept, we present the $34\sigma$ detection of a high-contrast M dwarf companion at $\approx0.1$" with a flux ratio of $\approx0.92\%$ around the field F2 star HD 148352. We developed an open-source Python package, breads, for the analysis of moderate-resolution integral field spectroscopy data in which the planet and the host star signal are jointly modeled. The diffracted starlight continuum is forward-modeled using a spline model, which removes the need for prior high-pass filtering or continuum normalization. The code allows for analytic marginalization of linear hyperparameters, simplifying posterior sampling of other parameters (e.g., radial velocity, effective temperature). This technique could prove very powerful when applied to integral field spectrographs like NIRSpec on the JWST and other upcoming first-light instruments on the future Extremely Large Telescopes., Comment: Accepted for publication in the Astronomical Journal on May 12, 2023

Rapid antigen screening can be effective in identifying infectious individuals in occupational settings to reduce transmission and outbreaks. We report results from a pilot project at the Greater Toronto Airports Authority (GTAA) and describe the operationalization. Toronto Pearson is a large international airport encompassing over 400 employers and, pre-pandemic, with approximately 50,000 employees.An employee screening program was piloted between March 8 and May 28, 2021, to implement rapid antigen testing for asymptomatic employees. Recruitment targeted enrolment of 400 employees and yielded participation of 717 from 58 companies. Employees were recommended to book three times per week for nasal swabs on site, and were tested on the Abbot PanbioA total of 5117 tests were performed on 717 individuals over 12 weeks; 5091 tests were negative (99.5%), and 22 individuals tested positive (3.1% positivity rate). One hundred twenty-four (17%) completed the post-participation survey. All respondents reported that testing did not change their behaviour at work with respect to public health recommendations, and only 1 (1%) reported behaviour change outside of work (socializing with family) as a result of the program.This pilot program identified 22 (3.1%) potentially infectious employees. Onsite testing was feasible and highly accepted by this group of employees who completed the survey. Education resulted in reasonable uptake and no substantial change in behaviour, although the survey response rate may limit generalizability. Home-based testing may facilitate larger recruitment.RéSUMé: LIEU: Le dépistage antigénique rapide peut être efficace pour repérer les personnes infectieuses en milieu de travail afin de réduire la transmission et les éclosions. Nous rendons compte des résultats d’un projet pilote mené par l’Autorité aéroportuaire du Grand Toronto (GTAA) et nous en décrivons l’opérationnalisation. L’aéroport Toronto Pearson est un vaste aéroport international qui compte plus de 400 employeurs et, avant la pandémie, environ 50 000 employés. INTERVENTION: Un programme de dépistage au travail a fait l’objet d’un projet pilote entre le 8 mars et le 28 mai 2021 pour mettre en œuvre le dépistage antigénique rapide chez les employés asymptomatiques. Le recrutement visait l’inscription de 400 employés et a donné lieu à une participation de 717 personnes dans 58 entreprises. Il était recommandé aux employés de s’inscrire à un prélèvement nasal sur place trois fois par semaine; le test antigénique rapide d’Abbot Panbio

This is the first of three articles exploring the aspects of clinical care for children with rare neurological disorders including uncertainties old and new. The disruptive technologies of genomic sequencing and advanced therapeutics such as gene-based therapies offer parents of children with severe but rare neurological conditions for the first-time unprecedented opportunities for 'precision medicine'. At the same time, the realities of limited genomic diagnostic yields and not infrequent detection of variants of uncertain significance, lack of natural history study data and management guidelines for individually rare neurogenetic conditions, means that high pre-genomic test expectations are all too often replaced by an accumulation of new uncertainties. This can add to the chronic traumatic stress experienced by many families but may also have under-recognised impacts for their clinicians, contributing to 'burn-out' and attendant negative psychosocial impacts. This first article aims to address how clinicians might manage the accumulation of uncertainties to be more helpful to patients and their families. Moreover, it seeks to address how clinicians can move forward providing compassionate care to their patients and a little more consideration for themselves.

Most invasive lobular breast cancers (ILC) are of the luminal A subtype and are strongly hormone receptor–positive. Yet, ILC is relatively resistant to tamoxifen and associated with inferior long-term outcomes compared with invasive ductal cancers (IDC). In this study, we sought to gain mechanistic insights into these clinical findings that are not explained by the genetic landscape of ILC and to identify strategies to improve patient outcomes. A comprehensive analysis of the epigenome of ILC in preclinical models and clinical samples showed that, compared with IDC, ILC harbored a distinct chromatin state linked to gained recruitment of FOXA1, a lineage-defining pioneer transcription factor. This resulted in an ILC-unique FOXA1–estrogen receptor (ER) axis that promoted the transcription of genes associated with tumor progression and poor outcomes. The ILC-unique FOXA1–ER axis led to retained ER chromatin binding after tamoxifen treatment, which facilitated tamoxifen resistance while remaining strongly dependent on ER signaling. Mechanistically, gained FOXA1 binding was associated with the autoinduction of FOXA1 in ILC through an ILC-unique FOXA1 binding site. Targeted silencing of this regulatory site resulted in the disruption of the feed-forward loop and growth inhibition in ILC. In summary, ILC is characterized by a unique chromatin state and FOXA1–ER axis that is associated with tumor progression, offering a novel mechanism of tamoxifen resistance. These results underscore the importance of conducting clinical trials dedicated to patients with ILC in order to optimize treatments in this breast cancer subtype. Significance: A unique FOXA1–ER axis in invasive lobular breast cancer promotes disease progression and tamoxifen resistance, highlighting a potential therapeutic avenue for clinical investigations dedicated to this disease. See related commentary by Blawski and Toska, p. 3668

Clinical Practice Guidelines (CPGs) have been shown to improve healthcare services and clinical outcomes. However, they are useful resources only to the degree that they are developed according to the most rigorous standards. Multiple studies have demonstrated significant variability between CPGs with regard to specific indicators of quality. The Ordre des psychologues du Québec (OPQ), the College of psychologists of Quebec, has published several CPGs that are intended to provide empirically supported guidance for psychologists in the areas of assessment, diagnosis, general functioning, treatment and other decision-making support. The aim of this study was to evaluate the quality of these CPGs.The Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument was used to assess the quality of the CPGs.Our results show that although there have been some modest improvements in quality of the CPGs over time, there are important methodological inadequacies in all CPGs evaluated.The findings of this study demonstrate the need for more methodological rigour in CPGs development as such, recommendations to improve CPG quality are discussed.

White matter hyperintensities (WMHs) are emblematic of cerebral small vessel disease, yet effects on the brain have not been well characterized at midlife. Here, we investigated whether WMH volume is associated with brain network alterations in midlife adults. Two hundred and fifty-four participants from the Coronary Artery Risk Development in Young Adults study were selected and stratified by WMH burden into Lo-WMH (mean age = 50 ± 3.5 years) and Hi-WMH (mean age = 51 ± 3.7 years) groups of equal size. We constructed group-level covariance networks based on cerebral blood flow (CBF) and gray matter volume (GMV) maps across 74 gray matter regions. Through consensus clustering, we found that both CBF and GMV covariance networks partitioned into modules that were largely consistent between groups. Next, CBF and GMV covariance network topologies were compared between Lo- and Hi-WMH groups at global (clustering coefficient, characteristic path length, global efficiency) and regional (degree, betweenness centrality, local efficiency) levels. At the global level, there were no between-group differences in either CBF or GMV covariance networks. In contrast, we found between-group differences in the regional degree, betweenness centrality, and local efficiency of several brain regions in both CBF and GMV covariance networks. Overall, CBF and GMV covariance analyses provide evidence that WMH-related network alterations are present at midlife.

Alternatives to oils with high saturated fatty acid content are often liquid oils (high in unsaturated fatty acids) that have a modified structure created either through additives or processing. Emulsifiers are additives that can be used as structuring agents of liquid fats; this process results in products such as oleogels, which can broaden the applications of these oils. This study assessed and compared the effects of mono- and diglycerides at 3%, 5%, 7% and 10% w/w on the mechanical and thermal properties of high-oleic palm oil (HOPO) oleogels. HOPO was heated to 75 °C and mixed with mono- or diglycerides at those four concentrations. The thermomechanical properties of the melted oleogels were assessed using differential scanning calorimetry (DSC). The melted oleogels were cooled to final temperatures of 5 °C, 10 °C and 15 °C under identical cooling rates, after which a puncture test (via a texture analyzer) was used to assess their textures. Finally, polarized light microscopy was used to assess the mechanical changes induced through emulsifier addition. The results showed that the use of mono- and diglycerides significantly modified the thermal and mechanical properties of the oleogels. The addition of saturated monoglycerides promoted a higher-temperature nucleation stage that did not previously occur in HOPO. The onset crystallization temperature increased with the addition of diglycerides, promoting crystallization at higher temperatures of the high-melting fraction of HOPO. The hardness of the oleogel generally increased with emulsifier addition and a reduction of the temperature. The effect of the temperature on the hardness was significantly greater in the diglyceride oleogel than in the monoglyceride oleogel. This study shows that the addition of mono- and diglycerides allows companies to customize their formulations to achieve desired results that may not previously have been possible, thereby facilitating novel uses for these oils within the industry.

Thousands of oil and gas structures have been installed in the world's oceans over the past 70 years to meet the population's reliance on hydrocarbons. Over the last decade, there has been increased concern over how to handle decommissioning of this infrastructure when it reaches the end of its operational life. Complete or partial removal may or may not present the best option when considering potential impacts on the environment, society, technical feasibility, economy, and future asset liability. Re-purposing of offshore structures may also be a valid legal option under international maritime law where robust evidence exists to support this option. Given the complex nature of decommissioning offshore infrastructure, a global horizon scan was undertaken, eliciting input from an interdisciplinary cohort of 35 global experts to develop the top ten priority research needs to further inform decommissioning decisions and advance our understanding of their potential impacts. The highest research priorities included: (1) an assessment of impacts of contaminants and their acceptable environmental limits to reduce potential for ecological harm; (2) defining risk and acceptability thresholds in policy/governance; (3) characterising liability issues of ongoing costs and responsibility; and (4) quantification of impacts to ecosystem services. The remaining top ten priorities included: (5) quantifying ecological connectivity; (6) assessing marine life productivity; (7) determining feasibility of infrastructure re-use; (8) identification of stakeholder views and values; (9) quantification of greenhouse gas emissions; and (10) developing a transdisciplinary decommissioning decision-making process. Addressing these priorities will help inform policy development and governance frameworks to provide industry and stakeholders with a clearer path forward for offshore decommissioning. The principles and framework developed in this paper are equally applicable for informing responsible decommissioning of offshore renewable energy infrastructure, in particular wind turbines, a field that is accelerating rapidly.

This report provides a summary of the first CMIP Forcings drop-in sessions held on 7 June 2023 across two timeslots (05:00 UTC and 16:00 UTC) to support equitable global participation. These sessions aimed to facilitate community discussion on the development and use of forcing datasets. Each session was chaired by one of the CMIP Panel Co-chairs, John Dunne (GFDL/NOAA) and Helene Hewitt (Met Office) and led by theForcings Task Teamco-leads,Paul Durack(PCMDI/LLNL) andVaishali Naik(GFDL/NOAA), with input from the wider members of the task team. Participants were introduced to the task team's members and stakeholders together with the core goals they are seeking to address. Further, feedback received in the recent Future CMIP Forcings Community Survey was outlined and how the task team is addressing issues raised here, to deliver to CMIP7 and tackle longer term scientific challenges, before opening the session for an interactive dialogue with participants.

BACKGROUND: Conventional cerebrovascular reactivity (CVR) estimation has demonstrated that many brain diseases and/or conditions are associated with altered CVR. Despite the clinical potential of CVR, characterization of temporal features of a CVR challenge remains uncommon. This work is motivated by the need to develop CVR parameters that characterize individual temporal features of a CVR challenge.METHODS: Data were collected from 54 adults and recruited based on these criteria: (1) Alzheimer's disease diagnosis or subcortical Vascular Cognitive Impairment, (2) sleep apnea, and (3) subjective cognitive impairment concerns. We investigated signal changes in blood oxygenation level dependent (BOLD) contrast images with respect to hypercapnic and normocapnic CVR transition periods during a gas manipulation paradigm. We developed a model-free, non-parametric CVR metric after considering a range of responses through simulations to characterize BOLD signal changes that occur when transitioning from normocapnia to hypercapnia. The non-parametric CVR measure was used to examine regional differences across the insula, hippocampus, thalamus, and centrum semiovale. We also examined the BOLD signal transition from hypercapnia back to normocapnia.RESULTS: We found a linear association between isolated temporal features of successive CO 2 challenges. Our study concluded that the transition rate from hypercapnia to normocapnia was significantly associated with the second CVR response across all regions of interest ( p CONCLUSION: This study demonstrates that it is feasible to examine individual responses associated with normocapnic and hypercapnic transition periods of a BOLD-based CVR experiment. Studying these features can provide insight on between-subject differences in CVR.

Accreting protoplanets are windows into planet formation processes, and high-contrast differential imaging is an effective way to identify them. We report results from the Giant Accreting Protoplanet Survey (GAPlanetS), which collected Hα differential imagery of 14 transitional disk host stars with the Magellan Adaptive Optics System. To address the twin challenges of morphological complexity and point-spread function instability, GAPlanetS required novel approaches for frame selection and optimization of the Karhounen–Loéve Image Processing algorithm pyKLIP. We detect one new candidate, CS Cha “c,” at a separation of 68 mas and a modest Δmag of 2.3. We recover the HD 142527 B and HD 100453 B accreting stellar companions in several epochs, and the protoplanet PDS 70 c in 2017 imagery, extending its astrometric record by nine months. Though we cannot rule out scattered light structure, we also recover LkCa 15 “b,” at Hα; its presence inside the disk cavity, absence in Continuum imagery, and consistency with a forward-modeled point source suggest that it remains a viable protoplanet candidate. Through targeted optimization, we tentatively recover PDS 70 c at two additional epochs and PDS 70 b in one epoch. Despite numerous previously reported companion candidates around GAplanetS targets, we recover no additional point sources. Our moderate Hα contrasts do not preclude most protoplanets, and we report limiting Hα contrasts at unrecovered candidate locations. We find an overall detection rate of ∼36 − 22 + 26 % , considerably higher than most direct imaging surveys, speaking to both GAPlanetS’s highly targeted nature and the promise of Hα differential imaging for protoplanet identification.

Background: Abnormalities in cerebral blood flow (CBF) are common in bipolar disorder (BD). Despite known differences in CBF between healthy adolescent males and females, sex differences in CBF among adolescents with BD have never been studied. Objective: To examine sex differences in CBF among adolescents with BD versus healthy controls (HC). Methods: CBF images were acquired using arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) in 123 adolescents (72 BD: 30M, 42F; 51 HC: 22M, 29F) matched for age (13–20 years). Whole brain voxel-wise analysis was performed in a general linear model with sex and diagnosis as fixed factors, sex–diagnosis interaction effect, and age as a covariate. We tested for main effects of sex, diagnosis, and their interaction. Results were thresholded at cluster forming p = 0.0125, with posthoc Bonferroni correction (p = 0.05/4 groups). Results: A main effect of diagnosis (BD > HC) was observed in the superior longitudinal fasciculus (SLF), underlying the left precentral gyrus (F =10.24 (3), p < 0.0001). A main effect of sex (F > M) on CBF was detected in the precuneus/posterior cingulate cortex (PCC), left frontal and occipital poles, left thalamus, left SLF, and right inferior longitudinal fasciculus (ILF). No regions demonstrated a significant sex-by-diagnosis interaction. Exploratory pairwise testing in regions with a main effect of sex revealed greater CBF in females with BD versus HC in the precuneus/PCC (F = 7.1 (3), p < 0.01). Conclusion: Greater CBF in female adolescents with BD versus HC in the precuneus/PCC may reflect the role of this region in the neurobiological sex differences of adolescent-onset BD. Larger studies targeting underlying mechanisms, such as mitochondrial dysfunction or oxidative stress, are warranted.

We synthesize observational datasets and a state of the art forced global ocean model to construct a multidecadal upper ocean heat budget for the North Atlantic for the period 1950 to 2020. Using multiple independent estimates of the variables allows us to provide robust uncertainty estimates for each term. Time-varying ocean heat transport convergence dominates the budget on multidecadal timescales in all regions of the North Atlantic. In the subpolar region (north of 45N) we find that the heat transport convergence is dominated by geostrophic currents whereas in the subtropics (26-45N) advection by ageostrophic currents is also significant. The geostrophic advection is dominated (especially in the subpolar regions) by anomalous geostrophic currents acting on the mean temperature gradient. The timescale and spatial distribution of the anomalous geostrophic currents are consistent with basin scale ‘thermal’ Rossby waves propagating westwards/northwestwards in the subpolar gyre. Multidecadal changes in North Atlantic Changes in ocean heat storage directly affect the climate of the surrounding continents, and hence it is important to understanding the mechanism behind these.

The Gaia-Multi-Peak (GMP) technique can identify large numbers of dual or lensed active galactic nuclei (AGN) candidates at sub-arcsec separation, allowing us to study both multiple super-massive black holes (SMBH) in the same galaxy and rare, compact lensed systems. The observed samples can be used to test the predictions of the models of SMBH merging once 1) the selection function of the GMP technique is known, and 2) each system has been classified as dual AGN, lensed AGN, or AGN/star alignment. Here we show that the GMP selection is very efficient for separations above 0.15" when the secondary (fainter) object has magnitude G0.5 selected by the GMP technique, and compare this sample with other such systems from the literature, concluding that GMP can provide a large number of confirmed dual AGNs at separations below 7 kpc., 14 pages, submitted. Comments welcome

In many social species, intergroup aggression is a cooperative activity that produces public goods such as a safe and stable social environment and a home range containing the resources required to survive and reproduce. In this study, we investigate temporal variation in intergroup aggression in a growing population of colobus monkeys to ask a novel question: “Who stepped-up to produce these public goods when the competitive landscape changed?”. Both whole-group encounters and male incursions occurred more frequently as the population grew. Males and females were both more likely to participate in whole-group encounters when monopolizable food resources were available, indicating both sexes engaged in food defence. However, only females increasingly did so over time, suggesting that when intergroup competition intensified, it was females who increasingly invested in home range defence. Females were also more active in male incursions at high population densities, suggesting they also worked harder to maintain a safe and stable social environment over time. This is not to say that males were chronic free-riders when it came to maintaining public goods. Males consistently participated in the majority of intergroup interactions throughout the study period, indicating they may have lacked the capacity to invest more time and effort.

IntroductionRNA polymerase III (Pol III) is a critical enzymatic complex tasked with the transcription of ubiquitous non-coding RNAs including 5S rRNA and all tRNA genes. Despite the constitutive nature of this enzyme, hypomorphic biallelic pathogenic variants in genes encoding subunits of Pol III lead to tissue-specific features and cause a hypomyelinating leukodystrophy, characterized by a severe and permanent deficit in myelin. The pathophysiological mechanisms in POLR3- related leukodystrophy and specifically, how reduced Pol III function impacts oligodendrocyte development to account for the devastating hypomyelination seen in the disease, remain poorly understood.MethodsIn this study, we characterize how reducing endogenous transcript levels of leukodystrophy-associated Pol III subunits affects oligodendrocyte maturation at the level of their migration, proliferation, differentiation, and myelination.ResultsOur results show that decreasing Pol III expression altered the proliferation rate of oligodendrocyte precursor cells but had no impact on migration. Additionally, reducing Pol III activity impaired the differentiation of these precursor cells into mature oligodendrocytes, evident at both the level of OL-lineage marker expression and on morphological assessment, with Pol III knockdown cells displaying a drastically more immature branching complexity. Myelination was hindered in the Pol III knockdown cells, as determined in both organotypic shiverer slice cultures and co-cultures with nanofibers. Analysis of Pol III transcriptional activity revealed a decrease in the expression of distinct tRNAs, which was significant in the siPolr3a condition.DiscussionIn turn, our findings provide insight into the role of Pol III in oligodendrocyte development and shed light on the pathophysiological mechanisms of hypomyelination in POLR3-related leukodystrophy.