Geographic, social, political, and economic factors shape access to advanced neurotechnologies, yet little previous research has explored the barriers, enablers, and areas of opportunity for equitable and meaningful access for diverse patient communities across Canada. We applied a mixed-mode approach involving semi-structured interviews and rating scale questions to consult with 24 medical experts who are involved in the care of patients who undergo functional neurosurgery targeting the brain. Seven major themes emerged from the qualitative analysis: Health care system, Neurotechnology features, Patient demographics, Target condition features, Ethics, Upstream barriers and enablers, and Areas of opportunity. Descriptive statistics of the Likert-scale responses suggest that interviewees perceive a disparity between the imperative of access to advanced neurotechnologies for people living in rural and remote areas and the likelihood of achieving such access. The results depict a complex picture of access to functional neurosurgery in Canada with pockets of excellence and a motivation to improve the availability of care for vulnerable populations through the expansion of distributed care models, improved health care system efficiencies, increasing funding and support for patient travel, and increasing awareness about and advocacy for advanced neurotechnologies.

OBJECTIVES/GOALS: Glioblastomas (GBMs) are heterogeneous, treatment-resistant tumors that are driven by populations of cancer stem cells (CSCs). In this study, we perform an epigenetic-focused functional genomics screen in GBM organoids and identify WDR5 as an essential epigenetic regulator in the SOX2-enriched, therapy resistant cancer stem cell niche. METHODS/STUDY POPULATION: Despite their importance for tumor growth, few molecular mechanisms critical for CSC population maintenance have been exploited for therapeutic development. We developed a spatially resolved loss-of-function screen in GBM patient-derived organoids to identify essential epigenetic regulators in the SOX2-enriched, therapy resistant niche. Our niche-specific screens identified WDR5, an H3K4 histone methyltransferase responsible for activating specific gene expression, as indispensable for GBM CSC growth and survival. RESULTS/ANTICIPATED RESULTS: In GBM CSC models, WDR5 inhibitors blocked WRAD complex assembly and reduced H3K4 trimethylation and expression of genes involved in CSC-relevant oncogenic pathways. H3K4me3 peaks lost with WDR5 inhibitor treatment occurred disproportionally on POU transcription factor motifs, required for stem cell maintenance and including the POU5F1(OCT4)::SOX2 motif. We incorporated a SOX2/OCT4 motif driven GFP reporter system into our CSC cell models and found that WDR5 inhibitor treatment resulted in dose-dependent silencing of stem cell reporter activity. Further, WDR5 inhibitor treatment altered the stem cell state, disrupting CSC in vitro growth and self-renewal as well as in vivo tumor growth. DISCUSSION/SIGNIFICANCE: Our results unveiled the role of WDR5 in maintaining the CSC state in GBM and provide a rationale for therapeutic development of WDR5 inhibitors for GBM and other advanced cancers. This conceptual and experimental framework can be applied to many cancers, and can unmask unique microenvironmental biology and rationally designed combination therapies.

We report the discovery of a bright ( $g = 14.5$ mag (AB), $K = 11.9$ mag (Vega)) quasar at redshift $z=0.83$ — the optically brightest (unbeamed) quasar at $z>0.4$ . SMSS J114447.77-430859.3, at a Galactic latitude of $b=+18.1^{\circ}$ , was identified by its optical colours from the SkyMapper Southern Survey (SMSS) during a search for symbiotic binary stars. Optical and near-infrared spectroscopy reveals broad Mg ii, H $\unicode{x03B2}$ , H $\unicode{x03B1}$ , and Pa $\unicode{x03B2}$ emission lines, from which we measure a black hole mass of $\log_{10}\! (M_{\mathrm{BH}}/\mathrm{M}_{\odot}) = 9.4 \pm 0.5$ . With its high luminosity, $L_{\mathrm{bol}} = (4.7\pm1.0)\times10^{47}\,\mathrm{erg\,s}^{-1}$ or $M_{i}(z=2) = -29.74$ mag (AB), we estimate an Eddington ratio of $\approx1.4$ . As the most luminous quasar known over the last ${\sim}$ 9 Gyr of cosmic history, having a luminosity $8\times$ greater than 3C 273, the source offers a range of potential follow-up opportunities.

Recent initiatives have focused on integrating transdiagnostic biobehavioral processes or dispositions with dimensional models of psychopathology. Toward this goal, biobehavioral traits of affiliative capacity (AFF) and inhibitory control (INH) hold particular promise as they demonstrate transdiagnostic stability and predictive validity across developmental stages and differing measurement modalities. The current study employed data from different modes of measurement in a sample of 1830 children aged 5–10 years to test for associations of AFF and INH, individually and interactively, with broad dimensions of psychopathology. Low AFF, assessed via parent-report, evidenced predictive relations with distress- and externalizing-related problems. INH as assessed by cognitive-task performance did not relate itself to either psychopathology dimension, but it moderated the effects observed for low AFF, such that high INH protected against distress symptoms in low-AFF participants, whereas low INH amplified distress and externalizing symptoms in low-AFF participants. Results are discussed in the context of the interface of general trait transdiagnostic risk factors with quantitatively derived dimensional models of psychopathology.

Mixed flora in urine cultures usually occur due to preanalytic contamination. In our outpatient urology clinic, we detected a high prevalence of mixed flora (46.2%), which was associated with female sex and older age. Patient education did not influence the rate of mixed flora. Future efforts should target high-risk patients.

The triarchic model was advanced as an integrative, trait-based framework for investigating psychopathy using different assessment methods and across developmental periods. Recent research has shown that the triarchic traits of boldness, meanness, and disinhibition can be operationalized effectively in youth, but longitudinal research is needed to realize the model's potential to advance developmental understanding of psychopathy. We report on the creation and validation of scale measures of the triarchic traits using questionnaire items available in the University of Southern California Risk Factors for Antisocial Behavior (RFAB) project, a large-scale longitudinal study of the development of antisocial behavior that includes measures from multiple modalities (self-report, informant rating, clinical-diagnostic, task-behavioral, physiological). Using a construct-rating and psychometric refinement approach, we developed triarchic scales that showed acceptable reliability, expected intercorrelations, and good temporal stability. The scales showed theory-consistent relations with external criteria including measures of psychopathy, internalizing/externalizing psychopathology, antisocial behavior, and substance use. Findings demonstrate the viability of measuring triarchic traits in the RFAB sample, extend the known nomological network of these traits into the developmental realm, and provide a foundation for follow-up studies examining the etiology of psychopathic traits and their relations with multimodal measures of cognitive-affective function and proneness to clinical problems.

A growing body of research supports the value of a multimodal assessment approach, drawing on measures from different response modalities, for clarifying how core biobehavioral processes relate to various clinical problems and dimensions of psychopathology. Using data for 507 healthy adults, the current study was undertaken to integrate self-report and neurophysiological (brain potential) measures as a step toward a multimodal measurement model for the trait of affiliative capacity (AFF) – a biobehavioral construct relevant to adaptive and maladaptive social-interpersonal functioning. Individuals low in AFF exhibit a lack of interpersonal connectedness, deficient empathy, and an exploitative-aggressive social style that may be expressed transdiagnostically in antagonistic externalizing or distress psychopathology. Specific aims were to (1) integrate trait scale and brain potential indicators into a multimodal measure of AFF and (2) evaluate associations of this multimodal measure with criterion variables of different types. Results demonstrated (1) success in creating a multimodal measure of AFF from self-report and neural indicators, (2) effectiveness of this measure in predicting both clinical-diagnostic and neurophysiological criterion variables, and (3) transdiagnostic utility of the multimodal measure at both specific-disorder and broad symptom-dimension levels. Our findings further illustrate the value of psychoneurometric operationalizations of biobehavioral trait dimensions as referents for clarifying transdiagnostic relationships between biological systems variables and empirically defined dimensions of psychopathology.

While medical nutrition therapy is an essential part of the care for critically ill patients, uncertainty exists about the right form, dosage, timing and route in relation to the phases of critical illness. As enteral nutrition (EN) is often withheld or interrupted during the intensive care unit (ICU) stay, combined EN and parenteral nutrition (PN) may represent an effective and safe option to achieve energy and protein goals as recommended by international guidelines. We hypothesise that critically ill patients at high nutritional risk may benefit from such a combined approach during their stay on the ICU. Therefore, we aim to test if an early combination of EN and high-protein PN (EN+PN) is effective in reaching energy and protein goals in patients at high nutritional risk, while avoiding overfeeding. This approach will be tested in the here-presented EFFORTcombo trial. Nutritionally high-risk ICU patients will be randomised to either high (≥2·2 g/kg per d) or low protein (≤1·2 g/kg per d). In the high protein group, the patients will receive EN+PN; in the low protein group, patients will be given EN alone. EN will be started in accordance with international guidelines in both groups. Efforts will be made to reach nutrition goals within 48–96 h. The efficacy of the proposed nutritional strategy will be tested as an innovative approach by functional outcomes at ICU and hospital discharge, as well as at a 6-month follow-up.

We present a sediment-mixing process model of till genesis based on data from surface tills of the Saginaw lobe terrain in lower Michigan. Our research uses a spatial approach to understanding glacial landsystems and till genesis. We sampled calcareous till at 336 upland sites and at 17 sites in lacustrine sediment of the Saginaw Lake plain. The loamy tills have bimodal grain-size curves, with a fine-texture mode near the silt–clay boundary and a sand mode. Spatial grouping analysis suggests that tills can be divided into six groups, each with different textures and clay mineral compositions that vary systematically down-ice. The similarity among groups with respect to the silt–clay mode and clay mineralogy argues for a common origin for the fines—illite-rich lacustrine sediment of the Saginaw Lake plain. Fine-textured sediments were probably entrained, transported, and deposited down-ice as till, which also becomes sandier and enriched in kaolinite, reflecting increasing mixing with shallow sandstone bedrock with distance from the lacustrine clay source. Clayey tills on the flanks of the Saginaw terrain may reflect proglacial ponding against nearby uplands. A process model of progressive down-ice mixing of preexisting fine lake sediments with crushed/abraded sandstone bedrock helps to better explain till textures compared with a purely crushing/abrasion process model.

Objectives: Concussions cause diverse symptoms that are often measured through a single symptom severity score. Researchers have postulated distinct dimensions of concussion symptoms, raising the possibility that total scores may not accurately represent their multidimensional nature. This study examined to what degree concussion symptoms, assessed by the Sport Concussion Assessment Tool 3 (SCAT3), reflect a unidimensional versus multidimensional construct to inform how the SCAT3 should be scored and advance efforts to identify distinct phenotypes of concussion. Methods: Data were aggregated across two prospective studies of sport-related concussion, yielding 219 high school and college athletes in the acute (<48 hr) post-injury period. Item-level ratings on the SCAT3 checklist were analyzed through exploratory and confirmatory factor analyses. We specified higher-order and bifactor models and compared their fit, interpretability, and external correlates. Results: The best-fitting model was a five-factor bifactor model that included a general factor on which all items loaded and four specific factors reflecting emotional symptoms, torpor, sensory sensitivities, and headache symptoms. The bifactor model demonstrated better discriminant validity than the counterpart higher-order model, in which the factors were highly correlated (r=.55–.91). Conclusions: The SCAT3 contains items that appear unidimensional, suggesting that it is appropriate to quantify concussion symptoms with total scores. However, evidence of multidimensionality was revealed using bifactor modeling. Additional work is needed to clarify the nature of factors identified by this model, explicate their clinical and research utility, and determine to what degree the model applies to other stages of injury recovery and patient subgroups. (JINS, 2018, 24, 793–804)

Based on the data from the Next Generation Virgo cluster Survey (NGVS), we statistically study the photometric properties of globular clusters (GCs), ultra-compact dwarfs (UCDs) and dwarf nuclei in the Virgo core (M87) region. We found an obvious negative color (g - z) gradient in GC system associate with M87, i.e. GCs in the outer regions are bluer. However, such color gradient does not exist in UCD system, neither in dwarf nuclei system around M87. In addition, we found that many UCDs are surrounded by extended, low surface brightness envelopes. The dwarf nuclei and UCDs show different spatial distributions from GCs, with dwarf nuclei and UCDs (especially for the UCDs with visible envelopes) lying at larger distances to the Virgo center. These results support the view that UCDs (at least for a fraction of UCDs) are more tied to dwarf nuclei than to GCs.

We present the first data release of the SkyMapper Southern Survey, a hemispheric survey carried out with the SkyMapper Telescope at Siding Spring Observatory in Australia. Here, we present the survey strategy, data processing, catalogue construction, and database schema. The first data release dataset includes over 66 000 images from the Shallow Survey component, covering an area of 17 200 deg2 in all six SkyMapper passbands uvgriz, while the full area covered by any passband exceeds 20 000 deg2. The catalogues contain over 285 million unique astrophysical objects, complete to roughly 18 mag in all bands. We compare our griz point-source photometry with Pan-STARRS1 first data release and note an RMS scatter of 2%. The internal reproducibility of SkyMapper photometry is on the order of 1%. Astrometric precision is better than 0.2 arcsec based on comparison with Gaia first data release. We describe the end-user database, through which data are presented to the world community, and provide some illustrative science queries.

Currently it is estimated that about 1 billion people globally have non-alcoholic fatty liver disease (NAFLD), a condition in which liver fat exceeds 5 % of liver weight in the absence of significant alcohol intake. Due to the central role of the liver in metabolism, the prevalence of NAFLD is increasing in parallel with the prevalence of obesity, insulin resistance and other risk factors of metabolic diseases. However, the contribution of liver fat to the risk of type 2 diabetes mellitus and CVD, relative to other ectopic fat depots and to other risk markers, is unclear. Various studies have suggested that the accumulation of liver fat can be reduced or prevented via dietary changes. However, the amount of liver fat reduction that would be physiologically relevant, and the timeframes and dose–effect relationships for achieving this through different diet-based approaches, are unclear. Also, it is still uncertain whether the changes in liver fat per se or the associated metabolic changes are relevant. Furthermore, the methods available to measure liver fat, or even individual fatty acids, differ in sensitivity and reliability. The present report summarises key messages of presentations from different experts and related discussions from a workshop intended to capture current views and research gaps relating to the points above.