A scoping review examining patient experience and what matters to people experiencing homelessness when seeking healthcare.

BACKGROUND: Homelessness is associated with significant health disparities. Conventional health services often fail to address the unique needs and lived experience of homeless individuals and fail to include participatory design when planning health services. This scoping review aimed to examine areas of patient experience that are most frequently reported by people experiencing homelessness when seeking and receiving healthcare, and to identify existing surveys used to measure patient experience for this cohort. METHODS: A scoping review was undertaken reported according to the PRISMA-ScR 2020 Statement. Databases were searched on 1 December 2022: MEDLINE, EMBASE, APA PsychINFO and CINAHL. Included studies focused on people experiencing homelessness, healthcare services and patient experience, primary research, published in English from 2010. Qualitative papers and findings were extracted and synthesized against a modified framework based on the National Institute for Health and Care Excellence guidelines for care for people experiencing homelessness, the Institute of Medicine Framework and Lachman's multidimensional quality model. People with lived experience of homelessness were employed as part of the research team. RESULTS: Thirty-two studies were included. Of these, 22 were qualitative, seven quantitative and three mixed methods, from the United States of America (n = 17), United Kingdom (n = 5), Australia (n = 5) and Canada (n = 4). Health services ranged from primary healthcare to outpatient management, acute care, emergency care and hospital based healthcare. In qualitative papers, the domains of 'accessible and timely', 'person-centred', and values of 'dignity and respect' and 'kindness with compassion' were most prevalent. Among the three patient experience surveys identified, 'accessible and timely' and 'person-centred' were the most frequent domains. The least frequently highlighted domains and values were 'equitable' and 'holistic'. No questions addressed the 'safety' domain. CONCLUSIONS: The Primary Care Quality-Homeless questionnaire best reflected the priorities for healthcare provision that were highlighted in the qualitative studies of people experiencing homelessness. The most frequently cited domains and values that people experiencing homelessness expressed as important when seeking healthcare were reflected in each of the three survey tools to varying degrees. Findings suggest that the principles of 'Kindness and compassion' require further emphasis when seeking feedback on healthcare experiences and the domains of 'safety', 'equitable', and 'efficiency' are not adequately represented in existing patient experience surveys.

Isolation of Murine Adipose-Derived Stromal/Stem Cells for Adipogenic and Osteogenic Differentiation or Flow Cytometry-Based Analysis.

Murine models of obesity or reduced adiposity are a valuable resource for understanding the role of adipocyte dysfunction in metabolic disorders. Adipose tissue stromal vascular cells or primary adipocytes derived from murine adipose tissue and grown in culture are essential tools for studying the mechanisms underlying adipocyte development and function. Herein, we describe methods for the isolation, expansion, and long-term storage of murine adipose-derived stromal/stem cells, along with protocols for inducing adipogenesis to white or beige adipocytes in this cell population and osteogenic differentiation. Isolation of the adipose stromal vascular fraction cells for flow cytometric analysis is also described.

Enigmatic persistence of aerobic methanotrophs in oxygen-limiting freshwater habitats.

Methanotrophic bacteria mitigate emissions of the potent greenhouse gas methane (CH4) from a variety of anthropogenic and natural sources, including freshwater lakes, which are large sources of CH4 on a global scale. Despite a dependence on dioxygen (O2) for CH4 oxidation, abundant populations of putatively aerobic methanotrophs have been detected within microoxic and anoxic waters and sediments of lakes. Experimental work has demonstrated active aerobic methanotrophs under those conditions, but how they are able to persist and oxidize CH4 under O2 deficiency remains enigmatic. In this review, we discuss possible mechanisms that underpin the persistence and activity of aerobic methanotrophs under O2-limiting conditions in freshwater habitats, particularly lakes, summarize experimental evidence for microbial oxidation of CH4 by aerobic bacteria under low or no O2, and suggest future research directions to further explore the ecology and metabolism of aerobic methanotrophs in O2-limiting environments.

No increase in corticospinal excitability during motor simulation provides a platform to explore the neurophysiology of aphantasia.

This scientific commentary refers to 'Explicit and implicit motor simulations are impaired in individuals with aphantasia', by Dupont  et al. (https://doi.org/10.1093/braincomms/fcae072) in Brain Communications.

40†years of the homeobox: either it is wrong or it is quite interesting.

Many genes that regulate development share a 180 bp DNA sequence, called the homeobox, encoding a 60 amino acid DNA-binding domain ( McGinnis et al., 1984c; Scott and Weiner, 1984). Because the homeobox is long enough to hybridize to related, but different, genes, it has been a powerful tool for discovering developmental regulators. This year is the 40th anniversary of the first homeobox report. Here, I describe work carried out at Indiana University that led to the discovery of the homeobox. The accompanying Perspective from McGinnis and Levine describes the independent discovery made at the Biozentrum in Basel ( McGinnis and Levine, 2024). At the time, the competition was lively but, as we all met each other - and realized that no one cares more about your work than competitors - we fortunately became friends and have enjoyed many years of following and respecting each other's work.

Contribution of extracerebral tracer retention and partial volume effects to sex differences in Flortaucipir-PET signal.

Clinically normal females exhibit higher 18F-flortaucipir (FTP)-PET signal than males across the cortex. However, these sex differences may be explained by neuroimaging idiosyncrasies such as off-target extracerebral tracer retention or partial volume effects (PVEs). 343 clinically normal participants (female = 58%; mean[SD]=73.8[8.5] years) and 55 patients with mild cognitive impairment (female = 38%; mean[SD] = 76.9[7.3] years) underwent cross-sectional FTP-PET. We parcellated extracerebral FreeSurfer areas based on proximity to cortical ROIs. Sex differences in cortical tau were then estimated after accounting for local extracerebral retention. We simulated PVE by convolving group-level standardized uptake value ratio means in each ROI with 6 mm Gaussian kernels and compared the sexes across ROIs post-smoothing. Widespread sex differences in extracerebral retention were observed. Although attenuating sex differences in cortical tau-PET signal, covarying for extracerebral retention did not impact the largest sex differences in tau-PET signal. Differences in PVE were observed in both female and male directions with no clear sex-specific bias. Our findings suggest that sex differences in FTP are not solely attributed to off-target extracerebral retention or PVE, consistent with the notion that sex differences in medial temporal and neocortical tau are biologically driven. Future work should investigate sex differences in regional cerebral blood flow kinetics and longitudinal tau-PET.

A comparison between erythrocytapheresis and venesection for the treatment of JAK2-mutated polycythaemia.

BACKGROUND: JAK2-mutated polycythaemia vera (PV) is associated with reduced survival because of thrombotic events and haematological disease transformation. Therapeutic venesection has traditionally been used to lower haematocrit, but the technique of erythrocytapheresis has emerged over the last decade. AIM: To compare erythrocytapheresis with venesection as treatment for PV by assessing medical efficacy and financial viability. METHODS: One hundred sixteen patients with PV who received red cell depletion therapy at Barwon Health between 2014 and 2021 were identified. The haematocrit drop after each session, interval between treatment times and number of sessions required to achieve a haematocrit <0.45 were compared with an independent t test. Thrombosis rates were compared with Pearson's chi-squared test. Cost-funding analysis was done by assessing the Weighted Inlier Equivalent Separation and National Weighted Activity Unit funding models. RESULTS: Patients treated with erythrocytapheresis achieved a greater haematocrit drop each treatment session (0.075 vs 0.03, P < 0.01), required fewer sessions to achieve a haematocrit <0.45 (1 vs 4, P < 0.01) and experienced fewer thrombotic complications (8.7% vs 32.1%, P = 0.02) than those treated with venesection. Cost-funding analysis demonstrated that erythrocytapheresis was more financially viable with a surplus of AU$297 per session compared to a deficit of AU$176 with venesection. Even if funding for venesection is increased, the cost of erythrocytapheresis may be mitigated by a lower number of procedures required per year (3.8 vs 5.3, P < 0.01). CONCLUSIONS: Erythrocytapheresis is more efficacious than venesection for the treatment of PV and is accompanied by rapid reductions in haematocrit and reduced thrombotic complications.

Short-term evidence of partner-induced performance biases in simultaneous and alternating dyad practice in golf.

Actions in social settings are often adapted based on co-actors. This adaptation can occur because one actor "co-represents" the actions and plans of another. Co-representation can result in motor contagion errors, whereby another's actions unintentionally interfere with (negatively impact) the actor. In sports, practice often takes place simultaneously or alternating with a partner. Co-representation of another's task could either harm or benefit skill retention and transfer, with benefits due to variable experiences and effortful processes in practice. Here, dyad groups that either alternated or simultaneously practiced golf putting to different (near vs. far) targets were compared to alone groups (n = 30/group). We focused on errors in distance from the target and expected overshooting for near-target partners paired with far-target partners (and undershooting for far-target partners paired with near-target partners), when compared to alone groups. There was evidence of co-representation for near-target partners paired with far-target partners. We also saw trial-to-trial error-based adjustments based on a partner's outcome in alternating dyads. Despite differences in practice between dyad and alone groups, these did not lead to costs or benefits at retention or transfer. We conclude that the social-context of motor learning impacts behaviours of co-actors, but not to the detriment of overall learning.

Characterizing the influence of various antimicrobials used for metaphylaxis against bovine respiratory disease on host transcriptome responses.

Currently, control against bovine respiratory disease (BRD) primarily consists of mass administration of an antimicrobial upon arrival to facility, termed "metaphylaxis." The objective of this study was to determine the influence of six different antimicrobials used as metaphylaxis on the whole blood host transcriptome in healthy steers upon and following arrival to the feedlot. One hundred and five steers were stratified by arrival body weight (BW = 247 ± 28 kg) and randomly and equally allocated to one of seven treatments: negative control (NC), ceftiofur (CEFT), enrofloxacin (ENRO), florfenicol (FLOR), oxytetracycline (OXYT), tildipirosin (TILD), or tulathromycin (TULA). On day 0, whole blood samples and BW were collected prior to a one-time administration of the assigned antimicrobial. Blood samples were collected again on days 3, 7, 14, 21, and 56. A subset of cattle (n = 6) per treatment group were selected randomly for RNA sequencing across all time points. Isolated RNA was sequenced (NovaSeq 6,000; ~35 M paired-end reads/sample), where sequenced reads were processed with ARS-UCD1.3 reference-guided assembly (HISAT2/StringTie2). Differential expression analysis comparing treatment groups to NC was performed with glmmSeq (FDR ≤ 0.05) and edgeR (FDR ≤ 0.1). Functional enrichment was performed with KOBAS-i (FDR ≤ 0.05). When compared only to NC, unique differentially expressed genes (DEGs) found within both edgeR and glmmSeq were identified for CEFT (n = 526), ENRO (n = 340), FLOR (n = 56), OXYT (n = 111), TILD (n = 3,001), and TULA (n = 87). At day 3, CEFT, TILD, and OXYT shared multiple functional enrichment pathways related to T-cell receptor signaling and FcεRI-mediated NF-kappa beta (kB) activation. On day 7, Class I major histocompatibility complex (MHC)-mediated antigen presentation pathways were enriched in ENRO and CEFT groups, and CEFT and FLOR had DEGs that affected IL-17 signaling pathways. There were no shared pathways or Gene Ontology (GO) terms among treatments at day 14, but TULA had 19 pathways and eight GO terms enriched related to NF- κß activation, and interleukin/interferon signaling. Pathways related to cytokine signaling were enriched by TILD on day 21. Our research demonstrates immunomodulation and potential secondary therapeutic mechanisms induced by antimicrobials commonly used for metaphylaxis, providing insight into the beneficial anti-inflammatory properties antimicrobials possess.

The association of circulating endocannabinoids with neuroimaging and blood biomarkers of neuro-injury.

BACKGROUND: Preclinical studies highlight the importance of endogenous cannabinoids (endocannabinoids; eCBs) in neurodegeneration. Yet, prior observational studies focused on limited outcome measures and assessed only few eCB compounds while largely ignoring the complexity of the eCB system. We examined the associations of multiple circulating eCBs and eCB-like molecules with early markers of neurodegeneration and neuro-injury and tested for effect modification by sex. METHODS: This exploratory cross-sectional study included a random sample of 237 dementia-free older participants from the Framingham Heart Study Offspring cohort who attended examination cycle 9 (2011-2014), were 65 years or older, and cognitively healthy. Forty-four eCB compounds were quantified in serum, via liquid chromatography high-resolution mass spectrometry. Linear regression models were used to examine the associations of eCB levels with brain MRI measures (i.e., total cerebral brain volume, gray matter volume, hippocampal volume, and white matter hyperintensities volume) and blood biomarkers of Alzheimer's disease and neuro-injury (i.e., total tau, neurofilament light, glial fibrillary acidic protein and Ubiquitin C-terminal hydrolase L1). All models were adjusted for potential confounders and effect modification by sex was examined. RESULTS: Participants mean age was 73.3 ± 6.2 years, and 40% were men. After adjustment for potential confounders and correction for multiple comparisons, no statistically significant associations were observed between eCB levels and the study outcomes. However, we identified multiple sex-specific associations between eCB levels and the various study outcomes. For example, high linoleoyl ethanolamide (LEA) levels were related to decreased hippocampal volume among men and to increased hippocampal volume among women (ß ± SE = - 0.12 ± 0.06, p = 0.034 and ß ± SE = 0.08 ± 0.04, p = 0.026, respectively). CONCLUSIONS: Circulating eCBs may play a role in neuro-injury and may explain sex differences in susceptibility to accelerated brain aging. Particularly, our results highlight the possible involvement of eCBs from the N-acyl amino acids and fatty acid ethanolamide classes and suggest specific novel fatty acid compounds that may be implicated in brain aging. Furthermore, investigation of the eCBs contribution to neurodegenerative disease such as Alzheimer's disease in humans is warranted, especially with prospective study designs and among diverse populations, including premenopausal women.

Extract of Artemisia dracunculus L. Modulates Osteoblast Proliferation and Mineralization.

Thiazolidinediones (TZD) significantly improve insulin sensitivity via action on adipocytes. Unfortunately, TZDs also degrade bone by inhibiting osteoblasts. An extract of Artemisia dracunculus L., termed PMI5011, improves blood glucose and insulin sensitivity via skeletal muscle, rather than fat, and may therefore spare bone. Here, we examine the effects of PMI5011 and an identified active compound within PMI5011 (2',4'-dihydroxy-4-methoxydihydrochalcone, DMC-2) on pre-osteoblasts. We hypothesized that PMI5011 and DMC-2 will not inhibit osteogenesis. To test our hypothesis, MC3T3-E1 cells were induced in osteogenic media with and without PMI5011 or DMC-2. Cell lysates were probed for osteogenic gene expression and protein content and were stained for osteogenic endpoints. Neither compound had an effect on early stain outcomes for alkaline phosphatase or collagen. Contrary to our hypothesis, PMI5011 at 30 µg/mL significantly increases osteogenic gene expression as early as day 1. Further, osteogenic proteins and cell culture mineralization trend higher for PMI5011-treated wells. Treatment with DMC-2 at 1 µg/mL similarly increased osteogenic gene expression and significantly increased mineralization, although protein content did not trend higher. Our data suggest that PMI5011 and DMC-2 have the potential to promote bone health via improved osteoblast maturation and activity.

Measuring Morality: An Examination of the Moral Foundation Questionnaire's Factor Structure.

Moral foundations theory proposes five domains of morality-harm, fairness, loyalty, purity, and authority. Endorsement of these moral domains is assessed by the Moral Foundations Questionnaire (MFQ), a 30-item scale that has undergone intense measurement scrutiny. Across five samples (N = 464,229), we show greatly improved model fit using a Bifactor model that accounts for two kinds of items in the MFQ: judgment and relevance. We add to this space by demonstrating how using this improved measurement structure changes the strength of correlations of the moral foundations with numerous attitudes, cognitive styles, and moral decision-making. Future research should continue to identify what, if anything, the relevance and judgment factors might substantively capture over and above the substantive domains of moral foundations. In the meantime, we recommend that researchers use the Bifactor model for its improved model structure, rather than dropping the relevant items as some have proposed.

Features characterising cardiac autonomic neuropathy in diabetes using ensembled classification.

OBJECTIVE: Using supervised machine learning to classify the severity of cardiovascular autonomic neuropathy (CAN). The aims were 1) to investigate which features contribute to characterising CAN 2) to generate an ensembled set of features that best describes the variation in CAN classification. METHODS: Eighty-two features from demographic, beat-to-beat, biochemical, and inflammation were obtained from 204 people with diabetes and used in three machine-learning-classifiers, these are: support vector machine, decision tree, and random forest. All data were ensembled using a weighted mean of the features from each classifier. RESULTS: The 10 most important features derived from the domains: Beat-to-beat, inflammation markers, disease-duration, and age. CONCLUSIONS: Beat-to-beat measures associate with CAN as diagnosis is mainly based on cardiac reflex responses, disease-duration and age are also related to CAN development throughout disease progression. The inflammation markers may reflect the underlying disease process, and therefore, new treatment modalities targeting systemic low-grade inflammation should potentially be tested to prevent the development of CAN. SIGNIFICANCE: Cardiac reflex responses should be monitored closely to diagnose and classify severity levels of CAN accurately. Standard clinical biochemical analytes, such as glycaemic level, lipidic level, or kidney function were not included in the ten most important features. Beat-to-beat measures accounted for approximately 60% of the features in the ensembled data.

Combined action observation and motor imagery improves learning of activities of daily living in children with Developmental Coordination Disorder.

Developmental coordination disorder (DCD) is characterised by poor motor coordination, which interferes with the ability to execute activities of daily living (ADLs). Combined action observation and motor imagery (AOMI) involves observing movement videos whilst imagining simultaneously the sensations of executing the same movement. Laboratory-based research indicates that AOMI can help improve movement coordination in children with DCD, but no previous research had investigated the efficacy of AOMI interventions for learning ADLs. This study investigated the efficacy of a home-based, parent-led, AOMI intervention for learning ADLs in children with DCD. Children with confirmed (n = 23) or suspected (n = 5) DCD (total sample n = 28), aged 7-12 years, were assigned to either an AOMI intervention or a control intervention (both n = 14). Participants attempted the following ADLs at pre-test (week 1), post-test (week 4), and retention test (week 6): shoelace tying, cutlery use, shirt buttoning, and cup stacking. Task completion times and movement techniques were recorded. The AOMI intervention produced significantly faster task completion times than the control intervention at post-test for shoelace tying, and significantly improved movement techniques for shoelace tying and cup stacking. Importantly, for children who could not tie shoelaces at pre-test (n = 9 per group), 89% of those following the AOMI intervention learnt the skill successfully by the end of the study, compared to only 44% of those following the control intervention. The findings indicate that home-based, parent-led, AOMI interventions can aid the learning of complex ADLs in children with DCD, and may be particularly effective for facilitating the learning of motor skills that do not currently exist within these children's motor repertoire.

Interdependent Self-Organizing Mechanisms for Cooperative Survival.

Cooperative survival "games" are situations in which, during a sequence of catastrophic events, no one survives unless everyone survives. Such situations can be further exacerbated by uncertainty over the timing and scale of the recurring catastrophes, while the resource management required for survival may depend on several interdependent subgames of resource extraction, distribution, and investment with conflicting priorities and preferences between survivors. In social systems, self-organization has been a critical feature of sustainability and survival; therefore, in this article we use the lens of artificial societies to investigate the effectiveness of socially constructed self-organization for cooperative survival games. We imagine a cooperative survival scenario with four parameters: scale, that is, n in an n-player game; uncertainty, with regard to the occurrence and magnitude of each catastrophe; complexity, concerning the number of subgames to be simultaneously "solved"; and opportunity, with respect to the number of self-organizing mechanisms available to the players. We design and implement a multiagent system for a situation composed of three entangled subgames-a stag hunt game, a common-pool resource management problem, and a collective risk dilemma-and specify algorithms for three self-organizing mechanisms for governance, trading, and forecasting. A series of experiments shows, as perhaps expected, a threshold for a critical mass of survivors and also that increasing dimensions of uncertainty and complexity require increasing opportunity for self-organization. Perhaps less expected are the ways in which self-organizing mechanisms may interact in pernicious but also self-reinforcing ways, highlighting the need for some reflection as a process in collective self-governance for cooperative survival.

Enhancing upper-limb neurorehabilitation in chronic stroke survivors using combined action observation and motor imagery therapy.

Introduction: For people who have had a stroke, recovering upper-limb function is a barrier to independence. When movement is difficult, mental practice can be used to complement physical therapy. In this within-participants study we investigated the effects of combined action observation and motor imagery (AO + MI) therapy on upper-limb recovery in chronic stroke survivors. Methods: A Graeco-Latin Square design was used to counterbalance four mental practice conditions (AO + MI, AO, MI, Control) across four cup-stacking tasks of increasing complexity. Once a week, for five consecutive weeks, participants (n = 10) performed 16 mental practice trials under each condition. Each trial displayed a 1st person perspective of a cup-stacking task performed by an experienced model. For AO, participants watched each video and responded to an occasional color cue. For MI, participants imagined the effort and sensation of performing the action; cued by a series of still-images. For combined AO + MI, participants observed a video of the action while they simultaneously imagined performing the same action in real-time. At three time points (baseline; post-test; two-week retention test) participants physically executed the three mentally practiced cup-stacking tasks, plus a fourth unpractised sequence (Control), as quickly and accurately as possible. Results: Mean movement execution times were significantly reduced overall in the post-test and the retention test compared to baseline. At retention, movement execution times were significantly shorter for combined AO + MI compared to both MI and the Control. Individual participants reported clinically important changes in quality of life (Stroke Impact Scale) and positive qualitative experiences of AO + MI (social validation). Discussion: These results indicate that when physical practice is unsuitable, combined AO + MI therapy could offer an effective adjunct for neurorehabilitation in chronic stroke survivors.

Influence of the At-Arrival Host Transcriptome on Bovine Respiratory Disease Incidence during Backgrounding.

Bovine respiratory disease (BRD) remains the leading disease within the U.S. beef cattle industry. Marketing decisions made prior to backgrounding may shift BRD incidence into a different phase of production, and the importance of host gene expression on BRD incidence as it relates to marketing strategy is poorly understood. Our objective was to compare the influence of marketing on host transcriptomes measured on arrival at a backgrounding facility on the subsequent probability of being treated for BRD during a 45-day backgrounding phase. This study, through RNA-Seq analysis of blood samples collected on arrival, evaluated gene expression differences between cattle which experienced a commercial auction setting (AUCTION) versus cattle directly shipped to backgrounding from the cow-calf phase (DIRECT); further analyses were conducted to determine differentially expressed genes (DEGs) between cattle which remained clinically healthy during backgrounding (HEALTHY) versus those that required treatment for clinical BRD within 45 days of arrival (BRD). A profound difference in DEGs (n = 2961) was identified between AUCTION cattle compared to DIRECT cattle, regardless of BRD development; these DEGs encoded for proteins involved in antiviral defense (increased in AUCTION), cell growth regulation (decreased in AUCTION), and inflammatory mediation (decreased in AUCTION). Nine and four DEGs were identified between BRD and HEALTHY cohorts in the AUCTION and DIRECT groups, respectively; DEGs between disease cohorts in the AUCTION group encoded for proteins involved in collagen synthesis and platelet aggregation (increased in HEALTHY). Our work demonstrates the clear influence marketing has on host expression and identified genes and mechanisms which may predict BRD risk.

The prevalence, correlation, and co-occurrence of neuropathology in old age: harmonisation of 12 measures across six community-based autopsy studies of dementia.

BACKGROUND: Population-based autopsy studies provide valuable insights into the causes of dementia but are limited by sample size and restriction to specific populations. Harmonisation across studies increases statistical power and allows meaningful comparisons between studies. We aimed to harmonise neuropathology measures across studies and assess the prevalence, correlation, and co-occurrence of neuropathologies in the ageing population. METHODS: We combined data from six community-based autopsy cohorts in the US and the UK in a coordinated cross-sectional analysis. Among all decedents aged 80 years or older, we assessed 12 neuropathologies known to be associated with dementia: arteriolosclerosis, atherosclerosis, macroinfarcts, microinfarcts, lacunes, cerebral amyloid angiopathy, Braak neurofibrillary tangle stage, Consortium to Establish a Registry for Alzheimer's disease (CERAD) diffuse plaque score, CERAD neuritic plaque score, hippocampal sclerosis, limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), and Lewy body pathology. We divided measures into three groups describing level of confidence (low, moderate, and high) in harmonisation. We described the prevalence, correlations, and co-occurrence of neuropathologies. FINDINGS: The cohorts included 4354 decedents aged 80 years or older with autopsy data. All cohorts included more women than men, with the exception of one study that only included men, and all cohorts included decedents at older ages (range of mean age at death across cohorts 88·0-91·6 years). Measures of Alzheimer's disease neuropathological change, Braak stage and CERAD scores, were in the high confidence category, whereas measures of vascular neuropathologies were in the low (arterioloscerosis, atherosclerosis, cerebral amyloid angiopathy, and lacunes) or moderate (macroinfarcts and microinfarcts) categories. Neuropathology prevalence and co-occurrence was high (2443 [91%] of 2695 participants had more than one of six key neuropathologies and 1106 [41%] of 2695 had three or more). Co-occurrence was strongly but not deterministically associated with dementia status. Vascular and Alzheimer's disease features clustered separately in correlation analyses, and LATE-NC had moderate associations with Alzheimer's disease measures (eg, Braak stage ρ=0·31 [95% CI 0·20-0·42]). INTERPRETATION: Higher variability and more inconsistency in the measurement of vascular neuropathologies compared with the measurement of Alzheimer's disease neuropathological change suggests the development of new frameworks for the measurement of vascular neuropathologies might be helpful. Results highlight the complexity and multi-morbidity of the brain pathologies that underlie dementia in older adults and suggest that prevention efforts and treatments should be multifaceted. FUNDING: Gates Ventures.

Predictors of Inpatient Racemic Epinephrine Use in Patients Admitted With Croup.

OBJECTIVE: Many patients hospitalized for croup receive no additional racemic epinephrine (RE) postadmission. We analyzed the association between inpatient racemic epinephrine (RE) use and demographic and emergency department (ED) parameters including timing between RE doses with a goal of identifying patients who may be low risk for ED discharge. METHODS: We completed a retrospective cohort study of previously healthy patients ages 2 months to <7 years old who were admitted with a diagnosis of croup from 2016 to 2019 at a freestanding tertiary-care children's hospital. Patients were eligible for this study if they received at least 1 RE treatment before admission. RESULTS: The cohort included 238 patients; 59 (24.7%) patients received additional RE during admission. The number of RE doses in the ED (P = .99) and the median time between RE doses (P = .71) were not different between inpatient RE and no inpatient RE groups. Younger patients (P = .045) and patients with tachypnea for age (odds ratio [OR] 2.33; 95% confidence interval = 1.2-4.4) were more likely to require RE during admission. Median length of hospitalization for patients receiving inpatient RE was significantly longer (38 hours vs 16.7 hours, P < .001), whereas readmit rates were similar between groups (5.1% vs 3.9%, P = .71). CONCLUSIONS: Fewer than 25% of admitted patients received inpatient RE. Age and tachypnea for age were associated with inpatient RE use. Reassessment of admission thresholds for multidose RE use may be warranted to prevent unnecessary hospitalizations.