Prevalence and Survival of Prolonged Venovenous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: An Analysis of the Extracorporeal Life Support Organization Registry.

OBJECTIVES: To examine trends in utilization and outcomes among patients with the acute respiratory distress syndrome (ARDS) requiring prolonged venovenous extracorporeal membrane oxygenation (VV ECMO) support. DESIGN: Retrospective observational cohort study. SETTING: Adult patients in the Extracorporeal Life Support Organization registry. PATIENTS: Thirteen thousand six hundred eighty-one patients that required ECMO for the support of ARDS between January 2012 and December 2022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mortality while supported with VV ECMO and survival to hospital discharge based on ECMO duration were examined utilizing multivariable logistic regression. Among the 13,681 patients supported with VV ECMO, 4,040 (29.5%) were supported for greater than or equal to 21 days and 975 (7.1%) for greater than or equal to 50 days. Patients supported with prolonged VV ECMO were less likely to be discharged alive from the hospital compared with those with short duration of support (46.5% vs. 59.7%; p < 0.001). However, among patients supported with VV ECMO greater than or equal to 21 days, duration of extracorporeal life support was not significantly associated with mortality (odds ratio [OR], 0.99; 95% CI, 0.98-1.01; p = 0.87 and adjusted OR, 0.99; 95% CI, 0.97-1.02; p = 0.48). Even in those supported with VV ECMO for at least 120 days (n = 113), 52 (46.0%) of these patients were ultimately discharged alive from the hospital. CONCLUSIONS: Prolonged VV ECMO support of ARDS has increased and accounts for a substantial portion of cases. Among patients that survive for greater than or equal to 21 days while receiving VV ECMO support, duration is not predictive of survival to hospital discharge and clinical recovery may occur even after very prolonged VV ECMO support.

TAPBPR employs a ligand-independent docking mechanism to chaperone MR1 molecules.

Chaperones tapasin and transporter associated with antigen processing (TAP)-binding protein related (TAPBPR) associate with the major histocompatibility complex (MHC)-related protein 1 (MR1) to promote trafficking and cell surface expression. However, the binding mechanism and ligand dependency of MR1/chaperone interactions remain incompletely characterized. Here in vitro, biochemical and computational studies reveal that, unlike MHC-I, TAPBPR recognizes MR1 in a ligand-independent manner owing to the absence of major structural changes in the MR1 α2-1 helix between empty and ligand-loaded molecules. Structural characterization using paramagnetic nuclear magnetic resonance experiments combined with restrained molecular dynamics simulations reveals that TAPBPR engages conserved surfaces on MR1 to induce similar adaptations to those seen in MHC-I/TAPBPR co-crystal structures. Finally, nuclear magnetic resonance relaxation dispersion experiments using 19F-labeled diclofenac show that TAPBPR can affect the exchange kinetics of noncovalent metabolites with the MR1 groove, serving as a catalyst. Our results support a role of chaperones in stabilizing nascent MR1 molecules to enable loading of endogenous or exogenous cargo.

Investigating the Impact of Tumor Biology and Social Determinants on Time to Diagnosis and Stage at Presentation of Wilms Tumor.

Delays in diagnosis and time to diagnosis generally are used interchangeably in cancer disparity research, but these terms may have important differences. Although these terms are related, we hypothesize that time to diagnosis is determined by the aggressiveness of the tumor based on intrinsic factors such as tumor biology, whereas delays in diagnosis are caused by extrinsic factors such as socioeconomic status, leading to presentation at higher stage of disease due to barriers of care. We conducted a retrospective study of 306 patients diagnosed with Wilms tumor at Children's Hospital Colorado between 1971 and 2016 identifying patient barriers as extrinsic markers and using unfavorable histology and loss of heterozygosity as markers of aggressive tumor biology. Multivariable logistic regression was performed. Patients with Medicaid were more likely to present greater than 4 days after initial symptoms compared to those with private insurance, and those with housing concerns were more likely to be diagnosed greater than 9 days from initial symptoms. Tumor biology was noted to be associated with higher stage at diagnosis, but patient barriers were not. These findings suggest the interplay between tumor biology, patient barriers, diagnostic timing, and stage at diagnosis is more complex, multifactorial, and in need of further study.

A novel configuration for providing continuous renal replacement therapy via the ECMO circuit in VV ECMO without alarm adjustment.

BACKGROUND: It is common for patients on venovenous extracorporeal membrane oxygenation (VV ECMO) to require continuous renal replacement therapy (CRRT). This can be done using separate vascular access for the CRRT circuit, by placing the CRRT hemofilter within the ECMO circuit, or through a separate CRRT circuit connected to the ECMO circuit. When a CRRT circuit is connected to the ECMO circuit, the inflow and outflow CRRT limbs can both be placed pre-ECMO pump or the CRRT circuit can span the ECMO pump, with the CRRT inflow post-ECMO pump and the outflow pre-ECMO pump. Both configurations require the CRRT alarms to be inactivated due to high positive pressure experienced post-pump and low negative pressure pre-pump. We describe a novel technique that does not require separate venous access and still allows the CRRT alarms to be activated. TECHNIQUE: The CRRT inflow line is connected to the post-oxygenator de-airing port. The CRRT outflow line is connected to the pre-pump side of the ECMO circuit. Pigtails allow for these connections and act as resistors negating the large range of pressures generated by the ECMO centrifugal pump. RESULTS: We implemented this configuration in 11 patients with 100% success rate allowing for alarms to be maintained in all patients. The median number of interruptions per 100 CRRT days was 11.7. The median CRRT filter lifespan was 2.2 days, and the average blood flow was maintained at 311 mL/min. CONCLUSIONS: This configuration allows for efficient use of CRRT in ECMO patients while maintaining the safety alarms on the CRRT machine.

Recurrent atypical teratoid/rhabdoid tumors (AT/RT) reveal discrete features of progression on histology, epigenetics, copy number profiling, and transcriptomics.

Atypical teratoid/rhabdoid tumors (AT/RT) are the most common malignant brain tumors manifesting in infancy. They split into four molecular types. The major three (AT/RT-SHH, AT/RT-TYR, and AT/RT-MYC) all carry mutations in SMARCB1, the fourth quantitatively smaller type is characterized by SMARCA4 mutations (AT/RT-SMARCA4). Molecular characteristics of disease recurrence or metastatic spread, which go along with a particularly dismal outcome, are currently unclear. Here, we investigated tumor tissue from 26 patients affected by AT/RT to identify signatures of recurrences in comparison with matched primary tumor samples. Microscopically, AT/RT recurrences demonstrated a loss of architecture and significantly enhanced mitotic activity as compared to their related primary tumors. Based on DNA methylation profiling, primary tumor and related recurrence were grossly similar, but three out of 26 tumors belonged to a different molecular type or subtype after second surgery compared to related primary lesions. Copy number variations (CNVs) differed in six cases, showing novel gains on chromosome 1q or losses of chromosome 10 in recurrences as the most frequent alterations. To consolidate these observations, our cohort was combined with a data set of unmatched primary and recurrent AT/RT, which demonstrated chromosome 1q gain and 10 loss in 18% (n = 7) and 11% (n = 4) of the recurrences (n = 38) as compared to 7% (n = 3) and 0% (n = 0) in the primary tumors (n = 44), respectively. Similar to the observations made by DNA methylation profiling, RNA sequencing of our cohort revealed AT/RT primary tumors and matched recurrences clustering closely together. However, a number of genes showed significantly altered expression in AT/RT-SHH recurrences. Many of them are known tumor driving growth factors, involved in embryonal development and tumorigenesis, or are cell-cycle-associated. Overall, our work identifies subtle molecular changes that occur in the course of the disease and that may help define novel therapeutic targets for AT/RT recurrences.

Children's Oncology Group's 2023 blueprint for research: Young investigators.

The Children's Oncology Group (COG) Young Investigators (YI) Committee is an administrative committee in which liaisons represent 30 COG committees, and was created to facilitate the integration of YIs into the organization, and prepare them for future COG leadership roles. The mentorship program has mentored over 400 YIs since 2005 and currently has 175 active participants. The COG YI Master Roster is a database YIs can join, which allows them to post their interests and accomplishments to COG leadership, and 321 YIs have already joined this list. The YI Committee has held virtual symposia designed to describe how COG operates and provide guidance on how YIs can reach their goals; over 300 YIs have attended these since 2021 and have consistently rated them as helpful. Through these and other elements of the program, the YI Committee remains committed to developing a future pipeline of new investigators.

Identifying patterns of neurocognitive dysfunction through direct comparison of children with leukemia, central nervous system tumors, and sickle cell disease.

PURPOSE: To quantify and compare the magnitude and type of neurocognitive dysfunction in at-risk children with central nervous system (CNS) tumors, acute lymphoblastic leukemia (ALL), and sickle cell disease (SCD) using a common instrument and metric to directly compare these groups with each other. METHODS: Fifty-three participants between the ages of 7 and 12 years (n = 27 ALL, n = 11 CNS tumor, n = 15 SCD) were enrolled and assessed using the NIH Toolbox Cognition Battery (NIHTCB). Participants with ALL or CNS tumor were 0-18 months posttherapy, while participants with SCD possessed the SS or Sß0 genotype, took hydroxyurea, and had no known history of stroke. RESULTS: Independent sample t-tests showed that participants with ALL and CNS tumor experienced greatest deficits in processing speed (ALL d = -0.96; CNS tumor d = -1.2) and inhibitory control and attention (ALL d = -0.53; CNS tumor d = -0.97) when compared with NIHTCB normative data. Participants with SCD experienced deficits in cognitive flexibility only (d = -0.53). Episodic memory was relatively spared in all groups (d = -0.03 to -0.32). There were no significant differences in function when groups were compared directly with each other by analysis of variance. CONCLUSIONS: Use of a common metric to quantify the magnitude and type of neurocognitive dysfunction across at-risk groups of participants by disease shows that participants perform below age-expected norms in multiple domains and experience dysfunction differently than one another. This approach highlights patterns of dysfunction that can inform disease- and domain-specific interventions.

Sociodemographic Disparities in Presentation and Survival of Pediatric Bone Cancers.

Osteosarcoma (OST) and Ewing sarcoma (ES) are the most common pediatric bone cancers. Patients with metastatic disease at diagnosis have poorer outcomes compared with localized disease. Using the Surveillance, Epidemiology, and End Results registries, we identified children and adolescents diagnosed with OST or ES between 2004 and 2015. We examined whether demographic and socioeconomic disparities were associated with a higher likelihood of metastatic disease at diagnosis and poor survival outcomes. In OST, Hispanic patients and those living in areas of high language isolation were more likely to have metastatic disease at diagnosis. Regardless of metastatic status, OST patients with public insurance had increased odds of death compared to those with private insurance. Living in counties with lower education levels increased odds of death for adolescents with metastatic disease. In ES, non-White adolescents had higher odds of death compared with white patients. Adolescents with metastatic ES living in higher poverty areas had increased odds of death compared with those living in less impoverished areas. Disparities in both diagnostic and survival outcomes based on race, ethnicity, and socioeconomic factors exist in pediatric bone cancers, potentially due to barriers to care and treatment inequities.

Vaccination practices of pediatric oncologists from eight states.

BACKGROUND: Vaccinations are a vital part of routine childhood and adolescent preventive care. We sought to identify current oncology provider practices, barriers, and attitudes towards vaccinating childhood and adolescent cancer patients and survivors. METHODS: We conducted a one-time online survey distributed from March-October 2018 to pediatric oncologists at nine institutions across the United States (N = 111, 68.8% participation rate). The survey included 32 items about vaccination practices, barriers to post-treatment vaccination, availability of vaccinations in oncology clinic, familiarity with vaccine guidelines, and attitudes toward vaccination responsibilities. Descriptive statistics were calculated in STATA 14.2. RESULTS: Participants were 54.0% female and 82.9% white, with 12.6% specializing in Bone Marrow Transplants. Influenza was the most commonly resumed vaccine after treatment (7030%). About 50%-60% were familiar with vaccine guidelines for immunocompromised patients. More than half (62.7%) recommended that patients restart most immunizations 6 months to 1 year after chemotherapy. Common barriers to providers recommending vaccinations included not having previous vaccine records for patients (56.8%) or lacking time to ascertain which vaccines are needed (32.4%). Of participants, 66.7% stated that vaccination should be managed by primary care providers, but with guidance from oncologists. CONCLUSIONS: Many pediatric oncologists report being unfamiliar with vaccine guidelines for immunocompromised patients and almost all report barriers in supporting patients regarding vaccines after cancer treatment. Our findings show that further research and interventions are needed to help bridge oncology care and primary care regarding immunizations after treatment.

Automated detection of archaeological mounds using machine-learning classification of multisensor and multitemporal satellite data.

This paper presents an innovative multisensor, multitemporal machine-learning approach using remote sensing big data for the detection of archaeological mounds in Cholistan (Pakistan). The Cholistan Desert presents one of the largest concentrations of Indus Civilization sites (from ca 3300 to 1500 BC). Cholistan has figured prominently in theories about changes in water availability, the rise and decline of the Indus Civilization, and the transformation of fertile monsoonal alluvial plains into an extremely arid margin. This paper implements a multisensor, multitemporal machine-learning approach for the remote detection of archaeological mounds. A classifier algorithm that employs a large-scale collection of synthetic-aperture radar and multispectral images has been implemented in Google Earth Engine, resulting in an accurate probability map for mound-like signatures across an area that covers ca 36,000 km2 The results show that the area presents many more archaeological mounds than previously recorded, extending south and east into the desert, which has major implications for understanding the archaeological significance of the region. The detection of small (<5 ha) to large mounds (>30 ha) suggests that there were continuous shifts in settlement location. These shifts are likely to reflect responses to a dynamic and changing hydrological network and the influence of the progressive northward advance of the desert in a long-term process that culminated in the abandonment of much of the settled area during the Late Harappan period.

Divergent semantic integration (DSI): Extracting creativity from narratives with distributional semantic modeling.

We developed a novel conceptualization of one component of creativity in narratives by integrating creativity theory and distributional semantics theory. We termed the new construct divergent semantic integration (DSI), defined as the extent to which a narrative connects divergent ideas. Across nine studies, 27 different narrative prompts, and over 3500 short narratives, we compared six models of DSI that varied in their computational architecture. The best-performing model employed Bidirectional Encoder Representations from Transformers (BERT), which generates context-dependent numerical representations of words (i.e., embeddings). BERT DSI scores demonstrated impressive predictive power, explaining up to 72% of the variance in human creativity ratings, even approaching human inter-rater reliability for some tasks. BERT DSI scores showed equivalently high predictive power for expert and nonexpert human ratings of creativity in narratives. Critically, DSI scores generalized across ethnicity and English language proficiency, including individuals identifying as Hispanic and L2 English speakers. The integration of creativity and distributional semantics theory has substantial potential to generate novel hypotheses about creativity and novel operationalizations of its underlying processes and components. To facilitate new discoveries across diverse disciplines, we provide a tutorial with code (osf.io/ath2s) on how to compute DSI and a web app ( osf.io/ath2s ) to freely retrieve DSI scores.

Rapid Development and Deployment of an Intensivist-Led Venovenous Extracorporeal Membrane Oxygenation Cannulation Program.

OBJECTIVES: To determine the safety and efficacy of a rapidly deployed intensivist-led venovenous extracorporeal membrane oxygenation cannulation program in a preexisting extracorporeal membrane oxygenation program. DESIGN: A retrospective observational before-and-after study of 40 patients undergoing percutaneous cannulation for venovenous extracorporeal membrane oxygenation in an established cannulation program by cardiothoracic surgeons versus a rapidly deployed medical intensivist cannulation program. SETTING: An adult ICU in a tertiary academic medical center in Camden, NJ. PATIENTS: Critically ill adult subjects with severe respiratory failure undergoing percutaneous cannulation for venovenous extracorporeal membrane oxygenation. INTERVENTIONS: Percutaneous cannulation for venovenous extracorporeal membrane oxygenation performed by cardiothoracic surgeons compared with cannulations performed by medical intensivists. MEASUREMENTS AND MAIN RESULTS: Venovenous extracorporeal membrane oxygenation cannulation site attempts were retrospectively reviewed. Subject demographics, specialty of physician performing cannulation, type of support, cannulation configuration, cannula size, imaging guidance, success rate, and complications were recorded and summarized. Twenty-two cannulations were performed by three cardiothoracic surgeons in 11 subjects between September 2019 and February 2020. The cannulation program rapidly transitioned to an intensivist-led and performed program in March 2020. Fifty-seven cannulations were performed by eight intensivists in 29 subjects between March 2020 and December 2020. Mean body mass index for subjects did not differ between groups (33.86 vs 35.89; p = 0.775). There was no difference in days on mechanical ventilation prior to cannulation, configuration, cannula size, or discharge condition. There was no difference in success rate of cannulation on first attempt per cannulation site (95.5 vs 96.7; p = 0.483) or major complication rate per cannulation site (4.5 vs 3.5; p = 1). CONCLUSIONS: There is no difference between success and complication rates of percutaneous venovenous extracorporeal membrane oxygenation canulation when performed by cardiothoracic surgeons versus medical intensivist in an already established extracorporeal membrane oxygenation program. A rapidly deployed cannulation program by intensivists for venovenous extracorporeal membrane oxygenation can be performed with high success and low complication rates.

Investigation of white blood cell characteristics in cerebrospinal fluid samples at pediatric brain tumor diagnosis.

PURPOSE: The role of white blood cells (WBC) in the pediatric central nervous system (CNS) tumor microenvironment is incompletely defined. We hypothesized that the WBC profile in cerebrospinal fluid (CSF) correlates with the presence of tumor cells and prognosis in pediatric CNS tumors, as well as other patient and disease characteristics, and differs by tumor type, thus giving insight into the tumor immune response. METHODS: We conducted a retrospective analysis of CSF WBC profiles at CNS tumor diagnosis in 269 patients at our institution. We examined total nucleated cell count, absolute counts, and percentages by WBC subtype. We compared CSF WBC values by tumor cell presence, patient vital status, tumor location, and the most common tumor types. RESULTS: Patients who died of their tumor had a lower CSF lymphocyte percentage and a higher absolute monocyte count in CSF at diagnosis. The presence of tumor cells in CSF was associated with fewer lymphocytes and monocytes. Ventricular tumors had higher CSF lymphocyte, monocyte, macrophage, and total nucleated cell counts than extraventricular tumors. Germ cell tumors, low-grade glioma, high-grade glioma, and ependymoma had lower macrophage counts or percentages compared to other tumor types. CONCLUSIONS: WBC profile in CSF at pediatric CNS tumor diagnosis correlates with patient prognosis and presence of metastatic cells, along with tumor type and other tumor characteristics like relationship to the ventricles. Prospective CSF profiling and study may be useful to future immunotherapy and other pediatric CNS tumor clinical trials.

Population-based analysis of CNS tumor diagnoses, treatment, and survival in congenital and infant age groups.

BACKGROUND: Congenital (< 3 months) and infant (3 to 11 months) brain tumors are biologically different from tumors in older children, but their epidemiology has not been studied comprehensively. Insight into epidemiological differences could help tailor treatment recommendations by age and increase overall survival (OS). METHODS: Population-based data from SEER were obtained for 14,493 0-19-year-olds diagnosed with CNS tumors 1990-2015. Congenital and infant age groups were compared to patients aged 1-19 years based on incidence, treatment, and survival using Chi-square and Kaplan-Meier analyses. Hazard ratios were estimated from univariate and multivariable Cox proportional hazards survival analyses. RESULTS: Between the < 3-month, 3-5-month, 6-11 month, and 1-19-year age groups, tumor type distribution differed significantly (p < 0.001). 5-year OS for all tumors was 36.7% (< 3 months), 56.0% (< 3-5 months), 63.8% (6-11 months), and 74.7% (1-19 years) (p < 0.001). Comparing between age groups by tumor type, OS was worst for < 3-month-olds with low-grade glioma, medulloblastoma, and other embryonal tumors; OS was worst for 3-5-month-olds with ependymoma, < 1-year-olds collectively with atypical teratoid-rhabdoid tumor, and 1-19-year-olds with high-grade glioma (HGG) (log rank p < 0.02 for all tumor types). Under 3-month-olds were least likely to receive any treatment for each tumor type and least likely to undergo surgery for all except HGG. Under 1-year-olds were far less likely than 1-19-year-olds to undergo both radiation and chemotherapy for embryonal tumors. CONCLUSIONS: Subtype distribution, treatment patterns, and prognosis of congenital/infant CNS tumors differ from those in older children. Better, more standardized treatment guidelines may improve poorer outcomes seen in these youngest patients.

Landscape-scale conservation mitigates the biodiversity loss of grassland birds.

The decline of biodiversity from anthropogenic landscape modification is among the most pressing conservation problems worldwide. In North America, long-term population declines have elevated the recovery of the grassland avifauna to among the highest conservationpriorities. Because the vast majority of grasslands of the Great Plains are privately owned, the recovery of these ecosystems and bird populations within them depend on landscape-scale conservation strategies that integrate social, economic, and biodiversity objectives. The Conservation Reserve Program (CRP) is a voluntary program for private agricultural producers administered by the United States Department of Agriculture that provides financial incentives to take cropland out of production and restore perennial grassland. We investigated spatial patterns of grassland availability and restoration to inform landscape-scale conservation for a comprehensive community of grassland birds in the Great Plains. The research objectives were to (1) determine how apparent habitat loss has affected spatial patterns of grassland bird biodiversity, (2) evaluate the effectiveness of CRP for offsetting the biodiversity declines of grassland birds, and (3) develop spatially explicit predictions to estimate the biodiversity benefit of adding CRP to landscapes impacted by habitat loss. We used the Integrated Monitoring in Bird Conservation Regions program to evaluate hypotheses for the effects of habitat loss and restoration on both the occupancy and species richness of grassland specialists within a continuum-modeling framework. We found the odds of community occupancy declined by 37% for every 1 SD decrease in grassland availability [loge (km2 )] and increased by 20% for every 1 SD increase in CRP land cover [loge (km2 )]. There was 17% turnover in species composition between intact grasslands and CRP landscapes, suggesting that grasslands restored by CRP retained considerable, but incomplete, representation of biodiversity in agricultural landscapes. Spatially explicit predictions indicated that absolute conservation outcomes were greatest at high latitudes in regions with high biodiversity, whereas the relative outcomes were greater at low latitudes in highly modified landscapes. By evaluating community-wide responses to landscape modification and CRP restoration at bioregional scales, our study fills key information gaps for developing collaborative strategies, and for balancing conservation of avian biodiversity and social well-being in the agricultural production landscapes of the Great Plains.

Functional Realignment of Frontoparietal Subnetworks during Divergent Creative Thinking.

Creative cognition has been consistently associated with functional connectivity between frontoparietal control and default networks. However, recent research identified distinct connectivity dynamics for subnetworks within the larger frontoparietal system-one subnetwork (FPCNa) shows positive coupling with the default network and another subnetwork (FPCNb) shows negative default coupling-raising questions about how these networks interact during creative cognition. Here we examine frontoparietal subnetwork functional connectivity in a large sample of participants (n = 171) who completed a divergent creative thinking task and a resting-state scan during fMRI. We replicated recent findings on functional connectivity of frontoparietal subnetworks at rest: FPCNa positively correlated with the default network and FPCNb negatively correlated with the default network. Critically, we found that divergent thinking evoked functional connectivity between both frontoparietal subnetworks and the default network, but in different ways. Using community detection, we found that FPCNa regions showed greater coassignment to a default network community. However, FPCNb showed overall stronger functional connectivity with the default network-reflecting a reversal of negative connectivity at rest-and the strength of FPCNb-default network connectivity correlated with individual creative ability. These findings provide novel evidence of a behavioral benefit to the cooperation of typically anticorrelated brain networks.

Thrombosis, Bleeding, and the Observational Effect of Early Therapeutic Anticoagulation on Survival in Critically Ill Patients With COVID-19.

BACKGROUND: Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19). OBJECTIVE: To evaluate the incidence of venous thromboembolism (VTE) and major bleeding in critically ill patients with COVID-19 and examine the observational effect of early therapeutic anticoagulation on survival. DESIGN: In a multicenter cohort study of 3239 critically ill adults with COVID-19, the incidence of VTE and major bleeding within 14 days after intensive care unit (ICU) admission was evaluated. A target trial emulation in which patients were categorized according to receipt or no receipt of therapeutic anticoagulation in the first 2 days of ICU admission was done to examine the observational effect of early therapeutic anticoagulation on survival. A Cox model with inverse probability weighting to adjust for confounding was used. SETTING: 67 hospitals in the United States. PARTICIPANTS: Adults with COVID-19 admitted to a participating ICU. MEASUREMENTS: Time to death, censored at hospital discharge, or date of last follow-up. RESULTS: Among the 3239 patients included, the median age was 61 years (interquartile range, 53 to 71 years), and 2088 (64.5%) were men. A total of 204 patients (6.3%) developed VTE, and 90 patients (2.8%) developed a major bleeding event. Independent predictors of VTE were male sex and higher D-dimer level on ICU admission. Among the 2809 patients included in the target trial emulation, 384 (11.9%) received early therapeutic anticoagulation. In the primary analysis, during a median follow-up of 27 days, patients who received early therapeutic anticoagulation had a similar risk for death as those who did not (hazard ratio, 1.12 [95% CI, 0.92 to 1.35]). LIMITATION: Observational design. CONCLUSION: Among critically ill adults with COVID-19, early therapeutic anticoagulation did not affect survival in the target trial emulation. PRIMARY FUNDING SOURCE: None.

Proximal humeral fracture-dislocations: which patterns can be reduced in the emergency department?

BACKGROUND: Shoulder fracture-dislocations can represent a challenging management scenario in the emergency department (ED) because of concern for the presence of occult fractures that may displace during a reduction attempt. The alternative, a closed reduction attempt in the operating room, has the benefit of full paralysis but requires additional resource utilization. There is limited guidance in the literature about the risks of an initial reduction attempt in the ED as a function of fracture pattern to help guide physicians with this decision. METHODS: This was a retrospective case review of adult patients with shoulder dislocations and fracture-dislocations seen in the ED at a level 1 trauma center over a 10-year period. Imaging and medical records were reviewed to evaluate whether the reduction attempt was successful, unsuccessful without worsening, or unsuccessful with worsening alignment of any fractures, as well as the ultimate clinical outcome. RESULTS: We identified 165 patients with fracture-dislocations and 484 patients with simple dislocations during the same period. Of the patients with fracture-dislocations, 103 had greater tuberosity fractures, 12 had nondisplaced surgical neck fractures, and 50 had displaced surgical neck fractures. None of the patients with simple dislocations had displacement during an ED reduction attempt, including 100 patients aged >65 years. Of the 103 patients with greater tuberosity fracture-dislocations, only 1 had displacement of a humeral shaft fracture during ED reduction. Displacement occurred in 6 of 8 patients with nondisplaced neck fractures who underwent an initial ED reduction attempt vs. 1 of 4 patients who underwent the initial reduction attempt in the operating room. ED reduction was attempted in 25 of the 50 displaced humeral neck fracture-dislocations and was successful in 10 of these (40%). CONCLUSIONS: For patients with greater tuberosity fracture-dislocations, there is a low rate of displacement with a reduction attempt in the ED, but an ED reduction attempt in nondisplaced neck fractures is not recommended because of the high rate of displacement. For displaced neck fractures, closed reduction can be successful in select patients. Finally, these data confirm prior reports that closed reduction of simple shoulder dislocations in patients aged >65 years is safe in the ED.

Rural residents' emotions, beliefs, and sources that influenced those beliefs regarding sex offender policies, practice, and the efficacy of treatment.

Public perceptions regarding a sex offender's likelihood to reoffend and the efficacy of sex offender policies and practices is often inconsistent with the extant literature in academia. Thus, there is a critical need to better understand what influences those beliefs regarding sex offender policies and practices. We collected data from 284 residents from government defined rural counties and sought to examine: (1) the sources that were most influential in shaping their beliefs regarding sex offender policies and practices; (2) what characteristics the "influential sources" had; and (3) the residents' emotional response when they think about "sex offenders". The majority of participants were supportive of registration, community notification, and use of the polygraph. Further, the results suggest that "academics and peer review articles" rarely influence beliefs. Rather, "personal experiences" and the emotions "rage" and "sadness" (but not anger or disgust) may be important in influencing rural residents' beliefs regarding sex offender treatment, castration, execution, and misconceptions regarding juveniles with a sex offense. We conclude by discussing: (1) potential factors that may affect why academics are not perceived as influential sources; and (2) possibilities for how scientists can influence rural residents' beliefs by utilizing personal experiences and anecdotal information that may spark emotion.

Connectome-Based Predictive Modeling of Creativity Anxiety.

While a recent upsurge in the application of neuroimaging methods to creative cognition has yielded encouraging progress toward understanding the neural underpinnings of creativity, the neural basis of barriers to creativity are as yet unexplored. Here, we report the first investigation into the neural correlates of one such recently identified barrier to creativity: anxiety specific to creative thinking, or creativity anxiety (Daker et al., 2019). We employed a machine-learning technique for exploring relations between functional connectivity and behavior (connectome-based predictive modeling; CPM) to investigate the functional connections underlying creativity anxiety. Using whole-brain resting-state functional connectivity data, we identified a network of connections or "edges" that predicted individual differences in creativity anxiety, largely comprising connections within and between regions of the executive and default networks and the limbic system. We then found that the edges related to creativity anxiety identified in one sample generalize to predict creativity anxiety in an independent sample. We additionally found evidence that the network of edges related to creativity anxiety were largely distinct from those found in previous work to be related to divergent creative ability (Beaty et al., 2018). In addition to being the first work on the neural correlates of creativity anxiety, this research also included the development of a new Chinese-language version of the Creativity Anxiety Scale, and demonstrated that key behavioral findings from the initial work on creativity anxiety are replicable across cultures and languages.