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We evaluated adverse drug events (ADE) by chart review in a random national sample of 428 Veterans with COVID-19 who received tocilizumab (n=173/428). ADEs (median time=5 days) occurred in 51/173 (29%) and included hepatoxicity (n=29) and infection (n=13). Concomitant medication discontinuation occurred in 22% of ADE patients; mortality was 39%.
Complex traumas are traumatic experiences that involve multiple interpersonal threats during childhood or adolescence, such as repeated abuse. These traumas are hypothesised to cause more severe psychopathology and poorer cognitive function than other non-complex traumas. However, empirical testing has been limited to clinical/convenience samples and cross-sectional designs.
To investigate psychopathology and cognitive function in young people exposed to complex, non-complex or no trauma, from a population-representative longitudinal cohort, and to consider the role of pre-existing vulnerabilities.
Participants were from the Environmental Risk Longitudinal Twin Study, a population-representative birth cohort of 2232 British children. At age 18 years (93% participation), we assessed lifetime exposure to complex and non-complex trauma, past-year psychopathology and current cognitive function. We also prospectively assessed early childhood vulnerabilities: internalising and externalising symptoms at 5 years of age, IQ at 5 years of age, family history of mental illness, family socioeconomic status and sex.
Participants exposed to complex trauma had more severe psychopathology and poorer cognitive function at 18 years of age, compared with both trauma-unexposed participants and those exposed to non-complex trauma. Early childhood vulnerabilities predicted risk of later complex trauma exposure, and largely explained associations of complex trauma with cognitive deficits, but not with psychopathology.
By conflating complex and non-complex traumas, current research and clinical practice underestimate the severity of psychopathology, cognitive deficits and pre-existing vulnerabilities linked with complex trauma. A better understanding of the mental health needs of people exposed to complex trauma could inform the development of new, more effective interventions.
Stable accessibility of partially hyperbolic systems is central to their stable ergodicity, and we establish its
-density among partially hyperbolic flows, as well as in the categories of volume-preserving, symplectic, and contact partially hyperbolic flows. As applications, we obtain on one hand in each of these four categories of flows the
-density of the
-stable topological transitivity and triviality of the centralizer, and on the other hand the
-density of the
-stable K-property of the natural volume in the latter three categories.
Prior studies of universal masking have not measured facemask compliance. We performed a quality improvement study to monitor and improve facemask compliance among healthcare personnel (HCP) during the coronavirus disease 2019 (COVID-19) pandemic.
Tertiary care center in West Haven, Connecticut
HCP including physicians, nurses, and ancillary staff
Facemask compliance was measured through direct observations during a 4-week baseline period after universal masking was mandated. Frontline and management HCP completed semi-structured interviews from which a multimodal intervention was developed. Direct observations were repeated during a 14-week period following implementation of the multimodal intervention. Differences between units were evaluated with chi-squared testing using the Bonferroni correction. Facemask compliance between baseline and intervention periods was compared using time series regression.
Among 1,561 observations during the baseline period, median weekly facemask compliance was 82.2% (range, 80.8%-84.4%). Semi-structured interviews were performed with 16 HCP. Qualitative analysis informed the development of a multimodal intervention consisting of audit and passive feedback, active discussion, and increased communication from leadership. Among 2,651 observations during the intervention period, median weekly facemask compliance was 92.6% (range, 84.6%-97.9%). There was no difference in weekly facemask compliance between COVID-19 and non-COVID-19 units. The multimodal intervention was associated with an increase in facemask compliance (β=0.023, p=0.002)
Facemask compliance remained suboptimal among HCP despite a facility-wide mandate for universal masking. A multimodal intervention consisting of audit and passive feedback, active discussion, and increased communication from leadership was effective in increasing facemask compliance among HCP.
We examined parent- and adolescent-reported executive functioning (EF) behaviors following pediatric traumatic brain injury (TBI) in the context of Online Family Problem-Solving Therapy (OFPST) and moderators of change in EF behaviors.
In total, 274 families were randomized to OFPST or an internet resource comparison group. Parents and adolescents completed the Behavior Rating Inventory of Executive Function at four time points. Mixed models were used to examine EF behaviors, assessing the effects of visit, treatment group, rater, TBI severity, age, socioeconomic status, and family functioning.
Parents rated their adolescents’ EF as poorer (F(3,1156) = 220.15, p < .001; M = 58.11, SE = 0.73) than adolescents rated themselves (M = 51.81, SE = 0.73). Across raters, EF behaviors were poorer for adolescents whose parents had less education (F(3,1156) = 8.60, p = .003; M = 56.76, SE = 0.98) than for those with more education (M = 53.16, SE = 0.88). Age at baseline interacted with visit (F(3,1156) = 5.05, p = .002), such that families of older adolescents reported improvement in EF behaviors over time. Family functioning also interacted with visit (F(3, 1156) = 2.61, p = .049), indicating more improvement in EF behaviors over time in higher functioning families. There were no effects of treatment or TBI severity.
We identified a discrepancy between parent- and adolescent-reported EF, suggesting reduced awareness of deficits in adolescents with TBI. We also found that poorer family functioning and younger age were associated with poorer recovery after TBI, whereas adolescents of parents with less education were reported as having greater EF deficits across time points.
The study examined the diagnosis experience of midlife family caregivers of a patient with a blood cancer, exploring similarities and differences between parent caregivers and adult-child caregivers.
Participants were between 30 and 65 years old and were family caregivers of a living patient with acute myeloid leukemia, acute lymphoblastic leukemia, or lymphoma. We conducted semi-structured interviews with parent caregivers (n = 20) and adult-child caregivers (n = 19) and a thematic analysis of the interview data.
Both types of caregivers report the patient experiencing (1) mis- and missed diagnosis (facing delayed diagnosis or treatment and having symptoms dismissed or overlooked) and (2) emotional distress (being in shock and survival mode, struggling with uncertainty, and confronting mortality). Adult-child caregivers also experienced relational shifts in assuming control of their parent's care, sometimes despite geographic distance, and struggled to distribute the care burden among family members.
Significance of results
Differences between the caregivers’ experiences emerged based on the relational role and the patient's place in the lifespan. Findings can be used to inform the development of support resources to address the needs of each group.
Stem cells give rise to the entirety of cells within an organ. Maintaining stem cell identity and coordinately regulating stem cell divisions is crucial for proper development. In plants, mobile proteins, such as WUSCHEL-RELATED HOMEOBOX 5 (WOX5) and SHORTROOT (SHR), regulate divisions in the root stem cell niche. However, how these proteins coordinately function to establish systemic behaviour is not well understood. We propose a non-cell autonomous role for WOX5 in the cortex endodermis initial (CEI) and identify a regulator, ANGUSTIFOLIA (AN3)/GRF-INTERACTING FACTOR 1, that coordinates CEI divisions. Here, we show with a multi-scale hybrid model integrating ordinary differential equations (ODEs) and agent-based modeling that quiescent center (QC) and CEI divisions have different dynamics. Specifically, by combining continuous models to describe regulatory networks and agent-based rules, we model systemic behaviour, which led us to predict cell-type-specific expression dynamics of SHR, SCARECROW, WOX5, AN3 and CYCLIND6;1, and experimentally validate CEI cell divisions. Conclusively, our results show an interdependency between CEI and QC divisions.
Incremental prediction of aggression from callous–unemotional (CU) traits is well established, but cross-cultural replication and studies of young children are needed. Little is understood about the contribution of CU traits in children who are already aggressive. We addressed these issues in prospective studies in the United Kingdom and Colombia. In a UK epidemiological cohort, CU traits and aggression were assessed at age 3.5 years, and aggression at 5.0 years by mothers (N = 687) and partners (N = 397). In a Colombian general population sample, CU traits were assessed at age 3.5 years and aggression at 3.5 and 5.0 years by mother report (N = 220). Analyses consistently showed prediction of age-5.0 aggression by age-3.5 CU traits controlling for age-3.5 aggression. Associations between age-3.5 CU traits and age-5.0 aggression were moderated by aggression at 3.5 years, with UK interaction terms, same informant, β = .07 p = .014 cross-informant, β = .14 p = .002, and in Colombia, β = .09 p = .128. The interactions arose from stronger associations between CU traits and later aggression in those already aggressive. Our findings with preschoolers replicated across culturally diverse settings imply a major role for CU traits in the maintenance and amplification of already established aggression, and cast doubt on their contribution to its origins.
In April 2019, the U.S. Fish and Wildlife Service (USFWS) released its recovery plan for the jaguar Panthera onca after several decades of discussion, litigation and controversy about the status of the species in the USA. The USFWS estimated that potential habitat, south of the Interstate-10 highway in Arizona and New Mexico, had a carrying capacity of c. six jaguars, and so focused its recovery programme on areas south of the USA–Mexico border. Here we present a systematic review of the modelling and assessment efforts over the last 25 years, with a focus on areas north of Interstate-10 in Arizona and New Mexico, outside the recovery unit considered by the USFWS. Despite differences in data inputs, methods, and analytical extent, the nine previous studies found support for potential suitable jaguar habitat in the central mountain ranges of Arizona and New Mexico. Applying slightly modified versions of the USFWS model and recalculating an Arizona-focused model over both states provided additional confirmation. Extending the area of consideration also substantially raised the carrying capacity of habitats in Arizona and New Mexico, from six to 90 or 151 adult jaguars, using the modified USFWS models. This review demonstrates the crucial ways in which choosing the extent of analysis influences the conclusions of a conservation plan. More importantly, it opens a new opportunity for jaguar conservation in North America that could help address threats from habitat losses, climate change and border infrastructure.
Child and adolescent mental health is understood to be highly embedded in the family system, particularly the parent-child relationship. Indeed, models of risk pathways to psychopathology emphasize interactions and transactions between the family environment and individual differences at the child level, including gene-environment interplay. Therapist knowledge regarding the role of the family in these pathways is central to the clinical competencies involved in the evidence-based treatment of children and adolescents. This chapter provides an overview of current theory regarding family contributions to the major forms psychopathology seen among children and adolescents. Attention is given to key family and parenting variables as they are conceptualized in the current literature, the mechanisms by which these variables contribute to the emergence and maintenance of psychopathology and the origins and determinants of parenting.
ABSTRACT IMPACT: Improved non-biased matching of clinical research professionals to PI needs will accelerate time to active project engagement for new hires. OBJECTIVES/GOALS: An ongoing challenge for HR recruiters when matching applicants to open job positions is the time-consuming screening effort, which relies on imprecise semantic searching. We propose building a precision-based matching tool using Natural Language Processing to automate the accurate and non-biased identification of suitable job candidates. METHODS/STUDY POPULATION: We conducted 30-45’ interviews with HR administration/recruitment specialists to delineate the recruitment and hiring process used to match CRC resumes to job descriptions (n=7). Next, CRC applicant resumes were evaluated by experts, first by independent review, followed by consensus and assignment of a final rating, 0= not qualified; 1= CRC1; 2= CRC2; 3= CRC3; 4= CRC4. Guidelines evolved after reviewing 6 batches of 50 unique resumes (300 total) and were based on applicant qualifications & experiences by job level, CRC 1-4. Using final guidelines an additional 3,145 resumes were rated. For uniform input into the NLP model, resume formats were converted and text contents extracted into multiple sections, i.e., education, professional experiences, etc. RESULTS/ANTICIPATED RESULTS: Guideline development: Rater agreement improved over time with poor agreement when no guidelines were present (.161- Kappa) to good agreement for final guidelines (.608- Kappa). Spearman’s rho correlation between guideline iterations and Kappa is large and positive (rho 0.886) indicating significant rater agreement. NLP Model: Resume to job description matching indicated a third of applications were qualified, a third overqualified, and a third underqualified, suggesting the majority of applicants were unable to identify their ‘best fit’ by job level. Our NLP model matched the candidate resume to CRC level with 73.3% accuracy; and achieved 79.2% accuracy when matching the applicant resume to the CRC job description. Refinement of the NLP Model is ongoing. DISCUSSION/SIGNIFICANCE OF FINDINGS: A precision-based NLP matching tool will improve applicant targeting for the hire of great, qualified candidates. Improved applicant to job matching offers several advantages, i.e., reduced bias with greater diversity and inclusion; reduced time-to-hire; ability to anticipate training needs; and a reduced time to active project engagement.
ABSTRACT IMPACT: Investigation of tumor-associated blood vessels may serve as an imaging biomarker of response to systemic therapy and cancer outcomes. OBJECTIVES/GOALS: Aberrancies in the tumor microvasculature limit the systemic delivery of anticancer agents, which impedes tumor response. Using human intravital microscopy (HIVM), we hypothesized that HIVM would be feasible in patients with peritoneal carcinomatosis (PC) and generate clinical utility. METHODS/STUDY POPULATION: During cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for PC, HIVM was performed in both tumor and non-tumor areas. The primary outcome was HIVM feasibility to measure vessel characteristics. We secondarily evaluated associations between HIVM vessel characteristics and oncologic outcomes (RECIST response to neoadjuvant therapy and disease-specific survival). RESULTS/ANTICIPATED RESULTS: Thirty patients with PC were enrolled. Nineteen patients (63.3%) received neoadjuvant therapy. HIVM was feasible in all patients. Compared to non-tumor (control) areas, PC areas had a lower density of functional vessels, higher proportion of non-functional vessels, smaller lumenal diameters, and lower blood flow velocity. Qualitative differences in these vessel characteristics were observed among patients who had partial response, stable disease, or progressive disease after receiving neoadjuvant therapy. However, no statistically significant relationships were found between HIVM vessel characteristics and oncologic outcomes. DISCUSSION/SIGNIFICANCE OF FINDINGS: These novel findings comprise the first-in-human, real-time evidence of the microscopic differences between normal and tumor-associated vessels and form the basis for our larger, ongoing clinical trial appropriately powered to determine the clinical utility of HIVM (NCT03823144).
Ice wedges are ubiquitous periglacial features in permafrost terrain. This study investigates the timing of ice wedge formation in the Fosheim Peninsula (Ellesmere and Axel Heiberg Islands). In this region, ice wedge polygons occupy ~50% of the landscape, the majority occurring below the marine limit in the Eureka Sound Lowlands. Numerical simulations suggest that ice wedges may crack to depths of 2.7–3.6 m following a rapid cooling of the ground over mean winter surface temperatures of −18°C to −38°C, corresponding to the depth of ice wedges in the region. The dissolved organic carbon (DOC)/Cl molar ratios suggest that the DOC in the ice wedges is sourced from snowmelt and not from leaching of the active layer. Based on 32 14CDOC measurements from 15 ice wedges, the wedges were likely developing between 9000–2500 cal yr BP. This interval also corresponds to the period of peat accumulation in the region, a proxy of increased moisture. Considering that winter air temperatures remained favorable for ice wedge growth throughout the Holocene, the timing of ice wedge formation reflects changes in snowfall. Overall, this study provides the first reconstruction of ice wedge formation from a high Arctic polar desert environment.
The fetal–placental–maternal unit can produce significant abnormalities in the neonate’s hematologic health at birth. A newborn can have disorders of white blood cells, red blood cells, or platelets, or any combination thereof. Neonatal cytopenias can result from dilution, peripheral destruction, or a defect in cellular production . Maternal illness can be the cause of such abnormalities (Table 23.1). Close communication between the obstetrical provider and the pediatrician is important. This can allow for anticipation of a problem in order to mitigate the consequences, or to discover the cause if an unexpected cytopenia is detected.
A recent suicidal drive hypothesis posits that psychotic experiences (PEs) may serve to externalize internally generated and self-directed threat (i.e., self-injurious/suicidal behavior [SIB]) in order to optimize survival; however, it must first be demonstrated that such internal threat can both precede and inform PEs. The current study conducted the first known bidirectional analysis of SIB and PEs to test whether SIB could be considered as a plausible antecedent for PEs. Prospective data were utilized from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative birth cohort of 2232 twins, that captured SIB (any self-harm or suicidal attempt) and PEs at ages 12 and 18 years. Cross-lagged panel models demonstrated that the association between SIB at age 12 and PEs at age 18 was as strong as the association between PEs at age 12 and SIB at age 18. Indeed, the best representation of the data was a model where these paths were constrained to be equal (OR = 2.48, 95% CI = 1.63–3.79). Clinical interview case notes for those who reported both SIB and PEs at age 18, revealed that PEs were explicitly characterized by SIB/threat/death-related content for 39% of cases. These findings justify further investigation of the suicidal drive hypothesis.