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The objectives of this study were to develop and refine EMPOWER (Enhancing and Mobilizing the POtential for Wellness and Resilience), a brief manualized cognitive-behavioral, acceptance-based intervention for surrogate decision-makers of critically ill patients and to evaluate its preliminary feasibility, acceptability, and promise in improving surrogates’ mental health and patient outcomes.
Part 1 involved obtaining qualitative stakeholder feedback from 5 bereaved surrogates and 10 critical care and mental health clinicians. Stakeholders were provided with the manual and prompted for feedback on its content, format, and language. Feedback was organized and incorporated into the manual, which was then re-circulated until consensus. In Part 2, surrogates of critically ill patients admitted to an intensive care unit (ICU) reporting moderate anxiety or close attachment were enrolled in an open trial of EMPOWER. Surrogates completed six, 15–20 min modules, totaling 1.5–2 h. Surrogates were administered measures of peritraumatic distress, experiential avoidance, prolonged grief, distress tolerance, anxiety, and depression at pre-intervention, post-intervention, and at 1-month and 3-month follow-up assessments.
Part 1 resulted in changes to the EMPOWER manual, including reducing jargon, improving navigability, making EMPOWER applicable for a range of illness scenarios, rearranging the modules, and adding further instructions and psychoeducation. Part 2 findings suggested that EMPOWER is feasible, with 100% of participants completing all modules. The acceptability of EMPOWER appeared strong, with high ratings of effectiveness and helpfulness (M = 8/10). Results showed immediate post-intervention improvements in anxiety (d = −0.41), peritraumatic distress (d = −0.24), and experiential avoidance (d = −0.23). At the 3-month follow-up assessments, surrogates exhibited improvements in prolonged grief symptoms (d = −0.94), depression (d = −0.23), anxiety (d = −0.29), and experiential avoidance (d = −0.30).
Significance of results
Preliminary data suggest that EMPOWER is feasible, acceptable, and associated with notable improvements in psychological symptoms among surrogates. Future research should examine EMPOWER with a larger sample in a randomized controlled trial.
Supraglacial ponds and ice cliffs can dramatically enhance ablation rates on debris-covered glaciers. Supraglacial ponds can also coalesce, forming moraine-dammed lakes at risk of glacial lake outburst flood (GLOF). Given Bhutanese glaciers have some of the highest ice loss rates in the Himalaya and GLOF vulnerability is high, we seek to advance our understanding of the spatial distribution and evolution of supraglacial ponds and ice cliffs. Here, we use high-resolution (3 m) Planet Labs satellite imagery to provide the first short-term, high-resolution dataset of supraglacial pond and ice cliff evolution for three glaciers along the Bhutan–Tibet border from 2016 to 2018. A total of 5754 ponds and 2088 ice cliffs were identified. Large intra-annual changes were observed, with ponded area changes and drainage events coinciding with the seasonality of the Indian Summer Monsoon. On average, ~19% of the total number of ponds had a coincident ice cliff. Pond spatial distribution was driven by ice-surface velocities, with higher numbers of ponds found in areas of low velocity (<8 m a−1). Our study provides the first detailed, quantitative investigation of supraglacial ponds and ice cliffs in Bhutan, providing a framework for further monitoring in this understudied, yet important, region of the Himalaya.
To conduct a meta-analysis of the effect of ketamine on psychopathology in healthy volunteers and patients with schizophrenia, and the experimental factors affecting this.
Ketamine is increasingly used to treat depression and other psychiatric disorders but can induce schizophrenia-like symptoms. Despite this, the consistency and magnitude of symptoms induced by ketamine, or what factors influence the effects of ketamine on these remain unknown.
MEDLINE, EMBASE and PsychINFO databases were searched for within-subject placebo controlled studies reporting symptoms using the Brief Psychiatric Rating Scale (BPRS) or Positive and Negative Syndrome Scale (PANSS) in response to an acute ketamine challenge in healthy participants or people with schizophrenia. Two independent investigators extracted study-level data for a random-effects meta-analysis. Total, positive and negative BPRS and PANSS scores were extracted. Sub-group analyses were conducted examining the effect of: blinding status, ketamine preparation, infusion method and time between ketamine and placebo condition. Standardized mean change scores were used as effect sizes for individual studies. Standardized mean changes between ketamine and placebo for total, positive and negative BPRS and PANSS were calculated.
Of 7819 citations retrieved, 36 studies involving healthy participants were included. The overall sample included 725 healthy volunteers exposed to both the ketamine and placebo condition. Ketamine induced a significant increase in transient psychopathology in healthy participants, for total (Standardized mean change (SMC) = 1.50 (95% CI = 1.23 to 1.77), p < 0.0001), positive (SMC = 1.55 (95% CI = 1.29 to 1.81), p < 0.0001) and negative (SMC = 1.16, (95% CI = 0.96 to 1.35), p < 0.0001) symptom ratings, relative to the placebo condition. This effect was significantly greater for positive symptoms than negative symptoms (p = 0.004). Bolus followed by constant infusion increased ketamine's effect on positive symptoms relative to infusion alone (p = 0.006). Single-day study design increased ketamine's effect on total symptoms (p = 0.007), but age and gender did not moderate effects. There were insufficient studies for meta-analysis of studies in schizophrenia. Of these studies, two found a significant increase in symptoms with ketamine administration in total and positive symptoms. Only one study found an increase in negative symptom severity with ketamine.
These findings show that acute ketamine administration induces schizophrenia-like symptomatology with large effect sizes but there is a greater increase in positive than negative symptoms, and when a bolus is used. These findings suggest bolus doses should be avoided in its therapeutic use to minimize the risk of inducing transient positive psychotic symptoms.
Symptoms may be more useful prognostic markers for mental illness than diagnoses. We sought to investigate symptom domains in women with pre-existing severe mental illness (SMI; psychotic and bipolar disorder) as predictors of relapse risk during the perinatal period.
Data were obtained from electronic health records of 399 pregnant women with SMI diagnoses from a large south London mental healthcare provider. Symptoms within six domains characteristically associated with SMI (positive, negative, disorganization, mania, depression, and catatonia) recorded in clinical notes 2 years before pregnancy were identified with natural language processing algorithms to extract data from text, and associations investigated with hospitalization during pregnancy and 3 months postpartum.
Seventy-six women (19%) relapsed during pregnancy and 107 (27%) relapsed postpartum. After adjusting for covariates, disorganization symptoms showed a positive association at borderline significance with relapse during pregnancy (adjusted odds ratio [aOR] = 1.36; 95% confidence interval [CI] = 0.99–1.87 per unit increase in number of symptoms) and depressive symptoms negatively with relapse postpartum (0.78; 0.62–0.98). Restricting the sample to women with at least one recorded symptom in any given domain, higher disorganization (1.84; 1.22–2.76), positive (1.50; 1.07–2.11), and manic (1.48; 1.03–2.11) symptoms were associated with relapse during pregnancy, and disorganization (1.54; 1.08–2.20) symptom domains were associated with relapse postpartum.
Positive, disorganization, and manic symptoms recorded in the 2 years before pregnancy were associated with increased risk of relapse during pregnancy and postpartum. The characterization of routine health records from text fields is relatively transferrable and could help inform predictive risk modelling.
ABSTRACT IMPACT: We present a minimally-invasive approach to monitoring heavy metal exposures in geographically disperse populations; this framework may encourage and facilitate greater participation in a broad range of related clinical studies that require biosampling. OBJECTIVES/GOALS: We hypothesize that microneedle array (MA) extraction of interstitial fluid (ISF) will enable minimally-invasive quantitation of heavy metal (HM) exposure. We establish analytical parameters for ICP-MS analysis of HMs in ISF, quantify baseline HM content in ISF vs other fluids, and characterize a mixed HM exposure model. METHODS/STUDY POPULATION: Recent advances in ISF extraction and analysis suggest a minimally-invasive to monitor HM exposure longitudinally in both urban and dispersed communities. ISF can be collected with MAs and is a rich source of disease and exposure biomarkers. To refine analytical methods, Human subjects with no underlying skin disease were recruited into the IRB-approved study. Each subject had blood and urine collected. ISF was also collected using 3D-printed MA-holders. The fluids were analyzed, using ICP-MS, to quantify the levels of uranium (U), cadmium (Cd), vanadium (V), and arsenic (As). Additionally, we analyzed 2,770 subjects from the public NHANES dataset from 2018-2019. Python and Scikit-learn were used to analyze the demographics, survey responses, and metal concentrations for these individuals. RESULTS/ANTICIPATED RESULTS: While several studies have described the surface water and sediment content of toxic metals, determining biological loads remains challenging due to the need to collect blood or urine from a dispersed rural population over time. Our preliminary results suggest similar HM concentrations in ISF, compared with blood in a small unexposed population. Analysis of subjects from the NHANES public datasets suggest similar baseline blood HM concentrations in diverse subject populations with some differences in Cd depending on smoking and e-cigarette usage. Correlation maps also suggest possible synergy between different metals with cobalt and chromium showing the highest correlation. The initial results from this study have been applied to develop a mixed HM exposure model in rats for further translational testing. DISCUSSION/SIGNIFICANCE OF FINDINGS: We present a minimally-invasive HM monitoring approach. Exposure to multiple HMs is suspected to have additive or synergistic harmful health effects. We ultimately envision a wearable microneedle patch that could be mailed to individuals or distributed through community centers, worn for a few hours, and returned to a central laboratory.
Although recognized as one of the most significant cultural transformations in North America, the reintroduction of the horse to the continent after AD 1492 has been rarely addressed by archaeological science. A key contributing factor behind this limited study is the apparent absence of equine skeletal remains from early historic archaeological contexts. Here, we present a multidisciplinary analysis of a horse skeleton recovered in Lehi, Utah, originally attributed to the Pleistocene. Reanalysis of stratigraphic context and radiocarbon dating indicates a historic age for this horse (cal AD 1681–1939), linking it with Ute or other Indigenous groups, whereas osteological features demonstrate its use for mounted horseback riding—perhaps with a nonframe saddle. DNA analysis indicates that the animal was a female domestic horse, which was likely cared for as part of a breeding herd despite outliving its usefulness in transport. Finally, sequentially sampled stable carbon, oxygen, and strontium isotope values from tooth enamel (δ13C, δ18O, and 87Sr/86Sr) suggest that the horse was raised locally. These results show the utility of archaeological science as applied to horse remains in understanding Indigenous horse pastoralism, whereas consideration of the broader archaeological record suggests a pattern of misidentification of horse bones from early historic contexts.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
Dopaminergic imaging is an established biomarker for dementia with Lewy bodies, but its diagnostic accuracy at the mild cognitive impairment (MCI) stage remains uncertain.
To provide robust prospective evidence of the diagnostic accuracy of dopaminergic imaging at the MCI stage to either support or refute its inclusion as a biomarker for the diagnosis of MCI with Lewy bodies.
We conducted a prospective diagnostic accuracy study of baseline dopaminergic imaging with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computerised tomography (123I-FP-CIT SPECT) in 144 patients with MCI. Images were rated as normal or abnormal by a panel of experts with access to striatal binding ratio results. Follow-up consensus diagnosis based on the presence of core features of Lewy body disease was used as the reference standard.
At latest assessment (mean 2 years) 61 patients had probable MCI with Lewy bodies, 26 possible MCI with Lewy bodies and 57 MCI due to Alzheimer's disease. The sensitivity of baseline FP-CIT visual rating for probable MCI with Lewy bodies was 66% (95% CI 52–77%), specificity 88% (76–95%) and accuracy 76% (68–84%), with positive likelihood ratio 5.3.
It is over five times as likely for an abnormal scan to be found in probable MCI with Lewy bodies than MCI due to Alzheimer's disease. Dopaminergic imaging appears to be useful at the MCI stage in cases where Lewy body disease is suspected clinically.
Background: Measles is a highly contagious virus that reemerged in 2019 with the highest number of reported cases in the United States since 1992. Beginning in March 2019, The Johns Hopkins Hospital (JHH) responded to an influx of patients with concern for measles as a result of outbreaks in Maryland and the surrounding states. We report the JHH Department of Infection Control and Hospital Epidemiology (HEIC) response to this measles outbreak using a multidisciplinary measles incident command system (ICS). Methods: The JHH HEIC and the Johns Hopkins Office of Emergency Management established the HEIC Clinical Incident Command Center and coordinated a multipronged response to the measles outbreak with partners from occupational health services, microbiology, the adult and pediatric emergency departments, marketing and communication and local and state public health departments. The multidisciplinary structure rapidly developed, approved, and disseminated tools to improve the ability of frontline providers to quickly identify, isolate, and determine testing needs for patients suspected to have measles infection and reduce the risk of secondary transmission. The tools included a triage algorithm, visitor signage, staff and patient vaccination guidance and clinics, and standard operating procedures for measles evaluation and testing. The triage algorithms were developed for phone or in-person and assessed measles exposure history, immune status, and symptoms, and provided guidance regarding isolation and the need for testing. The algorithms were distributed to frontline providers in clinics and emergency rooms across the Johns Hopkins Health System. The incident command team also distributed resources to community providers to reduce patient influx to JHH and staged an outdoor measles evaluation and testing site in the event of a case influx that would exceed emergency department resources. Results: From March 2019 through June 2019, 37 patients presented with symptoms or concern for measles. Using the ICS tools and algorithms, JHH rapidly identified, isolated, and tested 11 patients with high suspicion for measles, 4 of whom were confirmed positive. Of the other 26 patients not tested, none developed measles infection. Exposures were minimized, and there were no secondary measles transmissions among patients. Conclusions: Using the ICS and development of tools and resources to prevent measles transmission, including a patient triage algorithm, the JHH team successfully identified, isolated, and evaluated patients with high suspicion for measles while minimizing exposures and secondary transmission. These strategies may be useful to other institutions and locales in the event of an emerging or reemerging infectious disease outbreak.
Disclosures: Aaron Milstone reports consulting for Becton Dickinson.
Beothukis mistakensis from the Ediacaran System of Newfoundland, Canada demonstrates complex fractal-like morphology through the development of primary-, secondary- and tertiary-order Rangea-like units. The primary-order rangeomorph units observed in B. mistakensis are tightly juxtaposed, show no evidence of being independent of one another and are made up of chamber-like secondary-order – probably mesoglea-filled – units. The growth of these rangeomorph units demonstrates that the frond developed from the tip towards the basal region through ontogeny. The tertiary-order units of Beothukis are considered to represent surface morphology on the secondary-order units. This is in contrast to palaeobiological reconstructions of Beothukis that invoke three-dimensional fractal-like branches with independent units, which has been used to infer an osmotrophic mode of life. It is considered here that the fractal-like morphology of the lower surface of B. mistakensis was an adaptation to increase surface area to volume ratio. The quilted morphology of Beothukis proposed here is consistent with a sessile, reclining, phagocytotic and/or chemosymbiotic mode of life similar to that invoked for the reclining rangeomorph Fractofusus.
Results of in situ U–Pb dating of calcite spherulites, cone-in-cone (CIC) calcite and calcite fibres from a calcareous concretion of the upper Ediacaran of Finnmark, Arctic Norway, are reported. Calcite spherulites from the innermost layers of the concretion yielded a lower intercept age of 563 ± 70 Ma, which, although imprecise, is within uncertainty of the age of sedimentation based on fossil assemblages. Non-deformed CIC calcite from the bottom part of the concretion yielded an age of 475 ± 25 Ma, which is interpreted as the age of CIC calcite formation during a period of fluid overpressure induced during burial of the sediments. Deformed CIC calcite from the top part of the concretion yielded an age of 418 ± 23 Ma, which overlaps with a known Caledonian tectono-metamorphic event, and indicates a potential post-depositional overprint at this time. Calcite fibres that grew in small fissures along spherulite rims, which are interpreted as a recrystallization feature during deformation and formation of a cleavage, gave an imprecise age of 486 ± 161 Ma. Our results show that U–Pb dating of calcite can provide age constraints for ancient carbonates and syn- to post-depositional processes that operated during burial and metamorphic overprinting.
The updated common rule, for human subjects research, requires that consents “begin with a ‘concise and focused’ presentation of the key information that will most likely help someone make a decision about whether to participate in a study” (Menikoff, Kaneshiro, Pritchard. The New England Journal of Medicine. 2017; 376(7): 613–615.). We utilized a community-engaged technology development approach to inform feature options within the REDCap software platform centered around collection and storage of electronic consent (eConsent) to address issues of transparency, clinical trial efficiency, and regulatory compliance for informed consent (Harris, et al. Journal of Biomedical Informatics 2009; 42(2): 377–381.). eConsent may also improve recruitment and retention in clinical research studies by addressing: (1) barriers for accessing rural populations by facilitating remote consent and (2) cultural and literacy barriers by including optional explanatory material (e.g., defining terms by hovering over them with the cursor) or the choice of displaying different videos/images based on participant’s race, ethnicity, or educational level (Phillippi, et al. Journal of Obstetric, Gynecologic, & Neonatal Nursing. 2018; 47(4): 529–534.).
We developed and pilot tested our eConsent framework to provide a personalized consent experience whereby users are guided through a consent document that utilizes avatars, contextual glossary information supplements, and videos, to facilitate communication of information.
The eConsent framework includes a portfolio of eight features, reviewed by community stakeholders, and tested at two academic medical centers.
Early adoption and utilization of this eConsent framework have demonstrated acceptability. Next steps will emphasize testing efficacy of features to improve participant engagement with the consent process.
A physical oceanographic, geophysical and marine geological survey of Edward VIII Gulf, Kemp Coast, collected data from conductivity–temperature–depth casts, multi-beam bathymetric swath mapping and 3.5 kHz sub-bottom surveying. Modified circumpolar deep water (mCDW) is observed in Edward VIII Gulf, as well as notable bathymetric features including mega-scale glacial lineations and a 1750 m-deep trough. Sedimentological, geochemical, rock-magnetic and micropalaeontological analysis of two kasten cores document regional palaeoclimate and palaeo-oceanographic conditions over the past 8000 years, with a warm period occurring from c. 8 to 4 ka and a shift to cooler conditions beginning at c. 4 ka and persisting until at least 0.9 ka. Sediment packages > 40 m thick within deep troughs in Edward VIII Gulf present potential targets for higher-resolution Holocene and deglacial climate studies. Despite the presence of mCDW on the shelf, inland bed topography consisting of highland terrain suggests the likelihood of relative stability of this sector of the East Antarctic Ice Sheet.
The mechanism through which developmental programming of offspring overweight/obesity following in utero exposure to maternal overweight/obesity operates is unknown but may operate through biologic pathways involving offspring anthropometry at birth. Thus, we sought to examine to what extent the association between in utero exposure to maternal overweight/obesity and childhood overweight/obesity is mediated by birth anthropometry. Analyses were conducted on a retrospective cohort with data obtained from one hospital system. A natural effects model framework was used to estimate the natural direct effect and natural indirect effect of birth anthropometry (weight, length, head circumference, ponderal index, and small-for-gestational age [SGA] or large-for-gestational age [LGA]) for the association between pre-pregnancy maternal body mass index (BMI) category (overweight/obese vs normal weight) and offspring overweight/obesity in childhood. Models were adjusted for maternal and child socio-demographics. Three thousand nine hundred and fifty mother–child dyads were included in analyses (1467 [57.8%] of mothers and 913 [34.4%] of children were overweight/obese). Results suggest that a small percentage of the effect of maternal pre-pregnancy BMI overweight/obesity on offspring overweight/obesity operated through offspring anthropometry at birth (weight: 15.5%, length: 5.2%, head circumference: 8.5%, ponderal index: 2.2%, SGA: 2.9%, and LGA: 4.2%). There was a small increase in the percentage mediated when gestational diabetes or hypertensive disorders were added to the models. Our study suggests that some measures of birth anthropometry mediate the association between maternal pre-pregnancy overweight/obesity and offspring overweight/obesity in childhood and that the size of this mediated effect is small.
The Minnesota Center for Twin and Family Research (MCTFR) comprises multiple longitudinal, community-representative investigations of twin and adoptive families that focus on psychological adjustment, personality, cognitive ability and brain function, with a special emphasis on substance use and related psychopathology. The MCTFR includes the Minnesota Twin Registry (MTR), a cohort of twins who have completed assessments in middle and older adulthood; the Minnesota Twin Family Study (MTFS) of twins assessed from childhood and adolescence into middle adulthood; the Enrichment Study (ES) of twins oversampled for high risk for substance-use disorders assessed from childhood into young adulthood; the Adolescent Brain (AdBrain) study, a neuroimaging study of adolescent twins; and the Siblings Interaction and Behavior Study (SIBS), a study of adoptive and nonadoptive families assessed from adolescence into young adulthood. Here we provide a brief overview of key features of these established studies and describe new MCTFR investigations that follow up and expand upon existing studies or recruit and assess new samples, including the MTR Study of Relationships, Personality, and Health (MTR-RPH); the Colorado-Minnesota (COMN) Marijuana Study; the Adolescent Brain Cognitive Development (ABCD) study; the Colorado Online Twins (CoTwins) study and the Children of Twins (CoT) study.
The purpose of this update is to provide the most current information about both the Colorado Adoption Project (CAP) and the Longitudinal Twin Study (LTS) and to introduce the Colorado Adoption/Twin Study of Lifespan behavioral development and cognitive aging (CATSLife), a product of their merger and a unique study of lifespan behavioral development and cognitive aging. The primary objective of CATSLife is to assess the unique saliency of early childhood genetic and environmental factors to adult cognitive maintenance and change, as well as proximal influences and innovations that emerge across development. CATSLife is currently assessing up to 1600 individuals on the cusp of middle age, targeting those between 30 and 40 years of age. The ongoing CATSLife data collection is described as well as the longitudinal data available from the earlier CAP and LTS assessments. We illustrate CATSLife via current projects and publications, highlighting the measurement of genetic, biochemical, social, sociodemographic and environmental indices, including geospatial features, and their impact on cognitive maintenance in middle adulthood. CATSLife provides an unparalleled opportunity to assess prospectively the etiologies of cognitive change and test the saliency of early childhood versus proximal influences on the genesis of cognitive decline.