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In 2019, a 42-year-old African man who works as an Ebola virus disease (EVD) researcher traveled from the Democratic Republic of Congo (DRC), near an ongoing EVD epidemic, to Philadelphia and presented to the Hospital of the University of Pennsylvania Emergency Department with altered mental status, vomiting, diarrhea, and fever. He was classified as a “wet” person under investigation for EVD, and his arrival activated our hospital emergency management command center and bioresponse teams. He was found to be in septic shock with multisystem organ dysfunction, including circulatory dysfunction, encephalopathy, metabolic lactic acidosis, acute kidney injury, acute liver injury, and diffuse intravascular coagulation. Critical care was delivered within high-risk pathogen isolation in the ED and in our Special Treatment Unit until a diagnosis of severe cerebral malaria was confirmed and EVD was definitively excluded.
This report discusses our experience activating a longitudinal preparedness program designed for rare, resource-intensive events at hospitals physically remote from any active epidemic but serving a high-volume international air travel port-of-entry.
A combination of olanzapine and samidorphan (OLZ/SAM) is in development for schizophrenia to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain. The objective of this phase 1 exploratory study was to assess metabolic treatment effects of OLZ/SAM.
Healthy, non-obese adults (18–40 years) were randomized 2:2:1 to once-daily OLZ/SAM, olanzapine, or placebo for 21 days. Assessments included oral glucose tolerance test (OGTT), hyperinsulinemic-euglycemic clamp, weight gain, and adverse event (AE) monitoring. Treatment effects were estimated with analysis of covariance.
Sixty subjects were randomized (OLZ/SAM, n=24; olanzapine, n=24; placebo, n=12); 19 (79.2%), 22 (91.7%), and 11 (91.7%), respectively, completed the study. In the OGTT, olanzapine led to significant hyperinsulinemia (P<0.0001) and significantly reduced insulin sensitivity (2-hour Matsuda index) at day 19 vs baseline (P=0.0012), changes not observed with OLZ/SAM. No significant between-group differences were observed for change from baseline in clamp-derived insulin sensitivity index at day 21. Least squares mean weight change from baseline was similar with OLZ/SAM (3.16 kg) and olanzapine (2.87 kg); both were significantly higher than placebo (0.57 kg; both P<0.01). Caloric intake significantly decreased from baseline to day 22 with OLZ/SAM (P=0.015) but not with olanzapine or placebo. Forty-nine subjects (81.7%) experienced ≥1 AE (OLZ/SAM, 87.5%; olanzapine, 79.2%; placebo, 75.0%).
In this exploratory study, hyperinsulinemia and decreased insulin sensitivity were observed in the OGTT with olanzapine but not with OLZ/SAM or placebo. Clamp-derived insulin sensitivity index and weight changes were similar with OLZ/SAM and olanzapine in healthy subjects during the 3-week study.
UK Biobank is a well-characterised cohort of over 500 000 participants including genetics, environmental data and imaging. An online mental health questionnaire was designed for UK Biobank participants to expand its potential.
Describe the development, implementation and results of this questionnaire.
An expert working group designed the questionnaire, using established measures where possible, and consulting a patient group. Operational criteria were agreed for defining likely disorder and risk states, including lifetime depression, mania/hypomania, generalised anxiety disorder, unusual experiences and self-harm, and current post-traumatic stress and hazardous/harmful alcohol use.
A total of 157 366 completed online questionnaires were available by August 2017. Participants were aged 45–82 (53% were ≥65 years) and 57% women. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status. Lifetime depression was a common finding, with 24% (37 434) of participants meeting criteria and current hazardous/harmful alcohol use criteria were met by 21% (32 602), whereas other criteria were met by less than 8% of the participants. There was extensive comorbidity among the syndromes. Mental disorders were associated with a high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
The UK Biobank questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed because of selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
The chapter examines racist and colonialist assumptions in Bergson’s philosophy and outlines what is at stake in the various approaches to these assumptions that recent interpreters have taken. Focusing on two readers of Bergson, Léopold Sédar Senghor and Messay Kebede, the chapter shows how the Négritude movement deployed a Bergsonian epistemology to challenge the dominance and domination of a European conception of rationality, mobilizing instead what Senghor calls an “embracing reason.” Critically assessing recent identifications of racism, the racialization of bodies, and whiteness as a transcendental norm in Bergson’s philosophy, the author concludes that Bergson cannot altogether escape the charges, given that his central distinction between open and closed in Two Sources relies on a notion of “primitives” as an indispensable foil for the achievements of the mystics. The question then becomes to what extent Bergson’s thought can be mobilized to remedy the evils it cannot wholly be extricated from. In conclusion, the essay surveys contemporary appropriations of the conception of the open society and suggests that Senghor’s rearticulation of Bergson’s intuition as sympathetic "embracing reason" offers theoretical and practical ways to address racist and colonial discourses.
Non-invasive prenatal testing (NIPT) for the detection of foetal aneuploidy through analysis of cell-free DNA (cfDNA) in maternal blood is offered routinely by many healthcare providers across the developed world. This testing has recently been recommended for evaluative implementation in the UK National Health Service (NHS) foetal anomaly screening pathway as a contingent screen following an increased risk of trisomy 21, 18 or 13. In preparation for delivering a national service, we have implemented cfDNA-based NIPT in our Regional Genetics Laboratory. Here, we describe our validation and verification processes and initial experiences of the technology prior to rollout of a national screening service.
Data are presented from more than 1000 patients (215 retrospective and 840 prospective) from ‘high- and low-risk pregnancies’ with outcome data following birth or confirmatory invasive prenatal sampling. NIPT was by the Illumina Verifi® test.
Our data confirm a high-fidelity service with a failure rate of ~0.24% and a high sensitivity and specificity for the detection of foetal trisomy 13, 18 and 21. Secondly, the data show that a significant proportion of patients continue their pregnancies without prenatal invasive testing or intervention after receiving a high-risk cfDNA-based result. A total of 46.5% of patients referred to date were referred for reasons other than high screen risk. Ten percent (76/840 clinical service referrals) of patients were referred with ultrasonographic finding of a foetal structural anomaly, and data analysis indicates high- and low-risk scan indications for NIPT.
NIPT can be successfully implemented into NHS regional genetics laboratories to provide high-quality services. NHS provision of NIPT in patients with high-risk screen results will allow for a reduction of invasive testing and partially improve equality of access to cfDNA-based NIPT in the pregnant population. Patients at low risk for a classic trisomy or with other clinical indications are likely to continue to access cfDNA-based NIPT as a private test.
Multispectral imaging – the acquisition of spatially contiguous imaging data in a modest number (~3–16) of spectral bandpasses – has proven to be a powerful technique for augmenting panchromatic imaging observations on Mars focused on geologic and/or atmospheric context. Specifically, multispectral imaging using modern digital CCD photodetectors and narrowband filters in the 400–1100 nm wavelength region on the Mars Pathfinder, Mars Exploration Rover, Phoenix, and Mars Science Laboratory missions has provided new information on the composition and mineralogy of fine-grained regolith components (dust, soils, sand, spherules, coatings), rocky surface regions (cobbles, pebbles, boulders, outcrops, and fracture-filling veins), meteorites, and airborne dust and other aerosols. Here we review recent scientific results from Mars surface-based multispectral imaging investigations, including the ways that these observations have been used in concert with other kinds of measurements to enhance the overall scientific return from Mars surface missions.
Three new Llandovery (early Silurian) crinoids from Estonia provide an improved understanding of the paleogeographic aspects of the crinoid diversification following the end-Ordovician extinctions. The new taxa are Euspirocrinus hintsae new species (Rhuddanian eucladid), Oepikicrinus perensae new genus new species (Aeronian camerate), and Rozhnovicrinus isakarae new genus new species (Aeronian eucladid). This brings the total of described Llandovery crinoids in Estonia to eight nominal species and a further three taxa in open nomenclature. The Rhuddanian radiation in Baltica mirrored that on Laurentia and Avalonia and was dominated by Ordovician clades that continued to diversify during the Silurian. Known Aeronian crinoids from Estonia continue these clades, whereas new clades diversified on Laurentia and Avalonia. However, by the Wenlock, a largely cosmopolitan fauna existed on Laurentia, Avalonia, and Baltica.
Since the early discussions of polycentricity, the concept (and variations such as polycentric political systems, polycentric governance, polycentric order, etc.) has seen the development of numerous permutations, digressions, and contradictions. This chapter is meant to carefully step through key notions tied to polycentricity and polycentric governance. The chapter’s purpose is to discuss polycentric governance in particular, while giving some attention to polycentricity as a term from which polycentric governance originates. We build upon the classic version of polycentric governance as a 'polycentric political system', link this concept with broader conceptualizations of polycentricity, and survey the related ideas that have been investigated around the concepts of polycentric political systems, polycentric order, polycentric governance, and polycentric arrangements.
Application timing and environmental factors reportedly influence the efficacy of auxinic herbicides. In resistance-prone weed species such as Palmer amaranth (Amaranthus palmeri S. Watson), efficacy of auxinic herbicides recently adopted for use in resistant crops is of utmost importance to reduce selection pressure for herbicide-resistance traits. Growth chamber experiments were conducted comparing the interaction of different environmental effects with application time to determine the influence of these factors on visible phytotoxicity and hydrogen peroxide (H2O2) formation in A. palmeri. Temperature displayed a high degree of influence on 2,4-D and dicamba efficacy in general, with applications at the low-temperature treatment (31/20 C day/night) resulting in an increase in phytotoxicity compared with high-temperature treatments (41/30 C day/night). Application time across temperature treatments significantly affected 2,4-D–induced phytotoxicity, resulting in a ≥30% increase across rates with treatments at 4:00 PM compared with 8:00 AM. Temperature differential had a significant influence on dicamba efficacy based on visible phytotoxicity data, with a ≥46% increase with a high (37/20 C day/night) compared with a low differential (41/30 C day/night). Concentration of H2O2 in herbicide-treated plants was 34% higher under a high temperature differential compared with the low differential. Humidity treatments and application time interactions displayed undetected or inconsistent effects on visible phytotoxicity and H2O2 production. Overall, temperature-related influences seem to have the largest environmental effect on auxinic herbicides within conditions evaluated in this study. Leaf concentration of H2O2 appears to be generally correlated with phytotoxicity, providing a potentially useful tool in determining efficacy of auxinic herbicides in field settings.
Recent years have seen an exponential increase in the variety of healthcare data captured across numerous sources. However, mechanisms to leverage these data sources to support scientific investigation have remained limited. In 2013 the Pediatric Heart Network (PHN), funded by the National Heart, Lung, and Blood Institute, developed the Integrated CARdiac Data and Outcomes (iCARD) Collaborative with the goals of leveraging available data sources to aid in efficiently planning and conducting PHN studies; supporting integration of PHN data with other sources to foster novel research otherwise not possible; and mentoring young investigators in these areas. This review describes lessons learned through the development of iCARD, initial efforts and scientific output, challenges, and future directions. This information can aid in the use and optimisation of data integration methodologies across other research networks and organisations.
The initial classic Fontan utilising a direct right atrial appendage to pulmonary artery anastomosis led to numerous complications. Adults with such complications may benefit from conversion to a total cavo-pulmonary connection, the current standard palliation for children with univentricular hearts.
A single institution, retrospective chart review was conducted for all Fontan conversion procedures performed from July, 1999 through January, 2017. Variables analysed included age, sex, reason for Fontan conversion, age at Fontan conversion, and early mortality or heart transplant within 1 year after Fontan conversion.
A total of 41 Fontan conversion patients were identified. Average age at Fontan conversion was 24.5 ± 9.2 years. Dominant left ventricular physiology was present in 37/41 (90.2%) patients. Right-sided heart failure occurred in 39/41 (95.1%) patients and right atrial dilation was present in 33/41 (80.5%) patients. The most common causes for Fontan conversion included atrial arrhythmia in 37/41 (90.2%), NYHA class II HF or greater in 31/41 (75.6%), ventricular dysfunction in 23/41 (56.1%), and cirrhosis or fibrosis in 7/41 (17.1%) patients. Median post-surgical follow-up was 6.2 ± 4.9 years. Survival rates at 30 days, 1 year, and greater than 1-year post-Fontan conversion were 95.1, 92.7, and 87.8%, respectively. Two patients underwent heart transplant: the first within 1 year of Fontan conversion for heart failure and the second at 5.3 years for liver failure.
Fontan conversion should be considered early when atrial arrhythmias become common rather than waiting for severe heart failure to ensue, and Fontan conversion can be accomplished with an acceptable risk profile.
Formally established in the fall of 1947, the Laboratory of Archaeology at the University of Georgia is an archaeological research and collection repository. It is considered one of the premier institutions for curation of archaeological collections from the American Southeast. For over 70 years, the Laboratory has served as a repository for objects and associated records generated from archaeological projects and research undertaken by faculty, students, CRM professionals, and state and federal agencies. The Laboratory curates over 20,000 cubic feet of artifacts as well as paper and digital archives. In addition, the Laboratory houses the Georgia Archaeological Site File and manages data from more than 59,000 archaeological sites, including over 11,500 archaeological reports. In this paper, we explore implementation procedures for bringing legacy collections up to modern curation standards. We also outline how we migrate the data on paper records into the digital realm, articulating them within a comprehensive framework.
The Kalana Lagerstätte of early Aeronian (Llandovery, Silurian) age in central Estonia preserves a diverse shallow marine biota dominated by non-calcified algae. This soft-tissue flora and decalcified and calcified crinoids are preserved in situ, in a lens of microlaminated, dolomitized micrite interbedded in a sequence of dolomitized packstones and wackestones. Although the Lagerstätte is dominated by non-calcified algae, crinoids (together with brachiopods and gastropods) are among the most common organisms that were originally comprised of a carbonate skeleton. Two new crinoids are described from this unit, Kalanacrinus mastikae n. gen. n. sp. (large camerate) and Tartucrinus kalanaensis n. gen. n. sp. (small disparid). Interestingly, these two crinoids display contrasting preservation, with the more common large camerate preserved primarily as a decalcified organic residue, whereas the smaller disparid is preserved primarily in calcite. Preservation was assessed using elemental mapping of C, Ca, S, and Si. Columns have the highest portion of Ca, once living soft tissue is indicated by C, S was dispersed as pyrite or associated with organics, and Si is probably associated with clay minerals in the matrix. This new fauna increases our understanding of the crinoid radiation on Baltica following Late Ordovician extinctions.
Much of the peace agreement durability literature assumes that stronger peace agreements are more likely to survive the trials of the post-conflict environment. This work does an excellent job identifying which provisions indicate that agreements are more likely to endure. However, there is no widely accepted way to directly measure the strength of agreements, and existing measures suffer from a lack of nuance or reliance on subjective weighting. We use a Bayesian item response theory model to develop a principled measure of the latent strength of peace agreements in civil conflicts from 1975 to 2005. We illustrate the measure's utility by exploring how various international factors such as sanctions and mediation contribute to the strength or weakness of agreements.
A 2018 workshop on the White Mountain Apache Tribe lands in Arizona examined ways to enhance investigations into cultural property crime (CPC) through applications of rapidly evolving methods from archaeological science. CPC (also looting, graverobbing) refers to unauthorized damage, removal, or trafficking in materials possessing blends of communal, aesthetic, and scientific values. The Fort Apache workshop integrated four generally partitioned domains of CPC expertise: (1) theories of perpetrators’ motivations and methods; (2) recommended practice in sustaining public and community opposition to CPC; (3) tactics and strategies for documenting, investigating, and prosecuting CPC; and (4) forensic sedimentology—uses of biophysical sciences to link sediments from implicated persons and objects to crime scenes. Forensic sedimentology served as the touchstone for dialogues among experts in criminology, archaeological sciences, law enforcement, and heritage stewardship. Field visits to CPC crime scenes and workshop deliberations identified pathways toward integrating CPC theory and practice with forensic sedimentology’s potent battery of analytic methods.