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Background: Effective strategies to improve diagnostic stewardship around C. difficile infection (CDI) remain elusive. Electronic medical record-based solutions, such as ‘hard’ and ‘soft’ stops, have been associated with reductions in testing, but may not be sustainable due to alert fatigue. Additionally, data on the potential for undertesting, missed diagnoses, and the implications regarding patient harm or clusters of transmission are limited. In this study, we assessed the efficacy of a behavioral approach to diagnostic stewardship, while monitoring for unintended consequences. Methods: This quality improvement study was conducted January 2018–May 2019; baseline period: January–April 2018, implementation period: May–December 2018, sustainment period: January 2019–May 2019. First, we conducted an internal analysis and identified 3 barriers to appropriate testing: clinician’s perceived risk of CDI, inconsistent definition of diarrhea, and lack of involvement of nurses in diagnostic stewardship. A multidisciplinary team to address these barriers was then convened. The team utilized the Bristol stool scale to improve the reliability of diarrhea description, and created a guideline-concordant testing algorithm with clinicians and nurses. The primary outcome was the number of tests ordered. The secondary outcomes were the proportion of inappropriate tests and the proportion of delayed tests. Delayed tests were defined as CDI-compatible diarrhea based on the algorithm where the test was sent >24 hours after symptom onset. Results: During the baseline period, we detected no significant change in number of tests ordered month to month, with 194.2 tests ordered per month on average. During the postimplementation period, the number of tests ordered decreased by ~4.5 each month between January 2018 and May 2019 (P < .0001). The proportion of inappropriate tests steadily decreased from 54% to 30% across the 3 study periods, and the number of delayed testing changed from 11% to 1% then increased to 20% in the sustainment period. There were no cases of toxic megacolon associated with delayed testing. Conclusions: The decision to test for CDI is complex. Interventions that address this issue as a simple ‘right’ and ‘wrong’ fail to address the root cause of CDI overdiagnosis, and they have no embedded mechanism to detect unintended consequences. Our study demonstrates that by taking a behavioral approach and addressing clinicians’ safety concerns, we were able to sustain a significant reduction in testing. We could not determine the significance of the increase in delayed testing given the low numbers; however, further studies are needed to evaluate the safety of CDI reduction strategies through diagnostic stewardship only.
Background: Polymerase chain reaction (PCR) testing for the diagnosis of Clostridioides difficile infection (CDI) detects the presence of the organism; a positive result therefore cannot differentiate between colonization and the pathogenic presence of the bacterium. This may result in overdiagnosis, overtreatment, and risking disruption of microbial flora, which may perpetuate the CDI cycle. Algorithm-based testing offers an advantage over PCR testing as it detects toxin, which allows differentiation between colonization and infection. Although previous studies have demonstrated the clinical utility of this testing algorithm in differentiating infection from colonization, it is unknown whether the test changes CDI treatment decisions. Our facility switched from PCR to an algorithm-based testing method for CDI in June 2018. Objective: In this study, we evaluated whether clinicians’ decisions to treat patients are impacted by a test result that implies colonization (GDH+/Tox−/PCR+ test), and we examined the impact of this decision on patient outcomes. Methods: This is a retrospective cohort study of inpatients with a positive C. diff test between June 2017 and June 2019. The primary outcome was the proportion of patients treated for CDI. We compared this outcome in 3 groups of patients: those with a positive PCR test (June 2017–June 2018), those who had a GDH+/Tox−/PCR+ or a GDH+/Tox+ test result (June 2018–June 2019). Secondary outcomes included toxic megacolon, critical care admission, and mortality in patients with GDH+/Tox−/PCR+ who were treated versus those who were untreated. Results: Of patients with a positive PCR test, 86% were treated with CDI-specific antibiotics, whereas 70.4% with GDH+/Tox+ and 29.25% with GDH+/Tox−/PCR+ result were treated (P < .0001). Mortality was not different between patients with GDH+/Tox−/PCR+ who were treated versus those who were untreated (2.7% vs 3.4%; P = .12), neither was critical care admission within 2 or 7 days of test result (2% vs 1.4%; P = .15) and (4.1% vs 5.4%, P = .39), respectively. There were no cases of toxic megacolon during the study period. Conclusions: The change to an algorithm-based C. difficile testing method had a significant impact on the clinicians’ decisions to treat patients with a positive test, as most patients with a GDH+/Tox−/PCR+ result did not receive treatment. These patients did not suffer more adverse outcomes compared to those who were treated, which has implications for testing practices. It remains to be explored whether clinicians are using clinical criteria to decide whether or not to treat patients with a positive algorithm-based test, as opposed to the more reflexive treatment of patients with a positive PCR test.
We report electronic medical record interventions to reduce Clostridioides difficile testing risk ‘alert fatigue.’ We used a behavioral approach to diagnostic stewardship and observed a decrease in the number of tests ordered of ~4.5 per month (P < .0001). Although the number of inappropriate tests decreased during the study period, delayed testing increased.
We describe 14 yr of public data from the Parkes Pulsar Timing Array (PPTA), an ongoing project that is producing precise measurements of pulse times of arrival from 26 millisecond pulsars using the 64-m Parkes radio telescope with a cadence of approximately 3 weeks in three observing bands. A comprehensive description of the pulsar observing systems employed at the telescope since 2004 is provided, including the calibration methodology and an analysis of the stability of system components. We attempt to provide full accounting of the reduction from the raw measured Stokes parameters to pulse times of arrival to aid third parties in reproducing our results. This conversion is encapsulated in a processing pipeline designed to track provenance. Our data products include pulse times of arrival for each of the pulsars along with an initial set of pulsar parameters and noise models. The calibrated pulse profiles and timing template profiles are also available. These data represent almost 21 000 h of recorded data spanning over 14 yr. After accounting for processes that induce time-correlated noise, 22 of the pulsars have weighted root-mean-square timing residuals of
in at least one radio band. The data should allow end users to quickly undertake their own gravitational wave analyses, for example, without having to understand the intricacies of pulsar polarisation calibration or attain a mastery of radio frequency interference mitigation as is required when analysing raw data files.
The Brechin Lagerstätte of southern Ontario contains an exceptionally diverse and well-preserved Late Ordovician (Katian) crinoid fauna. We describe four genera and eight species of camerate crinoids from the Brechin Lagerstätte, including six new species. Consequently, the total diversity of the fauna now stands at 27 genera and 39 nominal species, thereby making it the most taxonomically diverse Ordovician crinoid fauna known. Taxa described include the diplobathrid Pararchaeocrinus kiddi new species and the monobathrids Glyptocrinus ramulosus Billings, 1856, Periglyptocrinus priscus (Billings, 1857a), Periglyptocrinus astricus new species, Periglyptocrinus kevinbretti new species, Periglyptocrinus mcdonaldi new species, Periglyptocrinus silvosus new species, and Abludoglyptocrinus steinheimerae new species. We summarize the taxonomic composition, diversity, and abundance distribution of all known crinoids from the Brechin Lagerstätte to better characterize the paleoecological structure and complexity of the community. We establish that the fauna is dominated by the subclass Pentacrinoidea, both in terms of abundance and species richness. In addition, we analyze species-level abundance data using Relative Abundance Distribution (RAD) models to evaluate the ecological complexity of the paleocommunity. We found that community structure of the Brechin Lagerstätte is best explained by an ecologically ‘complex’ RAD model, which suggests that species partitioned niches along multiple resource axes and/or the presence of multiple ecological ways of life. These results indicate that the Brechin Lagerstätte is significant not only for being the most taxonomically diverse Katian crinoid assemblage, but also for being an early ecologically complex fauna that developed in the wake of the Great Ordovician Biodiversification Event.
OBJECTIVES/GOALS: Diverse medication-based studies require longitudinal drug dose information. EHRs can provide such data, but multiple mentions of a drug in the same clinical note can yield conflicting dose. We aimed to develop statistical methods which address this challenge by predicting the valid dose in the event that conflicting doses are extracted. METHODS/STUDY POPULATION: We extracted dose information for two test drugs, tacrolimus and lamotrigine, from Vanderbilt EHRs using a natural language processing system, medExtractR, which was developed by our team. A random forest classifier was used to estimate the probability of correctness for each extracted dose on the basis of subject longitudinal dosing patterns and extracted EHR note context. Using this feasibility measure and other features such as a summary of subject dosing history, we developed several statistical models to predict the dose on the basis of the extracted doses. The models developed based on supervised methods included a separate random forest regression, a transition model, and a boosting model. We also considered unsupervised methods and developed a Bayesian hierarchical model. RESULTS/ANTICIPATED RESULTS: We compared model-predicted doses to physician-validated doses to evaluate model performance. A random forest regression model outperformed all proposed models. As this model is a supervised model, its utility would depend on availability of validated dose. Our preliminary result from a Bayesian hierarchical model showed that it can be a promising alternative although performing less optimally. The Bayesian hierarchical model would be especially useful when validated dose data are not available, as it was developed in unsupervised modeling framework and hence does not require validated dose that can be difficult and time consuming to obtain. We evaluated the feasibility of each method for automatic implementation in our drug dosing extraction and processing system we have been developing. DISCUSSION/SIGNIFICANCE OF IMPACT: We will incorporate the developed methods as a part of our complete medication extraction system, which will allow to automatically prepare large longitudinal medication dose datasets for researchers. Availability of such data will enable diverse medication-based studies with drastically reduced barriers to data collection.
To investigate changes in socio-economic inequalities in growth in height, weight, BMI and grip strength in children born during 1955–1993 in Guatemala, a period of marked socio-economic-political change.
We modelled longitudinal data on height, weight, BMI and hand grip strength using Super-Imposition by Translation and Rotation (SITAR). Internal Z-scores summarising growth size, timing and intensity (peak growth velocity, e.g. cm/year) were created to investigate inequalities by socio-economic position (SEP; measured by school attended). Interactions of SEP with date of birth were investigated to capture secular changes in inequalities.
Urban and peri-urban schools in the region of Guatemala City, Guatemala.
Participants were 40 484 children and adolescents aged 3–19 years of Ladino and Maya ancestry (nobservations 157 067).
The difference in height (SITAR size) between lowest and highest SEP decreased from −2·0 (95 % CI −2·2, −1·9) sd to −1·4 (95 % CI −1·5, −1·3) sd in males, and from −2·0 (95 % CI −2·1, −1·9) sd to −1·2 (95 % CI −1·3, −1·2) sd in females over the study period. Inequalities also reduced for weight, BMI and grip strength, due to greater secular increases in lowest-SEP groups. The puberty period was earlier and shorter in higher-SEP individuals (earlier SITAR timing and higher SITAR intensity). All SEP groups showed increases in BMI intensity over time.
Inequality narrowed between the 1960s and 1990s. The lowest-SEP groups were still >1 sd shorter than the highest. Risks remain for reduced human capital and poorer population health for urban Guatemalans.
Upper Ordovician (Katian) strata of the Lake Simcoe region of Ontario record a spectacularly diverse and abundant echinoderm fauna known as the Brechin Lagerstätte. Despite recognition as the most taxonomically diverse Katian crinoid paleocommunity, the Brechin Lagerstätte has received relatively little taxonomic study since Frank Springer published his classic monograph on the “Kirkfield fauna” in 1911.
Using a new collection of exceptionally preserved material, we evaluate all dicyclic inadunate crinoids occurring in the Brechin Lagerstätte, which is predominantly comprised of cladids (Eucladida and Flexibilia). We document 15 species across 11 genera, including descriptions of two new genera and four new species. New taxa include Konieckicrinus brechinensis n. gen. n. sp., K. josephi n. gen. n. sp., Simcoecrinus mahalaki n. gen. n. sp., and Dendrocrinus simcoensis n. sp.
Although cladids are not commonly considered major components of the Early Paleozoic Crinoid Macroevolutionary Fauna, which is traditionally conceived as dominated by disparids and diplobathrid camerates, they are the most diverse major lineage of crinoids occurring in the Brechin Lagerstätte. This unexpected result highlights the important roles of specimen-based taxonomy and systematic revisions in the study of large-scale diversity patterns.
Touch is world-directed, temporally extended, exploratory contact and movement. It was by modelling his theory of perception on touch that Alva Noë was able to show (in Action in Perception, 2006) that perceptual experience acquires content through our physical interactions with the world, that the detail we perceive in the world ‘is experienced by us as out there, not as in our minds’ (p. 33). In this essay, I share some thoughts on how understanding musical experience on these terms, as touch-like, may be a useful means of looking past the work-concept to the wider field of musical possibilities beyond. I begin by briefly considering the phenomenology of touch, which serves as the basis for the argument that follows.
The Brechin Lagerstätte (Katian, Ordovician) from the Lake Simcoe region of Ontario, Canada contains a diverse array of echinoderms. Here, we describe seven disparid and two hybocrinid crinoids (subclass Pentacrinoidea, infraclass Inadunata), including a new disparid species belonging to the Anomalocrinidae (order Homocrinida). In total, the disparids include Anomalocrinus astrictus n. sp.; Cremacrinus guttenbergensis Kolata, 1975; C. inaequalis Billings, 1859; Daedalocrinus bellevillensis Billings, 1883; Eustenocrinus springeri Ulrich, 1925; Iocrinus trentonensis Walcott, 1883; and Isotomocrinus tenuis Billings, 1857b. The hybocrinids include Hybocrinus tumidus Billings, 1857a and Hybocystites problematicus Wetherby, 1880. Previously known from only the holotype, three additional specimens of E. springeri expand our understanding of this unusual crinoid. Nomenclatural acts include: (1) the recommended designation of D. kirki Ulrich, 1925 as a junior synonym of D. bellevillensis is followed; (2) Hybocrinus pristinus Billings, 1858 is designated as a junior synonym of H. tumidus, and previous decisions are followed to retain Hybocystites eldonensis (Parks, 1908) as a junior synonym of H. problematicus; (3) although probably assignable to Anomalocrinus Meek and Worthen, 1865, the aberrant crinoid Glaucocrinus falconeri Parks and Alcock, 1912, and its genus Glaucocrinus Parks and Alcock, 1912, are designated as nomena dubia; (4) Iocrinus similis (Billings, 1857) is also designated as a nomen dubium; and (5) Iocrinus subcrassus torontoensis Fritz, 1925 is designated a junior synonym of I. subcrassus Meek and Worthen, 1865.
The Upper Ordovician (lower Katian) Bobcaygeon and Verulam formations from the Lake Simcoe region of Ontario contain a highly diverse echinoderm assemblage that is herein recognized as a Konservat-Lagerstätte. Although fossil crinoids have long been recognized from these formations, the fauna has not received a comprehensive taxonomic evaluation since Springer’s classic 1911 monograph. Recent extensive collection and preparation of new material from the Bobcaygeon and Verulam formations near Brechin, Ontario recovered numerous exceptionally preserved crinoid specimens with arms, stems, and attachment structures intact. The Brechin Lagerstätte is the most taxonomically diverse Katian crinoid fauna, with more than 20 crinoid genera represented in this collection.
Here, all dicyclic crinoids belonging to subclass Camerata from the Brechin Lagerstätte are evaluated. The following four genera and seven species are described from the fauna, including one new genus and four new species: Reteocrinus stellaris, Reteocrinus alveolatus, Archaeocrinus sundayae n. sp., Archaeocrinus maraensis n. sp., Priscillacrinus elegans n. gen. n. sp., Cleiocrinus regius, and Cleiocrinus lepidotus n. sp. The exceptional preservation of this collection provides an opportunity to describe more fully the morphologic and ontogenetic details of known Ordovician crinoid taxa, to conduct a taxonomic re-evaluation of many species, to describe new taxa, and to provide a framework for subsequent studies of crinoid community paleoecology.
A major goal of biological classification is to provide a system that conveys phylogenetic relationships while facilitating lucid communication among researchers. Phylogenetic taxonomy is a useful framework for defining clades and delineating their taxonomic content according to well-supported phylogenetic hypotheses. The Crinoidea (Echinodermata) is one of the five major clades of living echinoderms and has a rich fossil record spanning nearly a half billion years. Using principles of phylogenetic taxonomy and recent phylogenetic analyses, we provide the first phylogeny-based definition for the Clade Crinoidea and its constituent subclades. A series of stem- and node-based definitions are provided for all major taxa traditionally recognized within the Crinoidea, including the Camerata, Disparida, Hybocrinida, Cladida, Flexibilia, and Articulata. Following recommendations proposed in recent revisions, we recognize several new clades, including the Eucamerata Cole 2017, Porocrinoidea Wright 2017, and Eucladida Wright 2017. In addition, recent phylogenetic analyses support the resurrection of two names previously abandoned in the crinoid taxonomic literature: the Pentacrinoidea Jaekel, 1918 and Inadunata Wachsmuth and Springer, 1885. Last, a phylogenetic perspective is used to inform a comprehensive revision of the traditional rank-based classification. Although an attempt was made to minimize changes to the rank-based system, numerous changes were necessary in some cases to achieve monophyly. These phylogeny-based classifications provide a useful template for paleontologists, biologists, and non-experts alike to better explore evolutionary patterns and processes with fossil and living crinoids.
A diverse crinoid fauna is described from the Upper Ordovician (Katian) Fombuena Formation from the eastern Iberian Chains of Spain. New crinoids include the diplobathrid camerates Fombuenacrinus nodulus n. gen. n. sp., Goyacrinus gutierrezi n. gen. n. sp., Dalicrinus hammanni n. gen. n. sp., and Ambonacrinus decorus n. gen. n. sp.; the monobathrid camerate Eopatelliocrinus hispaniensis n. sp.; and the cladid Picassocrinus villasi n. gen. n. sp. A new occurrence of Heviacrinus melendezi Gil Cid, Domínguez Alonso, and Silván Pobes, 1996 is also documented from the Castillejo Formation (Darriwilian, Middle Ordovician) from the eastern Iberian Chains of Spain. The Fombuena Formation comprises a Gondwanan crinoid assemblage from a high paleolatitude and has the highest crinoid diversity of any currently known Katian Gondwanan fauna. This assemblage is compared to other Katian age faunas around the globe, and its paleobiogeographic implications are discussed.
We studied neuroinflammation in individuals with late-life, depression, as a
risk factor for dementia, using [11C]PK11195 positron emission
tomography (PET). Five older participants with major depression and 13
controls underwent PET and multimodal 3T magnetic resonance imaging (MRI),
with blood taken to measure C-reactive protein (CRP). We found significantly
higher CRP levels in those with late-life depression and raised
[11C]PK11195 binding compared with controls in brain regions
associated with depression, including subgenual anterior cingulate cortex,
and significant hippocampal subfield atrophy in cornu ammonis 1 and
subiculum. Our findings suggest neuroinflammation requires further
investigation in late-life depression, both as a possible aetiological
factor and a potential therapeutic target.
Sir Peter Maxwell Davies' Tenth Symphony was given its premiere by the London Symphony Orchestra and Chorus at the Barbican on 2 February 2014. The work concerns itself with both the architecture and the death of Francesco Borromini; while perhaps an unusual subject for a symphony, there is precedence in Maxwell Davies's work, as the same man is the subject of his Third Naxos Quartet, and the Third Symphony takes Brunelleschi as its subject. Maxwell Davies has suggested direct links between Borromini's creations and his own – in the programme note we discover that ‘the precise parameters and proportions by which a huge basilica of Borromini's was constructed’ control portions of the work – and indeed the architect's presence pervades the symphony. As well as guiding Maxwell Davies's constructive parameters in the instrumental movements, Borromini is the subject of the chorus' music throughout and almost becomes a character in an operatic scena in the final passage, as he plays out his own suicide to the backdrop of the chorus intoning the names of his most celebrated work. Yet this new symphony rarely betrays its rigorous origins, and aside from passages for percussion mimetic of building activity (hammers, vibraphone, anvils and so on) many aspects in fact suggest a softer, smoother musical language.