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The reported incidence of Clostridoides difficile infection (CDI) has increased in recent years, partly due to broadening adoption of nucleic acid amplification tests (NAATs) replacing enzyme immunoassay (EIA) methods. Our aim was to quantify the impact of this switch on reported CDI rates using a large, multihospital, empirical dataset.
We analyzed 9 years of retrospective CDI data (2009–2017) from 47 hospitals in the southeastern United States; 37 hospitals switched to NAAT during this period, including 24 with sufficient pre- and post-switch data for statistical analyses. Poisson regression was used to quantify the NAAT-over-EIA incidence rate ratio (IRR) at hospital and network levels while controlling for longitudinal trends, the proportion of intensive care unit patient days, changes in surveillance methodology, and previously detected infection cluster periods. We additionally used change-point detection methods to identify shifts in the mean and/or slope of hospital-level CDI rates, and we compared results to recorded switch dates.
For hospitals that transitioned to NAAT, average unadjusted CDI rates increased substantially after the test switch from 10.9 to 23.9 per 10,000 patient days. Individual hospital IRRs ranged from 0.75 to 5.47, with a network-wide IRR of 1.75 (95% confidence interval, 1.62–1.89). Reported CDI rates significantly changed 1.6 months on average after switching to NAAT testing (standard deviation, 1.9 months).
Hospitals that switched from EIA to NAAT testing experienced an average postswitch increase of 75% in reported CDI rates after adjusting for other factors, and this increase was often gradual or delayed.
Glucose intolerance during pregnancy – a major driver of gestational diabetes mellitus (GDM) – has significant short- and long-term health consequences for both the mother and child. As GDM prevalence continues to escalate, there is growing need for preventative strategies. There is limited but suggestive evidence that myo-inositol (MI) and probiotics (PB) could improve glucose tolerance during pregnancy. The present study tested the hypothesis that MI and/or PB supplementation would reduce the risk of glucose intolerance during pregnancy. Female C57BL/6 mice were randomised to receive either no treatment, MI, PB (Lactobacillus rhamnosus and Bifidobacterium lactis) or both (MIPB) for 5 weeks. They were then provided with a high-fat diet for 1 week before mating commenced and throughout mating/gestation, while remaining on their respective treatments. An oral glucose tolerance test occurred at gestational day (GD) 16·5 and tissue collection at GD 18·5. Neither MI nor PB, separately or combined, improved glucose tolerance. However, MI and PB both independently increased adipose tissue expression of Ir, Irs1, Akt2 and Pck1, and PB also increased Pparγ. MI was associated with reduced gestational weight gain, whilst PB was associated with increased maternal fasting glucose, total cholesterol and pancreas weight. These results suggest that MI and PB may improve insulin intracellular signalling in adipose tissue but this did not translate to meaningful differences in glucose tolerance. The absence of fasting hyperglycaemia or insulin resistance suggests this is a very mild model of GDM, which may have affected our ability to assess the impact of these nutrients.
The psychedelic research renaissance is gaining traction. Preliminary clinical studies of the hallucinogenic fungi, psilocybin, with psychological support, have indicated improvements in mood, anxiety and quality of life. A seminal, open-label study demonstrated marked reductions in depression symptoms in participants with treatment-resistant depression (TRD). The associated neurobiological processes involve alterations in brain connectivity, together with altered amygdala and default mode network activity. At the cellular level, psychedelics promote synaptogenesis and neural plasticity. Prompted by the promising preliminary studies, a randomized, double-blind trial has recently been launched across Europe and North America to investigate the efficacy of psilocybin in TRD. One of these centres is based in Ireland – CHO Area 7 and Tallaght University Hospital. The outcome of this trial will determine whether psilocybin with psychological support will successfully translate into the psychiatric clinic for the benefit of patients.
Medical residents are an important group for antimicrobial stewardship programs (ASPs) to target with interventions aimed at improving antibiotic prescribing. In this study, we compared antimicrobial prescribing practices of 2 academic medical teams receiving different ASP training approaches along with a hospitalist control group.
Retrospective cohort study comparing guideline-concordant antibiotic prescribing for 3 common infections among a family medicine (FM) resident service, an internal medicine (IM) resident service, and hospitalists.
Community teaching hospital.
Adult patients admitted between July 1, 2016, and June 30, 2017, with a discharge diagnosis of pneumonia, cellulitis, and urinary tract infections were reviewed.
All 3 medical teams received identical baseline ASP education and daily antibiotic prescribing audit with feedback via clinical pharmacists. The FM resident service received an additional layer of targeted ASP intervention that included biweekly stewardship-focused rounds with an ASP physician and clinical pharmacist leadership. Guideline-concordant prescribing was assessed based on the institution’s ASP guidelines.
Of 1,572 patients, 295 (18.8%) were eligible for inclusion (FM, 96; IM, 69; hospitalist, 130). The percentage of patients receiving guideline-concordant antibiotic selection empirically was similar between groups for all diagnoses (FM, 87.5%; IM, 87%; hospitalist, 83.8%; P = .702). No differences were observed in appropriate definitive antibiotic selection among groups (FM, 92.4%; IM, 89.1%; hospitalist, 89.9%; P = .746). The FM resident service was more likely to prescribe a guideline-concordant duration of therapy across all diagnoses (FM, 74%; IM, 56.5%; hospitalist, 44.6%; P < .001).
Adding dedicated stewardship-focused rounds into the graduate medical curriculum demonstrated increased guideline adherence specifically to duration of therapy recommendations.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Chemically defended benthic macroalgae that dominate shallow, hard bottom communities along the western Antarctic Peninsula support very high densities of mesograzers, particularly amphipods but also small gastropods. Previous studies have demonstrated that the macroalgae and amphipods form a mutualistic relationship. The chemically defended macroalgae provide the amphipods with a refuge from predation while the macroalgae benefit from the amphipods greatly reducing surface fouling by smaller algae. One of the three most important macroalgae in terms of overstory cover, Himantothallus grandifolius, forms huge blades that can carpet the benthos. Field observations suggest that gastropods may be higher in relative abundance in proportion to amphipods on H. grandifolius than on other overstory macroalgae. The present study documents the finding that natural abundances of gastropods on H. grandifolius maintained in mesocosms reduce fouling by microscopic algae, primarily diatoms. However, amphipods are probably also important in keeping the macroalga clean of diatoms in nature. In a smaller scale experiment, three gastropod species were differentially effective at reducing diatom coverage on H. grandifolius. The hypothesis that gastropods benefit from associating with H. grandifolius in potentially gaining a refuge from sea-star predation was also tested but not supported by the experimental results.
We experimentally investigate the two-phase interplay in an open-channel turbulent boundary layer laden with finite-size particles at global volume fractions between 4 and 25 %. The working fluid (water) and the dispersed phase (hydrogel spheres) have closely matched refractive indices, allowing us to measure the properties of both phases using particle image velocimetry and particle tracking velocimetry, respectively. The particles have a diameter of approximately 9 % of the channel depth and are slightly denser than the fluid. The negative buoyancy causes a strong vertical concentration gradient, characterized by discrete and closely spaced particle layers parallel to the wall. Even at the lowest considered volume fractions, the near-wall fluid velocity and velocity gradients are strongly reduced, with large mean shear throughout most of the channel height. This indicates that the local effective viscosity of the suspension is greatly increased due to the friction between particle layers sliding over one another. The particles consistently lag the fluid and leave their footprint on its mean and fluctuating velocity profiles. The turbulent activity is damped near the wall, where the nearly packed particles disrupt and suppress large-scale turbulent fluctuations and redistribute some of the kinetic energy to smaller scales. On the other hand, in the outer region of the flow where the local particle concentration is low, the mean shear produces strong Reynolds stresses, with enhanced sweeps and ejections and frequent swirling events.
We study experimentally the spatial distribution, settling and interaction of sub-Kolmogorov inertial particles with homogeneous turbulence. Utilizing a zero-mean-flow air turbulence chamber, we drop size-selected solid particles and study their dynamics with particle imaging and tracking velocimetry at multiple resolutions. The carrier flow is simultaneously measured by particle image velocimetry of suspended tracers, allowing the characterization of the interplay between both the dispersed and continuous phases. The turbulence Reynolds number based on the Taylor microscale ranges from
, while the particle Stokes number based on the Kolmogorov scale varies between
. Clustering is confirmed to be most intense for
, but it extends over larger scales for heavier particles. Individual clusters form a hierarchy of self-similar, fractal-like objects, preferentially aligned with gravity and with sizes that can reach the integral scale of the turbulence. Remarkably, the settling velocity of
particles can be several times larger than the still-air terminal velocity, and the clusters can fall even faster. This is caused by downward fluid fluctuations preferentially sweeping the particles, and we propose that this mechanism is influenced by both large and small scales of the turbulence. The particle–fluid slip velocities show large variance, and both the instantaneous particle Reynolds number and drag coefficient can greatly differ from their nominal values. Finally, for sufficient loadings, the particles generally augment the small-scale fluid velocity fluctuations, which however may account for a limited fraction of the turbulent kinetic energy.
To report functional recovery, symptomatic remission, and sustained symptomatic remission rates after treatment with aripiprazole once-monthly 400mg (AOM 400) administered every 4weeks for up to 52weeks as maintenance treatment in a mixed cohort of AOM 400 naïve (de novo) and experienced adults (rollover) with bipolar I disorder (BP-I).
This open-label study (NCT01710709) enrolled de novo patients with a diagnosis of BP-I and ≥1 previous manic or mixed episode and rollover patients who completed a randomized, double-blind, placebo-controlled study assessing the efficacy and safety of AOM 400 (NCT01567527). Efficacy was assessed by mean changes from baseline in Young-Mania Rating Scale (YMRS), Montgomery-Asberg Depressive Rating Scale (MADRS), and Clinical Global Impression- Bipolar Version-Severity of Illness (CGI-BP-S) scores. Sustained functional recovery was defined as a total score of ≤11 on the Functioning Assessment Short Test (FAST) for ≥8 consecutive weeks. Remission was defined as YMRS and MADRS total scores ≤12, and sustained remission was defined as meeting criteria for remission for 8 consecutive weeks. The study included a screening phase (6weeks) for de novo patients, an oral aripiprazole conversion phase (4–6weeks), an oral stabilization phase (4–12weeks), and an AOM 400 maintenance phase (up to 52weeks). Rollover patients entered directly into the AOM 400 maintenance phase.
A total of 464 subjects entered the maintenance phase and 63% (291/464) completed the trial. Of patients entering the maintenance phase, 379 (82%) were de novo and 85 (18%) were rollover. The most frequent reasons for discontinuation were withdrawal of consent (11%) and adverse events (AEs) (10%). Weight increase (1.5%, 7/464) and BP-I (0.9%, 4/464) were the most common reasons for discontinuation due to AEs. Improvements in mean YMRS, MADRS, CGI-BP-S, and FAST scores achieved in previous phases were maintained over 52weeks. Treatment-emergent AEs experienced by >10% of the patients were akathisia (14.7%), weight increased (13.4%), nasopharyngitis (12.1%), and insomnia (11.0%). A high proportion of de novo patients met the criteria for symptomatic remission (87.2%, 328/376) and sustained remission (77%, 292/379) by last visit. Rollover patients’ remission rate remained stable (98.8%, 84/85) by last visit. Of the rollover patients, 35/85 (43%) and 35/116 (36%) of de novo subjects met the criteria for sustained functional recovery after study completion.
Patients treated with AOM 400 maintained symptomatic and functional stability for up to 52weeks. Importantly, more than one-third of patients achieved sustained functional recovery using a strict criterion. Overall, AOM 400 was safe and well tolerated in patients with BP-I. Results support AOM 400 as a viable once-monthlyoption for maintenance treatment of BP-I.
These data were previously presented at the 31st ECNP Congress, 2018, Barcelona,Spain.
Funding Acknowledgements: The study was supported by Otsuka Pharmaceutical Development & Commercialization, Inc.
Most current models of nonnative speech perception (e.g., extended perceptual assimilation model, PAM-L2, Best & Tyler, 2007; speech learning model, Flege, 1995; native language magnet model, Kuhl, 1993) base their predictions on the native/nonnative status of individual phonetic/phonological segments. This paper demonstrates that the phonotactic properties of Japanese influence the perception of natively contrasting consonants and suggests that phonotactic influence must be formally incorporated in these models. We first propose that by extending the perceptual categories outlined in PAM-L2 to incorporate sequences of sounds, we can account for the effects of differences in native and nonnative phonotactics on nonnative and cross-language segmental perception. In addition, we test predictions based on such an extension in two perceptual experiments. In Experiment 1, Japanese listeners categorized and rated vowel–consonant–vowel strings in combinations that either obeyed or violated Japanese phonotactics. The participants categorized phonotactically illegal strings to the perceptually nearest (legal) categories. In Experiment 2, participants discriminated the same strings in AXB discrimination tests. Our results show that Japanese listeners are more accurate and have faster response times when discriminating between legal strings than between legal and illegal strings. These findings expose serious shortcomings in currently accepted nonnative perception models, which offer no framework for the influence of native language phonotactics.
Various paleoclimatic records have been used to reconstruct the hydrologic history of the Altiplano, relating this history to past variability of the South American summer monsoon. Prior studies of the southern Altiplano, the location of the world’s largest salt flat, the Salar de Uyuni, and its neighbor, the Salar de Coipasa, generally agree in their reconstructions of the climate history of the past ∼24 ka. Some studies, however, have highly divergent climatic records and interpretations of earlier periods. In this study, lake-level variation was reconstructed from a ∼14-m-long sediment core from the Salar de Coipasa. These sediments span the last ∼40 ka. Lacustrine sediment accumulation was apparently continuous in the basin from ∼40 to 6 ka, with dry or very shallow conditions afterward. The fossil diatom stratigraphy and geochemical data (δ13C, δ15N, %Ca, C/N) indicate fluctuations in lake level from shallow to moderately deep, with the deepest conditions correlative with the Heinrich-1 and Younger Dryas events. The stratigraphy shows a continuous lake of variable depth and salinity during the last glacial maximum and latter stages of Marine Oxygen Isotope Stage 3 and is consistent with environmental inferences and the original chronology of a drill core from Salar de Uyuni.
The effect of small noise in a smooth dynamical system is negligible on any finite time interval; in this paper we study situations where the effect persists on intervals increasing to ∞. Such an asymptotic regime occurs when the system starts from an initial condition that is sufficiently close to an unstable fixed point. In this case, under appropriate scaling, the trajectory converges to a solution of the unperturbed system started from a certain random initial condition. In this paper we consider the case of one-dimensional diffusions on the positive half-line; this case often arises as a scaling limit in population dynamics.
Here we present the synthesis of porous platinum–palladium macrobeams templated from high aspect ratio Magnus’ salt needle derivatives. The combination of [PtCl4]2− and/or [PdCl4]2− with [Pt(NH3)4]2+ ions results in salt needles ranging from 15 to 300 µm in length. Electrochemical reduction of the salt templates results in porous macrobeams with a square cross-section. Porous side wall texture and elemental composition was controlled with initial platinum to palladium salt ratio. Macrobeam free-standing films exhibited a specific capacitance up to 11.73 F/g and a solvent accessible surface area of 26.6 m2/g. These salt-templated porous platinum–palladium macrobeams offer a promising material for fuel cell catalysis.
The American College of Cardiology Quality Network enables national benchmarking and collaborative quality improvement through vetted metrics. We describe here our initial experience with the Quality Network.
Quarterly data for metrics pertaining to chest pain, Kawasaki disease, tetralogy of Fallot, elevated body mass index, and others were shared with the collaboratives for benchmarking. National improvement efforts focussed on counselling for elevated body mass index and 22q11.2 testing in tetralogy of Fallot. Improvement strategies included developing multi-disciplinary workgroups, educational materials, and electronic health record advances.
Chest pain metric performance was high compared with national means: obtaining family history (90–100% versus 51–77%), electrocardiogram (100% versus 89–99%), and echocardiogram for exertional complaints (95–100% versus 74–96%). Kawasaki metric performance was high, including obtaining coronary measurements (100% versus 85–97%), prescribing aspirin (100% versus 86–99%), follow-up with imaging (100% versus 85–98%), and documenting no activity restriction without coronary aneurysms (83–100% versus 64–93%). Counselling for elevated body mass index was variable (25–75% versus 31–50%) throughout quality improvement efforts. Testing for 22q11.2 deletion in tetralogy of Fallot patients was consistently above the national mean (60–85% versus 54–68%) with improved genetics data capture.
The Quality Network promotes meaningful benchmarking and collaborative quality improvement. Our high performance for chest pain and Kawasaki metrics is likely related to previous improvement efforts in chest pain management and a dedicated Kawasaki team. Uptake of counselling for elevated body mass index is variable; stronger engagement among numerous providers is needed. Recommendations for 22q11.2 testing in tetralogy of Fallot were widely recognised and implemented.
To evaluate whole-genome sequencing (WGS) as a molecular typing tool for MRSA outbreak investigation.
Investigation of MRSA colonization/infection in a neonatal intensive care unit (NICU) over 3 years (2014–2017).
Single-center level IV NICU.
NICU infants and healthcare workers (HCWs).
Infants were screened for MRSA using a swab of the anterior nares, axilla, and groin, initially by targeted (ring) screening, and later by universal weekly screening. Clinical cultures were collected as indicated. HCWs were screened once using swabs of the anterior nares. MRSA isolates were typed using WGS with core-genome multilocus sequence typing (cgMLST) analysis and by pulsed-field gel electrophoresis (PFGE). Colonized and infected infants and HCWs were decolonized. Control strategies included reinforcement of hand hygiene, use of contact precautions, cohorting, enhanced environmental cleaning, and remodeling of the NICU.
We identified 64 MRSA-positive infants: 53 (83%) by screening and 11 (17%) by clinical cultures. Of 85 screened HCWs, 5 (6%) were MRSA positive. WGS of MRSA isolates identified 2 large clusters (WGS groups 1 and 2), 1 small cluster (WGS group 3), and 8 unrelated isolates. PFGE failed to distinguish WGS group 2 and 3 isolates. WGS groups 1 and 2 were codistributed over time. HCW MRSA isolates were primarily in WGS group 1. New infant MRSA cases declined after implementation of the control interventions.
We identified 2 contemporaneous MRSA outbreaks alongside sporadic cases in a NICU. WGS was used to determine strain relatedness at a higher resolution than PFGE and was useful in guiding efforts to control MRSA transmission.
The Triarchic Psychopathy Measure (TriPM) provides Disinhibition, Boldness, and Meanness scales for assessing the three trait domains of the triarchic model. Here we examined the genetic and environmental etiology of these three domains, including evaluation of potential sex differences.
A total of 1016 men and women ages 19–20 years were drawn from the University of Southern California Risk Factors for Antisocial Behavior twin study.
Scores for the three TriPM scales were correlated to differing degrees, with the strongest phenotypic correlation between Disinhibition and Meanness. No sex differences were found in the genetic and environmental influences underlying these three domains, suggesting that the same genes and life experiences contribute to these traits in young men and women. For TriPM Disinhibition and Boldness, genetic factors explained about half or less of the variance, with the rest of the variance being explained by non-shared environmental factors. For TriPM Meanness, on the other hand, genetic, shared environmental, and non-shared environmental factors accounted for the variance. The phenotypic correlation between Disinhibition and Meanness was explained in part by common genes (26%), with the remainder attributable about equally to common shared (39%), and non-shared environmental influences (35%).
These findings contribute to our understanding of psychopathic personality traits by demonstrating the importance of heritable factors for disinhibition and boldness facets of psychopathy, and the importance of shared environmental influences for the meanness facet.
Small perturbations to a steady uniform granular chute flow can grow as the material moves downslope and develop into a series of surface waves that travel faster than the bulk flow. This roll wave instability has important implications for the mitigation of hazards due to geophysical mass flows, such as snow avalanches, debris flows and landslides, because the resulting waves tend to merge and become much deeper and more destructive than the uniform flow from which they form. Natural flows are usually highly polydisperse and their dynamics is significantly complicated by the particle size segregation that occurs within them. This study investigates the kinematics of such flows theoretically and through small-scale experiments that use a mixture of large and small glass spheres. It is shown that large particles, which segregate to the surface of the flow, are always concentrated near the crests of roll waves. There are different mechanisms for this depending on the relative speed of the waves, compared to the speed of particles at the free surface, as well as on the particle concentration. If all particles at the surface travel more slowly than the waves, the large particles become concentrated as the shock-like wavefronts pass them. This is due to a concertina-like effect in the frame of the moving wave, in which large particles move slowly backwards through the crest, but travel quickly in the troughs between the crests. If, instead, some particles on the surface travel more quickly than the wave and some move slower, then, at low concentrations, large particles can move towards the wave crest from both the forward and rearward sides. This results in isolated regions of large particles that are trapped at the crest of each wave, separated by regions where the flow is thinner and free of large particles. There is also a third regime arising when all surface particles travel faster than the waves, which has large particles present everywhere but with a sharp increase in their concentration towards the wave fronts. In all cases, the significantly enhanced large particle concentration at wave crests means that such flows in nature can be especially destructive and thus particularly hazardous.