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Metformin is widely used in pregnancy, despite lack of long-term safety for children. We hypothesised that metformin exposure in utero is associated with increased cardiovascular risk. We tested this hypothesis in a follow-up study of children born to obese mothers who had participated in a randomised controlled trial of metformin versus placebo in pregnancy (EMPOWaR). We measured body composition, peripheral blood pressure (BP), arterial pulse wave velocity and central haemodynamics (central BP and augmentation index) using an oscillometric device in 40 children of mean (SD) age 5.78 (0.93) years, exposed to metformin (n = 19) or placebo (n = 21) in utero. There were no differences in any of the anthropometric or vascular measures between metformin and placebo-exposed groups in univariate analyses, or after adjustment for potential confounders including the child’s behaviour, diet and activity levels. Post-hoc sample size calculation indicated we would have detected large clinically significant differences between the groups but would need an unfeasible large number to detect possible subtle differences in key cardiovascular risk parameters in children at this age of follow-up. Our findings suggest no evidence of increased cardiovascular risk in children born to obese mothers who took metformin in pregnancy and increase available knowledge of the long-term safety of metformin on childhood outcomes.
Cube arrays are one of the most extensively studied types of surface roughness, and there has been much research on cubical roughness with low-to-moderate surface coverage densities. In order to help populate the literature of flow over cube arrays with high surface coverage densities, we conduct direct numerical simulations (DNSs) of flow over aligned cube arrays with coverage densities $\lambda =0.25$ (for validation and comparison purposes), $0.5$, $0.6$, $0.7$, $0.8$ and $0.9$. The roughness are in the d-type roughness regime. Essential flow quantities, including the mean velocity profiles, Reynolds stresses, dispersive stresses and roughness properties, are reported. Special attention is given to secondary turbulent motions in the roughness sublayer. The spanwise-alternating pattern of the thin slots between two neighbouring cubes gives rise to spanwise-alternating regions of low- and high-momentum pathways above the cube crests. We show that the strength and spanwise location of these low- and high-momentum pathways depend on the surface coverage density, and that the high-momentum pathways are not necessarily located directly above the roughness elements. In order to determine the physical processes responsible for the generation and the destruction of these secondary turbulent motions, we analyse the dispersive kinetic energy (DKE) budget. The data shows that the secondary motions get their energy from the DKE-specific production term and the wake production term, and lose energy to the DKE-specific dissipation term.
Global health disasters are on the rise and can occur at any time with little advance warning, necessitating preparation. The authors created a comprehensive evidence-based Emergency Preparedness Training Program focused on long-term retention and sustained learner engagement.
A prospective observational study was conducted of a simulation-based mass casualty event training program designed using an outcomes-based logic model. A total of 25 frontline healthcare workers from multiple hospital sites in the New York metropolitan area participated in an 8-hour immersive workshop. Data was collected from assessments, and surveys provided to participants 3 weeks prior to the workshop, immediately following the workshop, and 3 months after completion of the workshop.
The mean percentage of total knowledge scores improved across pre-workshop, post-workshop and retention (3 months post-workshop) assessments (53.2% vs. 64.8% vs. 67.6%, P < 0.05). Average comfort scores in the core MCI competencies increased across pre-workshop, post-workshop and retention self-assessments (P < 0.01). Of the participants assessed at 3 months retention (n = 14, 56%), 50.0% (n = 7) assisted in updating their hospital’s emergency operations plan and 50.0% (n = 7) pursued further self-directed learning in disaster preparedness medicine.
The use of the logic model provided a transparent framework for the design, implementation, and evaluation of a competency-based EPT program at a single academic center.
Separating and reattaching turbulent flows induced by a forward-facing step subjected to an incoming fully developed turbulent channel flow are studied using direct numerical simulation. The step height is one quarter of the channel height, and the Reynolds number based on friction velocity and half-channel height at the inlet is 180. The three-dimensional spatio-temporal characteristics of separation bubbles upstream and downstream of the step are analysed with particular attention to the effects of impinging hairpin structures and the topology of principal stretching. Immediately upstream of the step, the fluctuating vorticity parallel to the mean streamlines is significant. On the frontal surface of the step, strong spanwise skin friction appears in the form of alternating positive and negative values in vertical strips. Over the step, the principal stretching switches orientation along a curve emanating from the leading edge, which is termed the principal stretching line (PSL). The reverse flows upstream and downstream of the step possess dominant and harmonic frequencies that mirror those of the incoming flow. As a hairpin structure leans over the step, the associated vorticity is deformed by the principal stretching. Specifically, PSL marks the lower bound of the deformed hairpin legs, and an opposite-signed pair of counter-rotating quasi-streamwise vortices are induced near the top surface of the step. Consequently, the separation bubbles upstream of and over the step are enlarged and suppressed, respectively. For a sufficiently strong hairpin structure interacting with the step, an open-type separation occurs upstream of the step, while dual separation bubbles appear over the step.
Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare tumefactive lesion with unclear pathogenesis. It is diagnosed by pathological findings of the typical histological features that include granular amorphous cores with palisading spindle to epithelioid cells, variable fibrous stroma, foreign-body reaction with giant cells, and calcification/ossification occasionally with psammoma bodies. However, its histopathology may be variable and currently immunohistochemistry plays a limited role in its diagnosis and understanding the pathogenesis. In this study, we examined 6 cases of CAPNONs including 3 intracranial and 3 spinal epidural lesions (age range: 59–69 years; 3 males and 3 females). Immunohistochemistry revealed that all CAPNON cores contain abundant positive deposits of neurofilament protein (NFP), which was supported by electron microscopy finding of filaments (8–13 nm in diameter). In comparison, no NFP positivity was found in 5 psammomatous/metaplastic meningiomas or 7 intervertebral tissue lesions with calcification/ossification. In addition, CAPNON cellular areas showed variable numbers of CD8+ cytotoxic T-cells with less CD4+ T-cells and a decreased ratio of CD4/CD8+ cells, versus the intervertebral tissue lesions without CD8+ or CD4+ cells. Our findings suggest that NFP may be a principal constituent of CAPNONs, and thus involved in the pathogenesis of CAPNON. Given the decreased CD4/CD8 ratio, the pathogenic process of CAPNON is possibly immune- mediated.
The presentation will enable the learner to:
1. Discuss histopathological features of calcifying pseudoneoplasm of the neuraxis (CAPNON) with variation of non-core components.
2. Explore diagnostic and pathogenic roles of immunohistochemical markers including neurofilament protein and CD4/CD8 in CAPNON.
ABSTRACT IMPACT: The knowledge acquired from my research can inform the development of early diagnostic methods for HIV-associated neurocognitive disorders. OBJECTIVES/GOALS: In the era of combination antiretroviral therapy (cART), the prevalence of HIV-associated neurocognitive disorders (HAND) remains high but the neural mechanisms are unclear. We examined whether older people with HIV (PWH) with minimal cognitive impairment have reduced functional connectivity in frontostriatal circuits compared to controls. METHODS/STUDY POPULATION: 99 PWH (mean age 56.6 years, 75% male, 62% Black, mean duration of HIV-infection 26.2 years ±9.3, 90% viral load <50 copies, 98% on stable cART) and 38 demographically-comparable controls (mean age 54.5 years, 71% male, 58% Black) participated in a cross-sectional study. A 7-domain neuropsychological battery and an Activities of Daily Living index were used to determine HAND diagnoses: 32 PWH met criteria for asymptomatic to mild HAND. Motor skill was assessed using the Grooved Pegboard Test by measuring performance speed. Structural MRI and resting-state functional MRI were collected. Seed-to-voxel analyses were conducted using 4 distinct regions in the striatum as seed regions. We used a voxel threshold of p<0.001 and cluster threshold of p<0.05 (FDR-corrected) after controlling for demographic variables. RESULTS/ANTICIPATED RESULTS: Compared to controls, PWH had lower resting state functional connectivity between the default mode region of the striatum (i.e., medial caudate) and bilateral superior frontal gyrus, supplementary motor cortex and paracingulate gyrus (p<0.05; cluster size: 567 voxels). Also, compared to controls, PWH had reduced resting state functional connectivity between the motor division of the striatum (i.e., posterior putamen) and anterior cingulate cortex and left supplementary motor cortex (p<0.05, cluster size: 405 voxels). Performance speed on the Grooved Pegboard motor test negatively correlated with functional connectivity between the motor region of the striatum and supplementary motor frontal regions in all participants (Spearman’s rho=-0.18, p=0.04). DISCUSSION/SIGNIFICANCE OF FINDINGS: Our results support the hypothesis that frontostriatal abnormalities are widely present in PWH and might play a key role in HAND development. Our data suggest that dysfunction within the frontostriatal circuits may be involved in motor impairment in PWH, and ongoing inflammation may contribute to motor impairment and frontostriatal injury.
We present a high-resolution seawater radiocarbon (Δ14C) record from a Porites coral collected from Masthead Island in the southern Great Barrier Reef (GBR) covering the years 1945–2017. The Δ14C values from 1945–1953 (pre-bomb era) averaged –49‰. As a result of bomb-produced 14C in the atmosphere, Δ14C values started to rise rapidly from 1959, levelled off at ∼131‰ in the late 1970s and gradually decreased to ∼40.3‰ by 2017 due to the decrease in the air-sea 14C gradient and the overturning of the 14C ocean reservoir (i.e., surface ocean to subsurface ocean; atmosphere to surface ocean). The Masthead Island record is in agreement with previous 14C coral records from the southern GBR. A comparison between surface ocean and atmospheric Δ14C suggests that, since 2010, the main reservoir of bomb-derived 14C has shifted from the atmosphere to the surface ocean, potentially resulting in reversed 14C flux in regions where the CO2 gradient is favorable. The high-resolution Masthead coral Δ14C sheds light on long-term variability in air-sea exchange and GBR regional ocean dynamics associated with climate change and in conjunction with the previous records provides a robust seawater 14C reference series to date other carbonate samples.
The c. 1.5–1.3 Ga Wilton package, the upper succession of the greater McArthur Basin, preserves detailed tectono-sedimentary evidence for the Mesoproterozoic evolution of the North Australian Craton (NAC). In addition, it is a valuable global sedimentary repository for the poorly explored Mesoproterozoic. New detrital zircon U–Pb age and Lu–Hf isotope data, collected from multiple, geographically separated, basins that make up the Wilton package, are compiled with previously published data to illuminate the basin evolution. The spatial and temporal variation in sedimentary provenance illustrates two major geographic changes that correspond to continent-scale tectonic convulsions of the NAC during the Mesoproterozoic. The first is shown by the influx of sediment sourced from east and southeast terranes. This is linked to rifting between Proterozoic Australia and Laurentia at c. 1.45 Ga, resulting in the uplift of the eastern margin of the NAC–SAC (South Australian Craton). The second basin geographic change is illustrated by a flux of southerly-sourced detritus that is interpreted to be tectonically driven by the uplift of the southern NAC, during the subduction/closure of the Mirning Ocean at c. 1.32 Ga. Spatially, sediment in the Wilton package is separated into two depositional systems: sedimentary rocks within the Birrindudu Basin, the western component of the Wilton package, have different detrital signatures relative to other Wilton package successions found east of the Daly Waters Fault Zone, in the Beetaloo Sub-basin, the McArthur Basin and the South Nicholson Basin. The Daly Waters Fault Zone is interpreted as an ancient bathymetric high, blocking sediment transport. Although they differ in sources, rocks in both the Birrindudu Basin and the eastern Wilton package record coeval shifts of basin provenance to southern sources. The coherent evolution of basin provenance indicates a consistent tectono-sedimentation history, and links the Birrindudu Basin and the other Wilton successions in a tectonic framework.
During the COVID-19 pandemic, the use of telemedicine as a way to reduce COVID-19 infections was noted and consequently deregulated. However, the degree of telemedicine regulation varies from country to country, which may alter the widespread use of telemedicine. This study aimed to clarify the telepsychiatry regulations for each collaborating country/region before and during the COVID-19 pandemic.
We used snowball sampling within a global network of international telepsychiatry experts. Thirty collaborators from 17 different countries/regions responded to a questionnaire on barriers to the use and implementation of telepsychiatric care, including policy factors such as regulations and reimbursement at the end of 2019 and as of May 2020.
Thirteen of 17 regions reported a relaxation of regulations due to the pandemic; consequently, all regions surveyed stated that telepsychiatry was now possible within their public healthcare systems. In some regions, restrictions on prescription medications allowed via telepsychiatry were eased, but in 11 of the 17 regions, there were still restrictions on prescribing medications via telepsychiatry. Lower insurance reimbursement amounts for telepsychiatry consultations v. in-person consultations were reevaluated in four regions, and consequently, in 15 regions telepsychiatry services were reimbursed at the same rate (or higher) than in-person consultations during the COVID-19 pandemic.
Our results confirm that, due to COVID-19, the majority of countries surveyed are altering telemedicine regulations that had previously restricted the spread of telemedicine. These findings provide information that could guide future policy and regulatory decisions, which facilitate greater scale and spread of telepsychiatry globally.
Atmospheric emissions from ships have not been subject to the same regulations as those on land until very recently. Carbon emissions from the shipping industry are low (per tonne of transported goods) relative to other areas of the transport sector, namely road traffic and aviation. Regulatory controls of atmospheric pollutants such as sulfur dioxide (SO2), nitrogen oxides (NOx) and particulate matter (PM) were imposed on land-based anthropogenic emissions, but not applied to ships.
Genetics hold promise of predicting long-term post-traumatic stress disorder (PTSD) outcomes following trauma. The aim of the current study was to test whether six hypothesized polygenic risk scores (PRSs) developed to capture genetic vulnerability to psychiatric conditions prospectively predict PTSD onset, severity, and 18-year course after trauma exposure.
Participants were 1490 responders to the World Trade Center (WTC) disaster (mean age at 9/11 = 38.81 years, s.d. = 8.20; 93.5% male; 23.8% lifetime WTC-related PTSD diagnosis). Prospective longitudinal data on WTC-related PTSD symptoms were obtained from electronic medical records and modelled as PTSD trajectories using growth mixture model analysis. Independent regression models tested whether six hypothesized psychiatric PRSs (PTSD-PRS, Re-experiencing-PRS, Generalized Anxiety-PRS, Schizophrenia-PRS, Depression-PRS, and Neuroticism-PRS) are predictive of WTC-PTSD outcomes: lifetime diagnoses, average symptom severity, and 18-year symptom trajectory. All analyses were adjusted for population stratification, 9/11 exposure severity, and multiple testing.
Depression-PRS predicted PTSD diagnostic status (OR 1.37, CI 1.17–1.61, adjusted p = 0.001). All PRSs, except PTSD-PRS, significantly predicted average PTSD symptoms (β = 0.06–0.10, adjusted p < 0.05). Re-experiencing-PRS, Generalized Anxiety-PRS and Schizophrenia-PRS predicted the high severity PTSD trajectory class (ORs 1.21–1.28, adjusted p < 0.05). Finally, PRSs prediction was independent of 9/11 exposure severity and jointly accounted for 3.7 times more variance in PTSD symptoms than the exposure severity.
Psychiatric PRSs prospectively predicted WTC-related PTSD lifetime diagnosis, average symptom severity, and 18-year trajectory in responders to 9/11 disaster. Jointly, PRSs were more predictive of subsequent PTSD than the exposure severity. In the future, PRSs may help identify at-risk responders who might benefit from targeted prevention approaches.
This study aimed to investigate the benefit of Bonebridge devices in patients with single-sided deafness.
Five patients with single-sided deafness who were implanted with Bonebridge devices were recruited in a single-centre study. Participants’ speech perception and horizontal sound localisation abilities were assessed at 6 and 12 months post-operatively. Speech intelligibility in noisy environments was measured in three different testing conditions (speech and noise presented from the front, speech and noise presented from the front and contralateral (normal ear) side separately, and speech presented from the ipsilateral (implanted Bonebridge) side and noise from the contralateral side). Sound localisation was evaluated in Bonebridge-aided and Bonebridge-unaided conditions at different stimuli levels (65, 70 and 75 dB SPL).
All participants showed a better capacity for speech intelligibility in quiet environments with the Bonebridge device. The speech recognition threshold with the Bonebridge device was significantly decreased at both short- and long-term follow up in the speech presented from the ipsilateral (implanted Bonebridge) side and noise from the contralateral side condition (p < 0.05). Additionally, participants maintained similar levels of sound localisation between the Bonebridge-aided and unaided conditions (p > 0.05). However, the accuracy of localisation showed some improvement at 70 dB SPL and 75 dB SPL post-operatively.
The Bonebridge device provides the benefit of improved speech perception performance in patients with single-sided deafness. Sound localisation abilities were neither improved nor worsened with Bonebridge implantation at the follow-up assessments.
Klebsiella pneumoniae is a common pathogen associated with nosocomial infections and is characterised serologically by capsular polysaccharide (K) and lipopolysaccharide O antigens. We surveyed a total of 348 non-duplicate K. pneumoniae clinical isolates collected over a 1-year period in a tertiary care hospital, and determined their O and K serotypes by sequencing of the wbb Y and wzi gene loci, respectively. Isolates were also screened for antimicrobial resistance and hypervirulent phenotypes; 94 (27.0%) were identified as carbapenem-resistant (CRKP) and 110 (31.6%) as hypervirulent (hvKP). isolates fell into 58 K, and six O types, with 92.0% and 94.2% typeability, respectively. The predominant K types were K14K64 (16.38%), K1 (14.66%), K2 (8.05%) and K57 (5.46%), while O1 (46%), O2a (27.9%) and O3 (11.8%) were the most common. CRKP and hvKP strains had different serotype distributions with O2a:K14K64 (41.0%) being the most frequent among CRKP, and O1:K1 (26.4%) and O1:K2 (17.3%) among hvKP strains. Serotyping by gene sequencing proved to be a useful tool to inform the clinical epidemiology of K. pneumoniae infections and provides valuable data relevant to vaccine design.
The classical taxonomy of fossil invertebrates is based on subjective judgments of morphology, which can cause confusion, because there are no codified standards for the classification of genera. Here, we explore the validity of the genus taxonomy of 75 species and morphospecies of the Follicucullidae, a late Paleozoic family of radiolarians, using a new method, Hayashi's quantification theory II (HQT-II), a general multivariate statistical method for categorical datasets relevant to discriminant analysis. We identify a scheme of 10 genera rather than the currently accepted 3 genera (Follicucullus, Ishigaconus, and Parafollicucullus). As HQT-II cannot incorporate stratigraphic data, a phylogenetic tree of Follicucullidae was reconstructed for 38 species using maximum parsimony. Six lineages emerged, roughly in concordance with the results of HQT-II. Combined with parsimony ancestral state reconstruction, the ancestral group of this family is Haplodiacanthus. Five other groups were discriminated, the Parafollicucullus, Curvalbaillella, Pseudoalbaillella, Longtanella, and Follicucullus–Cariver lineages. The morphological evolution of these lineages comprises a minimum essential list of eight states of four traits. HQT-II is a novel discriminant analytical multivariate method that may be of value in other taxonomic problems of paleobiology.
Toxoplasma gondii infections are common in humans and animals worldwide. Domestic free-range chickens (Gallus domesticus) are excellent sentinels of environmental contamination with T. gondii oocysts because they feed on the ground. Chickens can be easily infected with T. gondii; however, clinical toxoplasmosis is rare in these hosts. Chickens are comparatively inexpensive and thus are good sentinel animals for T. gondii infections on the farms. Here, the authors reviewed prevalence, the persistence of infection, clinical disease, epidemiology and genetic diversity of T. gondii strains isolated from chickens worldwide for the past decade. Data on phenotypic and molecular characteristics of 794 viable T. gondii strains from chickens are discussed, including new data on T. gondii isolates from chickens in Brazil. This paper will be of interest to biologists, epidemiologists, veterinarians and parasitologists.
Development of high energy density solid-state batteries with Li metal anodes has been limited by uncontrollable growth of Li dendrites in liquid and solid electrolytes (SEs). This, in part, may be caused by a dearth of information about mechanical properties of Li, especially at the nano- and microlength scales and microstructures relevant to Li batteries. We investigate Li electrodeposited in a commercial LiCoO2/LiPON/Cu solid-state thin-film cell, grown in situ in a scanning electron microscope equipped with nanomechanical capabilities. Experiments demonstrate that Li was preferentially deposited at the LiPON/Cu interface along the valleys that mimic the domain boundaries of underlying LiCoO2 (cathode). Cryogenic electron microscopy analysis of electrodeposited Li revealed a single-crystalline microstructure, and in situ nanocompression experiments on nano-pillars with 360–759 nm diameters revealed their average Young's modulus to be 6.76 ± 2.88 GPa with an average yield stress of 16.0 ± 6.82 MPa, ~24x higher than what has been reported for bulk polycrystalline Li. We discuss mechanical deformation mechanisms, stiffness, and strength of nano-sized electrodeposited Li in the framework of its microstructure and dislocation-governed nanoscale plasticity of crystals, and place it in the parameter space of existing knowledge on small-scale Li mechanics. The enhanced strength of Li at small scales may explain why it can penetrate and fracture through much stiffer and harder SEs than theoretically predicted.