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Objective Racially minoritized youth with T1D are made vulnerable to disproportionately adverse health outcomes compared to White peers due to enduring systems of oppression. Thus, understanding modifiable psychosocial factors associated with diabetes-related outcomes in racially minoritized youth may help to buffer deleterious effects of racism. One factor meriting exploration is racial-ethnic identity. There is currently limited research on measures fit to assess ethnic identity in youth with chronic illnesses. This study's purpose is to examine the factor structure, reliability, and validity of the revised Multigroup Ethnic Identity Measure (MEIM-R) in a racially- and income-diverse sample of youth with T1D across sociodemographic and illness-related proxies for one's positionality in oppressive systems. Method As part of a larger study examining resilience, 142 youth with T1D ages 12–18 (M age  =  14.66, SD age = 1.62, 55.6% Black/African-American, 44.4% White) completed the MEIM-R and various psychosocial measures. HbA1c levels and illness duration were extracted from medical records and caregivers reported income information. Confirmatory factor analyses compared the structural validity of competing MEIM-R models, and uniform and non-uniform differential item functioning (DIF) was explored across sociodemographic and illness-related factors. Results While a bifactor structure was supported, the MEIM-R was found to exhibit DIF by race and gender on multiple MEIM-R items and did not demonstrate linear bivariate relations with other psychosocial factors. Conclusions Since different MEIM-R item response patterns were observed across racial/ethnic and gender groups, caution is warranted in using this measure in racially and gender diverse youth with T1D. [ABSTRACT FROM AUTHOR]

Periodontitis is a chronic inflammatory disease driven by dysbiosis in subgingival microbial communities leading to increased abundance of a limited number of pathobionts, including Porphyromonas gingivalis and Treponema denticola. Oral health, particularly periodontitis, is a modifiable risk factor for Alzheimer disease (AD) pathogenesis, with components of both these bacteria identified in postmortem brains of persons with AD. Repeated oral inoculation of mice with P. gingivalis results in brain infiltration of bacterial products, increased inflammation, and induction of AD-like biomarkers. P. gingivalis displays synergistic virulence with T. denticola during periodontitis. The aim of the current study was to determine the ability of P. gingivalis and T. denticola , grown in physiologically relevant conditions, individually and in combination, to induce AD-like pathology following chronic oral inoculation of female mice over 12 weeks. P. gingivalis alone significantly increased all 7 brain pathologies examined: neuronal damage, activation of astrocytes and microglia, expression of inflammatory cytokines interleukin 1β (IL-1β) and interleukin 6 and production of amyloid-β plaques and hyperphosphorylated tau, in the hippocampus, cortex and midbrain, compared to control mice. T. denticola alone significantly increased neuronal damage, activation of astrocytes and microglia, and expression of IL-1β, in the hippocampus, cortex and midbrain, compared to control mice. Coinoculation of P. gingivalis with T. denticola significantly increased activation of astrocytes and microglia in the hippocampus, cortex and midbrain, and increased production of hyperphosphorylated tau and IL-1β in the hippocampus only. The host brain response elicited by oral coinoculation was less than that elicited by each bacterium, suggesting coinoculation was less pathogenic. [ABSTRACT FROM AUTHOR]

Public sector data associated with health are a highly valuable resource with multiple potential end-users, from health practitioners, researchers, public bodies, policy makers, and industry. Data for infectious disease agents are used for epidemiological investigations, disease tracking and assessing emerging biological threats. Yet, there are challenges in collating and re-using it. Data may be derived from multiple sources, generated and collected for different purposes. While public sector data should be open access, providers from public health settings or from agriculture, food, or environment sources have sensitivity criteria to meet with ethical restrictions in how the data can be reused. Yet, sharable datasets need to describe the pathogens with sufficient contextual metadata for maximal utility, e.g. associated disease or disease potential and the pathogen source. As data comprise the physical resources of pathogen collections and potentially associated sequences, there is an added emerging technical issue of integration of omics 'big data'. Thus, there is a need to identify suitable means to integrate and safely access diverse data for pathogens. Established genomics alliances and platforms interpret and meet the challenges in different ways depending on their own context. Nonetheless, their templates and frameworks provide a solution for adaption to pathogen datasets. [ABSTRACT FROM AUTHOR]

Insects exhibit remarkable adaptability in their locomotive strategies in diverse environments, a crucial trait for foraging, survival, and predator avoidance. Microvelia americana , tiny 2–3 mm insects that adeptly walk on water surfaces, exemplify this adaptability by using the alternating tripod gait in both aquatic and terrestrial terrains. These insects commonly inhabit low-flow ponds and streams cluttered with natural debris like leaves, twigs, and duckweed. Using high-speed imaging and pose-estimation software, we analyze M. americana movement on water, sandpaper (simulating land), and varying duckweed densities (10%, 25%, and 50% coverage). Our results reveal M. americana maintain consistent joint angles and strides of their upper and hind legs across all duckweed coverages, mirroring those seen on sandpaper. Microvelia americana adjust the stride length of their middle legs based on the amount of duckweed present, decreasing with increased duckweed coverage and at 50% duckweed coverage, their middle legs' strides closely mimic their strides on sandpaper. Notably, M. americana achieve speeds up to 56 body lengths per second on the deformable surface of water, nearly double those observed on sandpaper and duckweed, which are rough, heterogeneous surfaces. This study highlights M. americana 's ecological adaptability, setting the stage for advancements in amphibious robotics that emulate their unique tripod gait for navigating complex terrains. [ABSTRACT FROM AUTHOR]

We develop a stylized model that generates the following empirical predictions: the less (more) accessible the underlying market is ex ante , the more its liquidity improves (deteriorates) when basket trading becomes available. We empirically test these predictions using corporate bonds before and after the introduction of exchange-traded funds. Consistent with the model's prediction, liquidity improvement is larger for highly arbitraged, low-volume, and high-yield bonds, and for 144A bonds to which retail investor access is prohibited by law. Our article leads to a more nuanced understanding of the impact of basket security introduction than previous research suggested. [ABSTRACT FROM AUTHOR]

The Hubble constant (⁠|$H_0$|⁠), a crucial parameter in cosmology, quantifies the expansion rate of the universe so its precise measurement is important to understand the fundamental dynamics of our evolving universe. One of the major limitations of measuring |$H_0$| using time-delay cosmography is the presence of the mass-sheet degeneracy (MSD) in the lens mass modelling. We propose and quantitatively assess the use of galaxy–galaxy shear measurements to break the MSD in the strong lensing mass modelling. We use stacked galaxy–galaxy lensing profiles and corresponding covariance matrices from Huang et al. to constrain the MSD in lens mass modelling with a highly flexible mass profile. Our analyses show that if ideally all galaxy–galaxy lensing measurements from the Hyper Suprime-Cam survey can be used to constrain the MSD, we can achieve |$\sim 10~{{\ \rm per\ cent}}$| precision on the MSD constraint. We forecast that galaxy–galaxy lensing measurements from Legacy Survey of Space and Time (LSST)-like surveys can in general constrain the MSD with |$\sim 1\,\mathrm{ per\,cent}-3~{{\ \rm per\ cent}}$| precision. Furthermore, if we push weak lensing measurements to a lower angular scale of |$\sim 0.04\,\rm Mpc$|⁠ , a survey like LSST can provide |$\sim 1~{{\ \rm per\ cent}}$| precision on the MSD constraint, enabling a measurement of |$H_0$| at the 1 per cent level. We demonstrate that galaxy–galaxy weak lensing can robustly constrain the MSD independent of stellar kinematics of the deflector, with wide-field survey data alone. [ABSTRACT FROM AUTHOR]

Diets containing inorganic phosphate additives are unbalanced with respect to calcium and these diets have been linked to the development of altered bone metabolism. Using 2 randomized cross-over studies in healthy humans, we (1) characterized the hormonal and urinary response to 2 meals with the same reported phosphorus amount (562–572 mg), where one was manufactured with inorganic phosphate additives and a comparatively lower Ca:P molar ratio (0.26 vs 0.48), and (2) assessed how acute homeostatic mechanisms adapt following 5-d exposure to recommended dietary phosphorus amount (~700 mg P/d) compared to a diet enriched with inorganic phosphate additives (~1100 mg P/d). Participants were then challenged with 500 mg of oral phosphorus in the form of inorganic phosphate after an overnight fast following each diet condition. Measurements included serum calcium, phosphate, PTH, and fibroblast growth factor 23 , vitamin D metabolites, and urine calcium and phosphate excretion. Following the meal containing inorganic phosphate additives with a low Ca:P ratio, serum phosphate was higher and more phosphate was excreted in the urine compared to the low additive meal. Although the Ca:P and calcium content was lower in the high additive meal, the same amount of calcium was excreted into the urine. Subsequently, increasing only dietary phosphate through additives resulted in lower 24-h excretion of calcium. The oral phosphate challenge promoted urinary calcium excretion, despite no consumption of calcium, which was attenuated when pre-acclimated to a high phosphate diet. These data suggest that ingestion of inorganic phosphate promotes calcium excretion, but homeostatic mechanisms may exist to reduce calcium excretion that are responsive to dietary intake of phosphate. Future studies are required to evaluate potential implication of diets enriched with inorganic phosphate additives on bone health. Lay Summary: Excessive dietary phosphorus has been linked to the development of bone and vascular disorders. Further, highly bioavailable inorganic phosphate additives, which are unregulated, have been estimated to comprise approximately 50% of an individual's consumed dietary phosphorus. Using 2 randomized cross-over studies in young healthy participants, we assessed (1) the hormonal and urinary response to 2 meals with the same reported phosphate amount, but one manufactured with inorganic phosphate additives, and (2) how acute homeostatic mechanisms adapt following 5-d of a diet supplemented with inorganic phosphate additives. The results suggest that ingestion of meals containing phosphate additives promotes excess calcium excretion, but homeostatic mechanisms in young healthy adults are sufficient to reduce calcium excretion in response to a 5-d dietary intake of these phosphate additives. These findings indicate an important role of inorganic phosphate additives on acute and chronic calcium homeostasis that will need to be carefully explored for potential implications on bone and/or vascular outcomes. Together these findings also indicate the critical importance of bioavailability of phosphate and the balance with calcium in dietary management. Graphical Abstract [ABSTRACT FROM AUTHOR]

The ultraluminous infrared galaxy F13451+1232 is an excellent example of a galaxy merger in the early stages of active galactic nucleus (AGN) activity, a phase in which AGN-driven outflows are expected to be particularly important. However, previous observations have determined that the mass outflow rates of the warm ionized and neutral gas phases in F13451+1232 are relatively modest, and there has been no robust detection of molecular outflows. Using high-spatial resolution Atacama Large Millimeter/submillimeter Array CO(1–0) observations, we detect a kiloparsec-scale circumnuclear disc, as well as extended (r ∼ 440 pc), intermediate-velocity (300 < | v | < 400 km s−1) cold molecular gas emission that cannot be explained by rotational disc motions. If interpreted as AGN-driven outflows, the mass outflow rates associated with this intermediate-velocity gas are relatively modest (⁠|$\dot{M}_\mathrm{out}=22$| –27 M⊙ yr−1); however, we also detect a compact (r out < 120 pc), high-velocity (400 <  v  < 680 km s−1) cold molecular outflow near the primary nucleus of F13451+1232, which carries an order of magnitude more mass (⁠|$\dot{M}_\mathrm{out}$|  ∼ 230 M⊙ yr−1) than (and several times the kinetic power of) the previously detected warmer phases. Moreover, the similar spatial scales of this compact outflow and the radio structure indicate that it is likely accelerated by the small-scale (r  ∼ 130 pc) AGN jet in the primary nucleus of F13451+1232. Considering the compactness of the nuclear outflow and intermediate-velocity non-rotating gas that we detect, we argue that high-spatial resolution observations are necessary to properly quantify the properties of AGN-driven outflows and their impacts on host galaxies. [ABSTRACT FROM AUTHOR]

Objectives This study aims to elucidate the genomic dynamics driving the emergence of antimicrobial resistance (AMR), with a specific focus on the interplay between AMR and antimicrobial usage. Methods We conducted a comprehensive analysis using a ST239 methicillin-resistant Staphylococcus aureus (MRSA) dataset over a continuous 12-year period from a single hospital. Genomic analyses were performed tracking the changes in MRSA populations, particularly the emergence of reduced vancomycin susceptibility, and assessing the impact of glycopeptide use on these emergence events. Results Our findings reveal a significant correlation between hospital glycopeptide usage and the selection of MRSA strains with reduced vancomycin susceptibility. Genomic analyses provided insights into the molecular mechanisms driving resistance emergence, including the slowing of the molecular clock rate in response to heightened antimicrobial consumption. Conclusions In conclusion, this study the highlights the complex dynamics between AMR and antimicrobial use at the hospital level. The observed correlation between antimicrobial consumption and the development of less susceptible MRSA strains underscores the importance of antimicrobial stewardship programmes and the establishment of optimal consumption thresholds for mitigating AMR effectively. [ABSTRACT FROM AUTHOR]

In this study, a chilli pepper (Capsicum annuum) panel for post-harvest carotenoid retention was studied to elucidate underlying mechanisms associated with this commercial trait of interest. Following drying and storage, some lines within the panel had an increase in carotenoids approaching 50% compared with the initial content at the fresh fruit stage. Other lines displayed a 25% loss of carotenoids. The quantitative determination of carotenoid pigments with concurrent cellular analysis indicated that in most cases, pepper fruit with thicker (up to 4-fold) lipid exocarp layers and smooth surfaces exhibit improved carotenoid retention properties. Total cutin monomer content increased in medium/high carotenoid retention fruits and subepidermal cutin deposits were responsible for the difference in exocarp thickness. Cutin biosynthesis and cuticle precursor transport genes were differentially expressed between medium/high and low carotenoid retention genotypes, and this supports the hypothesis that the fruit cuticle can contribute to carotenoid retention. Enzymatic degradation of the cuticle and cell wall suggests that in Capsicum the carotenoids (capsanthin and its esters) are embedded in the lipidic exocarp layer. This was not the case in tomato. Collectively, the data suggest that the fruit cuticle could provide an exploitable resource for the enhancement of fruit quality. [ABSTRACT FROM AUTHOR]

Background WGS is increasingly being applied to healthcare-associated vancomycin-resistant Enterococcus faecium (VREfm) outbreaks. Within-patient diversity could complicate transmission resolution if single colonies are sequenced from identified cases. Objectives Determine the impact of within-patient diversity on transmission resolution of VREfm. Materials and methods Fourteen colonies were collected from VREfm positive rectal screens, single colonies were collected from clinical samples and Illumina WGS was performed. Two isolates were selected for Oxford Nanopore sequencing and hybrid genome assembly to generate lineage-specific reference genomes. Mapping to closely related references was used to identify genetic variations and closely related genomes. A transmission network was inferred for the entire genome set using Phyloscanner. Results and discussion In total, 229 isolates from 11 patients were sequenced. Carriage of two or three sequence types was detected in 27% of patients. Presence of antimicrobial resistance genes and plasmids was variable within genomes from the same patient and sequence type. We identified two dominant sequence types (ST80 and ST1424), with two putative transmission clusters of two patients within ST80, and a single cluster of six patients within ST1424. We found transmission resolution was impaired using fewer than 14 colonies. Conclusions Patients can carry multiple sequence types of VREfm, and even within related lineages the presence of mobile genetic elements and antimicrobial resistance genes can vary. VREfm within-patient diversity could be considered in future to aid accurate resolution of transmission networks. [ABSTRACT FROM AUTHOR]

Background and Objectives Informal (or family) caregivers to older adults with Alzheimer's disease or other related dementias (ADRD) could greatly benefit from innovative telecaregiving systems that support caregiving from a distance. The objective of this review is to better understand (a) who is involved in telecaregiving and their experiences; (b) the interventions currently available to support ADRD telecaregiving; and (c) the outcomes measured to assess the effects of ADRD telecaregiving interventions. Research Design and Methods A mapping review was conducted by systematically searching MEDLINE, CINAHL, Embase, and PsycINFO for all works published in English from 2002 to 2022. References of included publications were searched to identify additional empirical publications for inclusion. Results Sixty-one publications (describing 48 studies and 5 nonstudy sources) were included in the review. Currently available information on the demographics, experiences, challenges, and benefits of ADRD telecaregivers is summarized. We found that interventions to support telecaregiving could be classified into 7 categories of technological interventions and 3 categories of nontechnological interventions. Empirical studies on ADRD telecaregiving interventions investigated a variety of outcomes, the most prevalent being user experience. Discussion and Implications We conclude that (a) the paucity of literature on telecaregiving does not allow for a comprehensive understanding of the needs and day-to-day activities of ADRD telecaregivers; (b) interventions developed to support ADRD telecaregiving may not fully meet the needs of caregivers or care recipients; and (c) there is insufficient rigorous research establishing the effects of telecaregiving interventions on key ADRD-related outcomes. [ABSTRACT FROM AUTHOR]

With its near-to-mid-infrared high-contrast imaging capabilities, JWST is ushering us into a golden age of directly imaging Jupiter-like planets. As the two closest cold Jupiters, ε Ind A b and ε Eridani b have sufficiently wide orbits and adequate infrared emissions to be detected by JWST. To detect more Jupiter-like planets for direct imaging, we develop a gost -based method to analyse radial velocity data and multiple Gaia data releases simultaneously. Without approximating instantaneous astrometry by catalogue astrometry, this approach enables the use of multiple Gaia data releases for detection of both short-period and long-period planets. We determine a mass of |$2.96_{-0.38}^{+0.41}$|   M Jup and a period of |$42.92_{-4.09}^{+6.38}$|  yr for ε Ind A b. We also find a mass of |$0.76_{-0.11}^{+0.14}$|   M Jup , a period of |$7.36_{-0.05}^{+0.04}$|  yr, and an eccentricity of 0.26 |$_{-0.04}^{+0.04}$|   M Jup, for ε Eridani b. The eccentricity differs from that given by some previous solutions, probably due to the sensitivity of orbital eccentricity to noise modelling. Our work refines the constraints on orbits and masses of the two nearest Jupiters and demonstrate the feasibility of using multiple Gaia data releases to constrain Jupiter-like planets. [ABSTRACT FROM AUTHOR]

Despite being thought to play an important role in galaxy evolution, the true impact of outflows driven by active galactic nuclei (AGNs) on their host galaxies is unclear. In part, this may be because electron densities of outflowing gas are often underestimated: recent studies that use alternative diagnostics have measured much higher densities than those from commonly used techniques and consequently find modest outflow masses and kinetic powers. Furthermore, outflow ionization mechanisms – which are often used to probe acceleration mechanisms – are also uncertain. To address these issues, we have analysed archival HST/STIS spectra of the inner regions (r < 160 pc) of the nearby prototypical Seyfert galaxies NGC 1068 and NGC 4151, which show evidence of warm-ionized outflows driven by the central AGN. We derive high electron densities (103.6 <  n e < 104.8 cm−3) using the transauroral [O  ii ] and [S  ii ] emission line ratios for the first time with spatially resolved observations. Moreover, we find evidence that the gas along the radio axis in NGC 1068 has a significant AGN-photoionized matter-bounded component, and there is evidence for shock-ionization and/or radiation-bounded AGN-photoionization along the radio axis in NGC 4151. We also note that the outflow extents are similar to those of the radio structures, consistent with acceleration by jet-induced shocks. Taken together, our investigation demonstrates the diversity of physical and ionization conditions in the narrow-line regions of Seyfert galaxies, and hence reinforces the need for robust diagnostics of outflowing gas densities and ionization mechanisms. [ABSTRACT FROM AUTHOR]

The article presents The Annual Report of the Society for Financial Studies for 2019-2020 and provides an overview of SFS activities during 2019-2020, including all three journals, both Cavalcade conferences, and the SFS financial and policy report.

The 2018-2019 annual report for the Society for Financial Studies is presented.

Over the last few years, both Atacama Large Millimeter/submillimeter Array (ALMA) and Spitzer observations have revealed a population of likely massive galaxies at z > 3 that was too faint to be detected in Hubble Space Telescope (HST) rest-frame ultraviolet imaging. However, due to the very limited photometry for individual galaxies, the true nature of these so-called HST -dark galaxies has remained elusive. Here, we present the first sample of such galaxies observed with very deep, high-resolution NIRCam imaging from the Early Release Science programme CEERS. 30 HST -dark sources are selected based on their red colours across 1.6–4.4 |$\mu$| m. Their physical properties are derived from 12-band multiwavelength photometry, including ancillary HST imaging. We find that these galaxies are generally heavily dust-obscured (AV ∼ 2 mag), massive (log (M /M⊙) ∼ 10), star-forming sources at z ∼ 2−8 with an observed surface density of ∼0.8 arcmin−2. This suggests that an important fraction of massive galaxies may have been missing from our cosmic census at z > 3 all the way into the Epoch of Reionization. The HST -dark sources lie on the main sequence of galaxies and add an obscured star formation rate density of |$\mathrm{3.2^{+1.8}_{-1.3} \times 10^{-3} \,{\rm M}_{\odot }\,yr^{-1}\,Mpc^{-3}}$| at z ∼ 7, showing likely presence of dust in the Epoch of Reionization. Our analysis shows the unique power of JWST to reveal this previously missing galaxy population and to provide a more complete census of galaxies at z  = 2−8 based on rest-frame optical imaging. [ABSTRACT FROM AUTHOR]

Background Therapies to prevent recurrence of Clostridioides difficile infection (CDI) in pediatric patients are needed. Bezlotoxumab is a fully human monoclonal antibody approved for prevention of recurrent CDI in adults. We assessed the pharmacokinetics, safety, tolerability, and efficacy of bezlotoxumab in pediatric patients. Methods MODIFY III was a multicenter, double-blind, placebo-controlled study of bezlotoxumab in children (1 to <18 years) receiving antibacterial treatment for CDI. Participants were randomized 3:1 to receive a single infusion of bezlotoxumab (10 mg/kg) or placebo and were stratified by age at randomization (cohort 1: 12 to <18 years, cohort 2: 1 to <12 years). The primary objective was to characterize bezlotoxumab pharmacokinetics to support dose selection for pediatric patients; the primary endpoint was the area under the bezlotoxumab serum concentration–time curve (AUC0-inf). Safety, tolerability, and efficacy were monitored for 12 weeks post-infusion. Results A total of 148 participants were randomized and 143 were treated: 107 with bezlotoxumab and 36 with placebo (cohort 1 n = 60, cohort 2 n = 83; median age 9.0 years); 52.4% of participants were male and 80.4% were white. Geometric mean ratios (90% CI) for bezlotoxumab AUC0-inf were 1.06 (0.95, 1.18) and 0.82 (0.75, 0.89) h * μg/mL for cohorts 1 and 2, respectively. Bezlotoxumab 10 mg/kg was generally well-tolerated with an adverse event profile similar to placebo, including no treatment discontinuations due to adverse events. CDI recurrence was low and comparable for bezlotoxumab (11.2%) and placebo (14.7%). Conclusions The results of this study support the bezlotoxumab dose of 10 mg/kg for pediatric patients. Trial registration NCT03182907 at ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Motivation Native top-down proteomics (nTDP) integrates native mass spectrometry (nMS) with top-down proteomics (TDP) to provide comprehensive analysis of protein complexes together with proteoform identification and characterization. Despite significant advances in nMS and TDP software developments, a unified and user-friendly software package for analysis of nTDP data remains lacking. Results We have developed MASH Native to provide a unified solution for nTDP to process complex datasets with database searching capabilities in a user-friendly interface. MASH Native supports various data formats and incorporates multiple options for deconvolution, database searching, and spectral summing to provide a "one-stop shop" for characterizing both native protein complexes and proteoforms. Availability and implementation The MASH Native app, video tutorials, written tutorials, and additional documentation are freely available for download at https://labs.wisc.edu/gelab/MASH%5fExplorer/MASHSoftware.php. All data files shown in user tutorials are included with the MASH Native software in the download.zip file. [ABSTRACT FROM AUTHOR]

Active galactic nucleus (AGN)-driven outflows are now routinely used in models of galaxy evolution as a feedback mechanism; however, many of their properties remain highly uncertain. Perhaps the greatest source of uncertainty is the electron density of the outflowing gas, which directly affects derived kinetic powers and mass outflow rates. Here we present spatially resolved, wide spectral-coverage Xshooter observations of the nearby active galaxy IC 5063 (z  = 0.001131), which shows clear signatures of outflows being driven by shocks induced by a radio jet interacting with the ISM. For the first time, we use the higher-critical-density transauroral (TR) [S  ii ] and [O  ii ] lines to derive electron densities in spatially resolved observations of an active galaxy, and present evidence that the lines are emitted in the same spatial regions as other key diagnostic lines. In addition, we find that the post-shock gas is denser than the pre-shock gas, possibly due to shock compression effects. We derive kinetic powers for the warm ionized outflow phase and find them to be below those required by galaxy evolution models; however, other studies of different gas phases in IC 5063 allow us to place our results in a wider context in which the cooler gas phases constitute most of the outflowing mass. We investigate the dominant ionization and excitation mechanisms and find that the warm ionized outflow phase is dominated by AGN-photoionization, while the warm molecular phase has composite AGN-shock excitation. Overall, our results highlight the importance of robust outflow diagnostics and reinforce the utility of the TR lines for future studies of outflows in active galaxies. [ABSTRACT FROM AUTHOR]

Aims Non-renal extravasation of phosphate from the circulation and transient accumulation into tissues and extracellular fluid is a regulated process of acute phosphate homeostasis that is not well understood. This process is especially relevant in the setting of chronic kidney disease (CKD), where exposure to increased phosphate is prolonged due to inefficient kidney excretion. Furthermore, CKD-associated mineral dysregulation induces pathological accumulation of phosphate causing vascular calcification (VC). Our objective was to determine whether the systemic response to acute phosphate challenges is altered by VC. Methods and results After bolus phosphate administration, circulating and tissue deposition of this challenge was assessed in two rat models of VC using a radiolabelled phosphate tracer. In an adenine-induced model of CKD (N = 70), animals with VC had a blunted elevation of circulating 33PO4 following oral phosphate administration (P < 0.01), and the discordant deposition could be traced to the calcified arteries (11.4 [7.5–13.1] vs.43.0 [35.5–53.7] pmol/ng tissue, P < 0.001). In a non-CKD model of VC, calcification was induced with 0.5 ug/kg calcitriol and then withdrawn (N = 24). New phosphate uptake by the calcified vasculature correlated to the pre-existing burden of calcification (r = 38, P < 0.001) and was substantially attenuated in the absence of calcification stimulus (P < 0.01). Phosphate accrual was stimulated by the phosphate challenge and not present to the same degree during passive disposition of circulating phosphate. Further, the form of phosphate that deposited to the vasculature was predominately amorphous inorganic phosphate and not that which was bound in matured calciprotein particles. Conclusions In the process of calcification, arteries acutely deposit substantial amorphous phosphate while blunting the elevation in the circulation, thereby altering the systemic disposition of phosphate and identifying VC as a participatory mineral homeostatic organ. This study demonstrates the negative vascular consequence of acute fluctuations in circulating phosphate, and supports the importance of phosphate bioavailability and diet management in CKD patients as a mediator of cardiovascular risk. [ABSTRACT FROM AUTHOR]

Background Patch testing is an important investigation when dermatitis is unresponsive to, or worsened by, topical corticosteroid treatment. There is a balance to be struck between testing too many allergens, which is expensive, time consuming and risks causing sensitization, and testing too few, which risks missing the diagnosis. The current British Society for Cutaneous Allergy (BSCA) corticosteroid series comprises eight allergens and was last updated in February 2007. Aim To review and update the BSCA corticosteroid series. Methods We retrospectively analysed data from 16 patch test centres in the UK and Ireland for all patients who were patch tested to a corticosteroid series between August 2017 and July 2019. We recorded the allergens tested, the number and percentage tested to a corticosteroid series and the number of positive results for each allergen. We identified the allergens that test positive in ≥ 0.1% of selectively tested patients. Results Overall, 3531 patients were tested to a corticosteroid series in the 16 centres. The number of allergens tested ranged from 7 to 18 (mean 10). The proportion of patch test patients who were tested to a corticosteroid series ranged from 1% to 99%. Six allergens in the 2017 BSCA series tested positive in ≥ 0.1% of patients. Nine allergens not in the BSCA corticosteroid series tested positive in ≥ 0.1% of patients. Conclusion This audit demonstrates the importance of regular review of recommended series and the significant variations in practice. The new BSCA corticosteroid series that we recommend contains 13 haptens, with the addition of the patient's own steroid creams as appropriate. [ABSTRACT FROM AUTHOR]

Context: Dietary consumption of phosphate is increasing, and elevated serum phosphate is associated with increased cardiovascular disease (CVD) risk. Sex differences in phosphate homeostasis and response to changes in dietary phosphate intake, which are not captured by clinically measured analytes, may contribute to differences in CVD presentation and bone disease. Objective: To assess sex differences in acute phosphate homeostasis in response to a single oral phosphate challenge. Design: Cross-sectional. Setting: General community. Participants: 78 participants (40-76 years) with measured glomerular filtration rate >60 mL/min/1.73 m² and no clinically diagnosed CVD and 14 young healthy adults. Main Outcome Measures: To elucidate subtle alterations in phosphate homeostasis, we employ an acute challenge whereby the hormonal response, circulating mineral levels, and urinary excretion are assessed following an oral challenge of phosphate. Results: Although both males and females had similar changes in circulating phosphate, calcium, and parathyroid hormone in response to the challenge, females excreted ~1.9x more phosphate and ~2.7x more calcium than males, despite not consuming calcium. These sex differences were recapitulated in healthy young adults. This excretion response did not correlate to age, serum phosphate, or estradiol levels. The females with greater excretion of phosphate had higher levels of bone resorption markers compared to formation markers. Conclusions: Taken together, these data identify sex differences in acute phosphate homeostasis, specifically that females may mobilize and excrete endogenous sources of calcium and phosphate in response to oral phosphate compared to males. While high levels of dietary phosphate negatively impact bone, our results suggest that females may incur more risk from these diets. [ABSTRACT FROM AUTHOR]

Purpose Current Neurocritical Care Society guidelines on the management of cerebral edema recommend hypertonic saline (HTS) over mannitol in some scenarios, but practical questions remain regarding the appropriate administration method, concentration/dose, monitoring to ensure safe use, and storage. The aim of this article is to address these practical concerns based on the evidence currently available. Summary Many different hypertonic solutions have been studied to define the optimal hyperosmolar substance to relieve acute cerebral edema in patients with conditions such as acute ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and traumatic brain injury. Mannitol and HTS are the main hyperosmolar therapies in use in contemporary neurocritical care practice. Contemporary use of HTS has followed a circuitous path in regards to the practical aspects of dosing and formulation, with evidence mainly consisting of retrospective or observational data. The effectiveness of bolus doses of HTS to lower acutely elevated intracranial pressure is well accepted. Adverse events with use of HTS are often mild and non–clinically significant if appropriate monitoring of serum sodium and chloride concentrations is performed. Available evidence shows that peripheral administration of HTS is likely safe in certain circumstances. Timely utilization of HTS is complicated by regulatory requirements for safe storage, but with appropriate safeguards HTS can be stored in patient care areas. Conclusion HTS formulations, methods of administration, infusion rate, and storage vary by institution, and no practice standards exist. Central intravenous administration may be preferred for HTS, but peripheral intravenous administration is safe provided measures are undertaken to detect and prevent phlebitis and extravasation. The safe use of HTS is possible with proper protocols, education, and institutional safeguards in place. [ABSTRACT FROM AUTHOR]

Background Vitamin K activates matrix Gla protein (MGP), a key inhibitor of vascular calcification. There is a high prevalence of sub-clinical vitamin K deficiency in patients with end-stage kidney disease. Methods A parallel randomized placebo-controlled pilot trial was designed to determine whether 10 mg of phylloquinone thrice weekly versus placebo modifies coronary artery calcification progression over 12 months in patients requiring hemodialysis with a coronary artery calcium score (CAC) ≥30 Agatston Units (ClinicalTrials.gov identifier NCT01528800). The primary outcome was feasibility (recruitment rate, compliance with study medication, study completion and adherence overall to study protocol). CAC score was used to assess calcification at baseline and 12 months. Secondary objectives were to explore the impact of phylloquinone on vitamin K-related biomarkers (phylloquinone, dephospho-uncarboxylated MGP and the Gla-osteocalcin to Glu-osteocalcin ratio) and events of clinical interest. Results A total of 86 patients with a CAC score ≥30 Agatston Units were randomized to either 10 mg of phylloquinone or a matching placebo three times per week. In all, 69 participants (80%) completed the trial. Recruitment rate (4.4 participants/month) and medication compliance (96%) met pre-defined feasibility criteria of ≥4.17 and ≥90%, respectively. Patients randomized to phylloquinone for 12 months had significantly reduced levels of dephospho-uncarboxylated MGP (86% reduction) and increased levels of phylloquinone and Gla-osteocalcin to Glu-osteocalcin ratio compared with placebo. There was no difference in the absolute or relative progression of coronary artery calcification between groups. Conclusion We demonstrated that phylloquinone treatment improves vitamin K status and that a fully powered randomized trial may be feasible. [ABSTRACT FROM AUTHOR]

Background Obesity after traumatic brain injury (TBI) is a public health issue and no evidence-based weight loss interventions exist to meet the unique needs of individuals after TBI. Purpose To (a) examine the efficacy of the Diabetes Prevention Program Group Lifestyle Balance for TBI (GLB-TBI) weight-loss intervention compared to an attention control for primary (weight-loss) and secondary health outcomes; (b) determine participant compliance with the GLB-TBI; and (c) determine if compliance is associated with improved outcomes. Methods Individuals with moderate to severe TBI, age 18–64 years, ≥6 months postinjury, and body mass index of ≥25 kg/m2 were randomized to a 12-month, 22-session GLB-TBI intervention or attention control condition. Weight-loss (lbs.), anthropometric, biomarkers, and patient-reported outcomes were collected at baseline, 3, 6, and 12 months. Results The GLB-TBI group (n = 27) lost 17.8 ± 41.4lbs (7.9%) over the 12-month program and the attention control group (n = 27) lost 0 ± 55.4lbs (0%). The GLB-TBI group had significant improvements in diastolic blood pressure, triglycerides, and HDL cholesterol. GLB-TBI attendance was 89.6% and weekly self-monitoring of diet and activity was 68.8%. Relative to baseline, the GLB-TBI compliant group (≥80% attendance; ≥85% self-monitoring; n = 10) had a statistically significant decrease in weight at each assessment, the noncompliant group had a significant decrease between 6 and 12 months (n = 17), with no change in weight in the attention control group (n = 27). Conclusions Findings suggest for adults with TBI who are overweight or obese, participation in the GLB-TBI can significantly reduce weight and metabolic risk factors and increase self-reported habits for diet and exercise. [ABSTRACT FROM AUTHOR]

Background Most human immunodeficiency virus (HIV) seroconversions in people who have initiated preexposure prophylaxis (PrEP) occur in the context of insufficient adherence. We describe participants who seroconverted after being dispensed PrEP in a large PrEP implementation study in Australia. Methods Expanded PrEP Implementation in Communities in New South Wales was an implementation study of daily oral PrEP in individuals aged ≥18 years at high risk for acquiring HIV. HIV seroconversions were defined as a positive HIV test by either antigen, antibody, or detectable HIV viral load after enrollment. Insufficient adherence, measured by dispensing logs or participant self-report, was defined as <4 PrEP doses per week. Results A total of 9596 participants were enrolled and dispensed PrEP between 1 March 2016 and 30 April 2018; 30 were diagnosed with HIV by 31 March 2019. The median (interquartile range [IQR]) age was 31 (25–38) years, all identified as male, 29 (97%) identified as gay or homosexual, and 20 (69%) lived in a postcode with a low concentration of gay male residents. The median (IQR) days from first PrEP dispensing to diagnosis was 409 (347–656). There was no evidence that participants who seroconverted had been sufficiently adherent to PrEP. Nineteen (63%) participants who seroconverted were diagnosed with chlamydia, gonorrhoea, syphilis, or new hepatitis C infection. One participant had resistance to emtricitabine (M184V mutation) at diagnosis. Conclusions Participants who seroconverted were insufficiently adherent to PrEP despite being at high risk for acquiring HIV. Understanding the reasons for poor PrEP adherence in individuals who subsequently acquire HIV is critical to improving PrEP effectiveness. [ABSTRACT FROM AUTHOR]

Context: Gestational diabetes (GDM) imposes long-term adverse health effects on the mother and fetus. The role of magnetic resonance imaging (MRI) during early gestation in GDM has not been well-studied. Objective: To investigate the role of quantitative MRI measurements of placental volume and perfusion, with distribution of maternal adiposity, during early gestation in GDM. Methods: At UCLA outpatient antenatal obstetrics clinics, ∼200 pregnant women recruited in the first trimester were followed temporally through pregnancy until parturition. Two placental MRI scans were prospectively performed at 14 to 16 weeks and 19 to 24 weeks gestational age (GA). Placental volume and blood flow (PBF) were calculated from placental regions of interest; maternal adiposity distribution was assessed by subcutaneous fat area ratio (SFAR) and visceral fat area ratio (VFAR). Statistical comparisons were performed using the two-tailed t test. Predictive logistic regression modeling was evaluated by area under the curve (AUC). Results: Of a total 186 subjects, 21 subjects (11.3%) developed GDM. VFAR was higher in GDM vs the control group, at both time points (P<0.001 each). Placental volume was greater in GDM vs the control group at 19 to 24 weeks GA (P=0.01). Combining VFAR, placental volume and perfusion, improved the AUC to 0.83 at 14 to 16 weeks (positive predictive value [PPV]=0.77, negative predictive value [NPV]=0.83), and 0.81 at 19 to 24 weeks GA (PPV=0.73, NPV=0.86). Conclusion: A combination of MRI-based placental volume, perfusion, and visceral adiposity during early pregnancy demonstrates significant changes in GDM and provides a proof of concept for predicting the subsequent development of GDM. [ABSTRACT FROM AUTHOR]

Aim Difficulties in social functioning have been observed in youth at clinical high-risk (CHR) of psychosis even in those who do not go on to develop a psychotic illness. Few treatment studies have attempted to improve social functioning in this population. The aim of this study was to conduct a randomized trial comparing the effects of Cognitive-Behavioral Social Skills Training (CBSST) with a supportive therapy (ST). Methods Both CBSST and ST were weekly group therapies, delivered over 18 weeks. This was a 2-arm trial with single-blinded ratings and intention-to-treat analyses. Assessments occurred at baseline, end-of-treatment, and 12 months after the baseline assessment. The primary outcome was social and role functioning and defeatist performance attitudes were the secondary outcome. Attenuated positive and negative symptoms, anxiety, depression, self-efficacy, and beliefs about self and others were examined as exploratory outcomes. Results There were no significant differences between the 2 groups at baseline or either of the 2 follow-ups. However, at follow-ups, in each group there were significant improvements in clinical symptoms. These could not be attributed to group treatment since there was no control or wait-list group. Conclusions Since poor social functioning is one of the most observed difficulties in CHR individuals, and a decline in social functioning may be a significant predictor of later transition to psychosis, future work will be needed to find effective treatments for this decline in functioning for CHR youth. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES Endovascular aortic arch stent grafting with branched devices has shown initial promising results. The aim of this prospective, multicentre study was to evaluate 3-year outcomes of aortic arch stent grafting with NEXUS® Aortic Arch Stent Graft System (Nexus), a single-branch, bi-modular, off-the-shelf aortic arch stent graft system in high-risk patients. METHODS Patients treated with Nexus, either under the feasibility clinical study or as compassionate use procedures in 5 centres, were included in this study. The primary end point was overall survival. The secondary end points included the incidence of procedure-related unplanned intervention, stroke, paraplegia and endoleak. Clinical and radiologic follow-up was performed at each study site at 30 days, 6 months and on a yearly basis thereafter up to 3 years postoperatively. RESULTS We analysed data from a total of 28 patients. The overall median follow-up was 1132 (interquartile range: 809–1537). There were no device or procedure-related deaths between 1 and 3 years. Overall survival at 1 and 3 years was 89% and 71%, respectively. The cumulative incidence of unplanned reintervention at 1 and 3 years was 11% and 29%, respectively. There were no reports of stroke, paraplegia, aneurysm rupture, myocardial infarction or new aortic valve insufficiency. In this study's 1–3 year follow-up period, 1 type Ib (4%), 1 type II (4%) and 2 type III (8%; between Nexus' distal end and Thoracic endovascular aortic repair (TEVAR) extensions) endoleak were detected. CONCLUSIONS Endovascular aortic arch exclusion with the single-branch, off-the-shelf Nexus system provides promising clinical and radiologic results at 3-year follow-up in a high-risk patient cohort. [ABSTRACT FROM AUTHOR]

The Siberian silk moth, Dendrolimus sibiricus Tschetverikov, is a very serious pest of conifers in Russia and is an emerging threat in North America where an accidental introduction could have devastating impacts on native forest resources. Other Dendrolimus Germar species and related Eurasian lasiocampids in the genus Malacosoma (Hubner) could also present a risk to North America's forests. Foreign vessels entering Canadian and U.S. ports are regularly inspected for Lymantria dispar (Linnaeus) and for the presence of other potentially invasive insects, including suspicious lasiocampid eggs. However, eggs are difficult to identify based on morphological features alone. Here, we report on the development of two TaqMan (Roche Molecular Systems, Inc. Rotkreuz, Switzerland) assays designed to assist regulatory agencies in their identification of these insects. Developed using the barcode region of the cytochrome c oxidase I (COI) gene and run in triplex format, the first assay can detect Dendrolimus and Malacosoma DNA, and can distinguish North American from Eurasian Malacosoma species. The second assay is based on markers identified within the internal transcribed spacer 2 (ITS2) region and was designed to specifically identify D. sibiricus , while discriminating closely related Dendrolimus taxa. In addition to providing direct species identification in the context of its use in North America, the D. sibiricus assay should prove useful for monitoring the spread of this pest in Eurasia, where its range overlaps with those of the morphologically identical D. superans (Butler) and similar D. pini (Linnaeus). The assays described here can be performed either in the lab on a benchtop instrument, or on-site using a portable machine. [ABSTRACT FROM AUTHOR]

Background Increasing antimicrobial resistance (AMR) in Salmonella has been observed in the Philippines. We aimed to characterise the population and AMR mechanisms of Salmonella with whole genome sequencing (WGS) and compare it with laboratory surveillance methods. Methods The serotype, multilocus sequence type, AMR genes and relatedness between isolates were determined from the genomes of 148 Salmonella Typhi (S. Typhi) and 65 non-typhoidal Salmonella (NTS) collected by the Antimicrobial Resistance Surveillance Program during 2013–2014. Genotypic serotypes and AMR prediction were compared with phenotypic data. Results AMR rates in S. Typhi were low, with sparse acquisition of mutations associated with reduced susceptibility to fluoroquinolones or extended-spectrum beta-lactamases (ESBL) genes. By contrast, 75% of NTS isolates were insusceptible to at least one antimicrobial, with more than half carrying mutations and/or genes linked to fluoroquinolone resistance. ESBL genes were detected in five genomes, which also carried other AMR determinants. The population of S. Typhi was dominated by likely endemic genotype 3.0, which caused a putative local outbreak. The main NTS clades were global epidemic S. Enteritidis ST11 and S. Typhimurium monophasic variant (I,4,[5],12: i: -) ST34. Conclusion We provide the first genomic characterisation of Salmonella from the Philippines and evidence of WGS utility for ongoing surveillance. [ABSTRACT FROM AUTHOR]

Australia handled many aspects of the Covid-19 pandemic very well. The international border was closed early, contract tracing regimes were implemented quickly, and targeted lockdowns helped keep case and death rates per capita to relatively low levels. Yet in mid-2021, Australia's vaccine rollout was the slowest in the OECD. We estimate that an optimal vaccine rollout could have saved lives and averted at least A$31 billion in economic damage. The policy errors reflected a failure to heed basic economic concepts of portfolio diversification, option value, and dynamic optimization. We conclude with some policy lessons concerning pandemic preparedness for Australia and other countries. [ABSTRACT FROM AUTHOR]

Pore-forming toxins are an important component of the venom of many animals. Actinoporins are potent cytolysins that were first detected in the venom of sea anemones; however, they are occasionally found in animals other than cnidarians and are expanded in a few predatory gastropods. Here, we report the presence of 27 unique actinoporin-like genes with monophyletic origin in Mytilus galloprovincialis , which we have termed mytiporins. These mytiporins exhibited a remarkable level of molecular diversity and gene presence–absence variation, which warranted further studies aimed at elucidating their functional role. We structurally and functionally characterized mytiporin-1 and found significant differences from the archetypal actinoporin fragaceatoxin C. Mytiporin-1 showed weaker permeabilization activity, no specificity towards sphingomyelin, and weak activity in model lipid systems with negatively charged lipids. In contrast to fragaceatoxin C, which forms octameric pores, functional mytiporin-1 pores on negatively charged lipid membranes were hexameric. Similar hexameric pores were observed for coluporin-26 from Cumia reticulata and a conoporin from Conus andremenezi. This indicates that also other molluscan actinoporin-like proteins differ from fragaceatoxin C. Although the functional role of mytiporins in the context of molluscan physiology remains to be elucidated, the lineage-specific gene family expansion event that characterizes mytiporins indicates that strong selective forces acted on their molecular diversification. Given the tissue distribution of mytiporins, this process may have broadened the taxonomic breadth of their biological targets, which would have important implications for digestive processes or mucosal immunity. [ABSTRACT FROM AUTHOR]

An organization must make a binary choice in each of the two periods. The optimal choice depends on an unknown state of nature. The leader of the organization has a stock of political capital and observes a private signal of the state. The leader faces an intertemporal choice problem. She may choose to spend (some of) her political capital to increase the probability that the choice is not the one that would otherwise be made. Her political capital increases if the decision is correct ex post. We characterize the optimal use of political capital by the leader and how it evolves over time. We identify different leadership styles that depend on the initial stock of capital of the leader, the precision of her information, and the importance of the issue to her. We study how different leadership styles determine the evolution of power within the organization. Finally, we consider issues of optimal organizational design that structures the allocation of power to a leader. (JEL D21, D23, D71, D72). [ABSTRACT FROM AUTHOR]

This review identifies frequent design and analysis errors in aging and senescence research and discusses best practices in study design, statistical methods, analyses, and interpretation. Recommendations are offered for how to avoid these problems. The following issues are addressed: (a) errors in randomization, (b) errors related to testing within-group instead of between-group differences, (c) failing to account for clustering, (d) failing to consider interference effects, (e) standardizing metrics of effect size, (f) maximum life-span testing, (g) testing for effects beyond the mean, (h) tests for power and sample size, (i) compression of morbidity versus survival curve squaring, and (j) other hot topics, including modeling high-dimensional data and complex relationships and assessing model assumptions and biases. We hope that bringing increased awareness of these topics to the scientific community will emphasize the importance of employing sound statistical practices in all aspects of aging and senescence research. [ABSTRACT FROM AUTHOR]

Background Circular staplers are commonly used for reconstruction after radical resection for colorectal cancer. Pathological analysis of the anastomotic rings is common practice, although the benefits are unclear. The purpose of this study was to evaluate the usefulness of routine histopathological analysis of anastomotic rings in an original series and in a systematic review of the literature. Method The retrospective study was performed at two university-associated academic hospitals in Winnipeg, Canada, including patients investigated for colorectal cancers (within 30 cm of the anal verge) who underwent resection between 2007 and 2020. The systematic review involved Ovid MEDLINE, Embase, Scopus, and Web of Science databases, selecting for adult human studies involving analysis of anastomotic rings in elective colorectal cancer resections. The main outcome measure was the proportion of patients with cancer in the anastomotic ring specimens. The frequency of benign pathology findings and changes to patient management were also examined. Results Out of 673 eligible patients, 487 were included in the retrospective analysis. No patients had cancer within the anastomotic ring specimens. Twenty-five patients (5.1 per cent) had benign pathological findings within the anastomotic ring specimens, and patient management was never affected. In the systematic review, 27 articles were included in the final analysis out of 5848 records reviewed. The rate of cancer within anastomotic ring specimens was 0.34 per cent, and the rate of change in patient management was 0.19 per cent. Conclusion The likelihood of finding cancer within anastomotic rings is rare and their histopathological examination seldom changes patient management. [ABSTRACT FROM AUTHOR]

We map the current state of parliamentary and legislative studies through a survey of 218 scholars and a bibliometric analysis of 25 years of publications in three prominent sub-field journals. We identify two groupings of researchers, a quantitative methods, rational choice-favouring grouping and a qualitative methods, interpretivism-favouring grouping with a UK focus. Upon closer examination, these groupings share similar views about the challenges and future of the sub-discipline. While the sub-discipline is becoming more diverse and international, US-focused literature remains dominant and distinct from UK-focused literature, although there are emerging sub-literatures which are well placed to link them together. [ABSTRACT FROM AUTHOR]

Objectives Since 2016, use of nasal continuous positive airway pressure (nCPAP) in Nunavut for air transport in select patients has become common practice. This study examines the outcomes of patients transferred by air from the Qikiqtaaluk Region during air transport. We examined intubation rates, adverse events during transfer, and respiratory parameters at departure and upon arrival. Methods This was a retrospective review from September 2016 to December 2019 including patients under 2 years of age transferred by air on nCPAP from the Qikiqtaaluk Region of Nunavut. Results Data were collected for 40 transfers involving 34 unique patients. Six transfers were from remote communities in Nunavut to Iqaluit, and 33 transfers were from Iqaluit to CHEO. The primary outcome measure was whether the patient required intubation during transport, or urgent intubation upon arrival to CHEO. The median nCPAP setting during transport was 6 cm H2O (5–7 cm H2O) and at arrival to CHEO was 6 cm H2O (6–7 cm H2O). Six of the 33 (18.2%) patients required intubation during their hospital stay and five (15.2%) in a controlled ICU setting. There were no discernible adverse events that occurred during transport for 28 patients (84.5%). Four patients (12.1%) required a brief period of bag-mask ventilation and one patient had an episode of bradycardia. Conclusions nCPAP on air transport is a safe and useful method for providing ventilatory support to infants and young children with respiratory distress. [ABSTRACT FROM AUTHOR]

Background Acute kidney injury (AKI) is common in hospitalized patients and is associated with high morbidity and mortality. The Dublin Acute Biomarker Group Evaluation study is a prospective cohort study of critically ill patients (n = 717). We hypothesized that novel urinary biomarkers would predict progression of AKI and associated outcomes. Methods The primary (diagnostic) analysis assessed the ability of biomarkers levels at the time of early Stage 1 or 2 AKI to predict progression to higher AKI stage, renal replacement therapy (RRT) or death within 7 days of intensive care unit admission. In the secondary (prognostic) analysis, we investigated the association between biomarker levels and RRT or death within 30 days. Results In total, 186 patients had an AKI within 7 days of admission. In the primary (diagnostic) analysis, 8 of the 14 biomarkers were independently associated with progression. The best predictors were cystatin C [adjusted odds ratio (aOR) 5.2; 95% confidence interval (CI) 1.3–23.6], interleukin-18 (IL-18; aOR 5.1; 95% CI 1.8–15.7), albumin (aOR 4.9; 95% CI 1.5–18.3) and neutrophil gelatinase-associated lipocalin (NGAL; aOR 4.6; 95% CI 1.4–17.9). Receiver-operating characteristics and net reclassification index analyses similarly demonstrated improved prediction by these biomarkers. In the secondary (prognostic) analysis of Stages 1–3 AKI cases, IL-18, NGAL, albumin and monocyte chemotactic protein-1 were also independently associated with RRT or death within 30 days. Conclusions Among 14 novel urinary biomarkers assessed, cystatin C, IL-18, albumin and NGAL were the best predictors of Stages 1–2 AKI progression. These biomarkers, after further validation, may have utility to inform diagnostic and prognostic assessment and guide management of AKI in critically ill patients. [ABSTRACT FROM AUTHOR]

Aims: The DNA marker HF183 is a partial 16S rRNA gene sequence highly specific to human‐associated Bacteroides including Bacteroides dorei. While HF183 is used to assess human faecal contamination in aquatic environments worldwide, little is known about the existence of HF183 and B. dorei in human microbiomes outside of the human gastrointestinal tract and faeces. Methods and Results: Previously published human skin and urine microbiome data sets from five independent human body skin studies, the Human Microbiome Project (HMP) and three independent human urine studies were analysed. The HF183 gene sequence was detected in all skin data sets, with the ratios of positive samples ranging from 0.5% to 36.3%. Popliteal fossa (knee), volar forearm and inguinal (groin) creases were identified as hot spots. HF183 was detected in two of three urine data sets, with ratios of positive samples ranging from 0% to 37.5%. All HF183‐containing sequences from these data sets were classified as associated with B. dorei. Conclusions: HF183 is widespread on human skin and present in urine. Significance and Impact of Study: Skin and urine microbiomes could be sources of HF183 to environmental waters. Such non‐faecal sources of HF183 might explain low concentrations of HF183 in recreational waters when swimmers are present. [ABSTRACT FROM AUTHOR]

We study an agent's incentives to discover where her talents lie before putting them to productive use. In our setting, an agent can specialize and learn about the same type of talent repeatedly, or experiment and learn about different types of talent. While experimentation is efficient for a range of distributions of talent and initial signals, labor-market institutions play a crucial role for individual incentives to experiment. Institutions that give the agent sufficiently large bargaining power, provide incentives for experimentation, but for weak bargaining power, agents specialize. We also look at how competition in the labor market, human capital accumulation, and correlation across talents affect incentives to experiment. (JEL codes: D83; J24; J42) [ABSTRACT FROM AUTHOR]

Objective Negative symptoms and cognitive impairment in schizophrenia (SZ) remain unmet treatment needs as they are highly prevalent, associated with poor functional outcomes, and resistant to pharmacologic treatment. The current pilot randomized controlled trial examined the efficacy of an integrated Cognitive-Behavioral Social Skills Training and Compensatory Cognitive Training (CBSST-CCT) intervention compared to Goal-focused Supportive Contact (SC) on negative symptoms and cognitive performance. Methods Fifty-five adults with SZ or schizoaffective disorder with moderate-to-severe negative symptoms were randomized to receive 25 twice-weekly, 1-h manualized group sessions (12.5 weeks total duration) of either CBSST-CCT or SC delivered by master's level clinicians in five community settings. Assessments of negative symptom severity (primary outcomes) and neuropsychological performance, functional capacity, social skills performance, and self-reported functional ability/everyday functioning, psychiatric symptom severity, and motivation (secondary outcomes) were administered at baseline, mid-treatment, post-treatment, and 6-month follow-up. Results Mixed-effects models using baseline, mid-treatment, and post-treatment data demonstrated significant CBSST-CCT-associated effects on negative symptom severity, as assessed by the Scale for the Assessment of Negative Symptoms (p =.049, r = 0.22), with improvements in diminished motivation driving this effect (p =.037, r = 0.24). The CBSST-CCT group also demonstrated improved verbal learning compared to SC participants (p =.026, r = 0.36). The effects of CBSST-CCT appeared to be durable at 6-month follow-up. Conclusions CBSST-CCT improved negative symptom severity and verbal learning in high-negative-symptom individuals relative to SC. CBSST-CCT warrants larger investigations to examine its efficacy in treating negative symptoms, along with other symptoms, cognition, and, ultimately, real-world functional outcomes. Clinical Trial registration number NCT02170051. [ABSTRACT FROM AUTHOR]

Background Acute kidney injury (AKI) is associated with long-term morbidity and mortality. The effects of AKI on neurocognitive functioning remain unknown. Our objective was to quantify neurocognitive impairment after an episode of AKI. Methods Survivors of AKI were compared with age-matched controls, as well as a convenience sample of patients matched for cardiovascular risk factors with normal kidney function (active control group). Patients with AKI completed two assessments, while the active control group completed one assessment. The assessment included a standardized test: the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and a robotic assessment: Kinarm. Results The cohort consisted of 21 patients with AKI, 16 of whom completed both assessments, and 21 active control patients. The majority of patients with AKI had Kidney Disease: Improving Global Outcomes Stage 3 AKI (86%), 57% received dialysis and 43% recovered to ≤25% of their baseline serum creatinine by their first assessment. Compared with the RBANS, which detected little impairment, the Kinarm categorized patients as impaired in visuomotor (10/21, 48%), attention (10/20, 50%) and executive tasks (11/21, 52%) compared with healthy controls. Additionally, patients with AKI performed significantly worse in attention and visuomotor domains when compared with the active controls. Neurocognitive performance was generally not impacted by the need for dialysis or whether kidney function recovered. Conclusions Robotic technology identified quantifiable neurocognitive impairment in survivors of AKI. Deficits were noted particularly in attention, visuomotor and executive domains. Further investigation into the downstream health consequences of these neurocognitive impairments is warranted. [ABSTRACT FROM AUTHOR]

To fully constrain the orbits of low-mass circumstellar companions, we conduct combined analyses of the radial velocity data and the Gaia and Hipparcos astrometric data for eight nearby systems. Our study shows that companion-induced position and proper motion differences between Gaia and Hipparcos are significant enough to constrain orbits of low-mass companions to a precision comparable with previous combined analyses of direct imaging and radial velocity data. We find that our method is robust to whether we use Gaia Data Release 2 or Gaia Early Data Release 3, as well as whether we use all of the data or just proper motion differences. In particular, we fully characterize the orbits of HD 190360 b and HD 16160 C for the first time. With a mass of 1.8 ± 0.2  M Jup and an effective temperature of 123–176 K and orbiting around a Sun-like star, HD 190360 b is the smallest Jupiter-like planet with well-constrained mass and orbit, belonging to a small sample of fully characterized Jupiter analogues. It is separated from its primary star by 0.25 arcsec and thus may be suitable for direct imaging by the coronagraph instrument of the Roman Space Telescope. [ABSTRACT FROM AUTHOR]

Objective Using the Risk Index for Overdose or Serious Opioid-induced Respiratory Depression (CIP-RIOSORD) in patients returning to the emergency department (ED) for pain and discharged with an opioid prescription, we assessed overall opioid overdose risk and compared risk in opioid naive patients to those who are non-opioid naive. Design This was a secondary analysis from a prospective observational study of patients ≥ 18 years old returning to the ED within 30 days. Data were collected from patient interviews and chart reviews. Patients were categorized as Group 1 (not using prescription opioids) or Group 2 (consuming prescription opioids). Statistical analyses were performed using Fisher's exact and Wilcoxon's rank sum tests. Risk class and probability of overdose was determined using Risk Index for Overdose or Serious Opioid-induced Respiratory Depression (CIP-RIOSORD). Results Of the 389 enrollees who returned to the ED due to pain within 30 days of an initial visit, 67 (17%) were prescribed opioids. The majority of these patients were in Group 1 (60%). Both Group 1 (n = 40) and Group 2 (n = 27) held an average CIP-RIOSORD risk class of 3. Race significantly differed between groups; the majority of Group 1 self-identified as African American (80%) (P  = .0267). There were no differences in age, gender, or CIP-RIOSORD risk class between groups. However, Group 2 had nearly double the number of predictive factors (median = 1.93) as Group 1 (median = 1.18) (P  = .0267). Conclusions A substantial proportion of patients (25%) were high risk for opioid overdose. CIP-RIOSORD may prove beneficial in risk stratification of patients discharged with prescription opioids from the ED. [ABSTRACT FROM AUTHOR]