A repeating fast radio burst associated with a persistent radio source.

The dispersive sweep of fast radio bursts (FRBs) has been used to probe the ionized baryon content of the intergalactic medium1, which is assumed to dominate the total extragalactic dispersion. Although the host-galaxy contributions to the dispersion measure appear to be small for most FRBs2, in at least one case there is evidence for an extreme magneto-ionic local environment3,4 and a compact persistent radio source5. Here we report the detection and localization of the repeating FRB 20190520B, which is co-located with a compact, persistent radio source and associated with a dwarf host galaxy of high specific-star-formation rate at a redshift of 0.241 ± 0.001. The estimated host-galaxy dispersion measure of approximately [Formula: see text] parsecs per cubic centimetre, which is nearly an order of magnitude higher than the average of FRB host galaxies2,6, far exceeds the dispersion-measure contribution of the intergalactic medium. Caution is thus warranted in inferring redshifts for FRBs without accurate host-galaxy identifications.

Statistical and Machine Learning Analysis in Brain-Imaging Genetics: A Review of Methods.

Brain-imaging-genetic analysis is an emerging field of research that aims at aggregating data from neuroimaging modalities, which characterize brain structure or function, and genetic data, which capture the structure and function of the genome, to explain or predict normal (or abnormal) brain performance. Brain-imaging-genetic studies offer great potential for understanding complex brain-related diseases/disorders of genetic etiology. Still, a combined brain-wide genome-wide analysis is difficult to perform as typical datasets fuse multiple modalities, each with high dimensionality, unique correlational landscapes, and often low statistical signal-to-noise ratios. In this review, we outline the progress in brain-imaging-genetic methodologies starting from early massive univariate to current deep learning approaches, highlighting each approach's strengths and weaknesses and elongating it with the field's development. We conclude by discussing selected remaining challenges and prospects for the field.

Effectiveness of Mobile Applications for Trauma Care in Combat Casualty Simulations Throughout the Continuum.

INTRODUCTION: The U.S. Military uses handwritten documentation throughout the continuum of combat casualty care to document from point-of-injury, during transport and at facilities that provide damage control resuscitation and surgery. Proven impractical due to lack of durability and legibility in arduous tactical environments, we hypothesized that mobile applications would increase accuracy and completeness of documentation in combat casualty simulations. METHODS: We conducted simulations across this continuum utilizing 10 two-person teams consisting of a Medic and an Emergency or Critical Care Nurse. Participants were randomized to either the paper group or BATDOK and T6 Health Systems mobile application group. Simulations were completed in both the classroom and simulated field environments. All documentation was assessed for speed, completeness, and accuracy. RESULTS: Participant demographics averaged 10.8 ± 5.2 y of military service and 3.9 ± 0.6 h of training on both platforms. Classroom testing showed a significant increase in completeness (84.2 ± 8.1% versus 77.2 ± 6.9%; P = 0.02) and accuracy (77.6 ± 8.1% versus 68.9 ± 7.5%; P = 0.01) for mobile applications versus paper with no significant difference in overall time to completion (P = 0.19). Field testing again showed a significant increase in completeness (91.6 ± 5.8 % versus 70.0 ± 14.1%; P < 0.01) and accuracy (87.7 ± 7.6% versus 64.1 ± 14.4%; P < 0.01) with no significant difference in overall time to completion (P = 0.44). CONCLUSIONS: In deployed environments, mobile applications have the potential to improve casualty care documentation completeness and accuracy with minimal additional training. These efforts will assist in meeting an urgent operational need to enable our providers.

Bottlebrush Networks: A Primer for Advanced Architectures.

Bottlebrush networks (BBNs) are an exciting new class of materials with interesting physical properties derived from their unique architecture. While great strides have been made in our fundamental understanding of bottlebrush polymers and networks, an interdisciplinary approach is necessary for the field to accelerate advancements. This review aims to act as a primer to BBN chemistry and physics for both new and current members of the community. In addition to providing an overview of contemporary BBN synthetic methods, we developed a workflow and desktop application (LengthScale), enabling bottlebrush physics to be more approachable. We conclude by addressing several topical issues and asking a series of pointed questions to stimulate conversation within the community.

New insights into natural rubber biosynthesis from rubber-deficient lettuce mutants expressing goldenrod or guayule cis-prenyltransferase.

Lettuce produces natural rubber (NR) with an average Mw of > 1 million Da in laticifers, similar to NR from rubber trees. As lettuce is an annual, self-pollinating, and easily transformable plant, it is an excellent model for molecular genetic studies of NR biosynthesis. CRISPR/Cas9 mutagenesis was optimized using lettuce hairy roots, and NR-deficient lettuce was generated via bi-allelic mutations in cis-prenyltransferase (CPT). This is the first null mutant of NR deficiency in plants. In the CPT mutant, orthologous CPT counterparts from guayule (Parthenium argentatum) and goldenrod (Solidago canadensis) were expressed under a laticifer-specific promoter to examine how the average Mw of NR is affected. No developmental defects were observed in the NR-deficient mutants. The lettuce mutants expressing guayule and goldenrod CPT produced 1.8 and 14.5 times longer NR, respectively, than the plants of their origin. This suggests that, although goldenrod cannot synthesize a sufficiently lengthy NR, goldenrod CPT has the catalytic competence to produce high-quality NR in the cellular context of lettuce laticifers. Thus, CPT alone does not determine the length of NR. Other factors, such as substrate concentration, additional proteins, and/or the nature of protein complexes including CPT-binding proteins, influence CPT activity in determining NR length.

mobileOG-db: a Manually Curated Database of Protein Families Mediating the Life Cycle of Bacterial Mobile Genetic Elements.

Bacterial mobile genetic elements (MGEs) encode functional modules that perform both core and accessory functions for the element, the latter of which are often only transiently associated with the element. The presence of these accessory genes, which are often close homologs to primarily immobile genes, incur high rates of false positives and, therefore, limits the usability of these databases for MGE annotation. To overcome this limitation, we analyzed 10,776,849 protein sequences derived from eight MGE databases to compile a comprehensive set of 6,140 manually curated protein families that are linked to the "life cycle" (integration/excision, replication/recombination/repair, transfer, stability/transfer/defense, and phage-specific processes) of plasmids, phages, integrative, transposable, and conjugative elements. We overlay experimental information where available to create a tiered annotation scheme of high-quality annotations and annotations inferred exclusively through bioinformatic evidence. We additionally provide an MGE-class label for each entry (e.g., plasmid or integrative element), and assign to each entry a major and minor category. The resulting database, mobileOG-db (for mobile orthologous groups), comprises over 700,000 deduplicated sequences encompassing five major mobileOG categories and more than 50 minor categories, providing a structured language and interpretable basis for an array of MGE-centered analyses. mobileOG-db can be accessed at mobileogdb.flsi.cloud.vt.edu/, where users can select, refine, and analyze custom subsets of the dynamic mobilome. IMPORTANCE The analysis of bacterial mobile genetic elements (MGEs) in genomic data is a critical step toward profiling the root causes of antibiotic resistance, phenotypic or metabolic diversity, and the evolution of bacterial genera. Existing methods for MGE annotation pose high barriers of biological and computational expertise to properly harness. To bridge this gap, we systematically analyzed 10,776,849 proteins derived from eight databases of MGEs to identify 6,140 MGE protein families that can serve as candidate hallmarks, i.e., proteins that can be used as "signatures" of MGEs to aid annotation. The resulting resource, mobileOG-db, provides a multilevel classification scheme that encompasses plasmid, phage, integrative, and transposable element protein families categorized into five major mobileOG categories and more than 50 minor categories. mobileOG-db thus provides a rich resource for simple and intuitive element annotation that can be integrated seamlessly into existing MGE detection pipelines and colocalization analyses.

Blue Light-Mediated, Photocatalyst-Free Decarboxylative Alkylation of Heteroaryl Sulfinimines.

We report a diastereoselective, photocatalyst-free decarboxylative alkylation of (hetero)aryl sulfinimines using redox-active esters under blue light. High yields and diastereoselectivities can be achieved under mild conditions, and we demonstrate its utility as a synthetic method, especially for medicinal chemists.

Stereodynamics of adiabatic and non-adiabatic energy transfer in a molecule surface encounter.

Molecular energy transfer and reactions at solid surfaces depend on the molecular orientation relative to the surface. While such steric effects have been largely understood in electronically adiabatic processes, the orientation-dependent energy transfer in NO scattering from Au(111) was complicated by electron-mediated nonadiabatic effects, thus lacking a clear interpretation and posing a great challenge for theories. Herein, we investigate the stereodynamics of adiabatic and nonadiabatic energy transfer via molecular dynamics simulations of NO(v = 3) scattering from Au(111) using realistic initial orientation distributions based on accurate neural network fitted adiabatic potential energy surface and electronic friction tensor. Our results reproduce the observed stronger vibrational relaxation for N-first orientation and enhanced rotational rainbow for O-first orientation, and demonstrate how adiabatic anisotropic interactions steer molecules into the more attractive N-first orientation to experience more significant energy transfer. Remaining disagreements with experiment suggest the direction for further developments of nonadiabatic theories for gas-surface scattering.

Femoral Lengthening in Children: A Comparison of Motorized Intramedullary Nailing Versus External Fixation Techniques.

BACKGROUND: Femoral lengthening is associated with high complication rates often related to the type of surgical device used to perform the lengthening. The advent of intramedullary lengthening devices has promised a reduction in complications when compared with external fixation systems. The purpose of this study was to compare the clinical outcomes of femoral lengthening in children using a motorized intramedullary nail (Precice) versus an external fixation system (Taylor Spatial Frame-TSF; or Monolateral Rail System-MRS) at a single institution, single surgeon practice. METHODS: This study is a retrospective comparison of pediatric patients who had previously undergone femoral lengthening (±deformity correction). Patients ages 8 to 18 years of age were included and grouped based on whether they had undergone Precice nailing or external fixation (TSF or MRS) between 2010 and 2019. RESULTS: Twenty-seven patients (32 femurs) were included. Thirteen patients (15 femurs) had undergone Precice nailing and 14 patients (17 femurs) had undergone external fixation. The Precice group had significantly fewer problems, obstacles, and complications than the external fixation group, Precice 6.6%, 0%, 0%, respectively, and external fixation 47.1%, 29.4%, 0% respectively (P<0.01). Unplanned return to the operating room occurred in 4 cases, solely in the external fixation group. There were no differences in percentage of goal length achieved, Precice (mean 93.6%, range: 66.7% to 114.3%), external fixation (mean 96%, range: 76.9% to 117.5%) P=0.31 and total length achieved, Precice (mean: 44 mm, range: 20 to 80 mm), external fixation (mean: 46 mm, range: 10 to 70 mm) P=0.72. There was no difference in consolidation index, Precice (24.1 d/cm), external fixation (28.5 d/cm) P=0.36. The Precice group had a significantly shorter length of stay (mean: 2.2 d, range: 1 to 4 d), compared with the external fixation group (mean: 3.7 d, range: 2 to 8), P=0.01. CONCLUSIONS: Femoral lengthening in children using a motorized intramedullary nail was associated with a markedly reduced rate of complications and shorter length of stay compared with external fixation. LEVEL OF EVIDENCE: Level III.

The promoter sequences of lettuce cis-prenyltransferase and its binding protein specify gene expression in laticifers.

MAIN CONCLUSION: Promoters of lettuce cis-prenyltransferase 3 (LsCPT3) and CPT-binding protein 2 (LsCBP2) specify gene expression in laticifers, as supported by in situ ß-glucuronidase stains and microsection analysis. Lettuce (Lactuca sativa) has articulated laticifers alongside vascular bundles. In the cytoplasm of laticifers, natural rubber (cis-1,4-polyisoprene) is synthesized by cis-prenyltransferase (LsCPT3) and CPT-binding protein (LsCBP2), both of which form an enzyme complex. Here we determined the gene structures of LsCPT3 and LsCBP2 and characterized their promoter activities using ß-glucuronidase (GUS) reporter assays in stable transgenic lines of lettuce. LsCPT3 has a single 7.4-kb intron while LsCBP2 has seven introns including a 940-bp intron in the 5'-untranslated region (UTR). Serially truncated LsCPT3 promoters (2.3 kb, 1.6 kb, and 1.1 kb) and the LsCBP2 promoter with (1.7 kb) or without (0.8 kb) the 940-bp introns were fused to GUS to examine their promoter activities. In situ GUS stains of the transgenic plants revealed that the 1.1-kb LsCPT3 and 0.8-kb LsCBP2 promoter without the 5'-UTR intron are sufficient to express GUS exclusively in laticifers. Fluorometric assays showed that the LsCBP2 promoter was several-fold stronger than the CaMV35S promoter and was ~ 400 times stronger than the LsCPT3 promoter in latex. Histochemical analyses confirmed that both promoters express GUS exclusively in laticifers, recognized by characteristic fused multicellular structures. We concluded that both the LsCPT3 and LsCBP2 promoters specify gene expression in laticifers, and the LsCBP2 promoter displays stronger expression than the CaMV35S promoter in laticifers. For the LsCPT3 promoter, it appears that unknown cis-elements outside of the currently examined LsCPT3 promoter are required to enhance LsCPT3 expression.

Characterization of Phenolic Plant Exudates by Nuclear Magnetic Resonance Spectroscopy.

The class of plant exudates that contain the phenol functionality, termed phenolics, is defined, surveyed, and characterized by solid-state 13C NMR spectroscopy and by solution-state 1H NMR spectroscopy. Materials in this group are identified by the phenolic 13C resonance (from the ipso carbon of ArOH) at δ 145-160 (δ 160-167 for ArOR). The resonance patterns define several subclasses based on the collective similarity of their 13C spectra, specifically, aloetics from the genus Aloe, guaiacs from the genus Guaiacum and other eurosid and conifer genera, xanthics from the genus Garcinia, and kinos from the genus Eucalyptus and many other genera. Phenolic exudates often are mixed with terpenoid materials (the building block of exudates known as resins) and carbohydrates (the building block of exudates known as gums) to form hybrid subgroups such as guaiac gums, guaiac resins, and kino resins. There are numerous phenolic exudates not affiliated with any of these groups, both as pure phenolics and as hybrids (phenolic resins, phenolic gum resins, and phenolic waxes).

Zinc Gluconate Induces Potentially Cancer Chemopreventive Activity in Barrett's Esophagus: A Phase 1 Pilot Study.

BACKGROUND: Chemopreventive effects of zinc for esophageal cancer have been well documented in animal models. This prospective study explores if a similar, potentially chemopreventive action can be seen in Barrett's esophagus (BE) in humans. AIMS: To determine if molecular evidence can be obtained potentially indicating zinc's chemopreventive action in Barrett's metaplasia. METHODS: Patients with a prior BE diagnosis were placed on oral zinc gluconate (14 days of 26.4 mg zinc BID) or a sodium gluconate placebo, prior to their surveillance endoscopy procedure. Biopsies of Barrett's mucosa were then obtained for miRNA and mRNA microarrays, or protein analyses. RESULTS: Zinc-induced mRNA changes were observed for a large number of transcripts. These included downregulation of transcripts encoding proinflammatory proteins (IL32, IL1ß, IL15, IL7R, IL2R, IL15R, IL3R), upregulation of anti-inflammatory mediators (IL1RA), downregulation of transcripts mediating epithelial-to-mesenchymal transition (EMT) (LIF, MYB, LYN, MTA1, SRC, SNAIL1, and TWIST1), and upregulation of transcripts that oppose EMT (BMP7, MTSS1, TRIB3, GRHL1). miRNA arrays showed significant upregulation of seven miRs with tumor suppressor activity (-125b-5P, -132-3P, -548z, -551a, -504, -518, and -34a-5P). Of proteins analyzed by Western blot, increased expression of the pro-apoptotic protein, BAX, and the tight junctional protein, CLAUDIN-7, along with decreased expression of BCL-2 and VEGF-R2 were noteworthy. CONCLUSIONS: When these mRNA, miRNA, and protein molecular data are considered collectively, a cancer chemopreventive action by zinc in Barrett's metaplasia may be possible for this precancerous esophageal tissue. These results and the extensive prior animal model studies argue for a future prospective clinical trial for this safe, easily-administered, and inexpensive micronutrient, that could determine if a chemopreventive action truly exists.

An in vitro investigation of the survival and/or growth of Campylobacter jejuni in broiler digestate from different feed types.

Campylobacter spp. is the leading cause of bacterial gastroenteritis worldwide and poultry are the primary reservoir. The aim of this study was to investigate the survival and/or growth of Campylobacter jejuni NCTC 11168 in broiler digestate prepared from commercial starter, grower and finisher feed formulations. Bolton broth and digestates were prepared, inoculated with C. jejuni NCTC 11168 (approximately 3 log10 CFU per ml) and incubated under microaerobic conditions at 42°C for 24 h. Samples were taken at t = 0 (immediately after inoculation) and every 3 h thereafter, serially diluted and plated onto mCCDA. Campylobacter jejuni grew as expected in Bolton broth (control) reaching the early stationary phase after approximately 15 h. In contrast, although bacterial concentrations were maintained for at least 9 h, none of the feed digestates supported the growth of C. jejuni, which were not detected after 15 h. It is suggested that the nutrients available in the feed digestates are not enough to support C. jejuni growth and that additional factors may be at play in the avian gastrointestinal tract.

Pannexin 1 activation and inhibition is permeant-selective.

KEY POINTS: The large-pore channel pannexin 1 (Panx1) is expressed in many cell types and can open upon different, yet not fully established, stimuli. Panx1 permeability is often inferred from channel permeability to fluorescent dyes, but it is currently unknown whether dye permeability translates to permeability to other molecules. Cell shrinkage and C-terminal cleavage led to a Panx1 open-state with increased permeability to atomic ions (current), but did not alter ethidium uptake. Panx1 inhibitors affected Panx1-mediated ion conduction differently from ethidium permeability, and inhibitor efficiency towards a given molecule therefore cannot be extrapolated to its effects on the permeability of another. We conclude that ethidium permeability does not reflect equal permeation of other molecules and thus is no measure of general Panx1 activity. ABSTRACT: Pannexin 1 (Panx1) is a large-pore membrane channel connecting the extracellular milieu with the cell interior. While several activation regimes activate Panx1 in a variety of cell types, the selective permeability of an open Panx1 channel remains unresolved: does a given activation paradigm increase Panx1's permeability towards all permeants equally and does fluorescent dye flux serve as a proxy for biological permeation through an open channel? To explore permeant-selectivity of Panx1 activation and inhibition, we employed Panx1-expressing Xenopus laevis oocytes and HEK293T cells. We report that different mechanisms of activation of Panx1 differentially affected ethidium and atomic ion permeation. Most notably, C-terminal truncation or cell shrinkage elevated Panx1-mediated ion conductance, but had no effect on ethidium permeability. In contrast, extracellular pH changes predominantly affected ethidium permeability but not ionic conductance. High [K+ ]o did not increase the flux of either of the two permeants. Once open, Panx1 demonstrated preference for anionic permeants, such as Cl- , lactate and glutamate, while not supporting osmotic water flow. Panx1 inhibitors displayed enhanced potency towards Panx1-mediated currents compared to that of ethidium uptake. We conclude that activation or inhibition of Panx1 display permeant-selectivity and that permeation of ethidium does not necessarily reflect an equal permeation of smaller biological molecules and atomic ions.

Comparison of Whole-Genome Sequences of Legionella pneumophila in Tap Water and in Clinical Strains, Flint, Michigan, USA, 2016.

During the water crisis in Flint, Michigan, USA (2014-2015), 2 outbreaks of Legionnaires' disease occurred in Genesee County, Michigan. We compared whole-genome sequences of 10 clinical Legionella pneumophila isolates submitted to a laboratory in Genesee County during the second outbreak with 103 water isolates collected the following year. We documented a genetically diverse range of L. pneumophila strains across clinical and water isolates. Isolates belonging to 1 clade (3 clinical isolates, 3 water isolates from a Flint hospital, 1 water isolate from a Flint residence, and the reference Paris strain) had a high degree of similarity (2-1,062 single-nucleotide polymorphisms), all L. pneumophila sequence type 1, serogroup 1. Serogroup 6 isolates belonging to sequence type 2518 were widespread in Flint hospital water samples but bore no resemblance to available clinical isolates. L. pneumophila strains in Flint tap water after the outbreaks were diverse and similar to some disease-causing strains.

In situ study of sigma phase formation in Cr-Co-Ni ternary alloys at 800°C using the long duration experiment facility at Diamond Light Source.

The new long duration experiment facility on beamline I11 at Diamond Light Source has been used to study the kinetics of sigma phase formation in three Cr-Co-Ni alloys. Diffraction data acquired during in situ exposure at 800°C for 50 d showed progressive increases in the sigma fraction. This was accompanied by changes in the proportions of the other phases, which differed markedly between the alloys studied. These results demonstrate the capabilities of the long duration facility for the study of metallurgical phenomena over periods of months to years, a capability not previously available at a synchrotron source.

Probing Additive Loading in the Lamellar Phase of a Nonionic Surfactant: Gibbs Ensemble Monte Carlo Simulations Using the SDK Force Field.

Understanding solute uptake into soft microstructured materials, such as bilayers and worm-like and spherical micelles, is of interest in the pharmaceutical, agricultural, and personal care industries. To obtain molecular-level insight on the effects of solutes loading into a lamellar phase, we utilize the Shinoda-Devane-Klein (SDK) coarse-grained force field in conjunction with configurational-bias Monte Carlo simulations in the osmotic Gibbs ensemble. The lamellar phase is comprised of a bilayer formed by triethylene glycol mono- n-decyl ether (C10E3) surfactants surrounded by water with a 50:50 surfactant/water weight ratio. We study both the unary adsorption isotherm and the effects on bilayer structure and stability caused by n-nonane, 1-hexanol, and ethyl butyrate at several different reduced reservoir pressures. The nonpolar n-nonane molecules load near the center of the bilayer. In contrast, the polar 1-hexanol and ethyl butyrate molecules both load with their polar bead close to the surfactant head groups. Near the center of the bilayer, none of the solute molecules exhibits a significant orientational preference. Solute molecules adsorbed near the polar groups of the surfactant chains show a preference for orientations perpendicular to the interface, and this alignment with the long axis of the surfactant molecules is most pronounced for 1-hexanol. Loading of n-nonane leads to an increase of the bilayer thickness, but does not affect the surface area per surfactant. Loading of polar additives leads to both lateral and transverse swelling. The reduced Henry's law constants of adsorption (expressed as a molar ratio of additive to surfactant per reduced pressure) are 0.23, 1.4, and 14 for n-nonane, 1-hexanol, and ethyl butyrate, respectively, and it appears that the SDK force field significantly overestimates the ethyl butyrate-surfactant interactions.

'Careful goodbye at the door': is there role for antimicrobial stewardship interventions for antimicrobial therapy prescribed on hospital discharge?

BACKGROUND: Antimicrobial stewardship (AMS) interventions largely target inpatient antimicrobial prescribing. Literature on appropriateness of antimicrobials prescribed at the interface between hospital and the community is minimal. This study was designed to assess the appropriateness of antimicrobials prescribed on hospital discharge and evaluate the impact of AMS interventions. METHODS: Patients with discharge medications processed by the pharmacy were identified using a computerized pharmacy medication tracker over a four week period. The antimicrobials prescribed on discharge were assessed independently for appropriateness of antimicrobial choice, dose, frequency and duration. Data on various AMS interventions was collected. Univariate followed by multivariate logistic regression (MVLR) analysis was performed using SPSS V 23 (IBM, California). RESULTS: A total of 892 discharge prescriptions were processed by the pharmacy department, 236 of which contained antibiotic prescriptions. Of these, 74% were appropriate for antimicrobial choice, 64% for dose, 64% for frequency and 21% for duration. In particular, 71% of patients received a course in excess of Therapeutic Guidelines-Australia(TG-A) recommended length of treatment. On univariate analysis, discharge antimicrobial prescriptions were more likely to be appropriate for antimicrobial choice, frequency and duration; appropriate microbiological specimens were more likely to be taken and targeted therapy more likely to be given when the AMS team was involved. On MVLR, appropriateness with antimicrobial dosing frequency [OR 5.6(1.9-19.2)], microbiological specimens [OR 4.3(1.6-11.6)] and receipt of targeted therapy [OR 2.8(1.8-6.2)] with AMS involvement remained significant. CONCLUSIONS: A large discrepancy exists between antimicrobial regimens prescribed on hospital discharge and those recommended in consensus guidelines, particularly concerning duration of treatment. While AMS interventions are well established for improving antimicrobial prescribing in hospital inpatients, the hospital-community interface remains a challenge in terms of antimicrobial prescribing and exposes patients to potential harm. There is a clear need for AMS interventions to extend to antimicrobial therapy prescribed on discharge.

Extensive hepatitis A outbreak in an urban childcare facility in Ireland, associated with considerable adult morbidity.

Hepatitis A infection results in a spectrum of illness from asymptomatic disease to severe fulminant hepatitis. Since 2000, <50 cases have been reported annually in Ireland. We report on an outbreak of hepatitis A associated with a childcare facility(CCF) in 2015 in Ireland. Between January and July 2015, 12 outbreak-associated symptomatic hepatitis A cases were identified, including one delayed, retrospective diagnosis. Seven (58%) cases were adults, eight (67%) were male, six of the adults required hospitalisation. All 12 cases were confirmed on serology and the four cases that were genotyped were identical on phylogenetic analysis. Potential environmental exposures and hygiene practices at the CCF were investigated. Outbreak control measures included the provision of: hepatitis A information, infection prevention advice, hepatitis A vaccination to 554 CCF contacts, and voluntary closure of the CCF for deep-cleaning and staff education. From a healthcare perspective1, outbreak control costs were in excess of €45 000. This outbreak illustrates the considerable adult morbidity that can occur in hepatitis A outbreaks, highlights the challenges in controlling a large CCF-associated outbreak and the importance of early recognition by clinicians of hepatitis A.