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Purpose. The purpose of this study was to determine whether an internal mock board review course (MBC) could help students improve their National Board Dental Hygiene Examination (NBDHE) scores and study skills. This non-credit, pass or fail course was developed as a requirement for graduation. Methods and Materials. The fall content was based primarily on material from Dr. Esther Wilkins' Clinical Practice of the Dental Hygienist 8th Edition, along with supplemental Internet information. Multiple mock board quizzes were given prior to the end of February, when students must be certified for the spring examination. Results. Seventy-four students completed surveys at the beginning and end of the fall semester. When three years' worth of MBC scores were compared to actual NBDHE scores, the MBC scores were within five percentage points of the actual NBDHE scores 61% of the time. At the beginning of the MBC, 31% of the students thought they would achieve a score of 90% or above on the NBDHE. At the end of the MBC, student surveys indicated that 5% believed they would achieve 90% or above. Seven percent of the class actually did achieve above 90%, proving that the course successfully showed students the depth of study necessary to score 90% or better. Seventy-nine percent of responding students appreciated the 'jump start,' early study schedule, and review of background material. Conclusions. The internal board review course motivated students to study earlier than they would have on their own, and our MBC was able to accurately predict which students were ready to take the NBDHE in the spring semester (70% of the class). Because it is critical to find new and innovative ways to motivate students, further study is ongoing to improve performance for students who did not take the spring NBDHE, and to examine variables that affect student success [ABSTRACT FROM AUTHOR]

The effect of second-generation pneumococcal conjugate vaccines on invasive pneumococcal disease (IPD) strain distributions have not yet been well described. We analysed IPD isolates recovered from children aged <5 years through Active Bacterial Core surveillance before (2008–2009; n = 828) and after (2011–2013; n = 600) 13-valent pneumococcal conjugate vaccine (PCV13) implementation. We employed conventional testing, PCR/electrospray ionization mass spectrometry and whole genome sequence (WGS) analysis to identify serotypes, resistance features, genotypes, and pilus types. PCV13, licensed in February 2010, effectively targeted all major 19A and 7F genotypes, and decreased antimicrobial resistance, primarily owing to removal of the 19A/ST320 complex. The strain complex contributing most to the remaining β-lactam resistance during 2011–2013 was 35B/ST558. Significant emergence of non-vaccine clonal complexes was not evident. Because of the removal of vaccine serotype strains, positivity for one or both pilus types (PI-1 and PI-2) decreased in the post-PCV13 years 2011–2013 relative to 2008–2009 (decreases of 32–55% for PI-1, and >95% for PI-2 and combined PI-1 + PI-2). β-Lactam susceptibility phenotypes correlated consistently with transpeptidase region sequence combinations of the three major penicillin-binding proteins (PBPs) determined through WGS analysis. Other major resistance features were predictable by DNA signatures from WGS analysis. Multilocus sequence data combined with PBP combinations identified progeny, serotype donors and recipient strains in serotype switch events. PCV13 decreased the frequency of all PCV13 serotype clones and concurrently decreased the frequency of strain subsets with resistance and/or adherence features conducive to successful carriage. Our results serve as a reference describing key features of current paediatric IPD strains in the USA after PCV13 implementation. [ABSTRACT FROM AUTHOR]

The JUpiter Icy moons Explorer (JUICE) will investigate Ganymede's and Callisto's surfaces and subsurfaces from orbit to explore the geologic processes that have shaped and altered their surfaces by impact, tectonics, possible cryovolcanism, space weathering due to micrometeorites, radiation and charged particles as well as explore the structure and properties of the icy crust and liquid shell (Grasset et al., 2013). The best possible synergy of the JUICE instruments is required to answer the major science objective of this mission and to fully exploit the potential of the JUICE mission. Therefore, the JUICE team is aiming to define high priority targets on both Ganymede's and Callisto's surfaces to support the coordination of the planning activities by the individual instrument teams. Based on the science objectives of the JUICE mission and the most recent knowledge of Ganymede's and Callisto's geologic evolution we propose a collection of Regions of Interest (RoIs), which characterize surface features and terrain types representing important traces of geologic processes, from past and/or present cryovolcanic and tectonic activity to space weathering processes, which are crucial to understand the geologic evolution of Ganymede and Callisto. The proposed evaluation of RoIs is based on their scientific importance as well as on the opportunities and conditions to observe them during the currently discussed mission profile. • We propose a selection of Regions of Interest (RoIs) on Ganymede and Callisto's surface. • The RoIs represent surface features crucial to understand the evolution of these bodies. • The list helps to fully exploit the potential of the JUICE mission. • The list supports the observation planning and the synergy of the JUICE instruments. [ABSTRACT FROM AUTHOR]

Global climate warming leads to ever-increasing glacier mass loss. Pine Island Glacier in Antarctica is one of the largest contributors to global sea level rise (SLR). One of the biggest uncertainties in the assessment of glacier contribution to SLR at present are subglacial hydrology processes which are less well known than other ice dynamical processes. We use the Glacier Drainage System (GlaDS) model which couples both distributed and channelized components to simulate the basal hydrology of Pine Island Glacier with basal sliding and meltwater production taken from a full-Stokes Elmer/Ice model fitting observed surface velocities. We find ≈100 km long Rothlisberger channels up to 26 m in diameter extending up glacier from the grounding line along the main trunk of Pine Island Glacier delivering 51 m 3 s -1 of fresh water to the grounding line. Channelization occurs at high water pressure because of high basal melt rates (maximum of 1 m a -1 ) caused by high rates of shear heating in regions with fast ice flow (>1000 m a -1 ). We simulate a shallow "swamp" of 0.8 m water depth where flow transitions from a distributed system into the channels. We performed a set of 38 sensitivity experiments varying sheet and channel conductivity over 4 orders of magnitude. We find a threshold behavior in distributed sheet conductivity above which basal water pressures are unaffected by changing channel conductivities. Our findings suggest a strong need to better understand controls on basal water conductivity through the distributed system. This issue is critical to improve model-based predictive capability for the Pine Island Glacier and, more generally, the Antarctic Ice Sheet., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

We present the state of the art on the study of surfaces and tenuous atmospheres of the icy Galilean satellites Ganymede, Europa and Callisto, from past and ongoing space exploration conducted with several spacecraft to recent telescopic observations, and we show how the ESA JUICE mission plans to explore these surfaces and atmospheres in detail with its scientific payload. The surface geology of the moons is the main evidence of their evolution and reflects the internal heating provided by tidal interactions. Surface composition is the result of endogenous and exogenous processes, with the former providing valuable information about the potential composition of shallow subsurface liquid pockets, possibly connected to deeper oceans. Finally, the icy Galilean moons have tenuous atmospheres that arise from charged particle sputtering affecting their surfaces. In the case of Europa, plumes of water vapour have also been reported, whose phenomenology at present is poorly understood and requires future close exploration. In the three main sections of the article, we discuss these topics, highlighting the key scientific objectives and investigations to be achieved by JUICE. Based on a recent predicted trajectory, we also show potential coverage maps and other examples of reference measurements. The scientific discussion and observation planning presented here are the outcome of the JUICE Working Group 2 (WG2): " Surfaces and Near-surface Exospheres of the Satellites, dust and rings "., Competing Interests: Competing InterestsThe authors have no competing interests to declare that are relevant to the content of this article. Cecilia Tubiana, Claire Vallat and Olivier Witasse are Guest Editors of the collection “ESA’s Jupiter Icy Moons Explorer (JUICE): Science, Payload, and Mission”, but were not involved in the peer review of this article., (© The Author(s) 2024.)

Confining light by plasmonic waveguides is promising for miniaturizing optical components, while topological photonics has been explored for robust light localization. Here we propose combining the two approaches into a simple periodically perforated plasmonic waveguide (PPW) design exhibiting robust localization of long-range surface plasmon polaritons. We predict the existence of a topological edge state originating from a quantized topological invariant, and numerically demonstrate the viability of its excitation at telecommunication wavelength using near-field and waveguide-based approaches. Strong modification of the radiative lifetime of dipole emitters by the edge state, and its robustness to disorder, are demonstrated.

Background: Pneumococcal disease is a leading cause of bacterial pneumonia and invasive bacterial disease among children globally. The reason some strains of pneumococci are more likely to cause disease, and how interventions such as vaccines and antibiotics affect pneumococcal strains is poorly understood. We aimed to identify genetic regions under selective pressure and those associated with disease through the analysis of pneumococcal whole-genome sequences., Methods: Whole-genome sequencing was performed on pneumococcal isolates collected between January, 2005, and May, 2018, in Kathmandu, Nepal, which included programmatic ten-valent pneumococcal conjugate vaccine (PCV10) introduction in 2015. Isolates were from three distinct cohorts: nasopharyngeal swabs of healthy community-based children, nasopharyngeal swabs of children admitted to hospital with pneumonia, and sterile-site cultures from children admitted to hospital. Across these cohorts we examined serotype distribution, antibiotic resistance, strain distribution, and regions of recombination to determine genes that were undergoing diversifying selection. Genome-wide association studies comparing pneumonia and sterile-site isolates with healthy carriage were used to determine novel variants associated with disease., Findings: After programmatic introduction of PCV10, there was a decline in vaccine covered serotypes; however, strains that had expressed these serotypes continued to exist in the post-PCV population. We identified GPSC9 to be a strain of concern due to its high prevalence in disease, multidrug resistance, and ability to switch to an unencapsulated phenotype via insertion of virulence factor pspC into the cps locus. Antibiotic resistance loci to co-trimoxazole were found to be prevalent (pre-PCV10 78% vs post-PCV10 81%; p=0·27) and increasingly prevalent to penicillin (pre-PCV10 15% vs post-PCV10 32%; p<0·0001). Regions with multiple recombinations were identified spanning the surface protein virulence factors pspA and pspC and antibiotic targets pbpX, folA, folC, folE, and folP. Furthermore, we identified variants in lacE2 to be strongly associated with isolates from children with pneumonia and PRIP to be strongly associated with isolates from sterile sites., Interpretation: Our work highlights the effect of pneumococcal conjugate vaccines, antibiotics, and host-pathogen interaction in pneumococcal variation, and the pathogen's capability of adapting to these factors at both population-wide and strain-specific levels. Ongoing surveillance of disease-associated strains and further investigation of lacE2 and PRIP as serotype-independent targets for therapeutic interventions is required., Funding: Gavi, The Vaccine Alliance; WHO; Bill & Melinda Gates Foundation; Wellcome Sanger Institute; and US Centers for Disease Control and Prevention., Competing Interests: Declaration of interests RK receives a National Health and Medical Research Council (NHMRC) Emerging Leader Fellowship (GNT1174010). MJC is a National Institute for Health Research (NIHR) Academic Clinical Lecturer and was funded by a Wellcome Trust Clinical Fellowship (104439/Z/14/Z) for part of this work. AJP is Chair of UK Department of Health and Social Care's (DHSC) Joint Committee on Vaccination & Immunisation (JCVI). He is a member of WHO's Strategic Advisory Group of Experts. AJP is an NIHR Senior Investigator. The views expressed in this Article do not necessarily represent the views of DHSC, JCVI, NIHR, or WHO. AJP is chief investigator on clinical trials of Oxford University's COVID-19 vaccine funded by NIHR. Oxford University has entered a joint COVID-19 vaccine development partnership with AstraZeneca., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Streptococcus pneumoniae is a major human pathogen responsible for over 317000 deaths in children <5 years of age with the burden of the disease being highest in low- and middle-income countries including South Africa. Following the introduction of the 7-valent and 13-valent pneumococcal conjugate vaccine (PCV) in South Africa in 2009 and 2011, respectively, a decrease in both invasive pneumococcal infections and asymptomatic carriage of vaccine-type pneumococci were reported. In this study, we described the changing epidemiology of the pneumococcal carriage population in South Africa, by sequencing the genomes of 1825 isolates collected between 2009 and 2013. Using these genomic data, we reported the changes in serotypes, Global Pneumococcal Sequence Clusters (GPSCs), and antibiotic resistance before and after the introduction of PCV13. The pneumococcal carriage population in South Africa has a high level of diversity, comprising of 126 GPSCs and 49 serotypes. Of the ten most prevalent GPSCs detected, six were predominantly found in Africa (GPSC22, GPSC21, GPSC17, GPSC33, GPSC34 and GPSC52). We found a significant decrease in PCV7 serotypes (19F, 6B, 23F and 14) and an increase in non-vaccine serotypes (NVT) (16F, 34, 35B and 11A) among children <2 years of age. The increase in NVTs was driven by pneumococcal lineages GPSC33, GPSC34, GPSC5 and GPSC22. Overall, a decrease in antibiotic resistance for 11 antimicrobials was detected in the PCV13 era. Further, we reported a higher resistance prevalence among vaccine types (VTs), as compared to NVTs; however, an increase in penicillin resistance among NVT was observed between the PCV7 and PCV13 eras. The carriage isolates from South Africa predominantly belonged to pneumococcal lineages, which are endemic to Africa. While the introduction of PCV resulted in an overall reduction of resistance in pneumococcal carriage isolates, an increase in penicillin resistance among NVTs was detected in children aged between 3 and 5 years, driven by the expansion of penicillin-resistant clones associated with NVTs in the PCV13 era.

Streptococcus pneumoniae (the pneumococcus) is a leading cause of childhood mortality globally and in Cambodia. It is commensal in the human nasopharynx, occasionally resulting in invasive disease. Monitoring population genetic shifts, characterized by lineage and serotype expansions, as well as antimicrobial-resistance (AMR) patterns is crucial for assessing and predicting the impact of vaccination campaigns. We sought to elucidate the genetic background (global pneumococcal sequence clusters; GPSCs) of pneumococci carried by Cambodian children following perturbation by pneumococcal conjugate vaccine (PCV) 13. We sequenced pre-PCV13 (01/2013-12/2015, N =258) and post-PCV13 carriage isolates (01/2016-02/2017, N =428) and used PopPUNK and SeroBA to determine lineage prevalence and serotype composition. Following PCV13 implementation in Cambodia, we saw expansions of non-vaccine type (NVT) serotypes 23A (GPSC626), 34 (GPSC45) and 6D (GPSC16). We predicted antimicrobial susceptibility using the CDC-AMR pipeline and determined concordance with phenotypic data. The CDC-AMR pipeline had >90 % concordance with the phenotypic antimicrobial-susceptibility testing. We detected a high prevalence of AMR in both expanding non-vaccine serotypes and residual vaccine serotype 6B. Persistently high levels of AMR, specifically persisting multidrug-resistant lineages, warrant concern. The implementation of PCV13 in Cambodia has resulted in NVT serotype expansion reflected in the carriage population and driven by specific genetic backgrounds. Continued monitoring of these GPSCs during the ongoing collection of additional carriage isolates in this population is necessary.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are used in many consumer applications due to their stain repellency, surfactant properties, ability to form water-proof coatings and use in fire suppression. The production, application, transport, use and disposal of PFAS and PFAS-treated products have resulted in their wide-spread occurrence in environmental and biological systems. Concern over exposure to PFAS and their transformation products and metabolites has necessitated the development of tools to predict the transformation of PFAS in environmental systems and metabolism in biological systems. We have developed reaction libraries for predicting transformation products and metabolites in a variety of environmental and biological reaction systems. These reaction libraries are based on generalized reaction schemes that encode the process science of PFAS reported in the peer-reviewed literature. The PFAS reaction libraries will be executed through the Chemical Transformation Simulator, a web-based tool that is available to the public. These reaction libraries are intended for predicting the environmental transformation and metabolism of PFAS only.

Background: Pneumococcal disease outbreaks of vaccine preventable serotype 4 sequence type (ST)801 in shipyards have been reported in several countries. We aimed to use genomics to establish any international links between them., Methods: Sequence data from ST801-related outbreak isolates from Norway (n = 17), Finland (n = 11) and Northern Ireland (n = 2) were combined with invasive pneumococcal disease surveillance from the respective countries, and ST801-related genomes from an international collection (n = 41 of > 40,000), totalling 106 genomes. Raw data were mapped and recombination excluded before phylogenetic dating., Results: Outbreak isolates were relatively diverse, with up to 100 SNPs (single nucleotide polymorphisms) and a common ancestor estimated around the year 2000. However, 19 Norwegian and Finnish isolates were nearly indistinguishable (0-2 SNPs) with the common ancestor dated around 2017., Conclusion: The total diversity of ST801 within the outbreaks could not be explained by recent transmission alone, suggesting that harsh environmental and associated living conditions reported in the shipyards may facilitate invasion of colonising pneumococci. However, near identical strains in the Norwegian and Finnish outbreaks does suggest that transmission between international shipyards also contributed to those outbreaks. This indicates the need for improved preventative measures in this working population including pneumococcal vaccination., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [R.A.G received a PhD stipend from Pfizer 2009–2011. L.S is a co-investigator in an unrelated study, for which THL has received research funding from GlaxoSmithKline Vaccines. S.C.C: acts as principal investigator on studies conducted on behalf of University Hospital Southampton NHS Foundation Trust/University of Southampton that are sponsored by vaccine manufacturers but receives no personal payments from them. S.C.C. has participated in advisory boards for vaccine manufacturers but receives no personal payments for this work. S.C.C. has received financial assistance from vaccine manufacturers to attend conferences. All grants and honoraria are paid into accounts within the respective NHS Trusts or Universities, or to independent charities. N.K.F, C.L.S The Immunisation and Countermeasures Division, Public Health England - National Infection Service, London, UK provides vaccine manufacturers with post-marketing surveillance reports, which the Marketing Authorization Holders are required to submit to the UK Licensing authority in compliance with their Risk Management Strategy. A cost recovery charge is made for these reports. N.K.F and C.S. conduct contract research funded by vaccine manufacturers (including GlaxoSmithKline and Pfizer) on behalf of Public Health England. No personal remuneration is received. M.T reports grants from GlaxoSmithKline and Pfizer to the Finnish Institute for Health and Welfare for unrelated research projects in which she is a co-investigator. All remaining authors report no conflicts of interest.]., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

We demonstrate that a spin degree of freedom can introduce additional texture to higher order topological insulators (HOTIs), manifesting in novel topological invariants and phase transitions. Spin-polarized mid-gap corner states of various multiplicities are predicted for different HOTI phases, and novel bulk-boundary correspondence principles are defined based on bulk invariants such as total and spin corner charge. Those are shown to be robust to spin-flipping perturbations. Photonic realizations of spin-linked topological phases are demonstrated in engineered systems using pseudospin.

Background: The continuing impact of pneumococcal conjugate vaccines (PCVs) in regions with high pneumococcal transmission is threatened by the persistence of vaccine serotypes (VTs) and the emergence of nonvaccine serotypes (NVTs)., Methods: In 2016, we conducted a cross-sectional carriage survey (CSS5) in a community where PCV7 was first introduced in 2006 during a cluster-randomized trial conducted before nationwide introduction of PCV7 (2009) and PCV13 (2011). We estimated prevalence of PCV13 VT and NVT by age and compared these with earlier surveys before (CSS0), during (CSS1-3), and after the trial but before PCV13 (CSS4). Genomic analysis was conducted for the nontypeable pneumococci., Results: Prevalence of PCV13 VT carriage decreased during the 10 years between CSS0 and CSS5 across all age groups (67.6% to 13.5%, P < .001; 59.8% to 14.4%, P < .001; 43.1% to 17.9%, P < .001; and 24.0% to 5.1%, P < .001, in <2, 2-4, 5-14, and ≥15 years, respectively). However, there was no difference between CSS4 and CSS5 in children ≥2 years and adults (children <2 years, no data). The prevalence of PCV13 NVT increased between CSS0 and CSS5 for children <2 years but decreased in older children and adults. In CSS5, serotypes 3, 6A, and 19F were the most common VT and nontypeable isolates were the most common NVT. Among nontypeable isolates, 73.0% lost the ability to express a capsule. Of these, 70.8% were from a VT background., Conclusions: The decrease in PCV13 VT that has occurred since the introduction of PCV13 appears to have plateaued. Significant carriage of these serotypes remains in all age groups., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Patients' self-reports suggest that acute alcohol consumption may trigger a discrete atrial fibrillation (AF) event., Objective: To objectively ascertain whether alcohol consumption heightens risk for an AF episode., Design: A prospective, case-crossover analysis., Setting: Ambulatory persons in their natural environments., Participants: Consenting patients with paroxysmal AF., Measurements: Participants were fitted with a continuous electrocardiogram (ECG) monitor and an ankle-worn transdermal ethanol sensor for 4 weeks. Real-time documentation of each alcoholic drink consumed was self-recorded using a button on the ECG recording device. Fingerstick blood tests for phosphatidylethanol (PEth) were used to corroborate ascertainments of drinking events., Results: Of 100 participants (mean age, 64 years [SD, 15]; 79% male; 85% White), 56 had at least 1 episode of AF. Results of PEth testing correlated with the number of real-time recorded drinks and with events detected by the transdermal alcohol sensor. An AF episode was associated with 2-fold higher odds of 1 alcoholic drink (odds ratio [OR], 2.02 [95% CI, 1.38 to 3.17]) and greater than 3-fold higher odds of at least 2 drinks (OR, 3.58 [CI, 1.63 to 7.89]) in the preceding 4 hours. Episodes of AF were also associated with higher odds of peak blood alcohol concentration (OR, 1.38 [CI, 1.04 to 1.83] per 0.1% increase in blood alcohol concentration) and the total area under the curve of alcohol exposure (OR, 1.14 [CI, 1.06 to 1.22] per 4.7% increase in alcohol exposure) inferred from the transdermal ethanol sensor in the preceding 12 hours., Limitation: Confounding by other time-varying exposures that may accompany alcohol consumption cannot be excluded, and the findings from the current study of patients with AF consuming alcohol may not apply to the general population., Conclusion: Individual AF episodes were associated with higher odds of recent alcohol consumption, providing objective evidence that a modifiable behavior may influence the probability that a discrete AF event will occur., Primary Funding Source: National Institute on Alcohol Abuse and Alcoholism.

The dynamics of the Jovian magnetosphere are controlled by the interplay of the planet's fast rotation, its main iogenic plasma source and its interaction with the solar wind. Magnetosphere-Ionosphere-Thermosphere (MIT) coupling processes controlling this interplay are significantly different from their Earth and Saturn counterparts. At the ionospheric level, they can be characterized by a set of key parameters: ionospheric conductances, electric currents and fields, exchanges of particles along field lines, Joule heating and particle energy deposition. From these parameters, one can determine (a) how magnetospheric currents close into the ionosphere, and (b) the net deposition/extraction of energy into/out of the upper atmosphere associated to MIT coupling. We present a new method combining Juno multi-instrument data (MAG, JADE, JEDI, UVS, JIRAM and Waves) and modeling tools to estimate these key parameters along Juno's trajectories. We first apply this method to two southern hemisphere main auroral oval crossings to illustrate how the coupling parameters are derived. We then present a preliminary statistical analysis of the morphology and amplitudes of these key parameters for eight among the first nine southern perijoves. We aim to extend our method to more Juno orbits to progressively build a comprehensive view of Jovian MIT coupling at the level of the main auroral oval., (© 2021 The Authors.)

Background: Streptococcus pneumoniae serotype 19A remains a significant cause of invasive pneumococcal disease (IPD) in Ireland despite the successful introduction of a 13-valent pneumococcal conjugate vaccine (PCV13) in 2010 which reduced the overall incidence of IPD in children., Methods: Invasive Streptococcus pneumoniae serotype 19A isolates from the Irish reference laboratory between 2007-08 and 2017-18 were analysed using whole genome sequencing (WGS) to investigate the persistence of this vaccine-preventable serotype. We compared the entire national 19A collection to other international collections using a standardised nomenclature of Global Pneumococcal Sequencing Clusters (GPSC)., Results: Expansion of GPSCs and clonal complexes (CCs) may have been associated with vaccine introduction and antimicrobial prescribing policies. A sub-clade of GPSC1-CC320 (n = 25) unique to Ireland, included five of the ten vaccine failures/breakthrough cases identified (p = 0.0086). This sub-clade was not observed in a global GPSC1-CC320 collection. All isolates within the sub-clade (n = 25) contained a galE gene variant rarely observed in a global pneumococcal collection (n = 37/13454, p < 0.001) nor within GPSC1-CC320 (n = 19/227) (p < 0.001). The sub-clade was estimated to have emerged at the start of the PCV-vaccine era (ancestral origin 2000, range 1995-2004) and expanded in Ireland, with most isolated after PCV13 introduction (n = 24/25)., Conclusions: The identification of a sub-clade/variant of serotype 19A highlights the benefit of using WGS to analyse genotypes associated with persistence of a preventable serotype of S. pneumoniae. Particularly as this sub-clade identified was more likely to be associated with IPD in vaccinated children than other 19A genotypes. It is possible that changes to the galE gene, which is involved in capsule production but outside of the capsular polysaccharide biosynthesis locus, may affect bacterial persistence within the population. Discrete changes associated with vaccine-serotype persistence should be further investigated and may inform vaccine strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. This study was funded by an Investigator Initiated Research grant from Pfizer (W1243730). Sequencing was performed in the Wellcome Sanger Institute as part of the Global Pneumococcal Sequencing Consortium project which was supported by the Bill & Melinda Gates Foundation (OPP1034556), the Wellcome Sanger Institute (grants 098051 and 206194), and the US Centers for Disease Control and Prevention. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. This project was reviewed by Pfizer prior to submission. Pfizer did not have a role in data collection, study design, writing the manuscript or decision to submit it for publication., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: This study sought to identify acute changes in human atrial electrophysiology during alcohol exposure., Background: The mechanism by which a discrete episode of atrial fibrillation (AF) occurs remains unknown. Alcohol appears to increase the risk for AF, providing an opportunity to study electrophysiologic effects that may render the heart prone to arrhythmia., Methods: In this randomized, double-blinded, placebo-controlled trial, intravenous alcohol titrated to 0.08% blood alcohol concentration was compared with a volume and osmolarity-matched, masked, placebo in patients undergoing AF ablation procedures. Right, left, and pulmonary vein atrial effective refractory periods (AERPs) and conduction times were measured pre- and post-infusion. Isoproterenol infusions and burst atrial pacing were used to assess AF inducibility., Results: Of 100 participants (50 in each group), placebo recipients were more likely to be diabetic (22% vs. 4%; p = 0.007) and to have undergone a prior AF ablation (36% vs. 22%; p = 0.005). Pulmonary vein AERPs decreased an average of 12 ms (95% confidence interval: 1 to 22 ms; p = 0.026) in the alcohol group, with no change in the placebo group (p = 0.98). Whereas no statistically significant differences in continuously assessed AERPs were observed, the proportion of AERP sites tested that decreased with alcohol (median: 0.5; interquartile range: 0.6 to 0.6) was larger than with placebo (median: 0.4; interquartile range: 0.2 to 0.6; p = 0.0043). No statistically significant differences in conduction times or in the proportion with inducible AF were observed., Conclusions: Acute exposure to alcohol reduces AERP, particularly in the pulmonary veins. These data demonstrate a direct mechanistic link between alcohol, a common lifestyle exposure, and immediate proarrhythmic effects in human atria. (How Alcohol Induces Atrial Tachyarrhythmias Study [HOLIDAY]; NCT01996943)., Competing Interests: Funding Support and Author Disclosures This study was funded by National Institute of Alcohol Abuse and Alcoholism grant R01AA022222 (to Dr. Marcus). Technical support for the alcohol clamp procedure, including the Computer-Assisted Infusion Software (CAIS), was provided by Dr. Martin Plawecki, Dr. Sean O'Connor, Mr. Victor Vitvitskiy, and Mr. James Hays, Indiana Alcohol Research Center, Indiana University School of Medicine (P60 AA006711). Dr. Marcus has received research support from the National Institutes of Health, Patient-Centered Outcomes Research Institute, Medtronic, Eight, Jawbone, and Baylis; and is a consultant and holds equity interest in InCarda. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. All rights reserved.)

The land ice contribution to global mean sea level rise has not yet been predicted 1 using ice sheet and glacier models for the latest set of socio-economic scenarios, nor using coordinated exploration of uncertainties arising from the various computer models involved. Two recent international projects generated a large suite of projections using multiple models 2-8 , but primarily used previous-generation scenarios 9 and climate models 10 , and could not fully explore known uncertainties. Here we estimate probability distributions for these projections under the new scenarios 11,12 using statistical emulation of the ice sheet and glacier models. We find that limiting global warming to 1.5 degrees Celsius would halve the land ice contribution to twenty-first-century sea level rise, relative to current emissions pledges. The median decreases from 25 to 13 centimetres sea level equivalent (SLE) by 2100, with glaciers responsible for half the sea level contribution. The projected Antarctic contribution does not show a clear response to the emissions scenario, owing to uncertainties in the competing processes of increasing ice loss and snowfall accumulation in a warming climate. However, under risk-averse (pessimistic) assumptions, Antarctic ice loss could be five times higher, increasing the median land ice contribution to 42 centimetres SLE under current policies and pledges, with the 95th percentile projection exceeding half a metre even under 1.5 degrees Celsius warming. This would severely limit the possibility of mitigating future coastal flooding. Given this large range (between 13 centimetres SLE using the main projections under 1.5 degrees Celsius warming and 42 centimetres SLE using risk-averse projections under current pledges), adaptation planning for twenty-first-century sea level rise must account for a factor-of-three uncertainty in the land ice contribution until climate policies and the Antarctic response are further constrained.

Background: The widespread use of pneumococcal conjugate vaccine (PCV) has brought about a dramatic decrease in pneumococci of vaccine serotypes (VTs) but nonvaccine serotypes (NVTs) have emerged., Methods: We conducted a cross-sectional survey (CSS) among infants who received 3 doses of 13-valent PCV (PCV13) and their mothers 5 years (CSS3) after PCV13 introduction. Nasopharyngeal swab samples were collected and cultured for isolation of Streptococcus pneumoniae. Whole-genome sequencing of the nontypeable strains was performed. Data were compared with those from 2 previous surveys conducted before PCV13 introduction (CSS1) and 1 year later (CSS2)., Results: Among infants, VT carriage decreased from 33.3% (113/339) in CSS1 to 11.4% (40/351) in CSS3 (P = .001) while NVTs increased from 53.1% (180/339) in CSS1 to 74.4% (261/351) in CSS3 (P < .001). Among mothers, there was a significant decrease in VTs between CSS2 8.4% (29/347) and CSS3 5.6% (19/342) (P = .006). NVTs increased from 16.6% (55/331) in CSS1 to 32.2% (110/342) in CSS3 (P < .001). In CSS3, the most prevalent VTs were 7F in infants and 3 in mothers, and the most prevalent NVTs were serogroup 16 and nontypeables, respectively. Genomic analysis showed that VTs were more likely than NVTs to lose their ability to express the capsule., Conclusions: Five years after PCV13 introduction, we show both direct (infants) and indirect effects (mothers) of the vaccine, while NVT replacement has occurred in both groups. Ongoing circulation of VTs warrants further study of their relevance in any consideration of a reduced dose schedule., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.)