•Despite PCV13 introduction serotype 19A is responsible for ~ 10% of IPD in Ireland.•Sequencing revealed a diverse collection of clonal groups circulating within 19A.•Vaccine failure/breakthrough ...cases were more frequently associated with GPSC1-CC320 than other GPSCs (p = 0.0001).•A unique Irish sub-clade (n = 25) contained five of the ten 19A vaccine failure breakthrough cases.•All sub-clade isolates contained a galE gene rarely observed elsewhere (n = 37/13454).•The galE gene may contribute to the persistence of serotype 19A in this population.
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.
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).
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).
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.
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
We augment the heliospheric network of galactic cosmic ray (GCR) monitors using 2012–2017 penetrating radiation measurements from the New Horizons (NH) Pluto Energetic Particle Spectrometer ...Science Investigation (PEPSSI), obtaining intensities of ≳75 MeV particles. The new, predominantly GCR observations provide critical links between the Sun and Voyager 2 and Voyager 1 (V2 and V1), in the heliosheath and local interstellar medium (LISM), respectively. We provide NH, Advanced Composition Explorer (ACE), V2, and V1 GCR observations, using them to track solar cycle variations and short-term Forbush decreases from the Sun to the LISM, and to examine the interaction that results in the surprising, previously reported V1 LISM anisotropy episodes. To investigate these episodes and the hitherto unexplained lagging of associated in situ shock features at V1, propagating disturbances seen at ACE, NH, and V2 were compared to V1. We conclude that the region where LISM magnetic field lines drape around the heliopause is likely critical for communicating solar disturbance signals upstream of the heliosheath to V1. We propose that the anisotropy-causing physical process that suppresses intensities at ∼90° pitch angles relies on GCRs escaping from a single compression in the draping region, not on GCRs trapped between two compressions. We also show that NH suprathermal and energetic particle data from PEPSSI are consistent with the interpretation that traveling shocks and corotating interaction region (CIR) remnants can be distinguished by the existence or lack of Forbush decreases, respectively, because turbulent magnetic fields at local shocks inhibit GCR transport while older CIR structures reaching the outer heliosphere do not.
Predictions of marine ice-sheet behaviour require models that are able to robustly simulate grounding line migration. We present results of an intercomparison exercise for marine ice-sheet models. ...Verification is effected by comparison with approximate analytical solutions for flux across the grounding line using simplified geometrical configurations (no lateral variations, no effects of lateral buttressing). Unique steady state grounding line positions exist for ice sheets on a downward sloping bed, while hysteresis occurs across an overdeepened bed, and stable steady state grounding line positions only occur on the downward-sloping sections. Models based on the shallow ice approximation, which does not resolve extensional stresses, do not reproduce the approximate analytical results unless appropriate parameterizations for ice flux are imposed at the grounding line. For extensional-stress resolving "shelfy stream" models, differences between model results were mainly due to the choice of spatial discretization. Moving grid methods were found to be the most accurate at capturing grounding line evolution, since they track the grounding line explicitly. Adaptive mesh refinement can further improve accuracy, including fixed grid models that generally perform poorly at coarse resolution. Fixed grid models, with nested grid representations of the grounding line, are able to generate accurate steady state positions, but can be inaccurate over transients. Only one full-Stokes model was included in the intercomparison, and consequently the accuracy of shelfy stream models as approximations of full-Stokes models remains to be determined in detail, especially during transients.
This paper is the second in a series focused on providing a stable platform for the taxonomy of phytopathogenic fungi. It focuses on 25 phytopathogenic genera:
Alternaria
,
Bipolaris
,
Boeremia
,
...Botryosphaeria
,
Calonectria
,
Coniella
,
Corticiaceae
,
Curvularia
,
Elsinoe
,
Entyloma
,
Erythricium
,
Fomitiporia
,
Fulviformes
,
Laetisaria
,
Limonomyces
,
Neofabraea
,
Neofusicoccum
,
Phaeoacremonium
,
Phellinotus
,
Phyllosticta
,
Plenodomus
,
Pseudopyricularia
,
Tilletia
,
Venturia
and
Waitea
, using recent molecular data, up to date names and the latest taxonomic insights. For each genus a taxonomic background, diversity aspects, species identification and classification based on molecular phylogeny and recommended genetic markers are provided. In this study, varieties of the genus
Boeremia
have been elevated to species level.
Botryosphaeria
,
Bipolaris
,
Curvularia
,
Neofusicoccum
and
Phyllosticta
that were included in the One Stop Shop 1 paper are provided with updated entries, as many new species have been introduced to these genera.
•These results describe the first far-UV observations of lunar swirls, which help to address the ongoing debate about the origin of these enigmatic regions.•Swirls could represent very immature ...terrains, consistent with a solar wind standoff model.•FUV spectra are also consistent with compositional sorting; the swirls appear to be relatively abundant in feldspathic material.
Lunar swirls – the enigmatic, magnetically-anomalous regions – are observed for the first time at far-UV (FUV) wavelengths using LRO/LAMP. Swirls in both highlands and mare regions are spectrally relatively red (or less blue) than surrounding terrains, indicating a difference in weathering and/or composition in the swirls vs. non-swirl regions.
We compare spectra of the highlands swirl Gerasimovich with mature and immature low-Fe highlands regions as measured by LAMP and show that the swirl itself does not have the spectral characteristics of either the mature or the immature regions. Mature, weathered highlands regions are spectrally blue in the FUV; immature highlands are less blue, especially at wavelengths >∼160nm. In contrast, the Gerasimovich swirl is spectrally red at wavelengths >∼160nm. We also compare Reiner Gamma, a mare swirl, with mature and immature high-Ti mare regions as measured by LAMP. We find that the mature and immature high-Ti mare regions are spectrally indistinguishable while the Reiner Gamma spectra are less blue at wavelengths >∼160nm. We conclude that both swirls (Reiner Gamma and Gerasimovich) are consistent with less mature spectra than the immature terrains studied here, in accordance with the lower amounts of weathering expected in a solar wind standoff scenario. However, the swirl spectra are also consistent with greater abundances of feldspathic material, as we show that anorthite exhibits a characteristic red spectrum at wavelengths >∼160nm. Thus, the LAMP data are also consistent with a model wherein compositional sorting occurs at swirls.
BACKGROUND
Isohemagglutinins (anti‐A and anti‐B) mediate hemolytic transfusion reactions, antibody‐mediated rejection of solid‐organ transplants, and delayed engraftment after stem cell transplant. ...However, quantification of isohemagglutinins is often labor intensive and operator dependent, limiting availability and interfacility comparisons. We evaluated an automated, solid‐phase and agglutination‐based antibody titer platform versus manual gel testing.
STUDY DESIGN AND METHODS
Plasma samples were obtained from 54 randomly selected patients. Titers were determined by our laboratoryʼs standard assay (manual dilution followed by manual gel testing) and were compared to results obtained on a fully automated blood bank analyzer (Galileo NEO, Immucor). The analyzer determined immunoglobulin G (IgG) antibodies using solid‐phase and immunoglobulin M (IgM) antibodies by direct hemagglutination.
RESULTS
Isohemagglutinin titers obtained by manual gel versus the automated assay generally (>80%) agreed within one doubling dilution, and always (100%) agreed within two dilutions. Among O samples, the gel titer and the highest titer obtained with the automated assay (either IgG or IgM) were similar in paired, nonparametric analysis (p = 0.06 for anti‐A; p = 0.13 for anti‐B). Gel titers from group A and group B patients were slightly higher than the highest titer obtained using the automated assay (p = 0.04 for group A; p = 0.009 for group B), although these differences were within the accepted error of measurement.
CONCLUSION
Manual and automated methodologies yielded similar isohemagglutinin titers. Separate quantification of IgM and IgG isohemagglutinins via automated titration may yield additional insight into hemolysis, graft survival after ABO‐incompatible transplantation, and red blood cell engraftment after ABO‐incompatible stem cell transplant.
See editorial on page 441–443, in this issue
Streptococcus pneumoniae, also known as the pneumococcus, is an important cause of morbidity and mortality in the developed and developing world. Pneumococcal conjugate vaccines were first introduced ...for routine use in the USA in 2000, although the seven-valent pneumococcal conjugate vaccine (PCV7) was not introduced into the UK's routine childhood immunization programme until September 2006. After its introduction, a marked decrease in the incidence of pneumococcal disease was observed, both in the vaccinated and unvaccinated UK populations. However, pneumococci are highly diverse and serotype prevalence is dynamic. Conversely, PCV7 targets only a limited number of capsular types, which appears to confer a limited lifespan to the observed beneficial effects. Shifts in serotype distribution have been detected for both non-invasive and invasive disease reported since PCV7 introduction, both in the UK and elsewhere. The pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, Synflorix; GlaxoSmithKline) and 13-valent pneumococcal conjugate vaccine (PCV13, Prevenar 13; Pfizer) have been newly licensed. The potential coverage of the 10- and 13-valent conjugate vaccines has also altered alongside serotype shifts. Nonetheless, the mechanism of how PCV7 has influenced serotype shift is not clear-cut as the epidemiology of serotype prevalence is complex. Other factors also influence prevalence and incidence of pneumococcal carriage and disease, such as pneumococcal diversity, levels of antibiotic use and the presence of risk groups. Continued surveillance and identification of factors influencing serotype distribution are essential to allow rational vaccine design, implementation and continued effective control of pneumococcal disease.
Systemic lupus erythematosus (SLE), a disorder of the immune system, is potentially curable by allogeneic bone marrow transplantation (alloBMT). Until recently, alloBMT was limited by donor ...availability and toxicity. Reduced intensity conditioning (RIC) combined with post-transplantation cyclophosphamide (PTCy) has improved the availability and safety of alloBMT permitting its exploration in severe-refractory autoimmune illnesses. We report the six-year follow-up of a young female whose refractory SLE-associated nephrosis resolved after RIC alloBMT with PTCy.
Highlights ► Surveillance of pneumococcal carriage is needed to evaluate vaccine impact. ► Protocol variation reduces validity of comparisons between laboratories or nations. ► Adoption of WHO ...pneumococcal carriage method has not been uniform for collection to storage. ► Choice of swab and media frequently differ between studies. ► Requirement for further evidence to support optimal pneumococcal collection methods.
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