Abstract
Introduction
This study aims to assess the association of piperacillin/tazobactam and meropenem minimum inhibitory concentration (MIC) and beta-lactam resistance genes with mortality in the ...MERINO trial.
Methods
Blood culture isolates from enrolled patients were tested by broth microdilution and whole genome sequencing at a central laboratory. Multivariate logistic regression was performed to account for confounders. Absolute risk increase for 30-day mortality between treatment groups was calculated for the primary analysis (PA) and the microbiologic assessable (MA) populations.
Results
In total, 320 isolates from 379 enrolled patients were available with susceptibility to piperacillin/tazobactam 94% and meropenem 100%. The piperacillin/tazobactam nonsusceptible breakpoint (MIC >16 mg/L) best predicted 30-day mortality after accounting for confounders (odds ratio 14.9, 95% confidence interval CI 2.8–87.2). The absolute risk increase for 30-day mortality for patients treated with piperacillin/tazobactam compared with meropenem was 9% (95% CI 3%–15%) and 8% (95% CI 2%–15%) for the original PA population and the post hoc MA populations, which reduced to 5% (95% CI −1% to 10%) after excluding strains with piperacillin/tazobactam MIC values >16 mg/L. Isolates coharboring extended spectrum β-lactamase (ESBL) and OXA-1 genes were associated with elevated piperacillin/tazobactam MICs and the highest risk increase in 30-day mortality of 14% (95% CI 2%–28%).
Conclusions
After excluding nonsusceptible strains, the 30-day mortality difference from the MERINO trial was less pronounced for piperacillin/tazobactam. Poor reliability in susceptibility testing performance for piperacillin/tazobactam and the high prevalence of OXA coharboring ESBLs suggests that meropenem remains the preferred choice for definitive treatment of ceftriaxone nonsusceptible Escherichia coli and Klebsiella.
Piperacillin/tazobactam should be avoided for ceftriaxone nonsusceptible Escherichia coli and Klebsiella spp. bloodstream infections, especially when minimum inhibitory concentrations are > 16 mg/L. Further assessment of current testing is warranted given disparity between commonly used methods and broth microdilution.
DS Tuc Ab is a Neptune-sized planet that orbits around a G star in the 45 Myr old Tucana-Horologium moving group. Here, we report the measurement of the sky-projected angle between the stellar spin ...axis and the planet's orbital axis, based on the observation of the Rossiter-McLaughlin effect during three separate planetary transits. The orbit appears to be well aligned with the equator of the host star, with a projected obliquity of . In addition to the distortions in the stellar absorption lines due to the transiting planet, we observed variations that we attribute to large starspots, with angular sizes of tens of degrees. The technique that we have developed for simultaneous modeling of starspots and the planet-induced distortions may be useful in other observations of planets around active stars.
We demonstrate optical spin polarization of the neutrally charged silicon-vacancy defect in diamond (SiV^{0}), an S=1 defect which emits with a zero-phonon line at 946 nm. The spin polarization is ...found to be most efficient under resonant excitation, but nonzero at below-resonant energies. We measure an ensemble spin coherence time T_{2}>100 μs at low-temperature, and a spin relaxation limit of T_{1}>25 s. Optical spin-state initialization around 946 nm allows independent initialization of SiV^{0} and NV^{-} within the same optically addressed volume, and SiV^{0} emits within the telecoms down-conversion band to 1550 nm: when combined with its high Debye-Waller factor, our initial results suggest that SiV^{0} is a promising candidate for a long-range quantum communication technology.
Objective
Rheumatoid arthritis (RA) patients often develop rheumatoid factors (RFs), antibodies that bind IgG Fc, and anti–modified protein antibodies (AMPAs), multireactive autoantibodies that ...commonly bind citrullinated, homocitrullinated, and acetylated antigens. Recently, antibodies that bind citrulline‐containing IgG epitopes were discovered in RA, suggesting that additional undiscovered IgG epitopes could exist and that IgG could be a shared antigen for RFs and AMPAs. This study was undertaken to reveal new IgG epitopes in rheumatic disease and to determine if multireactive AMPAs bind IgG.
Methods
Using sera from patients with RA, systemic lupus erythematosus, Sjögren's disease (SjD), or spondyloarthropathy, IgG binding to native, citrulline‐containing, and homocitrulline‐containing linear epitopes of the IgG constant region was evaluated by peptide array, with highly bound epitopes further evaluated by enzyme‐linked immunosorbent assay (ELISA). Binding of monoclonal AMPAs to IgG‐derived peptides and IgG Fc was also evaluated by ELISA.
Results
Seropositive RA sera showed high IgG binding to multiple citrulline‐ and homocitrulline‐containing IgG‐derived peptides, whereas anti‐SSA+ sera from SjD patients showed consistent binding to a single linear native epitope of IgG in the hinge region. Monoclonal AMPAs bound citrulline‐ and homocitrulline‐containing IgG peptides and modified IgG Fc.
Conclusion
The repertoire of epitopes bound by AMPAs includes modified IgG epitopes, positioning IgG as a common antigen that connects the otherwise divergent reactivities of RFs and AMPAs.
We synthesize data on all known extant and fossil Coleoptera family-group names for the first time. A catalogue of 4887 family-group names (124 fossil, 4763 extant) based on 4707 distinct genera in ...Coleoptera is given. A total of 4492 names are available, 183 of which are permanently invalid because they are based on a preoccupied or a suppressed type genus. Names are listed in a classification framework. We recognize as valid 24 superfamilies, 211 families, 541 subfamilies, 1663 tribes and 740 subtribes. For each name, the original spelling, author, year of publication, page number, correct stem and type genus are included. The original spelling and availability of each name were checked from primary literature. A list of necessary changes due to Priority and Homonymy problems, and actions taken, is given. Current usage of names was conserved, whenever possible, to promote stability of the classification.New synonymies (family-group names followed by genus-group names): Agronomina Gistel, 1848 syn. nov. of Amarina Zimmermann, 1832 (Carabidae), Hylepnigalioini Gistel, 1856 syn. nov. of Melandryini Leach, 1815 (Melandryidae), Polycystophoridae Gistel, 1856 syn. nov. of Malachiinae Fleming, 1821 (Melyridae), Sclerasteinae Gistel, 1856 syn. nov. of Ptilininae Shuckard, 1839 (Ptinidae), Phloeonomini Ádám, 2001 syn. nov. of Omaliini MacLeay, 1825 (Staphylinidae), Sepedophilini Ádám, 2001 syn. nov. of Tachyporini MacLeay, 1825 (Staphylinidae), Phibalini Gistel, 1856 syn. nov. of Cteniopodini Solier, 1835 (Tenebrionidae); Agronoma Gistel 1848 (type species Carabus familiaris Duftschmid, 1812, designated herein) syn. nov. of Amara Bonelli, 1810 (Carabidae), Hylepnigalio Gistel, 1856 (type species Chrysomela caraboides Linnaeus, 1760, by monotypy) syn. nov. of Melandrya Fabricius, 1801 (Melandryidae), Polycystophorus Gistel, 1856 (type species Cantharis aeneus Linnaeus, 1758, designated herein) syn. nov. of Malachius Fabricius, 1775 (Melyridae), Sclerastes Gistel, 1856 (type species Ptilinus costatus Gyllenhal, 1827, designated herein) syn. nov. of Ptilinus Geoffroy, 1762 (Ptinidae), Paniscus Gistel, 1848 (type species Scarabaeus fasciatus Linnaeus, 1758, designated herein) syn. nov. of Trichius Fabricius, 1775 (Scarabaeidae), Phibalus Gistel, 1856 (type species Chrysomela pubescens Linnaeus, 1758, by monotypy) syn. nov. of Omophlus Dejean, 1834 (Tenebrionidae). The following new replacement name is proposed: Gompeliina Bouchard, 2011 nom. nov. for Olotelina Báguena Corella, 1948 (Aderidae).Reversal of Precedence (Article 23.9) is used to conserve usage of the following names (family-group names followed by genus-group names): Perigonini Horn, 1881 nom. protectum over Trechicini Bates, 1873 nom. oblitum (Carabidae), Anisodactylina Lacordaire, 1854 nom. protectum over Eurytrichina LeConte, 1848 nom. oblitum (Carabidae), Smicronychini Seidlitz, 1891 nom. protectum over Desmorini LeConte, 1876 nom. oblitum (Curculionidae), Bagoinae Thomson, 1859 nom. protectum over Lyprinae Gistel 1848 nom. oblitum (Curculionidae), Aterpina Lacordaire, 1863 nom. protectum over Heliomenina Gistel, 1848 nom. oblitum (Curculionidae), Naupactini Gistel, 1848 nom. protectum over Iphiini Schönherr, 1823 nom. oblitum (Curculionidae), Cleonini Schönherr, 1826 nom. protectum over Geomorini Schönherr, 1823 nom. oblitum (Curculionidae), Magdalidini Pascoe, 1870 nom. protectum over Scardamyctini Gistel, 1848 nom. oblitum (Curculionidae), Agrypninae/-ini Candèze, 1857 nom. protecta over Adelocerinae/-ini Gistel, 1848 nom. oblita and Pangaurinae/-ini Gistel, 1856 nom. oblita (Elateridae), Prosternini Gistel, 1856 nom. protectum over Diacanthini Gistel, 1848 nom. oblitum (Elateridae), Calopodinae Costa, 1852 nom. protectum over Sparedrinae Gistel, 1848 nom. oblitum (Oedemeridae), Adesmiini Lacordaire, 1859 nom. protectum over Macropodini Agassiz, 1846 nom. oblitum (Tenebrionidae), Bolitophagini Kirby, 1837 nom. protectum over Eledonini Billberg, 1820 nom. oblitum (Tenebrionidae), Throscidae Laporte, 1840 nom. protectum over Stereolidae Rafinesque, 1815 nom. oblitum (Throscidae) and Lophocaterini Crowson, 1964 over Lycoptini Casey, 1890 nom. oblitum (Trogossitidae); Monotoma Herbst, 1799 nom. protectum over Monotoma Panzer, 1792 nom. oblitum (Monotomidae); Pediacus Shuckard, 1839 nom. protectum over Biophloeus Dejean, 1835 nom. oblitum (Cucujidae), Pachypus Dejean, 1821 nom. protectum over Pachypus Billberg, 1820 nom. oblitum (Scarabaeidae), Sparrmannia Laporte, 1840 nom. protectum over Leocaeta Dejean, 1833 nom. oblitum and Cephalotrichia Hope, 1837 nom. oblitum (Scarabaeidae).
Changes in ocean‐circulation regimes in the northern North Atlantic and the Nordic Seas may affect not only the Arctic but potentially hemispheric or even global climate. Therefore, unraveling the ...long‐term evolution of the North Atlantic Current‐Norwegian Atlantic Current system through the Pleistocene glaciations could yield useful information and climatological context for understanding contemporary changes. In this work, ~50,000 km2 of 3‐D seismic reflection data are used to investigate the Pleistocene stratigraphy for evidence of paleo‐oceanographic regimes on the mid‐Norwegian margin since 2.58 Ma. Across 33 semicontinuous regional paleo‐seafloor surfaces ~17,500 iceberg scours have been mapped. This mapping greatly expands our spatiotemporal understanding of currents and iceberg presence in the eastern Nordic Seas. The scours display a dominant southwest‐northeast trend that complements previous sedimentological and numerical modeling studies that suggest northward‐flowing currents in the Norwegian Sea during the Pleistocene. This paleo‐oceanographic study suggests that through many of the Pleistocene glaciations, the location of surface ocean currents in the Norwegian Sea and, by extension, the eastern North Atlantic, were broadly similar to the present.
Plain Language Summary
The bridging location of the northern North Atlantic Ocean and the Nordic Seas between low and high latitudes means that environmental changes in one region can potentially be transmitted on a hemispheric or global scale. The Norwegian Atlantic Current crosses this region, and in the present‐day setting, it helps to bring heat up from the tropics and toward the Arctic. This heat exchange helps to keep the climate of NW Europe relatively mild. Over a longer time scale (e.g., the last 2.58 million years) the history of this current is poorly known, not least of all how it behaved through different ice ages. In this work we use evidence of floating icebergs in the Norwegian Sea to reconstruct the ocean currents that controlled the drift directions of the icebergs. This has shown that through many of the glacial periods in the last 2.58 million years, there is evidence for the Norwegian Atlantic Current still reaching high latitudes. This has important implications for understanding the main controls and stability of ocean currents in the region and how they may impact regional and global climate.
Key Points
50,000 km2 of 3‐D seismic reflection data are investigated on the mid‐Norwegian margin
Seismic geomorphological analysis shows ~17,500 iceberg scours buried throughout the stratigraphy
The geomorphological record shows that the Norwegian Atlantic Current persisted through multiple Pleistocene glacial stages
Summary
Background
Melanoma risk prediction models could be useful for matching preventive interventions to patients’ risk.
Objectives
To develop and validate a model for incident first‐primary ...cutaneous melanoma using clinically assessed risk factors.
Methods
We used unconditional logistic regression with backward selection from the Australian Melanoma Family Study (461 cases and 329 controls) in which age, sex and city of recruitment were kept in each step, and we externally validated it using the Leeds Melanoma Case–Control Study (960 cases and 513 controls). Candidate predictors included clinically assessed whole‐body naevi and solar lentigines, and self‐assessed pigmentation phenotype, sun exposure, family history and history of keratinocyte cancer. We evaluated the predictive strength and discrimination of the model risk factors using odds per age‐ and sex‐adjusted SD (OPERA) and the area under curve (AUC), and calibration using the Hosmer–Lemeshow test.
Results
The final model included the number of naevi ≥ 2 mm in diameter on the whole body, solar lentigines on the upper back (a six‐level scale), hair colour at age 18 years and personal history of keratinocyte cancer. Naevi was the strongest risk factor; the OPERA was 3·51 95% confidence interval (CI) 2·71–4·54 in the Australian study and 2·56 (95% CI 2·23–2·95) in the Leeds study. The AUC was 0·79 (95% CI 0·76–0·83) in the Australian study and 0·73 (95% CI 0·70–0·75) in the Leeds study. The Hosmer–Lemeshow test P‐value was 0·30 in the Australian study and < 0·001 in the Leeds study.
Conclusions
This model had good discrimination and could be used by clinicians to stratify patients by melanoma risk for the targeting of preventive interventions.
What's already known about this topic?
Melanoma risk prediction models may be useful in prevention by tailoring interventions to personalized risk levels.
For reasons of feasibility, time and cost many melanoma prediction models use self‐assessed risk factors. However, individuals tend to underestimate their naevus numbers.
What does this study add?
We present a melanoma risk prediction model, which includes clinically‐assessed whole‐body naevi and solar lentigines, and self‐assessed risk factors including pigmentation phenotype and history of keratinocyte cancer.
This model performs well on discrimination, the model's ability to distinguish between individuals with and without melanoma, and may assist clinicians to stratify patients by melanoma risk for targeted preventive interventions.
Linked Comment: Toland. Br J Dermatol 2020; 182:1089–1090.
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We purified, cloned, and expressed aggrecanase, a protease that is thought to be responsible for the degradation of cartilage aggrecan in arthritic diseases. Aggrecanase-1 a disintegrin and ...metalloproteinase with thrombospondin motifs-4 (ADAMTS-4) is a member of the ADAMTS protein family that cleaves aggrecan at the glutamic acid-373-alanine-374 bond. The identification of this protease provides a specific target for the development of therapeutics to prevent cartilage degradation in arthritis.
Background. Studies of Clostridium difficile outbreaks suggested that certain ribotypes (eg, 027 and 078) cause more severe disease than other ribotypes. A growing number of studies challenge the ...validity of this hypothesis. Methods. We conducted a cross-sectional study of C. difficile infection (CDI) to test whether ribotype predicted clinical severity when adjusted for the influence of other predictors. Toxigenic C. difficile isolates were cultured from stool samples, screened for genes encoding virulence factors by polymerase chain reaction (PCR) and ribotyped using high-throughput, fluorescent PCR ribotyping. We collected data for 15 covariates (microbiologie, epidemiologic, and laboratory variables) and determined their individual and cumulative influence on the association between C. difficile ribotype and severe disease. We then validated this influence using an independent data set. Results. A total of 34 severe CDI cases were identified among 310 independent cases of disease (11.0%). Eleven covariates, including C. difficile ribotype, were significant predictors of severe CDI in unadjusted analysis. However, the association between ribotypes 027 and 078 and severe CDI was not significant after adjustment for any of the other covariates. After full adjustment, severe cases were significantly predicted only by patients' white blood cell count and albumin level. This result was supported by analysis of a validation data set containing 433 independent CDI cases (45 severe cases; 10.4%). Conclusions. Ribotype is not a significant predictor of severe CDI when adjusted for the influence of any other variables separately or in combination. White blood cell count and albumin level are the most clinically relevant predictors of severe CDI cases.
The Internet of Things (IoT) has many important applications in multiple domains that include home automation, smart cities, healthcare, agriculture, and environment. IoT comprises a wide range of ...sensors and actuators that communicate with each other over cloud, fog, and edge level networks. Moreover, these devices use various communication protocols and are made by different manufactures. To deal with these diversities, IoT essentially needs interoperable communication interfaces among devices. Unfortunately, existing interoperability solutions are centralized and use fog or cloud level computing resources, making IoT communications latency-prone and poorly scalable. These issues could be handled effectively, if edge level devices could be made interoperable within the edge level and without needing fog or cloud level access. This article proposes a decentralized interoperability solution that stays fully within the edge level. The solution relies on controller devices that work on the interface boundaries of the edge devices. Unlike existing solutions, the proposed solution adopts a hierarchical interoperability model to handle interoperability at network, syntactical, semantic, and organizational levels. Our solution is nonproprietary, generic over vendors and platforms, and easily extendable to new devices. We compare our proposed solution with existing interoperability solutions for edge devices and show its mobility, efficiency, and flexibility.
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