W(h)ither Fossils? Studying Morphological Character Evolution in the Age of Molecular Sequences

A major challenge in the post-genomics era will be to integrate molecular sequence data from extant organisms with morphological data from fossil and extant taxa into a single, coherent picture of phylogenetic relationships; only then will these phylogenetic hypotheses be effectively applied to the study of morphological character evolution. At least two analytical approaches to solving this problem have been utilized: (1) simultaneous analysis of molecular sequence and morphological data with fossil taxa included as terminals in the analysis, and (2) the molecular scaffold approach, in which morphological data are analyzed over a molecular backbone (with constraints that force extant taxa into positions suggested by sequence data). The perceived obstacles to including fossil taxa directly in simultaneous analyses of morphological and molecular sequence data with extant taxa include: (1) that fossil taxa are missing the molecular sequence portion of the character data; (2) that morphological characters might be misleading due to convergence; and (3) character weighting, specifically how and whether to weight characters in the morphological partition relative to characters in the molecular sequence data partition. The molecular scaffold has been put forward as a potential solution to at least some of these problems. Using examples of simultaneous analyses from the literature, as well as new analyses of previously published morphological and molecular sequence data matrices for extant and fossil Chiroptera (bats), we argue that the simultaneous analysis approach is superior to the molecular scaffold approach, specifically addressing the problems to which the molecular scaffold has been suggested as a solution. Finally, the application of phylogenetic hypotheses including fossil taxa (whatever their derivation) to the study of morphological character evolution is discussed, with special emphasis on scenarios in which fossil taxa are likely to be most enlightening: (1) in determining the sequence of character evolution; (2) in determining the timing of character evolution; and (3) in making inferences about the presence or absence of characteristics in fossil taxa that may not be directly observable in the fossil record. Published By: Missouri Botanical Garde

The Fossil Calibration Database—A New Resource for Divergence Dating

Fossils provide the principal basis for temporal calibrations, which are critical to the accuracy of divergence dating analyses. Translating fossil data into minimum and maximum bounds for calibrations is the most important—often least appreciated—step of divergence dating. Properly justified calibrations require the synthesis of phylogenetic, paleontological, and geological evidence and can be difficult for nonspecialists to formulate. The dynamic nature of the fossil record (e.g., new discoveries, taxonomic revisions, updates of global or local stratigraphy) requires that calibration data be updated continually lest they become obsolete. Here, we announce the Fossil Calibration Database (http://fossilcalibrations.org), a new open-access resource providing vetted fossil calibrations to the scientific community. Calibrations accessioned into this database are based on individual fossil specimens and follow best practices for phylogenetic justification and geochronological constraint. The associated Fossil Calibration Series, a calibration-themed publication series at Palaeontologia Electronica, will serve as a key pipeline for peer-reviewed calibrations to enter the databas

The Fossil Calibration Database, A New Resource for Divergence Dating

Fossils provide the principal basis for temporal calibrations, which are critical to the accuracy of divergence dating analyses. Translating fossil data into minimum and maximum bounds for calibrations is the most important, and often least appreciated, step of divergence dating. Properly justified calibrations require the synthesis of phylogenetic, paleontological, and geological evidence and can be difficult for non- specialists to formulate. The dynamic nature of the fossil record (e.g., new discoveries, taxonomic revisions, updates of global or local stratigraphy) requires that calibration data be updated continually lest they become obsolete. Here, we announce the Fossil Calibration Database (http://fossilcalibrations.org), a new open- access resource providing vetted fossil calibrations to the scientific community. Calibrations accessioned into this database are based on individual fossil specimens and follow best practices for phylogenetic justification and geochronological constraint. The associated Fossil Calibration Series, a calibration-themed publication series at Palaeontologia Electronica, will serve as one key pipeline for peer-reviewed calibrations to enter the database

Quality indicators for responsible antibiotic use in the inpatient setting: a systematic review followed by an international multidisciplinary consensus procedure

Background This study was conducted as part of the Driving Reinvestment in Research and Development and Responsible Antibiotic Use (DRIVE-AB) project and aimed to develop generic quality indicators (QIs) for responsible antibiotic use in the inpatient setting. Methods A RAND-modified Delphi method was applied. First, QIs were identified by a systematic review. A complementary search was performed on web sites of relevant organizations. Duplicates were removed and disease and patient-specific QIs were combined into generic indicators. The relevance of these QIs was appraised by a multidisciplinary international stakeholder panel through two questionnaires and an in-between consensus meeting. Results The systematic review retrieved 70 potential generic QIs. The QIs were appraised by 25 international stakeholders with diverse backgrounds (medical community, public health, patients, antibiotic research and development, regulators, governments). Ultimately, 51 QIs were selected in consensus. QIs with the highest relevance score included: (i) an antibiotic plan should be documented in the medical record at the start of the antibiotic treatment; (ii) the results of bacteriological susceptibility testing should be documented in the medical record; (iii) the local guidelines should correspond to the national guidelines but should be adapted based on local resistance patterns; (iv) an antibiotic stewardship programme should be in place at the healthcare facility; and (v) allergy status should be taken into account when antibiotics are prescribed. Conclusions This systematic and stepwise method combining evidence from literature and stakeholder opinion led to multidisciplinary international consensus on generic inpatient QIs that can be used globally to assess the quality of antibiotic use

Antimicrobial Activities of Aztreonam-Avibactam and Comparator Agents against Enterobacterales Analyzed by ICU and Non-ICU Wards, Infection Sources, and Geographic Regions: ATLAS Program 2016–2020

Increasing antimicrobial resistance among multidrug-resistant (MDR), extended-spectrum β-lactamase (ESBL)- and carbapenemase-producing Enterobacterales (CPE), in particular metallo-β-lactamase (MBL)-positive strains, has led to limited treatment options in these isolates. This study evaluated the activity of aztreonam-avibactam (ATM-AVI) and comparator antimicrobials against Enterobacterales isolates and key resistance phenotypes stratified by wards, infection sources and geographic regions as part of the ATLAS program between 2016 and 2020. Minimum inhibitory concentrations (MICs) were determined per Clinical and Laboratory Standards Institute (CLSI) guidelines. The susceptibility of antimicrobials were interpreted using CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. A tentative pharmacokinetic/pharmacodynamic breakpoint of 8 µg/mL was considered for ATM-AVI activity. ATM-AVI inhibited ≥99.2% of Enterobacterales isolates across wards and ≥99.7% isolates across infection sources globally and in all regions at ≤8 µg/mL. For resistance phenotypes, ATM-AVI demonstrated sustained activity across wards and infection sources by inhibiting ≥98.5% and ≥99.1% of multidrug-resistant (MDR) isolates, ≥98.6% and ≥99.1% of ESBL-positive isolates, ≥96.8% and ≥90.9% of carbapenem-resistant (CR) isolates, and ≥96.8% and ≥97.4% of MBL-positive isolates, respectively, at ≤8 µg/mL globally and across regions. Overall, our study demonstrated that ATM-AVI represents an important therapeutic option for infections caused by Enterobacterales, including key resistance phenotypes across different wards and infection sources

Increased Killing of Staphylococci and Streptococci by Daptomycin Compared with Cefazolin and Vancomycin in an In Vitro Peritoneal Dialysate Model

Peritoneal dialysate fluid (PDF) is a bacteriostatic medium that compromises the antibacterial activity of cell wall-active agents. By use of an in vitro static model, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible S. aureus (MSSA), methicillin-susceptible Staphylococcus epidermidis (MSSE), and Streptococcus sanguis were exposed to daptomycin at concentrations of 10, 30, and 100 mg/liter, cefazolin at 125 mg/liter, and vancomycin at 25 mg/liter in cation-adjusted Mueller-Hinton Broth or Todd Hewitt Broth (for S. sanguis) and PDF at pHs of 5.5 and 7.4. The pH had no effect on antibacterial activity. Neither cefazolin nor vancomycin produced a bactericidal or a bacteriostatic effect versus MRSA, MSSA, MSSE, or S. sanguis in PDF, while all concentrations of daptomycin were bactericidal against all organisms in PDF. Daptomycin did not exhibit concentration-dependent activity in PDF. Daptomycin appears to be a promising agent for use in peritoneal dialysis-associated peritonitis, producing bacterial kill to a greater extent and at a higher rate than cefazolin or vancomycin in PDF

Mutant Prevention Concentrations of ABT-492, Levofloxacin, Moxifloxacin, and Gatifloxacin against Three Common Respiratory Pathogens

The purpose of this study was to compare the mutant prevention concentration (MPC) of ABT-492 to those of levofloxacin, moxifloxacin, and gatifloxacin against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. The fluoroquinolones had comparable mutation selection windows, which is the ratio of MPC/MIC, for all isolates