A genomic portrait of the emergence, evolution, and global spread of a methicillin-resistant staphylococcus aureus pandemic

The widespread use of antibiotics in association with high-density clinical care has driven the emergence of drug-resistant bacteria that are adapted to thrive in hospitalized patients. Of particular concern are globally disseminated methicillin-resistant Staphylococcus aureus (MRSA) clones that cause outbreaks and epidemics associated with health care. The most rapidly spreading and tenacious health-care-associated clone in Europe currently is EMRSA-15, which was first detected in the UK in the early 1990s and subsequently spread throughout Europe and beyond. Using phylogenomic methods to analyze the genome sequences for 193 S. aureus isolates, we were able to show that the current pandemic population of EMRSA-15 descends from a health-care-associated MRSA epidemic that spread throughout England in the 1980s, which had itself previously emerged from a primarily community-associated methicillin-sensitive population. The emergence of fluoroquinolone resistance in this EMRSA-15 subclone in the English Midlands during the mid-1980s appears to have played a key role in triggering pandemic spread, and occurred shortly after the first clinical trials of this drug. Genome-based coalescence analysis estimated that the population of this subclone over the last 20 yr has grown four times faster than its progenitor. Using comparative genomic analysis we identified the molecular genetic basis of 99.8% of the antimicrobial resistance phenotypes of the isolates, highlighting the potential of pathogen genome sequencing as a diagnostic tool. We document the genetic changes associated with adaptation to the hospital environment and with increasing drug resistance over time, and how MRSA evolution likely has been influenced by country-specific drug use regimens

C-axis lattice dynamics in Bi-based cuprate superconductors

We present results of a systematic study of the c axis lattice dynamics in single layer Bi2Sr2CuO6 (Bi2201), bilayer Bi2Sr2CaCu2O8 (Bi2212) and trilayer Bi2Sr2Ca2Cu3O10 (Bi2223) cuprate superconductors. Our study is based on both experimental data obtained by spectral ellipsometry on single crystals and theoretical calculations. The calculations are carried out within the framework of a classical shell model, which includes long-range Coulomb interactions and short-range interactions of the Buckingham form in a system of polarizable ions. Using the same set of the shell model parameters for Bi2201, Bi2212 and Bi2223, we calculate the frequencies of the Brillouin-zone center phonon modes of A2u symmetry and suggest the phonon mode eigenvector patterns. We achieve good agreement between the calculated A2u eigenfrequencies and the experimental values of the c axis TO phonon frequencies which allows us to make a reliable phonon mode assignment for all three Bi-based cuprate superconductors. We also present the results of our shell model calculations for the Gamma-point A1g symmetry modes in Bi2201, Bi2212 and Bi2223 and suggest an assignment that is based on the published experimental Raman spectra. The superconductivity-induced phonon anomalies recently observed in the c axis infrared and resonant Raman scattering spectra in trilayer Bi2223 are consistently explained with the suggested assignment.Comment: 29 pages, 13 figure

Subtype-specific differences in transmission cluster dynamics of HIV-1 B and CRF01_AE in New South Wales, Australia

Introduction: The human immunodeficiency virus 1 (HIV-1) pandemic is characterized by numerous distinct sub-epidemics (clusters) that continually fuel local transmission. The aims of this study were to identify active growing clusters, to understand which factors most influence the transmission dynamics, how these vary between different subtypes and how this information might contribute to effective public health responses. Methods: We used HIV-1 genomic sequence data linked to demographic factors that accounted for approximately 70% of all new HIV-1 notifications in New South Wales (NSW). We assessed differences in transmission cluster dynamics between subtype B and circulating recombinant form 01_AE (CRF01_AE). Separate phylogenetic trees were estimated using 2919 subtype B and 473 CRF01_AE sequences sampled between 2004 and 2018 in combination with global sequence data and NSW-specific clades were classified as clusters, pairs or singletons. Significant differences in demographics between subtypes were assessed with Chi-Square statistics. Results: We identified 104 subtype B and 11 CRF01_AE growing clusters containing a maximum of 29 and 11 sequences for subtype B and CRF01_AE respectively. We observed a > 2-fold increase in the number of NSW-specific CRF01_AE clades over time. Subtype B clusters were associated with individuals reporting men who have sex with men (MSM) as their transmission risk factor, being born in Australia, and being diagnosed during the early stage of infection (p 1.5 sequences / 6-months) and which consisted of a majority of infections among MSM. We also found four active growing CRF01_AE clusters containing only infections among MSM. Finally, we found 47 subtype B and seven CRF01_AE clusters that contained a large gap in time (>1 year) between infections and may be indicative of intermediate transmissions via undiagnosed individuals. Conclusions: The large number of active and growing clusters among MSM are the driving force of the ongoing epidemic in NSW for subtype B and CRF01_AE.Francesca Di Giallonardo, Angie N Pinto, Phillip Keen, Ansari Shaik, Alex Carrera, Hanan Salem, Christine Selvey, Steven J Nigro, Neil Fraser, Karen Price, Joanne Holden, Frederick J Lee, Dominic E Dwyer, Benjamin R Bavinton, Jemma L Geoghegan, Andrew E Grulich, Anthony D Kelleher, NSW HIV Prevention Partnership Project ... Mark Boyd ... et al

Cosmology with clusters of galaxies

In this Chapter I review the role that galaxy clusters play as tools to constrain cosmological parameters. I will concentrate mostly on the application of the mass function of galaxy clusters, while other methods, such as that based on the baryon fraction, are covered by other Chapters of the book. Since most of the cosmological applications of galaxy clusters rely on precise measurements of their masses, a substantial part of my Lectures concentrates on the different methods that have been applied so far to weight galaxy clusters. I provide in Section 2 a short introduction to the basics of cosmic structure formation. In Section 3 I describe the Press--Schechter (PS) formalism to derive the cosmological mass function, then discussing extensions of the PS approach and the most recent calibrations from N--body simulations. In Section 4 I review the methods to build samples of galaxy clusters at different wavelengths. Section 5 is devoted to the discussion of different methods to derive cluster masses. In Section 6 I describe the cosmological constraints, which have been obtained so far by tracing the cluster mass function with a variety of methods. Finally, I describe in Section 7 the future perspectives for cosmology with galaxy clusters and the challenges for clusters to keep playing an important role in the era of precision cosmology.Comment: 49 pages, 19 figures, Lectures for 2005 Guillermo Haro Summer School on Clusters, to appear in "Lecture notes in Physics" (Springer

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Partner-abusers as fathers: testing hypotheses about their child rearing and the risk of physical child abuse

Children of men who abuse their partners are at risk for behavior problems and physical abuse. Few studies have investigated the child rearing of these men. To investigate the quality of child rearing spouse abusers engage in, a total of 94 fathers of children participated. Fifty-six fathers were enrolled in a batterers intervention program and 39 fathers came from the community. The men reported on their parenting behavior and attitudes, problematic behaviors linked to abuse, and two types of abnormal behavior. Only one significant group difference was found between the violent and the nonviolent fathers. However, across the two samples, men who reported engaging in more psychological abuse had higher Child Abuse Potential Inventory (CAP) scores. Furthermore, fathers with elevated CAP scores (all but one were in the batterer intervention group) differed significantly from the other men on seven variables including anger, trauma symptoms, and borderline personality organization. Implications for understanding perpetrators of partner violence and the links to physical child abuse are discussed