A South Polar View of Late Paleozoic Glaciation: Physical Sedimentology and Provenance of Glacial Successions in the Tasmanian and Transantarctic Basins

The Late Paleozoic Ice Age (LPIA; ~ 374 – 256 Ma) is the longest Phanerozoic icehouse interval. this interval in Earth’s history was largely defined by extensive glaciation of the southern hemisphere at both polar and temperate latitudes. Glaciers are powerful climatic and geologic actors, especially during icehouse periods, and widespread glaciation can have a significant influence on both regional and global climate and geology. Therefore, constraining the characteristics of LPIA glaciers is essential to developing a global-scale understanding of this key climatic event in Earth’s history. The manuscripts in this dissertation examine the sedimentology, transport directions, stratigraphy, and detrital zircon provenance of the Pennsylvanian – Permian glacigenic succession from the LPIA at locations in the Transantarctic (Antarctica) and Tasmanian (Australia) basins. The Transantarctic and Tasmanian basins share many characteristics that make them interesting and important places to study LPIA glacigenic rocks. In both basins, sediments were deposited during a ~ 14 Myr icehouse interval spanning the Pennsylvanian-Permian boundary during which time glaciation is thought to have been the most extensive of the LPIA. During this interval, both basins were located at high (\u3e 60˚) southern latitudes along the Panthalassan margin of southeastern Gondwana. The similarities in paleogeographic, geologic, and temporal contexts between the Transantarctic and Tasmanian basins mean that characterizing and comparing LPIA glaciations in both areas is critical to understanding the late Paleozoic glacial maximum at polar latitudes. The works presented in this dissertation demonstrate that building an accurate, nuanced understanding of global glaciations during the LPIA, requires beginning at the local scale and building outward. Chapter 2 examines the Pagoda Formation of the Transantarctic Basin at four locations in the Shackleton Glacier Region of Antarctica. The dominant lithology in the Pagoda Fm at those locations is a massive, sandy, clast-poor diamictite. Depositional processes governing these diamictites were proglacial, subaqueous glacial processes, likely a combination of mass transport, iceberg rain-out, iceberg scouring, plume sedimentation, and subglacial till deposition. Some of the deposits are part of grounding-line fan systems. All glacigenic sediments in the Pagoda Fm at these locations were likely deposited during the retreat phase of a single, up to 90 m thick glacial sequence. Flow directions from these successions support the hypothesis that an ice center was present toward the Panthalassan margin of East Antarctica (Marie Byrd Land) during the LPIA. Chapter 3 describes the basal 415 m of the type section of the Wynyard Formation of the Tasmanian Basin, which outcrops along the coast of northwestern Tasmania. Facies associations in this succession include muddy massive diamictite, sandy massive diamictite, and rhythmically laminated fine-grained facies. Respectively, these sediments were deposited as a grounding-zone wedge, proglacial, proximal grounding line fan or morainal bank, and proglacial, glacier-distal cyclopelites. In this succession, the basal Wynyard Fm was deposited in glacier-proximal to glacier-distal, marine environments on a continental shelf at water depths below storm wave base. All facies associations contain mass transport and turbidite deposits that could have been driven by slope instability due to rapid deposition. The “Wynyard Glacier” was most likely an outlet glacier or ice stream draining a large ice cap or ice sheet. Chapter 4 is a detrital zircon geochronology provenance study of sandstones from the Wynyard Formation. These data represent the first such measurements from the Wynyard Formation anywhere in the basin. With these data, and using a “local first” approach, we demonstrated that all measured detrital zircon dates from the Wynyard Fm can be attributed to zircon sources that occur within 33 km of the sample location along the glacier’s flow path. Therefore, while the detrital zircon provenance signature of the Wynyard Fm also supports the hypothesis that the Wynyard Glacier flowed from south to north, this information does not impart insight into where the ice center was nucleated

Testing the Impact of Prebiotics on Anxiety-like Behaviors in Aged Male Rats

The composition of gut microbiota has direct impacts on neural structure, neurochemistry, and behavior. Specifically, the gut microbiota has been shown to modulate anxiety-like behaviors. In addition, administering prebiotics, compounds that promote the growth of commensal bacteria, has been demonstrated to reduce anxiety and anxiety-related behaviors. However, this effect has yet to be tested in older animals despite anxiety being implicated as a most common disorder in adult populations. Therefore, this study seeks to fill this knowledge gap by investigating the link between prebiotic interventions and anxiety-like behaviors in aged populations. It was hypothesized that older rats treated with the prebiotic fructooligosaccharide (FOS) would display an increase in exploratory behaviors, correlating to a decrease in anxiety, compared to the controls. Behavioral assays such as the open field test (OFT), elevated plus maze (EPM), and a social anxiety (SA) test were conducted. Results demonstrate moderate evidence that rats administered FOS had increased exploration in the center zone of the OFT. This finding suggests that FOS helps to modulate behavior in aged animals. With moderate evidence for increased exploration as evidence for decreased anxiety in FOS treated animals, this study provides a platform for further investigation of the role of modulating gut microbiota in older animals. Investigating the effects of senescence versus prebiotic treatment of the rats in this cohort was dampened by the limitations of the precedent of behavioral assays utilized on smaller, younger animals. As a result, this study calls for a widening of behavioral assay parameters to allow for effective data collection in an aging population

Evidence that two phenotypically distinct mouse PKD mutations, bpk and jcpk, are allelic

Evidence that two phenotypically distinct mouse PKD mutations, bpk and jcpk, are allelic. Numerous mouse models of polycystic kidney disease (PKD) have been described. All of these diseases are transmitted as single recessive traits and in most, the phenotypic severity is influenced by the genetic background. However, based on their genetic map positions, none of these loci appears to be allelic and none are candidate modifier loci for any other mouse PKD mutation. Previously, we have described the mouse bpk mutation, a model that closely resembles human autosomal recessive polycystic kidney disease. We now report that the bpk mutation maps to a 1.6 CM interval on mouse Chromosome 10, and that the renal cystic disease severity in our intersubspecific intercross progeny is influenced by the genetic background. Interestingly, bpk co-localizes with jcpk, a phenotyp-ically-distinct PKD mutation, and complementation testing indicates that the bpk and jcpk mutations are allelic. These data imply that distinct PKD phenotypes can result from different mutations within a single gene. In addition, based on its map position, the bpk locus is a candidate genetic modifier for jck, a third phenotypically-distinct PKD mutation

Occurrence of False Positive Results for the Detection of Carbapenemases in Carbapenemase-Negative Escherichia coli and Klebsiella pneumoniae Isolates

Adequate detection of the production of carbapenemase in Enterobacteriaceae isolates is crucial for infection control measures and the appropriate choice of antimicrobial therapy. In this study, we investigated the frequency of false positive results for the detection of carbapenemases in carbapenemase-negative Escherichia coli and Klebsiella pneumoniae clinical isolates by the modified Hodge test (MHT). Three hundred and one E. coli and K. pneumoniae clinical isolates were investigated. All produced extended spectrum β-lactamases (ESBLs) but were susceptible to carbapenems. Antimicrobial susceptibility testing was performed by the disk diffusion and agar dilution methods. The MHT was performed using the standard inoculum of test organisms recommended by the CLSI. Genes that encoded ESBLs and carbapenemases were identified by PCR and DNA sequencing. Among the 301 clinical isolates, none of the isolates conformed to the criteria for carbapenemase screening recommended by the CLSI. The susceptibility rates for imipenem, meropenem, and ertapenem all were 100.0%, 100.0%, and 100.0%, respectively. Of the 301 E. coli and K. pneumoniae isolates, none produced carbapenemase. The MHT gave a positive result for 3.3% (10/301) of the isolates. False positive results can occur when the MHT is used to detect carbapenemase in ESBL-producing isolates and clinical laboratories must be aware of this fact

Seventh BHD international symposium: recent scientific and clinical advancement.

The 7th Birt-Hogg-Dubé (BHD) International Symposium convened virtually in October 2021. The meeting attracted more than 200 participants internationally and highlighted recent findings in a variety of areas, including genetic insight and molecular understanding of BHD syndrome, structure and function of the tumor suppressor Folliculin (FLCN), therapeutic and clinical advances as well as patients' experiences living with this malady

Ten years of external quality assessment (EQA) of Neisseria gonorrhoeae antimicrobial susceptibility testing in Europe elucidate high reliability of data

BACKGROUND: Confidence in any diagnostic and antimicrobial susceptibility testing data is provided by appropriate and regular quality assurance (QA) procedures. In Europe, the European Gonococcal Antimicrobial Susceptibility Programme (Euro-GASP) has been monitoring the antimicrobial susceptibility in Neisseria gonorrhoeae since 2004. Euro-GASP includes an external quality assessment (EQA) scheme as an essential component for a quality-assured laboratory-based surveillance programme. Participation in the EQA scheme enables any problems with the performed antimicrobial susceptibility testing to be identified and addressed, feeds into the curricula of laboratory training organised by the Euro-GASP network, and assesses the capacity of individual laboratories to detect emerging new, rare and increasing antimicrobial resistance phenotypes. Participant performance in the Euro-GASP EQA scheme over a 10 year period (2007 to 2016, no EQA in 2013) was evaluated. METHODS: Antimicrobial susceptibility category and MIC results from the first 5 years (2007-2011) of the Euro-GASP EQA were compared with the latter 5 years (2012-2016). These time periods were selected to assess the impact of the 2012 European Union case definitions for the reporting of antimicrobial susceptibility. RESULTS: Antimicrobial susceptibility category agreement in each year was ≥91%. Discrepancies in susceptibility categories were generally because the MICs for EQA panel isolates were on or very close to the susceptibility or resistance breakpoints. A high proportion of isolates tested over the 10 years were within one (≥90%) or two (≥97%) MIC log2 dilutions of the modal MIC, respectively. The most common method used was Etest on GC agar base. There was a shift to using breakpoints published by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in the latter 5 years, however overall impact on the validity of results was limited, as the percentage categorical agreement and MIC concordance changed very little between the two five-year periods. CONCLUSIONS: The high level of comparability of results in this EQA scheme indicates that high quality data are produced by the Euro-GASP participants and gives confidence in susceptibility and resistance data generated by laboratories performing decentralised testing.The study was funded by the European Centre for Disease Prevention and Control (Framework Contract No. ECDC/2013/015). The funding body contributed to the design of the study, the interpretation of the data and to the writing of the manuscript.S

Loss of apical monocilia on collecting duct principal cells impairs ATP secretion across the apical cell surface and ATP-dependent and flow-induced calcium signals

Renal epithelial cells release ATP constitutively under basal conditions and release higher quantities of purine nucleotide in response to stimuli. ATP filtered at the glomerulus, secreted by epithelial cells along the nephron, and released serosally by macula densa cells for feedback signaling to afferent arterioles within the glomerulus has important physiological signaling roles within kidneys. In autosomal recessive polycystic kidney disease (ARPKD) mice and humans, collecting duct epithelial cells lack an apical central cilium or express dysfunctional proteins within that monocilium. Collecting duct principal cells derived from an Oak Ridge polycystic kidney (orpkTg737) mouse model of ARPKD lack a well-formed apical central cilium, thought to be a sensory organelle. We compared these cells grown as polarized cell monolayers on permeable supports to the same cells where the apical monocilium was genetically rescued with the wild-type Tg737 gene that encodes Polaris, a protein essential to cilia formation. Constitutive ATP release under basal conditions was low and not different in mutant versus rescued monolayers. However, genetically rescued principal cell monolayers released ATP three- to fivefold more robustly in response to ionomycin. Principal cell monolayers with fully formed apical monocilia responded three- to fivefold greater to hypotonicity than mutant monolayers lacking monocilia. In support of the idea that monocilia are sensory organelles, intentionally harsh pipetting of medium directly onto the center of the monolayer induced ATP release in genetically rescued monolayers that possessed apical monocilia. Mechanical stimulation was much less effective, however, on mutant orpk collecting duct principal cell monolayers that lacked apical central monocilia. Our data also show that an increase in cytosolic free Ca2+ primes the ATP pool that is released in response to mechanical stimuli. It also appears that hypotonic cell swelling and mechanical pipetting stimuli trigger release of a common ATP pool. Cilium-competent monolayers responded to flow with an increase in cell Ca2+ derived from both extracellular and intracellular stores. This flow-induced Ca2+ signal was less robust in cilium-deficient monolayers. Flow-induced Ca2+ signals in both preparations were attenuated by extracellular gadolinium and by extracellular apyrase, an ATPase/ADPase. Taken together, these data suggest that apical monocilia are sensory organelles and that their presence in the apical membrane facilitates the formation of a mature ATP secretion apparatus responsive to chemical, osmotic, and mechanical stimuli. The cilium and autocrine ATP signaling appear to work in concert to control cell Ca2+. Loss of a cilium-dedicated autocrine purinergic signaling system may be a critical underlying etiology for ARPKD and may lead to disinhibition and/or upregulation of multiple sodium (Na+) absorptive mechanisms and a resultant severe hypertensive phenotype in ARPKD and, possibly, other diseases

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

The Femme Fatale in Vogue:Femininity Ideologies in Fin-de-siècle America

This article explores how marketing influences ideologies of femininity. Tracing the evolution of femme fatale images in Vogue magazine in 1890s America, we develop a typology around four archetypal forms of the femme fatale that prevailed during this period. In doing so we respond to calls for more critical historical analyses on femininity. While studies on masculinity ideologies proliferate, there is a paucity of research on dissonant representations of femininity in popular culture media. The femme fatale, often a self-determined seductress who causes anguish to the men who become involved with her, is an intriguing and enduring challenge to traditional notions of femininity. Thus, in studying the femme fatale in her historical context and revealing the multiplicity of feminine ideologies contained within this trope, we contribute to a deeper understanding of marketing’s role in both reflecting and reinforcing societal assumptions, attitudes and problematics around gender norms.</p