A maximum rupture model for the central and southern Cascadia subduction zone—reassessing ages for coastal evidence of megathrust earthquakes and tsunamis

A new history of great earthquakes (and their tsunamis) for the central and southern Cascadia subduction zone shows more frequent (17 in the past 6700 yr) megathrust ruptures than previous coastal chronologies. The history is based on along-strike correlations of Bayesian age models derived from evaluation of 554 radiocarbon ages that date earthquake evidence at 14 coastal sites. We reconstruct a history that accounts for all dated stratigraphic evidence with the fewest possible ruptures by evaluating the sequence of age models for earthquake or tsunami contacts at each site, comparing the degree of temporal overlap of correlated site age models, considering evidence for closely spaced earthquakes at four sites, and hypothesizing only maximum-length megathrust ruptures. For the past 6700 yr, recurrence for all earthquakes is 370–420 yr. But correlations suggest that ruptures at ∼1.5 ka and ∼1.1 ka were of limited extent (<400 km). If so, post-3-ka recurrence for ruptures extending throughout central and southern Cascadia is 510–540 yr. But the range in the times between earthquakes is large: two instances may be ∼50 yr, whereas the longest are ∼550 and ∼850 yr. The closely spaced ruptures about 1.6 ka may illustrate a pattern common at subduction zones of a long gap ending with a great earthquake rupturing much of the subduction zone, shortly followed by a rupture of more limited extent. The ruptures of limited extent support the continued inclusion of magnitude-8 earthquakes, with longer ruptures near magnitude 9, in assessments of seismic hazard in the region

Fluorescence characterization of clinically-important bacteria

Healthcare-associated infections (HCAI/HAI) represent a substantial threat to patient health during hospitalization and incur billions of dollars additional cost for subsequent treatment. One promising method for the detection of bacterial contamination in a clinical setting before an HAI outbreak occurs is to exploit native fluorescence of cellular molecules for a hand-held, rapid-sweep surveillance instrument. Previous studies have shown fluorescence-based detection to be sensitive and effective for food-borne and environmental microorganisms, and even to be able to distinguish between cell types, but this powerful technique has not yet been deployed on the macroscale for the primary surveillance of contamination in healthcare facilities to prevent HAI. Here we report experimental data for the specification and design of such a fluorescence-based detection instrument. We have characterized the complete fluorescence response of eleven clinically-relevant bacteria by generating excitation-emission matrices (EEMs) over broad wavelength ranges. Furthermore, a number of surfaces and items of equipment commonly present on a ward, and potentially responsible for pathogen transfer, have been analyzed for potential issues of background fluorescence masking the signal from contaminant bacteria. These include bedside handrails, nurse call button, blood pressure cuff and ward computer keyboard, as well as disinfectant cleaning products and microfiber cloth. All examined bacterial strains exhibited a distinctive double-peak fluorescence feature associated with tryptophan with no other cellular fluorophore detected. Thus, this fluorescence survey found that an emission peak of 340nm, from an excitation source at 280nm, was the cellular fluorescence signal to target for detection of bacterial contamination. The majority of materials analysed offer a spectral window through which bacterial contamination could indeed be detected. A few instances were found of potential problems of background fluorescence masking that of bacteria, but in the case of the microfiber cleaning cloth, imaging techniques could morphologically distinguish between stray strands and bacterial contamination

Students’ Perceptions of Learning Processes as Co-Authors of Digital Tabletop Activities

We conducted a small-scale study in order to explore students’ perceptions of the learning processes when engaged as co-authors of content for collaborative higher order thinking skills learning tasks. We specifically designed the process to allow for self-critique – where authors can observe their creations being solved and therefore understand where they may improve their design. We collected data over a three-day period from a sample of twelve thirteen year olds, working in teams, authoring content for Digital Mysteries (a higher order thinking skills collaborative learning application based on the digital tabletop). The study was structured to follow Bloom’s taxonomy, a continuum of cognitive skills that develop during a learning process. We found that 1) rather than follow this continuum, skills developed in a non-linear manner due to the abstract nature of the authoring activity, and 2) the students’ demonstrated good metacognitive insights into the authoring task, technology and collaborative learning as a whole

Validation of a brief telephone battery for neurocognitive assessment of patients with pulmonary arterial hypertension

BACKGROUND: The effects of pulmonary arterial hypertension on brain function are not understood, despite patients' frequent complaints of cognitive difficulties. Using clinical instruments normally administered during standard in-person assessment of neurocognitive function in adults, we assembled a battery of tests designed for administration over the telephone. The purpose was to improve patient participation, facilitate repeated test administration, and reduce the cost of research on the neuropsychological consequences of acute and chronic cardiorespiratory diseases. We undertook this study to validate telephone administration of the tests. METHODS: 23 adults with pulmonary arterial hypertension underwent neurocognitive assessment using both standard in-person and telephone test administration, and the results of the two methods compared using interclass correlations. RESULTS: For most of the tests in the battery, scores from the telephone assessment correlated strongly with those obtained by in-person administration of the same tests. Interclass correlations between 0.5 and 0.8 were observed for tests that assessed attention, memory, concentration/working memory, reasoning, and language/crystallized intelligence (p ≤ 0.05 for each). Interclass correlations for the Hayling Sentence Completion test of executive function approached significance (p = 0.09). All telephone tests were completed within one hour. CONCLUSION: Administration of this neurocognitive test battery by telephone should facilitate assessment of neuropsychological deficits among patients with pulmonary arterial hypertension living across broad geographical areas, and may be useful for monitoring changes in neurocognitive function in response to PAH-specific therapy or disease progression

Lysyl-tRNA synthetase, a target for urgently needed M. tuberculosis drugs

Tuberculosis is a major global cause of both mortality and financial burden mainly in low and middle-income countries. Given the significant and ongoing rise of drug-resistant strains of Mycobacterium tuberculosis within the clinical setting, there is an urgent need for the development of new, safe and effective treatments. Here the development of a drug-like series based on a fused dihydropyrrolidino-pyrimidine scaffold is described. The series has been developed against M. tuberculosis lysyl-tRNA synthetase (LysRS) and cellular studies support this mechanism of action. DDD02049209, the lead compound, is efficacious in mouse models of acute and chronic tuberculosis and has suitable physicochemical, pharmacokinetic properties and an in vitro safety profile that supports further development. Importantly, preliminary analysis using clinical resistant strains shows no pre-existing clinical resistance towards this scaffold

Universal Sequence Replication, Reversible Polymerization and Early Functional Biopolymers: A Model for the Initiation of Prebiotic Sequence Evolution

Many models for the origin of life have focused on understanding how evolution can drive the refinement of a preexisting enzyme, such as the evolution of efficient replicase activity. Here we present a model for what was, arguably, an even earlier stage of chemical evolution, when polymer sequence diversity was generated and sustained before, and during, the onset of functional selection. The model includes regular environmental cycles (e.g. hydration-dehydration cycles) that drive polymers between times of replication and functional activity, which coincide with times of different monomer and polymer diffusivity. Template-directed replication of informational polymers, which takes place during the dehydration stage of each cycle, is considered to be sequence-independent. New sequences are generated by spontaneous polymer formation, and all sequences compete for a finite monomer resource that is recycled via reversible polymerization. Kinetic Monte Carlo simulations demonstrate that this proposed prebiotic scenario provides a robust mechanism for the exploration of sequence space. Introduction of a polymer sequence with monomer synthetase activity illustrates that functional sequences can become established in a preexisting pool of otherwise non-functional sequences. Functional selection does not dominate system dynamics and sequence diversity remains high, permitting the emergence and spread of more than one functional sequence. It is also observed that polymers spontaneously form clusters in simulations where polymers diffuse more slowly than monomers, a feature that is reminiscent of a previous proposal that the earliest stages of life could have been defined by the collective evolution of a system-wide cooperation of polymer aggregates. Overall, the results presented demonstrate the merits of considering plausible prebiotic polymer chemistries and environments that would have allowed for the rapid turnover of monomer resources and for regularly varying monomer/polymer diffusivities