Juan de Fuca slab geometry and its relation to Wadati-Benioff zone seismicity

A new model of the subducted Juan de Fuca plate beneath western North America allows first-order correlations between the occurrence of Wadati-Benioff zone earthquakes and slab geometry, temperature, and hydration state. The geo-referenced 3D model, constructed from weighted control points, integrates depth information from earthquake locations and regional seismic velocity studies. We use the model to separate earthquakes that occur in the Cascadia forearc from those that occur within the underlying Juan de Fuca plate and thereby reveal previously obscured details regarding the spatial distribution of earthquakes. Seismicity within the slab is most prevalent where the slab is warped beneath northwestern California and western Washington suggesting that slab flexure, in addition to expected metamorphic dehydration processes, promotes earthquake occurrence within the subducted oceanic plate. Earthquake patterns beneath western Vancouver Island are consistent with slab dehydration processes. Conversely, the lack of slab earthquakes beneath western Oregon is consistent with an anhydrous slab. Double-differenced relocated seismicity resolves a double seismic zone within the slab beneath northwestern California that strongly constrains the location of the plate interface and delineates a cluster of seismicity 10 km above the surface that includes the 1992 M7.1 Mendocino earthquake. We infer that this earthquake ruptured a surface within the Cascadia accretionary margin above the Juan de Fuca plate. We further speculate that this earthquake is associated with a detached fragment of former Farallon plate. Other subsurface tectonic elements within the forearc may have the potential to generate similar damaging earthquakes

New Labour's communitarianisms

This article argues that communitarianism can be analysed on different levels — sociological, ethical and meta—ethical — and along different dimensions — conformist/pluralist, more conditional/less conditional, progressive/conservative, prescriptive/voluntary, moral/socioeconomic and individual/corporate. We argue that New Labour's communitarianism is a response to both neo-liberalism and old social democracy. It is sociological, ethical and universalist rather than particularist on the meta-ethical level. Labour increasingly favours conditional, morally prescriptive, conservative and individual communitarianisms. This is at the expense of less conditional and redistributional socioeconomic, progressive and corporate communitarianisms. It is torn between conformist and pluralist versions of communitarianism. This bias is part of a wider shift in Labour thinking from social democracy to a liberal conservatism which celebrates the dynamic market economy and is socially conservative

Prognostic value of upper respiratory tract microbes in children presenting to primary care with respiratory infections:a prospective cohort study

BACKGROUND: The association between upper respiratory tract microbial positivity and illness prognosis in children is unclear. This impedes clinical decision-making and means the utility of upper respiratory tract microbial point-of-care tests remains unknown. We investigated for relationships between pharyngeal microbes and symptom severity in children with suspected respiratory tract infection (RTI). METHODS: Baseline characteristics and pharyngeal swabs were collected from 2,296 children presenting to 58 general practices in Bristol, UK with acute cough and suspected RTI between 2011–2013. Post-consultation, parents recorded the severity of six RTI symptoms on a 0–6 scale daily for ≤28 days. We used multivariable hurdle regression, adjusting for clinical characteristics, antibiotics and other microbes, to investigate associations between respiratory microbes and mean symptom severity on days 2–4 post-presentation. RESULTS: Overall, 1,317 (57%) children with complete baseline, microbiological and symptom data were included. Baseline characteristics were similar in included participants and those lacking microbiological data. At least one virus was detected in 869 (66%) children, and at least one bacterium in 783 (60%). Compared to children with no virus detected (mean symptom severity score 1.52), adjusted mean symptom severity was 0.26 points higher in those testing positive for at least one virus (95% CI 0.15 to 0.38, p<0.001); and was also higher in those with detected Influenza B (0.44, 0.15 to 0.72, p = 0.003); RSV (0.41, 0.20 to 0.60, p<0.001); and Influenza A (0.25, -0.01 to 0.51, p = 0.059). Children positive for Enterovirus had a lower adjusted mean symptom severity (-0.24, -0.43 to -0.05, p = 0.013). Children with detected Bordetella pertussis (0.40, 0.00 to 0.79, p = 0.049) and those with detected Moraxella catarrhalis (-0.76, -1.06 to -0.45, p<0.001) respectively had higher and lower mean symptom severity compared to children without these bacteria. CONCLUSIONS: There is a potential role for upper respiratory tract microbiological point-of-care tests in determining the prognosis of childhood RTIs

Gene regulatory network analysis predicts cooperating transcription factor regulons required for FLT3-ITD+ AML growth

Acute myeloid leukemia (AML) is a heterogeneous disease caused by different mutations. Previously, we showed that each mutational subtype develops its specific gene regulatory network (GRN) with transcription factors interacting within multiple gene modules, many of which are transcription factor genes themselves. Here, we hypothesize that highly connected nodes within such networks comprise crucial regulators of AML maintenance. We test this hypothesis using FLT3-ITD-mutated AML as a model and conduct an shRNA drop-out screen informed by this analysis. We show that AML-specific GRNs predict crucial regulatory modules required for AML growth. Furthermore, our work shows that all modules are highly connected and regulate each other. The careful multi-omic analysis of the role of one (RUNX1) module by shRNA and chemical inhibition shows that this transcription factor and its target genes stabilize the GRN of FLT3-ITD+ AML and that its removal leads to GRN collapse and cell death.</p

Precision measurements of the top quark mass from the Tevatron in the pre-LHC era

The top quark is the heaviest of the six quarks of the Standard Model. Precise knowledge of its mass is important for imposing constraints on a number of physics processes, including interactions of the as yet unobserved Higgs boson. The Higgs boson is the only missing particle of the Standard Model, central to the electroweak symmetry breaking mechanism and generation of particle masses. In this Review, experimental measurements of the top quark mass accomplished at the Tevatron, a proton-antiproton collider located at the Fermi National Accelerator Laboratory, are described. Topologies of top quark events and methods used to separate signal events from background sources are discussed. Data analysis techniques used to extract information about the top mass value are reviewed. The combination of several most precise measurements performed with the two Tevatron particle detectors, CDF and \D0, yields a value of \Mt = 173.2 \pm 0.9 GeV/$c^2$.Comment: This version contains the most up-to-date top quark mass averag

Assessment and improvement of the Plasmodium yoelii yoelii genome annotation through comparative analysis

Motivation: The sequencing of the Plasmodium yoelii genome, a model rodent malaria parasite, has greatly facilitated research for the development of new drug and vaccine candidates against malaria. Unfortunately, only preliminary gene models were annotated on the partially sequenced genome, mostly by in silico gene prediction, and there has been no major improvement of the annotation since 2002

Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans

Antibody responses to SARS-CoV-2 can be detected in most infected individuals 10–15 d after the onset of COVID-19 symptoms. However, due to the recent emergence of SARS-CoV-2 in the human population, it is not known how long antibody responses will be maintained or whether they will provide protection from reinfection. Using sequential serum samples collected up to 94 d post onset of symptoms (POS) from 65 individuals with real-time quantitative PCR-confirmed SARS-CoV-2 infection, we show seroconversion (immunoglobulin (Ig)M, IgA, IgG) in >95% of cases and neutralizing antibody responses when sampled beyond 8 d POS. We show that the kinetics of the neutralizing antibody response is typical of an acute viral infection, with declining neutralizing antibody titres observed after an initial peak, and that the magnitude of this peak is dependent on disease severity. Although some individuals with high peak infective dose (ID50 > 10,000) maintained neutralizing antibody titres >1,000 at >60 d POS, some with lower peak ID50 had neutralizing antibody titres approaching baseline within the follow-up period. A similar decline in neutralizing antibody titres was observed in a cohort of 31 seropositive healthcare workers. The present study has important implications when considering widespread serological testing and antibody protection against reinfection with SARS-CoV-2, and may suggest that vaccine boosters are required to provide long-lasting protection

Leukemic stem cells activate lineage inappropriate signalling pathways to promote their growth

Acute Myeloid Leukemia (AML) is caused by multiple mutations which dysregulate growth and differentiation of myeloid cells. Cells adopt different gene regulatory networks specific to individual mutations, maintaining a rapidly proliferating blast cell population with fatal consequences for the patient if not treated. The most common treatment option is still chemotherapy which targets such cells. However, patients harbour a population of quiescent leukemic stem cells (LSCs) which can emerge from quiescence to trigger relapse after therapy. The processes that allow such cells to re-grow remain unknown. Here, we examine the well characterised t(8;21) AML sub-type as a model to address this question. Using four primary AML samples and a novel t(8;21) patient-derived xenograft model, we show that t(8;21) LSCs aberrantly activate the VEGF and IL-5 signalling pathways. Both pathways operate within a regulatory circuit consisting of the driver oncoprotein RUNX1::ETO and an AP-1/GATA2 axis allowing LSCs to re-enter the cell cycle while preserving self-renewal capacity

Effect of birthweight measurement quality improvement on low birthweight prevalence in rural Ethiopia.

BACKGROUND: Low birthweight (LBW) (< 2500 g) is a significant determinant of infant morbidity and mortality worldwide. In low-income settings, the quality of birthweight data suffers from measurement and recording errors, inconsistent data reporting systems, and missing data from non-facility births. This paper describes birthweight data quality and the prevalence of LBW before and after implementation of a birthweight quality improvement (QI) initiative in Amhara region, Ethiopia. METHODS: A comparative pre-post study was performed in selected rural health facilities located in West Gojjam and South Gondar zones. At baseline, a retrospective review of delivery records from February to May 2018 was performed in 14 health centers to collect birthweight data. A birthweight QI initiative was introduced in August 2019, which included provision of high-quality digital infant weight scales (precision 5 g), routine calibration, training in birth weighing and data recording, and routine field supervision. After the QI implementation, birthweight data were prospectively collected from late August to early September 2019, and December 2019 to June 2020. Data quality, as measured by heaping (weights at exact multiples of 500 g) and rounding to the nearest 100 g, and the prevalence of LBW were calculated before and after QI implementation. RESULTS: We retrospectively reviewed 1383 delivery records before the QI implementation and prospectively measured 1371 newborn weights after QI implementation. Heaping was most frequently observed at 3000 g and declined from 26% pre-initiative to 6.7% post-initiative. Heaping at 2500 g decreased from 5.4% pre-QI to 2.2% post-QI. The percentage of rounding to the nearest 100 g was reduced from 100% pre-initiative to 36.5% post-initiative. Before the QI initiative, the prevalence of recognized LBW was 2.2% (95% confidence interval [CI]: 1.5-3.1) and after the QI initiative increased to 11.7% (95% CI: 10.1-13.5). CONCLUSIONS: A QI intervention can improve the quality of birthweight measurements, and data measurement quality may substantially affect estimates of LBW prevalence