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"Burke, Thomas"
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Teaching big history
\"Big History is a new field on a grand scale: it tells the story of the universe over time through a diverse range of disciplines that spans cosmology, physics, chemistry, astronomy, geology, evolutionary biology, anthropology, and archaeology, thereby reconciling traditional human history with environmental geography and natural history. Weaving the myriad threads of evidence-based human knowledge into a master narrative that stretches from the beginning of the universe to the present, the Big History framework helps students make sense of their studies in all disciplines by illuminating the structures that underlie the universe and the connections among them. Teaching Big History is a powerful analytic and pedagogical resource, and serves as a comprehensive guide for teaching Big History, as well for sharing ideas about the subject and planning a curriculum around it. Readers are also given helpful advice about the administrative and organizational challenges of instituting a general education program constructed around Big History. The book includes teaching materials, examples, and detailed sample exercises. This book is also an engaging first-hand account of how a group of professors built an entire Big History general education curriculum for first-year students, demonstrating how this thoughtful integration of disciplines exemplifies liberal education at its best and illustrating how teaching and learning this incredible story can be transformative for professors and students alike\"--Provided by publisher.
Book
Dysregulated transcriptional responses to SARS-CoV-2 in the periphery
SARS-CoV-2 infection has been shown to trigger a wide spectrum of immune responses and clinical manifestations in human hosts. Here, we sought to elucidate novel aspects of the host response to SARS-CoV-2 infection through RNA sequencing of peripheral blood samples from 46 subjects with COVID-19 and directly comparing them to subjects with seasonal coronavirus, influenza, bacterial pneumonia, and healthy controls. Early SARS-CoV-2 infection triggers a powerful transcriptomic response in peripheral blood with conserved components that are heavily interferon-driven but also marked by indicators of early B-cell activation and antibody production. Interferon responses during SARS-CoV-2 infection demonstrate unique patterns of dysregulated expression compared to other infectious and healthy states. Heterogeneous activation of coagulation and fibrinolytic pathways are present in early COVID-19, as are IL1 and JAK/STAT signaling pathways, which persist into late disease. Classifiers based on differentially expressed genes accurately distinguished SARS-CoV-2 infection from other acute illnesses (auROC 0.95 [95% CI 0.92–0.98]). The transcriptome in peripheral blood reveals both diverse and conserved components of the immune response in COVID-19 and provides for potential biomarker-based approaches to diagnosis.
The systemic immune features that distinguish COVID-19 from common infections remain incompletely elucidated. Here McClain et al. compare RNA sequencing in peripheral blood between subjects with SARS-CoV-2 and other respiratory infections and demonstrate dysregulated immune responses in COVID-19 with both heterogeneous and conserved components.
Journal Article
Comparative virulence analysis of seven diverse strains of Orientia tsutsugamushi reveals a multifaceted and complex interplay of virulence factors responsible for disease
Orientia tsutsugamushi is an obligate intracellular bacterium found in Leptotrombidium mites that causes the human disease scrub typhus. A distinguishing feature of O. tsutsugamushi is its extensive strain diversity, yet differences in virulence between strains are not well defined nor well understood. We sought to determine the bacterial drivers of pathogenicity by comparing seven strains using murine infections combined with epidemiological human data to rank each strain in terms of relative virulence. Murine cytokine expression data revealed that the two most virulent strains, Ikeda and Kato, induced higher levels of IL-6, IL-10, IFN-γ and MCP-1 than other strains, consistent with increased levels of these cytokines in patients with severe scrub typhus. We sought to identify the mechanistic basis of the observed differential virulence between strains by comparing their genomes, in vitro growth properties and cytokine/chemokine induction in host cells. We found that there was no single gene or gene group that correlated with virulence, and no clear pattern of in vitro growth rate that predicted disease. However, microscopy-based analysis of the intracellular infection cycle revealed that the only fully avirulent strain in our study, TA686, differed from all the virulent strains in its subcellular localisation and expression of its surface protein ScaC. This leads us to a model whereby drivers of pathogenicity in Orientia tsutsugamushi are distributed throughout the genome, likely in the large and varying arsenal of effector proteins encoded by different strains, and that these interact in complex ways to induce differing immune responses and thus differing disease outcomes in mammalian hosts.
Journal Article
From antiquity to ethnography : Keith Thomas, Brian Harrison and Peter Burke
'From Antiquity to Ethnography' is the first time a collection of these interviews is being published as a book. They have been conducted by one of England's leading social anthropologists and historians, Professor Alan Macfarlane. Filmed over a period of several years, the three conversations in this volume are part of the series 'Creative Lives and Works.' These transcriptions form a part a larger set of interviews that cut across various disciplines, from the social sciences and the sciences to the performing and visual arts. The current volume is on three of Britain's foremost social and cultural historians. The study of historical traditions, social mores and practices come alive in these conversations. We also learn about the painstaking nature of notetaking which the subject demands.
BOOK
Reimagining Public Health in the Aftermath of a Pandemic
The coronavirus disease 2019 (COVID-19) pandemic is an unprecedented challenge for society, affecting those already subject to unacceptable health inequalities and resulting in vast economic impacts. The pandemic reminds everyone of the value and necessity of public health. In the context of an era that will be shaped by COVID-19, we outline the coming series of challenges and transitions in public health and the needed actions over the next 5 years to reinvent our public health systems. Multiple limitations in current US and global public health systems have been uncovered by the pandemic, including insufficient preparedness and surveillance capabilities complicated by long-standing and worsening health inequalities and the rapid spread of misinformation that needs to be countered. We foresee 3 phases for public health over the next 5 years: (1) reactive crisis management, (2) efforts to maintain initial gains, and (3) efforts to sustain and enhance progress. A reinvented public health system will depend highly on leadership and political will, rethinking how we categorize and address population-level risk, employing 21st-century data sciences, and applying new communication skills.
Journal Article
Host glutathione is required for Rickettsia parkeri cell division and intracellular survival
Intracellular bacteria rely on eukaryotic metabolites for their fitness and pathogenesis. Yet, the mechanisms of how host metabolites promote bacterial physiology and immune evasion are often unclear. Here, we employed obligate cytosolic
Rickettsia parkeri
, which parasitizes over fifty host metabolites, to investigate bacterial utilization of host glutathione (GSH). We observed that GSH depletion impaired
R. parkeri
intracellular survival. Super-resolution microscopy revealed that GSH depletion caused bacterial chaining in the host cytosol, prohibiting proper actin-based motility and cell-to-cell spread. GSH was especially critical for bacterial survival in primary macrophages, where it enabled
R. parkeri
to evade ubiquitylation and antibacterial autophagy. Cell division and survival defects were restored by supplementing N-acetylcysteine, suggesting that GSH serves as a cysteine source for
R. parkeri
. Together, these data suggest that
Rickettsia
requires GSH as a nutrient source to promote cell division, actin-based motility, evasion of antibacterial autophagy, and intracellular survival. This knowledge contributes to the expanding paradigm that GSH plays diverse roles in the pathogenesis of intracellular bacteria and represents a potential target for host-acting therapeutics.
Rickettsia
species are bacterial pathogens that obligately reside in the host cell cytosol. Here, Sun et al. report that
Rickettsia
use host glutathione as a nutrient source that enables bacterial cell division and innate immune evasion.
Journal Article
Real-world outcomes of first-line pembrolizumab plus pemetrexed-carboplatin for metastatic nonsquamous NSCLC at US oncology practices
Evidence from real-world clinical settings is lacking with regard to first-line immunotherapy plus chemotherapy for the treatment of non-small cell lung cancer (NSCLC). Our aim was to describe outcomes for patients treated with first-line pembrolizumab-combination therapy for metastatic nonsquamous NSCLC in US oncology practices. Using an anonymized, nationwide electronic health record-derived database, we identified patients who initiated pembrolizumab plus pemetrexed-carboplatin in the first-line setting (May 2017 to August 2018) after diagnosis of metastatic nonsquamous NSCLC that tested negative for
EGFR
and
ALK
genomic aberrations. Eligible patients had ECOG performance status of 0–1. An enhanced manual chart review was used to collect outcome information. Time-to-event analyses were performed using the Kaplan–Meier method. Of 283 eligible patients, 168 (59%) were male; median age was 66 years (range 33–84); and the proportions of patients with PD-L1 tumor proportion score (TPS) of ≥ 50%, 1–49%, < 1%, and unknown were 28%, 27%, 28%, and 17%, respectively. At data cutoff on August 31, 2019, median patient follow-up was 20.3 months (range 12–28 months), and median real-world times on treatment (rwToT) with pembrolizumab and pemetrexed were 5.6 (95% CI 4.5–6.4) and 2.8 months (95% CI 2.2–3.5), respectively. Median overall survival (OS) was 16.5 months (95% CI 13.2–20.6); estimated 12-month survival was 59.5% (95% CI 53.3–65.0); rwProgression-free survival was 6.4 months (95% CI 5.4–7.8); and rwTumor response rate (complete or partial response) was 56.5% (95% CI 50.5–62.4). Median OS was 20.6, 16.3, 13.2, and 13.7 months for patient cohorts with PD-L1 TPS ≥ 50%, 1–49%, < 1%, and unknown, respectively. These findings demonstrate the effectiveness of pembrolizumab plus pemetrexed-carboplatin by describing clinical outcomes among patients with metastatic nonsquamous NSCLC who were treated at US oncology practices.
Journal Article