1983 research outputs found
Sort by
Augmenting Infectious Disease Surveillance: Bridging Traditional and Novel Data
No full textExisting data for monitoring infectious diseases have historically been plagued by delayed availability, poor representativity, and inadequate capture of morbidity and mortality. Digital epidemiology, designed to track infectious disease transmission using Big Data not originally conceived for that purpose, furnishes a complementary suite of methods to mitigate some of these challenges. Here we present three analytical approaches that harmonize traditional and digital data to improve the real-time characterization of emerging infectious diseases.
In Chapter 1, we evaluate the utility of multimodal data – namely COVID-19-related searches on Google, Twitter, and UpToDate as well as smart thermometer measurements, smartphone-derived human mobility patterns, and epidemic model predictions – as components of an early warning system for COVID-19’s 2020 transmission within the United States (US). Notably, we find that increases in activity of these digital proxies anticipate increases in confirmed cases and deaths by two to three weeks. We extend this finding by proposing and validating a multiproxy model that yields probabilistic estimates for the timing of a COVID-19 outbreak’s impending growth and decay.
In Chapter 2, we propose an uncertainty quantification approach using serosurveillance and postmortem surveillance data to estimate magnitudes of COVID-19’s underascertainment in African nations, where significant discrepancies between ground truth infections and reported cases have been reported. We observe concordance in the range of COVID-19 reporting rate estimates – from one in two to one in thousands of infections – for the aforementioned data sources, suggesting a key reason for low cumulative incidence in Africa has been significant underdetection and underreporting. We also explore the potential for Google and Twitter data to recapitulate local-in-time trends within national epidemic curves and, in some instances, serve as leading indicators of COVID-19 outbreaks.
Finally, in Chapter 3, we implement several classification models to investigate the relative contributions of ascertainment, importation, and transmission to spatiotemporal patterns of infectious disease seeding and subsequent spread, using the 2022 US mpox epidemic as a case study. We find that real-time data sources (i.e., air travel and Google) can predict the evolution of viral spread. In addition, through a post hoc analysis, we find that state-specific timings of index mpox cases mirror chronologies observed in non-mpox (i.e., COVID-19 and H1N1) pandemics and, therefore, that historical data sources may prove equally useful in ascertaining where and when an epidemic is liable to spread
“Likkle but Tallawah: Evolution and Phylogeography of a Caribbean Adaptive Radiation, the Anoline Lizards of Jamaica”
No full textUnderstanding diversification is a major goal of evolutionary biology, and the study of adaptive radiations has been a key part of this pursuit – especially replicate adaptive radiations, the natural experiments that help us illuminate the course of evolution. The four replicate radiations of Greater Antillean Anolis lizards have become a classic example of the power of such natural experiments. Yet, despite all we know about these four faunas, much remains unknown about the series of events that gave rise to each of these assemblages.
In Chapter 1, I inferred brand new nuclear and mitochondrial phylogenies for the Jamaican Anolis to investigate the relationships among species and to test previously-proposed hypotheses sug-gesting differences between the two phylogenies. Even though both tree topologies received strong support by traditional metrics, I found discordance between the nuclear and mitochondrial phylogenies at almost every major node, along with low concordance between the underlying data and the consensus topologies, suggesting that the evolutionary history of the Jamaican anoles proceeded in a not-strictly-treelike fashion. These findings also hold implications for processes operating early in the history of the Jamaican adaptative radiation, including putative mitochondrial capture. Moreover, with higher sample sizes and more widespread geographic sampling relative to previous studies, I discovered new relationships in both trees. I closed this species-level analysis by describing broad scale patterns of genetic variation across the clade, revealing that some species harbor much higher diversity than others, including geographically-structured variation.
In Chapter 2, I studied patterns of intraspecific diversity suggested by the results of the first chapter, and searched for evidence of independently-evolving lineages within each of Jamaica’s five widespread anole species. Here, I uncovered evidence for deep, spatially-circumscribed structuring of genetic variation in two species, diffuse clustering in a third, and shallow variation in the last two. After characterizing intraspecific genetic clusters across the landscape, I examined patterns of genetic exchange between clusters to test whether intraspecific variation follows an isolation-by-distance (IBD) pattern, where major barriers to dispersal occur, and which processes underlie shared variation among lineages. Results of these analyses showed that species vary in their fit to an IBD model, and the two species with deep structuring also exhibited clear evidence of barriers to dispersal along the edges of intraspecific lineage ranges. In the three species with evident clustering, I found evidence for non-ILS processes which pointed to major areas of elevated genetic exchange between lineages – and to areas where such exchange was depressed. I used the patterns discovered in the above analyses to compare the spatial distribution of lineages between co-distributed species, and to test whether mor-phological variation differs along the same lines as genetic variation. Taken together, these results also made it possible to test subspecies classifications in two of Jamaica’s anole species, proposed over half a century ago. My findings indicated strong evidence for subspecies hypothesis in one species, and mixed evidence for those of the second.
In Chapter 3, I used phylogenetic network inference to test the hypothesis of reticulate evolution suggested by the results in Chapter 1. Complementing the finding of high discordance in the bifurcating tree (Chapter 1), I uncovered evidence in the nuclear dataset consistent with ancient hybridization: the first between the two lineages involved in putative mitochondrial capture, the second in the history of the radiation’s only remote species. To put these events in context, and to better understand the past processes leading to presently-observed patterns, I assembled a new geological timeline of Jamaica, inferred a time-calibrated tree, and performed model-based biogeographic history estimation. The above-water geology of Jamaica over the past ~20 million years involves the piecemeal assembly of the island from three major blocks. Across this shifting landscape, I inferred a mid-Miocene origin for the Jamaican anole clade in the most topographically-complex block of the three, which also emerged from the Caribbean Sea earliest: the Blue Mountain Block in the east. Biogeographic history estimation supported this finding and revealed two pulses of concurrent diversification in three species groups: first, late Miocene splits between lineages along the Blue Mountains’ growing elevational gradient, and second, Pliocene divergences between lowland lineages on either side of the mountains.
Taken together, these results shed light on the potential processes underlying the diversification of a classic Caribbean adaptive radiation and illuminate the patterns we see in the present day
Theosis 2023—2024
No full textTHE USE OF THE PLOTINIAN SOUL TODAY
Anna Corrias
MYSTERIES ABIDE
A conversation on consciousness with Michael Pollan
THE BODY IN YORUBA TRADITION
Ayodeji Oggunaike
WATER WORLDS
Charles Stang
WAKING FROM THE FLESH DREAM
An interview with Alex and Allyson Grey
MAGIC AND TIME: LESSONS FROM THE TAROT
Giovanna ParmigianiVersion of Recor
Principal Investigator Responsibility for Flagging Research with Dual-Use or Pandemic Risk
No full textThe new United States Government Policy for Oversight of Dual-Use Research of Concern and Pathogens with Enhanced Pandemic Potential places primary responsibility on the proposing principal investigator to flag potential need for special review. This approach may carry significant risks, given that investigators have incentives to downplay the types of risks the policy aims to address, compounded by substantial opposition to the policy from many virologists. However, this commentary argues that such an approach is much more consistent with proven models of research oversight for protecting human subjects and animals and may be essential in the long run. It identifies the need for several independent but potentially mutually reinforcing preconditions for success — which will require creativity and investment not fully specified in the regulations: researcher training on dual-use and population-level biosafety risks, effective institutional-level support for and scrutiny of investigator evaluation, cultural change, checks and balances, and speedy evaluation of low-risk research
Profiling Essential Functions and Translation Control via Bacterial Optical Pooled Screening
No full textEarly cytology established the principle that cells of a given type, from a particular organism, are highly stereotyped in terms of both form and composition. The replicative process, therefore, is one characterized by precision, resulting in an orderly partition of contents and maintenance of subcellular organization. Single-celled model organisms represent an experimentally tractable prism through which replication can be understood. Escherichia coli stands out as the best-studied model for rapidly growing bacteria, which organize division, DNA replication and protein synthesis at the fastest rates known in nature. Moreover, dysfunction in proliferation is increasingly associated with antibiotic persistence and the acquisition of resistance, making a fundamental understanding of growth a health priority. Our ability to disentangle the myriad components of growth largely depends on timelapse microscopy, especially multigenerational imaging enabled by microfluidic cultivation. On the other hand, high-throughput genetic perturbation techniques like TNseq and CRISPRi are powerful tools to screen for the molecular basis of phenotypes. Few methods combine these techniques to perform systematic genetic screening of imaging phenotypes.
In this dissertation, I describe my development of multiplex timelapse imaging of E. coli in a microfluidic device and its application to measure cell cycle defects in a CRISPRi library targeting essential genes. In chapter 1, I describe MARLIN, a novel technique for bacterial optical pooled screening (OPS) in the mother machine microfluidic device. I show that MARLIN achieves multiplexing of 100k member genetic libraries, while measuring tens of millions of cell cycles per experiment. In chapter 2, I detail the use of MARLIN to collect imaging data for a ~30k sgRNA pooled CRISPRi library targeting all essential genes in E. coli. I demonstrate that the morphological and growth phenotypes of these knockdowns are reproducible and consistent with known gene function. In chapter 3, I use these data to quantify growth-size scaling among different translation perturbations. Based on these data, I demonstrate that slow translation elongation leads to a SpoT-dependent reduction in the size regulator (p)ppGpp. I use modeling to show that this mechanism accounts for many features of previously proposed E. coli growth laws. In chapter 4, I perform clustering analysis on our MARLIN-CRISPRi data to annotate genes of unknown/unrelated function as involved in division or replication, and validate a role for RNase E in promoting replication initiation
Expanding Heterogeneous Factors Deemed Important: Revisiting the Impact of Microfinance on Businesses
No full textThis paper revisits the experiment conducted by Angelucci et al. (2015) in which they ran a clustered randomized trial in Sonora, Mexico from 2009 to 2012 to estimate the impacts at the community level of offering microcredit to low-income women. The authors found that access to microcredit only marginally improved women’s lives. I analyze the dataset for heterogeneity and find that microcredit has a large impact on business growth among participants who owned a business before the experiment began and participants who lived in a rural area, which had higher credit constraints than urban areas. Among those who lived in a rural area, microcredit had large business returns for more educated people and women with no children. Since education and children are understudied heterogeneous factors, I analyze three more datasets, two from India and one from Ghana, to determine if my results in Mexico are portable to other settings. My results in these other settings show that education also leads to a higher impact from microfinance but the effect of children is influenced by context
A Shīʿī Scholar Between Safavid Iran and Mughal India: The Life, Works, and Thought of Nūrullāh Shūshtarī (956–1019/1550–1610)
No full textThis dissertation seeks to reconstruct the life, contextualize the works, and interpret the thought of Nūrullāh Shūshtarī (956–1019/1550–1610), a Shīʿī scholar who gained prominence during the late tenth/sixteenth and early eleventh/seventeenth centuries within the interconnected intellectual and religious histories of Safavid Iran and Mughal India. At the heart of my argument, I posit that Shūshtarī, drawing upon his familial lineage, educational pedigree, and vocational stature, sought to reshape the prevailing perceptions of his contemporaries of the pre-Safavid Shīʿī history. Concurrently, he ardently championed its doctrines and rituals in the face of critiques from his Sunni contemporaries.
The dissertation unfolds in two parts. In the first part, I chronologically follow Shūshtarī’s journey through four cities: Shushtar and Mashhad in Iran, and Lahore and Agra in India, each representing different phases of his life and career. The second part aims to craft a portrait of his selected scholarly contributions and ambitions, most prominently mirrored in his seminal work, Majālis al-muʾminīn, a ground-breaking historiographical endeavor, along with two of his writings dedicated to refuting Sunni criticism, namely, Maṣāʾib al-Nawāṣib and al-Ṣawārim al-muhriqa. I also seek to show that Shūshtarī’s intellectual endeavors unfolded within the evolving dynamics of Sunni-Shīʿī religious debates and the omnipresent Ottoman-Safavid rivalry during this pivotal era.
Utilizing an interdisciplinary framework, this dissertation integrates perspectives from both historical and religious studies to present a nuanced understanding of its subject matter. It seeks to serve as a bridge connecting Islamic intellectual and social history, thereby enriching the academic discourse on Sunni-Shīʿī relationships during a particularly transformative phase in the history of early modern Islamic societies. A notable aspect of this research is its use of primary textual sources across several languages, including Arabic, Persian, Urdu, and, to a certain degree, Turkish. Consequently, the dissertation asserts that an in-depth exploration of Shūshtarī’s life and contributions demands an interdisciplinary methodology, enriched by the employment of multilingual resources.
While the dissertation is a detailed exploration of Shūshtarī’s life, contributions, and the challenges he faced, it also positions him as a prism through which one can view the broader socio-religious and political landscapes of Safavid Iran, Mughal India, and the adjoining Ottoman territories. Through Shūshtarī’s narrative, the study captures a vivid panorama of intellectual exchanges, religious debates, and the intricate dance of authority and scholarship during a transformative period in Islamic history.
Yet, it bears emphasizing that this dissertation, despite its comprehensive purview, unveils only select aspects of Shūshtarī’s multifaceted character, leaving substantial terrains for subsequent scholarly exploration
The Ethics of Wonder: The Persian Qazvini Corpus (1300–1632)
No full textMy dissertation is a long-view analysis of Zakariya ibn Muhammad al-Qazvini’s Persian
ʿAjāʾib al-makhlūqāt wa gharāʾib al-mawjūdāt, comprising over thirty manuscripts produced in Iran
from 1300 to 1632. Through four case studies, it traces the scantly studied corpus from its
inception as an unillustrated text to its emergence as the most popular illustrated version of
Qazvini’s cosmography in the Islamic world. I argue that the Persian ʿAjāʾib, which contains
twenty-nine chapters not found in any Arabic version of Qazvini’s text, expanded possibilities of
ethical cultivation for its readers and centered human agency in its cosmic system.
The first chapter examines the Persian text as a work written by Qazvini himself,
positioning it as an equal counterpart to the Arabic version and situates the earliest extant codex
within the context of its creation in Ilkhanid Iran. Interpreting the Persian ʿAjāʾib text as a
complete, intentionally constructed cosmography enables a different reading of Qazvini and
prompts a reconsideration of his oeuvre. Chapter Two focuses on the dissemination and
popularity of the Persian ʿAjāʾib corpus as it becomes an illustrated book predominately made in
the commercial manuscript capital of Turkmen Shiraz from 1470–1490. Produced for a
“commercial market,” these manuscripts offer insights into the entangled interests and
imaginations of artistic, intellectual, and administrative communities of the late fifteenth century.
In my third chapter, I explore how the depiction of wonder and rarity in the early Safavid period
developed alongside contemporary aesthetic theories to produce pedagogical tools for readers. In
a 1545 illustrated manuscript, visual training exercises are derived from Neoplatonic philosophy
and Sufi concepts on the senses and soul transformation, as described in Qazvini’s text, to
provide a method of intellectual and moral education. The final chapter looks at a later Safavid
manuscript created in 1632. I argue that its artist(s) endeavored to revitalize the knowledge found
in the Persian ʿAjāʾib by drawing on contemporary textual and visual references. Through the
incorporation of tropes from single-page paintings, other illustrated literary traditions, and new
foreign media, Qazvini’s cosmography fostered novel forms of cultivation within a rapidly
expanding global environment
Compressed Air Assisted Bicycle: AirBike
No full textElectric bicycles are a popular transportation and commuting choice for urban environments. Unfortunately, the raw materials needed to produce the batteries powering these bikes are environmentally destructive to extract and unfairly exploit the communities in which they are mined. This project designed and built an alternative to the e-bike, without the environmental and humanitarian downsides, by storing energy in the form of compressed air. This novel design stores air inside the frame tubes of the bicycle, which is released into the air motor to produce forward motion when the cyclist presses a lever. The bike also has a regenerative braking system that recaptures energy through an onboard compressor, which pressurizes the air tank for later use. The tank can be refilled manually using this onboard compressor, or in a matter of seconds using a shop compressor. This first prototype is capable of providing ~50% of the required power to travel at 20mph for a duration of ~26 seconds. The report details the requisite next steps in producing a commercially viable product by presenting methods for weight reduction and increased assist duration. With further refinement, this product could prove to be the future of clean, efficient, and ethical assisted bicycle transportation
Evaluating Immunological Treatment and Prevention Strategies Using Single-Cell Genomics
No full textSingle cell genomics have transformed our ability to profile human biology in depth and breadth. In chapter 2, we use scRNA-seq to profile pediatric inflammatory bowel disease, delineating distinct mechanisms of inflammation in each of the disease’s major subtypes. Using information regarding study participants’ clinical course, we characterize features associated with biologic treatment use and nonresponse. Here, pairing gene expression measurements with T cell receptor sequencing allows us to identify novel T cell receptor phenotypes that may be responsible for incompletely understood differences in immunological presentation and differences in response to first-line treatment in inflammatory bowel disease. In chapter 3, we use scRNA-seq to identify the effects of a novel tuberculosis vaccine strategy. This effort contributes to the goal of identifying correlates of protection against TB infection, a longstanding obstacle in the development of effective TB vaccines. Overall, this body of work contributes to our biological understanding of immunological disease and response to immunomodulatory treatment in the setting of immunosuppressive biologics and immune-stimulating vaccines.Medical SciencesMedical Science