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From micro to macro: using a granular lens to analyze global complex systems
Get PDFIn this thesis, I take a complex systems perspective on the economy with the aim of tying granular activity and social behaviours among individuals to global economic and political phenomena. The thesis leverages tools from network science, machine learning, and dynamical systems to extract individual activity from noisy real-world data and subsequently model the macro-scale consequences of individual decisions.Several chapters of the thesis focus on social media activity and the financial system. I focus on the online investor discussion forum called WallStreetBets (WSB). The thesis first presents a data-driven analysis of WSB: initial experiments decompose the forum using a large language topic model and network tools. The findings show that assets that are closely linked within online user and topic networks are also likely to be highly correlated in their returns – this analysis offers insight into economic themes and investor preferences which drive asset co-movements.The following chapter delves into the mechanisms shaping individual perspectives. I use two different instrumental variable approaches to document that user sentiments about assets’ future performances are motivated, in part, by peers as well as by recent asset performance. I subsequently develop a theoretical case for how individual sentiment dynamics can drive changes in asset prices. I present several mathematical models, including a model with market-clearing, a dynamical systems model, and a model for bubble formation in the financial markets, which all demonstrate how ‘social investing’ can have market impact.The thesis then uses a mixture of mathematical and econometric tools to empirically estimates the effect of WSB activity on asset prices in several ways. I document: higher retail trader demand following WSB discussions, the price impact of idiosyncratic investor sentiment in viral content, and the significant activity of WSB users around bubble-like stock price run-ups. The thesis concludes that the unique features of social media, such as its scale and ability to facilitate the spread of information, make it an important market driver.After making a strong case for the importance of human behaviour within the economy, I strive to better understand evolving real-world network dynamics – the next section of the thesis presents both a new dataset and novel temporal clustering technique targeted towards better understanding the dynamics of turbulent networks. The thesis analyzes the evolution of several social and political movements using data from online Reddit forums (r/BlackLivesMatter, r/Brexit, r/climate, r/democrats, r/Republican) and the development of international relations through studying international events data.The key contributions of the thesis are analytical (developing several models to understand the macro impact of individual behaviour), empirical (extracting signal from noisy social-media data and leveraging network / causal frameworks to understand effects) and methodological (extending the network and data science toolkit to drive my analysis). The mathematical analysis within this thesis allows me to make a strong case for how social media activity has evolved over time and impacted society, as well as providing additional tools, datasets and algorithms to facilitate future research
Characterizing the Conformational Dynamics of the Ribose Transporter B Protein in Escherichia coli: Enhanced Sampling via Multiple Force Fields
Get PDFWe present a molecular dynamics simulation study of the E. coli ribose transporter protein B (RbsB), a conformationally labile protein found in the periplasm of the bacterium. The ribose transporter exhibits characteristics of both traditional type I and type II import systems. In our study, we observed the full conformational transition of the periplasmic binding protein RbsB for the first time. Our study revealed that in most scenarios (all but one) the conformational changes preceded the departure of ribose from the binding site, a process likely influenced by specific interactions at the binding interface. Indeed, our analyses of ribose binding revealed that specific salt bridges played a crucial role in stabilizing the closed conformation of RbsB. Our simulations also provided further evidence for a putative structural water molecule, which had also been observed from X-ray data. Crucially, our simulations were run with three different force fields: CHARMM36(m), AMBER ff19SB, and CHARMM36(m) with SIRAH coarse-grained water. This strategy enabled us to observe all of the conformational states that had been identified in structural studies. Thus, we argue that the subtle biases of individual force fields can be utilized to enhance conformational sampling
“The most stress comes from witnessing the abuse of children” — challenges faced by research assistants in community-based research in Mtwara, Tanzania
Get PDFBackground: Field workers or research assistants (RAs) are commonly employed within community-based trials. Training provided for RAs, however, is often limited to the technical elements of research, with little-to-no training to help them navigate the ethical challenges they may encounter while working in community-based settings. The main objective of this study was to explore the challenges faced by RAs working as part of a novel housing initiative, to describe the impact these challenges had on their work and wellbeing, and to outline approaches taken by RAs in facing these challenges. Methods: A qualitative interview guide was piloted and refined for key informant interviews (KIIs) with research assistants (RAs) working on the Star Homes intervention in Mtwara, southern Tanzania. A total of 16 KIIs were conducted with all available RAs. These data were supplemented with 47 documents that comprised 31 case studies and 16 observation notes. The interviews were conducted in Kiswahili, audio-recorded, transcribed verbatim, and translated into English. All transcripts underwent line-by-line coding in NVivo and were analysed using thematic analysis. Results: Principal challenges included difficulties related to RAs’ roles and responsibilities, including having to travel long distances for data collection. Most prominent, however, were ethical challenges, including witnessing the suffering of study participants. RAs unanimously expressed being most distressed by encountering children who were neglected or subjected to abuse, including several cases of child sexual abuse (CSA), as part of their work. Conclusions: Clear engagement strategies with communities and authorities are essential to support RAs in reporting and follow-up. Training and resources are urgently needed to prepare field staff, mitigate moral distress, and protect research participants from harmful behaviours
Peptidic Catalysts Conformationally Tuned for Fluoride Binding and Delivery
Get PDFKnowledge on how fluoride interacts with peptides is currently limited to in silico studies. Here, we report an experimental investigation on the ability of peptidic scaffolds to bind fluoride using TBAF·3H2O or CsF. For CsF, in-depth NMR and GOAT-DFT studies shed light on peptides acting as chelators to both fluoride and cesium ions. This finding led to the development of the first peptide-catalyzed fluorination reactions. These advances open a new avenue to investigate fluorination chemistry with peptide-based catalysts that are considered as the possible ancestors to enzymes
The Rogan-Gladen estimator for outcome misclassification
No full textOutcome measurement error is common in epidemiologic studies and often leads to bias in estimates of prevalences, risks, and their contrasts. The Rogan-Gladen estimator (1) provides an elegant solution to account for misclassification of a binary outcome when estimating risk or prevalence, which, in turn, can be used to produce valid estimates of contrasts in these measures. Here, we review the Rogan-Gladen estimator, provide intuition for its properties, and briefly illustrate how it can be combined with approaches to account for other sources of bias
Human steatohepatitis and the effects of HMGB1
No full textMetabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease, affecting nearly 40% of the global population, and its prevalence continues to rise. MASLD ranges from simple steatosis to the more advanced stages of metabolic dysfunction-associated steatohepatitis (MASH) and cirrhosis. Individuals with cirrhosis are at risk of developing hepatocellular carcinoma and death. Although recent FDA approvals of resmetirom and semaglutide establish MASH as a druggable disease, their efficacy remains modest and comparable to lifestyle interventions, underscoring the need for improvement.Therapeutic development has been hindered by an incomplete understanding of the mechanisms driving MASLD, compounded by the poor predictive value of animal models. I addressed these challenges by analysing patient-derived multi-omic data, which revealed mitochondrial bioenergetic deficits as a hallmark of advanced disease. I then developed 3 human in vitro models of MASH: fatty acid-challenged stem cell-derived hepatocyte-like cells, fatty acid-challenged primary hepatocytes isolated from healthy tissue and primary hepatocytes from steatotic livers with inherent mitochondrial dysfunction.Using these systems, I investigated the effects of an engineered non-oxidisable construct (double Box B, dBB) of High Mobility Group Box 1, which was previously shown to promote repair of skeletal muscle. dBB improved hepatocellular mitochondrial function and viability following fatty acid challenge. Although current therapeutics have shown clinical benefit in human MASH, direct effects on mitochondria remain to be validated. Together, my findings highlight the potential for upregulating mitochondrial function in the more advanced stages of MASLD
Dataset for Predictors of in-hospital mortality among paediatric snakebite patients in northeastern Nigeria: a survival analysis study
No full textSubset of full data (678 out of 723 paediatric patients) used for survival analyses in Uppal et al. "Predictors of In-Hospital Mortality Among Paediatric Snakebite Patients in Northeastern Nigeria: A Survival Analysis Study
Safety and personalised care in maternity services of England for women whose preferred language is not English: a critical race theory analysis of interpreter experiences
Get PDFIntroduction: Effective communication is central to safe, ethical maternity care. Women with cross-cultural communication needs are more likely to experience intersecting disadvantage, with poor maternal and infant outcomes. A professionally trained interpreter (PTI) can raise the quality of clinical care for patients to approach or equal that for patients without cross cultural communication needs. The need to improve interpreter services has been recognised at the strategic level of the NHS to improve safety and personalised care. However, evidence for how to achieve this is limited from the UK context.Methods: We explored the experiences of PTIs working in maternity services in England using qualitative interviews. We analysed the data thematically, informed by Critical Race Theory, which argues that inequality is deeply embedded in policy, law and institutional structures and practices. We discussed interim findings with our lived experience group.Results: We interviewed 28 interpreters with a range of qualifications who worked for language agencies or in-house NHS interpreting services. Our analysis constructed three themes: The ‘shady’ agency; ‘You can get anyone and you don’t know how experienced they are’; ‘you are never part of a team’. We found that institutional practices and outsourcing marginalises interpreters, compromising worker wellbeing and patient safety.Conclusion: To ensure patient safety, it is essential for the NHS to recognise the professional status of medical interpreters and integrate PTIs into the core clinical team. This will require investment in standardised interpreter training, access to supervision, and career development. Embedding interpreters in NHS safety culture is essential for equitable and effective care
Decoupled diversity and disparity after faunistic turnover in caviomorph rodents
Get PDFCaviomorph rodents diversified widely in the Americas. Within this group, the sister clades Octodontoidea (spiny rats and allies) and Chinchilloidea (chinchillas and allies) illustrate strikingly imbalanced evolution, with 195 extant species in the former and only six in the latter. Fossil evidence, however, documents greater past diversity and disparity in Chinchilloidea, including the largest known rodents. Here, we integrate data from extant and extinct species to investigate how evolutionary dynamics shaped these contrasting trajectories. Using a phylogenetic framework, we reconstructed patterns of body mass and craniodental evolution. The ancestral body mass was small, but Chinchilloidea expanded into a broader size range, showing significantly higher rates of body mass evolution than Octodontoidea. Subsequent Neogene and Quaternary extinctions erased much of this variation, reversing a ~30 million-year trend of greater body mass disparity. Craniodental disparity, however, followed a different trajectory: initially higher in Chinchilloidea, it later became greater in Octodontoidea after the Miocene. Importantly, craniodental disparity remained relatively stable in both clades despite major diversification and extinction events. These findings highlight the decoupling of taxonomic diversity, body mass and craniodental morphology, underscoring the complexity of evolutionary dynamics even for sister clades that evolved on the same continent
A python’s embrace? Insurance and the global clinical trial
Get PDFBackground: Regulatory barriers present significant challenges to clinical trial approval during both “peacetime” and pandemics, particularly for multi-country clinical trials sponsored by academic institutions and low- and middle-income countries (LMICs). While such barriers have been depicted as a “python’s embrace”, analyses of trial approval efficiency and ethical frameworks have largely overlooked clinical trial insurance. Methods: I interrogate the evolution of clinical trial indemnification mechanisms, rationales, and operationalisation over the past fifty years through a structured literature review. I then consider the procedural barriers faced by academic institutions conducting multi-country clinical research during the COVID-19 pandemic using a case study of the University of Oxford’s “COPCOV” trial, which was led by the Mahidol Oxford Tropical Medicine Research Unit in Bangkok, Thailand. This includes thematic analysis of more than 65 semi-structured interviews with trial stakeholders and analysis of insurance documents from the Trial Master File and hundreds of stakeholder emails. Results: Supplementary reinsurance policies cost over £110,000 during the COPCOV trial, delayed trial approvals by up to nine months in some countries, and were largely justified by sponsors based on concerns about reputational damage. I argue that risk frameworks grounded in financial risk management and the commercial sector have expanded within academic institutions and, when coupled with an expansion of national requirements for “local paper” insurance policies, create serious barriers to initiating trial sites in many LMICs. Conclusions: Two potential reform pathways, which are grounded in procedural or systemic reforms and should be led by LMIC-based policymakers, could help to de-barrier clinical trial insurance procedures and ensure that evidence of efficacious (and affordable) countermeasures are available during future global health emergencies