22689 research outputs found
Sort by
Evaluation of a low-cost sensor used to examine CO2 urban gradients
No full textLow-cost sensor networks can be used to examine the heterogeneity of greenhouse gas and air pollutant concentrations and to identify potential differences in exposure between populations. CO2 emissions are of particular interest as a known contributor to climate change and as a potential cause of short-term cognitive and physiological dysfunction, especially in urban areas, where concentrations are higher. We tested field calibration methods for low-cost CO2 sensors in a stationary ambient multipollutant monitoring network in Baltimore, MD using collocated reference CO2 data. We found that random forest machine learning models markedly outperformed multiple linear regression models. A random forest model with raw sensor data, barometric pressure, wind speed, and month as variables performed the best out of the models evaluated (R^2 = 0.47–0.61 for the validation dataset, with 89–97% of points falling within 5% of the reference). We applied the model to all the sensors in the network, using a novel method that selected periods with limited spatial variability to train the model at locations that were not collocated with a reference. Interpolated CO2 values were mapped to evaluate variability in Baltimore City. While our initial analysis found no strong associations between ground-level CO2 and several census-derived socioeconomic factors, more detailed investigation may be warranted
Dynamic and Static Autoregulation During Cerebral Reperfusion Following Cardiac Arrest
No full textCardiac arrest (CA) is a public health crisis in the United States. CA results in a severely hypoxic insult to the brain, damaging it and causing devastating neurological outcomes even after successful resuscitation. This thesis aims to explore the underlying mechanisms of cerebrovascular autoregulation and vascular injury in the aftermath of CA, as well as to review current methods for assessing cerebral blood flow and oxygenation.
The first chapter provides an in-depth examination of cerebrovascular autoregulation, a crucial physiological mechanism that maintains stable blood flow to the brain despite fluctuations in systemic blood pressure. The discussion then shifts to the vascular injury that ensues following CA, with a focus on the disruption of autoregulation.
In the next two chapters, the thesis delves into the methods employed to measure cerebral blood flow and cerebral oxygenation, including optical imaging, ionizing radiation-based imaging, ultrasound imaging, and so on. A comprehensive analysis of the advantages and limitations of these approaches is presented, along with the potential implications of their findings for patient prognosis and targeted therapeutic interventions. By exploring the complex interplay between cerebrovascular autoregulation, vascular injury, and brain function after CA, this thesis seeks to contribute to the growing body of knowledge that can ultimately improve patient outcomes and reduce the burden of this public health crisis.
In the fourth chapter, the focus is on employing cerebral vascular resistance (CVR)-based approaches to investigate impaired vascular injury and its association with cerebrovascular autoregulation. Our research establishes a foundation for quantifying post-CA CVR dysregulation and elucidating its connection with autoregulation. The derived metrics hold the potential to enhance clinicians' understanding of the complex aspects of brain injury following CA and aid in refining clinical interventions that maximize neurological recovery for CA survivors.
Nonetheless, during CA and following resuscitation, the severe ischemic-hypoxic and reperfusion injury not only leads to cerebrovascular damage but also impairs the nervous and cardiovascular systems. Consequently, a multimodal quantification system encompassing autoregulation, EEG, and ECG is essential for establishing comprehensive monitoring of resuscitated CA patients. This approach will aid in guiding the optimization of clinical management and interventions in an early phase, ultimately enhancing patient outcomes
Vaccine Policies and Programs for Reaching Older Adults in the United States: Considerations for Vaccine Access and Ethics
No full textOlder adults constitute a highly heterogeneous yet very important group for vaccination in the U.S. because they are at higher baseline risk for infectious diseases. A number of vaccines are available to prevent serious sequelae from infectious diseases and are specifically recommended for adults 65+. These vaccines include the shingles vaccine (recommended for adults 50+); pneumococcal vaccines; an array of different options for the influenza vaccine (including high-dose and adjuvanted products to stimulate a stronger immune response for older adults); and the Covid-19 vaccines. Different policy and programmatic strategies have been employed to reach older adults in the U.S. with vaccines, and measurements of progress on public health vaccination goals – including ethics goals derived from moral principles that are tenets of promoting public health – are critical for evaluating success of these strategies. This dissertation looks at questions of access to different vaccines for older adults through two different pharmacy-based approaches and critically analyzes how well current vaccine data pipelines and repositories are allowing measurement of ethically important public health goals of vaccination for this population
SHAPING THE IMF’S CLIMATE AGENDA: THE INTERPLAY OF STAFF EXPERTISE, MEMBER STATE PRIORITIES, AND LEADERSHIP INFLUENCES
No full textThis study investigates the factors influencing the International Monetary Fund's (IMF) climate change agenda. The study identifies three key factors influencing the IMF's climate policy: first, the intellectual contributions of IMF staff; second, the influence of member states; and third, the vision and priorities of the Fund's Managing Director.
The research employs a diverse dataset comprising IMF staff ideational documents, operational Article IV country reports, and policy documents from member states (specifically the Vulnerable Twenty (V20) Group of Ministers of Finance of the Climate Vulnerable Forum and the United States), as well as analyzing the speeches of the two most recent Managing Directors Christine Lagarde and Kristalina Georgieva. Concept frequency analysis is used to quantify the emphasis on climate-related concepts in IMF documents. The Climate Focus Index (CFI) and Adaptation-Mitigation Index (AMI) are introduced as metrics to assess the IMF's climate agenda.
The findings indicate a consistent upward trend in the IMF's focus on climate change across various indicators. This upward trend is driven by factors such as the growing body of climate science, the urgency of the climate crisis, and the IMF leadership's background in environmental economics. The preferred solutions proposed by the IMF lean predominantly towards mitigation strategies, with some variations in documents related to island nations and V20 countries. In conclusion, the study reveals that the IMF's climate agenda is shaped by the intellectual contributions of its staff, the influence of member states, and the vision and priorities of its leadership. While the United States can exert influence as a major shareholder, other factors, including staff expertise and global consensus, also play a significant role in shaping the Fund's climate policies. The research offers several policy recommendations to enhance the IMF's climate response, including increasing representation, fostering knowledge sharing, and addressing the balance between adaptation and mitigation. Implementing these suggestions can lead to a more comprehensive and equitable approach to address the challenges of climate change
SPOROZOITE METAMORPHOSIS IN THE LIVER: INVESTIGATION OF THE ROLE OF PLASMODIUM GRASP AND VPS4 IN MICRONEME ELIMINATION
No full textThe Plasmodium metamorphosis during liver stage requires morphologic and metabolic changes including clearance of micronemes, previously required for hepatocyte penetration. Experimental evidence indicates that Plasmodium utilizes machinery associated with unconventional protein secretion (UPS) pathway for micronemal clearance from liver stage. The UPS-related pathway is involved in sequestering and eliminating damaged organelles in double-membrane vesicles from endoplasmic reticulum to plasma membrane, bypassing the Golgi, instead requiring autophagy related genes 8 (ATG8), Golgi reassembly and stacking protein (GRASP) and vacuolar protein sorting-associated protein 4 (VPS4), in a process called exophagy. In exophagy, GRASP has been identified to localize autophagosomes or multivesicular bodies (MVB) and mediate their tethering to the plasma membrane for cargo expulsion. To investigate the role of GRASP during liver stage development and autophagy, the laboratory engineered a Plasmodium mutant, named PbGRASP-KO (Plasmodium berghei GRASP knockout). Analysis of the parasite size between the PbGRASP-KO and WT, as the sporozoite develops into its exoerythrocytic forms (EEF), suggest that GRASP may be involved in early-mid stage schizogony however is dispensable for liver stage development as seen through successful schizogony of PbGRASP-KO with mid-stage developmental defects. From quantification of TRAP signal in IFA and its normalization to EEF volume, we observe that GRASP is non-essential for microneme elimination despite a smaller EEF at 22h p.i. Interestingly, previous investigations reveal colocalization of GRASP with ATG8 and VPS4, proteins essential for microneme compartmentalization and MVB biogenesis (hypothesized), respectively. To understand the association of GRASP with exophagy machinery, we tried to develop a PbGRASP-specific antibody in mice through intraperitoneal immunization. The antibody was generated against a synthetic multi-epitope protein of PbGRASP, designed, generated, and purified in laboratory. Western blot and immunofluorescence analysis of the antibody activity compared between WT and PbGRASP-KO suggests that these antibodies detect non-specific proteins rather than PbGRASP as seen from lack of clear and distinct puncta of PbGRASP in WT. In addition, we also tried to clone another Plasmodium mutant, named PbVPS4-KO (Plasmodium berghei VPS4 knockout) to investigate the role of VPS4 in Plasmodium development, however to no avail. We conclude that GRASP may have a role in Plasmodium mid-stage development, but further analysis is required for understanding its involvement in microneme clearance
Embedding Health Equity into the Implementation of the Hospital Incident Command System During the COVID-19 Pandemic
No full textBackground: Disasters often have inequitable impacts on society, amplifying existing health inequities. Hospitals use the Hospital Incident Command System (HICS) to coordinate their disaster response, but equity is not included in its structure or implementation. The HICS was activated across the United States during the COVID-19 pandemic, which led to several novel strategies to incorporate equity. This dissertation aims to synthesize strategies to embed health equity into the HICS, examine their feasibility in various environments, and evaluate implementation influences to inform spread.
Methods: The literature was reviewed to identify how others have embedded equity into their HICS, and findings were categorized using thematic analysis. To understand the approaches used and their prevalence, a representative sample of Massachusetts hospitals were interviewed, and their responses were categorized using template analysis. Two health systems that intentionally embedded equity in their HICS were interviewed to identify factors that influenced implementation. The Consolidated Framework for Implementation Research was used as a foundation for the interviews, and transcripts were analyzed using a hybrid inductive-deductive case comparison approach.
Results: The literature review revealed three major themes; adding an equity representative to the HICS, incorporating equity into emergency plans, and connecting with the community. 14 Massachusetts hospitals were interviewed, and almost all took actions to embed equity into their HICS. The strategies included adding an equity representative, reviewing data, engaging with the community, and revising protocols. Strong predictors of adopting multiple approaches were hospitals that were Academic Medical Centers, in Metro Boston, and those that described a culture of equity. Interviews with 29 individuals from two health systems revealed several strategies to embed equity corresponding to the social determinants of health with a high degree of perceived success. Nine facilitators and five barriers to implementation were identified.
Conclusion: Several novel strategies to embed equity in the HICS were found to be feasible and acceptable in various contexts. Health system leaders and regulatory bodies must learn from the approaches described and incorporate health equity into the HICS now due to the predicted increase in natural disasters from climate change
Germ granule dynamics and roles in germ cell fate specification in C. elegans embryos
No full textGerm granules are conserved assemblies of RNA and proteins that are unique to the germline. In this work, we have studied two distinct germ granule types in the C. elegans germ plasm. First, we used P granules to investigate germ granule dynamics.
Previous studies of the P granule component PGL-1 showed that these condensates possessed liquid-like behaviors. We identified a second, less dynamic phase in P granules, formed by the intrinsically disordered protein MEG-3. MEG-3 is required for P
granule assembly and is enriched at the surface of PGL-3 condensates. Consistent with a gel-like phase, MEG-3 is resistant to dilution, high salt, aliphatic alcohols, and dissolves in SDS. Solidification of RNA granules has been linked to aging and
neurodegenerative diseases, however these findings suggest that gel-like polymers can be essential components of RNA granules.
We next describe a new condensate in the C. elegans germ plasm, called
“germline P-bodies”. Like P-bodies in the soma, germline P-bodies contain regulators of RNA translation and decay. Additionally, they contain the intrinsically disordered proteins MEG-1 and MEG-2, which were initially characterized as P granule proteins.
MEG-1 and MEG-2 are required to stabilize P-body components and regulate maternal mRNAs in the germline founder cell. meg-1 meg-2 mutants do not develop a germline
and are 100% sterile. This work identifies germline P-bodies as essential granules in the C. elegans germ plasm for germ cell fate specification
Atrial Fibrillation and Heart Failure with Preserved Ejection Fraction: Passive Bystander or Modifiable Risk Factor?
No full textAtrial fibrillation (AF) is the most common heart rhythm abnormality worldwide. Carrying a diagnosis of AF is associated with a concomitant rise in thromboembolic risk. Clinical management of AF has traditionally focused on two main pillars. First, the mitigation of cumulative thromboembolic risk with systemic anticoagulation which is uniformly elevated for all individuals. Second, a decision on selection of rate-controlling agents—drugs designed to avoid episodes of fast heartrates during this atrial arrhythmia, or rhythm control—therapeutic strategies initiated with the intent to reduce the amount of time an individual is in atrial fibrillation.
While our understanding of AF as a binary risk factor was reasonable in the thromboembolic setting, we postulate that the hemodynamic impairments brought about by AF in heart failure with preserved ejection fraction (HFpEF) should merit rhythm control strategies. Therefore, in the following analyses, we demonstrated that carrying a concomitant diagnosis of AF was associated with increased risk to heart failure exacerbation requiring hospitalization in a HFpEF population (Aim 1). We then demonstrated that individuals with HFpEF are more likely to have subclinical AF than their non-HFpEF counterparts using prospective ambulatory electrocardiographic monitoring (Aim 2).
While traditional studies have suggested that pursuing rhythm control had no benefit for heart failure and non-heart failure patients alike, recent studies looking at early intervention in AF demonstrated benefit in all-comers with newly diagnosed AF, as well as a subgroup analyses which demonstrated benefit in HF subgroups. We aimed to separate the temporal differences in rhythm management strategies used in historical studies (Aim 3), which suggest that progress in rhythm management therapeutics requires a re-investigation on whether rhythm management using modern approaches would be beneficial in the HFpEF population
Entity Linking in Low-Annotation Data Settings
No full textRecent advances in natural language processing have focused on applying and adapting large pretrained language models to specific tasks. These models, such as BERT (Devlin et al., 2019) and BART (Lewis et al., 2020a), are pretrained on massive amounts of unlabeled text across a variety of domains. The impact of these pretrained models is visible in the task of entity linking, where a mention of an entity in unstructured text is matched to the relevant entry in a knowledge base. State-of-the-art linkers, such as Wu et al. (2020) and De Cao et al. (2021), leverage pretrained models as a foundation for their systems. However, these models are also trained on large amounts of annotated data, which is crucial to their performance. Often these large datasets consist of domains that are easily annotated, such as Wikipedia or newswire text. However, tailoring NLP tools to a narrow variety of textual domains severely restricts their use in the real world.
Many other domains, such as medicine or law, do not have large amounts of entity linking annotations available. Entity linking, which serves to bridge the gap between massive unstructured amounts of text and structured repositories of knowledge, is equally crucial in these domains. Yet tools trained on newswire or Wikipedia annotations are unlikely to be well-suited for identifying medical conditions mentioned in clinical notes. As most annotation efforts focus on English, similar challenges can be noted in building systems for non-English text. There is often a relatively small amount of annotated data in these domains. With this being the case, looking to other types of domain-specific data, such as unannotated text or highly-curated structured knowledge bases, is often required. In these settings, it is crucial to translate lessons taken from tools tailored for high-annotation domains into algorithms that are suited for low-annotation domains. This requires both leveraging broader types of data and understanding the unique challenges present in each domain
RECYCLING LITHIUM-ION BATTERIES: REVIEWING IMPROVEMENTS TO THE PROCESS
No full textIncreasing adoption of battery storage, primarily driven by growing electric vehicle use, will increase the demand and production for Lithium-ion Batteries (LIBs). These batteries are inherently reliant on a finite resource pool – specifically for elemental Lithium (Li). There is tremendous effort around understanding how to mitigate uncertainties around the future of the Li supply chain through employing recycling methods like pyrometallurgy and hydrometallurgy after a pre-treatment step or direct recycling to recover or reuse valuable battery material. Though these strategies are broadly cost prohibitive today to a lack of existing battery waste stream, high energy input, high cost, high emissions, and low elemental recovery rates, improving their remaining technical limitations will make them more financially viable and pave the way for a more circular supply chain around LIBs. This review concluded that the most promising research avenues include the optimization of the pre-treatment step, blending of pyrometallurgical and hydrometallurgical strategies, and continuing to investigate electrode regeneration research (among a few others). While these improvements are being realized and the battery waste stream increases in volume, direct recycling methods like reuse for backup power applications should be utilized since they are independent of these existing technical and supply chain limitations. Supportive regulation around standardizing battery design, increasing the battery waste stream, and supporting continued investment in LIB recovery would also benefit the future of the supply chain and pave the way for a secure electrified future