Background: The cytokine MIF (Macrophage Migration Inhibitory Factor) has diverse physiological roles and is present at elevated concentrations in numerous disease states. However, its molecular heterogeneity has not been previously investigated in biological samples. Mass Spectrometric Immunoassay (MSIA) may help elucidate MIF post-translational modifications existing in vivo and provide additional clarity regarding its relationship to diverse pathologies.

Results: In this work, we have developed and validated a fully quantitative MSIA assay for MIF, and used it in the discovery and quantification of different proteoforms of MIF in serum samples, including cysteinylated and glycated MIF. The MSIA assay had a linear range of 1.56-50 ng/mL, and exhibited good precision, linearity, and recovery characteristics. The new assay was applied to a small cohort of human serum samples, and benchmarked against an MIF ELISA assay.

Conclusions: The quantitative MIF MSIA assay provides a sensitive, precise and high throughput method to delineate and quantify MIF proteoforms in biological samples.

Background: Cystatin C (CysC) is an endogenous cysteine protease inhibitor that can be used to assess the progression of kidney function. Recent studies demonstrate that CysC is a more specific indicator of glomerular filtration rate (GFR) than creatinine. CysC in plasma exists in multiple proteoforms. The goal of this study was to clarify the association of native CysC, CysC missing N-terminal Serine (CysC des-S), and CysC without three N-terminal residues (CysC des-SSP) with diabetic chronic kidney disease (CKD).

Results: Using mass spectrometric immunoassay, the plasma concentrations of native CysC and the two CysC truncation proteoforms were examined in 111 individuals from three groups: 33 non-diabetic controls, 34 participants with type 2 diabetes (DM) and without CKD and 44 participants with diabetic CKD. Native CysC concentrations were 1.4 fold greater in CKD compared to DM group (p = 0.02) and 1.5 fold greater in CKD compared to the control group (p = 0.001). CysC des-S concentrations were 1.55 fold greater in CKD compared to the DM group (p = 0.002) and 1.9 fold greater in CKD compared to the control group (p = 0.0002). CysC des-SSP concentrations were 1.8 fold greater in CKD compared to the DM group (p = 0.008) and 1.52 fold greater in CKD compared to the control group (p = 0.002). In addition, the concentrations of CysC proteoforms were greater in the setting of albuminuria. The truncated CysC proteoform concentrations were associated with estimated GFR independent of native CysC concentrations.

Conclusion: Our findings demonstrate a greater amount of CysC proteoforms in diabetic CKD. We therefore suggest assessing the role of cystatin C proteoforms in the progression of CKD.

Society is heavily dependent on a reliable electric supply; all infrastructure systems depend on electricity to operate. When the electric system fails, the impacts can be catastrophic (food spoilage, inoperable medical devices, lack of access to water, etc.). The social impacts, defined as the direct and indirect impacts on people, of power outages must be explored as the likelihood of power outages and blackouts are increasing. However, compared to other hazards, such as heat and flooding, the knowledge base on the impacts of power outages is relatively small. The purpose of this thesis is to identify what is currently known about the social impacts of power outages, identify where gaps in the literature exist, and deploy a survey to explore power outage experiences at the household level. This thesis is comprised of two chapters, a systematic literature review on the current knowledge of the social impacts of power outages and a multi-city survey focused on power outage experiences.

The first chapter comprised of a systematic literature review using a combined search of in Scopus which returned 762 candidate articles were identified that potentially explored the social impacts of power outages. However, after multiple filtering criteria were applied, only 45 articles met all criteria. Four themes were used to classify the literature, not exclusively, including modeling, social, technical, and other. Only papers that were classified as “social” - meaning they observed how people were affected by a power outage - or in combination with other categories were used within the review.

From the literature, populations of concern were identified, including minority demographics - specifically Blacks or African Americans, children, elderly, and rural populations. The most commonly reported health concerns were from those that rely on medical devices for chronic conditions and unsafe generator practices. Criminal activity was also reported to increase during prolonged power outages and can be mitigated by consistent messaging on where to receive assistance and when power will be restored. Providing financial assistance and resources such as food and water can reduce the crime rate temporarily, but the crime rate can be expected to increase once the relief expires. Authorities should expect looting to occur, especially in poorer areas, during prolonged power outages. Gaps in the literature were identified and future directions for research were provided.

The second chapter consists of a multi-city survey that targeted three major cities across the United States (Detroit, MI; Miami, FL; and Phoenix, AZ). The survey was disseminated through Amazon’s Mechanical Turk and hosted by Qualtrics. 896 participants from the three cities qualified to complete the full version of the survey. Three criteria had to be met for participants to complete the full survey including residing in one of the three target cities, living at their primary address for a majority of the year, and indicate they had experienced a power outage within the last five years.

Participants were asked questions regarding the number of outages experienced in the last five years, the length of their most recent and longest outage experienced, if they owned a generator, how they managed their longest power outage, if participants or anyone in their household relies on a medical device, the financial burden their power outage caused, and standard demographic- and income-related questions. Race was a significant variable that influenced the outage duration length but not frequency in Phoenix and Detroit. Income was not a significant variable associated with experiencing greater economic impacts, such as having thrown food away because of an outage and not receiving help during the longest outage. Additional assessments similar to this survey are needed to better understand household power outage experiences.

Findings from this thesis demonstrate traditional metrics used in vulnerability indices were not indicative of who experienced the greatest effects of power outages. Additionally, other factors that are not included in these indices, such as owning adaptive resources including medical devices and generators in Phoenix and Detroit, are factors in reducing negative outcomes. More research is needed on this topic to indicate which populations are more likely to experience factors that can influence positive or negative outage outcomes.

Access to air conditioned space is critical for protecting urban populations from the adverse effects of heat exposure. Yet there remains fairly limited knowledge of penetration of private (home air conditioning) and distribution of public (cooling centers and commercial space) cooled space across cities. Furthermore, the deployment of government-sponsored cooling centers is not based on the location of existing cooling resources (residential air conditioning and air conditioned public space), raising questions of the equitability of access to heat refuges.

Using Los Angeles County, California and Maricopa County, Arizona (whose county seat is Phoenix) we explore the distribution of private and public cooling resources and access inequities at the household level. We do this by evaluating the presence of in-home air conditioning and developing a walking-based accessibility measure to air conditioned public space using a combined cumulative opportunities-gravity approach. We find significant inequities in the distribution of residential air conditioning across both regions which are largely attributable to building age and inter/intra-regional climate differences. There are also regional disparities in walkable access to public cooled space.

At average walking speeds, we find that official cooling centers are only accessible to a small fraction of households (3% in Los Angeles, 2% in Maricopa) while a significantly higher number of households (80% in Los Angeles, 39% in Maricopa) have access to at least one other type of public cooling resource which includes libraries and commercial establishments. Aggregated to a neighborhood level, we find that there are areas within each region where access to cooled space (either public or private) is limited which may increase the health risks associated with heat.

Insulin-like growth factor 1 (IGF1) is an important biomarker for the management of growth hormone disorders. Recently there has been rising interest in deploying mass spectrometric (MS) methods of detection for measuring IGF1. However, widespread clinical adoption of any MS-based IGF1 assay will require increased throughput and speed to justify the costs of analyses, and robust industrial platforms that are reproducible across laboratories. Presented here is an MS-based quantitative IGF1 assay with performance rating of >1,000 samples/day, and a capability of quantifying IGF1 point mutations and posttranslational modifications. The throughput of the IGF1 mass spectrometric immunoassay (MSIA) benefited from a simplified sample preparation step, IGF1 immunocapture in a tip format, and high-throughput MALDI-TOF MS analysis. The Limit of Detection and Limit of Quantification of the resulting assay were 1.5 μg/L and 5 μg/L, respectively, with intra- and inter-assay precision CVs of less than 10%, and good linearity and recovery characteristics. The IGF1 MSIA was benchmarked against commercially available IGF1 ELISA via Bland-Altman method comparison test, resulting in a slight positive bias of 16%. The IGF1 MSIA was employed in an optimized parallel workflow utilizing two pipetting robots and MALDI-TOF-MS instruments synced into one-hour phases of sample preparation, extraction and MSIA pipette tip elution, MS data collection, and data processing. Using this workflow, high-throughput IGF1 quantification of 1,054 human samples was achieved in approximately 9 hours. This rate of assaying is a significant improvement over existing MS-based IGF1 assays, and is on par with that of the enzyme-based immunoassays. Furthermore, a mutation was detected in ∼1% of the samples (SNP: rs17884626, creating an A→T substitution at position 67 of the IGF1), demonstrating the capability of IGF1 MSIA to detect point mutations and posttranslational modifications.

Maricopa County is the home of the Phoenix metropolitan area, an expansive city with serious air quality concerns. To ameliorate air quality in the county, the Maricopa County Air Quality Department developed a website and mobile application called "Clean Air Make More" as a means of outreach and engagement. In doing this, the county has found a way to engender a bilateral relationship between individuals and their government agency. This study analyzes the effectiveness of Clean Air Make More in establishing this relationship and engaging the community in efforts to improve air quality. It concludes that the design of the application effectively meets user needs, but marketing efforts should target populations disposed to taking action regarding air quality.

Background:
Environmental heat exposure is a public health concern. The impacts of environmental heat on mortality and morbidity at the population scale are well documented, but little is known about specific exposures that individuals experience.

Objectives:
The first objective of this work was to catalyze discussion of the role of personal heat exposure information in research and risk assessment. The second objective was to provide guidance regarding the operationalization of personal heat exposure research methods.

Discussion:
We define personal heat exposure as realized contact between a person and an indoor or outdoor environment that poses a risk of increases in body core temperature and/or perceived discomfort. Personal heat exposure can be measured directly with wearable monitors or estimated indirectly through the combination of time–activity and meteorological data sets. Complementary information to understand individual-scale drivers of behavior, susceptibility, and health and comfort outcomes can be collected from additional monitors, surveys, interviews, ethnographic approaches, and additional social and health data sets. Personal exposure research can help reveal the extent of exposure misclassification that occurs when individual exposure to heat is estimated using ambient temperature measured at fixed sites and can provide insights for epidemiological risk assessment concerning extreme heat.

Conclusions:
Personal heat exposure research provides more valid and precise insights into how often people encounter heat conditions and when, where, to whom, and why these encounters occur. Published literature on personal heat exposure is limited to date, but existing studies point to opportunities to inform public health practice regarding extreme heat, particularly where fine-scale precision is needed to reduce health consequences of heat exposure.