Environmental hazards and disaster researchers have demonstrated strong associations between sociodemographic indicators, such as age and socio-economic status (SES), and hazard exposures and health outcomes for individuals and in certain communities. At the same time, behavioral health and risk communications research has examined how individual psychology influences adaptive strategies and behaviors in the face of hazards. However, at present, we do not understand the explanatory mechanisms that explain relationships between larger scale social structure, individual psychology, and specific behaviors that may attenuate or amplify risk. Extreme heat presents growing risks in a rapidly warming and urbanizing world. This dissertation examines the social and behavioral mechanisms that may explain inequitable health outcomes from exposure to concurrent extreme heat and electrical power failure in Phoenix, AZ and extreme heat in Detroit, MI. Exploratory analysis of 163 surveys in Phoenix, AZ showed that age, gender, and respondent’s racialized group identity did not relate to thermal discomfort and self-reported heat illness, which were only predicted by SES (StdB = -0.52, p < 0.01). Of the explanatory mechanisms tested in the study, only relative air conditioning intensity and thermal discomfort explained self-reported heat illness. Thermal discomfort was tested as both a mechanism and outcome measure. Content analysis of 40 semi-structured interviews in Phoenix, AZ revealed that social vulnerability was associated with an increase in perceived hazard severity (StdB = 0.44, p < 0.01), a decrease in perceived adaptation efficacy (StdB = -0.38, p = 0.02), and an indirect increase (through adaptive efficacy) in maladaptive intentions (StdB = 0.18, p = 0.01). Structural equation modeling of 244 surveys in Phoenix, AZ and Detroit, MI revealed that relationships between previous heat illness experience, perceived heat risk, and adaptive intentions were significantly moderated by adaptive capacity: high adaptive capacity households were more likely to undertake adaptive behaviors, and those decisions were more heavily influenced by risk perceptions and previous experiences. However, high adaptive capacity households had lower risk perceptions and fewer heat illness experiences than low adaptive capacity households. A better understanding of the mechanisms that produce social vulnerability can facilitate more salient risk messaging and more targeted public health interventions. For example, public health risk messaging that provides information on the efficacy of specific adaptations may be more likely to motivate self-protective action, and ultimately protect populations.

Urban climate conditions are the physical manifestation of formal and informal social forces of design, policy, and urban management. The urban design community (e.g. planners, architects, urban designers, landscape architects, engineers) impacts urban development through influential built projects and design discourse. Their decisions create urban landscapes that impact physiological and mental health for people that live in and around them. Therefore, to understand possible opportunities for decision-making to support healthier urban environments and communities, this dissertation examines the role of neighborhood design on the thermal environment and the effect the thermal environment has on mental health. In situ data collection and numerical modeling are used to assess current and proposed urban design configurations in the Edison Eastlake public housing community in central Phoenix for their efficacy in cooling the thermal environment. A distributed lagged non-linear model is used to investigate the relative risk of hospitalization for schizophrenia in Maricopa County based on atmospheric conditions. The dissertation incorporates both an assessment of design strategies for the cooling of the thermal environment and an analysis of the existing thermal environment’s relationship with mental health. By reframing the urban design of neighborhoods through the lens of urban climate, this research reinforces the importance of incorporating the community into the planning process and highlights some unintended outcomes of prioritizing the thermal environment in urban design.

To address the dearth of knowledge about person-based and trip-level exposure, we developed the Icarus model. Icarus uses mesoscale traffic model—activity-based model—to analyze the heat exposure of regions of interest at an individual level. The goal with Icarus was to design accurate, granular models of population and temperature behavior for a target region, which could be transformed into a heat exposure model by means of simulation and spatial-temporal joining. By combining and implementing the most robust software and data available, Icarus was able to capture person-based exposure with unparalleled detail. Here we describe the model methodology. We use the metropolitan region of Phoenix, Arizona, USA to carry out a case study using Icarus.

Human protein diversity arises as a result of alternative splicing, single nucleotide polymorphisms (SNPs) and posttranslational modifications. Because of these processes, each protein can exists as multiple variants in vivo. Tailored strategies are needed to study these protein variants and understand their role in health and disease. In this work we utilized quantitative mass spectrometric immunoassays to determine the protein variants concentration of beta-2-microglobulin, cystatin C, retinol binding protein, and transthyretin, in a population of 500 healthy individuals. Additionally, we determined the longitudinal concentration changes for the protein variants from four individuals over a 6 month period. Along with the native forms of the four proteins, 13 posttranslationally modified variants and 7 SNP-derived variants were detected and their concentration determined. Correlations of the variants concentration with geographical origin, gender, and age of the individuals were also examined. This work represents an important step toward building a catalog of protein variants concentrations and examining their longitudinal changes.

Studies on urban heat island (UHI) have been more than a century after the phenomenon was first discovered in the early 1800s. UHI emerges as the source of many urban environmental problems and exacerbates the living environment in cities. Under the challenges of increasing urbanization and future climate changes, there is a pressing need for sustainable adaptation/mitigation strategies for UHI effects, one popular option being the use of reflective materials. While it is introduced as an effective method to reduce temperature and energy consumption in cities, its impacts on environmental sustainability and large-scale non-local effect are inadequately explored. This paper provides a synthetic overview of potential environmental impacts of reflective materials at a variety of scales, ranging from energy load on a single building to regional hydroclimate. The review shows that mitigation potential of reflective materials depends on a set of factors, including building characteristics, urban environment, meteorological and geographical conditions, to name a few. Precaution needs to be exercised by city planners and policy makers for large-scale deployment of reflective materials before their environmental impacts, especially on regional hydroclimates, are better understood. In general, it is recommended that optimal strategy for UHI needs to be determined on a city-by-city basis, rather than adopting a “one-solution-fits-all” strategy.

Land surface energy balance in a built environment is widely modelled using urban canopy models with representation of building arrays as big street canyons. Modification of this simplified geometric representation, however, leads to challenging numerical difficulties in improving physical parameterization schemes that are deterministic in nature. In this paper, we develop a stochastic algorithm to estimate view factors between canyon facets in the presence of shade trees based on Monte Carlo simulation, where an analytical formulation is inhibited by the complex geometry. The model is validated against analytical solutions of benchmark radiative problems as well as field measurements in real street canyons. In conjunction with the matrix method resolving infinite number of reflections, the proposed model is capable of predicting the radiative exchange inside the street canyon with good accuracy. Modeling of transient evolution of thermal filed inside the street canyon using the proposed method demonstrate the potential of shade trees in mitigating canyon surface temperatures as well as saving of building energy use. This new numerical framework also deepens our insight into the fundamental physics of radiative heat transfer and surface energy balance for urban climate modeling.

Proteins can exist as multiple proteoforms in vivo, as a result of alternative splicing and single-nucleotide polymorphisms (SNPs), as well as posttranslational processing. To address their clinical significance in a context of diagnostic information, proteoforms require a more in-depth analysis. Mass spectrometric immunoassays (MSIA) have been devised for studying structural diversity in human proteins. MSIA enables protein profiling in a simple and high-throughput manner, by combining the selectivity of targeted immunoassays, with the specificity of mass spectrometric detection. MSIA has been used for qualitative and quantitative analysis of single and multiple proteoforms, distinguishing between normal fluctuations and changes related to clinical conditions. This mini review offers an overview of the development and application of mass spectrometric immunoassays for clinical and population proteomics studies. Provided are examples of some recent developments, and also discussed are the trends and challenges in mass spectrometry-based immunoassays for the next-phase of clinical applications.

Background: Most excess deaths that occur during extreme hot weather events do not have natural heat recorded as an underlying or contributing cause. This study aims to identify the specific individuals who died because of hot weather using only secondary data. A novel approach was developed in which the expected number of deaths was repeatedly sampled from all deaths that occurred during a hot weather event, and compared with deaths during a control period. The deaths were compared with respect to five factors known to be associated with hot weather mortality. Individuals were ranked by their presence in significant models over 100 trials of 10,000 repetitions. Those with the highest rankings were identified as probable excess deaths. Sensitivity analyses were performed on a range of model combinations. These methods were applied to a 2009 hot weather event in greater Vancouver, Canada.

Results: The excess deaths identified were sensitive to differences in model combinations, particularly between univariate and multivariate approaches. One multivariate and one univariate combination were chosen as the best models for further analyses. The individuals identified by multiple combinations suggest that marginalized populations in greater Vancouver are at higher risk of death during hot weather.

Conclusions: This study proposes novel methods for classifying specific deaths as expected or excess during a hot weather event. Further work is needed to evaluate performance of the methods in simulation studies and against clinically identified cases. If confirmed, these methods could be applied to a wide range of populations and events of interest.

Introduction: Apolipoprotein C-III (apoC-III) regulates triglyceride (TG) metabolism. In plasma, apoC-III exists in non-sialylated (apoC-III_0a without glycosylation and apoC-III[subscript 0b] with glycosylation), monosialylated (apoC-III₁) or disialylated (apoC-III₂) proteoforms. Our aim was to clarify the relationship between apoC-III sialylation proteoforms with fasting plasma TG concentrations.

Methods: In 204 non-diabetic adolescent participants, the relative abundance of apoC-III plasma proteoforms was measured using mass spectrometric immunoassay.

Results: Compared with the healthy weight subgroup (n = 16), the ratios of apoC-III_0a, apoC-III_0b, and apoC-III₁ to apoC-III₂ were significantly greater in overweight (n = 33) and obese participants (n = 155). These ratios were positively correlated with BMI z-scores and negatively correlated with measures of insulin sensitivity (S[subscript i]). The relationship of apoC-III₁ / apoC-III₂ with S_i persisted after adjusting for BMI (p = 0.02). Fasting TG was correlated with the ratio of apoC-III_0a / apoC-III₂ (r = 0.47, p<0.001), apoC-III_0b / apoC-III₂ (r = 0.41, p<0.001), apoC-III₁ / apoC-III₂ (r = 0.43, p<0.001). By examining apoC-III concentrations, the association of apoC-III proteoforms with TG was driven by apoC-III_0a (r = 0.57, p<0.001), apoC-III_0b (r = 0.56. p<0.001) and apoC-III₁ (r = 0.67, p<0.001), but not apoC-III₂ (r = 0.006, p = 0.9) concentrations, indicating that apoC-III relationship with plasma TG differed in apoC-III₂ compared with the other proteoforms.

Conclusion: We conclude that apoC-III_0a, apoC-III_0b, and apoC-III₁, but not apoC-III₂ appear to be under metabolic control and associate with fasting plasma TG. Measurement of apoC-III proteoforms can offer insights into the biology of TG metabolism in obesity.

The impetus for discovery and evaluation of protein biomarkers has been accelerated by recent development of advanced technologies for rapid and broad proteome analyses. Mass spectrometry (MS)-based protein assays hold great potential for in vitro biomarker studies. Described here is the development of a multiplex mass spectrometric immunoassay (MSIA) for quantification of apolipoprotein C-I (apoC-I), apolipoprotein C-II (apoC-II), apolipoprotein C-III (apoC-III) and their proteoforms. The multiplex MSIA assay was fast (∼40 min) and high-throughput (96 samples at a time). The assay was applied to a small cohort of human plasma samples, revealing the existence of multiple proteoforms for each apolipoprotein C. The quantitative aspect of the assay enabled determination of the concentration for each proteoform individually. Low-abundance proteoforms, such as fucosylated apoC-III, were detected in less than 20% of the samples. The distribution of apoC-III proteoforms varied among samples with similar total apoC-III concentrations. The multiplex analysis of the three apolipoproteins C and their proteoforms using quantitative MSIA represents a significant step forward toward better understanding of their physiological roles in health and disease.