ASU Scholarship Showcase

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.

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.

Research Summary:
Using U.S. Sentencing Commission data, this study assesses whether judicial downward departures are more prevalent among child pornography offenders compared with a matched sample of defendants convicted of other offenses. Additionally, we examine reasons given by judges when departing from the guidelines for these offenders. We found that child pornography defendants received significant reductions in sentences by way of judicial downward departures.

Policy Implications:
In 2007, the Supreme Court considerably altered the federal sentencing process. In Kimbrough v. United States (2007), the Court held that judicial departures were permissible on grounds of a policy disagreement. Many circuit courts have authorized sentencing judges to depart from the guidelines in child pornography cases based on such a policy disagreement. The findings of this study suggest that judicial downward departures for these offenders cannot be explained by individual characteristics, such as race, gender, or age, and may be indicative of a specific disagreement with this particular sentencing policy. An examination of the reasons provided by judges supports the hypothesis that judges may be attempting to remedy what they perceive as unjustly harsh sentencing guidelines.

Background: Extreme heat is a public health challenge. The scarcity of directly comparable studies on the association of heat with morbidity and mortality and the inconsistent identification of threshold temperatures for severe impacts hampers the development of comprehensive strategies aimed at reducing adverse heat-health events.

Objectives: This quantitative study was designed to link temperature with mortality and morbidity events in Maricopa County, Arizona, USA, with a focus on the summer season.
Methods: Using Poisson regression models that controlled for temporal confounders, we assessed daily temperature–health associations for a suite of mortality and morbidity events, diagnoses, and temperature metrics. Minimum risk temperatures, increasing risk temperatures, and excess risk temperatures were statistically identified to represent different “trigger points” at which heat-health intervention measures might be activated.

Results: We found significant and consistent associations of high environmental temperature with all-cause mortality, cardiovascular mortality, heat-related mortality, and mortality resulting from conditions that are consequences of heat and dehydration. Hospitalizations and emergency department visits due to heat-related conditions and conditions associated with consequences of heat and dehydration were also strongly associated with high temperatures, and there were several times more of those events than there were deaths. For each temperature metric, we observed large contrasts in trigger points (up to 22°C) across multiple health events and diagnoses.

Conclusion: Consideration of multiple health events and diagnoses together with a comprehensive approach to identifying threshold temperatures revealed large differences in trigger points for possible interventions related to heat. Providing an array of heat trigger points applicable for different end-users may improve the public health response to a problem that is projected to worsen in the coming decades.

Background: Extreme heat is a leading weather-related cause of mortality in the United States, but little guidance is available regarding how temperature variable selection impacts heat–mortality relationships.
Objectives: We examined how the strength of the relationship between daily heat-related mortality and temperature varies as a function of temperature observation time, lag, and calculation method.
Methods: Long time series of daily mortality counts and hourly temperature for seven U.S. cities with different climates were examined using a generalized additive model. The temperature effect was modeled separately for each hour of the day (with up to 3-day lags) along with different methods of calculating daily maximum, minimum, and mean temperature. We estimated the temperature effect on mortality for each variable by comparing the 99th versus 85th temperature percentiles, as determined from the annual time series.

Results: In three northern cities (Boston, MA; Philadelphia, PA; and Seattle, WA) that appeared to have the greatest sensitivity to heat, hourly estimates were consistent with a diurnal pattern in the heat-mortality response, with strongest associations for afternoon or maximum temperature at lag 0 (day of death) or afternoon and evening of lag 1 (day before death). In warmer, southern cities, stronger associations were found with morning temperatures, but overall the relationships were weaker. The strongest temperature–mortality relationships were associated with maximum temperature, although mean temperature results were comparable.

Conclusions: There were systematic and substantial differences in the association between temperature and mortality based on the time and type of temperature observation. Because the strongest hourly temperature–mortality relationships were not always found at times typically associated with daily maximum temperatures, temperature variables should be selected independently for each study location. In general, heat-mortality was more closely coupled to afternoon and maximum temperatures in most cities we examined, particularly those typically prone to heat-related mortality.

Background: Studies show that ex-prisoners often experience more health problems than the general population; unfortunately, these issues follow them upon their release from prison. As such, it is possible re-entry rates signal the need for neighborhood-based health care organizations (HCOs). We ask: are incarceration and re-entry rates associated with the availability of HCOs?

Methods: Using 2008 Central Business Pattern data, 2008 prison admissions and release data, and 2000 and 2010 census data, we test whether prison admission and release rates impact the availability of HCOs net of neighborhood characteristics in Arkansas using Logit-Poisson hurdle models with county fixed effects.

Results: We find that the incarceration and re-entry rates – together known as coercive mobility -- are related to whether a neighborhood has one or more HCOs, but not to the number of HCOs in a neighborhood.

Conclusion: Future public policies should aim to locate health care organizations in areas where there is significant churning of individuals in and out of prison.

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.

Rationale: Medical masks are commonly used by sick individuals with influenza-like illness (ILI) to prevent spread of infections to others, but clinical efficacy data are absent.

Objective: Determine whether medical mask use by sick individuals with ILI protects well contacts from related respiratory infections.

Setting: 6 major hospitals in 2 districts of Beijing, China.

Design: Cluster randomised controlled trial.

Participants: 245 index cases with ILI.

Intervention: Index cases with ILI were randomly allocated to medical mask (n=123) and control arms (n=122). Since 43 index cases in the control arm also used a mask during the study period, an as-treated post hoc analysis was performed by comparing outcomes among household members of index cases who used a mask (mask group) with household members of index cases who did not use a mask (no-mask group).

Main Outcome Measure: Primary outcomes measured in household members were clinical respiratory illness, ILI and laboratory-confirmed viral respiratory infection.

Results: In an intention-to-treat analysis, rates of clinical respiratory illness (relative risk (RR) 0.61, 95% CI 0.18 to 2.13), ILI (RR 0.32, 95% CI 0.03 to 3.13) and laboratory-confirmed viral infections (RR 0.97, 95% CI 0.06 to 15.54) were consistently lower in the mask arm compared with control, although not statistically significant. A post hoc comparison between the mask versus no-mask groups showed a protective effect against clinical respiratory illness, but not against ILI and laboratory-confirmed viral respiratory infections.

Conclusions: The study indicates a potential benefit of medical masks for source control, but is limited by small sample size and low secondary attack rates. Larger trials are needed to confirm efficacy of medical masks as source control.

Abnormalities in reward and punishment processing are implicated in the development of conduct problems (CP), particularly among youth with callous-unemotional (CU) traits. However, no studies have examined whether CP children with high versus low CU traits exhibit differences in the neural response to reward and punishment. A clinic-referred sample of CP boys with high versus low CU traits (ages 8–11; n = 37) and healthy controls (HC; n = 27) completed a fMRI task assessing reward and punishment processing. CP boys also completed a randomized control trial examining the effectiveness of an empirically-supported intervention (i.e., Stop-Now-And-Plan; SNAP). Primary analyses examined pre-treatment differences in neural activation to reward and punishment, and exploratory analyses assessed whether these differences predicted treatment outcome. Results demonstrated associations between CP and reduced amygdala activation to punishment independent of age, race, IQ and co-occurring ADHD and internalizing symptoms. CU traits were not associated with reward or punishment processing after accounting for covariates and no differences were found between CP boys with high versus low CU traits. While boys assigned to SNAP showed a greater reduction in CP, differences in neural activation were not associated with treatment response. Findings suggest that reduced sensitivity to punishment is associated with early-onset CP in boys regardless of the level of CU traits.