Evaluating geographic imputation approaches for zip code level data: an application to a study of pediatric diabetes

<p>Abstract</p> <p>Background</p> <p>There is increasing interest in the study of place effects on health, facilitated in part by geographic information systems. Incomplete or missing address information reduces geocoding success. Several geographic imputation methods have been suggested to overcome this limitation. Accuracy evaluation of these methods can be focused at the level of individuals and at higher group-levels (e.g., spatial distribution).</p> <p>Methods</p> <p>We evaluated the accuracy of eight geo-imputation methods for address allocation from ZIP codes to census tracts at the individual and group level. The spatial apportioning approaches underlying the imputation methods included four fixed (deterministic) and four random (stochastic) allocation methods using land area, total population, population under age 20, and race/ethnicity as weighting factors. Data included more than 2,000 geocoded cases of diabetes mellitus among youth aged 0-19 in four U.S. regions. The imputed distribution of cases across tracts was compared to the true distribution using a chi-squared statistic.</p> <p>Results</p> <p>At the individual level, population-weighted (total or under age 20) fixed allocation showed the greatest level of accuracy, with correct census tract assignments averaging 30.01% across all regions, followed by the race/ethnicity-weighted random method (23.83%). The true distribution of cases across census tracts was that 58.2% of tracts exhibited no cases, 26.2% had one case, 9.5% had two cases, and less than 3% had three or more. This distribution was best captured by random allocation methods, with no significant differences (p-value > 0.90). However, significant differences in distributions based on fixed allocation methods were found (p-value < 0.0003).</p> <p>Conclusion</p> <p>Fixed imputation methods seemed to yield greatest accuracy at the individual level, suggesting use for studies on area-level environmental exposures. Fixed methods result in artificial clusters in single census tracts. For studies focusing on spatial distribution of disease, random methods seemed superior, as they most closely replicated the true spatial distribution. When selecting an imputation approach, researchers should consider carefully the study aims.</p

Cooperative Interactions between TLR4 and TLR9 Regulate Interleukin 23 and 17 Production in a Murine Model of Gram Negative Bacterial Pneumonia

Toll like receptors play an important role in lung host defense against bacterial pathogens. In this study, we investigated independent and cooperative functions of TLR4 and TLR9 in microbial clearance and systemic dissemination during Gram-negative bacterial pneumonia. To access these responses, wildtype Balb/c mice, mice with defective TLR4 signaling (TLR4lps-d), mice deficient in TLR9 (TLR9−/−) and TLR4/9 double mutant mice (TLR4lps-d/TLR9−/−) were challenged with K. pneumoniae, then time-dependent lung bacterial clearance and systemic dissemination determined. We found impaired lung bacterial clearance in TLR4 and TLR9 single mutant mice, whereas the greatest impairment in clearance was observed in TLR4lps-d/TLR9−/− double mutant mice. Early lung expression of TNF-α, IL-12, and chemokines was TLR4 dependent, while IFN-γ production and the later expression of TNF-α and IL-12 was dependent on TLR9. Classical activation of lung macrophages and maximal induction of IL-23 and IL-17 required both TLR4 and TLR9. Finally, the i.t. instillation of IL-17 partially restored anti-bacterial immunity in TLR4lps-d/TLR9−/− double mutant mice. In conclusion, our studies indicate that TLR4 and TLR9 have both non-redundant and cooperative roles in lung innate responses during Gram-negative bacterial pneumonia and are both critical for IL-17 driven antibacterial host response

Associations of the plasma lipidome with mortality in the acute respiratory distress syndrome: a longitudinal cohort study

Abstract Background It is unknown if the plasma lipidome is a useful tool for improving our understanding of the acute respiratory distress syndrome (ARDS). Therefore, we measured the plasma lipidome of individuals with ARDS at two time-points to determine if changes in the plasma lipidome distinguished survivors from non-survivors. We hypothesized that both the absolute concentration and change in concentration over time of plasma lipids are associated with 28-day mortality in this population. Methods Samples for this longitudinal observational cohort study were collected at multiple tertiary-care academic medical centers as part of a previous multicenter clinical trial. A mass spectrometry shot-gun lipidomic assay was used to quantify the lipidome in plasma samples from 30 individuals. Samples from two different days were analyzed for each subject. After removing lipids with a coefficient of variation > 30%, differences between cohorts were identified using repeated measures analysis of variance. The false discovery rate was used to adjust for multiple comparisons. Relationships between significant compounds were explored using hierarchical clustering of the Pearson correlation coefficients and the magnitude of these relationships was described using receiver operating characteristic curves. Results The mass spectrometry assay reliably measured 359 lipids. After adjusting for multiple comparisons, 90 compounds differed between survivors and non-survivors. Survivors had higher levels for each of these lipids except for five membrane lipids. Glycerolipids, particularly those containing polyunsaturated fatty acid side-chains, represented many of the lipids with higher concentrations in survivors. The change in lipid concentration over time did not differ between survivors and non-survivors. Conclusions The concentration of multiple plasma lipids is associated with mortality in this group of critically ill patients with ARDS. Absolute lipid levels provided more information than the change in concentration over time. These findings support future research aimed at integrating lipidomics into critical care medicine.https://deepblue.lib.umich.edu/bitstream/2027.42/143134/1/12931_2018_Article_758.pd

Hypermethylation of ribosomal DNA in human breast carcinoma

We examined the methylation status of the transcribed domain of ribosomal DNA (rDNA) in 58 patients with breast cancer. The mean percent of methylation was significantly higher in breast tumours than that of normal control samples (P< 0.0001). This increased rDNA methylation was associated with oestrogen receptor non-expression (P< 0.0273) and with moderately or poorly differentiated tumours as compared to well differentiated tumours (P< 0.0475). Our results suggest that rDNA can be a useful marker for monitoring aberrant methylation during breast tumour progression. © 2000 Cancer Research Campaig

Associations of the plasma lipidome with mortality in the acute respiratory distress syndrome: a longitudinal cohort study

Abstract Background It is unknown if the plasma lipidome is a useful tool for improving our understanding of the acute respiratory distress syndrome (ARDS). Therefore, we measured the plasma lipidome of individuals with ARDS at two time-points to determine if changes in the plasma lipidome distinguished survivors from non-survivors. We hypothesized that both the absolute concentration and change in concentration over time of plasma lipids are associated with 28-day mortality in this population. Methods Samples for this longitudinal observational cohort study were collected at multiple tertiary-care academic medical centers as part of a previous multicenter clinical trial. A mass spectrometry shot-gun lipidomic assay was used to quantify the lipidome in plasma samples from 30 individuals. Samples from two different days were analyzed for each subject. After removing lipids with a coefficient of variation > 30%, differences between cohorts were identified using repeated measures analysis of variance. The false discovery rate was used to adjust for multiple comparisons. Relationships between significant compounds were explored using hierarchical clustering of the Pearson correlation coefficients and the magnitude of these relationships was described using receiver operating characteristic curves. Results The mass spectrometry assay reliably measured 359 lipids. After adjusting for multiple comparisons, 90 compounds differed between survivors and non-survivors. Survivors had higher levels for each of these lipids except for five membrane lipids. Glycerolipids, particularly those containing polyunsaturated fatty acid side-chains, represented many of the lipids with higher concentrations in survivors. The change in lipid concentration over time did not differ between survivors and non-survivors. Conclusions The concentration of multiple plasma lipids is associated with mortality in this group of critically ill patients with ARDS. Absolute lipid levels provided more information than the change in concentration over time. These findings support future research aimed at integrating lipidomics into critical care medicine.https://deepblue.lib.umich.edu/bitstream/2027.42/143134/1/12931_2018_Article_758.pd

Hazard and consequence analysis for waste emplacement at the Waste Isolation Pilot Plant

The Carlsbad Area Office established and analyzed the safety bases for the design and operations as documented in the WIPP Safety Analysis Report (SAR). Additional independent efforts are currently underway to assess the hazards associated with the long-term (10,000 year) isolation period as required by 40 CFR 191. The structure of the WIPP SAR is unique due to the hazards involved, and the agreement between the State of New Mexico and the DOE regarding SAR content and format. However, the hazards and accident analysis philosophy as contained in DOE-STD-3009-94 was followed as closely as possible, while adhering to state agreements. Hazards associated with WIPP waste receipt, emplacement, and disposal operations were systematically identified using a modified Hazard and Operability Study (HAZOP) technique. The WIPP HAZOP assessed the potential internal, external, and natural phenomena events that can cause the identified hazards to develop into accidents. The hazard assessment identified deviations from the intended design and operation of the waste handling system, analyzed potential accident consequences to the public and workers, estimated likelihood of occurrence, and evaluated associated preventative and mitigative features. It was concluded from the assessment that the proposed WIPP waste emplacement operations and design are sufficient to ensure safety of the public, workers, and environment, over the 35 year disposal phase

Factors influencing time to case registration for youth with type 1 and type 2 diabetes: SEARCH for Diabetes in Youth Study

The development of a sustainable pediatric diabetes surveillance system for the United States requires a better understanding of issues related to case ascertainment

Trends in the Prevalence of Ketoacidosis at Diabetes Diagnosis: The SEARCH for Diabetes in Youth Study

To estimate temporal changes in the prevalence of diabetic ketoacidosis (DKA) at diagnosis of type 1 or type 2 diabetes in youth and to explore factors associated with its occurrence

Projections of Type 1 and Type 2 Diabetes Burden in the U.S. Population Aged <20 Years Through 2050: Dynamic modeling of incidence, mortality, and population growth

To forecast the number of U.S. individuals aged <20 years with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) through 2050, accounting for changing demography and diabetes incidence

Adherence to Guidelines for Youths With Diabetes Mellitus

To describe demographic and clinical characteristics associated with self-reported receipt of tests and measurements recommended by the American Diabetes Association (ADA) for children and youths with diabetes