The Fall and Rise of US Inequities in Premature Mortality: 1960–2002

Nancy Krieger and colleagues found evidence of decreasing, and then increasing or stagnating, socioeconomic and racial inequities in US premature mortality and infant death from 1960 to 2002

The inverse hazard law: Blood pressure, sexual harassment, racial discrimination, workplace abuse and occupational exposures in US low-income black, white and Latino workers

http://dx.doi.org/10.1016/j.socscimed.2008.09.03

Exposing Racial Discrimination: Implicit & Explicit Measures–The My Body, My Story Study of 1005 US-Born Black & White Community Health Center Members

Background To date, research on racial discrimination and health typically has employed explicit self-report measures, despite their potentially being affected by what people are able and willing to say. We accordingly employed an Implicit Association Test (IAT) for racial discrimination, first developed and used in two recent published studies, and measured associations of the explicit and implicit discrimination measures with each other, socioeconomic and psychosocial variables, and smoking. Methodology/Principal Findings Among the 504 black and 501 white US-born participants, age 35–64, randomly recruited in 2008–2010 from 4 community health centers in Boston, MA, black participants were over 1.5 times more likely (p<0.05) to be worse off economically (e.g., for poverty and low education) and have higher social desirability scores (43.8 vs. 28.2); their explicit discrimination exposure was also 2.5 to 3.7 times higher (p<0.05) depending on the measure used, with over 60% reporting exposure in 3 or more domains and within the last year. Higher IAT scores for target vs. perpetrator of discrimination occurred for the black versus white participants: for “black person vs. white person”: 0.26 vs. 0.13; and for “me vs. them”: 0.24 vs. 0.19. In both groups, only low non-significant correlations existed between the implicit and explicit discrimination measures; social desirability was significantly associated with the explicit but not implicit measures. Although neither the explicit nor implicit discrimination measures were associated with odds of being a current smoker, the excess risk for black participants (controlling for age and gender) rose in models that also controlled for the racial discrimination and psychosocial variables; additional control for socioeconomic position sharply reduced and rendered the association null. Conclusions Implicit and explicit measures of racial discrimination are not equivalent and both warrant use in research on racial discrimination and health, along with data on socioeconomic position and social desirability

Analyzing historical trends in breast cancer biomarker expression: a feasibility study (1947–2009)

BACKGROUND/OBJECTIVES Determining long-term trends in tumor biomarker expression is essential for understanding aspects of tumor biology amenable to change. Limiting the availability of such data, currently used assays for biomarkers are relatively new. For example, assays for the estrogen receptor (ER), which are the oldest, extend back only to the 1970s. METHODS To extend scant knowledge about the feasibility of obtaining long-term data on tumor biomarkers, we randomly selected 60 breast cancer cases (10 per decade) diagnosed between 1947–2009 among women members of the Kaiser Permanente Northern California health plan to obtain and analyze their formalin-fixed paraffin-embedded (FFPE) tumor specimens. For each tumor specimen, we created duplicate tissue microarrays for analysis. RESULTS We located tumor blocks and pathology reports for 50 of the 60 cases (83%), from which we randomly sampled 5 cases per decade for biomarker analysis (n = 30). All 30 cases displayed excellent morphology and exhibited biomarkers compatible with histologic type and grade. Test–retest reliability was also excellent: 100% for ER; 97% for human epidermal growth factor receptor 2 and epidermal growth factor receptor; 93% for progesterone receptor and cytokeratin 5/6; and 90% for Ki67 and molecular phenotype; the kappa statistic was excellent (>0.9) for 4 of the 7 biomarkers, strong (0.6–0.8) for 2, and fair for only 1 (owing to low prevalence). CONCLUSIONS These results indicate immunostaining for biomarkers commonly used to evaluate breast cancer biology and assign surrogate molecular phenotypes can reliably be employed on archival FFPE specimens up to 60 years old

The impact of low input DNA on the reliability of DNA methylation as measured by the Illumina Infinium MethylationEPIC BeadChip

DNA methylation (DNAm) is commonly assayed using the Illumina Infinium MethylationEPIC BeadChip, but there is currently little published evidence to define the lower limits of the amount of DNA that can be used whilst preserving data quality. Such evidence is valuable for analyses utilizing precious or limited DNA sources. We used a single pooled sample of DNA in quadruplicate at three dilutions to define replicability and noise, and an independent population dataset of 328 individuals (from a community-based study including US-born non-Hispanic Black and white persons) to assess the impact of total DNA input on the quality of data generated using the Illumina Infinium MethylationEPIC BeadChip. We found that data are less reliable and more noisy as DNA input decreases to 40ng, with clear reductions in data quality; and that low DNA input is associated with a reduction in power to detect EWAS associations, requiring larger sample sizes. We conclude that DNA input as low as 40ng can be used with the Illumina Infinium MethylationEPIC BeadChip, provided quality checks and sensitivity analyses are undertaken

The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology

Black carbon exposure, socioeconomic and racial/ethnic spatial polarization, and the Index of Concentration at the Extremes (ICE)

Background: Scant data quantify associations between economic and racial/ethnic spatial polarization and individual&apos;s exposure to pollution. Methods: We linked data on the socioeconomic position (SEP) of 1757 urban working class white, black, and Latino adults (age 25-64; Boston, MA: 2003-2004; 2008-2010) to: (1) spatiotemporal model-based estimates of cumulative black carbon exposure at their exact residential address, and (2) their census tract values for the Index of Concentration at the Extremes (ICE) for SEP and race/ethnicity. Results: ICE measures, but not individual- and household-SEP, remained independently associated with black carbon exposure. Conclusions: The ICE may be useful for environmental health research. (C) 2015 Elsevier Ltd. All rights reserved

The Hyperemesis Impact of Symptoms Questionnaire: Development and validation of a clinical tool

Background The Hyperemesis Impact of Symptoms Questionnaire is a clinical tool designed to assess holistically the impact of the physical and psychosocial symptoms of hyperemesis gravidarum (HG) on individuals. Its purpose is to aid planning and implementation of tailored care for women with HG. To our knowledge no similar tool exists. Objective To assess the validity and reliability of the HIS questionnaire. Design As no similar tool exists, we compared the HIS with three tools that reflect its key areas: physical impact (Pregnancy Unique Quantification of Emesis – PUQE score and markers of severity of HG), psychological impact (Hospital Anxiety and Depression Score – HADS) and social impact (SF12 quality of life score). Setting A large regional referral, women and children's hospital in the North West of England. Participants The HIS was evaluated on 50 women admitted to hospital with HG and 50 women recruited from ante-natal clinic without severe nausea and vomiting of pregnancy and with an uncomplicated pregnancy. Results Good criterion validity was demonstrated by strong significant correlations with all three scores (PUQE, r = 0.75, p < 0.001, HADS, depression r = 0.76, p < 0.001, and SF12, mental component r = −0.65, p < 0.001). The HIS showed good internal consistency, Cronbach alpha 0.87, split half 0.80. Conclusions There is evidence for the validity and reliability of the HIS to assess the impact of the physical and psychosocial symptoms of HG. Further research is currently underway to establish the clinical utility of the HIS questionnaire in the care of women hospitalised with HG