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"Rozek, Laura S."
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Understanding Vaccine Hesitancy in the Context of COVID-19: The Role of Trust and Confidence in a Seventeen-Country Survey
by
King, Elizabeth J.
,
Jones, Pauline
,
Menon, Anil
in
Coronaviruses
,
COVID-19
,
COVID-19 vaccines
2021
Objectives: An effective vaccine to SARS-CoV-2 cannot be successfully deployed if a significant number of people worldwide are unwilling to accept it. We investigated the relationship between trust in scientists and medical professionals and perceptions of vaccine safety and effectiveness. We also build on past studies by exploring the relationship between confidence in global health organizations and vaccine hesitancy. Methods: We conducted an online survey in seventeen countries/territories across five world regions between May -June 2020. We assessed the relationship between COVID19 vaccine hesitancy, confidence in public health organizations, and trust in key experts and leaders. Results: Our findings strongly suggest that confidence in the World Health Organization combined with trust in domestic scientists and healthcare professionals is a strong driver of vaccine acceptance across multiple countries/territories. Conclusion: We find that hesitancy is widespread, and uptake would be insufficient to achieve herd immunity. There is widespread confidence in how public health organizations have responded to the current pandemic and this is related to vaccine acceptance. Our results also highlight the important role of trust in health care providers and scientists in reducing COVID19 vaccine hesitancy.
Journal Article
LRpath analysis reveals common pathways dysregulated via DNA methylation across cancer types
by
Karnovsky, Alla
,
Pande, Manjusha
,
Rozek, Laura S
in
Animal Genetics and Genomics
,
Biomedical and Life Sciences
,
Cancer
2012
Background
The relative contribution of epigenetic mechanisms to carcinogenesis is not well understood, including the extent to which epigenetic dysregulation and somatic mutations target similar genes and pathways. We hypothesize that during carcinogenesis, certain pathways or biological gene sets are commonly dysregulated via DNA methylation across cancer types. The ability of our logistic regression-based gene set enrichment method to implicate important biological pathways in high-throughput data is well established.
Results
We developed a web-based gene set enrichment application called LRpath with clustering functionality that allows for identification and comparison of pathway signatures across multiple studies. Here, we employed LRpath analysis to unravel the commonly altered pathways and other gene sets across ten cancer studies employing DNA methylation data profiled with the Illumina HumanMethylation27 BeadChip. We observed a surprising level of concordance in differential methylation across multiple cancer types. For example, among commonly hypomethylated groups, we identified immune-related functions, peptidase activity, and epidermis/keratinocyte development and differentiation. Commonly hypermethylated groups included homeobox and other DNA-binding genes, nervous system and embryonic development, and voltage-gated potassium channels. For many gene sets, we observed significant overlap in the specific subset of differentially methylated genes. Interestingly, fewer DNA repair genes were differentially methylated than expected by chance.
Conclusions
Clustering analysis performed with LRpath revealed tightly clustered concepts enriched for differential methylation. Several well-known cancer-related pathways were significantly affected, while others were depleted in differential methylation. We conclude that DNA methylation changes in cancer tend to target a subset of the known cancer pathways affected by genetic aberrations.
Journal Article
Breast Cancer Incidence Trends and Projections in Northeastern Thailand
by
Chindaprasirt, Jarin
,
Wirasorn, Kosin
,
Vachirodom, Damnern
in
Breast cancer
,
Cancer
,
epidemiology
2018
Background: The northeast has the lowest incidence of breast cancer of all regions in Thailand, although national rates are increasing. The heterogeneity in subnational trends necessitates a comprehensive evaluation of breast cancer incidence trends and projections to provide evidence for future region-specific strategies that may be employed to attenuate this growing burden. Methods: Joinpoint regression and age-period-cohort modeling were used to describe trends from 1988–2012. Data was projected from three separate models to provide a range of estimates of incidence to the year 2030 by age group. Results: Age-standardized rates (ASRs) increased significantly for all women from 1995–2012 by 4.5% per year. Rates for women below age 50 increased by 5.1% per year, while women age 50 years and older increased by 6% per year from 1988–2012. Projected rates show that women age 50 years and older have the largest projected increase in ASRs by 2030 compared to younger women and all women combined. Conclusions: Breast cancer trends in Khon Kaen are presently lower than other regions but are expected to increase and become comparable to other regions by 2030, particularly for women ages 50 years and older.
Journal Article
Global adoption of personal and social mitigation behaviors during COVID-19: The role of trust & confidence
2021
What influences the adoption of SARS-CoV-2 mitigation behaviors–both personal, such as mask wearing and frequent handwashing, and social, such as avoiding large gatherings and physical contact–across countries? Understanding why some individuals are more willing to change their behavior to mitigate the spread of a pandemic will not only help us to address the current SARS-CoV-2 pandemic but also to respond to future ones. Researchers have pointed to a variety of factors that may influence individual adoption of personal and social mitigation behaviors, including social inequality, risk perception, personality traits, and government policies. While not denying the importance of these factors, we argue that the role of trust and confidence has received insufficient attention to date. Our study explores whether there is a difference in the way trust and confidence in particular leaders and organizations affect individual compliance and whether this effect is consistent across different types of mitigation behaviors. Specifically, we utilize an original cross-national survey conducted during the first wave of the SARS-CoV-2 pandemic (May-June 2020) to investigate how trust in scientists, medical professionals, politicians, and religious leaders and confidence in global, national, and local health organizations affects individual compliance in 16 countries/territories across five world regions. Our analyses, which control for the aforementioned factors as well as several others, suggest that trust in politicians and confidence in national health ministries have the most consistent influence on whether individuals adopt both personal and social mitigation behaviors. Across our sample, we find that greater trust in politicians is associated with lower levels of individual compliance with public health directives, whereas greater confidence in the national health ministry is associated with higher levels of individual compliance. Our findings suggest the need to understand trust and confidence as among the most important individual level characteristics driving compliance when developing and delivering messaging about the adoption of mitigation behaviors. The content of the message, it seems, will be most effective when citizens across countries trust its source. Trusted sources, such as politicians and the national health ministry, should thus consider working closely together when determining and communicating recommended health behaviors to avoid contradicting one another.
Journal Article
Comprehensive Analysis of DNA Methylation in Head and Neck Squamous Cell Carcinoma Indicates Differences by Survival and Clinicopathologic Characteristics
2013
Head and neck squamous cell carcinoma (HNSCC) is the eighth most commonly diagnosed cancer in the United States. The risk of developing HNSCC increases with exposure to tobacco, alcohol and infection with human papilloma virus (HPV). HPV-associated HNSCCs have a distinct risk profile and improved prognosis compared to cancers associated with tobacco and alcohol exposure. Epigenetic changes are an important mechanism in carcinogenic progression, but how these changes differ between viral- and chemical-induced cancers remains unknown. CpG methylation at 1505 CpG sites across 807 genes in 68 well-annotated HNSCC tumor samples from the University of Michigan Head and Neck SPORE patient population were quantified using the Illumina Goldengate Methylation Cancer Panel. Unsupervised hierarchical clustering based on methylation identified 6 distinct tumor clusters, which significantly differed by age, HPV status, and three year survival. Weighted linear modeling was used to identify differentially methylated genes based on epidemiological characteristics. Consistent with previous in vitro findings by our group, methylation of sites in the CCNA1 promoter was found to be higher in HPV(+) tumors, which was validated in an additional sample set of 128 tumors. After adjusting for cancer site, stage, age, gender, alcohol consumption, and smoking status, HPV status was found to be a significant predictor for DNA methylation at an additional 11 genes, including CASP8 and SYBL1. These findings provide insight into the epigenetic regulation of viral vs. chemical carcinogenesis and could provide novel targets for development of individualized therapeutic and prevention regimens based on environmental exposures.
Journal Article
Descriptive Epidemiology of breast and gynecological cancers among patients attending Saint Paul’s Hospital Millennium Medical College, Ethiopia
by
Mondul, Alison M.
,
Hailu, Haimanot E.
,
Rozek, Laura S.
in
Breast cancer
,
Cancer patients
,
Cancer prevention
2020
Cancer is a leading cause of death in both more and less economically developed countries; the burden is expected to grow in less developed countries, such as Ethiopia. Lack of adequate information is one of the major problems preventing the design of cancer control strategies in Ethiopia.
To characterize gynecological and breast cancers among clients attending Gynecologic clinic of Saint Paul Hospital Millennium Medical college over 5 year period.
We retrospectively reviewed characteristics of 2,002 female cancer patients who visited the Oncology unit of Saint Paul's Hospital Millennium Medical College from 2014-2018. We estimated the proportion, pattern and trend of common types of gynecologic cancers as well as breast cancer. The ten years incidence projection was also computed.
From the 2,002 malignancies, cervical (46.7%) was the most frequent cancer followed by breast (29.3%) and ovarian cancers (13%). The majority of breast cancers were observed among younger patients whereas cervical cancer was predominantly observed among older women. An overall increment in number of breast and gynecologic cancer was observed over the five years period.
In this descriptive study, we found that breast and gynecologic cancers are important public health problems among women in Addis Ababa, and that the number of patients seeking care for these cancers is increasing. Additional studies are needed to identify risk factors for these cancers, particularly among younger women, to characterize the trends over time and to project the scope of the cancer problem expected in the future to inform cancer control programs. Increasing public awareness on the possible risk factors and screening is mandatory in addition to resource allocation for further studies and targeted intervention.
Journal Article
A Prospective Study of LINE-1DNA Methylation and Development of Adiposity in School-Age Children
by
Marín, Constanza
,
Mora-Plazas, Mercedes
,
Baylin, Ana
in
Adipose tissue
,
Adiposity
,
Anthropometry
2013
Repetitive element DNA methylation is related to prominent obesity-related chronic diseases including cancer and cardiovascular disease; yet, little is known of its relation with weight status. We examined associations of LINE-1 DNA methylation with changes in adiposity and linear growth in a longitudinal study of school-age children from Bogotá, Colombia.
We quantified methylation of LINE-1 elements from peripheral leukocytes of 553 children aged 5-12 years at baseline using pyrosequencing technology. Anthropometric characteristics were measured periodically for a median of 30 months. We estimated mean change in three age-and sex-standardized indicators of adiposity: body mass index (BMI)-for-age Z-score, waist circumference Z-score, and subscapular-to-triceps skinfold thickness ratio Z-score according to quartiles of LINE-1 methylation using mixed effects regression models. We also examined associations with height-for-age Z-score.
There were non-linear, inverse relations of LINE-1 methylation with BMI-for-age Z-score and the skinfold thickness ratio Z-score. After adjustment for baseline age and socioeconomic status, boys in the lowest quartile of LINE-1 methylation experienced annual gains in BMI-for-age Z-score and skinfold thickness ratio Z-score that were 0.06 Z/year (P = 0.04) and 0.07 Z/year (P = 0.03), respectively, higher than those in the upper three quartiles. The relation of LINE-1 methylation and annual change in waist circumference followed a decreasing monotonic trend across the four quartiles (P trend = 0.02). DNA methylation was not related to any of the adiposity indicators in girls. There were no associations between LINE-1 methylation and linear growth in either sex.
Lower LINE-1 DNA methylation is related to development of adiposity in boys.
Journal Article
The role of area‐level socioeconomic disadvantage in racial disparities in cancer incidence in metropolitan Detroit
2023
Background Neighborhood deprivation is associated with both race and cancer incidence, but there is a need to better understand the effect of structural inequities on racial cancer disparities. The goal of this analysis was to evaluate the relationship between a comprehensive measure of neighborhood‐level social disadvantage and cancer incidence within the racially diverse population of metropolitan Detroit. Methods We estimated breast, colorectal, lung, and prostate cancer incidence rates using Metropolitan Detroit Cancer Surveillance System and US decennial census data. Neighborhood socioeconomic disadvantage was measured by the Area Deprivation Index (ADI) using Census Bureau's American Community Survey data at the Public Use Microdata Areas (PUMA) level. Associations between ADI at time of diagnosis and cancer incidence were estimated using Poisson mixed‐effects models adjusting for age and sex. Attenuation of race‐incidence associations by ADI was quantified using the “mediation” package in R. Results ADI was inversely associated with incidence of breast cancer for both non‐Hispanic White (NHW) and non‐Hispanic Black (NHB) women (NHW: per‐quartile RR = 0.92, 95% CI 0.88–0.96; NHB: per‐quartile RR = 0.94, 95% CI 0.91–0.98) and with prostate cancer incidence only for NHW men (per‐quartile RR = 0.94, 95% CI 0.90–0.97). ADI was positively associated with incidence of lung cancer for NHWs and NHBs (NHW: per‐quartile RR = 1.12, 95% CI 1.04–1.21; NHB: per‐quartile RR = 1.37, 95% CI 1.25–1.51) and incidence of colorectal cancer (CRC) only among NHBs (per‐quartile RR = 1.11, 95% CI 1.02–1.21). ADI significantly attenuated the relationship between race and hormone receptor positive, HER2‐negative breast cancer (proportion attenuated = 8.5%, 95% CI 4.1–16.6%) and CRC cancer (proportion attenuated = 7.3%, 95% CI 3.7 to 12.8%), and there was a significant interaction between race and ADI for lung (interaction RR = 1.22, p < 0.0001) and prostate cancer (interaction RR = 1.09, p = 0.00092). Conclusions Area‐level socioeconomic disadvantage is associated with risk of common cancers in a racially diverse population and plays a role in racial differences in cancer incidence.
Journal Article
Exposure to phthalates among premenstrual girls from rural and urban Gharbiah, Egypt: A pilot exposure assessment study
2011
Background
Phthalates have been identified as endocrine active compounds associated with developmental and reproductive toxicity. The exposure to phthalates in premenstrual Egyptian females remains unknown. The objective of this study was to characterize phthalate exposure of a potentially vulnerable population of premenstrual girls from urban and rural Egypt.
Materials and methods
We collected one spot urine sample from 60 10-13 year old females, 30 from rural Egypt, and 30 from urban Egypt from July to October 2009. Samples were analyzed for 11 phthalate metabolites. Additionally, we collected anthropometrics as well as questionnaire data concerning food storage behaviors, cooking practices, and cosmetic use. Phthalate metabolite concentrations were compared between urban and rural Egyptians as well as to age and gender matched Americans.
Results
Monoethyl phthalate (MEP), was detected at the highest concentration in urine of Egyptian girls (median: 43.2 ng/mL in rural, 98.8 ng/mL in urban). Concentrations of urinary metabolites of di-(2-ethylhexyl) phthalate and dibutyl phthalate were comparable between Egyptians and age matched US girls. Storage of food in plastic containers was a statistically significant predictor of urinary mono-isobutyl phthalate (MiBP) concentrations when comparing covariate adjusted means.
Conclusions
Urinary concentrations of phthalate metabolites were similar in Egyptian and US populations, suggesting that phthalate exposure also occurs in developing nations. Dietary intake is likely an important route of exposure to phthalates in both urban and rural populations.
Journal Article
Plasminogen Is a Critical Host Pathogenicity Factor for Group A Streptococcal Infection
by
Wang, Xixi
,
Ringdahl, Ulrika
,
Homeister, Jonathon W.
in
Ancrod - pharmacology
,
Animals
,
Anticoagulants - pharmacology
2004
Group A streptococci, a common human pathogen, secrete streptokinase, which activates the host's blood clot-dissolving protein, plasminogen. Streptokinase is highly specific for human plasminogen, exhibiting little or no activity against other mammalian species, including mouse. Here, a transgene expressing human plasminogen markedly increased mortality in mice infected with streptococci, and this susceptibility was dependent on bacterial streptokinase expression. Thus, streptokinase is a key pathogenicity factor and the primary determinant of host species specificity for group A streptococcal infection. In addition, local fibrin clot formation may be implicated in host defense against microbial pathogens.
Journal Article