Publications by authors named "Julia Holmes"

12 Publications

  • Page 1 of 1

Radial Profile Analysis of Epithelial Polarity in Breast Acini: A Tool for Primary (Breast) Cancer Prevention.

Front Med (Lausanne) 2019 10;6:314. Epub 2020 Jan 10.

Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC, United States.

Preventing cancer is vastly better than treating the disease in terms of a patient's quality of life and healthcare costs. Yet, to screen for chemopreventative drugs or evaluate interventions aimed at lowering cancer risk, quantitative readouts of risk are needed. In the breast and in other organs of epithelial origin, apical-basal polarity is key to homeostasis and is one of the first tissue characteristics lost during cancer initiation. Therefore, apical-basal polarity may be leveraged as an "architectural" determinant of cancer risk. A classic approach to quantify the localization of epithelial polarity markers is visual scoring at the microscope by trained investigators. This approach is time-intensive and limited to low throughput. To increase the speed, accuracy, and scoring volume, we developed an algorithm that essentially replaces the human eye to objectively quantify epithelial polarity in microscopy images of breast glandular units (acini). Acini in culture are identified based on a nuclear stain and the corresponding masks are divided into concentric terraces of equal width. This positional information is used to calculate radial intensity profiles (RP) of polarity markers. Profiles with a steep slope represent polarized structures, whereas more horizontal curves are indicative of non-polarized acini. To compare treatment effects, RP curves are integrated into summary values of polarity. We envision applications of this method for primary cancer prevention research with acini organoids, specifically (1) to screen for chemoprevention drugs, (2) for toxicological assessment of suspected carcinogens and pharmacological hit compounds, and (3) for personalized evaluation of cancer risk and risk-reducing interventions. The RadialProfiler algorithm developed for the MATLAB computing environment and for users without prior informatics knowledge is publicly available on the Open Science Framework (OSF).
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http://dx.doi.org/10.3389/fmed.2019.00314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970192PMC
January 2020

Elevated leptin disrupts epithelial polarity and promotes premalignant alterations in the mammary gland.

Oncogene 2019 05 22;38(20):3855-3870. Epub 2019 Jan 22.

Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.

Obesity is a highly prevalent and modifiable breast cancer risk factor. While the role of obesity in fueling breast cancer progression is well established, the mechanisms linking obesity to breast cancer initiation are poorly understood. A hallmark of breast cancer initiation is the disruption of apical polarity in mammary glands. Here we show that mice with diet-induced obesity display mislocalization of Par3, a regulator of cellular junctional complexes defining mammary epithelial polarity. We found that epithelial polarity loss also occurs in a 3D coculture system that combines acini with human mammary adipose tissue, and establish that a paracrine effect of the tissue adipokine leptin causes loss of polarity by overactivation of the PI3K/Akt pathway. Leptin sensitizes non-neoplastic cells to proliferative stimuli, causes mitotic spindle misalignment, and expands the pool of cells with stem/progenitor characteristics, which are early steps for cancer initiation. We also found that normal breast tissue samples with high leptin/adiponectin transcript ratio characteristic of obesity have an altered distribution of apical polarity markers. This effect is associated with increased epithelial cell layers. Our results provide a molecular basis for early alterations in epithelial architecture during obesity-mediated cancer initiation.
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http://dx.doi.org/10.1038/s41388-019-0687-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525037PMC
May 2019

National Center for Health Statistics Guidelines for Analysis of Trends.

Vital Health Stat 2 2018 Apr(179):1-71

Many reports present analyses of trends over time based on multiple years of data from National Center for Health Statistics (NCHS) surveys and the National Vital Statistics System (NVSS). Trend analyses of NCHS data involve analytic choices that can lead to different conclusions about the trends. This report discusses issues that should be considered when conducting a time trend analysis using NCHS data and presents guidelines for making trend analysis choices. Trend analysis issues discussed include: choosing the observed time points to include in the analysis, considerations for survey data and vital records data (record level and aggregated), a general approach for conducting trend analyses, assorted other analytic issues, and joinpoint regression. This report provides 12 guidelines for trend analyses, examples of analyses using NCHS survey and vital records data, statistical details for some analysis issues, and SAS and SUDAAN code for specification of joinpoint regression models. Several an lytic choices must be made during the course of a trend analysis, and the choices made can affect the results. This report highlights the strengths and limitations of different choices and presents guidelines for making some of these choices. While this report focuses on time trend analyses, the issues discussed and guidelines presented are applicable to trend analyses involving other ordinal and interval variables.
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April 2018

Mortality among US-born and immigrant Hispanics in the US: effects of nativity, duration of residence, and age at immigration.

Int J Public Health 2015 Jul 29;60(5):609-17. Epub 2015 May 29.

Centers for Disease Control and Prevention, National Center for Health Statistics, 3311 Toledo Road, Room 6126, Hyattsville, MD, 20782, USA,

Objectives: We examined the effects of duration of residence and age at immigration on mortality among US-born and foreign-born Hispanics aged 25 and older.

Methods: We analyzed the National Health Interview Survey-National Death Index linked files from 1997-2009 with mortality follow-up through 2011. We used Cox proportional hazard models to examine the effects of duration of US residence and age at immigration on mortality for US-born and foreign-born Hispanics, controlling for various demographic, socioeconomic and health factors. Age at immigration included 4 age groups: <18, 18-24, 25-34, and 35+ years. Duration of residence was 0-15 and >15 years.

Results: We observed a mortality advantage among Hispanic immigrants compared to US-born Hispanics only for those who had come to the US after age 24 regardless of how long they had lived in the US. Hispanics who immigrated as youths (<18) did not differ from US-born Hispanics on mortality despite duration of residence.

Conclusions: Findings suggest that age at immigration, rather than duration of residence, drives differences in mortality between Hispanic immigrants and the US-born Hispanic population.
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http://dx.doi.org/10.1007/s00038-015-0686-7DOI Listing
July 2015

Aging differently: Physical limitations among adults aged 50 years and over: United States, 2001-2007.

NCHS Data Brief 2009 Jul(20):1-8

Centers for Disease Control and Prevention National Center for Health Statistics, Hyattsville, Maryland, USA.

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July 2009

Use and in-hospital mortality associated with two cardiac procedures, by sex and age: national trends, 1990-2004.

Health Aff (Millwood) 2007 Jan-Feb;26(1):169-77

National Center for Health Statistics, Hyattsville, Maryland, USA.

This study used data from the National Hospital Discharge Survey to examine sex- and age-specific trends in use and in-hospital mortality associated with coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) among adults age forty-five and older during 1990-2004. Although use rates for PCI increased 58 percent over the study period, CABG use rates declined. In-hospital death rates declined or stayed the same even though comorbidities increased for patients who received the procedures. PCI and CABG use rates for men were at least twice those for women, although women generally had more comorbidities and higher in-hospital death rates.
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http://dx.doi.org/10.1377/hlthaff.26.1.169DOI Listing
May 2007

Beyond the initial indicators: lessons from the OECD Health Care Quality Indicators Project and the US National Healthcare Quality Report.

Int J Qual Health Care 2006 Sep;18 Suppl 1:45-51

Health Care Quality Indicators Project, Organization for Economic Cooperation and Development, 2 Rue André Pascal, 75775 Paris, Cedex 16, France.

Unlabelled: Interest in comparative quality measurement and evaluation has grown considerably over the past two decades because of factors such as the recognition of widespread variation in clinical practice, the increased availability of evidence about medical effectiveness, and increasing concern about the cost and quality of health care. This article describes and contrasts two current efforts to develop health performance reporting systems: one, an international initiative-the Health Care Quality Indicator (HCQI) Project, sponsored by the Organization for Economic Cooperation and Development (OECD); and the other, a national project-the National Healthcare Quality Report (NHQR), sponsored by the US Agency for Healthcare Quality and Research. There are a number of lessons learned from a comparison of the two efforts that are relevant for the future of each project and for other indicator-based reporting efforts in quality of health care. These lessons are discussed in the article and include: Conceptual frameworks should be established to guide the selection of indicators. Choices should be made early on in the process to focus on a wide range of clinical conditions or to report on a few priority areas.

Methods: should be developed to add and subtract indicators while maintaining a stable set of indicators to track over time. Resources should be allocated to communication strategies and how best to present data results to diverse audiences. Mechanisms should be put in place to maintain project momentum.
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http://dx.doi.org/10.1093/intqhc/mzl027DOI Listing
September 2006

Preparing the national healthcare disparities report: gaps in data for assessing racial, ethnic, and socioeconomic disparities in health care.

Med Care 2005 Mar;43(3 Suppl):I9-16

Agency for Healthcare Research and Quality, US Department of Health and Human Services, Rockville, MD 20850, USA.

Background: Efforts to quantify, monitor, understand, and reduce disparities in health care are critically dependent on the collection of high-quality data that support such analyses. In producing the first National Healthcare Disparities Report (NHDR), a number of gaps in data were encountered that limited the ability to assess racial, ethnic, and socioeconomic disparities in health care.

Objectives: The objectives of this study were to identify and quantify gaps in data related to disparities in health care and discuss efforts to fill these gaps in future NHDRs.

Findings: : Data on specific racial, ethnic, and socioeconomic groups were often not collected or collected in formats that differed from federal standards. When collected, data were often insufficient to generate reliable estimates for specific racial, ethnic, and socioeconomic groups. These effects were magnified when attempting to assess disparities within many of the agency's priority populations such as women, children, the elderly, low-income populations, and rural residents. Future NHDRs begin to fill some of these gaps in data, but some gaps will likely persist and new gaps will likely arise as the availability of data for specific populations vary from year to year.

Conclusions: Gaps in data limit the ability to address racial, ethnic, and socioeconomic disparities in health care. Although many federal efforts are underway to improve data collection, some groups and populations pose unique challenges for data collection that will be difficult to overcome.
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March 2005

Heart disease and prevention: race and age differences in heart disease prevention, treatment, and mortality.

Med Care 2005 Mar;43(3 Suppl):I33-41

National Center for Health Statistics, Centers for Disease Control and Prevention, US Department of Health and Human Services, Hyattsville, MD 20782, USA.

Objective: The objective of this study was to analyze race and age differences in the distribution of health promotion and cardiovascular screening tests, and the prevalence of serious heart disease and cardiovascular mortality in the United States. DATA SOURCES/STUDY POPULATION: Data are from 7 federal datasets represented in the first National Healthcare Quality Report and the National Healthcare Disparities Report, and include surveys, administrative and vital statistics data systems. The study analyzes blacks and whites.

Measures: Counseling on diet and nutrition, exercise, and tobacco during an outpatient visit indicate the availability of health promotion services, and screening for high blood pressure and cholesterol represent preventive services. Hospitalizations for heart-related conditions and use of certain cardiac procedures identify serious heart disease. Deaths from coronary artery disease and stroke are the heart-related mortality measures.

Principal Findings: Counseling and education services tend to occur more on outpatient visits by individuals aged 45 to 64 years than in younger age groups. Screening rates among individuals aged 45 to 64 years of approximately 90% for hypertension and 80% for high cholesterol suggest progress in early detection of cardiac risk factors. However, blacks aged 45 to 64 years are 5.6 times more likely than their white counterparts to be hospitalized for hypertension, approximately one third less likely to receive a cardiac procedure, and almost twice as likely to die of coronary heart disease.

Conclusions: Although findings indicate few racial differences in health promotion services in ambulatory care or screening for cardiac risk factors, the prevalence of serious cardiovascular disease, use of cardiac procedures, and heart-related mortality suggest continuing racial disparities in heart disease.
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March 2005

Measurement challenges in developing the national healthcare quality report and the national healthcare disparities report.

Med Care 2005 Mar;43(3 Suppl):I17-23

National Center for Health Statistics, Centers for Disease Control and Prevention, US Department of Health and Human Services, Hyattssville, MD 20782, USA.

Objectives: The objective of this study was to describe 2 measurement challenges faced in the development of the National Healthcare Quality Report (NHQR) and the National Healthcare Disparities Report (NHDR): the use of federal data on race and ethnicity and the selection of measures of socioeconomic status (SES).

Methods: Over 30 federal and nonfederal data systems were examined to identify measures of race, ethnicity, and SES and to evaluate the characteristics and relative quality of the data.

Results: The availability and quality of data on race, ethnicity, and SES vary by factors such as the type of data (population or establishment based-survey, administrative/claims data, or vital statistics), the source of information (self, proxy, other, or some combination), and the transition to new federal standards. No single measure of SES could be identified, so a mix of measures is presented, including income, education, and expected source of payment (ESOP). Income relative to federal poverty level was used as the preferred SES measure from person-based surveys. Selected analyses linking hospital discharge data to annual median household income from US census data were presented for data derived from administrative data systems. Educational attainment was the variable used for examining SES using data from the Vital Statistics System.

Conclusions: The first NHQR and NHDR maximized the presentation of data by accommodating the variation among data systems while at the same time imposing some standardization in the coding and classification of data on race, ethnicity, and SES.
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http://dx.doi.org/10.1097/00005650-200503001-00004DOI Listing
March 2005

Translating research into practice: are physicians following evidence-based guidelines in the treatment of hypertension?

Med Care Res Rev 2004 Dec;61(4):453-73

National Center for Health Statistics, Centers for Disease Control and Prevention, USA.

Despite the widespread availability of evidence-based guidelines for treating hypertension, recent evidence suggests that physicians may not be prescribing first-line drugs for their patients with high blood pressure. Using administrative claims data from 1998 through 2000, this study investigates whether drug treatment provided to 6,736 hypertensives in a privately insured, non-HMO population follows practice guidelines. The authors also examine physician and patient-related factors associated with guideline adherence in a subset of patients with newly diagnosed hypertension. Among members with high blood pressure alone, only 38 percent were on a diuretic, while less than a third were prescribed a beta-blocker, the JNC VI recommended first-line antihypertensives for essential hypertension. Approximately half of individuals with high blood pressure and certain comorbidities received non-first-line interventions. Such findings indicate the need to reconsider how guidelines are communicated and shared with medical practitioners and patients, particularly in light of the drug industry's promotion of newer, more expensive drugs.
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http://dx.doi.org/10.1177/1077558704269501DOI Listing
December 2004