Research Briefs

Research Briefs: highlight studies that bridge social science, culture, and medicine. BCC reports on methods, key findings, and implications of key research. We support evidence-based medicine and initiatives aimed at fostering a new social contract between society, the medical profession, and the health care system.

Quality of Life, Overall Survival, and Costs of Cancer Drugs Approved Based on Surrogate Endpoints

A study analyzing the annual cost and clinically meaningful benefit of 18 cancer drugs approved by the U.S. Food and Drug Administration’s (FDA) Accelerated Approval Program between 2008 and 2012 found that despite showing an initial benefit, most did not ultimately improve overall survival or quality of life. In addition, the vast majority of drugs approved through the FDA’s accelerated system maintain their approvals even if later studies find them to be dangerous or inferior to existing treatments.

Source: Rupp T, Zuckerman D. “Quality of Life, Overall Survival, and Costs of Cancer Drugs Approved Based on Surrogate Endpoints.” JAMA Internal Medicine. 2017;177(2):276-277. doi:10.1001/jamainternmed.2016.7761.

Breast Cancer Representations in Canadian News Media: A Critical Discourse Analysis of Meanings and the Implications for Identity

Mass media has been a significant vehicle for disseminating breast cancer’s social status and cultural meanings for decades. But analyses of mass media also reveal taken for granted assumptions and prevailing meanings about the disease within the context of prevailing discourses. This study explores the cultural construction of breast cancer within Canada’s two national newspapers. The discourses of biomedicine and healthism worked in conjunction with the subject positions of breast cancer survivor, good consumer, and medical expert to privilege technoscience and regulate women’s health, ultimately serving the medical industry itself.

Source: Kerry R. McGannon, Tanya R. Berry, Wendy M. Rodgers & John C. Spence. 2016. “Breast cancer representations in Canadian news media: a critical discourse analysis of meanings and the implications for identity.” Qualitative Research in Psychology, 13:2, 188-207, DOI: 10.1080/14780887.2016.1145774.

Couples Dealing With Breast Cancer – The Role of Husbands in Supporting their Wives (Poland)

This Polish study explores how spouses cope with a wife’s breast cancer diagnosis and what kinds of support they provide. The researchers find that despite the increased visibility of cancer in Poland, the medicalized focus on the disease is so strong that there is little information available to the public about its impact on family life or the caregiver role. A lack of social support systems from health professionals, within public institutions, and even within the breast cancer support groups themselves place the full burden of care within the family domain. As a result, families become isolated and overloaded, often experiencing feelings of incompetence, frustration, and helplessness. What’s more, ubiquitous stereotypical gender expectations about women’s and men’s caregiving roles, solidly lodged in Polish culture, do not prepare men to take care of their sick wives and young children. The resultant miscommunications inhibit social support further.

Source: Zierkiewicz, Edyta and Mazurek, Emilia. 2015. “Dealing with breast cancer – the role of husbands in supporting their wives.” STUDIA HUMANISTYCZNE AGH. [].

Breast-conserving Therapy Yielded Better Outcomes Than Mastectomy for Early-stage Patients

Breast-conserving surgery plus radiation therapy, when compared to mastectomy without radiation therapy, resulted in improved overall survival after 10 years for patients with early-stage breast cancer. At a median 11.3-year-follow-up and after statistically adjusting for confounding factors (such as age, tumor characteristics, and use of adjuvant therapies), women with breast-conserving surgery plus radiation therapy, were about 21 percent more likely to be alive after 10 years compared with their counterparts who had a mastectomy.

Source: van Maaren MC, de Munck L, de Bock GH, et al. “Higher 10-year overall survival after breast conserving therapy compared to mastectomy in early stage breast cancer: a population-based study with 37,207 patients.” Presented at: San Antonio Breast Cancer Symposium; December 8-12, 2015; San Antonio, TX. Abstract: S3-05. Presentation details provided by OncLive.

Screening Mammography Rates in the Medicare Population before and after the 2009 U.S. Preventive Services Task Force Guideline Change

This study explores how the 2009 guidelines on screening mammography released by the US Preventive Services Task Force (USPSTF) may have affected screening mammography rates among women aged 65 and older. After the release of the new guidelines the researchers found an immediate and significant — though short-term — decrease in screening for all groups studied. Three years later after the initial decline, the screening rate stabilized for women aged 65 to 74 and continued to decline for those aged 75 and older. The research strongly suggests: “Behavioral changes should be anticipated when professional organizations issue competing guidelines; their important public policy implications may impact distinct demographic groups differently, and their results may not be fully quantifiable for many years after their implementation.”

Source: Miao Jiang, Danny R. Hughes, and Richard Duszak Jr. “Screening Mammography Rates in the Medicare Population before and after the 2009 U.S. Preventive Services Task Force Guideline Change: An Interrupted Time Series Analysis.” Women’s Health Issues, Vol. 25, Iss. 3 (May/June 2015), pp: 239–245.

Breast Cancer Mortality After a Diagnosis of DCIS

A recent study by Dr. Steven A. Narod and colleagues provides evidence that for most women diagnosed with ductal carcinoma in situ, DCIS, the condition will not impact life expectancy. It supports a mounting call for research to determine which cases of DCIS would benefit from milder interventions or preventive strategies rather than more aggressive treatments. But for the very small percentage of uncommon DCIS cases that ultimately prove lethal (less than one percent), research is needed to find more effective treatments.

Source: Narod, Steven A. et al., “Breast Cancer Mortality After a Diagnosis of Ductal Carcinoma In Situ,” JAMA Oncology, Aug.20, 2015, online. Doi:10.1001/jamaoncol.2015.2510.

Breast Cancer Screening, Incidence, and Mortality Across US Counties

A study published in JAMA Internal Medicine finds that more widespread breast cancer screening does not save lives as once believed. It does, however, lead to widespread overdiagnosis, as it detects cancers that would not have been fatal or harmful. This ecological study of breast cancer is important because overdiagnosis is not directly observable in individuals. Thus, it is crucial to analyze patterns and frequencies. It is the first study to compare such a large number of counties with diverse screening rates.

Source: Harding C, Pompei F, Burmistrov D, Welch H, Abebe R, Wilson R. 2015. “Breast Cancer Screening, Incidence, and Mortality Across US Counties.” JAMA Intern Med. Published online July 06, 2015.

Five Years of Cancer Drug Approvals: Pricing Models Reflect What the Market Will Bear

The price of cancer drugs regularly exceeds $100,000 per year. Although some argue that high drug costs are necessary for the development of novel and successful treatments, an analysis reported in JAMA Oncology found no relationship between the novelty of the drug and improvement in survival. The authors conclude that “current pricing models are not rational but simply reflect what the market will bear.”

Source: S. Mailankody and V. Prasad. 2015. “Five Years of Cancer Drug Approvals: Innovation, Efficacy, and Costs,” JAMA Oncology [ doi:10.1001/jamaoncol.2015.0373].

FDA Approves New Breast Cancer Drug

On February 3, 2015, the U.S. Food and Drug Administration approved a new drug for the treatment of ER+ (Estrogen-Receptor positive) and HER2- (Human Epidermal Growth Factor Receptor 2 –negative) breast cancers. The drug, called Ibrance (palbociclib) was granted FDA approval through the agency’s accelerated approval program, based on promising results from a Phase II clinical trial. Women receiving both LetrozoKle and Ibrance had a “progression free survival” (the amount of time, post-treatment, that someone has a disease without worsening symptoms) that was, on average, nearly twice as long as those who received Letrozole alone (20.2 months compared to 10.2). A Phase III trial is underway that may offer insight on the drug’s benefits for overall mortality.

Source: Finn SR et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. The Lancet 2015, 26: 25-35.

Tamoxifen for Prevention of Breast Cancer: Extended Long-Term Follow-Up of the IBIS-I Breast Cancer Prevention Trial

The longest randomized controlled trial to date on breast cancer chemoprevention with tamoxifen (a synthetic drug that blocks the effects of estrogen), IBIS-I, recently reported, after 16 years of follow-up, a 29 percent reduction in breast cancer (invasive and noninvasive types) for ‘high-risk’ women taking the drug for 5 years. The reduction in breast cancer risk occurred only in estrogen-receptor positive (ER+) breast cancer cases. With no survival benefit, treating healthy women with tamoxifen, to “chemoprevent” breast cancer exposes them to major harms, including deep vein clots, endometrial cancer, and possibly death from breast and endometrial cancers. The IBIS-I update highlighted risk reduction in getting breast cancer, but downplayed the data showing no survival benefit as well as the trend toward increased deaths from breast and endometrial cancers.

Source: Jack Cuzick et al. for IBIS-I Investigators. 2015. “Tamoxifen for prevention of breast cancer: Extended long-term follow-up of the IBIS-I breast cancer prevention trial,” Lancet Oncology [16:67-75].

JAMA Editorial on “Opting Out of Mammography”

Independent journalist Christie Aschwanden explains in the Journal of the American Medical Association how she decided (without the help of her doctor) to opt out of screening mammograms, not just in her 40s but indefinitely. She describes that soon after her 40th birthday, her gynecologist handed her a mammogram prescription. It came with no explanation of why the test was needed, what the doctor (based on her clinical experience) expected to find, a discussion of possible screening outcomes or best and worst case scenarios, or what would happen if she didn’t have the test. Having read every major study published on screening mammography during her career as a science writer, Aschwanden had questions and reservations the clinician did not want to discuss. Left to her own devices, she ultimately made her own informed decision.

Source: Aschwanden C. “Why I’m Opting out of Mammography.” JAMA Intern Med. Published online December 01, 2014.

Changing the Landscape for People Living with Metastatic Breast Cancer

The Metastatic Breast Cancer Alliance (MBCA), a 29-member coalition of breast cancer groups, individual members, and pharmaceutical companies (established Oct., 2013) released a 132-page report identifying important gaps in what we know about metastatic breast cancer. Even though between 20 percent and 30 percent of those diagnosed with “early-stage” breast cancer later develop the metastatic form of the disease, little is known about which patients have recurrences, how well they respond to treatments, how long they live, how well their medical care serves them, or how they tend to their emotional, physical, and practical needs. There is little epidemiological data or scientific research on this population, a lack of information and support services, and a gap in public awareness about the breast cancer that kills more than 40 thousand women and men every year. Over the past few decades, the duration of survival after metastatic diagnosis has increased by only a matter of months. The report analyzed clinical trials, funded research grants, patient responses to surveys, literature articles on quality of life and epidemiological studies, and interviews with select organizational leaders and MBC researchers.

Source: Metastatic Breast Cancer Alliance. 2014. “Changing the Landscape for People Living with Metastatic Breast Cancer,” c/o Avon Foundation, 777 Third Avenue, New York, NY 10017.

Cholesterol Molecule Influences Growth of ER+ Cancers

In a large portion of human breast cancers, cancer growth is closely linked to the amount of estrogen in the body. For all intents and purposes, estrogen fuels growth in these Estrogen Receptor Positive (ER+) Cancers. However, a group of researchers recently discovered that another common molecule may play a similar role. When the body breaks down cholesterol, one of its first by-products is a molecule called 27-HC. Studying mice and cancerous tissues, researchers demonstrated that 27-HC promotes growth in ER+ cancers. Besides estrogen, 27-HC is the first known molecule to stimulate such growth.

Source: Wu Q et al. 2013. “27-Hydroxycholesterol Promotes Cell-Autonomous, ER-Positive Breast Cancer Growth,” Cell Reports [14;5(3):637-4].

Prenatal and Postnatal BPA Exposure

Bisphenol-A (BPA) is a chemical used in a variety of everyday consumer products, including bicycle helmets, the plastics used to manufacture water bottles, baby bottles and utensils and the linings of many food cans. For more than a decade scientific evidence has accumulated to suggest that exposure to BPA, a chemical that is useful as a building block for plastics and epoxy resins and also closely resembles estrogen, may be linked to a host of health problems, including the development of cancers.

Sources: (1) Breast Cancer Fund. 2013. “Disrupted development: the dangers of prenatal BPA exposure,” URL: Accessed September 26, 2013; (2) Leonardo Trasande. 2014. “Further Limiting Bisphenol A In Food Uses Could Provide Health And Economic Benefits,” Health Affairs, [33(2): 316-323.]

Abolishing Mammography Screening Programs? A View from the Swiss Medical Board

One of the leading public and international health institutes in Europe, the Swiss Medical Board, was called to prepare a review of mammography screening in January of 2013. The board released a report of its findings, which were made public on February 2, 2014. Based on the board’s review of available evidence, it concluded that: (1) no new systematic screening mammography programs should be introduced, (2) all forms of mammography screening must be evaluated for quality, (3) women must be given clear and balanced information on the benefits and harms of screening, and (4) systematic mammography screening programs in Switzerland–due to the tool’s limited utility for reducing mortality and the increased likelihood of harm from overdiagnosis and overtreatment—should be phased out. The board’s strong recommendation differs dramatically from the “early detection is the best protection” slogans that pervade many breast cancer awareness campaigns and public health promotion programs internationally.

Source: Nikola Biller-Andorno, Peter Jüni. 2014. “Abolishing Mammography Screening Programs? A View from the Swiss Medical Board,” The New England Journal of Medicine [Apr. 16].

Choosing Contralateral Mastectomy

Contralateral prophylactic mastectomy (CPM) is a procedure in which a woman with breast cancer in one breast elects to have both the affected breast and healthy breast removed at the same time. Between 1998 and 2008, CPM procedures increased 15% among breast cancer patients in the United States. While removing a healthy breast does reduce the risk of developing cancer in that breast, even without surgery the actual risk of developing such cancer is very low for most women. Thus, CPM often does not improve survival among those who elect to have it. Researchers found that even when women knew about the lack of survival benefit and risks to quality of life associated with this generally safe surgery, many low risk breast cancer patients still chose to remove the healthy breast. This research sheds light on the fears and anxieties that may drive decision making among patients and has implications for communication strategies aimed at making evidence-based treatment decisions.

Source: Cemal et al. 2013. “A paradigm shift in U.S. breast reconstruction: Part 2. The influence of changing mastectomy patterns on reconstructive rate and method,” Plastic and Reconstructive Surgery [131(3):320e-6e].

Breast Cancer Survival Disparities

When researchers look at data on survival rates between black and white women diagnosed with breast cancer, they find a rather significant disparity. White women tend to live longer after diagnosis than do black women. Racial disparities in cancer survival have been acknowledged for some time, though it is recognized that the reasons for this disparity are extremely complex.

Source: Silber et al. 2013. “Characteristics associated with differences in survival among black and white women with breast cancer,” Journal of the American Medical Association [310(4):389-97].

Future Blood Test for Breast Cancer

For many years, researchers have explored possible “biomarkers” (e.g. Her2Neu) for breast cancer. These are molecules that would allow clinicians to easily test for breast cancer with non-invasive, less costly diagnostic tests. In addition to diagnostics, the identification of certain biomarkers  has  revealed different types of breast cancer that have significantly better or worse outcomes. Researchers at the Houston Methodist Research Institute published research that they believe could one day lead to a blood test using nanotechnology. The current research is promising, but has many years to go before it may have real clinical application.

Source: Li Y et al. 2014. “Circulating Proteolytic Products of Carboxypeptidase N for Early Detection of Breast Cancer,” Clinical Chemistry [60(1):233-4].

Canadian National Breast Screening Study

One of the largest studies of screening mammography, the Canadian National Breast Screening Study, found no mammography screening benefit for women aged 40 to 59 compared to clinical breast exam and routine care while exposing average-risk women to overdiagnosis and overtreatment. This randomized controlled trial followed nearly 90,000 women for up to 25 years.

Source: Miller AB, Wall C, Baines CJ, Sun P, To T, Narod SA et al. Twenty Five Year Follow-up for Breast Cancer Incidence and Mortality of the Canadian National Breast Screening Study: Randomized Screening Trial. BMJ. 348:g366. doi: 10.1136/bmj.g366.

Annual Report to the Nation on the Status of Cancer

The American Cancer Society, the Centers for Disease Control and Prevention, the National Cancer Institute, and the North American Association of Central Cancer Registries collaborate annually to provide updates on cancer incidence and death rates and trends in these outcomes for the United States. This year’s Annual Report to the Nation on the status of cancer, 1975-2010 includes the prevalence of comorbidity (the simultaneous presence of two chronic diseases or conditions in a patient, such as diabetes, chronic lung disease, cardiovascular disease and others) at the time of first cancer diagnosis among Medicare patients with lung, colorectal, breast, or prostate cancer. The report also reported on survival among these cancer patients based on the level of comorbidity found.

Source: Edwards BK, Noone AM, Mariotto AB, Simard EP, Boscoe FP, Henley SJ, Jemal A, Cho H, Anderson RN, Kohler BA, Eheman CR, Ward EM, et al. 2013. Annual Report to the Nation on the Status of Cancer, 1975-2010, Featuring Prevalence of Comorbidity and Impact on Survival Among Persons with Lung, Colorectal, Breast, or Prostate Cancer. Cancer.

The Cancer Care System in Crisis

A report from the Institute of Medicine (IOM) released September 10, 2013 calls the system of cancer care in the United States a crisis. The 17-member IOM committee that wrote the report, “Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis,” was charged with examining opportunities for, and challenges to, the delivery of high-quality cancer care as well as developing recommendations for improvement. The committee reviewed the coordination, organization, complexity, and costs of care; payment reform, disparities and access to high-quality care; quality metrics and outcomes reporting; and the growing need for survivorship care, palliative care, and family caregiving. The take-home message: “Cancer care is often not as patient centered, accessible, coordinated, or evidence based as it could be.”

Source: Laura Levit, Erin Balogh, Sharyl Nass, and Patricia A. Ganz, Editors. 2013. Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis. Institute of Medicine, The National Academies Press, Washington, D.C.

How to Evaluate On-Line Health Information

A national survey from the PEW Research Center’s Internet & American Life Project (released Jan. 2013) reported that one in three American adults surveyed had gone online to try to figure out what kind of medical condition they or someone else might have. Of these “online diagnosers,” 46 percent sought professional attention about the condition and 41 percent reported that a medical professional confirmed their diagnosis. The survey did not investigate whether the information people found online was accurate, unbiased, or based on a clear body of evidence.

Source: Susannah Fox and Maeve Duggan. 2013. “Health Online 2013,” Pew Research Center’s Internet & American Life Project, Washington, D.C. 20036. [Jan.] URL:, Accessed July 6, 2013.

“On Death and Fear”: Personal Reflection from an Oncologist 

A personal reflection published in the Journal of Clinical Oncology (PDF) by Ayelet Shai and Gilad Hirschberger reveals an unspoken truth: that oncologists who treat people with terminal illness face a fundamental inner conflict between the desire to provide empathic treatment and a natural urge to distance themselves from illness and the unsettling reminder of their own mortality.

Source: Ayelet Shai and Gilad Hirschberger. 2013. ”On Death and Fear: A Personal Reflection on the Value of Social Psychology Research to the Practice of Oncologists,” Journal of Clinical Oncology [Sep;51:2499].

Addressing Peace of Mind in Contralateral Prophylactic Mastectomy for Breast Cancer

The use of prophylactic mastectomy in the U.S. among patients with invasive breast cancer in only one breast has increased dramatically in the past two decades. Although removal of the noncancerous breast has been shown to reduce the risk for developing cancer in that breast, there is conflicting evidence on whether or not the practice actually reduces breast cancer mortality or overall death. A recent Viewpoint in the Journal of the American Medical Association states that the sense of urgency for cancer treatment and concern that any delay could worsen prognosis, coupled with a general belief that “bigger is better” when it comes to surgery, leaves patients at risk for unnecessary harm and overtreatment.

Source: Steven J. Katz, MD, MPH and Monica Morrow, MD. 2013. ”Contralateral Prophylactic Mastectomy for Breast Cancer: Addressing Peace of Mind,” JAMA [Aug;310(8):793-4].

“Carcinoma”: What’s in a name?

As part of a National Cancer Institute working group, Dr. Laura J. Esserman MD, MBA of Mt Zion Carol Franc Buck Breast Cancer Center along with colleagues Ian Thompson MD of the University of Texas Health Science Center at San Antonio and Brian Reid MD, PhD of Fred Hutchinson Cancer Research Center in Seattle, Washington, wrote an article in the Journal of the American Medical Association explaining the working group’s recommendations to reclassify some conditions currently called “cancer.” The consensus that certain conditions should be reclassified comes after years of considerable discussion in the scientific and medical communities about how certain cancer diagnoses actually contribute to overdiagnosis and overtreatment.

Source: Laura J. Esserman, MD, MBA; Ian M. Thompson, Jr, MD; Brian Reid, MD, PhD. 2013. ”Overdiagnosis and Overtreatment in CancerAn Opportunity for Improvement,” JAMA [Jul;310(8):797-798].

Chemoprevention Is No Magic Bullet

A new set of guidelines from the National Institute for Health and Care Excellence in the UK now recommends chemoprevention drugs to women who have not been diagnosed with breast cancer but are considered high-risk. The new guidelines, hailed as “historic” also suggest that the drugs tamoxifen and raloxifene may be appropriate for women of moderate risk. Before jumping on the bandwagon, it’s important to read the fine print and ask some tough questions.

SourceFamilial Breast Cancer, NICE clinical guideline 164, National Institute for Health and Care Excellence Level 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT [ISBN 978-1-4731-0160-9].

Enhanced Support for Shared Decision Making

An article in Health Affairs, ”Enhanced Support for Shared Decision Making Reduced Costs of Care for Patients with Preference-Sensitive Conditions” – compares the effects of patients who received a usual level of support for making a medical decision with the effects of having more enhanced support. This study suggests that the amount of care desired from some patients under a shared decision making model might be less than the level currently provided. There is a growing body of evidence that patients who are more actively involved in their health care have better outcomes and incur lower medical costs.

Source: David Veroff, Amy Marr, and David Wennberg. 2013. ”Enhanced Support for Shared Decision Making Reduced Costs of Care for Patients with Preference-Sensitive Conditions,” Health Affairs [Feb;32(2):285-93].

“The Right Trials”

Patricia S. Steeg, chief of the Center for Cancer Research at the National Cancer Institute, argues in Nature that most people with breast cancer die as a result of metastases (spread). Clinical trials, however, are only designed to evaluate a drug’s ability to shrink established tumors rather than its ability to block metastatic processes. Unless clinical trials are redesigned to study metastasis-preventive compounds, Steeg says, we are not likely to see a decline in breast cancer metastasis.

Source: Patricia S. Steeg. 2012. ”The Right Trials,” Nature [May;485:S58-S59].

“The Komen–Planned Parenthood Controversy: Bringing the Politics of Breast Cancer Advocacy to the Forefront”

Professors Lori Baralt of California State University, Long Beach and Tracy A. Weitz of University of California, San Francisco published a commentary in Women’s Health Issues about the Komen-Planned Parenthood Controversy and the long history of politicization that preceded the incident. They argue that the scandal was largely presented in mass media as the first time political interests interfered with Komen’s practices. Far from being an isolated matter Komen’s organizational decision-making about grants to Planned Parenthood is part of a longer political and economic history.

Source: Lori Baralt and Tracy A. Weitz. 2012. ”The Komen–Planned Parenthood Controversy: Bringing the Politics of Breast Cancer Advocacy to the Forefront,” Women’s Health Issues [22-6:e509-e512].

“How a Charity Oversells Mammography”

Professors Steven Woloshin, MD, and Lisa M. Schwartz, MD, of the Department of Veterans Affairs Medical Center and the Dartmouth Institute for Health Policy and Clinical Practice, published an article in a medical journal criticizing the breast cancer charity Susan G. Komen for the Cure for exaggerating and distorting medical information. The researchers argue that, “there is a big mismatch between the strength of evidence in support of screening and the strength of Komen’s advocacy for it.” Komen’s 2011 advertising campaign “simply tells women to get screened, overstates the benefit of mammography and ignores harms altogether.”

Source: Steven Woloshin and Lisa M. Schwartz. 2012. ”How a charity oversells mammography,” British Medical Journal [22-6:e509-e512].

NBCC’s Misguided Cancer Goal or Savvy Strategy?

In November 2012, an editorial in the international science journal Nature arguing that the influential advocacy group, the National Breast Cancer Coalition, was making false promises. The essay stated that NBCC’s 2020 Deadline campaign was promising something science could not yet deliver. The campaign marked a major change in public discourse about whether the dream of eradicating breast cancer was really possible based on existing evidence. Was it really so misguided?

Source: 2012. ”Misguided Cancer Goal,” Nature [Nov;491:637].

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