Table of Contents
From the Editors ......................................................................................................................................... 1
RERF News
Report on the 42nd Scientific Advisory Committee Meeting, 2015 ..................................................... 2
20th Meeting of the Hiroshima Local Liaison Council......................................................................... 5
Hiroshima RERF Holds Fifth Public Lecture ....................................................................................... 5
Nagasaki RERF Holds Fifth Public Lecture ......................................................................................... 7
US Ambassador to Japan Caroline Kennedy Pays Visit to Hiroshima RERF ....................................... 8
US Consul General, Consulate General Osaka-Kobe, Pays Visit to Hiroshima RERF ........................ 9Media Explanatory Session about Thyroid Findings Held ................................................................. 10
Regional Television Crew Visits RERF to Film Educational Story about Radiation .......................... 11
PR Professional Speaks to Hiroshima and Nagasaki RERF ............................................................... 11
Fourth ABCC-RERF History Forum Held, by Hiroaki Katayama...................................................... 12
RERF Receives Award from Latvia for Chernobyl Assistance ........................................................... 13
Media Forums Held at Nagasaki and Hiroshima RERF ..................................................................... 13
US Journalism Students Visit RERF ................................................................................................... 14
Staff News ........................................................................................................................................... 15
Visiting Research Fellow..................................................................................................................... 15
Conference and Workshop Reports
RERF International Training Course: An Update on Advanced Technologies in Radiotherapy(HICARE/IAEA) ............................................................................................................................. 17
RERF International Training Course: Training for Cambodia Breast Cancer Specialists Held at
Hiroshima RERF ............................................................................................................................. 18
RERF International Symposium: Application of “Omics” to Radiation Research,by Robert L. Ullrich ........................................................................................................................ 19
RERF International Workshop: Meeting on Dosimetry Issues, by Harry M. Cullings ....................... 20
Seminar Held at RERF: Hiroshima Statistical Study Group—High-Dimensional Data Methods
for Proteomics, by Harry M. Cullings ............................................................................................. 23
Science Articles
Association of Radiation Dose with Prevalence of Thyroid Nodules among Atomic Bomb
Survivors Exposed in Childhood (2007–2011), by Misa Imaizumi ................................................ 25
Skin Cancer Incidence among Atomic Bomb Survivors from 1958 to 1996,
by Hiromi Sugiyama ....................................................................................................................... 27
Handling Incomplete Smoking History Data in Survival Analysis, by Kyoji Furukawa .................... 29
Human Interest Notes
Participating in the Health Examination/Consultation Project for A-bomb Survivors Living inSouth Korea, by Daisuke Haruta ..................................................................................................... 30
In Memoriam: Arthur Canfield Upton, MD ........................................................................................ 31
Facts and Figures
Preservation of RERF’s Biosamples, by Yoshiaki Kodama ................................................................ 32
Research Protocols and Recent Publications
Full-scale Research Protocol Approved in November 2014–April 2015 ............................................ 34
Recent Publications ............................................................................................................................. 34
Cover photographs:[LEFT] U.S. Ambassador to Japan Caroline Bouvier Kennedy (right) and Chairman Toshiteru Okubo(left) exchanging gifts in Chairman’s Office, with Mr. Jeffrey Miller (Energy Attaché, U.S. Dept. ofEnergy; center); see page 8[RIGHT] Dr. Norio Takahashi, Consultant, Associate Chief of Research Office, being interviewed for
local BSS TV variety program by comic duo Daisuke and Hanako Miyagawa; see page 11

update 1

From the Editors

From the Editors
Welcome to the Summer issue of Update for2015. The sakura have come and gone, and so has
the Hiroshima Flower Festival, and despite ourbest intentions of going to press earlier, it appears
that we will be getting this issue published in its
English version in late June, much as we did lastyear.
We have had a mild spring again this year. The
sakura were in full bloom for a tragically shorttime due to the rainy weather, and “if one blinked,
one missed it” this year. Golden Week, however,was glorious. We are now nearing the start of rainyseason, typically a full month or more of fairly constant precipitation, some of it quite heavy.
This year marks the 70th year since the atomic
bombings and the 40th anniversary of the founding of RERF. With the passage of that much time,
one might imagine that there would be some majorchanges on the horizon. And in fact, some important new developments are taking place at RERF.
One of these is a big new initiative to deal with thespace and energy demands of RERF’s extremely
valuable collection of biosamples, including a large
robotic freezer system scheduled to go into operation later in the fall that will keep samples in ultracold storage in a large chamber to be accessed onlyby the mechanical sample-handling system.
Another is a new study of a different populationfrom the atomic bomb survivors—the Fukushima
nuclear accident emergency workers—which wasrecently awarded to RERF and will draw upon
the accumulated expertise of our scientific staff.
Although this cohort was exposed to ionizing radiation, it has important differences from the cohorts

of atomic bomb survivors, such as its smaller size,
lower maximum doses, chronic vs. the survivors’
acute exposure, clearly delineated occupational status, and less diversity of gender and age at exposure.
We have a full issue with the usual kinds ofofferings: a full complement of science articles,
news items including the 42nd meeting of the Scientific Advisory Committee, a report on a visit to
RERF by the U.S. Ambassador to Japan, and fiveconference and workshop reports. We hope you
enjoy this issue!
May 20, 2015

Harry M. Cullings
Editor-in-Chief
Technical Editors
Jeffrey L. Hart
Setsumi Harachi
Tomoe MatsumotoThis newsletter is published twice a year by the Radiation Effects Research Foundation (RERF;
formerly the Atomic Bomb Casualty Commission), established in April 1975 as a private, nonprofit Japanese foundation. It is supported by the government of Japan through its Ministry of
Health, Labour and Welfare and by the United States through its Department of Energy (DOE), inpart by DOE contract DE-HS0000031 with the National Academy of Sciences. RERF became apublic interest incorporated foundation on April 1, 2012.
RERF conducts research and studies—for peaceful purposes—on medical effects of radiation
and associated diseases in humans, with a view to contributing to maintenance of the health andwelfare of the atomic-bomb survivors and to enhancement of the health of all humankind.
Editor-in-Chief: Harry M. Cullings, Chief, Department of Statistics
Technical Editors: Jeffrey L. Hart, Chief, Setsumi Harachi, Tomoe Matsumoto, Public Relations& Publications Office
Editorial Policy
Contributions to RERF Update receive editorial review only and do not receive scientific peer
review. The opinions expressed herein are those of the authors only and do not necessarily reflect
RERF policies or positions.
Contact: Mailing address: RERF Public Relations & Publications Office, 5-2 Hijiyama Park,
Minami-ku, Hiroshima 732-0815 Japan
Telephone: 81-82-261-3131; Facsimile: 81-82-263-7279
Internet: http://www.rerf.jp/

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RERF Update Volume 26, Issue 1, 2015

RERF News

update 2

Report on the 42nd Scientific Advisory Committee Meeting, 2015
The 42nd Scientific Advisory Committee (SAC)
meeting to review RERF’s research activities washeld March 2–4, 2015, in Hiroshima. The SAC
consists of 10 scientists, five each from Japanand the United States. The co-chairs this year
were Dr. Michael Cornforth (University of Texas
Medical Branch) and Dr. Yoichi Gondo (RIKEN
BioResource Center). The SAC has a new member, Dr. Francesca Dominici (Harvard University
School of Public Health), replacing Dr. Sally
Amundson (Columbia University), to whom we
owe gratitude for her outstanding, dedicated service
to RERF. RERF requested to have more focused
reviews this year of the departments of Genetics
and Radiobiology/Molecular Epidemiology. To
aid the focused reviews, two additional experts
were appointed temporarily to the SAC—Dr. Ryo
Kominami (Niigata University) and Dr. Ralf Kittler(University of Texas Southwestern). Their insights
were very valuable, and it was a great pleasure for
us to work with these excellent scientists.
RERF Chairman Dr. Toshiteru Okubo opened
the meeting with a warm welcome to all, emphasizing the importance of SAC’s work to the mission of
RERF. He briefly summarized progress on several
items, including the plans for a working-groupresearch structure and purchase of a robotic biorepository to facilitate integrated biosample storage
and use. Particularly noteworthy is a new long-term
study of Fukushima nuclear emergency workers.
Next, Vice Chairman Dr. Roy E. Shore spoke
on responses to SAC recommendations and on
new research achievements. In response to the2014 SAC recommendations, RERF has formed ahigh-level committee to assign priorities to studies
based on relevance to RERF’s mission and importance of the science; is introducing new technologies (“omics”) to take advantage of the valuable
resource of data and biosamples; is working todevelop high-quality studies throughout their life
cycle, from planning through strong data methodologies, analyses and manuscripts; and is facilitating public understanding through press conferences, media forums, and public forums.
Dr. Shore followed with highlights of RERF’s
research accomplishments during 2014. Among
the research achievements were manuscripts on
the associations of radiation with thyroid nodules,3liver cancer,5 cognitive deficits, retinal macular degeneration, and chromosome aberrations.4
Papers also were published on A-bomb neutron
dosimetry1 and fallout rain exposure,6 and on
assessing the joint effects of smoking and radiation
on lung cancer risk.2 Improvements in the DS02
dosimetry input data having to do with increasing
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the accuracy of A-bomb survivor locations and amore comprehensive application of the DS02 terrain shielding module were completed and havebeen implemented. New radiation research initiatives included to begin a third round of clinicalexaminations of the children of A-bomb survivors,
to conduct echocardiographic screening of A-bomb
survivors, and to explore radiation-associatedmetabolomic patterns. Significant progress was
also made in conducting analyses and preparing
reports on an 11-year update of cancer incidence
data in the Life Span Study (LSS) of over 95,000
A-bomb survivors and an update of cancer andnoncancer mortality among about 76,000 childrenof the survivors.
RERF scientists have continued their active
involvement with international radiation-protection
and risk-assessment organizations, such as the
ICRP (International Commission on RadiologicalProtection) and UNSCEAR (United Nations Scientific Committee on the Effects of Atomic Radiation). They also gave a number of invited lecturesabroad and have collaborations with investigators
at over 40 different institutions in Europe, America,or Asia, and nearly 40 in Japan.
Dr. Robert L. Ullrich, Associate Chief ofResearch, presented plans for restructuring RERF
research programs. The broad outline of research
priorities includes the roles of radiation in cancer,
genetic damage, and cardiovascular disease. The
merger of the departments of Genetics and Radiobiology/Molecular Epidemiology into the Department of Molecular Biosciences is underway, withthe current four laboratories of Cell Biology, Cytogenetics, Immunology, and Biochemical Genetics
remaining the same for the present. An early task
will be the development of a five-year plan of goals
and directions for the new Department.
A second element of restructuring relates to thedevelopment of research clusters, initially in theareas of cancer, genetics, and cardiovascular andother non-neoplastic diseases. These are intended
to enhance communication, collaboration, andmentoring, and to both develop and critically evaluate integrated, multidisciplinary research projects(“program projects”), with a focus on salient radiation research questions. These projects would havetheir own funding and budget management andwould be held accountable for research innovationand productivity.
Dr. Kazunori Kodama, Chief Scientist, reported
on the Biosample Center, which provides for
integrated storage and management of various
types of biosamples, including blood constituents, urine, pathology tissues, and teeth. RERF
RERF Update Volume 26, Issue 1, 2015

RERF Newshas a rich repository of historical biosamples, forexample, about 490,000 serum, 100,000 plasma,and 130,000 lymphocyte samples from A-bomb
survivors and their offspring. To facilitate the storage of frozen samples, a robotic −80°C biorepository is being installed that will accommodate all
existing frozen samples and those obtained overthe next two decades. Work is ongoing to prepareand document samples for when the system begins
operation in September 2015.
Dr. Okubo reported on the new RERF grant to
conduct a long-term cohort study of Fukushima
nuclear emergency workers. The cohort consists ofabout 20,000 workers who conducted emergency
operations at the Fukushima Daiichi nuclear plant
between March 14 and December 16, 2011, theperiod when the permissible dose limit was raised
from 100 mSv to 250 mSv. RERF is serving as thelead institution and coordinating center, but sincethose workers are now scattered throughout Japan,
a number of medical institutions are being enlisted
to conduct yearly health examinations of the workers in a standardized fashion with informed consent. The examinations will include, among otherthings, biosample collection and screening for thyroid and other cancers, cataracts, and psychologicaleffects. The data will be linked to information on
estimated whole-body and thyroid doses, as well as
to cancer-incidence and mortality data.
The SAC provided a written report of their recommendations; a brief statement of the key generalrecommendations is as follows:• The SAC was pleased to see that RERF is in thecourse of merging the departments of Genetics
and Radiobiology/Molecular Epidemiology, andof forming Working Groups to develop focusedresearch initiatives. However, they cautionedthat upper management needs to implement thechanges thoughtfully to assure that the innovations increase research effectiveness.
• RERF must prioritize its development of“omics” research and give prime attention to thedevelopment of computational and statisticalinformatics capability. Hiring a computational
biologist should be a priority.
• Regarding sample and data sharing, RERF
needs to learn how to leverage its unique dataand sample base for the purpose of forging
research alliances that can help with its mission.
RERF should anticipate overtures made on
behalf of outside research entities for access tobiological data and physical samples, and consider beforehand how to deal with and prioritize
requests from potential collaborators.
• The collection and preservation of biosamples isamong the most important responsibilities of
RERF. A database for access to sample identification, location, and other information is underReturn to Table of Contents

update 3
way and should include all samples with associated information from every department. Issuesof intellectual rights and cross-platform databases also need to be addressed.
• New plans for the biosample repository are
impressive. The SAC notes that researchers willneed information about the quality of samples,particularly regarding their intended use forstudies involving the newer technologies ofmetabolomics, proteomics, and transcriptomics.
• It is important for RERF to place a high priority
on recruiting young researchers. Attracting topnotch talent in this environment will be challenging and requires a firm commitment on thepart of RERF. RERF needs to project an image
to prospective recruits that showcases its uniqueresearch opportunities and that reassures themthat they can make a career at RERF.
• There is a need for further prioritization, at various levels. Among these was the way that research
proposals were assessed as to overall quality andtestable hypotheses connected to RERF’s mission.
• RERF’s recent commitment to the Fukushima
accident is a positive development, especially interms of public relations, but care needs to betaken that resources are not diverted away from
RERF’s primary mission.
• The public lecture forums that have been conducted in Hiroshima and Nagasaki are appreciated by the SAC.
Selected highlights of the recommendations to
the departments with the primary focus this year
include:• Department of Genetics: The SAC considers theuse of appropriate and rigorous computational
analyses essential for gleaning useful information from genomic data, and this requires extensive bioinformatics expertise and computational
infrastructure. To obtain sufficient expertise werecommend the recruitment of an investigatorwith a research and publication record in computational biology to establish a bioinformatics
group at RERF.
• Department of Radiobiology/Molecular Epidemiology: Aging is probably related to impairment of the immune system, such as decreases
in the number and function of T cells and otherimmune-related cells. However, these changes
have not yet been related to chronic or persistent
inflammation or to the development of cancer
and other age-related common diseases. Further
study of this issue in that context is encouraged.
In summary, the SAC highlighted the uniquerole RERF plays in determining radiation risks andthe high continuing potential for studies that makeimportant contributions. The committee urged the
RERF Update Volume 26, Issue 1, 2015

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RERF News
prompt development and publication of new results
regarding issues of scientific and public-healthconcern and suggested ways to address new technological challenges in the basic sciences.
RERF Scientific Advisors
Dr. Michael N. Cornforth, Co-chairperson, Professor and Director of Biology Division,
Department of Radiation Oncology, Universityof Texas Medical Branch
Dr. Yoichi Gondo, Co-chairperson, Team Leader,
Mutagenesis and Genomics Team, RIKEN BioResource Center
Dr. Kazuo Sakai, Director, Research Center for
Radiation Protection, National Institute ofRadiological Sciences
Dr. Tomotaka Sobue, Professor, Department ofSocial and Environmental Medicine, Graduate
School of Medicine, Osaka University
Dr. Shunichi Yamashita, Director, Vice President,
Nagasaki University
Dr. Michiaki Kai, Member of the Board of Trustees, Professor, Environmental Health Science,
Department of Health Sciences, Oita University
of Nursing and Health Sciences
Dr. Marianne Berwick, Distinguished Professor,
Department of Internal Medicine and Department of Dermatology, University of New
MexicoDr. David G. Hoel, Distinguished University Professor, Department of Medicine, Medical University of South Carolina and Principal Scientist, Exponent, Inc.
Dr. Anatoly Dritschilo, Professor and Chairman,
Department of Radiation Medicine, Georgetown University School of Medicine
Dr. Francesca Dominici, Professor of Biostatistics, Biostatistics Department, and Senior Associate Dean for Research, Harvard School of
Public Health (Absent)

Special Scientific Advisors
Dr. Ryo Kominami, Professor Emeritus, Niigata
University, and Part-time Research Staff,
RIKEN Tsukuba Institute
Dr. Ralf Kittler, Assistant Professor of Pharmacology and Director of McDermott Next Generation Sequencing Core Laboratory, The University of Texas Southwestern Medical Center
References
1. Cullings HM, Pierce DA, Kellerer AM. Accounting
for neutron exposure in the Japanese atomic bomb
survivors. Radiat Res, 2014; 182:587–598.
2. Furukawa K, Preston DL, Misumi M, Cullings HM.
Handling incomplete smoking history data in survival analysis. Stat Methods Med Res, 2014 (October
26). doi:10.1177/0962280214556794. [Epub aheadof print]
3. Imaizumi M, Ohishi W, Nakashima E, Sera N,
Neriishi K, Yamada M, Tatsukawa Y, Takahashi I,
Fujiwara S, Sugino K, Ando T, Usa T, Kawakami A,
Akahoshi M, Hida A. Association of radiation dosewith prevalence of thyroid nodules among atomic
bomb survivors exposed in childhood (2007–2011).
JAMA Intern Med. 2015;175:228–36.
4. Nakano M, Nishimura M, Hamasaki K, Mishima
S, Yoshida M, Nakata A, Shimada Y, Noda A,
Nakamura N, Kodama Y. Fetal irradiation of rats
induces persistent translocations in mammary epithelial cells similar to the level following adultirradiation, but not in hemato-lymphoid cells. Radiat
Res, 2014; 181(2):172–6.
5. Ohishi W, Cologne JB, Fujiwara S, Suzuki G,
Hayashi T, Niwa Y, Akahoshi M, Ueda K, Tsuge M,
Chayama K. Serum interleukin-6 associated with
hepatocellular carcinoma risk: A nested case-control
study. Int J Cancer, 2014; 134(1):154–63.
6. Sakata R, Grant EJ, Furukawa K, Misumi
M, Cullings HM, Ozasa K, Shore RE. Long-term
effects of the rain exposure shortly after the atomic
bombings in Hiroshima and Nagasaki. Radiat Res,
2014; 182:599–606.

42nd Scientific Advisory Committee meeting participants, at Hiroshima RERF Hijiyama Hall
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RERF Update Volume 26, Issue 1, 2015

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RERF News

20th Meeting of the Hiroshima Local Liaison Council
Progress Status of Biosample Storage Reported

The 20th meeting of the Hiroshima Local Liaison Council (HLLC), a body composed of local
advisors and established for incorporation of local
community input in RERF’s operations, was heldat the Hiroshima RERF Auditorium on December
1, 2014. Of the 15 Council members, 13 including
2 proxies attended the meeting and expressed many
valuable opinions.
The Council members were introduced by Mr.
Eiji Akimoto, RERF Chief of Secretariat, following which RERF Chairman Toshiteru Okubo, in his
opening remarks, explained the objectives of theestablishment of the liaison council. After greetings by HLLC Chairman Dr. Toshimasa Asahara(President, Hiroshima University), the meeting’s
proceedings began, with Dr. Okubo reporting on
RERF’s present status. Dr. Okubo’s explanation
was followed by reports made by Vice Chairman
and Executive Director Roy E. Shore on recent
progress in research and the status of the ClinicalStudy of the F1 Offspring of A-bomb Survivors,
by Chief Scientist Kazunori Kodama on the statusof the RERF Biosample Center, by Dr. Okubo on
progress made in the collaborative study with the
U.S. National Institute of Allergy and Infectious
Diseases (NIAID), and by Executive Director
Takanobu Teramoto on RERF’s public relations
activities. Each of these reports was followed by aquestion-and-answer session.

It also was reported that a contract had beenentered into in September 2014 for the purchaseof a robotic biorepository for biosample storage toreplace the deep freezers used previously, and that
operation of the new equipment was scheduled to
begin by the end of September 2015.
In an exchange in one of the question-andanswer sessions, a Council member requested that
RERF enhance the approaches it employs to widely
disseminate the foundation’s research activities andresults to the public.
After completion of the meeting’s proceedings,
Dr. Okubo expressed his appreciation to the participating Council members, thereby concluding the20th HLLC meeting.

20th Local Liaison Council meeting held at Hiroshima RERF
Auditorium

Hiroshima RERF Holds Fifth Public Lecture
At the end of last year, on November 22, 2014,
RERF held a public lecture for citizens based on
the theme “Considering Uses for RERF’s Stored
Samples—Part 2.” The event was held in the International Culture Hall on the first basement floorof the main building of the International Culture
Center, Hiroshima YMCA, located in downtown
Hiroshima. A total of 184 persons attended theevent to listen to three lectures and a panel discussion. This year’s theme was the second in a
two-part lecture series, beginning last year, which
touched on the issue of uses for the biosamples
stored at RERF. It was the fifth public lecture organized by Hiroshima RERF.
Sometime after studies were initiated in 1947,
ABCC-RERF started the storing of biosamples
such as blood and urine provided by the survivorsof the atomic bombings and their children. Over
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the years, many such samples have been collected,
particularly as a part of the medical examinations
in which members of the RERF Adult HealthStudy participate on a biennial basis. To store such
samples in a centralized location and introduce
to RERF the latest and most appropriate methods
for storage, the RERF Biosample Center was
established on April 1, 2013, with preparations
ongoing to construct a robotic biorepository system. At the same time, efforts are being made tocreate a framework for the storage process, suchas improving organization of tissue samples not
yet registered in a database, as well as enhancing
and investigating quality-control and ethical issues,
with the aim of appropriate use of the samples both
inside and outside of RERF.
The biosamples stored at RERF have been collected with understanding and cooperation fromRERF Update Volume 26, Issue 1, 2015

RERF News
the A-bomb survivors, as well as from the local
communities of Hiroshima and Nagasaki. It istherefore crucial that fundamental policies for the
management and use into the future of such biosamples be determined on the basis of input RERF
receives from study participants and the public.
For these reasons, RERF decided to hold a public
discussion, in continuation from last year, about thetheme Considering Uses for RERF’s Stored Samples—Part 2, based on the idea of having RERF
researchers present lectures with local people serving as panelists in a panel discussion.
There were three talks at the event, with thefirst, titled “What we have learned about A-bombradiation health effects,” delivered by Dr. Atsuko
Sadakane, Associate Research Scientist, RERF
Department of Epidemiology. The next two talks
were based on the topic “What we can learn fromstored biosamples,” with Dr. Yoichiro Kusunoki,
Chief, Department of Radiobiology/Molecular
Epidemiology, speaking on “The history of healthand disease as told by genetic changes,” and Dr.
Waka Ohishi, Chief, Department of Clinical Studies, presenting a lecture titled “Seeking signs ofimpending disease.”
Based on these three keynote lectures, a panel
discussion was held, with Dr. Yasuyoshi Komizo,
Chairman, Hiroshima Peace Culture Foundation,acting as panel chair. The discussion featured
debate among the panelists, as well as a questionand-answer period with the audience. The panelists
were Mr. Hiroshi Harada (A-bomb Witness, former
Director, Hiroshima International Peace Office,Director, Hiroshima Peace Memorial Museum), Dr.
Kenichi Arita (Respiratory Department Director,
Hiroshima Red Cross Hospital & Atomic-bomb
Survivors Hospital), Ms. Yumi Kanezaki (Chugoku
Shimbun Hiroshima Peace Media Center), and
Ms. Akiko Furutani (President, Hiroshima Interpreter & Guide Association). Participating in thediscussion on behalf of RERF were Dr. Kazunori
Kodama (Chief Scientist/then Director of the
RERF Biosample Center), Dr. Kusunoki, and Dr.
Ohishi.
The panelists expressed a variety of opinions,with Mr. Harada emphasizing his view that thebiosamples should be utilized not only for the
A-bomb survivors but also for unexposed persons.
He added his hope that opportunities for exchange
can be expanded to ensure that information is communicated as effectively as possible and that the
samples can be used for the cause of peace as an
asset shared by all of humanity. Dr. Arita indicatedhis hospital’s determination to diligently care forthe samples received from the A-bomb survivors,
explaining that such samples are closely tied to theconcept of human dignity. With that in mind, hecalled the establishment of the RERF Biosample
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update 6
Center “significant,” and requested that continued
debate surrounding such issues take place in otheropen forums in the future. Ms. Kanezaki talked
about how communication with the public about
RERF’s research results represents a major issue,
relating her own experience in her job as a journalist of struggling to understand technical terminology used by scientists. She stressed the importanceof communication of such issues as methods forclearly explaining RERF’s research results, how
to ensure good health, and other such information
to the A-bomb survivors who have donated theirsamples to the organization for study. Ms. Furutani,from her perspective as an interpreter and guide,
proposed that RERF do more to market its facility
tours for those interested in learning about radiation effects on human health.
After Chairman Komizo emphasized the importance of listening to the opinions of the publicregarding the limits and conditions placed on useof RERF’s biosamples, Dr. Kodama remarked that
RERF was prepared to embark on the creation ofstandards for collaborative sample use, but that collaborative research would be conducted at the beginning with the involvement of RERF researchers,
rather than starting right away with only scientists
unaffiliated with RERF. He said that RERF would
later seek a way for such external researchers to use
the samples in their own collaborative research.
Questions and comments from the audience
included a statement that RERF should remain an
organization able to continue its international contributions from Hiroshima. There were also questions about preservation of thyroid cancer samples
in the radiation-contaminated areas of Belarus, andwhether the samples of those who entered the cities soon after the A-bombings of Hiroshima andNagasaki (early entrants) were included in the
RERF stored samples.
Despite the fact that this fifth of the RERF
series of public lectures featured the fairly technical theme ‘uses for stored samples,’ more people

Large crowd gathers for Hiroshima RERF’s fifth Public
LectureRERF Update Volume 26, Issue 1, 2015

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RERF News
attended this year’s public lecture in Hiroshima
than last year’s event, with college students also inevidence. Perhaps most importantly, the public lecture offered an opportunity to engage in a conversa-

tion with the public about the uses of RERF’s biosamples, stored over so many years, given that thebiosamples are the heritage of not only RERF, butalso of Hiroshima, Nagasaki, and the entire world.

Nagasaki RERF Holds Fifth Public Lecture

Nagasaki RERF holds its fifth Public Lecture

Nagasaki RERF held its fifth public lecture
event at the Nagasaki Atomic Bomb Museum Hall
on January 31, 2015. The lecture series is designed
to enhance communication by conveying information to the general public, including atomic bomb
survivors and their offspring, about results from
RERF’s long-standing research on A-bomb radiation health effects.
This most recent public lecture event was thesecond in a series of two lectures, following thefirst held last year, having the theme “Considering
Uses for RERF’s Stored Samples—Part 2,” with theaim of obtaining feedback from the Nagasaki public about possible uses for the biosamples stored at
RERF, including in collaborative research. Offeredin the format of a panel discussion, the event was
attended by more than 100 people.
RERF Chairman Toshiteru Okubo opened thelecture event by remarking, “The samples in thecustody of RERF have been collected with theunderstanding and cooperation of A-bomb survivors and local communities. I believe that it isimportant to create a basic policy toward future
management and utilization of these samples byreferring to opinions expressed by cooperating parties and the general public. We hope that all of you
will provide us with your honest feedback.”
The event’s first speaker, Dr. Misa Imaizumi,
Chief, Divisions of Radiology and Clinical Laboratories, Department of Clinical Studies, Nagasaki
RERF, elaborated on the topic “What we havelearned about A-bomb radiation health effects.”
Based on the idea of what we can learn from storedbiosamples, Dr. Yoichiro Kusunoki, Chief, DepartReturn to Table of Contents

ment of Radiobiology/Molecular Epidemiology,
spoke on “The history of health and disease as
told by genetic changes,” followed by a lecture
by Dr. Ayumi Hida, Acting Chief, Department ofNagasaki Clinical Studies, titled “Seeking signs ofimpending disease.”
In the panel discussion following the aforementioned keynote lectures, the panelists exchanged
opinions under the guidance of the panel chair Dr.
Takehiko Koji, Chief, Nagasaki University Graduate School of Biomedical Sciences. The panelists
included Dr. Masahiro Nakashima, Professor,
Department of Tumor and Diagnostic Pathology,
Atomic Bomb Disease and Hibakusha Medicine
Unit, Atomic Bomb Disease Institute, Nagasaki
University; Ms. Miyako Jodai, Atomic Bomb Survivor Representative, The 69th Nagasaki Peace
Ceremony “Pledge for Peace”; Mr. Tokusaburo
Nagai, Director, Nagasaki City Nagai Takashi
Memorial Museum; and from RERF, Chief Scientist Kazunori Kodama, Dr. Kusunoki, and Dr. Hida.
The panelists expressed the following opinions:
Mr. Nagai commented that “the samples donatedby A-bomb survivors are as valuable as precious
jewels and represent a huge source of information.” He added, “RERF is requested, however,to take special care in handling personal information.” Ms. Jodai stated, “After undergoing healthexaminations at RERF, my image of the foundation
completely changed. Data obtained in Nagasaki
should be utilized in cases of radiation emergencies, including in the recent nuclear disaster inFukushima.” Dr. Nakashima mentioned, “It is
important to obtain the understanding of A-bomb
survivors who have donated samples, create astructure for the preservation of samples, build aframework to promote shared use of biosamples
and related collaborative research, and develop
rules concerning use of such samples.”In the question-and-answer session that followed, many audience members expressed theirown ideas, including, “I think RERF is currently
working on the development of rules concerning
the use of stored biosamples, but will such rules
cover outside investigators?” said one. “I feel as
if communication between scientists and A-bomb
survivors is lacking somehow. Releasing information about research results and carrying out related
RERF Update Volume 26, Issue 1, 2015

update 8

RERF NewsPR activities is therefore crucial.”
The event concluded with closing remarks
by Executive Director Takanobu Teramoto, who

expressed his gratitude for the participation in the
public lecture and the valuable opinions expressed
therein.

Panelists at Nagasaki RERF Public Lecture (please refer to article for names andaffiliations of panelists)

US Ambassador to Japan Caroline Kennedy Pays Visit to Hiroshima RERF
On April 17, 2015, RERF had the pleasure ofreceiving a brief visit from Ms. Caroline Bouvier
Kennedy, Ambassador Extraordinary and Plenipotentiary to Japan, a position to which Ambassador
Kennedy was nominated by U.S. President Barack
Obama on July 24, 2013, and officially confirmedby the U.S. Senate on October 16, 2013. She is thefirst female U.S. Ambassador to Japan. Ambassador Kennedy was accompanied on her visit to
RERF by Ms. Roshni Nirody (Special Assistantto the Ambassador), Mr. Jeffrey Miller (Energy
Attaché, U.S. Department of Energy), Mr. Allen
Greenberg (U.S. Consul General Osaka-Kobe), andthree officers/staff members from the U.S. Consulate Osaka-Kobe.
The group was hosted by RERF Chairman

US Ambassador Caroline Kennedy on RERF facility tour
with Chairman Toshiteru Okubo
Return to Table of Contents

Toshiteru Okubo and other RERF Directors andsenior staff in Dr. Okubo’s office. After official
greetings and introductions, Dr. Okubo provided
the group with overviews on the history of RERF
and the Atomic Bomb Casualty Commission(ABCC), RERF’s predecessor organization, as
well as with details about the various cohortsthat ABCC-RERF has studied over the years.
Ambassador Kennedy asked detailed questions
about the research being undertaken at RERF,
especially in terms of the offspring (F1) generation.
Following the initial overview meeting, a facility tour was provided to the Embassy team, during
which descriptions of the clinical examination areas
were presented by Dr. Okubo together with Dr.
Waka Ohishi, Chief, Department of Clinical Studies. Thereafter, Dr. Okubo guided the group to therecently established Biosample Center, where heand Dr. Yoshiaki Kodama, Director of the Biosample Center, explained the significance of centralized
storage of RERF’s more than 900,000 biosamples.
This was the second visit to RERF for Ambassador Kennedy. On January 11, 1978, her uncle,
Senator Edward M. Kennedy, from the U.S. stateof Massachusetts and the brother of President John
Fitzgerald Kennedy (JFK), visited the RERF laboratory in Hiroshima. Accompanying him on his trip
were his wife and three children, three of his sisters, as well as Caroline Kennedy, JFK’s daughter,and Michael Kennedy, JFK’s nephew (please refer
to our March 14, 2013, Facebook article on thevisit). Dr. Okubo presented Ambassador Kennedy
RERF Update Volume 26, Issue 1, 2015

RERF Newswith a copy of a photograph of Senator Kennedy
taken during his visit to RERF, as the group passedby the same framed photograph on their way to the
Biosample Center.
We truly appreciated the opportunity to explain

update 9
our organization and its scientific results to Ambassador Kennedy and her staff. We feel confident thatthe findings from our research can serve to remind
all those who visit RERF of the importance of ourscientific program.

Ambassador Caroline Kennedy and staff outside Hiroshima RERF with RERF Directors, senior staff

US Consul General, Consulate General Osaka-Kobe, Pays Visit to Hiroshima RERF
On December 8, 2014, RERF had the pleasureof receiving a visit from Mr. Allen Greenberg,
Consul General, U.S. Consulate General OsakaKobe, Japan, a position to which Mr. Greenberg
was appointed in August 2014. Mr. Greenberg was
accompanied on his visit to RERF by Mr. Brian
DaRin (Consul, Political and Economic Affairs),
and Ms. Naomi Shibui (Economic Assistant).
The group was hosted by RERF Chairman
Toshiteru Okubo and other RERF Directors andsenior staff in Dr. Okubo’s office and given overviews on the history of RERF and the Atomic Bomb
Casualty Commission (ABCC), RERF’s predecessor organization, as well as on RERF’s past, present,
and expected future research and other activities.
Mr. Greenberg and his staff exhibited keen interestin the research being undertaken by RERF.
Following the initial overview meeting, an
extensive facility tour was provided to the Consulate team, where more detailed descriptions of
the responsibilities and activities of the various
research departments of RERF were presented.
Each of the group members asked relevant questions of the RERF staff and showed interest inunderstanding the basic knowledge that ABCCRERF has collected about radiation health effects
based on the organization’s long-term studies of
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A-bomb survivors in Hiroshima and Nagasaki
since the founding of ABCC in 1947.
We truly appreciated the opportunity to explain
our organization and its scientific results to senior
officials of the U.S. government’s diplomatic
ranks. We feel confident that the findings from ourresearch can serve to remind all those who visit
RERF of the importance of continuing our scientific program, which involves the long-term studyof the health effects in the A-bomb survivors andtheir children of radiation from the atomic bombings of Hiroshima and Nagasaki in 1945.

Mr. Allen Greenberg, Consul General (left), US Consulate
General Osaka-Kobe, with RERF Chairman Toshiteru
Okubo

RERF Update Volume 26, Issue 1, 2015

update 10

RERF NewsMedia Explanatory Session about Thyroid Findings Held
The Great East Japan Earthquake, on March 11,
2011, and the subsequent radiation release fromthe Tokyo Electric Power (TEPCO)’s Fukushima
Daiichi nuclear power plant have heightened theconsciousness of Japan’s public regarding radiation
exposure and development of thyroid nodules/cancer, particularly in children. Given that situation,
on February 2, 2015, RERF held a simultaneous
explanatory session, “Recent papers related to thyroid cancer and nodules in A-bomb survivors,” atboth the Hiroshima and Nagasaki laboratories.
The aim of such explanatory sessions is thecommunication of complex scientific concepts inlanguage that is accessible to the media. Nine journalists in Hiroshima and six in Nagasaki attended
the event, representing both local and national
news outlets; the laboratories in the two cities wereconnected by teleconferencing.
The journalists in attendance expressed keeninterest in learning from the RERF researchers
experienced in investigating thyroid diseases,
which have been shown to be linked to radiation exposure in the case of the Hiroshima andNagasaki atomic bombings. Increased incidencesof these diseases have been reported in the children
living in Fukushima prefecture at the time of theradiation accident, although whether the increase isdue to radiation exposure or the result of increased
testing remains an open question.
First, Dr. Kyoji Furukawa, Associate Senior
Scientist, RERF Department of Statistics, provided background information from the Hiroshima
Laboratory on radiation and thyroid cancer risk in
the A-bomb survivors, based on his March 2013
paper titled “Long-term trend of thyroid cancer
risk among Japanese atomic-bomb survivors: 60
years after exposure.” Following Dr. Furukawa’s
talk, members of the media in both Hiroshima
and Nagasaki asked questions of a fairly technicalnature, such as about the difference in definition
between excess relative risk and relative risk inthyroid cancer.
Next, Dr. Misa Imaizumi, Chief, Division ofRadiology, Chief, Division of Clinical Laboratories, Department of Clinical Studies, Nagasaki
RERF, spoke from the Nagasaki Laboratory on her
paper “Association of Radiation Dose With Preva-

Return to Table of Contents

lence of Thyroid Nodules Among Atomic Bomb
Survivors Exposed in Childhood (2007–2011)”(see page 25), which was published online at theend of December 2014 and announced publicly forthe first time at the media event.
When questioned by journalists in both
Hiroshima and Nagasaki about whether the resultsfrom her study could be used to explain the apparent increase in thyroid nodules in Fukushima, Dr.
Imaizumi responded by saying that the results
could not be applied directly, since her study was
based on A-bomb survivors who were exposed toradiation at ages of less than 10 years and examined when they were aged 60. She did emphasize,
however, that her data could be used as reference
information in terms of protecting the health of the
Fukushima children many years into the future.
The detailed questions and interest the media
members exhibited at the explanatory event suggest that RERF’s efforts to broaden journalists’understanding of health effects caused by radiation
exposure have been effective as an educational
tool. The media can use the information to better
inform the public not only about RERF’s atomic
bomb-related health information, but also about
information related to other instances of radiation
exposure throughout the world, including the caseof Fukushima.

Media explanatory session about thyroid findings held at
Hiroshima and Nagasaki RERF, with Dr. Kyoji Furukawa,
Associate Senior Scientist, Statistics Dept., at podium, andDr. Misa Imaizumi, Chief, Radiology Division, Chief, ClinicalLaboratories Division, Nagasaki Clinical Studies Dept., onscreen from Nagasaki

RERF Update Volume 26, Issue 1, 2015

update 11

RERF NewsRegional Television Crew Visits RERF to Film Educational
Story about Radiation
Two episodes of a popular educational television program hosted by comic duo Daisuke andHanako Miyagawa, titled “Let’s See…,” werefilmed at the Hiroshima RERF Laboratory on
December 16, 2014. The short program is producedby the regional Broadcasting System of San-in, or
BSS, and explores somewhat knotty environmental, energy, and other issues that seem simple but
in reality are not. In these episodes, two questions
were posed to RERF: Where does radiation exist?
And, what effects does radiation have on people?
Dr. Norio Takahashi, a consultant for the RERF
Associate Chief of Research’s Office, demonstrated to the film crew how to measure radiation invarious places using a dosimeter. He also instructed
the crew that radiation exists in nature, is used in
medicine in X-ray imaging and other technologies,
and has health effects depending on the radiation
doses to which an individual is exposed.
The two separate episodes were broadcast on
February 8 and 15, 2015, but only in Japan’s San-in
region (on the Japan Sea side of the main island of
Honshu) not Hiroshima. Nevertheless, appearing

on the program provided RERF with a good platform from which to inform the public, albeit within
a limited framework, about the organization. It wasalso useful for us as an institute engaged in scientific issues, because we were able to ascertain thatsuch basic questions attracted great interest fromthe general public.

Dr. Norio Takahashi, Consultant, Associate Chief of Research
Office, explaining differences in radiation exposures to
Daisuke (right) and Hanako (center) Miyagawa for BSS program “Let’s See…”

PR Professional Speaks to Hiroshima and Nagasaki RERF
Public relations dates back to around the turn ofthe 20th century, with Britain or America thought
to be the starting point of the profession in its modern form. Public relations tools are used by RERF
for communicating research results to the public
and obtaining understanding of our objectives
and operations as a research organization. Despite
RERF’s surrounding environment, which has longdemanded nuanced yet open communication withstakeholders, we are relative newcomers to thefield: RERF’s Public Relations and Publications
Office was only established on January 1, 2006.
On February 20, 2015, to foster deeper understanding among staff regarding the field and practice of public relations, RERF invited a specialist
from Hakuhodo, Inc., in Tokyo, to address thetheme of public relations in a lecture to all staff,
and about specific ideas related to strategy in aworkshop to staff involved in communicating withthe public. Hakuhodo is the oldest advertising firmin Japan and has a significant public relations arm.
The company’s footprint is global, with offices
located throughout the world.
The lecturer, Mr. Masahiko Haga, was accomReturn to Table of Contents

panied by two other Hakuhodo staff, bringing thetotal to three. Mr. Haga holds the titles of Consultant and Senior Director at Hakuhodo. He has been
involved in the field of public relations with thecompany for several decades, most notably, at the
beginning of his career, in work on the 1985 Japan
Airlines Flight 123 accident in Japan’s Gunma
prefecture that resulted in more than 500 deaths,
then during 1992–1995 in efforts to help establish
J-League professional soccer in Japan.
The lecture was attended by about 70 staff members in Hiroshima, and in Nagasaki by teleconferencing. Mr. Haga touched on the basics of public
relations, including the fundamental workings of themedia and social media, as well as the importanceof working with, as well as utilizing, the media forcommunicating RERF’s message. He explained,
using past examples of Hakuhodo-led projects, how
RERF can market its accomplishments by emphasizing the importance of RERF’s research to global
considerations, such as the establishment of worldwide radiation protection standards.
The training session that followed was attended
by around 30 employees in Nagasaki and Hiroshima
RERF Update Volume 26, Issue 1, 2015

update 12

RERF News
engaged directly in public relations work. Mr. Haga
spoke on a wide range of issues, including the history of public relations, and noted that the start ofpublic relations in Japan probably began after theend of World War II, with the arrival of U.S. General Douglas MacArthur. MacArthur’s headquarters
aimed to persuade Japan to accept an open democratic government by, in part, setting up public relations offices in each of Japan’s prefectures.
After Mr. Haga’s talk, staff directly involved inpublic relations work broke up into small groups anddiscussed methods that could help inform the public
about RERF. Each of the groups then presented
the best of its ideas. One recurrent theme in thegroup presentations was the idea that the research
results RERF has reported over the years need to beconveyed to younger generations by, for example,
conducting small public lectures in locations apartfrom the cities of Hiroshima and Nagasaki or having
RERF researchers travel to schools to teach children
about the basics of radiation health effects.
The three Hakuhodo staffers, using the sameformat, announced their unique proposals for

RERF’s future public relations activities, including
the idea of holding a picnic in the Hijiyama area
and inviting the public to join in, which sounded
like an appropriate plan as the weather started toturn to spring with a hint of warmth in the air following a cold winter.

PR specialist from Hakuhodo, Inc. Mr. Masahiko Haga
speaks about effective communications to PR staff at
Hiroshima RERF

Fourth ABCC-RERF History Forum Held
Hiroaki Katayama, Chief
Department of Information Technology
The fourth ABCC-RERF History Forum, organized by the Historical Materials Management
Committee, was held at the Hiroshima RERF
Auditorium on April 9, 2015. The series of History Forums, which began in April 2013 at theNagasaki Laboratory, are designed to offer current
RERF employees the opportunity to hear firstperson accounts by individuals employed during
the days of the Atomic Bomb Casualty Commission (ABCC). These vivid, detailed presentations
help sharpen and deepen the understanding among
current employees about the history of studies ofA-bomb survivors conducted at ABCC-RERF.
The featured speakers at the fourth History
Forum were Ms. Kiyoko Minato and Ms. Hisae
Tanaka, both of whom served as nurses at ABCC.
Ms Minato, who retired in 1966, joined ABCC in
1949 as it prepared to open temporary facilities in
Ujina. Thoroughly trained by American nurses, she
conducted health examinations of job candidates
and made home visits for examinations associatedwith genetics studies. Ms. Tanaka, who retired
from RERF in 1987, joined ABCC in 1951 andwas engaged in nursing activities in various areas,
including outpatient clinics in internal medicine
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and pediatrics.
Both Ms. Minato and Ms. Tanaka rememberedcountless details of their work in those early days,
and gave interesting, straightforward descriptions, such as how a nurse would stay with eachexaminee during his or her tests and examinations
to offer support. They described how medicines
were prescribed at the clinics when necessary, andFourth ABCC-RERF history forum held at Hiroshima RERF;
Ms. Kiyoko Minato (center) and Ms. Hisae Tanaka (right)
with Executive Director Takanobu Teramoto

RERF Update Volume 26, Issue 1, 2015

update 13

RERF News
recalled how rooms were established in the 1950s
to accommodate 10 inpatient beds for people who
needed to be hospitalized, information that wassure to be news to many in the audience. Examinees wore gowns, rare in those days, not only
because they made examination easier but also
out of consideration for examinees who did notwant to be viewed by others. Ms. Minato and Ms.
Tanaka used actual examination instruments asthey explained these matters. Executive Director
Teramoto proved a hearty moderator for the forum,and both former nurses, who appeared somewhat

nervous at the outset, gradually began to relax andsmile, creating a friendly atmosphere among theattendees.
The History Materials Management Committee
hopes to continue to provide such opportunities forformer employees to talk about their experiences at
ABCC. Such information is valuable in promoting
accurate recognition and understanding of ABCC
activities. Please visit the official RERF website fordetails, in Japanese, of the History Forums (http://
www.rerf.or.jp/history/histforum.html). An English
version will be available shortly.

RERF Receives Award from Latvia for Chernobyl Assistance
RERF has for many years provided training for
medical workers and researchers from Latvia andlent its cooperation to the health management of
the military veterans and other emergency personnel who worked at the Chernobyl nuclear accident
site. On October 13, 2014, for those contributions,
RERF was presented with an honorary award by
the Latvian Republican Union Chernobyl, a socialorganization of such workers, at Pauls Stradins
Clinical University Hospital in Riga, Latvia.
President Arnolds Vērzemnieks, the leader of theLatvian Republican Union Chernobyl, honored Dr.
Tomonori Hayashi, Assistant Chief, RERF Department of Radiobiology/Molecular Epidemiology,
with a certificate of merit and medals.

Dr. Tomonori Hayashi, Assistant Chief, Radiobiology/Molecular Epidemiology Dept., holding certificate of merit andmedals awarded to RERF

Media Forums Held at Nagasaki and Hiroshima RERF
RERF in Nagasaki and Hiroshima conducted
the fourth round of media forums in April 2015 toexpand knowledge among members of the media
about studies into the health effects of A-bombradiation conducted at RERF. The Nagasaki forum,
held on April 22 in the conference room on the 3rd
floor of the Nagasaki Laboratory, included sevenmedia representatives from seven companies.
The Hiroshima forum, which took place at theHiroshima Laboratory on April 24, hosted 10 representatives from 7 media outlets.
The purpose of the forums is to present new
research achievements and increase understanding
among media representatives about studies thathave been conducted for nearly 70 years at ABCCRERF to provide them with knowledge they can
Return to Table of Contents

use to inform the public in an easy-to-comprehend
manner. At this year’s forums, the media participants were encouraged to ask questions at any
point during the explanations provided by RERF
directors.
At the Nagasaki forum, RERF Chairman
Toshiteru Okubo first outlined the “Epidemiological Study of Health Effects in Fukushima Emergency Workers,” which will be initiated on a fullscale this fiscal year. Participants asked numerous
questions including how ABCC-RERF data could
be used to help people exposed to radiation in
the Fukushima nuclear accident. Then, Executive
Director Takanobu Teramoto explained the RERF
“FY2015 event and activity plans.”
Two days later, at the Hiroshima forum, media
RERF Update Volume 26, Issue 1, 2015

update 14

RERF News
participants raised questions with regard to the
Epidemiological Study of Health Effects inFukushima Emergency Workers, asking how many
people’s addresses were known among the about
20,000 emergency workers who were potential
study participants. Those attending the forum alsoinquired about the number of people whose consent had been obtained among these candidates
and about the future prospects for relevant studies. In response to the presentation of the RERF
FY2015 event and activity plans, questions arose
about whether more detailed examinations than inprior studies would be conducted in the upcoming
third cycle of the ongoing Clinical Study of the F1
Offspring of A-bomb Survivors.
Questions were posed vigorously in both
Nagasaki and Hiroshima, evidence that the forums
are accomplishing their original goal of helping themedia convey complex scientific information to the
public in a readily understandable manner. RERF

hopes to continue these forums to maintain positive
working relations with the media.

Media forum held at Hiroshima RERF, with Chairman
Toshiteru Okubo (left) and Executive Director Takanobu
Teramoto as speakers

US Journalism Students Visit RERF
Two journalism students from Indiana University (IU), located in Bloomington, Indiana, visited
Hiroshima RERF on March 17 and 18, 2015. MaryShown and Kami Mackin belonged to a student
group from an IU international reporting class that
had traveled to Japan. The group of 16 students, led
by an IU professor, visited Hiroshima to study such
topics as the atomic bombings and ABCC-RERF’s
research into the bombings’ radiation healtheffects. All of the students were tasked with writing
stories about Hiroshima given that 2015 is the 70th
year since the atomic bombings of Hiroshima andNagasaki.
At RERF, Mss. Shown and Mackin interviewed
Dr. Eric J. Grant, Assistant Chief, RERF Department of Epidemiology, to familiarize themselveswith RERF’s findings. The two also spoke with
Mr. Jeffrey L. Hart, Chief, Public Relations andPublications Office, about RERF’s history andcommunications efforts with regard to the public
and the media.
Ms. Shown is a senior working toward a degree
in journalism and biology, with a concentration inscientific and international reporting. Ms. Mackin
is a junior in the same journalism program, with afocus on international reporting and war correspondence for print. The students showed particularinterest in the methods ABCC used in the earlystages of research to encourage A-bomb survivors
to participate in the organization’s studies, in addition to RERF’s research.
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For most of the week they spent in Japan, the IU
students were in Hiroshima reporting on the current anti-nuclear weapons movement and visiting
with a group of survivors in a nursing home specifically designed for hibakusha. After Hiroshima, thestudents traveled to Tokyo, where they covered ananti-nuclear protest and made a trip to the Yasukuni
Shrine (for a more detailed account, access their
Japan trip blog at: http://mediaschool.indiana.edu/
japan-2015/).
RERF strives to accommodate requests forcooperation in educational activities. We wish
Mary and Kami the best with their projects andlook forward to seeing how their RERF experienceplays out in their future careers. We hope their visit
inspires other students to contact RERF for information related to radiation’s health effects.

Indiana University students Ms. Mary Shown (center) and
Ms. Kami Mackin (left) after interview with Dr. Eric Grant,
Assistant Chief, Epidemiology Dept.

RERF Update Volume 26, Issue 1, 2015

update 15

RERF News

Staff News
Yoshiaki Kodama, Senior Scientist (fixed-term
research scientist), completed his term as Chief ofthe Department of Genetics as of December 31,
2014, and assumed the position of Director of the
Biosample Center, effective January 1, 2015. John
B. Cologne, Senior Scientist of the Department of
Statistics, retired under the mandatory age limit asof March 31. He was reappointed as Senior Scientist (fixed-term research scientist) of the samedepartment effective April 1, in order to continue
research. On the other hand, Keiko Ueda, Fixedterm Research Scientist of the Division of Clinical Laboratories, Department of Clinical Studies,
Masayuki Hidaka, Postdoctoral Scientist of the
Department of Genetics, and Yiqun Hu, Postdoctoral Scientist of the Laboratory of Immunology,
Department of Radiobiology/Molecular Epidemiology, resigned upon term expiration as of March
31. Kazumasa Sekihara, research scientist of theLaboratory of Cytogenetics, Department of Genet-

ics, resigned upon term expiration as of April 30.
Also, Kiyohiro Hamatani’s term as Adjunct Specialist (research scientist) of the Laboratory of Cell
Biology, Department of Radiobiology/Molecular
Epidemiology expired on March 31. He was reappointed as Consultant to the same department,
effective April 1, to continue research at RERF.
RERF presents awards to employees for theirlong-term service in April every year. This year,
eight employees—five employees for 30 yearsof service, two employees for 20 years, andone employee for 10 years—were awarded in
Hiroshima. Among them were research scientists
Tomonori Hayashi, Assistant Department Chiefof the Department of Radiobiology/Molecular
Epidemiology, and Kyoji Furukawa, Associate
Senior Scientist of the Department of Statistics,
awarded for 20 years and 10 years, respectively. In
Nagasaki, one general employee was awarded for
20 years of service.

Visiting Research Fellow
Caitlin M. Milder, Visiting Student Fellow of the
Department of Epidemiology from October 24,
2013 to October 10, 2014, rejoined RERF to conduct research as Visiting Research Fellow of thesame department for one year (February 23, 2015–
February 22, 2016). She introduces herself below.
I am a returning Visiting Research Fellow training under Dr. Eric J. Grant in the Department of
Epidemiology. I am the recipient of a fellowship
through the National Academy of Sciences (NAS)with U.S. Department of Energy funding that willallow me to continue my work here for one more
year. I am delighted to be back at RERF, continuing the projects I worked on during my first year
at RERF, from October 2013 to October 2014, andbroadening my research at the institution.
I have long been interested in Japan. As anundergraduate student at the University of Arizona,
I majored in both physiology and East Asian studies, with a focus on Japanese. By the end of mytime at the university, I had studied abroad for six
months in Tokyo and completed a Japanese-toEnglish medical translation for a journal article
concerning nephrotic syndrome.
I am therefore very excited for the opportunity
to see more of Japan. Last year, I took trips to anumber of cities in Honshu and Kyushu, where
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I expanded my ideas about Japan and Japaneseculture. This year, I hope to take weekend trips tocontinue to gain insights into regional Japanesereligion, art, and language. As I did last year, I
will take language classes to improve my Japaneseabilities. I look forward to speaking with everyone
at RERF in both English and Japanese.
This past year, I graduated with a master ofscience in public health from the Johns Hopkins
Bloomberg School of Public Health. My former
year at RERF enabled me to achieve this goal: I
am grateful to RERF and its employees for having
helped me to complete my practical requirements.
During my last year at RERF, I contributed tomultiple projects being conducted at the institu-

Ms. Caitlin Milder, visiting research fellow, returns to RERF

RERF Update Volume 26, Issue 1, 2015

RERF Newstion. I participated in the National Cancer Institute(NCI) collaborative LSS cancer incidence studies,and I contributed to the F1 cohort studies. I also
helped publish the material from the Low-Dose
Symposium held in 2013 which should shortly beavailable for public review.
This year, I have a number of aims I want torealize at RERF. First, I want to contribute moreto the NCI collaborative LSS cancer incidence
studies. I believe that the results from these studies
will be important to how exposures are handled in

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update 16
the future, and I want to play a bigger role in thatprocess. I aim to finish what remains of my projects
from the previous year. I will also strive to improve
my presentation abilities as well as my skills in statistical software, particularly Epicure, to allow me
to make this opportunity a productive educational
experience.
I look forward to working with everyone here at
RERF again, to contributing to its research, and to
expanding my knowledge of radiation and radiation epidemiology.

RERF Update Volume 26, Issue 1, 2015

Conference and Workshop Reports

update 17

RERF International Training Course:
An Update on Advanced Technologies in Radiotherapy (HICARE/IAEA)
A group of 27 physicians and researchers
from 15 countries—including Bangladesh, China,
Mongolia, Nepal, Thailand, and the UnitedStates—visited Hiroshima for the training program“HICARE/IAEA International Training Course:
An Update on Advanced Technologies in Radiotherapy,” sponsored by the Hiroshima International
Council for the Radiation-exposed (HICARE) andthe International Atomic Energy Agency (IAEA).
The training was designed to provide instruction
involving “effective and safe radiotherapy to cancer
patients through the optimal utilization of modern
radiotherapy technologies.”
HICARE was designated a “Collaborating Centre for: Capacity Building in Radiation Effects andHuman Health” by the IAEA on May 26, 2014, a
designation that will last at least four years. As an
IAEA Collaborating Centre, HICARE conducts
training programs for physicians and researchers.
The designation is considered to be internationalrecognition of HICARE’s technical expertise andadvanced level of research. HICARE is a collectionof 10 entities, including RERF, Hiroshima Prefecture, Hiroshima City, and Hiroshima University.
HICARE is the second IAEA Collaborating Centre
in Japan.
The recent training course was the third
HICARE/IAEA course held jointly since 2013,
and the first to be conducted since HICARE wasdesignated an IAEA Collaborating Centre. In thefirst joint training session, nine overseas trainees
participated, with 12 participants at the second session. The total of 27 trainees at the recent training
course thus represents a significant increase.
On the first day of the training course, January
19, 2015, RERF Chairman Toshiteru Okubo, who
also serves as HICARE President, gave the opening address. The initial day of the event took place

Dr. Kazunori Kodama (foreground), Chief Scientist, speaks
to HICARE/IAEA International Training Course group at
Hiroshima RERF
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Dr. Kodama (left) explains ABCC-RERF history to HICARE/
IAEA International Training Course groupat the Oriental Hotel Hiroshima and covered novel
radiation treatment technologies, clinical applications, and the basic physics of such treatments.
After gathering at the same hotel the next day,January 20, to attend talks on cancer treatments
worldwide, the group of 27 trainees moved to theHiroshima University Hospital on January 21 tolisten to an overview of the hospital and witness
demonstrations of target and organs-at-risk (OAR)
delineations within the framework of radiation
medical therapy.
The next day, January 22, the group visited
RERF, where Dr. Kazunori Kodama, Chief Scientist, introduced the organization in a presentation.
Dr. Kodama, along with Dr. Toshiya Inaba, Director of the Hiroshima University Research Institutefor Radiation Biology and Medicine, serve as theliaison officers between the HICARE and IAEA
organizations. At the RERF Auditorium, each of
the trainees was awarded a certificate for completion of the training course. The group then spent
the afternoon touring the Hiroshima Peace Memorial Museum and the Atomic Bomb Dome, a building that stands as a monument to the destruction
caused by the A-bombing and serves as a designated UNESCO World Heritage Site.
About the importance of the meeting, Dr.
Kodama remarked that in 10 or 20 years, there will
be a “big jump” in the number of cancer patients
who survive radiation treatment, because certain
cancers can now be cured. But, according to Dr.
Kodama, those same people may be at increased
risk of development of secondary cancers due tothe radiation used to often successfully treat theinitial cancer. In radiotherapy, radiation is used
to expose cancer tissue, but at the same time, thetreatment “gives radiation to normal tissues and
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Conference and Workshop Reports
they [patients] suffer risks of other diseases,” hesaid.
Dr. Kodama went on to say that the research
results from RERF can go a long way toward making people understand the long-term health effects
from radiation exposure. He added about the trainees, “They have to also learn about radiation risks,”

update 18
rather than study only the beneficial effects.
Several of the trainees remarked how the visit toJapan gave them a chance to learn about advanced
radiotherapy technologies not currently available intheir own countries, testimony to the importance ofthe training course.

RERF International Training Course:
Training for Cambodian Breast Cancer Specialists Held at Hiroshima RERF
explanation of radiation effects on immunologiThree Cambodian physicians and two medical
cal functions in A-bomb survivors. He explained
officers from the Cambodia Ministry of Healthindividual differences in stomach cancer suscepvisited the Hiroshima RERF Laboratory for several
tibility to radiation exposure, especially the relahours on April 15, 2015, to study the health effects
tionship between radiation exposure and stomachof A-bomb radiation exposure as part of their traincancer risks by genotype of immunosuppressive
ing in breast cancer examination. The Cambodian
gene IL10, a subject that has been reported ingroup was accompanied by Honorary Professor
international scientific journals. Dr. Hayashi also
Koki Inai of Hiroshima University.
described the relationship between radiation expoFollowing an introductory video about RERF
sure and developmental mechanisms of thyroid
and its scientific mission, Dr. Atsuko Sadakane,cancer among A-bomb survivors. In response to a
RERF Associate Senior Scientist and Acting Chief,question about whether thyroid cancer cases that
Laboratory of Pathology, Department of Epidedeveloped early after A-bomb radiation exposure
miology, addressed the visitors by outlining thewere considered to be a direct effect of radiation
RERF Life Span Study (LSS) and its results. She
on DNA, Dr. Hayashi noted the likelihood that
described the LSS research methodology and sumsome thyroid cancer cases developing early after
marized research results concerning risks of morexposure were related to radiation. He added that,
tality and cancer incidence, with a focus on breast
because numerous leukemia cases were observed
cancer incidence, due to A-bomb radiation expoamong A-bomb survivors within about 10 years
sure. The trainees were especially interested in theafter exposure, some of them were likely to haveremarkably long duration of the LSS—the study
been caused by the direct effects of radiation on
was initiated in 1950—and asked many questions
DNA.
regarding ways to interpret research results and theBased on their many questions and comments,
significance of certain numerical values.
the Cambodian visitors appeared to find theirDr. Mai Utada, Research Scientist, DepartRERF visit both interesting and fruitful.
ment of Epidemiology, talked to the visitors about
Hiroshima’s cancer registry system. She explainedthat accurate information on cancer cases
has been obtained in Hiroshima based on
three cancer registries: the Hiroshima City
Cancer Registry, Hiroshima Prefectural
Cancer Registry, and Hiroshima Prefectural
Tumor Registry. These cancer registries
have been operated jointly with cooperation
among local governments, medical institutes, medical associations, and RERF,
which has been entrusted to perform theactual work of the registries. The trainees
were especially interested in items included
on a notification form for the Hiroshima
Prefectural Cancer Registry.
Next, RERF’s Dr. Tomonori Hayashi,
Assistant Chief, Department of RadiobiolGroup of Cambodian breast cancer specialists receiving training at
ogy/Molecular Epidemiology, presented an
Hiroshima RERF
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Conference and Workshop Reports

RERF International Symposium:
Application of “Omics” to Radiation Research
Robert L. Ullrich
Associate Chief of Research
An international symposium was held at
Hiroshima RERF on December 2 and 3, 2014, titled“Application of ‘Omics’ to Radiation Research.”
This symposium was made possible through funding from the Japan Ministry of Health, Labour andWelfare (MHLW) international exchange program.
Many of the participants were from overseas andthe working language of the symposium wasEnglish, with all presentations, including those ofJapanese scientists, made in that language.
The purposes of this symposium were twofold:
first, to provide the opportunity for RERF scientists
to become familiar with the latest cutting-edge“omics” technologies, including proteomics, proteogenomics, and metabolomics, and how they could
be applied to identify biomarkers and molecularchanges associated with mechanisms of radiationinduced disease in the survivors of the atomic
bombings; second, to familiarize the outside
participants with the opportunities through collaborative research programs to better understandradiation risks, develop new tools to facilitate theearly diagnosis of disease processes important tothe survivors, and improve treatment approaches.
Such collaborative studies using these newtechnologies have the potential to make a major
impact on understanding of disease processes suchas cancer and cardiovascular disease that is likely
to result in improvement of the lives of people
throughout the world.
Topics in the symposium included presentations
from RERF scientific staff on the current statusof the Adult Health Study (AHS), transcriptomic
and proteomic analysis, lipidomics and integrated“omics” approaches, and metabolomics. Fourinternationally known Japanese scientists and threeleading scientists from the United States wereinvited speakers. The symposium was attended by
the RERF scientific staff, who also acted as discussants or moderators, by a number of scientists
from academic and research institutions in Japan,
as well as by international observers from Europe
and the United States. Session I, involving the current status of RERF AHS studies, was chaired by
Dr. Yoshiaki Kodama, then Chief, RERF Department of Genetics. The session was opened by Dr.
Kazunori Kodama, Chief Scientist, then Director,
Biosample Center, who introduced RERF’s Life
Span Study (LSS) and AHS biosamples and theirsignificance to radiation research. Dr. Waka Ohishi,
Chief, Department of Clinical Studies, went into
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further details about AHS studies, as a follow-up to
Dr. Kodama’s presentation. Dr. Tomonori Hayashi,
Assistant Chief, Department of Radiobiology/
Molecular Epidemiology, gave a general summaryof RERF AHS immunology and National Institute of Allergy and Infectious Diseases (NIAID)
immunosenescence studies. A discussion ensued,
followed by a group photo session and lunch at
Hijiyama Hall.
Session II, with the theme transcriptomics(study of all RNA molecules and their functions)and proteomics (study of all proteins produced
by an organism), began in the afternoon, and Dr.
Yoichiro Kusunoki, Chief, Department of Radiobiology/Molecular Epidemiology, chaired the session. Dr. Sumio Sugano, Professor, Division of
Biosciences, Department of Medical Genome
Sciences, Graduate School of Frontier Sciences,
University of Tokyo, spoke about single cell transcriptome analysis using next generation sequencers, followed by Dr. David R. Goodlett, Professor
and Isaac E. Emerson Chair of Pharmaceutical
Sciences, University of Maryland School of Pharmacy, who spoke on label free proteomics for clinical analysis.
After a short break, Session III, relating to thefields of lipidomics (study of pathways and networks of cellular lipids in biological systems) andintegrated “omics,” was chaired by Dr. Ohishi, with
Dr. Kazutaka Ikeda, Senior Researcher, Laboratory
for Metabolomics, Center for Integrative Medical
Sciences, Riken, giving a presentation on the topic
of multi-lipidomics platforms for focusing globallyon lipo-quality. Dr. Mark R. Emmett, Professor,
Department of Biochemistry and Molecular Biology, Sealy Center for Molecular Medicine, University of Texas Medical Branch, then spoke on usesof integrated “omics” in cancer research. The day’s
events concluded with a reception hosted by RERF
that was held at Andersen, a popular European-stylebakery/restaurant in downtown Hiroshima.
Session IV, held the next day, December 3, waschaired by Dr. Hayashi under the theme metabolomics (study of metabolites present within an
organism, cell, or tissue). Dr. Albert J. Fornace,
Professor, Molecular Cancer Research Chair at
Lombardi Comprehensive Cancer Center, and Professor, Department of Biochemistry and Molecular& Cellular Biology and Department of Oncology, Georgetown University, opened the session
with his description of ongoing developments in
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Conference and Workshop Reports
radiation metabolomics. Dr. Mitsuhiro Yanagida,
Professor, G0 Cell Unit, Okinawa Institute of Science and Technology Graduate University (OIST),
spoke on the issue of the science of blood metabolomics in humans. After a short break, Dr. Daisuke
Miura, Associate Professor, Metabolic ProfilingResearch Group, Innovation Center for Medical
Redox Navigation, Kyushu University, discussed
a matrix-assisted laser desorption/ionization mass
spectrometry (MALDI-MS: a soft ionization technique used in mass spectrometry for analysis of
biomolecules)-based imaging technique and its
application to pathological analysis.
Session V, which was time set aside for general

discussion, marked the conclusion of the meeting and was finished with closing remarks by Dr.
Robert L. Ullrich, Associate Chief of Researchand the organizer of the event. Japanese o-bento
lunches for the speakers rounded out the itinerary.
This “omics” symposium focused on a newresearch field for RERF and has already led to newresearch projects being developed by RERF scientists. In addition, the symposium has stimulated
important scientific discussions between RERF
scientists and leading scientists in Japan, as well as
enhanced overseas researchers’ interest in RERF asa laboratory in which they can become involved incollaborative research into radiation effects.

Participants in the RERF International Workshop “Application of ‘Omics’ to Radiation Research”
outside Hiroshima RERF

RERF International Workshop:
Meeting on Dosimetry Issues
Harry M. Cullings, Chief
Department of Statistics
On March 25–26, 2015, an international workshop was held at Hiroshima RERF on dosimetryissues related to calculation of doses for the atomic
bomb survivors. This workshop was the third in anannual series of meetings. The plan for this workshop was to begin by summarizing the recently
completed work on dosimetry at RERF, followedby discussions related to a new plan for improved
organ dosimetry. Following these topics was a discussion of particular categories of survivors with
Return to Table of Contents“unknown doses,” which made up the majority of
the agenda.
After a brief greeting, Dr. Harry M. Cullings,
Chief, RERF Department of Statistics, began
the meeting with a summary of recent changes
to survivors’ DS02 dose estimates, as a result of
the various projects included in the recent work
at RERF during 2010–2014. This work included
cross-checking, prioritization, and selection of thebest U.S. Army map coordinates for each survivor
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Conference and Workshop Reports
based on all available original source documents,
as well as restoration of digits (tens of yards) that
had been truncated for many survivors due to limitations in early data processing systems. In addition, geometrically corrected pre-bombing aerial
photographs were prepared and assembled into
photographic maps of Hiroshima and Nagasaki
called “orthophotographic mosaics,” and thesewere used to correct distortions in the U.S. Armymaps, resulting in more accurate location information for survivors.
A major improvement in terrain shielding input
data was achieved by using high-resolution digitalterrain elevation data. Finally, the upgrade included
a number of miscellaneous improvements such asa “fix” to the DS02 code for combining the shielding of houses and terrain features, and a change inthe way that neutron and gamma-ray componentsof dose are handled when total shielded kerma
exceeds 4 Gy.
Dr. Cullings showed various histograms ofthe new dose estimates, scatter plots of new vs.
old doses, and tables related to changes in dose
estimates. There were no major changes in the frequency distributions of dose estimates for the LSS.
The overall effect of the changes on risk estimatesis expected to be small, although some relatively
subtle matters such as curvature in the doseresponse may be affected. The effects on major risk
estimates for the LSS are currently being evaluated.
A manuscript combining three previous manuscripts on the new dose estimates is being preparedand is expected to be submitted to an appropriate
journal.
In the next presentation, Dr. Cullings describeda new plan for a binational working group on organ
dosimetry to be created and funded by RERF. The
plan is to combine the existing DS02 shielded
fluences with newly created computational phantoms (models of the human body) to derive new
calculations of doses to tissues and organs. The
new phantoms would replace simple models of thehuman body developed in the 1980s, based on geometrical shapes such as cones and cylinders, andwould have more anatomical detail and body sizes.
These would include a pediatric series, male- andfemale-specific adolescent and adult phantoms, andtrimester-specific fetal phantoms. In addition to the
15 organs originally included in DS86, additionalorgans including the esophagus, heart, kidney,major blood vessels, prostate, thymus, and various
teeth would be calculated. Finally, there would be
new combined “body + workbench” and “body +machine tool” phantoms for factory workers thatwere behind a workbench or free-standing machine
tool to allow correct calculation of partial-bodyshielding. The binational working group held
its first meeting May 20–21, 2015, at Hiroshima
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update 21
RERF (a report on this meeting is expected toappear in the next Update).
In the next presentation, Dr. Stephen D. Egbert
discussed a number of factors that the organ dose
working group would need to consider in its work,
particularly in regard to how the radiation transport
calculations would be performed. He began with ahistory of organ dose calculation, noting that modifications of the T65D dosimetry system were thefirst calculations of organ doses by use of transmission factors (ratio of organ dose to dose in air at thesame location) that were not assumed to depend on
any other factors such as distance or house shielding. Then in 1985 the DS86 leakage tables werecreated for 15 organs in 3 sizes of phantoms. Thesetables could be used with any shielded fluence calculated by DS86 (and later, DS02) and have beenused for 30 years.
Next, Dr. Egbert discussed basic possible
parameters for the new effort, and in particular herecommended several target values of statisticalprecision for the new tables, starting with 1% standard error due to sampling statistics, for total organdose. He compared the advantages and disadvantages of a forward Monte Carlo transport code
(Monte Carlo N-Particle, or MCNP) and an adjoint(backwards calculation in time) code (Monte Carlo
Adjoint Shielding, or MASH). Key points werethat MCNP was more modern and up-to-date than
MASH in its inputs such as scattering probabilities(“cross sections”) but is extremely inefficient forthis problem, and leakage tables would have to be
developed by post hoc processing of the results.
Another important point was that conversion factors for converting fluence to dose would have to be
developed in some cases and should be improvedin others, particularly for heterogeneous organs andtissues involving an interface between two media,
such as red bone marrow (soft tissue interface withbone), skin and lens of eye (soft tissue interface
with air), and tooth enamel (small, sharply defined
inclusions of enamel interfacing with dentin/pulp,
soft tissue of the mouth, and bone in the jaw).
Following Dr. Egbert’s presentation, the focus
shifted to a discussion of survivors in two DS02
categories of shielding, namely categories “10”and “11,” for which there is no DS02 module tocalculate survivors shielding. The purposes of this
discussion were to illuminate the detailed shielding
situations of a large fraction of the survivors whocurrently have “unknown” doses and to suggest
possible situations that might be amenable to dose
calculation with modest effort, as well as to examine the assumptions under which survivors at longenough distances have their doses calculated in thecurrent implementation of DS02 using averagedtransmission factors (TF).
Several members of the Master File Section
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Conference and Workshop Reports
Table: Details of DS02 categories 10 and 11
OutsideCity

H
N

ds02cat

In open

BehindWall

InsideBehindtree

Terrain

Factory

Barrack

Tram orTrain

Concretebuilding

Earthcoveredshelter

Other

Total

10

58

6

6

0

20

18

1

1

3

6

119

11

50

87

7

19

65

31

192

56

17

42

566

10

15

0

132

57

30

47

1

2

1

11

296

11

37

21

16

111

109

13

3

11

254

49

624

160

114

161

187

224

109

197

70

275

108

1,605

Total

Note: H: Hiroshima; N: Nagasaki

provided details on what is known about the shielding of survivors in these categories. Mr. Tadaaki
Watanabe, Master File Section, Department of
Epidemiology, began by presenting some detailed
information and tables. Of 7,070 survivors with“unknown” doses, DS02 categories 10 and 11
comprise 5,863 (about 83%), of whom 5,448 arein category 11. Only about 27% of the survivors
in these categories have shielding histories, but
virtually all of them have some substantial information about their shielding on other early forms.
Although DS02 category 10 is commonly referred
to as “average outside,” only about 69% of thesurvivors involved were outside, and the other 31%
were actually inside at the time of the bombing.
Similarly, although DS02 category 11 is commonly referred to as “average inside,” only about
68% of the survivors involved were inside, and theother 32% were actually outside at the time of thebombing. Mr. Watanabe showed a detailed table,
reproduced above, of the types of shielding for all
survivors in DS02 categories 10 and 11.
Next, Mr. Takashi Oda, Master File Section,
Department of Epidemiology, reviewed detailed
information about three of the categories for persons who were outside: “in open,” “behind a wall,”and “behind a tree.” Although the DS86 and DS02
implementation manuals and associated materials
suggest that DS02 category 10 includes anumber of survivors who were “in open” but did
not have flash burns, and persons who were “inopen with flash burns” are supposed to be
categorized as DS02 category 0 (“in open”),
there were 108 survivors in both DS02 categories
10 and 11 who were actually “in open” andmore than half had flash burns, suggesting it
might be feasible to reclassify them as DS02
category 0 with calculated doses. Persons who
were classified as being “behind a wall”
appeared similar to those who were found to bebehind more massive earthen barriers in otherrecent work at RERF. That is to say, it might
be possible to perform dose calculations forthem based on their drawings in the cases where
drawings exist.
Return to Table of Contents

Mr. Hiroshi Fuchi, Master File Section, Department of Epidemiology, then reviewed the detailsof persons in DS02 categories 10 and 11 who
were inside of a building, i.e., in either factories or“barracks” type buildings. Some of the survivors
who were in factories appeared to have actually
been in the modeled parts of modeled buildingsin Nagasaki, making reclassification possible forthem. Others were clearly in other types of factorybuildings or in sheds on the sides of larger buildings. Of the barracks type buildings, many cases
shown were small buildings such as sheds, toilet
buildings, and guard shacks. It is not clear whether
the materials and construction of these barracks
type buildings, especially the small ones in light of
their small size compared to “9P” houses, would
allow the use of the 9P house model for them withsuitable adjustments.
Next, Dr. Cullings gave a talk that reviewed
aspects of the history of the DS02 categories 10
and 11, the rules for when they are calculated withaveraged transmission factors (TFs) as opposed tobeing classified as “unknown dose,” and how theaveraged transmission factors are calculated. A
point that emerged from these detailed presentations is that the “average outdoor” and “averageany” TFs are based on assumptions that are notcompletely consistent with the actual makeup of
the shielding situations to which they are being
applied, and may not be accurate estimates of thetrue mean TFs of the survivors to whom they arebeing applied. Furthermore, it may be possible toestimate better averaged TFs, and if it is, it may
be reasonable to apply them at proximal as well as
distal distances.
Dr. Cullings closed by reviewing criteria forpossible calculation of currently “unknown” dose
estimates, including cost and feasibility, and theprecision and potential bias of feasible estimates.
Finally, he pointed out that computational methods
and resources have changed dramatically since thetime 30 years ago when DS86 was created.
Dr. Eric J. Grant, Assistant Chief, Departmentof Epidemiology, gave a closing talk that provided
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Conference and Workshop Reports
an illustration of the power of modern computational methods. He considered survivors who wereclassified as “in open,” but may have had nontrivial
shielding from nearby buildings and other structures, or tree canopy. He pointed out that technologies exist to create three-dimensional imagery ormathematical models from sources such as aerial
photographs and/or survivors’ shielding history
diagrams. After showing some examples gleaned
from the Geographical Information System (GIS)
used for map work at RERF, he picked an example
neighborhood and showed panoramic views from athree-dimensional model that he created in Google
Sketchup™. He pointed out some advantages forsurvivors in DS02 categories 10 and 11 that are
categorized as “in open”:• Most were interviewed and have shielding
histories.
• Many were located at close ranges and havehigh doses.
• They could add to the statistical power of
RERF studies.
• They would alleviate concerns regarding
biases due to “unknown doses” and help us
maximize the use of our data.
He pointed out, however, that implementing his
idea might require developing some new models
or methods for situations not well represented by
RERF’s current GLOBE models (e.g., the model
house cluster of DS86) and methods.
With that the meeting ended on a positive note,with tangible ideas for possible future improvements to the dosimetry of survivors without shielding histories and ways to reduce the number ofsurvivors with “unknown” doses, as well as a preview of upgrades being considered for organ dose
calculation.

Participants in the RERF International Workshop on dosimetry issues
in Hiroshima RERF’s Auditorium

Seminar Held at RERF: Hiroshima Statistical Study Group —High-Dimensional Data Methods for Proteomics
Harry M. Cullings, Chief
Department of Statistics
For a number of years, RERF has been hosting the Hiroshima Statistical Study Group, whichmeets about once a month to hear a talk aboutsome aspect of statistics. Members of the groupcome from RERF and local universities such as
Hiroshima University. On January 23, 2015, thegroup was treated to a talk by Dr. Inge Koch,
Associate Professor at the School of Mathematical
Sciences of the University of Adelaide, Australia,
who was visiting Hiroshima University. Dr. Koch isan expert in high-dimensional data and has written
Return to Table of Contents

a book on the topic, “Analysis of Multivariate andHigh-Dimensional Data,” published by Cambridge
University Press. The title of Dr. Koch’s talk was“Analysis of Spatial Data from Proteomics Imaging
Mass Spectrometry.”
Mass spectrometry (MS) has become a versatileand powerful tool in proteomics for the analysis ofcomplex biological systems. It works by separating
proteins into peptides, ionizing them and electromagnetically accelerating them, then counting theions as they reach a detector. In the instrument of
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Conference and Workshop Reports
interest to Dr. Koch’s work, the masses of these
peptides are measured by the “time of flight” thatelapses between the ionization and arrival at thedetector, which generates a spectrum with thousands of very sharp peaks at different mass values.
Unlike the common MS techniques, the more
recent imaging mass spectrometry (IMS) preserves
the spatial distribution inherent in tissue samples
by measuring analyte masses at thousands of individual locations across a specially prepared tissue
sample. IMS data consist of tens of thousands ofspectra measured over at the tissue locations, andeach spectrum or profile consists of ion counts orion intensities at a large range of masses, which
are the variables. Each spectrum arises from a grid
point on the surface of a tissue section, from which
we obtain knowledge about the spatial distributionof the spectra.
Motivated by the requirements in cancer
research to differentiate cell populations and tissue types of such data accurately and efficiently,
Dr. Koch’s group developed a combined cluster
analysis and feature extraction approach to identify subsets of the spectral masses that distinguishcancerous tissue from adjacent normal tissue. She
illustrated this approach using IMS data obtained
from tissue sections of patients with ovarian cancer. To overcome problems with signal gain that
depends on location in the tissue section, peaks areconverted to binary data (present or absent) and a“differences in proportion of occurrence statistic”

Return to Table of Contents

update 24(DIPPS) is developed. In this way, the spectrum fora point on a tissue sample, which exhibits the ion
intensities of masses of peptides, can be used without any particular knowledge of the spectrum thatis generated by any particular protein or peptide.
These ideas were applied to the cancerous andnon-cancerous regions of patient tissue sections tosummarize the variables which best characterize
cancer tissue in a single image that has a naturalinterpretation. Comparisons of DIPPS maps andtheir associated “cancer” variables for tissue
samples from different cancer patients demonstrate
the similarity or diversity of cancer tissue from different patients.

Dr. Inge Koch (center), Associate Professor at the Schoolof Mathematical Sciences of the University of Adelaide,
Australia, after talk to Hiroshima Statistical Study Group,with two group members, Dr. Hirofumi Wakaki (left), Professor, Hiroshima University, and Dr. Yasunori Fujikoshi (right),
Professor Emeritus, Hiroshima University

RERF Update Volume 26, Issue 1, 2015

update 25

Science Articles

Association of Radiation Dose with Prevalence of
Thyroid Nodules among Atomic Bomb Survivors
Exposed in Childhood (2007–2011)*
Misa Imaizumi
Department of Clinical Studies, Nagasaki, RERF
*This article is based on the following publication:
Misa Imaizumi, Waka Ohishi, Eiji Nakashima, Nobuko Sera, Kazuo Neriishi, Michiko
Yamada, Yoshimi Tatsukawa, Ikuno Takahashi, Saeko Fujiwara, Takao Ando, Toshiro Usa,
Atsushi Kawakami, Masazumi Akahoshi, and Ayumi Hida: Association of Radiation Dose with
Prevalence of Thyroid Nodules among Atomic Bomb Survivors Exposed in Childhood (2007–2011). JAMA Intern Med 2015 (February); 175(2):228–236 (doi: 10.1001/jamainternmed.
2014.6692)

Study Findings
A thyroid study conducted among A-bomb survivors 62–66 years after exposure to radiation inchildhood (at less than 10 years of age) revealed
a significant association between the prevalence*of larger thyroid nodules (those with a diameterof 10 mm or more, or those with past surgery for a
nodule) and A-bomb radiation dose to the thyroid;
however, no association was observed for small
nodules of less than 10 mm in diameter.
*The term “prevalence” here refers to the percentage of the population with a disease at thetime of examination, regardless of whether or
not they had been previously diagnosed.
Explanation
Adult Health Study (AHS) participants were
examined to investigate the association between
thyroid nodules and A-bomb radiation in survivors exposed in childhood (at less than 10 yearsof age). The AHS has examined the health statusof A-bomb survivors in Hiroshima and Nagasaki
since 1958 through biennial medical assessments.
[Note]The term thyroid nodule refers to a benign ormalignant growth in the thyroid gland. Thyroid
ultrasound-based observation classifies such
nodules into two major types: cysts or solid
nodules. Nearly all cysts are benign, while solid
nodules are further classified into malignant
tumors (mostly cancers) and benign nodules.
Benign nodules include benign tumors, hyperplasia, and thyroiditis-related nodules. Thyroid
nodules that are not malignant usually do not
require treatment; however, in the case of large
nodules with pressure symptoms or when the
Return to Table of Contents

possibility of malignancy cannot be ruled out,
treatment may be necessary. This study focusedon relatively large thyroid nodules (diameter of
10 mm or more, or post-surgical cases), which
are likely to emerge as a clinical problem. The
study also reviewed small nodules less than 10
mm in diameter, which are unlikely to be a clinical problem.
1. Objectives
It is known that the risk of thyroid cancer ishigher after radiation exposure in childhood compared with exposure in adulthood. Determining
whether or not the effects of radiation exposureon the thyroid appear among adults many years
after exposure in childhood is an important publichealth issue. On the other hand, thyroid ultrasonography can detect thyroid nodules in 17–67% of thegeneral population who have had little exposure
to radiation. This study aims to elucidate the association between thyroid nodules and A-bomb radiation among A-bomb survivors more than 60 years
after exposure in childhood.
2. Methods
Thyroid examinations, including thyroid ultrasonography, were conducted on 3,087 A-bomb survivors participating in the AHS between 2007 and2011 who were less than 10 years old at the time of
exposure. The study investigated the association of
thyroid dose with the prevalence of larger thyroid
nodules (diameter of 10 mm or more, or post-surgical cases), as well as small thyroid nodules (diameter of less than 10 mm) among 2,688 survivors forwhom A-bomb radiation dose to the thyroid had
been estimated. The mean age of participants was
RERF Update Volume 26, Issue 1, 2015

Science Articles
68.2 years; 1,213 were males and 1,455 females;
the median dose was 0.182 Gy (182 mGy); and thedose range was 0–4.040 Gy.
3. Results(1) The prevalence (17.6% of those examined) oflarger thyroid nodules (diameter of 10 mm or
more, or post-surgical cases) was significantly
associated with thyroid radiation dose; theestimated excess odds ratio** per gray (Gy) of
thyroid dose was 1.65 (95% confidence interval(CI): 0.89, 2.64). We conducted the analyses byclassifying the thyroid nodules into solid nodules and cysts, and then further classifying thesolid nodules as malignant tumors or benign
nodules. Respective analyses detected a significant association between nodule prevalence
and thyroid dose.
**In this study, we considered the odds ratio tobe nearly equivalent to relative risk; The odds
ratio represents how many times higher therisk is for the radiation-exposed group thanfor the control group (i.e., those with a radiation dose of zero Gy). The excess odds ratio isrepresented by the odds ratio minus one andshows the portion of relative risk that can be
attributed to radiation exposure.
(2) The study revealed that age at exposure significantly affected the association between theprevalence of larger thyroid nodules (diameterof 10 mm or more, or post-surgical cases) andradiation, and that the effects of radiation weregreater with earlier childhood exposure. On

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update 26
the other hand, the radiation risk did not vary
substantially by sex, family history of thyroid
disease, presence of antithyroid antibodies, orintake of seaweed.
[Note]
Generally speaking, thyroid nodules occur
with greater frequency in females and in thosewith a family history of thyroid disease and arealso frequently observed in chronic thyroiditis
patients (those with positive blood tests for
antithyroid antibodies). It is also known thatthe nodules are affected by intake of iodine,and seaweed is rich in iodine. Consequently, we
examined whether or not these factors affected
the degree of radiation risk for thyroid nodules.
(3) No significant association was observed
between small thyroid nodules (diameter ofless than 10 mm) and radiation dose to the thyroid.
More than 60 years after exposure to radiation in childhood, instances of larger thyroid
nodules (diameter of 10 mm or more, or postsurgical cases) were associated with radiation
dose; however, such an association was notobserved for small thyroid nodules (diameterof less than 10 mm). The term thyroid nodule
refers to a variety of clinical states, including cancers, benign tumors, hyperplasia, andthyroiditis-related changes. The difference in
effects of radiation in relation to the size of
nodules may provide clues to the mechanisms
through which radiation exposure affects theclinical state of thyroid nodules.

RERF Update Volume 26, Issue 1, 2015

update 27

Science Articles

Skin Cancer Incidence among Atomic Bomb
Survivors from 1958 to 1996*
Hiromi Sugiyama
Department of Epidemiology, Hiroshima, RERF
*This article is based on the following publication:
Hiromi Sugiyama, Munechika Misumi, Masao Kishikawa, Masachika Iseki, Shuji Yonehara,
Tomayoshi Hayashi, Midori Soda, Yukiko Shimizu, Ritsu Sakata, Eric J. Grant, Fumiyoshi
Kasagi, Kiyohiko Mabuchi, Akihiko Suyama, Kotaro Ozasa: Skin Cancer Incidence among
Atomic Bomb Survivors from 1958 to 1996. Radiat Res 2014 (May); 181(5):531–9 (doi:
10.1667/RR13494.1)

Study Findings
Researchers observed that exposure to radiation
is associated with a significant risk of developing
basal cell skin cancer, with a dose-response threshold of 0.63 Gy and risk increasing as the age at
exposure decreases.
Commentary
1. Objective
Researchers have reported a clearly increased
risk of skin cancer, especially basal cell cancer,
in association with exposure to ionizing radiation,
based on studies of A-bomb survivors, workers
in the field of radiation medicine, and individuals
with a history of radiation treatment. The Radiation
Effects Research Foundation (RERF) previously
reported radiation risks for skin cancer based on
cases diagnosed during the period from 1958 to
1987 in the Life Span Study (LSS) population.
In the present study, the observation period was
extended for nine years, and radiation risks for skincancer according to histological type as well as theeffects of ultraviolet radiation on radiation risks
were investigated.
2. Methods
The subjects of this study were 80,158 of the120,321 individuals in the LSS population who
were alive in 1958, when both local cancer registries in Hiroshima and Nagasaki began operations,and whose radiation dose was estimated by the latest dosimetry system (DS02). Pathological review
was conducted on potential skin tumors diagnosed
from 1958 to 1996 to estimate radiation risks forfirst primary cancers by histological type. A Poisson regression model was used for the analysis.
3. Results(1) Radiation risks for basal cell cancer
With regard to basal cell cancer (123 cases),
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the best fit was a linear-threshold model with athreshold dose of 0.63 Gy (95% confidence interval[CI]: 0.32, 0.89); the excess relative risk at 1 Gy of
exposure (ERR1Gy) was estimated to be 0.74 (95%
CI: 0.26, 1.6) for those age 30 at exposure. The risk
was estimated to increase by 11% with each oneyear decrease in age at exposure; thus the ERR1Gy
was estimated to be about 7 after exposure at age
10. On the other hand, attained age did not significantly affect radiation risks.
(2) Relationship between ultraviolet radiation andradiation risks for basal cell cancer
The ERR1Gy of basal cell cancer on skin areas
likely to be exposed to ultraviolet radiation, suchas the face and hands, was estimated at 0.6 (95%
CI: <0, 2.1), and the ERR1Gy of areas unlikely to be
exposed to ultraviolet radiation, such as the trunkand extremities except for hands, was estimatedas 2.3 (95% CI: 0.61, 6.7). Although there was no
statistically significant difference between the two(P = 0.15), the results suggest that radiation risks
were higher for the areas unlikely to be exposed toultraviolet radiation.
(3) Radiation risks for squamous cell cancer in situ
(Bowen’s disease)
When a linear model was used, the ERR1Gy ofsquamous cell cancer in situ (64 cases) was 0.71
(95% CI: 0.063, 1.9). However, by city, the ERR1Gyof squamous cell cancer in situ (Bowen’s disease)in Hiroshima (56 cases) was not significant, at
0.28 (95% CI: <0, 1.9), whereas that in Nagasaki(8 cases) was extremely high, at 17.6 (95% CI:
3.0, 149); and a statistically significant difference
existed between the two (P < 0.001). However, thenumber of cases in Nagasaki was small, and there
may have been a difference between Hiroshima
and Nagasaki in the diagnosis of squamous cell
cancer in situ and in the rate of reporting to local
RERF Update Volume 26, Issue 1, 2015

update 28

Science Articles
cancer registries. Therefore, it was difficult to draw
a conclusion about whether any significant doseresponse relationship existed.
(4) Radiation risks for other histological types
There was no significant dose response relationship for malignant melanoma (10 cases), squamouscell cancer (114 cases), Paget disease (10 cases),or other skin cancers (15 cases). The null result for
malignant melanoma with regard to radiation doseis especially notable since that is the most serious

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form of skin cancer.
The results of this study show that a linear
dose-response relationship with a threshold doseof 0.63 Gy exists between basal cell cancer andA-bomb radiation, and that the lower the age is
at exposure, the higher the radiation risk. There
was no significant relationship between radiation
exposure and malignant melanoma, squamous cell
cancer, or Paget disease.

RERF Update Volume 26, Issue 1, 2015

update 29

Science Articles

Handling Incomplete Smoking History Data
in Survival Analysis*
Kyoji Furukawa
Department of Statistics, RERF
*This article is based on the following publication:
Kyoji Furukawa, Dale L. Preston, Munechika Misumi, and Harry M. Cullings: Handling
Incomplete Smoking History Data in Survival Analysis. Stat Methods in Med Res 2014
(October 26) (electronic version prior to print publication) (doi: 10.1177/0962280214556794)

Study Findings
This study proposes a new method based on
multiple imputation* for analysis involving incomplete smoking history data, a situation that could
be problematic when analyzing cancer incidence
data in the Life Span Study (LSS) of atomic bomb
survivors. Applying the proposed approach to the
LSS lung cancer incidence analysis, we observed
the radiation-associated lung cancer risk to belarger among moderate smokers than heavy smokers. The smoking-radiation interaction, which had
been estimated to be unusually strong in the previous analysis using a naive approach (relatively
simple methodology to analyze missing data) withmissing data indicators, was slightly weaker in thecurrent analysis, which seems to be more interpretable. The proposed approach is expected to reduce
estimation bias that might be unavoidable in naive
analyses while preserving efficiency by using all
available information, which should lead to radiation risk estimation with improved precision.
*A method to analyze data involving missing observations by averaging the estimation
results across multiple imputed data sets.
Explanation
In studying the radiation effects on, for example,
cancer incidence among atomic bomb survivors, it
is important to account for effects of other important risk factors, such as smoking habit. However,data for such risk factors are frequently missing or
only available incompletely. Generally, the choiceof a method to analyze data involving missing data
may have large impacts on the results of risk estimation. In particular, it is well known that a naive
approach, such as the simple deletion of subjects
with missing data, can lead to substantial bias inestimation. This study proposed a new approach
using multiple imputation for analysis involving
missing or incompletely observed smoking history
data, applied it to analysis of the LSS lung cancer
incidence, and compared the estimation results
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with those based on the simpler missing-dataapproaches.
1. Study purpose
To develop a new multiple imputation method
to analyze data involving missing or incompletely
observed time-dependent smoking history data andapply it to the LSS lung cancer incidence analysis.
2. Study methods
In analyzing the LSS lung cancer incidence
during the period 1958–1999, about 40% of the105,401 eligible subjects had no smoking data, andmany of the others had smoking history known for
only part of the time period. As a new approachof multiple imputation for incompletely observed
smoking history data, prediction models for the ageof smoking initiation and, given initiation, smoking
intensity and cessation age, were estimated; basedon which missing smoking data were predicted andimputed. Complete data sets including the imputed
data were analyzed by multiple imputation.
3. Study results
In an analysis of the LSS lung cancer incidence,
we confirmed that when one had both radiation
exposure and smoking habit, the radiation-associated excess relative risk of lung cancer would
be higher if he/she were a moderate smoker thana heavy smoker. The smoking-radiation interaction, which had been found to be unusually strongby a naive approach using indicators for missing
data, was slightly weaker with the new approach,which seems to be more interpretable for the joint
effect of radiation exposure and smoking habit. The
proposed approach is particularly appealing in alarge-scale cohort study such as the LSS, since it
can reduce estimation bias that might be unavoidable in naive analyses while maintaining efficiency
by retaining known information, which is expected
to lead to radiation risk estimation with improved
precision.
RERF Update Volume 26, Issue 1, 2015

Human Interest Notes

update 30

Participating in the Health Examination/Consultation
Project for A-bomb Survivors Living in South Korea
Daisuke Haruta, Research Scientist
Department of Clinical Studies, Nagasaki
The Health Examination/Consultation Project for A-bomb Survivors Living in South Korea
has been conducted biannually since 2004 by the
Nagasaki prefectural and city governments as partof an assistance program for the survivors currently
residing in that country. The latest trip marks the22nd of this project, and it was my third time toparticipate, following the first trip to Gwangju andDaejeon and the second to Seoul. This project aims
at dispelling concerns about late effects of A-bombradiation exposure and contributing to the good
health of the A-bomb survivors in South Korea,
through health examinations and consultations
provided by medical teams dispatched from Japan.
Since A-bomb survivors reside throughout
South Korea, the project targets cities and regions
where a relatively large number of A-bomb survivors are concentrated, such as Seoul, Daegu,
Hapcheon, Busan, Masan, Gwangju, Pyeongtaek,
Daejeon, Ulsan, Jeju, and Gyeongsangnam-do. Our
six-day schedule covered the Daegu region during
the period February 1–6, 2015 (essentially fourdays, with the first and last days spent for travel).
The project work was carried out by an eightmember team consisting of five internal medicine
specialists from Nagasaki City, one public healthnurse from the Nagasaki municipal government,
and two staff members from the Nagasaki prefectural government.
On the first day of the project, we flew from
Fukuoka Airport to Gimhae International Airport inBusan and from there traveled about two hours bybus to Daegu. After arriving in the city, we took afacility tour of the Daegu Red Cross Blood Center,
where the health examinations/consultations werescheduled, and also visited a market. We were toldthat Daegu did not have many sightseeing spots,
and our visit to the market was our only tourist
activity during our stay.
During the four-day period from the second
through the fifth days of the project, we studied theresults of examinations conducted at local hospitals
prior to our visit, and via interpreters, provided
the A-bomb survivors with explanations on theexamination results as well as health consultation
and advice. Participating in the project for the thirdtime, I had a somewhat better understanding of
how to handle my work and could carry it out relaReturn to Table of Contents

tively smoothly.
Daegu has more project participants than otherregions, with our five physicians having had consultations with 289 A-bomb survivors in total. In
terms of the latest project in Daegu, the prevalenceof lifestyle diseases was high, as in other areas,
but it was noteworthy for me that the prevalenceof diseases in the orthopedic area (osteoarthritis,
rheumatoid arthritis, and disc herniation) was highcompared with past times. On the last day of the
project, we left our hotel at 5:30 a.m. for Gimhae
International Airport for a 9:00 flight back to Japan.
Having participated in this project on multiple
occasions, I keenly felt that, like the A-bomb survivors in Japan, those living in South Korea still
suffer from the effects of A-bomb radiation exposure and that they need continued psychologicaland economic support. What otherwise impressed
me were that many A-bomb survivors in South
Korea desire friendly relations with Japan; winterin South Korea can be very cold; kimchi made inJapan better suits my taste; and my family told
me that I smelled of garlic even some time afterI returned to Japan. I hope that I can continue tobe of some help in dispelling concerns among the
A-bomb survivors in South Korea through thisproject.
I would like to express my appreciation to theresearch scientists and staff members at the RERF
Nagasaki Laboratory who supported my participa-

Health Examination/Consultation Project for A-bomb Survivors Living in South Korea visits South Korea (Dr. Daisuke
Haruta, author, at bottom left)

RERF Update Volume 26, Issue 1, 2015

update 31

Human Interest Notes
tion in this 22nd Health Examination/Consultation
Project for A-bomb Survivors Living in South
Korea, as well as to the employees and volunteer

staff members from the Korean Red Cross and to
our interpreters for their support during our stay inSouth Korea.

In Memoriam:
Arthur Canfield Upton, MD(February 27, 1923–February 14, 2015)
Arthur Canfield Upton, M.D., former directorof the U.S. National Cancer Institute (NCI) (1977–1980) and president of the American Association
for Cancer Research (AACR) (1963–1964), diedon February 14, 2015, at the age of 92. Dr. Upton
served on RERF’s Scientific Council (present-day
Scientific Advisory Committee, or SAC) as anindependent scientific advisor for seven years during the 1970s and 1980s. In that role, he provided
RERF with advice on RERF’s research activities
from a specialist’s perspective.
Dr. Upton was internationally recognized for his
research on the health effects of ionizing radiationand other hazardous environmental agents. He wasalso emeritus professor of environmental medicine
and clinical professor of environmental and community medicine at the University of Medicine andDentistry–Robert Wood Johnson Medical School
in Newark, New Jersey.
Dr. Upton was appointed director of the NCI by
President Jimmy Carter in 1977. He used his extensive knowledge of environmental carcinogenesis tomake environmental issues one of his first initiatives. In 1980, he became director of the Institute ofEnvironmental Medicine at New York University,
whose members were instrumental in establishing
the Environmental Protection Agency (EPA) andother environmental protection organizations.
Born on February 27, 1923, Upton received
his medical degree in 1946 from the University ofMichigan in Ann Arbor. In the course of his career,
Dr. Upton published nearly 400 articles, books,
and technical reports on the health effects of ionizing radiation and other hazardous environmental
agents, and he held leadership positions on theprincipal national and international professionalorganizations concerned with the prevention andmedical management of such effects, serving aspresident of the AACR, the American Society for
Experimental Pathology, the Radiation Research

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Society, and the International Association for
Radiation Research.
In recognition of his contributions, he waselected as a member to the Institute of Medicine of
the United States National Academies, Honorary
Membership in the Peruvian Oncology Society,
the Japanese Cancer Association, the New York
Academy of Sciences, as well as the American
Registry of Pathology, and received many otherhonors, including the E.O. Lawrence Award, theLovelace Medical Foundation Award for Excellence in Environmental Research, and the Distinguished Achievement Award of the Society for
Risk Analysis.
Dr. Upton is survived by his wife Elizabeth (theformer Elizabeth Perry), three children—Rebecca
Tobey, Melissa P. Upton, and Bradley Upton—ninegrandchildren, and seven great grandchildren.
RERF would like to offer its condolences to Dr.
Upton’s family and express our heartfelt appreciation for Dr. Upton’s significant contributions to thefield of radiation research over so many years,
including to the research conducted at RERF.

In memoriam: Arthur Canfield Upton, MD, ScientificCouncillor (1984)

RERF Update Volume 26, Issue 1, 2015

update 32

Facts and Figures

Preservation of RERF’s Biosamples
Yoshiaki Kodama, Director
Biosample Center
The Atomic Bomb Casualty Commission(ABCC) and the Radiation Effects Research
Foundation (RERF) have for many years collectedvarious biosamples from A-bomb survivors andtheir offspring (including blood, urine, tissue, tooth
samples, as well as microscope slide and autopsy
samples), a portion of which are preserved for
future research.
For example, we have preserved blood samples
such as serum, plasma, and lymphocytes donatedby Adult Health Study (AHS) participants throughbiennial (every two years) health examinations
since 1969, and by participants of the ClinicalStudy of the F1 Offspring of A-bomb Survivors(FOCS) through 2002–2006 health examinations
and during subsequent quadrennial (every four
years) examinations starting in 2010. In each case,consent was obtained from study participants. We
also began preserving urine samples from AHS and
FOCS participants in 2002.
As a result of these efforts, approximately

900,000 tubes of blood and urine samples fromabout 20,000 AHS and 10,000 FOCS participants
are currently preserved, most in a frozen state;other biosamples, including about 700,000 paraffin-embedded samples and 1,400,000 microscopeslide samples are stored separately (refer to thetable below for sample numbers). Since all thesematerials are extremely valuable for clarification of
the health effects of A-bomb radiation, we plan tocontinue such biosample collection and preservation into the future.
RERF’s biosamples had been collected and preserved by individual research departments or individual research scientists in accordance with theirrespective research protocols. As a result, various
problems emerged in preparing for the centralized
utilization of the biosamples, including the absenceof standardized methods for sample preparationand difficulty in creation of biosample databases.
In addition, we encountered a number of hardware
issues: preservation of samples in both Hiroshima

Table. Approximate breakdown of RERF’s biosamples (as of the end of
November 2013)
Biosamples

Total quantity (approximate)

1. Serum

490,000 tubes

2. Plasma

180,000 tubes

3. Lymphocytes

120,000 tubes

4. Urine

110,000 tubes

5. Paraffin embedded blocks

700,000 blocks

6. Microscope slide samples

1,400,000 slide samples

Serum, plasma, urine and other samples are stored in deep
Lymphocytes and other materials are stored in liquid
freezers (Hiroshima RERF).
nitrogen tanks (Hiroshima RERF).
Figure 1. Deep freezer room (left) and liquid nitrogen tank room
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RERF Update Volume 26, Issue 1, 2015

Facts and Figures
and Nagasaki locations, an important countermeasure against disasters such as fire and earthquake, islimited to a very small portion of the biosamples;and current countermeasures to protect the large
number of deep freezers in the event of power outage are not necessarily sufficient.
To address such issues, we established the
RERF Biosample Center in April 2013. Employing
specialist staff to prepare samples using standardized methods, creating centralized managementof biosamples and standardization of biosample
quality, and compiling a biosample information
database, the Biosample Center serves as a centralized, functional biosample “bank” for this valuable
material. These efforts are expected to promote
effective use of RERF’s biosamples for a wide
range of studies.
The biggest problem in the creation of the Biosample Center was a shortage of space for preserving the samples. As previously mentioned, nearly
900,000 tubes of biosamples are preserved in deep
freezers or liquid nitrogen tanks, and already both
Hiroshima and Nagasaki laboratories lack adequate
space to accept any more (Figure 1). Because it
has been difficult to secure more storage space,
we were confronted with the task of how to store

update 33
the ever-increasing numbers of biosamples. To
address this challenge, we explored the introduction of a robotic biorepository system (automatedbiosample storage) and decided to launch thesystem (Figure 2) at the Hiroshima Laboratory in
FY2015. The robotic biorepository will employ asupersized deep freezer system with a computerautomated sample-selection function and liquid
nitrogen backup cooling function in the event ofan extended power outage. The storage capacityof this system will depend on the size of biosample storage tubes; for example, it will be able toaccommodate more than three million small-sized
tubes. The introduction of the new equipment is
expected to bring about various advantages, including conservation of space, energy, and workload,
improved operation efficiency, and enhanced risk
management. We project that the robotic biorepository system will provide enough storage space forthe coming 20 years in Hiroshima. Introduction ofa robotic biorepository at the Nagasaki Laboratoryis also planned for some time in the future.
As of now, full-fledged operation of the robotic
biorepository at the Hiroshima Laboratory isscheduled to begin in October 2015.

Figure 2. Robotic biorepository (−80°C BioStore II: Operation is scheduled to start in October 2015)

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RERF Update Volume 26, Issue 1, 2015

update 34

Research Protocols and Recent Publications

Full-scale Research Protocol Approvedin November 2014–April 2015

Recent Publications

RP 1-15 Effects of ionizing radiation on
impairments of glucose and lipid metabolism
and impact on risks of arteriosclerotic diseases and cancers
Yoshimi Tatsukawa, Ayumi Hida, Michiko Yamada,Young Min Kim, Harry M. Cullings, Nobuko Sera,
Ritsu Sakata, Waka Ohishi, Shuhei Nakanishi,
Masayasu Yoneda
Impairment of glucose metabolism and lipid
metabolism are major risk factors for arteriosclerotic diseases, but the effects of atomic bombradiation on those conditions are unclear. The
Adult Health Study (AHS) cohort of atomic bomb
survivors, which has been followed by biennial
health examinations since 1958 and has obtained
medical information at each examination cycle,
is comprised of suitable subjects for assessing theeffects of radiation on conditions such as diabetes
and dyslipidemia. Furthermore, the AHS cohort
was expanded in 2008 to include about 1,900
younger survivors (<10 years old at the time ofbombing [ATB]), and various biomarkers for glucose and lipid metabolism have been measured inthem as well as in the original cohort. Since theexpansion group includes a large number of lightly
exposed individuals relative to the original cohort,
it will provide more precise information on dose
response. In this proposed research protocol (RP),
we will use a longitudinal study format to examine
whether radiation exposure is associated with thedevelopment of diabetes and whether any such
association is influenced by the city of exposureand age ATB.
It is well known that radiation exposure is associated with increased risk for many cancers. Recent
studies have also suggested an association between
radiation exposure and the risk of arteriosclerotic
diseases; however, the underlying mechanism
remains elusive. Diabetes and dyslipidemia aremajor risk factors for arteriosclerotic diseases.
Recent epidemiological studies have also shownthat diabetes is associated with risk for not only
arteriosclerotic diseases but some cancers as well.
This RP will also investigate whether radiation
exposure is associated with increased risks of arteriosclerotic disease and cancer through impaired
glucose and/or lipid metabolism, using ‘causal
modeling’ to evaluate intermediate variables. We
will use a cross-sectional study design, to investigate an association between radiation exposureand HbA1c, insulin resistance, lipid levels (such as
HDL cholesterol), and biomarkers involving glucose and lipid metabolism (such as adiponectin).

Akamatsu S, Hayes CN, Tsuge M, Miki D,
Akiyama R, Abe H, Ochi H, Hiraga N, Imamura
M, Takahashi S, Aikata H, Kawaoka T,
Kawakami Y, Ohishi W, Chayama K: Differences
in serum microRNA profiles in hepatitis B and C
virus infection. J Infect Dis 2015 (March);
70(3):273–87.

Return to Table of Contents(Japanese): the original article is in Japanese.

Allemani C et al.; the CONCORD Working Group(RERF: Sugiyama H, Utada M): Global surveillance of cancer survival 1995–2009: analysis
of individual data for 25676887 patients from279 population-based registries in 67 countries (CONCORD-2). Lancet 2014 (March);
385(9972): 62038–9.
Bernstein JL et al., The WECARE Study Collaborative Group (RERF: Shore RE): Contralateralbreast cancer after radiotherapy among BRCA1and BRCA2 mutation carriers: A WECARE
Study Report. Europ J Cancer 2013 (September);
49(14):2979–85.
Chayama K, Hayes CN, Ohishi W, Kawakami Y:
Treatment of chronic hepatitis C virus infectionin Japan: update on therapy and guidelines. J
Gastroenterol 2013 (January); 48(1):1–12.
Cologne JB: Uncertainties in the estimation ofradiation risks and probability of disease causation (NCRP Report No. 171) [Book Review].
Health Phys 2013 (May); 104(5):532–3.
Crowley KD, Cullings HM, Landes RD, Shore RE,
Ullrich RL: Comments on estimating risks of
low radiation doses—A critical review of the
BEIR VII Report and use of the linear no-threshold (LNT) hypothesis by Edward J. Calabreseand Michael K. O’Connor. Radiat Res 2015
(April); 183(4):476–81. (RERF Report 2-15)
Cullings HM: Impact on the Japanese atomic bomb
survivors of radiation received from the bombs.
Health Phys 2014 (February); 106(2):281–93.
Cullings HM, Pierce DA, Kellerer AM: Accounting
for neutron exposure in the Japanese atomic
bomb survivors. Radiat Res 2014 (December);
182(6):587–98. (RERF Report 9-13)
Grant EJ, Ozasa K, Ban N, de Gonzalez AB,
Cologne JB, Cullings HM, Doi K, Furukawa K,
Imaoka T, Kodama K, Nakamura N, Niwa O,
Preston DL, Rajaraman P, Sadakane A, Saigusa
RERF Update Volume 26, Issue 1, 2015

Recent Publications
S, Sakata R, Sobue T, Sugiyama H, Ullrich RL,
Wakeford R, Yasumura S, Milder C, Shore RE: A
report from the 2013 International Symposium:
The evaluation of the effects of low-dose radiation exposure in the Life Span Study of atomic
bomb survivors and other similar studies. Health
Phys 2015 (May); 108(5):551–6. (RERF Report
12-14)
Hamatani K: Molecular oncology study using preserved solid cancer tissue specimens developingin A-bomb survivors—With a focus on papillary thyroid cancer. Nagasaki Igakkai Zasshi[Nagasaki Med J] 2014 (September); 89(Special
issue):195–201. (Proceedings of the 55th Late
A-bomb Effects Research Meeting, 2014) (Japanese)
Haraguchi A, Fujishima K, Ando T, Mori F,
Imaizumi M, Abiru N, Yamasaki H, Matsumoto
K, Takamura N, Kawakami A: Multiple drug
combination of anti-diabetic agents as a predictor
for poor clinical response to liraglutide. Minerva
Endocrinol 2014 (December); 39(4):289–97.
Haruta D, Akahoshi M, Hida A, Sera N, Imaizumi
M, Ichimaru S, Nakashima E, Takahashi I,
Ohishi W, Fukae S, Maemura K: Prognostic significance of premature ventricular contractions
without obvious heart diseases determined bystandard 12-lead electrocardiography considering their morphology. Ann Noninvasive Electrocardiol 2015 (April). doi: 10.1111/anec.12275.
[Epub ahead of print]. (Commentary and Review
Series 1-14)
Hayashida N, Imaizumi M, Shimura H, Furuya
F, Okubo N, Asari Y, Nigawara T, Midorikawa
S, Kotani K, Nakaji S, Ohtsuru A, Akamizu T,
Kitaoka M, Suzuki S, Taniguchi N, Yamashita
S, Takamura N: Thyroid ultrasound findings in afollow-up survey of children from three Japanese
prefectures: Aomori, Yamanashi, and Nagasaki.
Sci Rep 2013 (March); 5:9046. doi: 10.1038/
srep09046.
Hayashida N, Imaizumi M, Shimura H, Okubo
N, Asari Y, Nigawara T, Midorikawa S, Kotani
K, Nakaji S, Otsuru A, Akamizu T, Kitaoka M,
Suzuki S, Taniguchi N, Yamashita S, Takamura
N: Thyroid ultrasound findings in children
from three Japanese prefectures: Aomori,
Yamanashi and Nagasaki. PLoS ONE 2013
(December); 8(12):e83220. doi: 10.1371/journal.
pone.0083220.
Hu Y, Yoshida K, Kajimura J, Kyoizumi S,
Kusunoki Y, Cologne JB, Ohishi W, Hayashi I,
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update 35
Nakachi K, Hayashi T: The relationship between
CD14 gene polymorphism and risks of colorectal
cancer subsites among atomic bomb survivors.
Nagasaki Igakkai Zasshi [Nagasaki Med J]
2014 (September); 89(Special issue):257–61.
(Proceedings of the 55th Late A-bomb Effects
Research Meeting, 2014) (Japanese)
Ikeoka T, Ando T, Imaizumi M, Ueki I, Usa T,
Kawakami A: Moderate to severe nausea inradioactive iodine (RAI) therapy is associatedwith the RAI dose per body weight and was
not prevented by ramosetron. Endocrine 2014
(May); 46(1):131–7.
Imaizumi M, Ohishi W, Nakashima E, Sera N,
Neriishi K, Yamada M, Tatsukawa Y, Takahashi
I, Fujiwara S, Sugino K, Ando T, Usa T,
Kawakami A, Akahoshi M, Hida A: Associationof radiation dose with prevalence of thyroid nodules among atomic bomb survivors exposed inchildhood (2007–2011). JAMA Intern Med 2015
(February); 175(2):228–36. (RERF Report 9-14)
Ito Y et al., the J-CANSIS Research Group (RERF:
Sugiyama H): Long-term survival and conditional survival of cancer patients in Japan using
population-based cancer registry data. Cancer
Sci 2014 (November); 105(11):1480–6.
Kerr GD, Egbert SD, Al-Nabulsi I, Beck HL,
Cullings HM, Endo S, Hoshi M, Imanaka T,
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Kodama Y: Genetic effects of atomic bomb radiation on humans. Fukushima Nuclear Accident:
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Kusunoki Y, Yoshida K, Kubo Y, Yamaoka M,
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on human immune responses. Report 27: Inverse
associations between obesity indicators andthymic T-cell production levels in A-bomb survivors. Nagasaki Igakkai Zasshi [Nagasaki Med
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(Proceedings of the 55th Late A-bomb Effects
Research Meeting, 2014) (Japanese)
Landes RD, Lensing SY, Kodell RL, Hauer-Jensen
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update 36

Recent Publications
M: Practical advice on calculating confidence
intervals for radioprotection effects and reducing animal numbers in radiation countermeasureexperiments. Radiat Res 2013 (December);180(6):567–74.
Nakamura N: Cancer risks and mechanisms ofradiation carcinogenesis (Radiation risk at low
doses: Series 2). Nagase Landauer Newsletter2014 (March); No.435:2. (Japanese)
Nakamura N: Thoughts on Fukushima (Radiation
risk at low doses: Series 4). Nagase Landauer
Newsletter 2014 (May); No.437:2. (Japanese)
Nakamura N: What is radiation? (Radiation risk at
low doses: Series 1). Nagase Landauer Newsletter 2014 (February); No.434:2. (Japanese)
Nakamura N: How to think about low dose risksof radiation? Nihon Hoshasen Koushu Anzen
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(Japanese)
Nakamura N: Hiroshima and Nagasaki, low doserisks (Radiation risk at low doses: Series 3).
Nagase Landauer Newsletter 2014 (April);
No.436:2. (Japanese)
Nakamura N, Sakata R: Explanation on “no ageat-exposure effect on the relative risk of breast
cancer in atomic-bomb survivors.” Hoshasen
Seibutsu Kenkyu [Radiat Biol Res Commun]
2013 (December); 48(4):388–400. (Japanese)
Nakashima E, Neriishi K, Hsu WL: Radiation may
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standing height via subclinical inflammation in
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Epidemiol Res Int 2015 (January); Vol 2015(ID295958):10 pages. doi: 10.1155/2015/295958.
(RERF Report 17-11)
Ohishi W, Chayama K: The relationship of elevatedIL-6 and increased risk of hepatocellular carcinoma. Nippon Rinsho [Jpn J Clin Med] 2015
(January); 73(Suppl 1):217–21. (Japanese)
Ostroumova E, Rozhko A, Hatch M, Furukawa
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Survey. J Epidemiol 2015 (January); 25(1):80–7.
Sakai A, Ohira T, Hosoya M, Ohtsuru A, Satoh H,
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(RERF Report 7-14)
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Kazuki Y, Osaki M, Oshimura M, Ishigaki Y,
Hamasaki K, Kodama Y, Yuasa S, Fukuda K,
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Tekwe CD, Carter RL, Cullings HM, Carroll RJ:
Multiple indicators, multiple causes measureRERF Update Volume 26, Issue 1, 2015

Recent Publications

update 37

ment error models. Stat Med 2014 (November);
33(10):4469–81.
Walsh L, Roy Shore RE, Auvinen A, Jung T,
Wakeford R: Risks from CT scans—what dorecent studies tell us? J Radiol Prot 2014
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Walsh L, Zhang W, Shore RE, Auvinen A, Laurier
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Yamada M, Landes RD, Mimori Y, Nagano Y,
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Research Foundation Adult Health Study. J Neurol Sci 2015 (April); 351(1-2):115–9. (RERF
Report 11-14)

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RERF Update Volume 26, Issue 1, 2015

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