FY2019 Plans of Activities
I. Plans of Major Activities
Because much of RERF’s research involves longitudinal or large scale long-term studies thattake a significant time to plan and conduct, so a number of ongoing plans for such studies
have already been presented under research achievements. Here we provide highlights of new
research plans or selected plans of note.
1. Research Projects Examining A-bomb Survivors Health1) Radiation and Cancer:
 Updated cancer incidence: A series of papers on cancer incidence risk following radiation
exposure for individual sites in the LSS during 1958–2009 will be published in 2019 incollaboration with US National Cancer Institute. Individual organ sites or organ systems
expected to be submitted for internal review in 2019 include: upper digestive system,
hepato-biliary-pancreatic, uterine, prostate, urinary tract, CNS, and ovary. Papers tosummarize the results of individual sites including investigation of different curvature
between sexes will be submitted to international journals.
 Radiation risk at low dose levels: Current efforts on cancer incidence risk analysis at lowdose levels will be developed, in a collaboration between the Epidemiology and Statistics
Departments. Analysis of the non-linear dose-response for all solid cancer incidence risk inmales will be continued including analyses of dose-responses for cancer of individual sites.
Analyses of potential confounding by geospatial factors and variation in baseline rates, andmodeling of baseline rates, will be continued including preparation for studies of mortality
risk in the LSS including non-cancer diseases. Dose errors as well as the potential impact
of exposure to residual radiation and medical radiation will also be considered. Risk
analyses using mechanistic models will be continued in collaboration between RERF andthe Helmholtz Zentrum München.
 Liver cancer program project: A multidisciplinary program project on radiation and livercancer will be developed involving researchers from the Departments of Statistics,
Molecular Biosciences, and Epidemiology within the cancer research cluster (Projects
involve: identification of novel biomarkers for detection, mechanisms, and radiation
sensitivity of HCC; mechanisms of radiation-associated HCC with HBV/HCV;
mechanisms of radiation-associated non-B/non-C HCC using mouse models; and statisticaland epidemiological methodological issues). Overall objectives are to clarify immunologic
and metabolic mechanisms of radiation-associated HCC in order to: 1) better understandthe underlying biological and clinical aspects; 2) obtain more-precise estimates of risk; and3) be able to apportion probability of causation in radiation-associated HCC.
 Breast cancer: As a part of potential program project, we are considering designing anested case-control study of breast cancer starting in 2019. We would use the Toshiba
Japonica Array developed for analyzing gene polymorphisms in the Japanese population to
examine polymorphisms potentially involved in the development of radiation-associatedbreast cancer. In order to conduct a genome study using a cohort of all AHS subjects, DNA
samples extracted from old smear samples must be used. For this reason, it is necessary to
determine whether SNP analysis using the Japonica Array is possible by amplifying thewhole genome using a very small amount of DNA obtained from blood smear samples
stored for many years. In FY 2019, DNA extraction from preserved blood smear samples

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will be carried out to examine a suitable preparation method for REPLI-g amplified DNA.
Then, we will evaluate DNA availability by analyzing those DNA samples with the
Japonica Array.
 Myelodysplastic Syndrome (MDS): We will continue our collaborative program with
Nagasaki University and Kyoto University to determine mutations in serially collectedblood samples from individuals developing MDS using genomic analysis. Sequencing is
expected to be completed in early 2020.
2) Radiation and Non-Cancer Effects:
 Cardiovascular disease program project: As part of a new program project that is being
reviewed in the Non-cancer Research Cluster, we will develop strategies for assessment ofclonal hematopoiesis potentially linking to radiation-associated noncancer diseases,
specifically arteriosclerosis, in the AHS. Our hypothesis in this program project is thatsomatic mutations in epigenetic modifier genes (TET2, DNMT3A, ASXL1, etc) inhematopoietic stem cells drive clonal hematopoiesis, resulting in accumulation of proinflammatory monocytes and T cells. Endogenous danger signals―alarmins―may also be
involved in inflammatory phenotypes of monocytes and T cells. To strengthen the
hypothesis, we will also develop mouse and mathematical simulation models to evaluateclonal expansion of hematopoietic stem cells (HSCs) and pro-inflammatory phenotypes
following radiation exposure.
 Neurocognitive function: Analysis of radiation effects on the Neurocognitive Questionnaire(NCQ) and the Cognitive Abilities Screening Instrument (CASI) will be expanded toinclude subjects exposed in utero.
 Cataracts: We will complete evaluation of cataract severity by June 2019 and start analysis
the relationships between several types of cataracts and radiation among subjects who were
<15 years of age at the time of bombings (excluding in utero-exposed subjects) incollaboration with Department of Statistics. Continue ophthalmologic examinations among
in utero-exposed subjects until March 2020 and start scoring cataract severity in July 2019.
3) Immunologic Effects of Radiation:
 T-cell immunity and liver cancer: Both adaptive and innate immunity play crucial roles inhepatocellular carcinoma (HCC) development and progression. The T-cell immune
response is the most important defense mechanism against viral hepatitis and HCC, but onsome occasions exacerbates HCC, whereas macrophages promote liver fibrosis andsuppress anti-viral T-cell responses. To test the hypothesis that radiation exposure may
accelerate the progression to HCC through dysregulation of T-cell immunity and innate
inflammatory response, we will analyze longitudinal data of immune cell parameters in
AHS subjects (e.g., naïve T-cell, NK-cell, and monocyte counts), in relation to radiationdose, hepatitis virus infection, inflammation, liver steatosis, fibrosis, and HCC.
2. Research Projects on the Health of A-bomb Survivors Children (F1) F1 cohort study: A cancer incidence paper is expected, but it is difficult to estimate themigration rates of F1 cohort members out of cancer registry areas. In addition, the RERF
Epidemiology Department does not have sufficient information regarding subjects’
addresses although the current address of the cohort members provides substantial
information for personal identification on crosscheck with cancer patients recorded incancer registries. It is because we have no direct contact with them and cannot collect suchinformation from municipality offices without agreement by the subjects under legal2restrictions that difficulties arise. On the other hand, subjects in the F1 Offspring ClinicalStudy (FOCS) have been contacted by the RERF Clinical Studies Department every year
for the health examination program. Therefore, collection of cancer incidence informationof F1 subjects from the national cancer registry system will focus on the subjects in the
FOCS by using the contact address as a personal identifier.
 FOCS: We will continue to conduct health examinations among the cohort members ofboth the AHS and F1 follow-up clinical studies. A high-priority activity in the coming year
will be to form a working group to assess appropriate methodology and develop a plan fora risk analysis of the F1 Clinical Study (FOCS) data when the current cycle (third
longitudinal cycle; fourth round overall including the preliminary cross-sectional study)
comes to a close. The FOCS design combines baseline disease prevalence with subsequent
incidence (the latter among participants who were disease-free at baseline). The study
outcomes comprise a number of clinical endpoints, many of which are stages in diseasedevelopment; the analysis can therefore employ disease transition models. Illness-deathprocesses should also be considered given that truncation due to death can cause bias inlongitudinal studies. The working group will conduct its assessment in close collaboration
with Clinical Studies researchers. The goal in the coming year is to develop an outline ofsteps to be taken in the following several years so that a formal analysis plan can be inplace to allow us to conduct preliminary analyses at the time the current (third) FOCS
cycle (fourth round) ends in the fall of 2022 (albeit some data will continue to accumulate
for several years beyond that as backup exams are conducted, so that final analyses basedon the fourth round is expected to be completed a few years after that).
 Integrated genetics program (F1 umbrella project): An integrated program project forradiation effects on the F1 generation including F1 mortality and cancer incidence followup, FOCS, genomic analysis of trios, and related animal studies will be developed in the
Genetic Research Cluster.
 Sequencing: As a major part of studies related to the development of the F1 umbrella
project, we plan to conduct WGS analysis of human trio (parents and a child) samples
including atomic bomb survivors and their offspring. As a first step, we plan a preliminary
experiment using a small number of trio samples. In FY2019, we will develop an
experimental plan using the newest technologies and prepare an experimental environment
for the conduct of that project, including physical resources for sequencing data analysis,
an information security system for the genomic data, and a world-wide scale collaboration
network for the project. One of the most important issues is getting an understanding of
this WGS project with stake holders (atomic bomb survivors and their children) andcitizens. So, we will make a series of communication and education programs for citizens.
 Transmission of germ-line mutations: To mechanistically understand how radiation
exposure induces mutations in spermatogonia stem cells and how their mutations transmit
to the next generation, we have initiated an in vitro culture approach to examine mouse
spermatogonia cells (hereinafter GS, germline stem cells). Irradiated GS cell culture will
be characterized by aCGH and WGS analyses, and then they will be transplanted into
Busulfan-treated testes of adult male mice.We will then examine the offspring derived
from the GS cells for heritable genetic changes. Along with this experiment, efficiency ofspermatogenesis from the transplanted GS cells will be analyzed by testis tissue crosssections. Spermatogonia stem cell division (mitosis) and subsequent meiotic division are
divided in several steps, where some of the steps are characterized by specific antigens
such as PCNA/Ddx4 (spermatogonia), Stra8 (preleptotene), Spo11 (early prophase), Hspa2(late spermatocyte). These antigens, cell morphology and localization in seminiferous
tubules could determine the progression of meiosis of transplanted GS cells.

33. Research to Elucidate Individual Radiation Doses and the Effects of A-bombs
 Radiation dosimetry and dose error: We will continue to support and collaborate with theorgan dosimetry working group, based on their recommendations. In relation to dose
uncertainty, we will assess the impact of dose uncertainty on the dose-response at low
doses, based on plug-in estimators that can accommodate both classical and Berkson (or,grouping) error; and reconstruction of a marginal distribution of unobservable true doses
among the LSS, based on pre-bombing population estimates, sampling fractions, andestimated shielding distributions, in parallel with development of methods that avoid
assumptions regarding the parametric distribution of unobservable true doses.
We will also investigate an alternative approach to dose-error handling by treatingradiation dose as a latent variable in MIMIC (causal) models and compare this to thestandard use of regression calibration substitution dose estimates. A key component of thiswork will be to assess the impact of dose-error handling on inference regarding indirect
effects of radiation on latent-factor indicators.
Missing data represent, perhaps, the most extreme case of measurement error. In DS02R1,
survivors with unknown or complex shielding histories not accommodated by thedosimetry system have unknown doses. A goal for the coming year is to begin constructing
imputation models for missing doses by using all available information from the dosimetry
system, and compare results to findings based on exclusion of survivors with missing dose.
4. Project to Release of Research Results and to Collaborate with Other Scientific
Organizations
 Continuing collaborations: Long term collaborations are listed below and these are
expected to continue in 2019:a. Partnership with the University of Washington
b. Partnership with Kurume Universityc. Collaborations with the US National Cancer Instituted. Collaborations with the University of Florida
e. Collaborations with Outside Investigators:
39 Japanese Institutions
18 North American Institutions
14 European Institutions
3 Asian, Oceanian Institutions
Nuclear Emergency Workers Study (NEWS): 11 Japanese Institutions
5. Training Programs for Domestic and Overseas Specialists
RERF will hold a training seminar for non-epidemiologist radiation researchers to learn thebasics of epidemiological research and increase understanding of radiation health risks. In
addition, RERF will train persons capable of working in the fields of radiation protection,
radiation emergency medical care, and radiobiological research.
Activity plans for FY2019i) RERF will hold an epidemiological training seminar for radiation biologists in Japanagain in FY2019 for enhanced understanding of results from epidemiology research on
A-bomb survivors.
ii) RERF will accept overseas research trainees to support the activities of suchorganizations as the Hiroshima International Council for Health Care of the Radiation-4

exposed (HICARE), the Nagasaki Association for Hibakusha’s Medical Care
(NASHIM), and the Japan International Cooperation Agency (JICA).
iii) RERF will accept students from domestic and overseas schools/universities for facility
tours, and will provide training sessions on the foundation’s research activities.
iv) RERF will continue to review directions as to its training activities and publicly invite
overseas trainees in the International Exchange Research Program for FY2019 also.
6. Public Information Programs
Activity plans for FY2019i) RERF Open House event
RERF will hold its 25th and 23rd Open House events at the Hiroshima and Nagasaki
RERF Laboratories, respectively. The event will feature various programs, including
exhibitions as well as lectures, and is once again scheduled to be held during FY2019
in Hiroshima and Nagasaki in August.
ii) RERF Public Lecture
RERF will hold public lectures to provide the general public with an opportunity toenhance their understanding of the foundation’s research and to learn more about
radiation’s health effects.
iii) Enhance social media activities
RERF will expand its reach through use of social media networks, by putting moreemphasis on Facebook content and initiating a Twitter account. The Twitter project
would take place only in an English version to begin and move to Japanese after we cantest the kind of response RERF tweets receive in English from the international
community.
iv) Improve-media-relations projectThis new project was initiated with two meetings (one with broadcast media, one withprint media) at the beginning of 2019 (Jan.), with the aim of increasing the probability
for neutral coverage of ABCC/RERF and its research results by the media. Such mediacommunication meetings will be held again during FY2019, aiming at fostering closer
relations with the media.
v) Enhancement of new RERF website
Following the launch of the new RERF website in FY2018, the information on the
homepage will continue to be updated and enhanced. A focus will be placed inparticular on effectively conveying readily understandable information to the public,
such as by using more video and other methods.
vi) Creation of new online news-delivery system
Following the discontinuation of the printed Update newsletter at the end of 2016, a
new email magazine system (a subscriber-list online news-delivery system, by which
RERF will regularly send out informative email to people who subscribe to the service
to read the latest about RERF) will be created and used to not only distribute the latest
research results and information about RERF events and activities but also to attract
subscribers to RERF as “members,” by offering a sense of “buy-in” with respect to
RERF as an organization.

5vii) Improvement of social media techniques
RERF will attempt to attract younger people to our cause through the use of social
media, such as Facebook and Twitter, by joining with the independent U.S.-based
Think Global School (TGS) high school once again in FY2019, as was done in FY2018.
To help us attract more young followers, TGS will collaborate with RERF to improve
our Facebook page content and to formulate project plans geared toward use of Twitterand other social media platforms.
viii) School Visit ProgramThis program was first established in FY2016 in an attempt to convey to young school
students the reality of radiation health effects. Each year, the number of requests forsuch classes increasing yearly and a now firm stable of teachers being established haveprovided the opportunity to teach an increased number of classes. In FY2019, in
addition to the conventional school visit program, we will also work to expand the
project by teaching students about radiation and about how to teach the basics ofradiation to their peers, in a student-led education drive.
ix) Other public relations activities• RERF will actively promote the foundation’s important scientific papers to thedomestic and overseas media via press releases and press conferences.
• With the aim of improving public understanding of RERF research, the Officeinitiated in FY2018 a new series of paper synopses that explain research with simpler
prose and smaller word counts than used previously in our “summary explanation”
series for specialists. Through continuation of this series in FY2019, the Office will
aim to improve understanding by the public of RERF work.
• In continuation from RERF’s first-ever press conference at the Foreign
Correspondents’ Club of Japan in February 2017, as well as the joint press meetingwith ICRP at the University of Tokyo in December of the same year, RERF will hold
another such event in Tokyo during FY2019.
• A persistent goal again this fiscal year is the training of more RERF personnel tohandle the tours in English for overseas visitors.
• With the aim of improved transparency related to RERF research and establishment ofgood communication with the public, in particular A-bomb survivors and theirchildren, by increasing our effort at communicating RERF’s research, the PublicAwareness Campaign Working Group was formed in January 2019. The Working
Group will attempt to provide information on important topics such as the humangenome and our gene studies, and so on.
• RERF will continue to target small public groups of A-bomb survivors and theirchildren, who will be invited to come to RERF and speak with directors and staff
about ABCC/RERF history and research results, with the aim of achieving greater
understanding about RERF with more personal, small-scale opportunities.
II. Activities necessary for the above projects
1. Research Resource Center
The Research Resource Center (RRC) is a core RERF infrastructure to store, document,
and index all RERF resources and to integrate research data with biosample data topromote research.

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A White Paper has been completed that lays out a 3-year timeline for getting the RRC
through its primary phases of development. Seen broadly, there are two main areas ofdevelopment.
1. A data integration project
2. An archiving/preservation project
The data integration project will require expertise and software that is not available within
RERF. Therefore, outside experts will need to be brought in to help the initial installationand development. Over the past 18 months a number of experts around the world havebeen consulted to identify systems at other institutions that may be suitable for our needs.
Recently, the “Gen3” system, a “Data Commons” used by the NIH and other institutions
was investigated. Gen3 is a cloud-based software platform for managing, analyzing,
harmonizing and sharing large datasets. Gen3 is an open source platform for developing
data commons. RERF management has decided to proceed with a pilot project using Gen3
to test if it is compatible with the scientific needs at RERF.
The archiving/preservation project is for protecting RERF assets. Research assets collected
since 1947 represent the entire life history of one of the world’s most unique cohorts andare impossible to replicate. World experts have been invited to RERF including Dr.
Christy Henshaw, Digital Production Manager at the Wellcome Trust. Priorities for which
resources will be scanned first have been set and production procedures are being worked
out, including software installation requirements.
A location for the RRC has been selected and will include an archiving room withtemperature and humidity controls (already installed), a scanning room, a secure networkroom for collaborative whole-genome-sequence studies, a developer’s area, and aclassroom area.
2. Planned employment of general employees
Currently, the age-distribution for RERF employees is uneven as many employees are ofadvanced ages. Almost 70% of employees, excluding those reemployed, are 50 years old
or older. For the smooth intergenerational succession of duties, we will consider
postponing mandatory retirement ages, or both, while taking account of governmental andsocial factors. We will discuss the merger of sections and offices within RERF and sharing
duties among employees from different departments/sections, cutting and reducing
workloads. We will continue to actively convert employees with limited terms of
appointment, including temporary employees, to permanent staff members and hire fixedterm general employees after carefully considering the necessity of their duties, RERF’s
financial situation, and our personnel cap.
3. Continuation of long-term leadership training
To raise employee motivation for becoming management-level personnel, we haveplanned a total of six leadership training sessions for those in assistant section chief
positions or lower over a four-fiscal-year period starting from FY2017. The fourth andfifth sessions will be held in July and November FY2019, respectively, in Hiroshima andNagasaki. The training theme for this fiscal year is leader communication training, such as
sharing a common goal, giving proper instructions, and motivating their subordinates, andleadership training. Through this training, participants are expected to learn about capacity
and resourcefulness required for the leaders.

74. Introduction of an attendance and work management system
On June 29, 2018, a package of work-style reforms bills passed and became laws. So,
RERF needs to promote work style reforms and streamline clerical work. We will
introduce an attendance management system in FY2019 to objectively discern the working
hours of all staff and create workflows for all paid leave forms and overtime forms. By
doing so, we aim to streamline attendance management duties and make salarycalculations more efficient by linking attendance management data to the payroll system.
Attendance management means that companies properly grasp their employees’ working
status. In concrete terms, all staff members will keep IC cards and pass their cards througha card reader that will be placed at the entrance to record and check the time at which theycome into work and go home, work effort, overtime work, and application and acquisitionof paid holidays. Most Japanese central government ministries and agencies already use
this attendance system.
5. Facility upgrades(1) Facility upgrades to the Hiroshima Laboratory
We are in the second year of a three-year plan we are implementing to replace all air
conditioners currently in use by FY2020, as the units are deteriorating and some containbanned fluorocarbons.
(2) Facility upgrades in Nagasaki
RERF will renovate the exterior walls for the second time to prevent water from leaking
due to deteriorating exterior wall paint, and pieces of exterior walls from falling due tocracks. The first renovation was conducted in FY2003. RERF and the Nagasaki Prefectural
Board of Education will share the costs.
6. Continuation of internal audit process
As in FY2018, RERF will sign another entrustment contract for internal audit with anoutside auditing company in FY2019.
7. Revision of regulations
The internal audit conducted by Deloitte Touche Tohmatsu LLC found that RERF had
neither prepared rules regarding expenses for meetings nor ethical regulations on
preventing corruption such as bribery. RERF had not prepared written rules on taxi use,
either. As a public interest incorporated foundation operating with national subsidies,
RERF has decided to prepare strict rules on expenses for meetings and disbursement oftaxi fares and ethical regulations on preventing corruption.

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