Highly asymmetric probability distribution from a finite-width upward step during inflation

We study a single-field inflation model in which the inflaton potential has an upward step between two slow-roll regimes by taking into account the finite width of the step. We calculate the probability distribution function (PDF) of the curvature perturbation $P[{\cal{R}}]$ using the $\delta N$ formalism. The PDF has an exponential-tail only for positive ${\cal{R}}$ whose slope depends on the step width. We find that the tail may have a significant impact on the estimation of the primordial black hole abundance. We also show that the PDF $P[{\cal{R}}]$ becomes highly asymmetric on a particular scale exiting the horizon before the step, at which the curvature power spectrum has a dip. This asymmetric PDF may leave an interesting signature in the large scale structure such as voids.Comment: 19 pages, 7 figure

Public attitudes in Japan toward the creation and use of gametes derived from human-induced pluripotent stem cells

ヒトiPS細胞を用いた配偶子の作製と利用をめぐる日本の一般市民を対象にした調査. 京都大学プレスリリース. 2021-10-25.[Aim:] To ascertain to what extent the Japanese general public accept the creation and use of in vitro derived (IVD)-gametes derived from human-induced pluripotent stem cells. [Materials & methods:] We conducted an online survey and obtained answers from 3096 respondents. [Results:] 78.6% of the respondents answered that they would accept the creation and use of IVD-gametes for research purposes, 51.7% answered that they would accept the creation and use of embryos with IVD-gametes for research purposes, and 25.9% answered that they would accept childbirth using embryos with IVD-gametes. [Discussion:] The results that approximately half of the respondents answered that they would accept the creation of embryos with IVD-gametes, which has not been allowed in the current Japanese research guidelines, is astonishing

Human genome editing in clinical applications: Japanese lay and expert attitudes

ヒトを対象としたゲノム編集の利用に関する調査研究. 京都大学公式プレスリリース. 2023-09-27.Capturing the lay public's opinions on genome editing of human embryos. 京都大学プレスリリース. 2023-10-12.Background: The world’s first gene-edited babies, reported by the Chinese scientist He Jiankui, prompted an outcry of criticism and concerns worldwide over the use of genome editing for reproductive purposes. Many countries and academic associations opposed to heritable genome editing (HGE) called for public discussion involving various stakeholders. To hold a discussion of this nature and form a consensus concerning HGE, we must understand under what conditions stakeholders consider HGE acceptable and the reasons for which they deem it unacceptable. Methods: Laypeople and researchers were surveyed in May 2019. They were asked about the degree of their acceptance toward somatic genome editing (SGE) and HGE; those who answered “acceptable depending on the purpose” were queried further regarding their acceptance in the contexts of specific clinical purposes. Results: Responses were obtained from 4, 424 laypeople and 98 researchers. The percentage of respondents choosing each option in attitudes to HGE was, from largest to smallest: “acceptable depending on purpose” (laypeople 49.3%; researchers 56.1%), “not acceptable for any purpose” (laypeople 45.8%; researchers 40.8%), and “acceptable for any purpose” (laypeople 5.0%; researchers 3.1%). In an additional question for those who answered “acceptable depending on the purpose, ” laypeople found the following purposes acceptable: infertility treatment (54.5%), treatment of life-threatening diseases (52.2%), and treatment of debilitating diseases (51.4%). Meanwhile, the degree of acceptance for enhancement purposes was 10.7, 7.9, 6.2, and 5.5% for physical, cognitive, health, and personality enhancements, respectively. In contrast, acceptance among the researchers was 94.5% and 92.7% for the treatment of life-threatening and debilitating diseases, respectively, compared with 69.1% for infertility treatment. Researchers’ acceptance for enhancement purposes was similar to that of the lay participants, with 12.7, 9.1, 10.9, and 5.5% for physical, cognitive, health, and personality enhancement, respectively. Conclusion: In the past, debates regarding the acceptability of human genome editing in clinical applications tend to focus on HGE in many countries. Society will now need to debate the acceptability of both types of human genome editing, HGE and SGE

Does the Act on the Safety of Regenerative Medicine in Japan ensure “safety”?: Implications of low adverse event reporting

再生医療法に基づく再生医療で生じる有害事象の報告状況を調査 --報告件数の少なさは何を意味するのか？. 京都大学プレスリリース. 2023-11-20.Does the Act on the Safety of Regenerative Medicine in Japan ensure “Safety”？ : Implications of low adverse event reporting. 京都大学プレスリリース. 2023-11-20.Public document analysis reveals that the adverse events reported for therapeutic administration under the Act on the Safety of Regenerative Medicine (ASRM) in Japan are substantially fewer than those under the Pharmaceuticals and Medical Devices Act. This study highlights the flawed reporting mechanisms and unmet legislative intentions of the ASRM

Human genome editing in clinical applications: Japanese lay and expert attitudes

Background: The world’s first gene-edited babies, reported by the Chinese scientist He Jiankui, prompted an outcry of criticism and concerns worldwide over the use of genome editing for reproductive purposes. Many countries and academic associations opposed to heritable genome editing (HGE) called for public discussion involving various stakeholders. To hold a discussion of this nature and form a consensus concerning HGE, we must understand under what conditions stakeholders consider HGE acceptable and the reasons for which they deem it unacceptable.Methods: Laypeople and researchers were surveyed in May 2019. They were asked about the degree of their acceptance toward somatic genome editing (SGE) and HGE; those who answered “acceptable depending on the purpose” were queried further regarding their acceptance in the contexts of specific clinical purposes.Results: Responses were obtained from 4,424 laypeople and 98 researchers. The percentage of respondents choosing each option in attitudes to HGE was, from largest to smallest: “acceptable depending on purpose” (laypeople 49.3%; researchers 56.1%), “not acceptable for any purpose” (laypeople 45.8%; researchers 40.8%), and “acceptable for any purpose” (laypeople 5.0%; researchers 3.1%). In an additional question for those who answered “acceptable depending on the purpose,” laypeople found the following purposes acceptable: infertility treatment (54.5%), treatment of life-threatening diseases (52.2%), and treatment of debilitating diseases (51.4%). Meanwhile, the degree of acceptance for enhancement purposes was 10.7, 7.9, 6.2, and 5.5% for physical, cognitive, health, and personality enhancements, respectively. In contrast, acceptance among the researchers was 94.5% and 92.7% for the treatment of life-threatening and debilitating diseases, respectively, compared with 69.1% for infertility treatment. Researchers’ acceptance for enhancement purposes was similar to that of the lay participants, with 12.7, 9.1, 10.9, and 5.5% for physical, cognitive, health, and personality enhancement, respectively.Conclusion: In the past, debates regarding the acceptability of human genome editing in clinical applications tend to focus on HGE in many countries. Society will now need to debate the acceptability of both types of human genome editing, HGE and SGE

Public attitudes in Japan toward the reproductive use of gametes derived from human-induced pluripotent stem cells

ヒトiPS細胞を用いた配偶子の作製と利用をめぐる日本の一般市民を対象にした調査. 京都大学プレスリリース. 2021-10-25.[Purpose:] To investigate the interests of the Japanese general public in the reproductive use of in vitro derived (IVD)-gametes. [Methods:] We conducted an online survey and obtained answers from 3096 respondents. [Results:] More than half of the respondents agreed with the reproductive use of IVD-gametes by infertile heterosexual married couples but disagreed with the same use by unmarried or homosexual individuals. Nearly 70.0% disagreed with the use for designing a baby. [Discussion:] In Japan at present, the use of IVD-gametes that deviate from societal values regarding reproduction and family prescribed by the conventional marriage system is unlikely to be accepted. It is also unlikely to be accepted for non-treatment purposes in reproduction

Genome editing of human embryos for research purposes: Japanese lay and expert attitudes

ヒトを対象としたゲノム編集の利用に関する調査研究. 京都大学公式プレスリリース. 2023-09-27.Capturing the lay public's opinions on genome editing of human embryos. 京都大学プレスリリース. 2023-10-12.Background: Multiple surveys of the general public and experts on human genome editing have been conducted. However, many focused only on editing in clinical applications, with few regarding its use for basic research. Given that genome editing for research purposes is indispensable for the realization of clinical genome editing, understanding lay attitudes toward genome editing in research, particularly using human embryos, which is likely to provoke ethical concerns, is helpful for future societal discussion. Methods: An online survey was conducted with Japanese laypeople and researchers to ascertain their views regarding human genome editing for research purposes. Participants were queried about their acceptance as a function of the target of genome editing (germ cells, surplus IVF embryos, research embryos, somatic cells); then, those who answered “acceptable depending on the purpose” were asked about their acceptance in the context of specific research purposes of genome editing. Participants were also asked about their expectations and concerns regarding human genome editing. Results: Replies were obtained from 4, 424 laypeople and 98 researchers. Approximately 28.2–36.9% of the laypeople exhibited strong resistance to genome editing for research purposes regardless of their applications. In contrast, 25.5% of the researchers demonstrated resistance only to genome editing in research embryos; this percentage was substantially higher than those concerning the other three targets (5.1–9.2%). Approximately 50.4–63.4% of laypeople who answered “acceptable depending on the purpose” approved germline genome editing for disease research; however, only 39.3–42.8% approved genome editing in basic research to obtain biological knowledge. In contrast, the researchers displayed a lower degree of acceptance of germline genome editing for research purposes related to chronic diseases (60.9–66.7%) than for other research purposes (73.6–90.8%). Analysis of responses concerning expectations and concerns indicated that laypeople who would not accept genome editing of human embryos did not necessarily worry about “instrumentalization of the embryo.” They also had substantially low expectations for recognized advantages of genome editing, including “advances in science” and “reduction of intractable diseases, ” compared with other groups of respondents. Conclusion: The assumptions shared among experts in conventional bioethical debates and policy discussions on human genome editing are not self-evident to laypeople

Current status of umbilical cord blood storage and provision to private biobanks by institutions handling childbirth in Japan

[Background] The Act Regarding the Promotion of the Appropriate Supply of Hematopoietic Stem Cells for Transplant regulates only how public banks store and provide umbilical cord blood (UCB) for research or transplantation. Japan had no laws to regulate how the private banks manage the procedures, harvesting, preparation, and storage of such blood. As a result, the status of UCB distribution remains unknown. We conducted a survey to investigate the current status of UCB storage and provision to private biobanks by Japanese institutions that handle childbirth. [Methods] Questionnaire forms were mailed to 3, 277 facilities handling childbirth that were registered in the Japan Council for Quality Health Care website. [Results] Of the 1, 192 institutions handling childbirth that participated in the survey (response rate: 36.7%), 34.4% responded that they currently provide UCB to private biobanks, while 16.1% of facilities did so in the past. Moreover, some institutions currently provide or formerly provided UCB to medical treatment facilities (2.6%), research institutions (5.9%), companies (2.2%), or overseas treatment facilities, research institutions, or companies (0.3%). A certain number of institutions handling childbirth did not even provide explanations or obtain consent when the UCB was harvested from private bank users. [Conclusions] This is the first study to determine the status of UCB provision to private banks by Japanese institutions handling childbirth. Future studies will need to examine in detail how institutions handling childbirth provide explanations to private bank users and UCB providers as well as how these institutions obtain consent

Discovery and informing research participants of incidental findings detected in brain magnetic resonance imaging studies : Review and multi‐institutional study

Background: Brain imaging studies using magnetic resonance imaging (MRI ) sometimes reveal incidental findings (IFs) that might be relevant to some of the health issues in research participants. Although professional communities have discussed how to manage these IFs, there is no global consensus on the concrete handling procedures including how to inform participants of IFs. Methods: First, this study reviewed previous studies for the number of IFs discovered in brain imaging studies using MEDLINE. Second, a multi‐institutional study determined the number of IF discoveries and evaluated the method of informing participants at multiple institutions, which participated in a national brain science project in Japan. Results: Both the review and multi‐institutional study showed that IFs with a high urgency level were discovered in 0–2.0% of participants, including healthy volunteers, and that the rate of IF discovery in general was higher in studies conducted in elderly population. Moreover, multi‐institutional study suggested the criteria used to judge whether or not to inform participants of IFs may differ by institution. Conclusions: Our results suggest that in order to ensure informing the participants of high urgency IFs, physicians who are capable of interpreting brain images clinically should review all brain images, and the establishment of a support system is required for brain imaging studies at nonmedical institutions. Since the method of informing participants of IFs might affect their understanding and acceptance of IFs, which are related to managing risks of false “clean bill of health” or psychological impacts of informing IFs, further research focusing on communication of IFs is needed