This paper describes the development and present status of seismic evaluation and seismic retrofit of existing buildings mainly for low-rise and medium-rise reinforced concrete buildings in Japan. First, since the seismic evaluation of existing buildings has close relationships with the seismic design of new buildings, a brief history of the development of seismic design, seismic evaluation, and seismic retrofit is provided in terms of major earthquake disasters mostly in Japan and associated with some major events in the U.S. Then, the development of seismic evaluation and retrofit is reviewed, focusing on the items in which the author has been deeply involved. This provides insight into previous earthquake damage, methodologies for seismic evaluation, the basic concept of the Standard for Seismic Evaluation of Existing Reinforced Concrete Buildings, studies on the demand criteria for seismic safety, and the present status of seismic evaluation and retrofit. Finally, the typical methods of seismic retrofit and some examples of retrofitted buildings in Japan are explained. Therefore, the seismic performance of existing buildings is usually highly dependent on the seismic codes that were utilized when they were designed and constructed, as the seismic codes are occasionally revised and updated based on the developments in earthquake engineering. Whenever the codes are revised, many existing buildings become outdated and are referred to as “existing nonconforming buildings” that do not satisfy the newly revised seismic codes. However, this does not always mean that all of the nonconforming buildings become vulnerable to earthquakes given the redundancies in their seismic capacities. Therefore, as earthquake countermeasures, it is essential to evaluate the seismic capacities of nonconforming buildings before an earthquake event, to find those with poor redundancies, and to upgrade or reconstruct them. In this paper, finding buildings with seismically poor redundancies through an evaluation of their capacities is referred to as “seismic evaluation”, and upgrading their performance is referred to as “seismic retrofit” or “seismic retrofitting”. The background and history of the development of seismic evaluation and retrofitting, an outline of their procedures, the current status of their applications, 2In this chapter, a brief history of seismic design for new buildings and seismic evaluation and retrofitting of existing buildings is presented together with major earthquake disasters that mostly occurred in Japan. Major events in the U.S., one of the leading countries in the field of earthquake engineering, are also listed to help international readers understand earthquake countermeasures for buildings in Japan.Since seismic codes were developed in earthquake-prone countries at the beginning of the twentieth century, the seismic resistance of buildings has been improved, although their levels vary according to the years of design and construction. To understand how seismic capacity has been improved in approximately the past one hundred years, it may be convenient to divide history into the following four periods: the pre-seismic code period, the first-generation seismic code period (first period), the second-generation seismic code period (second period), and the third-generation seismic code period (third period), according to the development of seismic design, seismic evaluation, and seismic retrofitting methods, as shown in Fig. In the pre-seismic code period, most buildings were constructed without any consideration of earthquake engineering criteria, or with some consideration based on the engineers’ own studies and/or experience of past earthquake damage. The buildings in this period are called “nonengineered buildings” or “nonearthquake engineered buildings” and are shown in Fig. The first period started in the first half of the twentieth century. Seismic codes were adopted in most earthquake-prone countries or regions beginning in the 1920s. In Japan, the first seismic code was adopted in the Urban Building Law in the year following the 1923 Great Kanto earthquake disaster. In the U.S., the Field Act and Riley Act on seismic design for school buildings and other buildings, respectively, passed the California State Legislature after the Long Beach earthquake occurred in 1933. The seismic design method during this period was based on the so-called working stress design. This method considers an earthquake force to be a static lateral force, calculates the stresses of structural members elastically, and verifies that the calculated stresses are less than the allowable stresses defined according to the strengths of materials in seismic codes. The ratio of static lateral force to building weight is called a seismic coefficient or Sano-seismic coefficient, which was proposed by Sano, T. in 1912.In the second half of the twentieth century, some buildings that were designed according to the first-generation seismic codes, labeled as “insufficiently engineered buildings” in Fig.  the seismic capacities of buildings have been significantly improved. Similar concepts were adopted in the Mexico City Building Code in 1976, the report of the Applied Technology Council (ATC-3-06) in 1978, and the Uniform Building Code in 1988, among others.The second period started in the 1980s with this code revision. The fundamental concept of the revised seismic design codes was to practically consider the ultimate strength, ductility (deformability), and nonlinear earthquake response of structures. More specifically, the method used a “design seismic force (required strength)” that reduced the elastic earthquake response depending on the ductility of the building. Since the Japanese seismic design code in the Building Standard Law (Urban Building Law before 1950) was revised to upgrade the demand criteria in accordance with this concept in 1981, was published in 1977 by the Japan Association for Special Building Safety (JASBS), which has been referred to as the Japan Building Disaster Prevention Association (JBDPA) since 1979, before the 1981 revision of the seismic design code in Japan. Similar standards and guidelines for steel buildings, wooden houses, and reinforced concrete-encased steel (SRC) buildings were published until 1983 by the JBDPA. For government facilities, the Guideline for Seismic Inspection and Repairs of Governmental Facilities in the Comprehensive Earthquake Proof Plan Standardization for Governmental Facilities was published by the Building and Repairs Association, which has been referred to as the Public Buildings Association since 1987. However, seismic evaluation and retrofitting were not implemented very often during the second period, except in the limited area of the Shizuoka Prefecture in Japan, until the Great Hanshin-Awaji earthquake disaster, which occurred due to the 1995 Hyogo-ken Nanbu earthquake.Another important issue that was studied in the last half of the first period and promoted in the second period was the seismic evaluation and retrofitting of existing buildings, which is the main topic of this paper. In Japan, the Standard for Seismic Evaluation and Guidelines for Seismic Retrofit of Existing Reinforced Concrete Buildings was enacted for existing buildings in 1995. The Seismic Evaluation Standards issued by the JBDPA and the guideline issued by the Building and Repair Association were adopted as equivalent methods to the seismic evaluation method defined in the act.The Great Hanshin-Awaji earthquake disaster triggered the transition to the third period by improving the seismic codes of the second period and further promoting seismic evaluation and retrofitting. In this earthquake, there were very few cases of collapse or serious damage to buildings designed and constructed according to the second-generation seismic codes, but there were several buildings that had to be demolished because they could not maintain their functions after damage; thus, further improvement of the seismic codes was needed. Additionally, since most of the buildings that collapsed or were severely damaged were constructed before the second period, further study and implementation of seismic evaluation and retrofitting were required. To this end, research began to improve the seismic codes for new buildings, and at the same time, the Act on Promotion of Seismic Retrofit of Buildings was published in 1987. The 1994 Northridge earthquake occurred in California just one year before the 1995 Hyogo-ken Nanbu earthquake in Japan, accelerating seismic evaluation and retrofitting. The report of the Applied Technology Council (ATC-40) for the seismic evaluation and retrofitting of concrete buildings and the Handbook for Seismic Evaluation of Buildings (FEMA 310) were published in 1996 and 1998, respectively.In the U.S., the Greene Act-1 and the Greene Act-2 passed the California State Legislature in 1967 and 1968, respectively, to set a deadline for school districts to inspect the seismic safety of pre-Field Act school buildings. The importance of seismic evaluation and retrofitting of existing buildings was recognized, and studies were carried out. The report of the Applied Technology Council for seismic evaluation of existing buildings (ATC-14)The third period started around the end of the last century. The purpose of the third-generation seismic codes was to provide design methods to meet a wide range of seismic performance objectives required for the building process, not just collapse prevention. They aimed to introduce the concept of a performance-based design method, rather than a specification-based design method, into the seismic design. and 1998, and by the Building Council of the Ministry of Construction in 1997. In response to the recommendations, the seismic code from the second period would continue to be used with some minor modifications, and a new optional seismic calculation method of estimation of the story displacement response based on the equivalent linear stiffness and damping was added as a performance-based seismic design in the seismic code revised in 2000.In Japan, reports to recommend the importance of developing performance-based seismic design codes were issued by the task committee at the Architectural Institute of Japan (AIJ), chaired by the author in 1995 which focused on a performance-based seismic design, was proposed by the Structural Engineers Association of California in 1995. Several existing model building codes, including seismic codes, were unified into the International Building Code in 2000.In the U.S., VISION 2000, was amended in 2005 and 2013, and the Standard for Seismic Evaluation and Guidelines for Seismic Retrofit of Existing Reinforced Concrete Buildings was revised in 2007 and 2017. In the U.S., various methods have been integrated; at present, the International Existing Building Code and Seismic Evaluation and Retrofit of Existing Buildings (ASCE 41-17) are available.In conjunction with these trends, measures for seismic evaluation and retrofitting employed in the second period were updated. In Japan, the Act on Promotion of Seismic Retrofit of Buildings3: (1) the hypocenter was located approximately 180 km east of the city of Hachinohe, which was one of the most severely damaged areas, at a depth of 20 km; (2) the magnitude was 6.8 on the Richter scale; (3) the death toll, including those who were missing, was 52; (4) approximately 3,000 wooden houses were severely damaged; (5) approximately 20 newly constructed reinforced concrete buildings experienced severe damage, with a ratio of severe damage to medium damage of approximately 10%; and (6) the maximum ground acceleration observed on the soft ground of the Hachinohe port area was 23% of gravity. Based on these statistics, the disaster was not as serious as recent large-scale earthquakes. However, its impact on professionals in the earthquake engineering community was very strong. Low-rise reinforced concrete school buildings designed according to the existing seismic design codes and constructed with strong workmanship were damaged, as shown in Fig. As described earlier, bitter lessons from damaging earthquakes have always inspired the earthquake engineering community to develop new concepts and technology and implement them in society. The lessons learned from the buildings damaged by the 1968 Tokachi-oki earthquake accelerated the development of rational methods for seismic design, seismic evaluation, and seismic retrofitting. This chapter provides an overview of the earthquake, the damage, and the lessons learned as a result. The characteristics of the earthquake and damage are as follows chaired by Umemura, H. in 1969 and modified by the author. The vertical axis shows the lateral force, representing the earthquake lateral force response in terms of the seismic coefficient, and the horizontal axis shows the lateral deformation in terms of the story drift angle. The curves in the figure schematically show the force–displacement relationships, i.e., the so-called backbone curves, of several types of buildings.Investigations to clarify why such damage was caused have been carried out by many researchers and institutions, including AIJ. Figure In the figure, reinforced concrete buildings in the damaged area are classified into three types: I, II, and III, showing the characteristics of buildings with many shear walls, with some shear walls, and with less or no shear walls, respectively. Type IV shows the characteristics of high-rise buildings that did not exist in the damaged area. The symbols ○ and × are the deformation limits of intact buildings and damaged buildings, respectively, and the symbol ● shows the earthquake response of the buildings. It is evident that the buildings had various levels of strength, even if they were designed using the same seismic coefficient of 0.2, and that the buildings’ responses varied according to the building type, as shown by the symbol ●. The figure shows that buildings with a deformation limit (ductility), marked by ○, beyond the earthquake response point, marked by ●, survived; otherwise, buildings failed at the point marked by ×. Therefore, the ultimate strength, ductility, and nonlinear earthquake response are recognized as essentials in the future seismic design and have since become important considerations for building engineers. was published by AIJ in 1964, and the first high-rise building in Japan, the Kasumigaseki Building, was completed in the same year as the 1968 Tokachi-oki earthquake. Thus, researchers and engineers who were interested or engaged in the design of high-rise buildings could have recognized the importance of considering the ultimate strength, ductility, and nonlinear earthquake response in discussing seismic performance at that time.The Design Guide for High-Rise Buildings Such an analysis was useful to understand the reasons why buildings were damaged, but it was difficult in practice to use this analysis method for the design of low-rise or medium-rise buildings given the additional complications as compared to high-rise buildings. Therefore, studies to develop more rational but practical design methods that consider the nonlinear dynamic behavior of buildings during earthquakes have been carried out since then. A consensus on the concept of future seismic design methods was obtained from researchers and engineers around the late 1970s. The main goal was to reduce the seismic force to linear elastic systems according to the ductility of the building and to consider the ductility in determining the ultimate strength required for the building. This idea can be considered a practical application of the results of basic research that has been carried out since the 1960s.Therefore, studies analyzing low-rise and medium-rise buildings using nonlinear earthquake response analysis for high-rise buildings were carried out. where the ratio of the strength required for the building (required strength) to the seismic response force to the linear elastic system, which is usually called a standard seismic force, is defined as the force reduction coefficient (Ds coefficient). The same concept was adopted in Mexican and U.S. seismic codes during the second period, where the Q factor, Rw factor, or R factor are employed to represent the force reduction factor as the reciprocal of the Ds coefficient, i.e., the ratio of the standard seismic force to the required strength.Adopting this concept, the seismic design code was revised in 1981 in Japan,During this period, projects for developing seismic evaluation methods, which will be reviewed in the next chapter, were carried out based on concepts similar to those mentioned above.4Some of the seismic evaluation methods developed in the 1970s for reinforced concrete buildings are summarized in this chapter. by the Building Research Institute estimates the lateral strength of a building from the cross-sectional area of structural elements, such as walls and columns, and judges the seismic safety of the building according to the ductility of the structural elements, which is based on their aspect ratios. The method of estimating the strength is based on Ref. The method proposed for reinforced concrete low-rise buildingsReference et al. during an investigation of the methods for evaluating the safety of existing school buildings at the University of California, Berkeley, including the abstract of Ref. Reference Is-index, the concept of which will be described briefly in the next chapter. The standards and guidelines have been revised three times, in 1990, 2001, and 2017, and even now, they are used for most seismic evaluation and retrofitting projects in Japan.Reference As mentioned in the Introduction, seismic evaluation is applied to evaluate the redundancy of buildings designed with older seismic codes. In general terms, it is one way for seismic evaluation to confirm the safety of buildings designed under the first-generation seismic code by redesigning them with the second-generation seismic code. However, this method has the following drawbacks: (1) seismic codes usually include uncalculated specifications, and buildings designed according to older codes are often judged unsafe because they do not meet the current specifications; (2) redesigning existing buildings according to updated seismic codes is not practical because it is more complicated and time-consuming than a new construction; and (3) the deterioration of seismic performance over time is not taken into account. Seismic evaluations that do not require seismic redesigns are therefore needed. Additionally, the Seismic Evaluation Standard preemptively employed the concept of the second-generation seismic code. Therefore, it was acceptable for practical application, although it was quantitatively less accurate due to its simplified procedure. These are the reasons why the Seismic Evaluation Standard formulated in the first period is still in use today, in the third period, with repeated revisions.5 consists of three different levels of procedures: first-level, second-level, and third-level procedures. The first-level procedure is the most simplified while the third-level procedure requires the most elaborate calculations. These three evaluation procedures share the same basic concept, which is described in the following section, and the second-level procedure has been most widely applied to existing buildings in Japan to date.The Standard for Seismic Evaluation of Existing Reinforced Concrete Buildings Is-index) for each story and each direction, as will be described next, and better performance is expected for a higher index value. The story of a building with an index higher than the seismic demand index (Iso-index) is deemed safe. The definition of the Iso-index will be discussed in Chapter 6.In the standard, the seismic performance of a building is expressed by the seismic index of the structure (Is-index represents the seismic force level that a building can survive and is defined by the product of three indices: a basic seismic index of structure (E0-index), which is calculated from the lateral strength and ductility (or deformability); an irregularity index (SD-index), which accounts for disadvantages due to irregularities in the plane and along the height of a building; and a time index (T-index), which considers the deterioration of strength and ductility after construction.The E0-index is given by the product of the strength index (C-index) and the ductility index (F-index), which denote the lateral strength and deformability of a building, respectively. The E0-index for structures having members with different deformability values  is calculated based on the C-index and F-index of each member in the story. The F-index is formulated based on a similar concept to the 1/Ds in the Japanese seismic code and the Q, Rw, or R in the Mexican and U.S. codes. A checklist is provided to find other indices, the SD-index and T-index, to eliminate complicated calculations.The Is-index is the same as those of the dynamic analysis of the earthquake response for high-rise buildings and the seismic design based on a required strength method in the second period. However, this approach has a distinctive feature in the adoption of the unknown factor or solution, as shown in Fig.  As discussed in Chapter 3, seismic force, strength, and ductility are the three major parameters that govern the nonlinear earthquake response of a building. Figure This is a simplified method to predict the nonlinear earthquake response of a building without performing dynamic response computation, although the basic concept of estimation of the C-index, the ductility is considered in the F-index, and the solution is the Is-index, showing the level of the seismic force corresponding to the standard seismic force in the required strength method when a story drift reaches a deformation limit of the building. Namely, since the F-index of the wall that fails under shear force is defined as 1.0, the Is-index can be considered equivalent to the nonlinear seismic response force when the response displacement of the shear wall reaches the assumed deformation limit of 0.4% in terms of the story drift angle, as described in the commentary of the standard.In the dynamic analysis of the earthquake response, shown in the top row of Fig. Is-index in the Seismic Evaluation Standard can be calculated without determination of the intensity and characteristics of the earthquake ground motion because the solution itself presents these results. It is possible to rank buildings and/or stories in terms of seismic safety without predetermining the expected ground motion.It might be obvious that the dynamic analysis and the seismic design methods in the second period cannot start before determination of the seismic force obtained from the intensity and characteristics of the earthquake ground motion. However, the Iso-index) was not determined at this time but was left for future study. However, several examples of Is-indices of buildings damaged by the 1968 Tokachi-oki earthquake were estimated and are included in the appendix of the Seismic Evaluation Standard as a reference for stakeholders.When the evaluation standard was developed, discussion about the intensity and characteristics of expected earthquake ground motions continued, and a consensus had not yet been reached in Japan. Therefore, it was considered that a proposal to estimate the relative seismic performance would be more acceptable to stakeholders such as engineers, building owners, and authorities than to judge a structure as seismically safe or unsafe, as seismic safety depends on the intensity of the ground motions and the level of acceptable damage. Furthermore, since this was a newly developed method, it was necessary to apply it to damaged buildings to verify its accuracy. For those reasons, the value of the seismic demand index  for the seismic demand index (Iso-index) in the Shizuoka Prefecture. Simplifying the proposed criteria, the Shizuoka Prefecture issued the guideline in 1979.To support the Tokai earthquake countermeasures in the Shizuoka Prefecture, the advisory committee chaired by Umemura, H., with the author as the secretary general, called the Committee for Seismic Performance of Reinforced Concrete Buildings, was established in the JASBS in 1977. One of the projects carried out by the committee was to draft the criteria for judging seismic safety of reinforced concrete buildings in the Shizuoka Prefecture. The task committee chaired by Murakami, M. was established and proposed the seismic safety index (ET) is estimated using Eq. [The proposed seismic safety index  of a building, as shown in Table Es-index for buildings failing under shear, while those in parentheses are for buildings failing under flexure. They were obtained using data in Ref. Co and CI are the modification factors that allow for the amplification of ground motion due to site configuration, ranging from 1.0 to 1.25, and the importance factors ranging from 1.0 to 1.5, respectively.The 6.3In 1978, several earthquakes hit Japan, and many buildings were damaged. One earthquake was the Izu-Oshima Kinkai earthquake in the Shizuoka Prefecture on January 14, which was not a scenario under the Tokai earthquake study, and the other was the Miyagi-ken-oki earthquake on June 12. Studies applying the Seismic Evaluation Standard to reinforced concrete buildings suffering from earthquake damage were carried out.Is-indices from the second-level screening procedure of buildings in several cities along the shore of the Izu Peninsula in the Shizuoka Prefecture and in the Sendai city in the Miyagi Prefecture, which suffered from the earthquakes mentioned above, along with those of buildings that suffered from the 1968 Tokachi-oki earthquake. The black circle (●), half-black circle , and white circle (○) correspond to severe damage, medium damage, and little or no damage, respectively. From the figure, it is suggested that Is-indices of 0.5 to 0.6 in the second-level screening procedure represent the difference between damaged and undamaged buildings that experienced ground motions of approximately 30% of gravity. However, one problem is a lack of data for undamaged buildings.Figure 6.4Is-index of the first-level and second-level screening procedures was developed in 1978 by the task committee chaired by the author in the Committee for Seismic Performance of Reinforced Concrete Buildings. The program was released by the JBDPA under the sponsorship of the Shizuoka Prefecture in 1980. Utilizing this program, the Is-indices of many public buildings in the Shizuoka Prefecture were estimated by local structural engineers. Studies comparing and combining the Is-index data of buildings in the Shizuoka Prefecture and those of damaged buildings in past earthquakes were carried out.As described in section 6.2, the seismic evaluation of reinforced concrete buildings in the Shizuoka Prefecture started in 1977, just after the Seismic Evaluation Standard was published. To help accelerate the use of this standard, a computer program to calculate the Is-indices of existing buildings cited from Refs. Is-indices on the first story based on the second-level screening procedure of approximately 1,600 public buildings, mostly reinforced concrete three- or four-story school buildings, in the Shizuoka Prefecture. The number of Is-indices is approximately double the number of buildings because the Is-indices are calculated in both the longitudinal and transverse directions of the floor plan. Curve ① is the probability density function approximating the bar charts using a log-normal distribution function. The shaded bar chart in Fig. Is-indices of buildings suffering from medium and severe damage described in section 6.3. The total number of damaged building data points is adjusted to 10% of the number of building data points in the Shizuoka Prefecture, as the damage ratios in past earthquakes are estimated to be approximately 10%. Figure ET), which is the same as the Iso-index of the Seismic Evaluation Standard, of approximately 0.6–0.7 is the lower bound to prevent medium or severe structural damage from the seismic intensity levels of past earthquakes, such as the 1968 Tokachi-oki and/or 1978 Miyagi-ken-oki earthquakes, as shown in the previous sections.Figure ET) may not be considered deterministic but probabilistic, as illustrated in Fig. ET indices is estimated using the reliability theory according to curve ① and the shaded bar chart of the adjusted distribution of the Is-indices of damaged buildings in Fig. Figure Is-indices of the damaged buildings calculated by curve ① in this figure and curve ② in Fig. ET index is proportional to the level of ground motion, the mean value of curve ② is increased by approximately 1.5 times and 2.0 times, keeping the variance values constant, and the distribution of buildings that are expected to experience damage is calculated again by the reliability theory, as shown in Fig. Curve ③ in Fig. The methodology mentioned above has been used in the damage assessment of the Tokai earthquake in the Shizuoka Prefecture since 1993.6.5Iso) was adopted in the Seismic Evaluation Standard in 1990. The level of this seismic criteria may be deemed approximately on the same level of the seismic code of Japan in the second period. The seismic safety of a building is judged as follows:In view of the studies mentioned above, a seismic demand index , G: ground index , and U: usage index .When Eq.  is satis7Even in the second period, buildings were damaged due to earthquakes such as the 1983 Nihonkai-Chubu, 1987 Chiba-ken Toho-oki, and 1993 Hokkaido Nansei-oki earthquakes in Japan. Most of the seriously damaged buildings were constructed in the first period or in the pre-seismic code period, as expected. These buildings would have been evaluated as vulnerable if their seismic capacity had been evaluated before the earthquakes. However, since the Building Standard Law of Japan, where the seismic code is involved, is not retroactive, the seismic evaluation and retrofitting of existing buildings have not spread on a country-wide basis, except for the Shizuoka Prefecture. Therefore, many vulnerable buildings were left without seismic evaluation and/or retrofitting until the 1995 Hyogo-ken Nanbu earthquake. The vulnerability of existing buildings was also verified by studies applying the Seismic Evaluation Standard to buildings suffering from earthquake damage, which is described in Chapter 8. Recognizing the serious vulnerability of older buildings, the Government of Japan immediately enacted the Act on Promotion of Seismic Retrofit of Buildings in December 1995, which is described in Chapter 9.The disaster due to the Hyogo-ken Nanbu earthquake, called the Great Hanshin-Awaji earthquake disaster, brought a drastic change to the processes of seismic evaluation and retrofitting. Awareness has spread nationwide on the importance of seismic evaluation and seismic retrofitting for earthquake disaster mitigation, which has been accelerated since then. As mentioned in Chapter 2, it was reported that most of the buildings that were severely damaged or collapsed were those designed before the second period, and most of the deaths out of more than 6,400 were caused by damaged buildings or houses.8Is-indices of reinforced concrete school buildings damaged in the 1995 Hyogo-ken Nanbu earthquake are explained here. Table  Among 631 reinforced concrete school buildings, 8% experienced severe damage or collapse, and 30% suffered from moderate damage or higher. Since a minor revision was made in the seismic code in 1971 before the major revision in 1981, this table is divided into pre-1971, 1971–1981, and post-1981 sections. No serious damage occurred to the school buildings constructed in the second period after 1981. The Is-indices of approximately 100 randomly selected school buildings were calculated, and the relationships between the Is-indices and the damage grades were investigated, as shown in Fig. Is-indices indicated that the seismic capacities increased for more recent construction years and that the Is-indices of most heavily damaged buildings were less than 0.6.Some studies to verify the relationship between the damage grades and  shows the distribution of Is-indices of buildings that suffered from moderate damage or higher, adjusting the damage ratio to 29% on curve ① in Fig. Is-index of 0.6 is the border between severe damage and moderate damage, (2) an Is-index of approximately 0.9 is needed to prevent moderate damage, and (3) the intensity of ground motions might be approximately 1.5 times those of the 1968 Tokachi-oki earthquake and the 1978 Miyagi-ken-oki earthquake. This is because the distribution of damaged buildings could be approximated by curve ④ in Fig. Figure 12From these studies, it is strongly suggested that the damage to reinforced concrete school buildings could have been significantly mitigated if their seismic capacities had been evaluated and seismic retrofitting had been conducted on the buildings judged unsafe before the earthquake occurred. Unfortunately, no school buildings had been seismically evaluated in the area affected by the disaster.92 of floor area, and a large number of occupants such as schools, gymnasiums, hospitals, theaters, stadiums, auditoriums, department houses, office buildings, etc. The act was amended twice, in 2006 and 2013. The latest act required seismic evaluation by owners of all existing buildings, including single-family houses. The act also set the deadline to implement seismic evaluation by the owners of buildings classified as the highest priority such as hospitals, shops, hotels, schools, nursing homes for the aged, etc. The Is-indices of such buildings and the retrofitting or demolishing schedules of the buildings judged vulnerable are disclosed periodically by local governments.The Act on Promotion of Seismic Retrofit of Buildings, enacted in 1995, required that seismic evaluation be conducted by the owners of buildings constructed before 1981 and having a large size, such as more than two stories and more than 1,000 m However, the Ministry of Education, Culture, Sport, Science and Technology recently reported on their website that almost all of them have been evaluated as seismically safe, including retrofitted or reconstructed buildings .Since the act was enacted, seismic evaluation and seismic retrofitting have been promoted rapidly. For example, approximately eighty-five thousand public school buildings were constructed before 1981, approximately 65% of which still existed in 2004.https://www.mlit.go.jp/jutakukentiku/house/jutakukentiku_house_fr_000043.html, in Japanese).However, the seismic evaluation of private buildings has progressed more slowly than that of public buildings. A 2018 report on the website of the Ministry of Land, Infrastructure, Transport and Tourism estimates that approximately fifty thousand buildings accommodating a large number of people and constructed in or before the first period were left vulnerable  installing reinforced concrete walls to increase the strength, (2) installing steel-framed braces to increase the strength, and (3) jacketing columns with steel plates or carbon fiber sheets to increase the ductility, as shown in Figs. Although there are few data to quantify the effectiveness of such seismic retrofitting, most of the buildings that collapsed or were severely damaged in the 2004 Niigata-ken Chuetsu earthquake, the 2011 Great East Japan earthquake, or the 2016 Kumamoto earthquake were vulnerable buildings designed under codes from before the second period, and few of the damaged buildings had been retrofitted before the events. As mentioned earlier, Shizuoka Prefectural Government has been taking measures for seismic evaluation and retrofitting for a long time in anticipation of the Tokai earthquake, and seismic countermeasures have been completed for almost all public buildings. Fortunately, the Tokai earthquake has not yet occurred. However, a series of countermeasures taken by the Shizuoka Prefectural Government has become a role model for other local governments.Recently, a seismic base isolation system has been utilized for retrofitting, primarily to preserve the original architectural design and interior. To reduce the seismic response of the building, seismic isolators with supplementary vibration damping devices are installed between the existing building and a newly constructed foundation on the ground. For seismic isolators, laminated rubber bearings composed of alternate layers of rubber and steel plates, friction bearings, or ball bearings are usually used. Lead, steel, or oil dampers are also used to increase damping. In such cases, the Seismic Evaluation Standard is applied when seismically evaluating the original building, but advanced methods such as time-history response analysis are used when confirming the seismic performance of the retrofitted building. Examples for retrofitting with base isolation systems can be found in the following projects, where the author was involved as an advisor.Is-index did not satisfy the demand criteria. Therefore, the museum building was retrofitted in 1998 with a base isolation system using high damping laminated rubber bearings to preserve the original architecture. This was the first trial of the base isolation system for seismic retrofitting in Japan. Thus, strong-motion seismometers have been installed by the Building Research Institute, and the accelerograms due to the 2011 Great East Japan earthquake disaster were recorded. As shown in Fig. 2 on the ground surface near the building and approximately 100 cm/sec2 at the newly constructed basement, which supported the base isolation devices, at the first floor, and at the top floor. In other words, the seismic motion applied to the building base was not amplified even at the top of the building, where it would be expected to be double or triple if the base isolation system had not been installed. The building had no damage and was registered as a world heritage site in 2016. This is a rare example where the impact of seismic retrofitting has been verified quantitatively.The National Museum of Western Art is a reinforced concrete three-story building with a basement constructed according to the design of the world-famous architect Le Corbusier in Tokyo in 1959, as shown in Fig. The second example is the Tokyo Railway Station Marunouchi building constructed in 1914 according to the design of Tatsuno, K., who was one of the pioneers of modern architecture in Japan. The original building was a three-story building with two domes and a partial basement made of a brick-infilled steel structure. However, the top floor and domes were destroyed by bombing in 1945; the building was repaired as a two-story building without domes in 1947. Based on the historic and cultural value, it was decided to restore the building to its original design in 2002. The project to restore and retrofit it using a base isolation system was completed in 2012, as shown in Fig.  a base isolation system was used for retrofitting in 2019 to preserve the original architecture as shown in Fig. The last example is the east building of the Kagawa Prefectural Office in the Takamatsu city designed by Tange, K. in collaboration with Tsuboi, Y. for structural design and constructed in 1958. Since this building is one of the distinguished examples of modernist architecture in Japan,11Nearly half a century has passed since the author started studying the seismic evaluation and retrofitting of existing reinforced concrete buildings. As described in this paper, the author has been developing methods for seismic evaluation and retrofitting, verifying them, and disseminating them through JBDPA. Unfortunately, however, during the first two decades, seismic evaluation was not a matter of public concern except in limited areas, such as the Shizuoka Prefecture in Japan, since it was less appealing to stakeholders than the design and construction of new buildings. This was because people were hesitant to invest in seismic evaluations to determine the vulnerability of buildings that they normally use without any problems and/or in their seismic retrofitting in case of a major earthquake that rarely occurs. However, the situation has changed since the Great Hanshin-Awaji earthquake disaster in 1995, which caused the loss of more than six thousand human lives and valuable properties. Damage surveys have shown that disasters could have been considerably mitigated if seismic evaluation and retrofitting had been carried out in advance, and the Act on Promotion of Seismic Retrofit of Buildings was enacted for existing buildings. Many buildings have been seismically evaluated, and vulnerable buildings have been retrofitted or reconstructed since then. However, it will take more time to complete this project, which is a pressing issue among earthquake-prone countries and regions. In concluding this review paper, the author would like to express that “This is one of the most important and economical measures for earthquake disaster mitigation. We have the tools. Take actions immediately”.


Neurodevelopmental diseases are common disorders caused by the disruption of essential neurodevelopmental processes. Recent human exome sequencing and genome‐wide association studies have shown that mutations in the subunits of the SWI/SNF (BAF) complex are risk factors for neurodevelopmental diseases. Clinical studies have found that ARID1A (BAF250a) is the most frequently mutated SWI/SNF gene and its mutations lead to mental retardation and microcephaly. However, the function of ARID1A in brain development and its underlying mechanisms still remain elusive.Arid1a conditional knockout mouse line. Cell proliferation, cell apoptosis and cell differentiation of NSPCs were studied by immunofluorescence staining. In addition, RNA‐seq and RT‐PCR were performed to dissect the molecular mechanisms of Arid1a underlying cortical neurogenesis. Finally, rescue experiments were conducted to evaluate the effects of Neurod1 or Fezf2 overexpression on the differentiation of NSPCs in vitro.The present study used Cre/loxP system to generate an Arid1a reduces cortical thickness in the developing cortex. Arid1a loss of function inhibits the proliferation of radial glial cells, and increases cell death during late cortical development, and leads to dysregulated expression of genes associated with proliferation and differentiation. Overexpression of Neurod1 or Fezf2 in Arid1a cKO NSPCs rescues their neural differentiation defect in vitro.Conditional knockout of Arid1a plays an important role in regulating the proliferation and differentiation of NSPCs during cortical development, and proposes several gene candidates that are worth to understand the pathological mechanisms and to develop novel interventions of neurodevelopment disorders caused by Arid1a mutations.This study demonstrates for the first time that  Arid1a mutations are closely related to mental retardation and microcephaly, the function of Arid1a in brain development and its underlying mechanisms still remain elusive. The present study demonstrates for the first time that Arid1a plays an important role in regulating the proliferation and differentiation of neural stem/progenitor cells during cortical development, and proposes several gene candidates that are worth to understand the pathological mechanisms and to develop novel interventions of neurodevelopment disorders caused by Arid1a mutations.Although  Loss of Arid1a decreases the number of deep‐layer cortical neurons and increases cell death during late embryonic cortical development. In addition, Arid1a deletion leads to a decrease in the proliferation of RGCs and an increase in the proliferation of IPCs in the developing cortex. Global transcriptome analysis after Arid1a deletion reveals dysregulated expression of genes that are associated with the proliferation and differentiation of NSPCs. Overexpression of Neurod1 or Fezf2 in Arid1a cKO NSPCs rescues the neural differentiation defect in vitro. These results together highlight the essential roles of Arid1a in cortical development and support that loss of function of Arid1a contributes to microcephaly.Here, we generated 22.1Arid1af/f mouse was a kind gift from Dr. Zhong Wang at University of Michigan and Dr. Chun‐sheng Han at the Institute of Zoology, Chinese Academy of Sciences. Mice were genotyped by PCR using primers  and conditions used by The Jackson Laboratory. The Arid1af/f mice and Emx1‐cre mice (JAX Stock No. 005628) were crossed for the generation of Arid1a conditional knockout (cKO) mice. All experiments involving mice were approved by the Animal Committee of the Institute of Zoology, Chinese Academy of Sciences.All mice used in the current study have a C57BL6 background. The 2.2Arid1af/‐: Emx1‐cre male mice and Arid1af/f female mice together. The vagina of the female mouse was examined at 9 am the next day. When the vaginal suppository appeared, it was E0.5. Embryonic brains of E12.5, E14.5 and E16.5 were fixed in 4% paraformaldehyde overnight and dehydrated with 30% sucrose.We accurately obtain mouse embryos in the following ways: after 5 pm on the first day, we put 2.3Pregnant mice were given intraperitoneal injections with 100 mg/kg BrdU based on the weight of the mouse; the concentration of stock BrdU is 10 mg/ml . Embryonic brains were harvested 2 h after BrdU pulsing at E12.5, E14.5 or E16.5.2.4Brains were cut into 10‐µm‐thick cryosections. For immunofluorescence analyses, brain slices were washed three times in PBS (10 min each time). To detect BrdU incorporation, fixed brain slices were pre‐treated with 1 M HCl for 30 min at 37°C. The slices were then washed with 0.1 M borate buffer (pH 8.5) for 30 min (15 min each time) and with PBS for 30 min (10 min each time). Slices were fixed in 4% paraformaldehyde for 15 min at room temperature and washed three times in PBS (10 min each time). Next, the slices were blocked in a blocking solution  at room temperature for 2 h. The slices were then incubated with the primary antibodies  diluted in the blocking solution at 4°C overnight and labelled using the appropriate secondary antibodies  at room temperature for 2 h.2.5The total protein of cortical tissues was extracted using RIPA buffer, and the protein concentration was defined using BCA protein assay kit . Western blotting was conducted according to published approaches.2.6Arid1a WT or cKO forebrains according to procedures with TRIzol reagent . After quality quantification, the total RNA was converted to cDNA library and analysed by Illumina HiSeq 2500 platform. The RNA‐seq data are available in SRA with accession number PRJNA726035.The total RNA was extracted from E16.5 For RT‐PCR analysis, total RNA was transcribed into cDNA using TransScript One‐Step gDNA Removal and cDNA synthesis Kit . Then, cDNA was quantified by using Hieff® qPCR SYBR® Green Master Mix in a 20 μl reaction system according to instructions. The PCR steps were performed as follows: initial pre‐denaturation at 95°C for 5 min, amplification for 45 cycles of 94°C for 10 s, 60°C for 30 s at, 72°C for 30 s, and final extension at 72°C for 10 min. All samples were run in triplicate. The analysis of relative gene expression was performed by the 2‐ΔΔCT method. GAPDH was used as endogenous control to normalize the RNA content of samples. All the primers used for RT‐PCR in this study are listed in Table 2.7Nhe1/EcoR1 restriction sites of the CD511 vector. The following primers were used: Neurod1‐OE‐F, 5′‐GACGGCTAGC GCCACCATGACCAAATCATACAGCGAGAGCGGGC‐3′; Neurod1‐OE‐R, 5′‐CCGGAATTCCTTGTCATCGTCGTCCTTGTAATCCTAATCGTGAAAGATGGCATTAAGCTGGGC‐3′; Fezf2‐OE‐F, 5′‐GACGGCTAGCGCCACC ATGGCCAGCTCAGCTTCCCTGGAGACCA‐3′; Fezf2‐OE‐R, 5′‐CCGGAATTCCTTGTCATCGTCGTCCTTGTAATCTCAGCTCTGAACTGTCCTGGCTAGGTCC‐3′.To generate the Neurod1‐OE plasmid or Fezf2‐OE plasmid, a pair of primers were annealed, and the product was inserted into the 2.8Lentivirus production was performed as described previously.2.9NSPCs were isolated from Arid1a WT and cKO forebrain at E16.5 as described previously.5 cells/well. Following lentiviral infection for 48 h, NSPCs were incubated with DMEM/F‐12 medium containing 1% N2 supplement , 1% Antibiotic‐Antimycotic, 5 µM forskolin  and 1 µM retinoic acid  for 3 days. NSPCs were then fixed with 4% paraformaldehyde for 20 min and stained with Tuj1 antibody.Differentiation of NSPCs assays was performed as previously.2.10Confocal images were acquired using Zeiss LSM 710 and LSM880 Fast Airyscan confocal microscopes and analysed by ZEN software.2.11t tests were performed using GraphPad Prism software. Statistical significance was defined as *p < 0.05, **p < 0.01 and ***p < 0.001. Unless otherwise indicated, all data are presented as mean ± SEM.Experiments were conducted in at least three biological replicates for each group. Immunostaining quantification analysis was performed with ImageJ. Positive cells were counted by a rectangle with a width of 100 µm on the cortex, and at least 10 sections were examined for each embryo. For statistical analyses, unpaired two‐tailed Student's 33.1Arid1a in the development of CNS, we first tested the expression pattern of Arid1a in the brain of E16.5 embryos. The immunostaining results showed that Arid1a was ubiquitously expressed in the nucleus of NSPCs in the VZ/SVZ and of neurons in the cortical plate (CP)  Figure . Co‐immus Figure . In addis Figure . Furthers Figure . Taken tArid1a in cortical development, we generated Arid1a cKO mice by crossing Arid1af/f mice with Emx1‐Cre mice that drive cortex‐specific Cre expression beginning at E9.5  neurons as well as Brn2‐expressing later‐born neurons between Arid1a cKO and WT mice  to label S phase dividing cells, and animals were euthanized 2 h later. Arid1a cKO resulted in a significant increase in BrdU incorporation at E16.5  cells was reduced significantly, whereas the proliferation of IPCs (Tbr2+BrdU+) was significantly increased in Arid1a cKO mice compared to that in WT mice  in Arid1a cKO mice compared with control littermates, of which 239 genes were up‐regulated and 319 genes were down‐regulated   Figure . Gene Ons Figure . The down Figure . Furthers Figure .Wnt2b, Wnt5a, Wnt8b, Nfact4 and Ror2 were up‐regulated in Arid1a cKO cortex  with publicly available Arid1a ATAC‐seq data showed that Arid1a deletion in RGCs led to a dramatic decrease in the activity of neurogenic genes, including Neurod1 and Fezf2  and Fezf2 (Fezf2‐OE) respectively. The elevated protein levels of Neurod1 and Fezf2 were validated in 293T cells, which were transfected with lenti‐NeuroD1‐OE and lenti‐ Fezf2‐OE, respectively (Figure Arid1a cKO NSPCs to evaluate whether overexpression of Neurod1 or Fezf2 in Arid1a cKO NSPCs could rescue their neural differentiation defect. Indeed, our results showed that overexpression of Neurod1 or Fezf2 was sufficient to enhance the neural differentiation ability of Arid1a cKO NSPCs (Figure Neurod1 and Fezf2 are functional downstream targets of Arid1a during cortical development.To further identify y Figure . Secondls Figure . These r4Arid1a plays an essential role in embryonic cortical neurogenesis. Conditional knockout of Arid1a decreases the generation of deep‐layer neurons and increases cell death, which results in a thinner cortex during late embryonic development. Arid1a loss of function inhibits the proliferation of RGCs but promotes the proliferation of IPCs in the developing cortex. Overexpression of Neurod1 or Fezf2 in Arid1a cKO NSPCs can rescue the neural differentiation defect in vitro. The present study provides direct experimental evidence that Arid1a loss of function contributes to abnormal cortical neurogenesis.Neurogenesis is under the precise temporal and spatial control by many transcription factors.Arid1a cKO mice, thinner cortex is detected beginning at E14.5. In consistent with this, the markers of deep‐layer neurons, Tbr1 and Ctip2, are significantly decreased at E16.5 in Arid1a cKO mice, wherever the markers of upper‐layer neurons, Brn2 and Satb2, do not significantly changed (Figure Arid1a regulates differentiation of NSPCs along with other BAF subunits. In addition, Arid1a deficiency increases cell death in the developing cortex from E12.5 to E16.5. As most TUNEL‐positive cells are located in VZ/SVZ, we speculate that RGCs and/or IPCs are prone to die in Arid1a cKO cortex, which should also contribute to the reduced thickness of Arid1a cKO cortex. We identify that Neurod1 and Fezf2 are functional downstream targets of Arid1a to regulate neural differentiation. As currently there is no commercially available ARID1A antibody for chromatin immunoprecipitation analysis of tissues, we analysed the ChIP‐seq and ATAC‐seq data for ARID1A deposited in public databases from embryonic stem cellsArid1a has enrichment on Neurod1 and Fezf2 loci which support our identification ARID1A directly regulates Neurod1 and Fezf2 in the nervous system. To our surprise, our results showed that the expression of Brg1, the central ATPase subunit of SWI/SNF, was significantly down‐regulated after Arid1a deletion. However, the publicly available ChIP‐seq of BRG1 from E16.5 cortical neurons shows Brg1 has no enrichment on the same Neurod1 and Fezf2 loci, suggesting that Brg1 and Arid1a might have different regulatory mechanisms in neural progenitor/stem cells, while they are the main core components in SWI/SNF complex. The regulatory difference between BRG1 and ARID1A also hints that ARID1A function might be independent of the SWI/SNF complexes in neural progenitor/stem cells or in nervous system. Of course, more investigations are further needed to provide in other systems in the future.In d Figure . ConsideArid1a is a nuclear protein and widely expressed in different human tissues including brain.Arid1a is ubiquitously expressed in all kinds of brain cells, suggesting its pivotal role not only in NSPCs but also in other cell types. Moreover, higher expression levels of WNT/β‐catenin signal pathway‐associated genes such as Wnt2b, Wnt5a, Wnt8b, Nfact4 and Ror2 were observed in Arid1a cKO cortex. Given that WNT/β‐catenin signalling is critical for the proper proliferation and differentiation of NSPCs during embryonic development,Arid1a plays an important role in regulating the proliferation and differentiation of NSPCs during cortical development, and proposes several gene candidates that are worth to explore the pathological mechanisms and to develop novel interventions of neurodevelopment diseases caused by Arid1a mutations.In summary, this study demonstrates for the first time that The authors declare that they have no conflict of interest.C.‐M.L. and X.L. involved in conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript; S.‐K.D. and P.‐P.L. performed collection and assembly of data.Fig S1Click here for additional data file.Fig S2Click here for additional data file.Fig S3Click here for additional data file.Fig S4Click here for additional data file.Fig S1‐4Click here for additional data file.Table S1Click here for additional data file.


Since 2019, a university-community partnership has connected undergraduate students with older adults from independent living and community-based settings  for a photography-based intergenerational program. This study compares the implementation and impacts of this photography-based intergenerational program both in an in-person format before the COVID-19 pandemic (n=34) and an online format during the COVID-19 pandemic (n=25). Pre- and post- results from older adult and undergraduate student participants regarding social connection and evaluation comments from program participants and staff were compared between the pre-pandemic, in-person format, and the same program’s offering the next year in a virtual format. Results indicate that the benefits of this intergenerational photography program were experienced at a similar level during and before COVID-19. Findings demonstrate that intergenerational programs could effectively continue in remote formats, while also identifying potential challenges in implementation for staff regarding managing logistics and maintaining engagement among participants.


Free-roaming dogs are a worldwide problem that cause a wide array of issues in society. In Chile, a law protecting companion animals, and describing the role of responsible owners, was promulgated in 2017, followed by a national program aimed at mitigating dog-related problems throughout the country. The aim of this review is to explain and discuss certain components of the program and to provide suggestions for future changes. A simple model was created to assist managers in Chilean municipalities to more closely estimate the local dog population. The recommendations include the collection of baseline data and a dog population size estimate prior to implementing interventions, as well as the development of clear objectives, achievable goals and indicators, and the investment of public funds in long-term sustainable strategies such as education and enforcement rather than offering free veterinary services.Free-roaming dogs are a worldwide problem, with Chile having some of the highest human-to-dog ratios in the world. In 2017, Law 21.020 was promulgated and the federal government developed a national responsible pet ownership program. The objectives of this article are to describe and discuss the dog-related components of the program, to design a tool for determining human-to-dog ratios in Chile, and to make recommendations to managers to improve the program outcomes. The overarching goal of the program was to mitigate the conflict between humans and dogs, but many of the interventions were animal-focused and the indicators did not consider the perception of the Chilean public. Using human density data and known dog populations, we found that as the human density increased, there were fewer dogs per person. Veterinary services and sterilizations were the mainstay of the program and were offered for free to citizens. Education was offered to all ages through public events, as well as municipality and organization activities. The identification of dogs was obligatory for dog owners. Enforcement was not included in the program. The recommendations are to conduct preintervention baseline data collections and to tailor interventions and indicators appropriately; to use dog population size estimates determined at the local level rather than a country-wide estimate; to replace free veterinary services with low-cost sterilization campaigns; to create sustainable plans for education; and to create enforcement teams in communities. Free-roaming dogs (FRDs) are a worldwide problem, particularly in developing countries ,2,3,4. DThere are a number of international guidelines from organizations such as the World Organization for Animal Health   and the It is important to note that although these guidelines exist, there is no “one size fits all” formula to follow to solve the FRD issue. Countries and communities are all unique and require a tailored approach depending on the local situation. Sadly, many countries spend years investing in DPM programs, resulting in disappointing results, often because the approach is generic or unrelated to the issues in situ or because the execution is scattered and uncoordinated .While FRDs in Chile have been identified as a national, sociocultural, and animal welfare issue for decades ,11, the Chile, a country in South America with 17,574,003 inhabitants , has gaiAlthough Chile does not have canine rabies, a host of canine zoonoses ,21,22 anIn 2006, household surveys were done in Chile to evaluate factors influencing the quality of life of the citizens. They found that 50.4% of citizens said that conflicts associated with the presence of free-roaming dogs and cats were the number one problem that should be prioritized in their communities. In 2015, this number had dropped to 48.2%; however, in that same survey, 63% of respondents stated that FRDs constituted a serious or very serious problem. Then, in 2018, the survey was repeated and the majority of respondents said that FRDs and other animals were the most serious problem in their neighborhoods, surpassing even that of crime .Municipalities are given the lion’s share of the responsibility for managing the country’s FRD problem. However, in many cases there is an insufficient capacity or insufficient staffing to deal with such a complex issue, or there are limited economic resources to allocate to baseline data collection. Therefore, a clear analysis of the local situation is unavailable. Yet, published data suggest that Chile differs markedly between regions in terms of dog ownership practices, such as the numbers of dogs that residents own, emphasizing the importance of understanding the human–canine dynamic before implementing new interventions. A lack of clarity about these dynamics and the ensuing problems on a site-by-site basis can result in programs with unclear objectives, ineffective interventions, or a lack of coordination from municipality to municipality ,31.The objectives of this article are: (1) to describe and discuss general components of the national companion animal management plan as it pertains to dogs only, with a particular emphasis on veterinary services, education in responsible pet ownership, and registration and identification; (2) to provide a tool for determining the human-to-dog ratios in Chile for their use in municipalities where a specific dog population estimate is not available; and finally, (3) to make recommendations for some adaptations to the strategies and indicators of the DPM plan that could potentially improve the intervention outcomes and the long-term sustainability of the program.The first draft of the responsible pet ownership bill dates back to 2009 and primarily describes the liability for damages caused by potentially dangerous animals. The bill remained in Congress for years, during which time the scope was amplified to include content related to general pet ownership. In the meantime, in 2014 the government released funds for a pilot sterilization program in 67 (19%) municipalities and then, in 2015, in a further 162 (46.9%) out of a total of 345 municipalities in the country. In 2016, the program expanded to include the microchipping of pets and public outreach about the responsible ownership (RO) of cats and dogs . Then, iThe Cholito Law, or the Responsible Pet Ownership Law (Law 21.020), complements the 2009 “Law on the Protection”of Animals” (Law 20.380) which, although it originally did state that animals are sentient beings and deserving of protection, was deficient in details about how to comply with the law and also continued to consider animals as personal property. The new law (Law 21.020), aims to generate a social and cultural change in the way that citizens interact with companion animals and describes a set of obligations that a person agrees to when he or she decides to keep a pet; that is, to provide it with food, a home, and to treat the pet in an appropriate manner, as well as providing them with veterinary care and not subjecting them to suffering or abandonment in addition to respecting public health and safety regulations . The newIn 2018, following the release of Law 21.020, the government launched the National Program for Responsible Ownership of Companion Animals , hereafter referred to as PTRAC. Municipalities and NGOs working in the field of veterinary medicine, welfare, and/or responsible pet ownership, and who registered in a National Registry, were permitted to apply for public funds to implement the PTRAC . From 20The overarching goal of the PTRAC was centered around the conflict between people, companion animals, and animal welfare. The main objective was to contribute to a better quality of life for all the citizens of Chile by promoting the appropriate coexistence between people and animals, as well as having people live responsibly with companion animals . Many ofThe average age of sterilizationsThe percentage of the coverage of animals accessing veterinary services through, exclusively, municipal clinics for the first timeThe percentage of the coverage of municipalitiesThe rate of change of the number of illnesses that animals presentThe percentage of municipalities that continued the program after national funding with their own resourcesThe rate of change in the number of infractions of the Responsible Ownership LawThe rate of change of dogs that are free-roamingIn order to measure the progress of the program and evaluate for success, seven indicators were created that were related to program performance:These indicators, however, have no associated timelines to assess temporal progress or clear indications of what the expected outcome was. While the main goal was to improve the quality of life of the Chilean public, there are no human-related indicators to specifically address this goal; rather, the indicators are focused on indices related to veterinary care, coverage, fines, or the number of FRDs, for example .Based on the literature, there is a very wide range of reported ratios of humans and dogs in Chile, ranging from 10.7:1  to 1.1:1There have been many articles that describe the different methodologies for calculating a dog population estimate ,39,40. TUnderstandably, every small community may not have the economic means or expertise to conduct a household survey or a canine census; therefore, given the importance of having a dog population estimate prior to the commencement of any interventions, we developed an alternative tool for estimating the ratio based on the local human density.comuna in Chile). A dataset based on previous work by Astorga et al. and other recently published papers .Between 2017 and 2020, a total of 177 education projects were financed. The government also offered an online course about RO to successful applicants and government employees involved in the program, and although participation was encouraged, it was not required. While each NGO was vetted for prior experience in education delivery and the validity of the proposed project during the proposal stage, there were no requirements to measure and report on the impacts of any of the programs on the target audience. The accountability for awarded funds was based on how the funds were spent and the numbers of children or schools participating, for example, but not on knowledge gained, retention, or changes in attitudes.Although the PTRAC states that RO education should be delivered under a strategic framework with methodologies that allow for the continuity of the program that achieves significant and extensive learning for the whole community, the entire education budget allocated to NGOs went from approximately USD 240,000 in 2018, to USD 303,000 in 2019, down to only USD 65,000 in 2020 for the whole country, and the total allowable time for which NGOs were allocated to execute their projects went from eight, down to a maximum of four, months.As part of the PTRAC, the plan was to develop five national registries for the following: (1) all cats and dogs in the country, (2) dangerous breeds, (3) NGOs that work in the field of small animal health or welfare, (4) breeders and sellers, and (5) shelters. As of the end of 2019, only the national registries for all cats and dogs and the NGOs were operational .The deadline for compliance with Law 21.020, stating that all dogs and cats required identification through internal or external means, was 12 February 2019. The accepted means of identification include a microchip for internal identification, and a tattoo or a collar with identification tags containing a unique code designated by the government is accepted for external identification. From 2015 through to 2018, there was a steady increase in microchipping through the PTRAC program, possibly as a result of the national public outreach campaign or, alternatively, because the implantation with a microchip was obligatory for any animals sterilized at any of the PTRAC campaigns . One yeaAlthough the draft law for responsible pet ownership was frozen in the Chilean parliament for many years, it was thanks to public pressure that the Law of Responsible Pet Ownership (Law 21.020) in 2017 was finally approved. Before this date, pets were considered “property” and now they are considered sentient beings requiring certain standards of care, health, and management. The government then moved to the next step to develop a companion animal program (PTRAC) and allocated significant public funds toward its implementation. They have dedicated time and money to seek public and municipal buy-in and have had great success with the numbers of municipalities that are participating in the program, stretching from the north to the south of the country. Despite the country experiencing significant social unrest in 2019 and then the pandemic in 2020 and 2021, resulting in the available funds being greatly reduced, the government has continued to make DPM a priority. As with any new program, there are a number of pitfalls that could be addressed to greatly improve the efficiency and impact of the PTRAC. Below, we discuss some of these and suggest a few alternative possibilities for consideration.In published recommendations for the design of a DPM program, the most critical step is to do an assessment of the human perception of the problem, pet demographics, and a local needs and resources assessment within a geographic area ,9. This For example, in some communities the primary concerns may be the fecal or garbage contamination of public spaces. The public perception of change, following targeted interventions such as the availability of dog-specific parks with fecal collection bags, the presence of enforcement officers, and/or dog-proof garbage containers, for example, would then be important and appropriate indicators.In a study in remote Australia, the community members’ perceptions about dog conflicts were documented, and the researchers found that they were not as interested in how many dogs there were. Rather, community members sought a balance between the services that the FRDs provided to their community  and the negative public health effects, including bites and attacks on humans, zoonoses, and poor community hygiene due to dog feces and garbage . This hiIn terms of the Chilean PTRAC, baseline information would have been valuable to assess what strategies were actually needed. For example, in one city of approximately 145,000 inhabitants in south-central Chile, a subsidized municipal veterinary clinic was erected to provide free services. According to the College of Veterinarians for this region, the city held 30–40 small animal veterinarians registered in the College of Professional Veterinarians , an unknown number of unregistered veterinarians (registration with the College is not obligatory in Chile), and a veterinary college  with specialty clinic services. According to an article on veterinary economics , a city Indicators were developed to evaluate the PTRAC; however, the lack of a clear and direct linkage between them, the objectives, and the goals, severely hindered the ability to measure successes in each of the PTRAC strategies . SMART ghttps://reportesrem.minsal.cl/ (accessed on 2 September 2021)). Between 2003 and 2012, it was estimated that bites caused by dogs may have cost the national healthcare system as much as USD 177.9 million, and this estimate does not factor in losses due to the burden of disease borne by individuals in the community, such as a loss of income, and disability [Although the Chilean public was listed as the main beneficiary of the PTRAC, and free-roaming dogs have been reported as posing a significant risk to the public affecting the quality of life for the citizens of Chile , it is ssability . UnfortuThe human-to-dog ratio of 5.1:1 was used across the entire country to estimate the owned dog population. Two immediate concerns arise in regard to the universal use of this ratio. Firstly, estimates were taken exclusively from urban municipalities only in central Chile in 2002, failing to consider the differences in rural areas and in the rest of the country. Secondly, they were related to human population estimates from 2017. This method fails to account for the known differences that can be found in human-to-dog ratios between rural and urban areas across the country, as well as the temporal changes in the human population between the time the human-to-dog estimates were measured and the human population values they relate to.In Latin America, we found reported ratios of humans to dogs ranging from 3.4:1 and 4.3:1 in Mexico ,57, 4.0:Chile has published ratios of humans to dogs that are similar to these other countries, such as 6.4:1 in Santiago , 5.2–6.2Interestingly, the dog population estimate did not appear to have been used to determine community-specific interventions and goals; rather, it seems that the same strategies were applied across all sites, independent of the sociocultural uniqueness of communities, whether the site was rural or urban, and what the dog population estimate was. A local needs assessment would have greatly aided in determining the requirements for technical capacities, the accessibility of veterinary care, sterilization or microchipping, and priority areas for disease control and the control of dog abandonment. With a clear picture of the differing community-specific needs, public funds could have been allocated toward appropriate strategies and priority areas.Here we presented a statistical tool (a model) that allows for more reliable estimates of these ratios to be derived for municipalities where human density is known, but the total number of dogs in unknown. Using this model, we can predict the ratio of humans to dogs for a given human density, resulting in an estimate that is more accurate than the default 5.1 ratio commonly used across the whole range of human densities in the country.2), where the confidence interval does not overlap with the default 5.1 , which essentially assumes a constant ratio for all municipalities, the outputs of this model constitute an improvement in the estimation of more accurate values of the ratio of humans to dogs. The model is a particularly useful tool in municipalities with lower human densities  to determine whether a pet owner is eligible to receive low-cost services. In communities that are determined as having a sufficient number of private clinics for the pet-owning population, the low-cost services could even be offered through these existing private clinics as an additional service. In this scenario, owners eligible for a subsidy would be required to pay a percentage of the cost, and the government could contribute the remainder. This would serve multiple purposes; for example, it would reduce the need for additional and costly brick and mortar municipal clinics in places where there are already sufficient services, as well as reducing the need for additional veterinary surgeons to be employed in every municipality. Spay/neuter campaigns could be offered in existing clinics, rather than community centers, and this would allow for surgeries to be performed under aseptic conditions with the correct equipment, supplies, drugs, and personnel nearby should there be an emergency. Lastly, it would engage local veterinarians and involve them in the PTRAC program, allowing them to have enhanced opportunities to interact with, and educate, all sectors of the community about responsible ownership. This opportunity could lead to longer-term relationships between the government and private sector veterinarians, and between pet owners and their veterinarians. It would also release an enormous amount of public funds to support other areas of the program, for example, pre-program assessments, baseline date collection, education, and enforcement.The identification and registration of dogs is the foundation of any DPM program to create compliance and sustainability. However, if the data are stored in a registry and there is no active enforcement program in place, the full effect of the activity is nullified. An important requirement in the process of developing a new public policy is to evaluate the willingness of the public to comply with the law and the ability of local municipalities to enforce the new regulations . It is nIf a government wants to improve regulatory compliance, it is critical that it first understands the obstacles to compliance, what motivates the target individuals to comply with the regulation, and what the target group is doing in real life . This shOnce the public is aware of the new law, voluntary compliance is seldom sufficient to incite permanent change and a key determinant of government effectiveness is how well they achieve their policy objectives . To put In fact, in a study in remote Australia, it was found that survey respondents were loath to confront their neighbors or call the enforcement department regarding dog-related complaints, and instead chose a “weary acceptance and passive resentment” that tended to create underlying social tensions in the neighborhood . In the As part of Law 21.020, there is a fine for owners whose pets are not identified and registered. Initially, only permanent identification  was deemed acceptable, but this was later changed to include collars with identification tags as acceptable due to public pressure. Collars and tags used alone, however, are not reliable, as they are easily removed, applied to other animals, and pose a potential danger for FRDs that can become caught or hung up on fences, for example . While aPerhaps, in those communities where there was already sufficient veterinary infrastructure, a better strategy other than investing in sterilization campaigns or building municipal clinics could have been to build enforcement teams of animal control officers, for example. Having enforcement personnel on the ground in these communities, although it will always be opposed by some, can also be very validating for community members that are asking for visible action. Their perception of the problems and the associated actions taken by the municipality as the program is unrolled can be an important indicator to evaluate whether the program has the desired effect of people and pets living together in a more harmonious manner.The enforcement of legislation can strongly support community efforts to manage dog-associated problems and it is a critical element for the sustainability of the program as a whole. Fines and registration fees can also contribute to the long-term sustainability of the program . Sadly, Enforcement alone is not considered an effective enough tool to change human behavior, and other strategies, such as education, are used in combination to attain the desired change . The PTRIn the case of Chile, there was no budget allocated from the program for the enforcement of the Cholito Law, and the entire education budget allocated to NGOs went from approximately USD 240,000 in 2018, to USD 303,000 in 2019, down to only USD 65,000 in 2020 for the whole country. One of the main goals of the program is to improve the human relationship with pets. This has been successfully demonstrated through RO education programs ,74,75, bAlthough the Chilean government has made great strides in bringing forward a law to protect companion animals and a program to reduce conflict between pets and the public, the strategies chosen to achieve this goal have some fundamental flaws. Specifically, we recommend reassessing the PTRAC program to include the collection of baseline data at the community level. An analysis to assess the existing resources and needs, and a dog census or population estimate, should be the minimum baseline data required prior to any intervention. In communities where a dog population estimate is logistically or economically impossible, a more specific statistical tool, such as that included in this article to estimate the dog population based on human density, should be used. In each community where a DPM program is designed, we recommend the development of appropriate intervention strategies and SMART goals, as well as the use of some simple indicators that are all based on the initial baseline data results for each community. This would greatly assist managers in determining whether goals are being met and could lend more accountability for the use of public funds. Fund allocation should be adjusted according to the prioritization of problem areas based on the initial assessments results and demonstrated need so that funds are used prudently. The delivery of free veterinary services should be eliminated and, instead, the government could consider low-cost alternatives. Funds that would otherwise have been spent on free services could then be invested in long-term strategies aimed at human behavior change such as education and enforcement.


Idiopathic granulomatous mastitis (IGM) is an uncommon, benign, chronic inflammatory breast disease of unknown etiology, unpredictable duration, and unclear therapy.A 41-year-old woman presented with pathological nipple discharge for which ductoscopy was performed. Post-ductoscopy, the patient developed abscesses in her breast with histopathological confirmation of granulomatous mastitis (GM).IGM has an unknown etiology and atypical presentation. This is the only case described in which IGM occurred after ductoscopy. This can be related to trauma-induced GM or underlying IGM aggravated by ductoscopy. •Idiopathic granulomatous mastitis (IGM) has an atypical presentation.•Radiological findings are non-specific in diagnosing IGM.•GM can occur after ductoscopy. Whether this is trauma-induced GM or underlying IGM aggravated by ductoscopy remains unknown. Symptoms of IGM are a mass, pain, erythema, swelling, fistula, areolar retraction, ulceration, and abscesses We describe a case of a woman who developed abscesses after ductoscopy, diagnosed as IGM on biopsy. To the best of our knowledge, IGM after ductoscopy has not been previously described. This report was written in line with the SCARE criteria 2A 41-year-old gravida 3, para 3 woman presented to the outpatient clinic with a 2-year history of right-sided pathological nipple discharge (PND) with unremarkable medical history and drug history. She had milky/brown nipple discharge, which started days before her menstruation and persisted during her menstruation. Physical examination of the breast was normal. Mammography suggested a retroareolar cyst in the right breast shown in a. UltrasFour days after ductoscopy, she developed pain and a palpable mass of 4–5 cm in the lower-outer quadrant. Ultrasound showed duct ectasia, not suspicious for infection or malignancy shown in c. Histol2.1A breast radiologist (AF) retrospectively analyzed the ultrasounds and mammography. The mammography showed more asymmetry in the retromamillar region right than left. The ultrasound images before ductoscopy showed duct ectasia, some with thickened duct wall. This can be related to granulomatous mastitis, but it was very limited in these images and not immediately suspect. The ultrasounds images after ductoscopy showed again duct ectasia, now filled with echogenic material. Therefore, the thickening of the wall was less clear. Because there was no vascularization, the images were not immediately suspect for granulomatous mastitis.3Corynebacterium KroppenstedtiiIGM is an uncommon benign chronic inflammatory breast disease first described by Kessler and Wolloch in 1972 This case study is the first to report the unusual presentation and complicated diagnosis of a patient with IGM after ductoscopy. In our case, we hypothesize that the patient may have suffered from PND, with GM as an underlying cause, and the ductoscopy procedure aggravated the chronic inflammatory disease, which led to the formation of abscesses in the breast. Another hypothesis is that the patient was suffering from PND from another cause, and the ductoscopy was a traumatic event that led to “trauma-induced GM”. In three previously reported cases, a possible “trauma-induced GM” was also described: in one case induced by a foreign body Ductoscopy is a minimally invasive procedure with mild and rare complications. Only mild nipple pain, bacterial mastitis, and perforation of the ductal lining have been reported The diagnosis and treatment of IGM are challenging because of a lack of valid data. Currently, the application of corticosteroids and the use of surgery in cases with insufficient response to conservative treatment is the most common approach 4IGM has an unknown etiology and atypical presentation. Radiological findings are non-specific in diagnosing IGM. This is the only case described in which IGM occurred after ductoscopy. Whether this concerns trauma-induced GM or underlying IGM aggravated by ductoscopy remains unknown. With this case report, we want to create awareness of the rare presentation of this condition after ductoscopy.S. Makineli and A.J. WitkampWritten informed consent was obtained from the patient for publication of this case report and accompanying images.None declared.Ethics approval was not required for case reports according to guidelines in the Netherlands.Not commissioned, externally peer-reviewed.S. Makineli: conceptualization, methodology, project administration, resources, writing – original draft.P.J. van Diest: methodology, supervision, validation, writing – review and editing.M.A. Fernandez: writing – original draftA.J. Witkamp: conceptualization, methodology, supervision, validation, writing – review and editing.The authors declare that they have no conflict of interest.


The findings of this study point at mtDNAcn as a potential biological marker of acute stress and suggest that experiencing an earthquake during pregnancy or before gestation can have programing effects in the unborn child. Long-term follow-up of newborns to women who experience stress prenatally, particularly that derived from a natural disaster, is warranted.An altered mitochondrial DNA copy number (mtDNAcn) at birth can be a marker of increased disease susceptibility later in life. Gestational exposure to acute stress, such as that derived from the earthquake experienced on 19 September 2017 in Mexico City, could be associated with changes in mtDNAcn at birth. Our study used data from the OBESO  perinatal cohort in Mexico City. We compared the mtDNAcn in the umbilical cord blood of 22 infants born before the earthquake, 24 infants whose mothers were pregnant at the time of the earthquake (exposed), and 37 who were conceived after the earthquake (post-earthquake). We quantified mtDNAcn by quantitative real-time polymerase chain reaction normalized with a nuclear gene. We used a linear model adjusted by maternal age, body mass index, socioeconomic status, perceived stress, and pregnancy comorbidities. Compared to non-exposed newborns (mean ± SD mtDNAcn: 0.740 ± 0.161), exposed and post-earthquake newborns  had increased mtDNAcn,  Mitochondria play an essential role during gestation, and their correct functioning is fundamental for optimal pregnancy development and resolution , protectChildren’s mitochondriomics could be modified by psychosocial stress, and its completion could enrich our knowledge in this science . A recenLatin America is a region with high seismic activity. Chile, Ecuador, Haiti, Peru, Guatemala, and Mexico are among the countries that have experienced the strongest and most deadly earthquakes . Mexico The data came from the ongoing OBESO  perinatal cohort in Mexico City, which studies obesity and maternal metabolic profile as predictors of fetal body composition, obesity, and neurodevelopment during infancy. Women were invited to participate at the National Institute of Perinatology (INPer); they were recruited in their first trimester (11.0–13.6 weeks determined by ultrasound) and followed throughout pregnancy and the child’s first years. Inclusion criteria included the following: being ≥18 years old, no previous comorbidities , a pregestational BMI ≥ 18.5, no current treatment that can affect carbohydrate or lipid metabolism , and a fetus without structural congenital malformations. The first participant was recruited in January 2017, and the first child was born in July of the same year. The project was approved by the institutional review board of the INPer (3300-11402-01-575-17), and all women signed informed consent before participating.n = 22 infants born before 19 September 2017 (non-exposed group), n = 24 newborns from women who were pregnant when the earthquake happened and were born between 18 October 2017 and June 2018 (exposed during pregnancy), and n = 37 newborns conceived after the earthquake and born between July 2018 and June 2019 (exposed before pregnancy). Our study included 83 mother–infant pairs: ® Green , reactions were run in a StepOne™ Real-Time PCR System  with previously described PCR conditions [Umbilical cord blood was collected at birth using vacutainer tubes with EDTA and processed within 2 h of the collection. Blood was centrifuged at 1500 rpm for 10 min at room temperature, and the buffy coat was separated, washed, and stored at −80 °C until DNA extraction. DNA was isolated using the wizard DNA extraction kit , following the manufacturer’s instructions. Quantification of mtDNAcn was performed in triplicate by quantitative real-time polymerase chain reaction (qRT-PCR), using 12.5 ng of DNA and QuantiTect SYBRnditions ,21. The nditions , and norDetailed information was obtained on maternal pregestational body mass index (BMI), socio-demographic characteristics , and gender, weight, length, and head circumference of newborns. Information on pregnancy comorbidities  developed during pregnancy was also collected. Pre-existing stress was evaluated using the perceived Stress Scale-4 (PSS-4) collected during the 1st and 3rd trimester visits .p < 0.05 were considered statistically significant.We analyzed the normality of our data using the Kolmogorov–Smirnov test and compared the maternal characteristics and comorbidities , as well as mtDNAcn, of non-exposed newborns, those exposed during pregnancy, and those conceived after the earthquake, compared by one-way ANOVA for continuous variables, and the chi-square test for non-parametric data. A linear regression model was used to analyze the association between exposure groups and mtDNAcn adjusted by maternal age, BMI, pre-existing stress, and pregnancy comorbidities. Additionally, based on previous evidence linking perinatal susceptibility to maternal age , the assp = 0.817) and maternal pregestational BMI (p = 0.8) among the study groups. A total of 42 gave birth to a girl, and 41 gave birth to a boy. Almost half of the women reported middle socioeconomic status, which was not significantly different between the study groups (p = 0.73). Perceived stress in the first trimester was different compared to the third trimester of pregnancy, and no significant difference among the study groups was found in maternal comorbidities, such as preeclampsia and gestational diabetes. The results of the demographic, socioeconomic, and clinical characteristics of the mother–newborn dyads are shown in p-value < 0.001), and this increase was greater for those whose mothers were pregnant after the earthquake , without losing statistical significance  in the group exposed during pregnancy, whereas in the non-exposed group and group exposed after the earthquake, there was no association   .In this study, we found that infants born to women who were pregnant during the 2017 Mexico City earthquake had a higher mtDNAcn than those born before the earthquake. Interestingly, we observed a stronger mtDNAcn increase in infants conceived after the earthquake than in those born before this event, which could imply that acute stress during pregnancy can have both short- and long-term consequences. Understanding the biological implication of mtDNAcn increase or decrease has emerged as a relatively new area of research. We found no reference for what can be considered a normal mtDNAcn; studies have usually used their population as a reference, and the parameters reported are only valid for that population. Furthermore, mtDNAcn is tissue specific and dependent on the stage of life . During 2.5 and maternal lifetime trauma [Our results are also in line with studies about chemical environmental exposures during pregnancy that have found an association with altered mtDNAcn in the offspring; however, results are inconclusive on whether the copy number increases or decreases. A study showed a positive association between third-trimester manganese exposure and cord blood mtDNAcn ; other se trauma . Intriguingly, infants conceived after the earthquake had an even higher mtDNAcn than those born to women pregnant during the time of the earthquake. We hypothesized that this could be associated with post-traumatic stress  and the The 2017 earthquake affected thousands of inhabitants of Mexico City, with over 200 deaths and 400 injured persons, plus extended physical damage to the buildings and infrastructure of the city. It was the strongest earthquake felt in the city since 1985, which happened on the same calendar date and had thousands of casualties. Beyond psychosocial stress, earthquakes can physically affect individuals due to the environmental changes they generate . In the An additional finding was the difference in the association between maternal age and mtDNAcn depending on the exposure. For those women that experienced the earthquake while pregnant, there was a statistically significant increase in mtDNAcn in their newborns as maternal age increased. mtDNAcn depends on different factors such as tissue type, sex, and age . We hypoMost environmental health studies focus on chemical exposures; the results of our study add to the existing research and highlight the importance of including stress, and in this case, acute stress, as a relevant prenatal exposure. As is true of many chemicals, with stress, there can be overlapping or similar mechanisms that are affected and therefore similar health outcomes. For example, previous studies have shown that co-exposure to stress and lead is associated with the functioning of the hypothalamic–pituitary–adrenal axis . Our resTo our knowledge, this is the first study linking mtDNAcn to acute stress derived from an earthquake. We are unaware of other studies of mtDNAcn alterations as a result of prenatal exposure to stress derived from a natural disaster. In this sense, this study is a pioneer in evaluating a biological response to this type of event. We are aware of our limited sample size; however, our cohort was uniquely positioned to carry out this study since we were collecting umbilical cord blood as part of our research protocol. Unfortunately, the cohort started only a few months prior to the earthquake, and after it, recruitment slowed down dramatically because some areas of the city were severely damaged. We are unaware of other birth cohorts that collected umbilical cord blood in Mexico City before and after the earthquake, and which also analyze mtDNAcn. Since previous studies have shown associations between stress and epigenetic changes, such as Project Ice Storm (REF), we could speculate that if the sample size were increased, the associations would be stronger, narrowing the confidence intervals. Therefore, although this is a small sample, this study provides evidence for future work, not only in Mexico (a country with high seismic activity) but also in others with similar stressful natural disasters. Lastly, another limitation of our study was the analysis of mtDNAcn only in umbilical cord blood. In order to gain a more complete picture of the mother–infant biological response, and to answer whether this response is generalized or tissue specific, analysis of mtDNAcn in different tissues, such as maternal blood or placental tissue, would be desirable. OBESO is an ongoing cohort; we look forward to continuing the follow-up of these children, including their neurodevelopment and the long-term permanence of the mitochondrial response. The findings of this study point at mtDNAcn as a potential biological marker of acute stress and suggest that experiencing an earthquake during pregnancy or before gestation can have programing effects in the unborn child. Future studies should clarify if an altered mtDNAcn could reflect susceptibility to diseases immediately or later in life.