White Paper for Aged Society, which set the primary goal to enable seniors to deal with daily life more independently. Although ‘third places’ enable seniors to live independently, the third places that Taiwanese seniors like are not well understood. Consequently, by investigating third places, this study will investigate the environment of achieving successful aging and happiness among seniors. This study uses the questionnaire survey, and the data of this study were collected from October to November 2018 in Taichung City Central District. A questionnaire survey was conducted in several administrative agencies and participants were selected by random sampling among the over-55-year-old citizens who were already retired. An estimate of 90% confidence limits with 5% marginal error gave us a sample size of 257. This study finally received 200 efficient samples. The women’s top five choices of third places are the traditional market, supermarket, restaurant, daily necessities shop, and coffee shop. The men’s top five choices of third places are the traditional market, supermarket, daily necessities shop, restaurant, and a friend’s house. For seniors familiar with the concept of third places, the more often they go to third places, the higher happiness they achieve. This result investigates the importance of having awareness of third places for seniors. Therefore, we should encourage them to go to third places and engage in social activities frequently to achieve successful aging.Taiwan has actively promoted the concept of "successful aging" in recent years. The Executive Yuan drafted the  Internationally, the proportion of a society’s population that is comprised of persons aged 65 or older is called the “aging rate”. If a society’s aging rate exceeds 7%, it is an aging society; if the rate surpasses 14%, it is an aged society; and if it exceeds 20%, it is a super-aged society. Taiwan entered the stage of aging society in 1993, and aged society in 2018. It is predicted to become a super-aged society in 2026, which would mean it took just eight years to go from an aged society to a super-aged society. In 2065, there will be about four persons aged 65 or older for every 10 persons, and one person aged 85 in these four persons [Due to various social changes, such as longer life expectancy, medical advances, and improved health behaviors, the proportion of old age people in the population is increasing. If older adults cannot live independently (depend on the care of others) and are more frequently bedridden, it is not only pain that they suffer, but also places a heavy burden on their family, society, and the country. The government has a greater responsibility for supporting older adults and in prolonging independent living with increased support provided by the social network .Although society nowadays can provide services for the elderly such as nursing care, medical care, housing and community care, as well as welfare institution care, some of the welfare policies for seniors fail to provide sufficient care to all who need it because of some restrictions on their qualifications or their conditions. These seniors who are not properly cared for need to be informed and help by community-based support system in order to have access to social well-being.Taiwan has actively promoted the concept of “successful aging” since 2007 . The so-Currently, most researchers in Taiwan are focusing on investigating the nursing care of disabled seniors, or on dividing the seniors’ needs into senior learning and leisure. In fact, most seniors are afraid of facing the aging process, or of being less needed at home and in the workplace . The thiThis study includes the relevant theory of successful aging, the definition and characteristics of the third places, and the definition and cognition of happiness. In consequence, the foundation of the design research method is established.The concept of “third place” was introduced in the American sociologist Oldenburg’s book  “The greOldenburg believes that “the third place” is one of the important elements that composes a good life. However, there was no English word that could express the concept of informal public gathering places at the time, so he proposed the term “the third place” to express the core settings of informal public life, and defined it as a generic term for informal public places apart from work and the home, which have regular, voluntary, and informal gatherings.Oldenburg considered the third place should have eight basic characteristics: neutral ground, leveler (a leveling place), conversation is the main activity, accessibility and accommodation, the regulars, a low profile, the mood is playful, a home away from home. He listed the following types of possible third places: coffee shops, bars, book stores, gyms, hair salons, movie theaters, art galleries, and other public places in which you can relax. Frumkin et al. associate third places with public health ,9.Seniors in Taiwan believe they can still play an important role in the family. However, differences in Taiwan's population ratio and family structure have also changed the seniors’ plans and expectations for family life. Some scholars believe that the focus of the life of the seniors should be able to enrich themselves, not only being limited to their own families , and theThe third place offers stress relief from the everyday demands of both home and work. It also provides a feeling of safety and security by being publicly accessible and promoting open and visible interaction .According to Taiwanese government’s long-term care policy (Long-Term Care 2.0 in Taiwan) in 2017, constructing the comprehensive community care service system creates a comprehensive care system that integrates medical care, LTC(Long-Term Care) services, housing, prevention, and social assistance to allow people with disability to receive the care they need within a 30-minute drive. The smallest service station is Tier C—LTC stations around the blocks must be reachable within 10 minutes on foot, and its main function is to provide respite service in the neighborhood. However, long-term care and community care service system are regarded as a negative term by most seniors in Taiwan, so healthy seniors have very low utilization and high rejection [Successful aging has many synonyms such as active aging, productive aging, harmonious aging, healthy aging, vital aging, positive aging, robust aging, optimal aging, and aging well ,15.Research on successful aging has pointed out that a happy senior life must fulfill three important factors: physiological, psychological, and social ,17,18. TBaltes and Baltes used the concepts of variability and plasticity to define successful aging as a process of psychological adaptation, which contains three elements: selection, optimization, and compensation, referred to as the SOC model. Baltes believed that in order to achieve successful aging, the key point is how to choose and adapt to a suitable lifestyle, and then, through learning, training to maintain the optimum state. It can make up for the original motivation that decreases or disappears with age and can live an efficient and functional life after adjustment . For exaGeorge LK proposed Continuity Theory, also called Personality Theory. It mainly emphasizes that senior citizens have consistency in their activities, personalities, and relationships despite their declining physical, mental, and social status, from their adolescence, early adulthood and midlife, and considered that successful aging can only be achieved by maintaining the stability of individuals in activities, personalities and social relationships . ContinuHappiness is quite a subjective and personal experience . AccordiPsychological well-being is a well-known component of the Sociology of Aging. There is a huge overlap among life satisfaction, happiness, moral and psychological well-being. Some scholars evaluated it with autonomy, environmental mastery, personal growth, positive relations with others, purpose in life, and self-acceptance ,27.Tang HJ conducted her research on psychological happiness satisfaction of seniors lived in southern Taiwan. She divided happiness into four dimensions: take control of life and self-growth, positive relationships with others, autonomy, and self-satisfaction. The study found that if seniors can achieve all the above four dimensions, their overall happiness condition will be good . NeighboBased on research purpose, the communication approach of this study used self-administered survey, and the questionnaire including “personal basic data “, “third places” and “happiness”. In order to increase the validity of the questionnaire, face-to-face interview was conducted. Thirty seniors and caregivers were invited and interviewed. An initial survey instrument was tested to verify if the survey questions were clear in meaning and wording. After receiving feedback from respondents, appropriate adjustments were made to fit seniors living in Taiwan. The data of this study were collected from October to November 2018. This study used Taichung City Central District, the fastest aging population in Taiwan, as the research area. The Taichung Cultural City Midtown Project provides activities for local people in the Central District, while promoting community-friendly relations, and planning many open multi-functional spaces for rest and use. The area has a population of 18,557, and there were 5458 (29.4%) people aged over 55 years in October 2018 . A questionnaire study was conducted in several administrative agencies, and selected by random sampling the over-55-year-old citizens who were already retired collectors through oral inquiry. An estimate of 90% confidence limit with 5% marginal error gave us a sample size of 257. This study finally received 200 efficient samples. The response rate was 77.28 percent.The questionnaire of this study was divided into three parts. The first part requested personal basic data including six terms: gender, age, education, marital status, financial status, and living situation. Two items among them—marital status and living situation—were included to understand the current conditions in the first places of senior citizens.The second part was a survey of third places. It included whether the participants understood the concept of third places, their third places, their social places, and the frequency with which they visited those places.The third part was a questionnaire of happiness, and we obtained the happiness average value in this part. The study used the Oxford Happiness Questionnaire (OHQ), as we could obtain the results of questionnaire rapidly, so the interaction with older participants was better. The OHQ is derived from the Oxford Happiness Inventory (OHI). The OHI was designed by Argyle and used to survey English people’s happiness scale. It pointed out that English people’s happiness consists of seven major sources: optimism, social commitment, positive emotion, sense of control, physical health, self-satisfaction, and psychological vigilance. OHI comprises 29 items, each involving the selection of one of four options that are different for each item.The OHQ includes similar items to those of the OHI, each presented as a single statement which can be endorsed on a uniform 6-point Likert scale. The revised instrument is compact, easy to administer and allows endorsements over an extended range. When tested against the OHI, the validity of the OHQ was satisfactory and the associations between the scales and a battery of personality variables known to be associated with well-being were stronger for the OHQ than for the OHI. The scores range from one to six, and the average score can be used to determine the level of happiness. The higher the score, the higher the level of happiness ,33.In efficient samples, When pretesting the questionnaire, seniors who refused to go to social places had a low willingness to answer the questionnaire. In the formal questionnaire survey, the subjects were changed to elderly people who would go to social places and asked if they knew the third place theory. This study used a t-test to examine the difference between the awareness of third places and happiness, where the independent variables was awareness of third places and the dependent variable was happiness levels. The awareness of third places refers to the seniors who know the definition of the third place and have their own favorite third places. The number of the participants having the awareness of third places is 77 (38.5%), while those not aware is 123 (61.5%). Those in the former group had a mean of happiness of 4.05/6.0, while for the latter it was 3.83/6.0 see . ResultsFor more detailed analysis, we check the happiness levels among different participants’ frequency. This study used one-way ANOVA to compare the mean of happiness between groups of participants considering the awareness of third place; the independent variable was frequency and the dependent variable was happiness level. In comparison, the participants without an awareness of third places who go to social places in other frequency had a happiness value of 3.93/6.0. This was followed by “two or three times a week” (3.91/6.0), “once a week” and “once or twice a month” (3.77/6.0), and “at least once a day” (3.6/6.07). It was concluded that there is no significant difference in mean awareness of third places and frequency of visits with the mean of happiness. Although these differences were not significant, it is still worthy of further study. For broader perspective it would be possible to assume, that lower happiness may result in lower motivation to go out to third places.The data for social places of seniors in Taiwan are shown in This study used ANOVA to determine the difference between the mean of happiness and living situation. There may be some possible limitations in this study. This study is based on study time and conditions, so the research object was seniors living in the metropolitan area of Taiwan. The factors affecting social willingness and ability to go out are complex and diverse. This study only studies the gender, age, education level, marital status, financial status, and living situation of seniors, and does not discuss other factors. This study adopts the questionnaire survey method for investigation. Therefore, it is related to the respondents' understanding of the meaning of the question and the self-evaluation, which may cause errors in measurement. Therefore, the inference of the results of this study is limited to literate seniors living in the metropolitan area of Taiwan.The concept of the third place is not popular in Taiwan, and there are few studies. There are many studies on the happiness of seniors in various aspects, but there are few researches on the happiness of the living and social places of retired people. Based on the above literature review, aging in place is a very important social issue and government policy, and lifestyle in Taiwan is very encouraging for seniors to go out of their home into the community. The third place satisfies such living needs. Once the third place that seniors like is determined and a survey of happiness is used, various possibilities for the third place can be obtained.According to the results of this study, some conclusions can be made as follows:1. Results show that senior citizens with awareness of third places have more happiness than those that do not. Whether or not senior citizens are unaware of third places, there is no significant correlation between their frequency of going to third places and happiness. Therefore, we should encourage them to go to third places and engage in social activities frequently to achieve successful aging.2. The traditional market and supermarket are the favorite third places for senior citizens in Taiwan. The traditional market especially occupies a very high proportion in the choices of female seniors, while there is no item of significantly high proportions in the choices of male seniors. In addition, the proportion of those choosing “restaurant” is much higher in male senior citizens than in female senior citizens. Moreover, there is only one difference in the top five choices of men and women: for men, this is the inclusion of “friend’s house”, and for women “restaurant”. These two results are worth researching further. The Taiwan government uses most of senior welfare budget for community centers, senior citizen adult education institutions, and day care centers. In this study, the latter two types of place (senior citizen adult education institution and day care center) are low-ranking among the favorite social places for senior citizens. This situation should be reviewed and improved. In order to encourage more non-governmental organizations to participate in the aging industry, and even more people can participate in local creation, the results of this study are expected to give more choices to operators and users of third places, caregivers of senior citizens and senior citizens, and building an age-friendly environment.In addition, the research object of this study is limited to healthy seniors living in metropolitan areas. The follow-up research objects should be seniors living in rural areas and remote areas, and investigate the needs of seniors with reduced mobility. Further study should focus on the attraction of different third places for seniors, the different choices between seniors with different lifestyles, and the correlation between happiness and various third places. The senior citizens in Taiwan have very low efficiency and willingness to fill out the questionnaires. In this context, an observation method and interview method are suggested to use for deeper research in the senior citizens’ preferences and behaviors related to third places.


Investigation of the slopes in the Wenchuan earthquake shows that tension failures appear in the upper part in many landslides. The typical failure mode can be generalized as “tensile-rupture and sheared-sliding” (TRSS). In this paper, the distinct element method (DEM) is employed to simulate the gradual failure process of the Tangjiashan landslide under the excitation of the Wenchuan earthquake. It is found that the first failure is the appearance of deep tension cracks on the top, and then shearing slip along the bottom. The posterior fracture is deep, steep, and rough, and the bottom shear slip surface has a relatively gently dip. The simulation shows the failure mode of TRSS in the slope can be well reproduced, and the geological and mechanical mechanisms can be revealed in the DEM model. A large earthquake is capable of triggering thousands of landslides over a large area3. In general, the presence of discontinuities has a profound influence on the stability of rock slopes5. A novel method for correcting scanline-observational bias of discontinuity orientation is proposed to for discontinuities modelling6.The term “landslide” describes a wide variety of processes that result in the downward and outward movement of slopes consisting of rock, soil, tailings, or a combination of them. Seismically induced landslide in mountainous regions is one of the most serious geological hazards. Slope failures resulting from earthquakes often cause extensive damage to lifeline systems and transportation networks7 has been most commonly adopted, in which a landslide is described by the type of movement and materials. Keefer2 categorized earthquake-induced landslides into two types, landslides in rock and landslides in soil. Landslides in rock is further divided into two classes, i.e., (a) disrupted slides and falls; (b) coherent slides. Hutchinson8 provided a classification considering geology and hydrogeology environment. A European classification was developed from the EPOCH project, which was suitable for European conditions9. Dikau et al.10 provided a classification of the landslide, combining the opinions of Hutchinson8 and EPOCH9.For the problems they care about, many researchers have put forward corresponding classification methods. Some of them are listed in Table 11. Based on the geologic condition, the slope failure modes can also be described by whether it is obviously controlled by discontinuities12. In the occurrence of the Wenchuan earthquake in 2008, many catastrophic landslides were triggered in the earthquake zone. Huang et al.13 defined a classification of slope failure under the Wenchuan earthquake considering the failure mechanism and dynamic process. This approach is more targeted but may encounter difficulties in the application and promotion. However, considering geo-mechanics and dynamic features, Dai et al.14 classified the landslides in the Wenchuan earthquake into four broad categories: shallow, disrupted landslides; rock falls; deep-seated landslides; and rock avalanches.Located between pacific seismic zone and Euro-Asia seismic zone, China suffers from frequent earthquakes and endure heavy disasters. According to the characteristics of slope movement, the landslides in the southeast of China can be classified into four types: pushing landslide, hauling landslide, bedding landslide and avalanching landslide18 developed a method to classify the landslides induced by the Wenchuan earthquake into five types; it is changed to four types later as adjustment. In their system, the basic and internal deformation and failure mode in the large-scale landslides induced by strong shock are classified based on the type of tension-cracks and shearing sliding. In their investigations, Zheng et al.19, Xu et al.17and Yan et al.20 found that in the Wenchuan earthquake the tensional failures appear in the upper part of the most landslides, and in some slopes some rock and soil masses were even thrown out through the top fractures. The impact of the earthquakes on the slope can be assessed quantitatively, but is still very difficult to achieve, considering the complexity and variety of landslide types21.Xu et al.22 to model the progressive failure process of the rock slope loaded by a strong seismic shock and analyze the TRSS failure mechanism of the landslide during earthquake.Ten years after Wenchuan earthquake, we can have new insights into the failure mechanism of the landslides induced by the earthquake. In this study, we use term “tensile-rupture and sheared-sliding” (TRSS) to describe this kind of destruction phenomenon, that is, under the earthquake condition, the first location of the slope failure is the appearance of tension cracks on the crest, and then shearing sliding along the bottom slip surface; after the tensile fracture and shear fissure are connected, landslide will be formed. The failure mechanism of landslides induced by the earthquake has been mostly qualitatively analyzed by the geologic field exploration. However, there is little or no information available in the literature on synthetic engineering geologic analysis and dynamic response computation of landslides under excitation of an earthquake. Based on the geologic data and analysis methods proposed by the early researchers and the experience in numerical modeling in recent years, we applied Distinct Element Method23. Under gravity loading, the stresses of the shallow part of the slope are: the vector of maximum principal stress is basically parallel to the slope surface and the vector of minimum principal stress is basically perpendicular to the slope surface. In this stress state, shear stress concentration occurs near the slope toe, as confirmed by some existing studies, e.g., in Jumikis24. It is also possible that there will be shearing deformation and failure along the middle, gentle dip discontinuities of the slope.Analytical solutions for the elastic medium under gravity with an irregular surface of a slope are difficult. The problem may be studied by the photoelastic method or finite element methods19 applied FLAC3D strength reduction with the functions of tensile and shear failure to study the failure of a slope under earthquake loading. The study shows that the dynamic failure of the slope is a composition of the tensile failure in the upper part and the shear failure in the lower part instead of shear sliding failure. Xu et al.17 found from the vibration platform experiments that the strong inertial force produced from the earthquake is the main cause of landslides. The strong horizontal seismic inertia force induces the vertical fracture perpendicular to the direction of the seismic force on the slope top firstly, at the same time, it also drives the fracture of the lateral deformation along the horizontal direction. The nearly horizontal outward tension-shearing fracture is generated, and the global instability of the slope occurs eventually.Zheng et al.25 think that the most important changes in their perception and understanding of rock fracture in the earth's crust have come about because of the application of fracture mechanics in geophysics. The concepts are equally valid and applicable in many other fields of research, such as in geotechnical engineering where the failure of jointed rock masses and failure in soil slopes are of major concern26. In essence, fracture mechanics concerns the study of stress concentrations caused by sharp tipped flaws and the conditions for the propagation of these flaws. The theory of linear elastic fracture mechanics (LEFM) uses an analytical approach that will provide useful analytical steps. This method is valid provided that any region of non-linear behavior is negligibly small compared with the length of the crack and the dimensions of the cracked body27. There are three basic modes of crack tip displacement, which are termed model-I, tensile, mode-II, in-plane shear and mode-III, anti-plane shear. A key concept in the use of fracture mechanics is that extension of a fracture will occur once a critical value of stress intensity factor, Kc, or crack extension force, Gc, has been reached or exceeded. When θ = 0, the Kc value for mode-I and Mode-II can be defined asσy is the tensile stress normal to the crack surface, r is the distance measured from the crack.Li and Ricep is Poisson’s ratio, E is Young’s modulus.For fracture in each of the fundamental modes of crack tip displacement, the crack extension force for plane strain and assuming linear elasticity is given byK or G has been reached, the crack propagation is known as fast or catastrophic fracture. There are several kinetic laws for crack extension and they share the common formv is the crack velocity. The specific form of the crack velocity dependence on K or G depends on the precise mechanism whereby the energy barrier to crack extension is overcome. The subcritical crack growth is a general view of crack growth during long-term loading. The cracks formed under earthquake should belong to catastrophic crack propagation. With the help of theory of LEFM, the velocity of crack expansion under earthquake can only be calculated primarily, it’s limited to the several simple conditions. It seems that numerical simulations will result in more comprehensive results.Once the critical value of It can be inferred that, under the condition of strong earthquake and the amplification effect of elevation, the stress produced by horizontal seismic wave will be much higher than the tensile strength of rock mass, therefore, the vertical fracture surface nearly parallel to the slope surface is easy to be generated Fig. . Evident28 provided that the presence of tension fractures on the top of a slope should be taken as an attention of potential failure. This conclusion is also applicable to the analysis of slope stability under seismic conditions. It is possible to use UDEC interfaces to model Mode I crack propagation29. We have used UDEC30 to analyze the occurrence and development of the tensile-shear failure mode in seismic dynamic loading of an ideal jointed rock slope33. The Tongkou River snakes through the landslide area  occurred along the LCFZ with an epicenter depth of 19 km . The seismic intensity in the area of the landslide was XI. Tangjiashan slide was induced by the earthquake almost simultaneously, and it was the most hazardous of the 40 or so valley-blocking landslides triggered by the shock of the world34. The main strata of the slope are the lower Cambrian system/(∈1), contains siltstone, silicalite, marlite, and mudstone. The rocks are well bedded striking EW and dip moderately to steeply towards the north. The landslide also involved the alluvial deposit of Quaternary sediments . These strata of the slope are dipping outward (North direction) and forming a bedding slope of steep incline  will barrel down into the river. The people in Beichuan County (around 6.5 km downstream) will suffer the worst battering if the blockage cannot be excavated timely. The engineer used digging equipment and explosives to dig a drainage channel in the dam to ease water from the dangerous lake and relieve the pressure behind it. On June 7, 2008, the channel was completed and the water can flow downstream.After the landslide occurrence, with a volume of 20 million m36. The mechanical parameters of rock masses and joints are listed in Tables UDEC is used as a computing tool here. As for the Tangjiashan slope model, the blocks in UDEC are assumed as the elastic-perfectly plastic bodies following the Mohr–Coulomb failure criterion this time; the joints are considered as face-contacted Coulomb sliding model. In the DEM, a rock mass is represented as an assembly of discrete blocks. Joints are viewed as interfaces between distinct bodies. The contact forces and displacements at the interfaces of a stressed assembly of blocks are found through a series of calculations that trace the movements of the blocks. In turn, movements result from the propagation through the block system of disturbances caused by applied loads or body forces. This is a dynamic process in which the speed of propagation depends on the physical properties of the model2 in the vertical direction and 5.81 m/s2 in the horizontal direction. Cui et al.32 and Cao et al.33 did not explain the specific channel of horizontal acceleration wave. Xu et al.37 pointed out the horizontal acceleration data he adopted was in an east–west direction. He considered the two horizontal accelerations were equal and the vertical acceleration was 2/3 of the other directions. In this study, we used three accelerations collected form Bajiao town seismic station. The two horizontal accelerations are synthesized following the principle of vector summation as the input horizontal wave. The input vertical acceleration is real data from Bajiao town seismic station. The dynamic analysis conditions are listed in Table Bajiao town seismic station is the nearest station recording the seismic wave to the landslide Fig. a, the diαd is the local damping ratio; ∆t is the time increment.For deformable blocks, the equations of motion are expressed by the following equation, which incorporates local damping:mi is the mass associated with block node i; and ki is the measure of the stiffness of the elements surrounding the node i.The solution scheme used for the distinct element method is conditionally stable. A limiting timestep that satisfies the stability criterion for both calculation of internal block deformation and inter-block relative displacement is determined. The timestep required for the stability of block deformation computations is estimated asThe actual input seismic wave shown in Fig. The UDEC model need to be at an initial force-equilibrium state under gravity loading before the seismic excitation is applied to the slope. Figure 35. The air cushion effect is similar to the Tsaoling landslide in Taiwan during the Chi-Chi earthquake38. Since the frictional resistance between the landslide body and the sliding surface is reduced by the action of air cushion, the landslide body tends to move at a high sliding velocity. The front of landslide body sharply slides down until it is blocked by the opposite slope which angel is 25°–40° and the high-speed landslide rapidly moves downwards and then climbs up the opposite slope. At the moment, the back of the landslide body is continuously sliding down until blocks the river and then, the dam-created lake is formed. That is, after the accumulation phase, a negative terrain between the toe and the head of the landslide is formed at the end.The slope goes into the sliding phase when the deformation accumulates to a certain degree. The high potential energy of the landslide body is converted into kinetic energy continuously during the sliding process, and the strong friction will produce huge heat. When the landslide body is sliding at a high velocity, the air under it is hard to evacuate rapidly and form the air cushion to sustain the landslide body. According to local villagers, the duration of airwave caused by the earthquake is less than 0.5 minThe movement process of the landslide body during the whole sliding process can be observed clearly in the model as demonstrated in Fig. The occurrence condition of TRSS is closely related to geological condition, earthquake wave and topographic condition, which can be investigated using the method that we developed in this study, although our focus here is to understand the failure mechanisms behind the observed failure mode. The pattern of TRSS is commonly observed in the Wenchuan earthquake area. It is reproducible in both the idealized conceptual model Fig.  and the In this paper, we focused on the landslide failure mode of TRSS which was commonly observed in the Wenchuan earthquake. Based on the results in the DEM simulation of the slopes under dynamic loading, the failure mechanism of TRSS landslide was analyzed. The stability of the Tangjiashan slope under seismic wave excitation was calculated, and the gradual failure process of the landslide was also simulated. It is found that the discontinuities distribution and strong seismic force are important reasons for the formation of TRSS. This study shows that DEM modeling is an effective way to understand the geological and mechanical mechanisms behind the landslide induced by seismic loading through reproducing the gradual disintegration process and the discontinuous characteristics of the landslide. In a word, we couple engineering geologic analysis and numerical computation to verified a seismic-induced landslide type-TRSS.


Fever developed in 665 of 6336 patients (10.5%) with a mean peak body temperature of 38.3 °C . Multivariate analysis revealed that fever-associated risk factors after EBUS-TBNA are older age , p = 0.015), bronchoscopic washing , p = 0.012), more than four samples of EBUS-TBNA , p = 0.007), hemoglobin levels before EBUS-TBNA , p < 0.001), CRP levels before EBUS-TBNA , p < 0.001), and a diagnosis of EBUS-TBNA tuberculosis , p < 0.001). Clinicians should be aware of the possibility of fever after EBUS-TBNA because it is common. Additional, prospective, large-scale research should assess the need for prophylactic antibiotics for EBUS-TBNA.Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive diagnostic for mediastinal and hilar lymphadenopathy/mass. This study investigated fever incidence and associated risk factors after EBUS-TBNA in 6336 patients who underwent EBUS-TBNA at Asan Medical Center from October 2008 to February 2018. Bronchoscopists evaluated participants’ medical records for fever the 24 h following EBUS-TBNA. Patients were placed in either a Fever group ( Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) recently replaced mediastinoscopy for the determination of lymph node staging and diagnosis of thoracic diseases . Real-tiThe major complications recently published in case reports are empyema, lung abscess, mediastinal abscess, intramural hematoma of the pulmonary artery, hemopneumo mediastinum, needle breakage, and pericarditis ,14,15,16Incidence of fever after bronchoscopy has been reported to range from 5–14.2% ,19,20,21This study was a single center, retrospective study conducted at Asan Medical Center, Seoul, South Korea. We selected patients who underwent EBUS-TBNA between October 2008 and February 2018 . The purThe subjects evaluated for fever by a physician every six to eight hours during the first 24 h following EBUS-TBNA; then were divided into two groups (Fever group or non-Fever group) according to presence or absence of febrile complication. Fever was defined as a temperature rise of axillary measurement point more than 37.8 °C. Patients who had a fever for 24 h prior to EBUS/EBUS-TBNA did not receive the procedure.Patient demographic characteristics and clinical data were retrieved from database and electronical medical records. Clinical manifestation included age, sex, fever, height, weight, and forced expiratory volume in one second (FEV1). Comorbidity included diabetes mellitus, hypertension, and hepatitis. Clinical data included smoking history, past medical history, sample number in EBUS-TBNA, diagnosis following EBUS-TBNA, additional procedures within 24 h of EBUS-TBNA, antibiotic use within three days of EBUS-TBNA, mortality , and laboratory tests.Additional procedures within 24 h of EBUS-TBNA included bronchoscopic washing, bronchoscopic biopsy, core needle biopsy, transbronchial lung biopsy, incisional biopsy, endoscopic ultrasound-guided fine-needle aspiration, core needle biopsy of the liver, surgical biopsy, and excisional biopsy. Antibiotics were classified as first-generation cephalosporin, third-generation cephalosporin, penicillin with beta-lactamase inhibitor, quinolone, macrolide, carbapenem, glycopeptide, and others. Laboratory tests included measurement of the values of C-reactive protein (CRP), white blood cell (WBC), hemoglobin, platelet, neutrophil, lymphocyte, eosinophil, monocyte, basophil, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, gamma-glutamyl transferase (GGT), blood urea nitrogen (BUN), low density lipoprotein (LDL), and high density lipoprotein (HDL). Laboratory measurement were evaluated within one week prior to EBUS-TBNA.The primary assessed outcome was the incidence of fever after EBUS-TBNA. Secondary assessed outcomes were risk factors associated with a fever after EBUS-TBNA.18F-FDG-PET-CT.An expert pulmonologist (physician who has experienced EBUS-TBNA for over 10 years in department of respiratory medicine) performed the EBUS-TBNA procedures. Patients were placed in a conscious sedated state with midazolam. Lidocaine was administered for local anesthesia. A standard conventional flexible bronchoscopy  was initially used to examine the tracheobronchial tree. A linear array ultrasonic bronchoscope  with a dedicated 22-gauge needle  was subsequently used to perform all needle aspiration procedure. Lymph node or mass confirmed by imaging were located by ultrasound. TBNA was performed two or three times to obtain sample using real-time ultrasonic needle guidance through 2.2 mm working channel in the bronchoscope. When necessary, doppler ultrasound was used to identify vessels. TBNA was performed from distant lymph node/mass to avoid needle contamination by sampling highly suspected of metastasis on chest CT or p < 0.20. A two-tailed p-value of less than 0.05 was considered statistically significant. The data were analyzed using SPSS statistic software  and R packages .Categorical variables were analyzed using a chi-square test, and continuous variables were analyzed using Student’s t test. The odds ratios (OR) for the risk of fever after EBUS-TBNA were analyzed using a multivariate logistic regression model, including age, sex, any variables with a The Institutional Review Board of Asan Medical Center approved this study (IRB No. S2018-0440). The board waived informed consent because of the retrospective nature of the study. This study was performed according to the ethical standards of the Declaration of Helsinki, as revised in 2008.Of the 6773 cases who underwent EBUS, 6336 were included in this study except for 347 who did not undergo EBUS-TBNA . The incp < 0.001): (10 y ≤ age < 40 y) and (70 y ≤ age < 100 y) had a higher rate in the Fever group than in the non-Fever group, and (40 y ≤ age < 70 y) had a lower rate in the Fever group than in the non-Fever group (p > 0.05). A past medical history of tuberculosis and the 90 day mortality in the Fever group were significantly higher than in the non-Fever . There was no significant difference between the two groups in a past medical history of malignancy (p = 0.620). However, there was a significant difference in the past medical history of lung cancer (p = 0.002) (er group . There w= 0.002) .p = 0.004). More than four EBUS-TBNA samples in Fever group was a significantly higher rate than in the non-Fever group  (p < 0.001)  . An EBUS< 0.001) .p < 0.001, p = 0.030, and p = 0.039, respectively). The mean number of additional procedures in the Fever group were significantly higher than in the non-Fever group . Only EBUS-TBNA in the Fever group was significantly lower than in the non-Fever group . However, each of the ≥1 and ≥2 categories of additional procedures in the Fever group were significantly higher than in the non-Fever group   .p < 0.001). Hemoglobin, lymphocyte, protein, calcium, phosphorus, sodium, chloride, and cholesterol before EBUS-TBNA in the Fever group were significantly higher than in the non-Fever group   .p = 0.015), bronchoscopic washing , p = 0.012), more than four samples of EBUS-TBNA , p = 0.007), hemoglobin before EBUS-TBNA , p < 0.001), CRP before EBUS-TBNA , p < 0.001), and tuberculosis diagnosis following EBUS-TBNA , p < 0.001) (< 0.001) .We used receiver operating characteristic (ROC) curves to assess the statistical performance of the models for risk factors associated with a fever after EBUS-TBNA. The area under ROC was 0.712 .Fever after EBUS-TBNA was 10.5% (665 patients of 6336) in our study. A few previous studies have reported the incidence of fever after EBUS-TBNA. Kim et al.  reportedTo the best of our knowledge, this is the first study for revealing the risk factors related to fever after EBUS-TBNA. In a retrospective study of 552 patients who underwent EBUS-TBNA, Kim et al.  did not Although the cause of fever after EBUS-TBNA is unclear, transient bacteremia may be one of the possibilities of fever. Previous studies reported that transient bacteremia caused by oropharyngeal bacteria after EBUS-TBNA is a possible cause of fever after EBUS-TBNA ,11. Haasp < 0.001). There was significant difference in the case of receiving prophylactic antibiotics in the Fever group: bronchoscopic washing (p = 0.001), age (p = 0.044), hemoglobin before EBUS-TBNA (p < 0.001), and CRP before EBUS-TBNA (p < 0.001) (not presented). Antibiotics with the highest percentages between the Fever group and the non-Fever group were third-generation cephalosporin (28.9%), and penicillin with beta-lactamase inhibitors (29.4%), respectively  and all medications (including prophylactic antibiotics) are required to confirm the relationship between fever and EBUS-TBNA.


The presence and magnitude of SARS-CoV-2 IgG, IgM, and Neutralizing Antibody (NAbs) response was investigated in study cohort comprised of 58 volunteers who survived COVID-19 in a Virginia LTC facility. All subjects were confirmed positive by PCR nasal swab at least once and blood samples were drawn a minimum of 14 days post symptom onset or first positive COVID-19 test. The cohort was split between LTC residents , and the LTC staff ; the age difference between groups was statistically significant (P<0.001). Serum IgG measurement was quantitative over 5 orders of magnitude (0.6-1250µg/mL) and IgM was qualitative, measured with sandwich ELISA; NAbs were measured with surrogate virus neutralization assay (sVNT) competition ELISA (both Genscript). The convalescent older adult LTC patients were fully immuno-competent and showed no significant difference in IgG, IgM, or NAbs compared to the younger staff group. All older adults developed NAbs and were positive for either IgG, IgM, or both. All study participants were then grouped by age range and IgG, IgM, and NAbs compared between the following groups: ≤ 50 yrs old(n=20), 51-60(n=6), 61-70(n=8), 71-80(n=14), 81-90(n=6), and ≥91(n=4). There was no significant difference in immune response parameters between the age groups. Furthermore, repeat testing at 3 months on a subset of participants showed that NAbs, IgG and IgM persist. We conclude that development of competent immune response was age-independent, and that presence of NAbs in serum suggests older adults may develop true immunity.


Chronic diseases are responsible for over 70% of all deaths globally. While some self-management programs have been shown to be efficacious in preventing or altering trajectories for some chronic conditions, scaling-up and sustaining such programs beyond tightly-controlled study conditions remain a major challenge. CISSS-Laval partnered with the Cardiovascular Health Awareness Program team to co-develop Cible-santé/prévention and evaluate the first cohort of participants enrolled in the program, in order to better understand the program’s implementation and scope. The objective of the current study was to describe the profile of attendees and the level of engagement of participants in a new, region-wide cardiometabolic disease self-management program offered in Laval, Canada.This was a prospective study with no comparison group. Potential participants were identified and referred to the program from April to December 2015 by their primary care health professional practicing in one of the city’s interdisciplinary primary care clinics. They had their blood pressure, waist circumference and body mass index measured by trained volunteers, and completed a questionnaire on health habits, level of activation and the risk of developing prediabetes and type 2 diabetes over the next 10 years.A descriptive analysis of the first cohort of 141 Cible-Santé/prévention participants showed very low attendance. Furthermore, only 1 in 10 of enrolled participants completed the full program. The program typically attracted adults with some risk factors associated with their conditions , but with an already high level of knowledge, skills and confidence to participate in self-management activities.This study provides a portrait of new participants to a self-management cardiometabolic disease program, which highlights the potential of supporting patients ready to make changes but also exposes the difficulty of attracting a larger number and diversity of participants and in encouraging completion of the program.The online version contains supplementary material available at 10.1186/s12889-021-10558-6. Chronic diseases — including cardiovascular diseases, cancers, chronic respiratory diseases and diabetes — are responsible for over 70% of all deaths globally. Modifiable risk factors that include smoking, physical inactivity and unhealthy diets are the main drivers behind the growing epidemic of chronic diseases . While sParticipation rates in health promotion and chronic disease self-management programs are generally low , despiteProgram type and program location also influence attendance. The participation rates are higher when programs are offered in a variety of time and place settings, when there is no need for referral and when participation is free or low cost . Elzen aThe objective of the current study was to describe the profile of attendees and the level of engagement of participants in a new, region-wide cardiometabolic disease self-management program offered in Laval, Canada. The study took place in 2015 and looked at the first cohort of Cible-Santé/prévention participants.This was a prospective study with no comparison group.The intervention took place from April to December 2015 in one of the Local community services centres of Laval, a large predominantly French-speaking suburban community in the Greater Montreal region of the province of Quebec, Canada.Groupe de médecine de famille or GMF), had to be 18 years old or over, understand French and had to have at least one of the following conditions: type 2 diabetes, pre-diabetes, hypertension, pre-hypertension, cardiovascular disease, dyslipidemia, stroke/transient ischemic attack, heart failure, kidney failure, metabolic syndrome or peripheral vascular disease. There were no exclusion criteria.To be eligible for Cible-Santé/prévention program, patients had to be registered with one of Laval’s interdisciplinary primary care clinics  servicing over 400,000 residents of Laval, the second largest city in the province of Québec, Canada. The goal of the program was to help participants modify some of their unhealthy lifestyles in order to support the self-management of their cardiometabolic diseases. The program was led by an interdisciplinary team  trained in motivational interviewing techniques , 12. TheCISSS-Laval partnered with the Cardiovascular Health Awareness Program team to co-develop Cible-santé/prévention and evaluate the first cohort of participants enrolled in the program, in order to better understand the program’s implementation and scope. CHAP is a patient-centred, interdisciplinary, multi-faceted, community-led, cardiovascular disease prevention and management program targeting older Canadian adults. It was felt that a more detailed health profile of new participants could assist CISSS-Laval managers to optimize the recruitment strategies to make the program available to a wider range of participants and to better meet their needs. These findings might also offer useful insights that can inform similar future programs.Potential participants were identified and referred to the program by their primary care health professional practicing in one of the city’s interdisciplinary primary care clinics. Referral to the program was at the discretion of the health care professional, i.e., they were not required to refer all eligible patients or even a minimum number of patients. Referrals were sent to CISSS-Laval appointment centre, who subsequently contacted potential participants to enrol them into the program.Cible-Santé/prévention participants were invited to attend three group-based workshops and five individual follow-up sessions with a nutritionist, kinesiologist or nurse over an eight-month period. At their first group workshop, all first Cible-Santé/prévention cohort patients were invited to participate in a CHAP evaluation session.Building on 20 years of work around CHAP –22, the Data on demographic characteristics, health status, risk factors and patient activation were collected at baseline and were self-reported by participants  is a 13-item survey that assesses the knowledge, skills and confidence for self-management of one’s own health, and was developed by Dr. Judith Hibbard, Dr. Bill Mahoney and colleagues at the University of Oregon . To calcAll respondents who reported not being diagnosed with type 2 diabetes or being unsure were asked to complete the Canadian Diabetes Risk Questionnaire (CANRISK). Developed by the Public Health Agency of Canada, this validated questionnaire-based tool assesses the risk of developing pre-diabetes and type 2 diabetes in the next 10 years . Each anDuring the sessions, physical measurements were taken by trained volunteers and included waist circumference, weight and height , as well as participant blood pressure, using an automated measuring device, the Microlife WatchBP Office Afib, which allows dual-cuff measurement and atrial fibrillation detection .The total number of patients referred by health professionals practicing in one of the GMFs in Laval has not been recorded. Participants were initially referred by their primary care health professional (this number was not recorded). Afterwards, 270 participants registered for Cible-Santé/prevention Fig. . Of thesn = 141). More than half of the participants were 55 years of age or older, and the majority were female  had a waist circumference of more than 88 cm for women and more than 102 cm for men, and nearly 70% (97/140) were classified as obese. Over 17% had a diagnosis of hypertension (not shown in table) and more than a third had blood pressure above > 140/ 90 mmHg).Approximately half of participants reported eating the recommended daily servings of fruits and vegetables (four to six servings), and over a third of participants reported very little to no physical activity (16.8 and 18.3%) Table . Nearly n = 73) completed the CANRISK. More than 60% were classified as having high or very high risk of developing pre-diabetes or diabetes.Of all 141 participants who had participated in a CHAP evaluation session, 68 (48.2%) reported being diabetic  abandoned the program due to lack of motivation; some felt they had achieved their goals already and were satisfied with the changes made.First, Cible-Santé/prévention was a new program introduced in the already large spectrum of services provided by the regional health authority. Given that this was the first cohort of participants, a more comprehensive communication strategy might help raise awareness about the program and its goals. Second, the evidence suggests that when programs are offered in a variety of time and place settings, participation rates are typically higher . Cible-SThe profile of Cible-Santé/prévention participants suggests that they tend to engage in a relatively healthy lifestyle. This is also consistent with what is found in the literature, which suggests that people who engage in health promotion or self-management programs are more likely to already be adhering to healthier lifestyles . It is dNearly half of participants were considered highly activated (Level 4 of the PAM). People who engage in these types of programs are more likely to have a better understanding of their condition than patients who do not participate . Since hA limitation of the study is the lack of data regarding the number of professionals who referred their patients to the program, and the reasons for never attending a Cible-Santé/prevention workshop after registering. This study was conducted in a real care setting and in collaboration with program managers, which explains the absence of certain data (missing denominator). This would have allowed us to know the proportion of referred patients who subsequently enrolled in the program, and thus know the number of patients who follow-up on such referrals.Another limitation of this study is the lack of a control group. Having a comparison group with similar baseline characteristics, that would not have participated in this chronic disease self-management program or maybe enrolled in a different program, would have enabled us to better assess the characteristics associated with recruitment and participation.Finally, some measures were self-reported by respondents, including physical activity level, fruit and vegetable consumption, and smoking status, which may have influenced the validity of the responses given. Otherwise, trained volunteers under the supervision of a nurse took physical measurements, including blood pressure, body mass index and waist circumference, on-site.The study was the first evaluation of this new regional cardiometabolic disease self-management program. It was intended to describe attendance, activation and health profiles of first-cohort participants, and can serve as a precursor to further testing of the program. An evaluation of its effectiveness and impact on health outcomes and behaviours would help determine whether the Cible-Santé/prévention needs to be continued in its actual form, be redesigned or abandoned.The evaluation by the CHAP team made it possible to draw a health profile of the first cohort of Cible-Santé/prévention participants. CHAP volunteers were trained to adequately measure blood pressure, body mass index and waist circumference, and to assist participants in completing their questionnaires. The results showed a very low attendance and program completion rate. The program typically attracted adults with some risk factors associated with their chronic conditions , but with an already high level of knowledge, skills and confidence to participate in self-management activities.This study provides a portrait of new participants to a cardiometabolic disease self-management program, which highlights the potential of supporting patients ready to make changes but also exposes the difficulty of attracting a larger number and diversity of participants and in encouraging completion of the program. Further studies are needed to assess the effect of the program on self-management skills and health outcomes of participants, test several recruitment strategies to increase the diversity of the target population and to compare participants’ health profiles with non-participants.Additional file 1.


We used well-established measures with appropriate psychometric properties. The study used a quasi-experimental design of pre-test/post-test repeated measurements with a control group. First, a multivariate analysis of variance (MANOVA) and then descriptive analyses and variance analyses (ANOVAs) were carried out by the adolescents randomly assigned to the experimental and control conditions. Then, a multivariate analysis of covariance (MANCOVA) was performed on the study’s variables as a whole. Descriptive and covariance analyses of the post-test scores were carried out , in order to demonstrate the impact of the program. The effect size was reckoned (Cohen’s d). The results confirm statistically-significant differences in: Health-Related Quality of life, positive affect and mental health. The study provides an effective intervention tool which has been experimentally validated. The overall results allow for emphasizing the importance of the implementation of programs aimed at encouraging social and emotional learning throughout adolescence as protective resources in fostering emotional and behavioral adjustment in adolescents.The aim of this study is to experimentally assess the effects of an intervention program through a video game called “Aislados” for the improvement of subjective well-being, mental health and trait emotional intelligence of a sample of adolescents ( The aim of education is the integral development of the personality of the students, promoting cognitive, personal and social competencies. Therefore, schools should not only promote the academic growth of students but also their personal growth ,2. Some The European Council considers personal and social skills and learning to learn as key competencies for a successful life in society and of equal importance to the other seven key competencies such as digital or multilingual competencies . ResearcIn addition, the WHO defines SEL as a collection of life skills  and, theThe evaluation of the effectiveness of the SEL programs shows positive results on academic achievement of the students, on mental health, on psychological and social adjustment and on positive behaviors in health ,9,13,14.Among the different strategies that can be used to introduce and teach social emotional learning skills to kids and young people, games are a good option to create fun environments to engage them in learning activities that help kids become more self-aware, develop positive relationships, show empathy towards others, manage emotions, use self-control, resolve conflicts, and make positive decision . InsofarVideo games are one of the most popular recreational activities among young people nowadays . ExploriIn the other hand, this negative impact of video games has been questioned in recent studies ,27,28 thFocusing on emotional intelligence (EI) and well-being, the use of video games among adolescents, like popular Pokemon Go, has been confirmed as a tool for the enhancement in selective attention, concentration and sociability  and, in There are examples of successfully application of video games educational strategies for the improvement of socioemotional skills. For instance, the application of the video game “Spock” show how the emotional intelligence capacity  and the http://www.aislados.es/ financed by the Government Delegation for the National Plan on Drugs). It has been designed as a protective resource for adolescents by means of improving their psychological well-being and empowering them to avoid young risk behaviors related to addictions, violence or emotional disorders. This strategy has been recently proven by the evidences that show how emotional indicators like self-esteem, quality of interpersonal relationships, control of life events, and management of negative emotions, can lead to depression and social and educational impairment, becoming an important risk factor for substance misuse [The current study presents an intervention program called “Aislados” that considers the theoretical assumptions of Social and Emotional Learning (SEL) by using video games as an educational tool. “Aislados” is an educational program for middle and high school students developed in 2016 by the Interdisciplinary Service of Attention to Drug Dependencies  and founded by National Spanish Plan against Drug addictions . Both games, video game and role-playing game, are based in the same principles and educational structure and has to be completed by educational sessions driven by teachers. Video game and role-game are educational strategies very suitable for SEL interventions as stated by Weissberg et al.  when thehttps://www.youtube.com/watch?v=I6N41WREYbY&list=PLLrCXpyb6EFLnQWoDScEc33VsUqPE-5kx&index=3 (Spanish with English subtitles available through YouTube translation). The player interacts with those characters getting involved in conversations to get information for task achievement or solving riddles that are included in the video game. Thus, the “Aislados” video game provides a virtual environment where the main goal of students is to reach a full understanding of the character’s personalities and emotional states, developing positive affect towards characters and deploying emotional intelligence to understand the problems and situations involved at every conversation or interaction. Very interestingly, those activities are being held individually by students, in a way that makes more interactions possible and a more flexible environment for each student to develop their own emotional strategies to solve game tasks, which is an opportunity for the personalization of the learning process of this type of socio-emotional competencies. The intervention program is complemented through explicit instruction (sessions) by teachers for full understanding of emotional situations and decisions taken by players (students) during the game. Thus, the idea that SEL-based programs should encourage activities both inside and outside the classroom, including reaching the community, is emphasized [“Aislados” video game consists of a set of virtual characters deployed in an imaginary boat traveling to some newly discovered islands : the cognitive component (satisfaction with life) and the affective component (positive and negative affect) ,48. The Currently psychological research is interested in the study of how positive psychological variables affect personal development ; this isIn sum, the aim of research is to assess the effects of this intervention program for the improvement of SWB, mental health and trait emotional intelligence among a sample of Spanish adolescents of middle and high school age. We adopted a quantitative approach to explore the following specific hypotheses regarding the impact of “Aislados” Program on Spanish adolescents: (1) It will enhance the SWB; (2) It will increase mental health (MH); (3) It will increase trait EI (TEI).n = 97) and control (n = 90) condition in the pre-test stage. The data were provided by middle and high school students (53% girls). The sample has been made up of 187 adolescents, aged 12 to 17 (M = 13.82 SD = 1.62). A non-probabilistic sampling was used, but subjects are assigned at random to the experimental  students previously removed from school for disciplinary reasons; (b) students with special educational needs related to intellectual disability; and (c) students not attending at least 75% of the intervention programme sessions. In this study, we used well-established measures with appropriate psychometric properties see .This self-report version contains 10 items to assess subjective Health-Related Quality of Life (HRQL) and well-being; it provides an index of global HRQoL covering physical, psychological and social facets. It is related to the cognitive component of well-being. The questionnaire can be completed by children and adolescents aged from 8 to 18 years. Questions are on 5-point Likert scales from “never” to “always” or from “not at all” to “extremely”. SWLS is a short 5-item self-report questionnaire where people judge whether their life is satisfying on a 7-point rating scale, from 1 = strongly disagree to 7 = strongly agree. The scale provides a global measure of life satisfaction. It is related to the cognitive component of well-being.PANAS is a self- reported adjective checklist designed for the assessment of 20 different feelings and emotions. It contains two subscales with ten items each, representing two constructs: positive affect  and negative affect . It is related to the affective component of well-being. Participants used a 5-point scale ranging from 1 = ‘‘very slightly or not at all’’ to 5 = ‘‘extremely’’.MH-5 is one of the subscales of the SF-36 Health Questionnaire. MH-5 is a short 5-item self-report questionnaire that assesses general mental health, specifically depressive and anxious symptomatology in the past month. It is related to the cognitive component of well-being. Participants respond to a 6-point rating scale, ranging from 1  to 6 (never). It is a self-report inventory designed to measure global trait emotional intelligence which contains 30 items, with Likert scale response options ranging from (1) “Completely disagree” to (7) “Completely agree”. The measure provides a total score which is obtained by adding up the 30 items. The study followed a quasi-experimental design of repeated measures (pre-test and post-test) including a control group, where following variables were assessed: Health-Related Quality of Life (KIDSCREEN), Satisfaction with Life (SWLS), Positive Affect (PA) and Negative Affect (NA), Mental Health (MH), Trait Emotional Intelligence (TEI). Students were requested to complete anonymously the measures mentioned before. All participants were assured that the data would be kept confidential and would be used for research purposes only. Specifically, the participants of the experimental group were informed of the purpose of the investigation.At first, the tests were applied to the experimental and control groups. Subsequently, the intervention program was implemented in experimental groups during the school day and within school schedule. In the following academic year, after the evaluation of the effects of the program, the control group participated in the program in the same way as experimental group; within the Tutorial Action Plan of the Guidance Department, whereby activities usually focus on social skills and guidance, personal, academic and professional. Specifically, the intervention consisted of 28 h-long sessions, with duration of 55 min each, carried out weekly during a school year. The sessions were carried out during the tutoring hour in secondary education (weekly timetable). The program was implemented by secondary teachers who voluntarily decided to participate in “Aislados” training. After the intervention, in the post-test stage, pretest measures were administered again to the experimental and control groups. Control groups received the same intervention after the study.Teachers received official training supported by the Department of Education through a 10-h workshop about the implementation of the program. In addition, weekly coordination meetings were held to agree on the development of each of the sessions in class, as well as the explanation of the instructions of the video game to the students .The video game “Aislados” is inspired by the four elements that facilitate the implementation of programs according to The Collaborative for Academic, Social, and Emotional Learning (CASEL): (1) Sequenced (connected and coordinated activities to foster skills development); (2) Active (active forms of learning to help students master new skills); (3) Focused ; (4) Explicit  .The “Aislados” video game includes interactive activities that aim to improve socio-emotional skills. The video game presents hypothetical situations that require the implementation of intrapersonal and interpersonal competencies. Students have to decide which answer alternative is most appropriate for the situation. Its primary objective is to improve teenagers’ emotional intelligence skills such as self-esteem, assertiveness and decision making, in order to manage their social life improving health and well-being and avoiding addictions and violence. Program sessions are detailed in First, a multivariate analysis of variance (MANOVA) was performed with total pretest scores from the variables included in the study in order to confirm the possible pretest difference in the variables, as a whole, between experimental group participants and control group participants. Second, in order to determine the program’s effect, descriptive and variance analyses (ANOVAs) were carried out with each one of the scores obtained for the instruments used during the pretest phase. Third, having confirmed the homogeneity of the two groups a priori, and in order to determine whether the change was significantly different in experimental group versus control group participants, a multivariate analysis of covariance (MANCOVA) was performed on the study’s variables as a whole. Besides, descriptive analyses and analyses of covariance were performed on posttest scores (posttest ANCOVAs co-varying for pretest scores), in order to analyze the impact of the program for every variable of the study. Lastly, the effect size was analyzed (Cohen’s d)  .Results obtained in the pretest or basal evaluations are first presented, followed by the results for evaluating the impact of the “Aislados” Program in the variables studied. p = 0.241, with a small effect size .The pretest MANOVA results did not reveal statistically significant differences between the groups prior to the intervention, Wilks’ Lambda, Λ = 0.472, F (5182) = 0.742, Results from the ANOVAs in the pretest phase see  showed tp = 0.004, with an average effect size . Results from the pretest-posttest MANCOVA revealed significant differences between the two conditions, Wilks’ Lambda, Λ = 1.414, F  = 4.373, d = 0.22), Positive Affect (d = 0.38) and Mental Health (d = 0.29).Analyses of covariance (ANCOVAs) were subsequently performed on the pretest-posttest scores in each one of the variables in the experimental and control groups. The results are shown in The present study analyses the effects of video game intervention program called “Aislados” for the improvement of SWB, mental health and trait emotional intelligence among a sample of Spanish adolescents of middle and high school age. There is a growing body of literature on SEL intervention programs; these studies provide evidence that SEL competencies can be beneficial to students, whether in or out of school . HoweverResults showed statistically significant differences between adolescents that received the intervention compared to those that did not participate in the program. Differences between both groups refer to some variables that were assessed. Then, the findings show that “Aislados” produced improvements in experimental group participants in terms of the following variables: (1) a significant increase in health-related quality of life, related to the cognitive component of SWB (CWB); (2) a significant increase in positive affect, related to the affective component of well-being (AWB); (3) a significant increase in mental health; (4) There are no significant improvements in trait emotional intelligence.First, these results support the effectiveness of the “Aislados” program in improving of some SWB components, partially confirming hypothesis 1. The results are consistent with those found in other studies which have shown efficacy of SEL programs to improve SWB in children and adolescents ,5,15. ThSecond, the results confirm hypothesis 2 and reveal that the “Aislados” program would improve participants’ mental health (MH). These findings are similar to those found in various meta-analysis and research studies that show improvements in mental health, as well as the reduction of emotional problems through the implementation of SEL-based programs ,8,9. FroFinally, the results fail to confirm hypothesis 3, which stated that the “Aislados” program would improve participants’ trait EI (TEI). The data do not match that obtained in other studies finding that EI increases when students participate in a video game ,42. ThesIt is important to point out some research limitations; first, regarding the generalizability of the results, obtained in a specific sample of secondary students from Spain. Furthermore, future studies should consider involving university students. Also, the study could be replicated in international contexts. In sum, although preliminary but promising, further research with the “Aislados” program is required to replicate and extend these findings and to test its application with larger and more diverse samples of students. A limitation of the present study refers to the critique of the heterogeneity of interventions that claim to be based on SEL and the possible comparison of results . This meIn addition, it is advisable to carry out a long-term follow-up evaluation in order to examine whether the “Aislados” program effects were maintained over time ,72.Despite of limitations, the results show that the program produced a positive effect, promoting an increase in SWB and providing benefits in the quality of life related to health, positive affect and mental health in adolescents. Regarding the future lines of research, it would be convenient to evaluate the effect of “Aislados” on other variables such as socio-educational adaptation, social competence, interpersonal relationships or academic performance. For future studies, it would be necessary to examine the Aislados program’s effects on health-related quality of life (HRQOL) in line with other findings related to internet addiction and other online activities .Likewise, it would be advisable to consider the possibility of investigating the influence of socio-emotional competencies and the psychological characteristics of the teachers who apply the intervention program.In view of the results, we want to highlight the importance of implementing programs during adolescence and youth to promote emotional and behavioral adjustment to improve both personal growth and well well-being. Those results can also improve academic performance and prevent/reduce of risky personal behaviors and act as protective resources for coping daily demands. Those are conclusions related to the significant increase of SWB, mental health and trait emotional intelligence that has been proved by the analytical study.Taken together, the findings reported in this study mainly support the importance of implementing programs to promote crucial social and personal competencies in the citizens of the future. Education administrators need to apply innovative strategies for teaching those new competencies related to social and emotional skills. In this regard, “Aislados” video game and its related intervention program have been proved as an effective educational strategy for that purpose. This educational program has been implemented in several educational activities in and out of school and is currently implemented in two countries Spain and Dominican Republic in the context of educational projects. Empirical evaluations of these experiences are being held to a better understanding on how this can help students belonging to different cultural contexts to develop skills related to SEL and to prevent health problems.


Diarrheal and acute respiratory infections remain a major cause of death in developing countries especially among children below 5 years of age. About 80% of all hospital attendances in Kenya can be attributed to preventable diseases and at least 50% of these preventable diseases are linked to poor sanitation. The purpose of this study was to assess the impact of a community-based health education program, called Familia Nawiri, in reducing the risk of diarrhea and respiratory infections among people living in three rural Kenyan communities.Cases were defined as patients attending the health facility due to diarrhea or a respiratory infection while controls were patients attending the same health facility for a non-communicable disease defined as an event other than diarrhea, respiratory infection. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a logistic regression model to assess the risk of diarrheal or respiratory infection in association with exposure to the health education program.There were 324 cases and 308 controls recruited for the study with 57% of the cases and 59% of the controls being male. Overall, 13% of cases vs. 20% of control patients were exposed to the education program. Participants exposed to the program had 38% lower odds of diarrhea and respiratory infections compared to those not exposed to the program . A similar risk reduction was observed for participants in the study who resided in areas with water improvement initiatives . Variables in the adjusted model included water improvement projects in the area and toilet facilities.Findings from this study suggest participants exposed to the education program and those residing in areas with water improvement initiatives have a reduced risk of having diarrhea or respiratory infection. Diarrhea and acute respiratory infections remain a major cause of death in low income countries especially among children below 5 years of age accounting for about 9 and 13% of annual deaths respectively . FurtherWhile notable progress has been made - including a 53% decrease in the worldwide mortality rate of children below 5 years between 1990 and 2015 . The GloHand washing is one of the best studied hygiene practices in resource constrained settings. Findings from randomized controlled trials (RCTs) and observational studies on hand washing with soap have shown reduction in diarrhea of between 30 and 47% , 11. A 2A World Bank review found hygiene promotion including hand washing to be the most cost effective intervention for disease prevention at a cost of approximately $3.4 for each disability-adjusted life-year saved . DespiteThis study evaluates a community-based health education program implemented in selected parts of Kenya. The program was implemented by Familia Nawiri , a social venture program initiated in Kenya by Novartis, a multinational pharmaceutical company in three rural settings in Embu, Kirinyaga and Nakuru counties . The eduThe purpose of this study was to evaluate the Familia Nawiri community based health education program in reducing the risk of diarhoea and respiratory infections by comparing the odds of exposure to the education program in cases diagnosed with diarhoea or respiratory infections to the odds of exposure to the education program in controls without diarhoea or respiratory infections.The program focused on community-based health education at a group level as a way of encouraging lasting behaviour change. The groups comprised of women, men, church, youth and table banking  groups with majority being women. The choice to deliver the health education through the group platform was based on the high prevalence of self-help and informal money saving group among others in the rural setting , 29. SinThe hygiene education curriculum comprised two parts, namely, personal and environmental hygiene. Key messages under personal hygiene included body hygiene, dental hygiene, proper hand washing practices and the importance of good hygiene in preventing contagious diseases. Messages on hand washing were coupled with a demonstration on proper hand washing procedure. Key messages on environmental hygiene included main water sources, water treatment methods, importance of clean environment including household surfaces, floors, clothes, outside living area, bathroom, latrines, cooking areas and dishes. There was also an emphasis on having improvised hand washing stations with soap near the toilet facilities to encourage hand washing at critical times, including a demonstration on how to construct these hand washing stations. Each group received at least 2 sessions on each part of the hygiene curriculum, each session lasting 20–40 min. The education sessions took place during the regular meetings for the different groups. The sizes of the groups differed depending on the purpose of the group’s existence but mainly ranged from 10 to 200 - though not all members attended the education sessions. For this study we are not able to report the actual number of people who attended the awareness sessions as these were not recorded at the program level. The education sessions were conducted in a participatory manner with both the health educators and the participants contributing to the questions and discussions.A health facility-based case-control design was used to assess the impact of the education program on reducing the risk of diarrhea and respiratory infections. The rationale for this approach was based on the fact that there were no baseline outcome measurements available to allow for a before and after design. An RCT or a prospective observational study would be a more appropriate design in certain situations to evaluate the effect of an intervention. However, in our case, the program sponsors designed and implemented the program without a specific plan to do an assessment of the effect of the program. When we decided to assess the program, it had already been implemented, and therefore, any prospective assessment was not feasible anymore, and therefore we decided to conduct a case-control analysis bearing in mind the limitations inherent to that design.The study was carried out in three counties in Kenya, namely Nakuru (Molo constituency), Kirinyaga (Mwea constituency) and Embu (Manyatta constituency) which were the initial pilot sites for the Familia Nawiri community health education program.A total of six health facilities in Nakuru County, eight in Kirinyaga County and five in Embu County were selected based on their location in the target areas where the education program had been implemented. Participants were eligible for the study if they attended the health facility during the study period (June 2014 to November 2014) and if they were residents of the same village for more than 6 months. Children who were accompanied to the health facilities by a parent or a legal guardian who was willing to take part in the study and able to provide written informed consent on behalf of the minor were also included in the study. Where children were recruited into the study, data on the main caregiver such as attendance of Familia Nawiri Health Education program were obtained from the accompanying parent or guardian. Cases were defined as patients attending the health facilities because of diarrhea or respiratory infection. In line with the definition by the Ministry of Health of Kenya , the worMobile electronic data collection was employed for this study. The questionnaire used was adapted from a previously published World Health Organization questionnaire  that hadData collected included socio-demographic factors, hygiene practices, and behaviour . Personal hygiene was assessed using a series of practice and behaviour questions. Seven of the questions related to critical hand washing time points such as before eating, after handling child’s stool and after visiting the toilet. The behaviour was then evaluated as a whole and awarded a composite score with each correct answer yielding 1 point while every wrong answer yielding zero points. Factors causing diarrhea and the health seeking behaviour for illness due to diarrhea and respiratory infections were assessed in a similar fashion.The CHEWs underwent an intensive one-day training prior to commencing data collection. The training focused on the data collection protocol including basics of conducting interviews, pretesting of the survey instruments for suitability and appropriateness, field logistics, general orientation to using the mobile devices and the data collection software, accessing the questionnaire on the phone, trouble shooting and handling technical difficulties with the mobile device. Special attention was paid during training on interview techniques especially the avoidance of asking ‘leading’ questions. A pilot test in which the CHEWs conducted interviews with each other and inputting dummy data into the app, was conducted prior to starting data collection in order to allow them to gain familiarity with the app, to test our processes and to allow minor adjustments to the data collection instrument.The sample size for this frequency-matched case-control study was estimated using formulary as described by  for a bip-value until a final model was obtained.Data were entered into Stata software, StataCorp.2013  (for anap = 0.03) [adjusted for other water improvement projects and presence of toilet facility]. Table Overall, 640 questionnaires were completed by 330 cases and 310 controls. Out of the completed questionnaires, 8 (1.3%) were excluded on the basis of incomplete interviews, leaving 632 for the final analysis (324 cases and 308 controls). At least 153 (47%) of the cases and 143 (46%) of the controls from Embu County, while 85 (26%) of the cases and 82 (27%) of the controls were from Kirinyaga and 86 (27%) cases and 83 (27%) of the controls were from Nakuru County. The median age of cases was 20 years (IQR: 2–35 years) while that of controls was 23 years (IQR: 2–35 years). The proportion of males was higher, both in cases (57%), and controls (59%). Among the cases, 79% presented with respiratory tract infections while 21% presented with diarrhea. Among the controls, the most frequently mentioned presenting conditions included accident or injury 11%, Family planning services 11%, skin conditions 11%, burns 5%, sexually transmitted infections 5%, hypertension 4%, fever 4%, dental problems 2%, diabetes 1% among others. Table This study set out to evaluate the Familia Nawiri community health education program on risk reduction for diarrhea and respiratory infections. Findings from the study revealed favorable results for this hygiene education program. Overall, after adjusting for potential confounders, participants exposed to the hygiene education program had 38% lower odds of having diarrhea or a respiratory infection compared to participants who were not exposed to the hygiene education program . Our findings are consistent with estimates from other studies assessing effects of hand washing with soap and WASH educational intervention on reducing the incidence of diarrhea and respiratory infections , 13, 14.P = 0.03), they provide some support of an association between hygiene education and morbidity of diarrhea and respiratory tract infections.It cannot be excluded with certainty that unmeasured bias or confounding e.g. recall bias with respect to exposure to the Familia Nawiri education sessions, residing in areas with water improvement initiatives and attending other health education programs, may have impacted the results in either direction, i.e. either increasing or decreasing the odds ratio. However, since our findings were statistically significant  activities tailored to the social and cultural context and infrastructure development.


P < 0.001) and positive lymph node metastasis . Pooled results showed that overexpression of PRAME is positively correlated with poor disease-free survival , progression-free survival , metastasis-free survival , and overall survival . In summary, these data are suggesting that PRAME is tumorigenic and may serve as a prognostic biomarker for cancer.Numerous studies have demonstrated that preferentially expressed antigen in melanoma (PRAME) is abnormally expressed in various solid tumours. However, the clinicopathological features and prognostic value of the PRAME expression in patients with cancer remain unclear. Accordingly, we performed a meta-analysis to accurately assess the association of the expression level of PRAME with clinicopathological features and cancer prognosis. Relevant study collection was performed in PubMed, Web of Science, and Embase until 28 February 2020. A total of 14 original studies involving 2,421 patients were included. Our data indicated that the PRAME expression was significantly associated with tumour stage (OR = 1.99, 95% CI: 1.48–2.67,  Cancer has become a major public health problem worldwide. According to a previous study, approximately 1,735,350 new cancer cases and 609,640 million cancer deaths occurred in the United States in 2018 [Cancer/testis antigens (CTAs) represent a heterogeneous group of tumour antigens and are regarded as ideal potential biomarkers for detection and targets in cancer immunotherapy because of their restricted expression pattern and immunogenicity . In receTo our knowledge, this meta-analysis is the first complete overview to clarify the clinicopathological features and prognostic value of PRAME based on the information from all previously published studies.In accordance with the PRISMA statement, we conducted a systematic literature search of PubMed, Web of Science, and Embase using “PRAME” OR “preferentially expressed antigen in melanoma” as keywords. The search concluded in this study was updated in February 2020. We manually reviewed the references of the retrieved articles to identify potentially eligible studies.Eligible articles met the inclusion criteria based on the following: (1) articles assessed the prognostic or clinical value of PRAME in solid tumours, (2) articles published in English, and (3) articles provided odds ratios (ORs) or information that allowed manual calculation of the 95% confidence intervals (CIs). The articles excluded were (1) duplicated publications; (2) reviews, comments, letters, and conference abstract; (3) and articles without usable data.Two investigators extracted the data from selected studies independently, including the first author's name, year of publication, country, cancer type, number of cases, detection method, tumour stage, number of patients with positive PRAME and negative PRAME expression, HRs, and 95% CIs for DFS, PFS, MFS, and OS. The HRs and 95% CIs were directly extracted from the adequate information in the article; otherwise, we used the Engauge Digitizer version 4.1 software to estimate the survival data from Kaplan-Meier curves.Q tests (chi-squared tests) and the I2 statistic. The fixed-effects model was adopted when there was no obvious heterogeneity (P > 0.1 and I2 < 50%). Otherwise, a random-effects model was applied. Egger's test was used to assess publication bias. Sensitivity analysis was conducted to investigate the stability of the total pooled results by removing studies one by one. P < 0.05 was considered statistically significant.The quality of the selected studies was independently evaluated by two reviewers using the Newcastle-Ottawa Scale (NOS). All statistical analyses were performed using the Stata statistical software version 14.0 . Heterogeneity among studies was assessed using Cochrane's The flow diagram is shown in The main features of the 14 eligible studies are summarized in I2 = 43.4%, P = 0.079), we used the fixed-effects model to pool data. The stratified data showed that the PRAME overexpression was significantly associated with tumour stage  (Nine articles investigated the associations between PRAME expression and tumour stage. There were 604 cases of III–IV stage and 559 cancer cases of I–II stage . Since t< 0.001) . The resI2 = 8.8%, P = 0.349), we used the fixed-effects model to pool data. The stratified data showed that the PRAME overexpression was significantly associated with lymphatic metastasis  (Four articles investigated the associations between PRAME expression and lymphatic metastasis. These were 158 cases of positive lymphatic metastasis and 190 cases of negative lymphatic metastasis . Since t< 0.001) . The resI2 = 28.9%, P = 0.239), we used the fixed-effects model to pool data. As seen in P < 0.001). The overall results suggest that PRAME overexpression is an indicator of poor DFS in patients with cancer.There were four studies, comprising a total of 858 patients, provided data for us to analyse the correlation between PRAME and DFS. Since the low heterogeneity , we used the fixed-effects model to pool data. As seen in P = 0.042). The overall results suggest that PRAME overexpression is an indicator of poor PFS in patients with cancer.There were three studies, comprising a total of 603 patients, provided data for us to analyse the correlation between PRAME and PFS. Since the low heterogeneity , we used the random-effects model to pool data. As seen in P = 0.034). The overall results suggest that PRAME overexpression is an indicator of poor MFS in patients with cancer.There were four studies, comprising a total of 689 patients, provided data for us to analyse the correlation between PRAME and MFS. Since the obvious heterogeneity , we used the fixed-effects model to pool data. As seen in P < 0.001). The overall results suggest that PRAME overexpression is an indicator of poor OS in patients with cancer.There were twelve studies, comprising a total of 1,978 patients, provided data for us to analyse the correlation between PRAME and OS. Since the low heterogeneity (P < 0.001) and non-Asian patients with cancers . Meanwhile, there was an obvious relationship between the high PRAME expression and the OS of patients with sample sizes of ≥100  and <100 . In addition, there was an obvious relationship between the high PRAME expression and the OS of patients with different testing methods .Because of heterogeneity in the samples, subgroup analysis was performed for study location, sample size, and testing index . There wPublication bias was evaluated by funnel plot and Egger's test. Because of the small sample size of LNM, DFS, PFS, and MFS, we had not conducted publication bias analysis. The results indicated no significant publication bias was observed in this analysis .Sensitivity analysis was performed to assess the influence of each study omission on the overall outcome. The results suggested that there was no significant influence of the pooled HR by omitting any study, indicating our analysis was robust .P < 0.001) and positive lymph node metastasis (P < 0.001). The results of the overall analysis revealed that the overexpression of PRAME is positively related to poor DFS (P < 0.001), PFS (P = 0.042), MFS (P = 0.034), and OS (P < 0.001). The results of the heterogeneity in the subgroup analyses also showed that our results were stable for all variables. Therefore, these results indicated that PRAME might serve as a clinicopathological and prognostic biomarker for malignancy.There is growing evidence that the overexpression of PRAME can contribute to the differences in the prognostic outcome between different kinds of solid tumors. To the best of our knowledge, this study describes the first meta-analysis to analyse the association between the level of PRAME and the clinicopathological features and prognostic value of patients in solid tumours comprehensively and systematically. In this study, we included 14 retrospective studies with a total of 2,421 patients. Remarkable positive associations were identified between the PRAME expression and clinicopathological characteristics, including advanced clinical stage (n = 31) of acute myeloid leukemia patients, and the rates of OS and DFS were higher than in patients with no or low expression (P < 0.05). Moreover, Abdelmalak et al. [P < 0.001, <0.001, respectively) compared with negative PRAME expressers. These studies suggest that PRAME overexpression is a predictor for better prognostic outcome in acute leukemia, which is completely opposite to the prognostic results of solid tumors in our meta-analysis. However, large-scale and prospective cohort studies will ultimately be needed to validate the good prognostic outcome of PRAME overexpression in acute leukemia.Numerous studies have reported PRAME expression in various malignancies. In solid malignancies, including hepatocellular carcinoma , 8, uveak et al.  reportedAs we all know, DNA methylation is an epigenetic mechanism often affecting gene expression and modifying the function of the genes. PRAME has been reported to be epigenetically regulated by DNA methylation in malignancies. Field et al.  found thNCT01149343, NCT01853878, and NCT00423254) [Although the function of PRAME has not yet been fully elucidated, a number of studies have addressed this issue. It is known that PRAME can bind to the retinoic acid receptor in the presence of retinoic acid, which suggests that it serves as a transcription regulator of nuclear receptor signaling . PRAME k0423254) .There were several limitations in this study that should be acknowledged. Firstly, the articles included were from only three databases ; thus, the data collection may be incomplete. Secondly, different criteria were applied in these studies for defining PRAME positive or negative, because of the lack of uniform cut-off values in PRAME expression. Thirdly, HRs with 95% CIs were calculated by digitizing and extracting from the survival curves in several papers, which inevitably brought minor statistical deviations. Furthermore, the effects of some factors, such as age and gender, were not considered in this analysis because of insufficient data. Therefore, high-quality studies are urgently needed to draw more accurate conclusions.Our meta-analysis provided credible evidence that the overexpression of PRAME was significantly related to the TNM stage, LNM, and poor prognosis. In addition, PRAME might serve as an attractive therapeutic target in the treatment of malignant tumors. However, considering the limitations of individual study, large-scale and prospective cohort studies will ultimately be needed to validate the results of our study.