No differences between the groups emerged concerning the emotional reactions reported. In contrast, mothers and children of different ages reported different self-regulation and other-regulation strategies. Moreover, maternal strategies had different effects on children’s wellbeing. The integration of qualitative and quantitative results was informative to understand how families adapted to the radical changes of everyday life related to the pandemic. The implications for developing interventions in such similar stressful situations to promote family wellbeing are discussed.The COVID-19 pandemic caused many enduring changes in the everyday life of families, with negative effects on parents’ and children’s wellbeing. However, there is a lack of studies in the literature exploring the emotional reactions and coping strategies of both mothers and children of different ages. Furthermore, most studies used only self-reports. This study aimed to identify the emotions and coping strategies of children, adolescents and their mothers and to verify the association between maternal and child wellbeing. A mixed-method design using interviews and questionnaires was applied to collect information on wellbeing  and coping strategies of both mothers ( Between the end of 2019 and the beginning of 2020, the COVID-19 pandemic began, affecting the life of people all around the world with effects that are still present. On March 9th, the Italian population was forced to stay indoors to avoid the spread of this new virus. Families were forced to spend time in the same physical space for three months. Smart working and distance learning were introduced, school closures were compulsory and meetings in public spaces were forbidden. Some of these limitations and the several modifications of everyday social life aimed to contain infections such as the use of masks, social distancing, distance learning etc., lasted for months after the first lockdown.This situation negatively affected families’ routines and behaviors ,2 with nPrevious studies conducted after potentially traumatic disasters evidenced that the potential short and long negative effects of stressful circumstances on children’s mental health is mediated by how the family handled the stress. For example, the quality of the caregiver supportive verbal communications to the child  was associated with children’s positive coping strategies after the 2010 Chilean earthquake , with leDuring and right after the beginning of COVID-19, many scholars aimed to explore the effects of everyday life modifications on children and parents’ wellbeing in several different countries, i.e., ,11,12. HTo contribute to this field of studies, the present research, using both quantitative and qualitative data, explored the emotional reactions and coping strategies of children, adolescents, and their mothers nine months after the beginning of COVID-19, in December 2020. This moment in time was very critical; even though the first lockdown had ended, the frequency of infections was still high. Children were requested to go to school following many restrictions  and social lives were strongly modified. An in-depth exploration of children and parents’ emotional reactions might help in understanding the impact of such strong modifications of family life on parents and children of different ages. The findings will inform the design of clinical and psychosocial interventions directed at families during this and similar situations.The majority of studies exploring children’s emotional reactions to COVID-19 related to modifications of their everyday life were conducted during the first lockdown (March–April 2020); only a few of them directly collected children’s opinions using mainly parent reports.When interviewed about their wellbeing, children reported mixed emotions linked to the different impacts of the situation on their life. Missing their grandparents, playing with their friends, being able to go outside and having missed milestone events, such as birthday celebrations or graduations, made children interviewed in China, Spain and Australia feel bored, lonely, and sad ,14,15,16It is well known that the pandemic impacted lives for many months worldwide, with implications that are still present even if the emergency is almost over. However, only a few studies explored the long-lasting effects of COVID-19 modifications on everyday life after the first lockdown. Moreover, most of the studies considered a wide range of ages, failing to explore the specificities of children and adolescents’ reactions. The results of a qualitative study conducted in Austria a few months after the lockdown showed how children’s (from kindergarten age to 18 years old) emotional reactions varied according to age and were quite different from what was reported in studies conducted during the lockdown . SpecifiTo sum up, the lockdown had a mixed impact on children’s wellbeing. Scholars also reported the presence of positive reactions related to some aspects of modifications of life. An exploration of both positive and negative emotional reactions is necessary to fully understand the complexity of the experience. Moreover, emotional reactions could differ among ages with children and adolescents, experiencing two crucial developmental periods, showing different emotional reactions and different strategies used to cope with those emotions. While children might rely more on the family for emotional support and to share time and pleasure, adolescents are focused on relations with their peers, which often conflicts with parents. A crucial limit of the literature is the only focus on the lockdown experience; this was very useful to understand the immediate effects of the pandemic. However, understanding the long-lasting effects of the modifications of everyday life still present months after the beginning of the emergency and how that could be replicated if similar situations happen again is now necessary.The changes in everyday life caused by COVID-19 also had a negative impact on parents’ wellbeing. The major COVID-19 pandemic’s restrictions and the rules imposed by the government to prevent contagions made parents feel angry, frustrated, and stressed by daily inconveniences, especially related to school, work and family members (as reported in a study conducted in the United Stated) . In partWith the extension of the first lockdown, parents expressed concerns about the long-term impacts of the COVID-19 pandemic on their children’s lives, specifically their mental health, education, and opportunities . In addiBecause the family condition impacted that much on parents’ emotional reactions, we might expect to find differences between the parents of children’s and adolescents’ reactions. However, to the best of our knowledge only one study conducted in Austria explored the difference between the negative emotions of parents of children of different ages . ParentsAs for children, the COVID-19 pandemic had some positive effects on parents’ wellbeing. Among the reported positive aspects of forced cohabitation, one was the creation of stronger bonds with family members and the ability to spend more quality time with their children and partner. In addition, improvements in sibling relationships were observed that had not occurred when schools were open ,15,17.In conclusion, the COVID-19 pandemic had both positive and negative effects on parents’ emotional sphere. Their emotional reactions varied according to their offspring’s age; however, only few studies explored these differences. In addition, most studies were conducted during the first lockdown, leaving a gap in the knowledge of long-term effects of the COVID-19 pandemic on parental wellbeing.Coping strategies refer to the regulatory processes people used to manage their emotions and behaviors under stress . They arStudies reported that children of different ages from Spain and the United States used several coping strategies to regulate the emotional distress caused by the COVID-19 pandemic ,23. Pre-Some scholars found that specific pre-COVID-19 frequently used coping strategies were associated with children’s emotional wellbeing during lockdown  ,22,24,25While younger children’s emotions were still externally regulated by their parents, adolescents gradually learned to self-regulate their emotions, showing different resources than children to cope with the COVID-19 inconveniences and to make new meaning of experiences related to the lockdown  . AppraisParents’ strategies to deal with the pandemic’s impact on their personal and family life consisted of the tendency to regulate their own emotions and to regulate their children’s emotions.Spending time outdoors in their own backyard and accepting that the lockdown was not up to them helped to enjoy moments and to maintain their wellbeing (as reported in studies conducted China and United States) ,29. OtheParents’ strategies to regulate children emotions impacted on children’s wellbeing. Negative parental coping strategies, such as rumination and communication difficulties, were associated with high perceived stress in both parents and children in the United States . MoreoveOne of the major strategies that parents used to protect children from the negative impact of the pandemic was structuring family life during the lockdown to maintain as much as possible the habits and schedules of everyday life. This was conducted with attention to promoting the independence of their children by involving them in the care of the house or by giving them responsibilities. For example, younger children set the table or helped prepare food, while older children assisted with groceries, helped parents to take care of younger siblings or helped them with schoolwork. This strategy was employed in Chinese families with children of all ages, but the routine of young children was structured primarily by the parents, while adolescents were actively included in its creation and supported in respecting it independently . An addiTo regulate negative emotions caused by children’s exposure to COVID-19 news, parents of children preferred to communicate information with their own words or to use a restrictive mediation style to avoid exposing them directly to false or negative COVID-19 news ,26. In cOlder children were also encouraged to use social media and electronic devices for home education and to maintain social contacts independently .In summary, during the lockdown, parents used several coping strategies to manage their own distress and to manage their children’s emotions and behaviors. While the latter were more explored, little is known on the strategies used by parents to cope with their own distress. Studies conducted in several countries evidenced that children and adolescents who were exposed to familiar protective factors, such as emotional support from parents, a well-defined daily routine and good communication with friends and parents, were more resilient to pandemic stress. On the contrary, children and adolescents who lack familiar protective factors are more likely to develop anxiety and depression . MoreoveWe conducted a mixed-method study using questionnaires and interviews directed at mothers and children of different ages nine months after the beginning of the first lockdown (December 2020). The use of this method filled a gap in the literature because current studies examined these issues using only questionnaires, mostly filled in online. The choice to use a mixed method was made to obtain more information to help better understand which emotional reactions were associated with COVID-19 difficulties and which emotion regulation strategies were applied by mothers, children, and adolescents. In addition, the use of this method fills a gap in reading, as current studies address these issues using only quantitative methods, predominantly with online parent report questionnaires. Moreover, our study is original because it addresses these issues by dividing subjects into age groups and considering both the mother’s and child’s perspectives. An additional limitation of the literature that we aimed to fill is that most studies were conducted during the first lockdown, allowing only emotional reactions to be captured in the early period of the pandemic. Our study was conducted in Italy, one of the first countries affected by the pandemic after China. Even if the literature is quite homogeneous in findings of children and parenting reactions to the pandemic in several countries with different cultural background, an exploration of the situation in Italy and a comparison with other countries’ findings would be an important contribution to the literature.(1)To identify emotional reactions in children, adolescents, and their mothers.(2)To identify the emotional coping strategies used to cope with the COVID-19 pandemic by children, adolescents, and their mothers.(3)To identify the association between maternal wellbeing and emotional and behavioral problems in children and adolescents.The main aim of the study was to explore the emotional reactions and emotional coping strategies used by children, adolescents, and their mothers with the following specific aims:Based on these objectives, we hypothesize that (1) emotional reactions and (2) coping strategies would differ by ages in the two groups , and that (3) the psychological wellbeing of mothers is associated with that of their children/adolescents.Sixty-five mothers with their children participated in the study. Subjects belonged to a previous project. The sample consisted of 35 children (8–10 years old), 30 adolescents (11–13 years old) and their mothers. The final sample consisted of 65 mothers divided into two groups based on the age of their children: 35 mothers of children (M age = 42.17 (4.40) and 30 mothers of adolescents (M age = 41.63 (4.48). In terms of maternal education, the sample was composed of 9.5% less than a high school degree, 61.9% high school degree and 28.6% master’s degree. All participants were Italian, all mothers were married and/or co-habiting with the father of the child. Each family had an average of two children.Mothers were contacted by phone in December 2020 and those who agreed to participate received the links to the online survey for the mother and the link to the online survey for the child. Appointments for the interviews (one with the mother and one with the child) were scheduled.Children and their mothers signed the written consent form and completed the online survey composed by a set of questionnaires. Telephone interviews with mothers and children were conducted independently a few days after the first contact.Mothers answered a set of specific questions related to their family condition. The first three questions addressed to what extent  when the pandemic was over, she thought she would need financial support and psychological support for herself and her child . Mothers were also asked how often their child asked questions, read or talked about COVID-19 .An ad-hoc index was computed to evaluate the amount of contact the parent had with people directly affected by the virus, following the assumption that the greater the number of contacts, and the closer to the parent were the people, the greater the impact on psychological wellbeing would be. One point was given for each of the following if present: the parents tested positive for the virus, a familiar or close friend tested positive, a familiar/close friend was hospitalized, a familiar/close friend died. A half point was given if the parent knew a person (not familiar or close friend) who tested positive, was hospitalized or died.An ad-hoc index was computed to evaluate mothers’ concerns about possible COVID-19 infection and the consequences on their own and others’ physical and mental health . The questionnaire included four items . To obtain the score of each scale, items are summed. Cronbach’s α in the current study was 0.86.Difficulties experienced by parents and children during the pandemic were investigated with a newly developed pool of 13 items. Parents and children were asked to indicate  how difficult they were perceiving, during the last week, dealing with several aspects related to the COVID-19 period . To obtain the score of each scale, items are summed. Cronbach’s α in the current study was 0.85.Individual perceptions of maternal wellbeing were investigated using short form of the Depression Anxiety Stress Scales-21 (DASS-21) . The queThe perception of parenting stress in the parent–child interaction was investigated using the sub-scale of dysfunctional parent–child interactions of the Parenting-Stress Index (PSI-4) . The scaBehavioral and psychological problems in children were investigated using both mothers’ and children’s reports of the Italian version of the Strengths and Difficulties Questionnaire (SDQ) . The curChildren answered a set of specific questions related to assessing the possible changes on technology use during the pandemic. Children were asked how much time  they played video games throughout the day . They were asked how many times a day they heard their friends on a video call  (from 1 = never to 3 = two or more time). In addition, how many hours they watched TV was investigated  . Finally, they were asked how often they searched for information about COVID-19  . To obtain the score of each scale, items are summed. The Cronbach’s α for this scale was 0.49.As for mothers, an ad-hoc index was computed to evaluate children and adolescents’ concerns about possible COVID-19 infection and the consequences on their own and others’ physical and mental health. The questionnaire included four items : During the past month how concerned were you: about being infected; about the possibility that your friends and family members might be infected; about the possibility that your physical health might be affected by COVID-19; about the possibility that your mental health might be affected by COVID-19?). To obtain the score of each scale, items are summed. The Cronbach’s α for this scale was 0.75.Difficulties experienced by children and adolescents during the pandemic period were investigated with a newly developed pool of 8 items. Children and adolescents were asked to indicate  how difficult they were perceiving, during the last month, dealing with several aspects related to the COVID-19 period such as falling asleep, waking up in the morning, getting along with my parents, staying away from my friends, etc. To obtain the score of each scale, items are summed. The Cronbach’s α for this scale was 0.69.To explore the emotional reactions and strategies used to cope with COVID-19-related difficulties, telephone interviews were conducted with mothers and their children. For the children, the questions concerned the difficulties they experienced during the COVID-19 period at school, at home and with friends. They were also asked what emotions they felt about these difficulties and what strategies they used to cope with them see . For motMothers’ and children’s scores at each questionnaire were computed. Descriptive analyses were performed to examine the distribution of answers to questions. Differences between groups were examined with a one-way ANOVA. Associations among variables were examined with Pearson’s correlations in the two groups.A theoretical thematic analysis was used to identify the dominant themes across the entire data set. The data analysis was conducted according to Braun and Clarke’s Thematic Analysis framework ,40. We aThe type of analysis adopted can also be described as semantic, as the data were organized and summarized to underline patterns in the explicit content of participants’ responses. We focused on the meanings clearly included in the interviewees’ words, providing an accurate description of the data, rather than an interpretation that goes beyond what participants said.First, the interviews were fully transcribed by a research assistant. Then, we proceeded with the familiarization with the data, reading the participants’ answers several times. Three members of the research team identified codes by selecting and tagging parts of the text considered pertinent to understanding the reactions and the coping strategies adopted by mothers and children to front the pandemic. They produced a list of extracted codes that was then discussed within the entire research group to define macro-areas relevant to the research questions. This progressive organization in themes was carried out by combining, splitting or redefining codes in order to reach consensual clusters of concepts featuring the research areas of investigation. All the data were analyzed in their original language, Italian.In reporting the results, we decided to present the final list of themes and codes with exemplificative quotes from the interviews and include all of them in tables. We specified with participants our availability of answering doubts, questions and on giving them information and feedback when requested on the study’s findings.The exploration of frequencies of answers to the living characteristics questions gave interesting information about the two groups. In total, 44% of children declared spending 2 h or more per day playing videogames versus 23% of adolescents. Concerning video-calling friends, 47% of children and 47% of adolescents declared doing it at least 2 or more times a day. More than 50% of children and 30% of adolescents watch TV for more than 2–3 h a day. A total of 64% of children and 66% of adolescents reported reading and talking about COVID-19 often and always during the last month. Mothers of children and adolescents declare on average to need low economic  and psychological  support for themselves and psychological support  for their children.One-way ANOVA results showed that mothers of adolescents reported higher parenting stress and less worries about COVID-19 than the mothers of children see . No signPearson’s correlations among maternal-reported and child-reported behavioral and emotional problems assessed with the SDQ were very high across all scales (mean r = 0.48) . For thiPearson’s correlations among maternal wellbeing  and children’s emotional and behavioral problems (SDQ) evidenced significant associations in the two groups see . MothersAssociations among COVID-19-related variables and wellbeing are presented in A higher number of difficulties in adjusting to COVID-19 modifications of everyday life was associated with mothers’ high anxiety and stress only in the group of children. In both groups, more preoccupations about COVID-19 were associated with high maternal anxiety and stress, and with high depression only in the children group.The emergency situation associated to the world pandemic significantly impacted on the emotional, physical and cognitive levels of functioning of the participant mothers. Themes that emerged are described on The qualitative analysis, consistent with the quantitative results, showed that the themes that emerged from the interviews of mothers of children and mothers of adolescents were similar see . Indeed,The main emotional reactions to the COVID-19 event among the mothers can be classified in the following categories: fear of being infected by and infecting other people; sense of vulnerability and powerlessness; feeling of irritability/agitation/frustration/anger; apathy and sadness; anxiety, worry and uncertainty; feeling of loneliness and inadequacy/insecurity.Concerning the physical discomfort, COVID-19 impacted all mothers mainly in terms of sleep problems  and feelings of tiredness. Mothers of children also reported an impact in terms of psychosomatic reactions .Regarding the cognitive impact of the situation, all mothers reported difficulties in concentration and lack of attention. While mothers of children described these difficulties in terms of feelings of confusion, mothers of adolescents experienced it as an overthinking tendency.The coping strategies could be classified as two different types: self-regulation strategies and other-regulation strategies. Examining the maternal ability of managing the situation is particularly relevant because, as evidenced by the quantitative data, mothers’ levels of COVID-19-related worries are positively associated with the level of the offspring’s emotional difficulties. For both samples, self-regulation strategies included rationalization of emotions and thoughts in order to develop acceptance and pro-activity to front what is experienced as inevitable. Besides that, participants found comfort in practicing hobbies and sports, to keep their creativity alive, take care of their body–mind system and distract themselves from the problematic situation. In this respect, mothers of adolescents were more generic in reporting the ways they found to keep themselves busy, referring to these activities mainly as a way to avoid thinking at the situation. Mothers of children, instead, detailed the activities more in depth, referring to specific hobbies, sports and personal interests they dedicated time to. They also sought information and read up on the continuously evolving situation to better understand it.Instead, mothers of teenagers adopted a self-isolation strategy—that was, being able to take some time alone to lessen the emotional overload—which instead was not mentioned by mothers of children, probably because they were not allowed to do so, given the age of their offspring. This difference seems to align with quantitative results that show that mothers of children had more worries related to COVID-19 and its impact than mothers of adolescents, who were probably less worried also due to the possibility of adopting temporary self-isolation as an adaptative regulation strategy.Mothers who adopted other-regulation strategies specifically referred to a way to regulate their emotions based on interpersonal dialogue and searching for other people’s support. This covered both deep exchanges with relatives—who are part of, or live close to, the family nucleus—and more sporadic interactions with friends, neighbors, and acquaintances. As expected, both groups of mothers mainly relied on other members of the family nucleus, them being the only people with whom it was possible having face-to-face interactions during the pandemic. Concerning the ways mothers of both groups managed their children’s challenges of the emergency situation, we found several emotional and behavioral parenting strategies.The emotional strategies first included engaging in an open and transparent dialogue with their children, which embraced: encouraging self-narration and disclosure about their feelings as well as explanation and clarification of what the situation is like and what they could expect in future. Mothers of teenagers experienced more difficulties in engaging in an open dialogue, so they tended to adopt a more directive style, giving concrete advice on how to manage time. This result supports and enlightens the quantitative analysis showing that mothers of adolescents are characterized by a higher level of parenting stress, but not a higher level of generic stress.Second, mothers tried to appease and reassure, adopting a downplaying attitude to underline to children the transitory character of the situation and to adolescents its shared nature .Other parenting strategies embraced pushing the children to engage themselves in daily activities and keeping their routines, as well as playing and sharing practical/intellectual activities together.All the mothers tended to be more tolerant and indulgent toward the use of technological devices such as mobile phones and tablets, applying a less invasive attitude in order to give children and teens a space free from control.Especially with children, mothers tried to take advantage of the enforced physical presence within the domestic environment and the related constrained proximity, to develop closer emotional intimacy and connection. On the contrary, mothers of adolescents tended to push them into seeing friends, when possible, to prevent the risk of social isolation.Children and adolescents reported a number of emotional reactions as shown in First is the fear of contagion for oneself and significant others, which was more common among adolescents, who thought more at the possibility to ‘bring COVID-19 home’ and infecting the elderly family.Second is worries and anxiety, which for children denoted a general sense of danger and referred to a number of scenarios: the possibility of losing other people, such as grandparents; school mates not respecting the COVID-19 rules; the preoccupation of unintentionally not respecting all the social limitations imposed by the pandemic (such as the use of masks); the difficulty in seeing the end of the pandemic, and thus the restoration of usual relationships, that end up in the worry of a never-ending story. For teenagers, worries and anxiety were specifically linked to the school context and to a general feeling of wasting time, and the uncertainty about the situation tended to end up in a self-closing mood.Third is sadness and depressive mood, manifested through frequent and “unexplained” crying and associated to a general feeling of isolation, disconnection and distance from other people. In particular, both groups reported sadness due to: the great number of dead people; lack of affective interactions with both peers and the elderly; the impossibility to greet friends in cases of the transition from one school cycle to another; the nostalgia for a past era of freedom contrasted with a present and a prospective future full of restrictions.Fourth is the feeling of boredom and lack of fun moments. Children especially reported that they struggled in finding what to do within the house walls, so they tended to spend a lot of time asking themselves what to do, while doing nothing. Adolescents especially associated boredom to a sense of decrease in creativity and motivation and to feelings of emptiness and loneliness.Concerning the coping mechanisms adopted by children and adolescents, self-regulation strategies for both groups relied on hobbies and diversions, such as playing, reading, listening to music, playing music instruments, drawing, watching movies, TV, video games and, in a limited number of cases, reorganizing personal spaces. To deal with negative emotions, some children attempted to avoid thinking about the situation and adopted an apparently indifferent stance, while other children relied on positive thinking, i.e., recalling beautiful moments of the past spent with significant people and friends. Adolescents tended to keep emotions and thoughts for themselves, avoiding talking and sharing feelings with others.Regarding the external strategies of regulation, children mainly count on the family context. For example, they tend to help parents in daily accomplishments and engage in activities with siblings. They sometimes directed a clear request for help, asking the other members of the family to spend time with them. Adolescents relied more on friends, with whom they interacted via video/phone calls and chatting, but also mentioned their parents as a source of support. Indeed, quantitative analysis showed that, among the teenagers, those with higher level of emotional difficulties tend to rely on parents especially for information seeking about COVID-19. Another form of external regulation mentioned by both the samples is represented by engaging in interactions with pets.The present study aimed to verify, during the period of the second lockdown, the emotional reactions and coping strategies used by children, adolescents and their mothers, and their associations. The mixed research design of the study, through the administration of self-reports and interviews, provided insight both on the specific strategies and emotional reactions of children and their mothers and into how the way mothers dealt with stressful situations related to the COVID-19 pandemic affected the wellbeing of children and adolescents. Furthermore, the division of the children’s sample by age helped in the identification of different patterns across groups.In relation to the first hypothesis, no relevant differences between children and adolescents and between mothers of children and mothers of adolescents emerged in the reported emotional reactions. Regarding the emotional reactions of children and adolescents, the interviews revealed differences in the causes associated with the emotion . The same emotions have been reported in previous studies, but none of these explored differences based on the age of the subjects ,26,41. IConsistent with the literature, mothers in both groups, during the second lockdown, reported similar reactions ,17. To tIn relation to the second hypothesis, the results helped to fill the gap in the literature on the differences between self-regulation and other-regulation strategies used to cope with the changes related to the stressful situation. Children used more cognitive avoidance to cope with negative emotions, whereas adolescents engaged more in extra-familiar activities and hobbies as self-regulation strategies. Maybe, adolescents who possess more cognitive strategies to understand the stressful event were able to choose activities that allow them to self-regulate. As other-regulation strategies, children sought help from family members, whereas adolescents relied on friends, using social media ,28. ThisThe interviews reveled that in both groups, mothers used self-regulatory strategies, such as engaging in hobbies and seeking information about COVID-19 . HoweverFinally, in relation to the third hypothesis, the quantitative results evidenced a significant association between maternal and child wellbeing. This contributed to understanding how the way the mother handled a stressful event influenced the child’s psychological wellbeing . In the Despite the important results reported, the present study presents some limitations. First, the small sample, and the homogenous cultural context where the study was conducted, limit the generalizability of findings. Second, the cross-sectional design limits the possibility to explore causations. Third, we did not explore the emotional reactions and coping strategies of other family members, such as fathers. Finally, even if we know that the economic level of our participants was middle-high, we do not have detailed information about the socio-economic condition of the families. Future longitudinal studies on the topic investigating the long-term effects of the pandemic on the psycho-emotional wellbeing of both children and adolescents, in larger samples and including the full family perspectives are needed.Despite these limits, the present study gives a picture of how mothers and their children coped with the challenges related to COVID-19′s modification of everyday life. This further underlines the need to use multi-informant exploration of phenomena. Moreover, our results are consistent with the literature concerning other cultural contexts, and consequently could not be considered culturally specific. This is important, because even if the different countries reacted differently to the pandemic applying different restrictions, the impact on families was similar and mainly related to the restrictions of social life such as the closing of schools and the absence of opportunities to meet with peers and relatives. The use of a mixed methodology evidenced how the solo use of questionnaires or interviews, as well as only the use of one respondent, limit the complexity of findings. Both scholars and clinicians should include in their exploration of the phenomena information from several perspectives, and their integration in order to increase their understanding.Our findings contribute to capturing important information about how the families of children and adolescents may react when faced with stressful events that may involve the entire family system . In this way, intervention as well as preventive projects should be developed considering the specific family needs in relation to the age of the children.In conclusion, it is recommended to intervene on the parent–child interaction to promote family wellbeing. In general, interventions should be based on promoting the maintenance of daily routines , emotional closeness of parents and fostering an open dialogue to enable children and adolescents to understand and emotionally manage stressful events. In addition, it would be useful to promote parental support projects to help them decrease the stress caused by the everyday family routine modifications to foster more adaptive parenting, a fundamental variable to prevent children and adolescents’ emotional and behavioral problems.


Pelargonium sidoides called Bi121, with data on its antiviral activity against different SARS-CoV-2 variants and the underlying fractions of Bi121 responsible for this activity. The authors narrow down the activity to one specific compound called Neoilludin B and show RNA-intercalating activity of the compound in RNA viruses by an in silico structural modelling. Due to the omnipresent medical need in the recent past, we highly appreciate research and development of therapeutics against SARS-CoV-2 in general and respective antiviral phytopharmaceutical drugs in particular. However, we have severe concerns about certain aspects presented in the aforementioned study and therefore want to draw the attention of the journal editors, reviewers, and readers of the article towards these aspects.The article “Significant Broad-Spectrum Antiviral Activity of Bi121 against Different Variants of SARS-CoV-2” by Subhadra et al. [One major prerequisite for valid scientific studies is reproducibility. To facilitate reproducibility, a comprehensive characterization of the study material is crucial. While working in the field of pharmacology and medical sciences, studied drugs need to be sufficiently characterized. If the used drug is a single compound with a known chemical structure, an unambiguous name and/or structure of the molecule needs to be provided, with the specification of the purity of the substance, e.g., 98% (m/m) acetylsalicylic acid. Working with plant extracts as active principles, on the other hand, makes this characterization of the studied drug more complicated since plant extracts are multicomponent mixtures, with thousands of individual compounds in different concentrations. This is further complicated by seasonal and geographical variabilities of the plant material used for extraction. Thus, concentrations of the compounds in a plant vary from season to season due to variations, e.g., in precipitation and other environmental factors. Yet another factor is the process used for extraction of the plant material. The use of different solvents, extraction times, temperatures, pressures, etc., will affect the concentrations of the different compounds in the final extract. Also, the plant material itself needs to be properly authenticated since some plants within a plant family look quite similar and the possibility of adulteration and/or false authentication needs to be ruled out. Due to this multidimensionality of plant extracts as active substances, the characterization of the used material should at least include a deposit of a voucher specimen, the thorough description of the extraction process, and chemical fingerprints by methods that are suitable for the assessment of substance mixtures, like high performance liquid chromatography (HPLC), thin layer chromatography (TLC), nuclear magnetic resonance (NMR), and the like. A consensus statement on the best practice in characterizing multicomponent mixtures like plant extracts was recently published, covering all these aspects in deep detail .Pelargonium sidoides extract Bi121 was prepared following a protocol described in literature [Pelargonium sidoides extract EPs® 7630 published previously in another MDPI journal [® 7630 and thus also chromatographic profiles could be so similar that they become indistinguishable, this theoretical assumption is very unlikely due to the following reasons:1.® 7630 is identical. At least some seasonal variability is to be expected.It is very unlikely that the respective plant material used for preparation of the analyzed extract batches Bi121 and EPs2.® 7630 are different. Bi121 is prepared by extraction of the plant material with pure water using ultrasonication followed by an adsorption to polyvinylpyrrolidone with a subsequent elution with NaOH to enrich the polyphenols. In contrast, EPs® 7630 is extracted with an aqueous 11% (m/m) ethanol solution with deviating further processing steps. The different extraction solvents and the different subsequent processing should yield different phytochemical compositions of the two extracts and thus differences in HPLC profiles.The extraction processes of Bi121 and EPs3.The most striking argument is that the described HPLC methods used to generate the HPLC chromatograms in ,4, respeIn the study of Subhadra et al. , the Pelterature , with so journal : Please  journal . AlthougFrom a scientific point of view, the fact that the HPLC profile presented by Subhadra et al. is identical to an HPLC profile formerly published by another independent research group appears to be startling, and it is necessary to exclude any implication of plagiarism of the figure in order to be in accordance with prevailing scientific publication standards.Apart from the characterization of the extract Bi121, one further point of discussion is the putative identification of Neoilludin B as an active substance. Illudins were found only in mushrooms so far, and literature on this compound class is scarce. While finding new and unexpected compounds in plants is a common occurrence for natural product researchers, a finding that a (so far) mushroom-specific compound is found in plants must be supported by a higher evidence level, like isolation of the compound followed by structure verification by NMR. The identification by Subhadra et al. using compound library comparison based on only mass spectrometric data is very putative since isomeric substances cannot be excluded, and any other substance having the same sum formula may be the active substance. Furthermore, even if the presence of Neoilludin B is confirmed, it must be excluded that the substance was introduced by an adulteration of the plant material with (parasitic) mushrooms, which leads back to the need for proper authentication of the plant material. A higher evidence level for the identification of the substance is required for the study in particular since the active principle of Neoilludin B is further underlined by an in silico target prediction and validation. A potential false identification of the active substance would render these in silico studies useless.Considering all the aforementioned arguments, concerns are raised on what conclusions may be drawn from this study, where the standardization of the studied drug is not specified, the studied drug is not characterized by the assignment of “characteristic compounds” to the presented annotated HPLC peaks, the HPLC profile itself is at least suspicious of plagiarism, and the postulation of the active principle is based on a very putative identification of a single compound. These concerns render the validity of the study very limited and call for a more comprehensive phytochemical reassessment of the studied material.


Mak et al.), effects of musical experience in combination with age , effects of tinnitus , and effects of the spatial location of sounds in the perception of emotional valence .Functional and structural asymmetries are present in many regions of the brain. The present Research Topic continues the description of studies on hemispheric asymmetries in the auditory domain  of musicians and non-musicians of different ages during passive listening to instrument sounds and harmonic complex tones. For the P1 latency and amplitude, they observed differences in dependence on age and musical experience between the hemispheres. In children with musical experience, the P1 latency in the left hemisphere was shorter than in non-musicians but no differences were observed in adolescents and adults. Furthermore, the P1 amplitude in the right hemisphere was smaller in musicians than in non-musicians in children, larger in adults, and not different in adolescents. In all age groups in both hemispheres, the associated co-activation of the orbitofrontal cortex was shorter in musicians than in non-musicians and coincided in musicians with the P1. This means that musical experience leads to a different interaction between primary and secondary auditory responses and orbitofrontal co-activation.Li et al., using arterial spin labeling, investigated the lateralization of cerebral blood flow (CBF) in the auditory cortex of patients with tinnitus. They observed hemispheric differences in CBF for people with and without tinnitus, with a higher CBF in the left primary auditory cortex than in the right one and a higher CBF in the right secondary and associative auditory regions than in the left ones. However, in the secondary auditory cortex, the CBF in the tinnitus patients was less lateralized to the right than in people without tinnitus. CBF in the primary auditory cortex was higher in people with tinnitus than those without tinnitus. This was interpreted as abnormal neuronal activity that might cause tinnitus. They hypothesized that patients with a higher CBF in the left primary auditory cortex have more difficulties adapting to tinnitus because of a correlation between this measure and tinnitus severity.Grisendi et al. investigated brain activity elicited by human vocalizations in comparison with other environmental sounds and their modulation through emotional valence, as well as the effect of their source localization with respect to the listener. As similarly known for other sensory modalities  study, The studies constituting the present volume indicate that auditory hemispheric asymmetries concern multifaceted subjects that range from auditory pathology to ordinary perception. In the literature, very different techniques have been used to investigate the different features of the two hemispheres with regard to auditory perception, including dichotic listening (Brancucci and San Martini, NA: Writing—original draft, Writing—review and editing. AB: Writing—original draft, Writing—review and editing.


In response to concerns about increasingly intense Atlantic hurricanes, new federal climate and environmental justice policies aim to mitigate the unequal impact of environmental disasters on economically and socially vulnerable communities. Recent research emphasizes that standard procedures for restoring power following extreme weather could be one significant contributor to these divergent outcomes. Our paper evaluates the hypothesis that more economically and socially vulnerable communities experience longer-duration power outages following hurricanes than less vulnerable communities do, conditional on the severity of the impact of the storm itself. Using data from eight major Atlantic hurricanes that made landfall between January 2017 and October 2020 and induced power outages for over 15 million customers in 588 counties in the Southeast, we demonstrate a significant relationship between socioeconomic vulnerability and the duration of time that elapses before power is restored for 95% of customers in a county. Specifically, a one-decile change in the socioeconomic status theme in the Social Vulnerability Index, a measure of vulnerability produced by the Centers for Disease Control and Prevention and the Agency for Toxic Substances and Disease Registry, produces a 6.1% change in expected outage duration in a focal county. This is equivalent to a 170-min average change in the period of time prior to power restoration. Using data from eight major Atlantic hurricanes that made landfall between January 2017 and October 2020, we demonstrate a significant relationship between socioeconomic vulnerability and the duration of time that elapses before power is restored for 95% of customers in a county. A one-decile change in the socioeconomic status theme in the Social Vulnerability Index produces a 6.1% change in expected outage duration in a focal county, which is equivalent to a 170-min average change in the period of time prior to power restoration.In response to concerns about increasingly intense Atlantic hurricanes, new federal climate and environmental justice policies aim to mitigate the impact of environmental disasters on economically and socially vulnerable communities , 2. The procedurally fair, the recovery routines in widespread use throughout the United States could exacerbate existing sources of inequality.Recent research emphasizes that standard procedures for restoring power following extreme weather could be one significant contributor to these divergent outcomes. These procedures, which first prioritize critical infrastructure, then commercial and industrial firms, and then seek to recover as many households as quickly as possible , 13, areOur paper evaluates the hypothesis that more economically and socially vulnerable communities experience longer duration power outages following hurricanes than less vulnerable communities do, conditional on the severity of the impact of the storm itself. Using data from eight major Atlantic hurricanes that made landfall between January 2017 and October 2020 and caused power outages for over 15 million customers in 588 counties in the Southeast, we demonstrate a significant relationship between socioeconomic vulnerability and the duration of time that elapses before power is restored for 95% of customers in a county. Specifically, a one-decile change in the socioeconomic status theme in the Social Vulnerability Index (SVI), a measure of vulnerability produced by the Centers for Disease Control and Prevention and the Agency for Toxic Substances and Disease Registry (CDC/ATSDR), produces a 6.1% change in expected outage duration in a focal county. This is equivalent to a 170-min average change in the period of time prior to power restoration. SVI themes related to household composition, racial & ethnic minority status, and housing type & transportation, in contrast, do not exhibit a statistically significant relationship with outage duration.Our paper builds on decades of research in engineering and the social sciences that analyze the distributional effects of natural disasters on economically and socially vulnerable communities. Prior research demonstrates that vulnerable communities are less able to anticipate natural disasters, cope with their acute impact, and then recover from the damage they cause . This reRecent federal policies related to climate and environmental justice focus, in particular, on the intersection between economic and social vulnerability and the impact of climate change. The CDC/ATSDR SVI, which we use in our paper to measure the economic and social vulnerability of communities to prolonged storm-caused power outages, combines socioeconomic indicators related to poverty, housing costs, education, and health insurance, with additional indicators associated with household characteristics, racial & ethnic minority status, and housing type & transportation in order to “assess community need during emergency preparedness planning” and “identify communities that will need continued support to recover following an emergency or natural disaster” . The CouOne of the most disruptive acute effects of hurricanes for economically and socially vulnerable households is long-duration power outages. Long-duration outages can impact health through, e.g. increased exposure to carbon monoxide, decreased access to clean water, consumption of spoiled food, or lack of shelter . OutagesThere is strong statistical evidence that more economically and socially vulnerable communities are more likely to experience extended power outages . BuHowever, existing case-based empirical analyses that focus on one storm in a limited geographic region face the difficult statistical challenge of disentangling the impact of the storm itself from the characteristics of communities impacted by the storm, two variables that exhibit strong spatial dependence , 34. WhaOur analysis combines large-scale data on storm-caused power outages in the Southeast with data on the economic and social vulnerability of affected communities, characteristics of hurricanes, and storm-related risks.Our data on power failures span eight major Atlantic hurricanes that made landfall between 2017 and 2020 , 36. TheWe evaluate the impact of the hurricanes on nine states in the Southeast . The dependent variable in our study is the duration of time that a county experiences a power outage following hurricane landfall. Outage duration for each affected county is computed as the duration of time that elapses between the time at which the number of disrupted customers reaches its peak level and the time it drops below 5% of the customers served. A county is thus included in our dataset if at least 5% of all customers served experienced power outages during a given hurricane. In our statistical analyses, we focus on outages that last for more than one hour, consistent with minimum duration for an outstanding outage that affected at least 50,000 customers to be considered an “emergency situation” by the US Department of Energy , althougSocioeconomic vulnerability, the second as Household characteristics vulnerability, the third as Racial & ethnic minority status vulnerability, the fourth as Housing type & transportation vulnerability. We refer to the aggregate SVI index as Overall social vulnerability. Vulnerability for each theme is compiled using data from the American Community Survey on income level, age, language spoken at home, and type of housing, among others , where ranki,v is the rank of i according to v and N is the total number of counties. For each of the four themes, the percentile rankings for each variable are summed to compute a theme-level index. To compute the overall SVI, the four theme-level indices are summed for each county, then each county receives a percentile ranking according to this sum. Note that, although the SVI can be computed on the level of the census tract, our ability to use more granular data on economic and social vulnerability is constrained by the county-level unit of analysis in the power outage data. The variables used to compute each SVI theme are listed in Fig. We measure the economic and social vulnerability of communities using the CDC/ATSDR SVI, computed on the county level . SVI, whWe gather additional data to control for the severity of the storm and other characteristics of counties that are likely to be correlated with outage duration. We compute the maximum number of households that experience an outage in a county for a given storm to control for the direct impact of a hurricane on the local power grid. Data on hurricane wind speed is collected from the National Hurricane Center (NHC) . NHC repe floods . Our modFigure We begin our analysis by visualizing the relationship between social vulnerability and outage duration conditional on storm severity. Figure The plots in Fig. While the local polynomial regression curve in the top-left panel of Fig. We next present the results of a series of spatial durbin models (SDMs) in order to evaluate the claim that more socioeconomically vulnerable communities experience longer outage duration, conditional on the impact of the storm itself. The SDM is a linear regression model that includes controls for the spatial lag of both the dependent and independent variables in the model in order to return an unbiased estimate of the impact of the covariates of interest .We estimate the following model in our baseline specification of the SDM:i in storm s. s. i. i’s spatial neighbors for storm s. i’s spatial neighbors. β is a vector of coefficents associated with ee, e.g. , p. 192–The regression results for the baseline specification are presented in Table Interpretation of the coefficients of an SDM is complicated by endogenous feedback loops among spatial neighbors. An increase in socioeconomic vulnerability in a focal county, e.g. has a first-order effect of increasing the expected outage duration of the focal county but also a second-order effect whereby it changes the expected duration in a neighboring county which feeds back into the expected duration of the focal county. We report the average direct impact implied by the model, which is the average change in the logarithm of duration in a focal county resulting from a change in the socioeconomic vulnerability of that focal county, accounting for both first-order and higher-order effects. The average direct impact is thus similar to the interpretation of a slope parameter in a classic linear regression model. Based on the coefficients in Model 1, the average direct impact of socioeconomic vulnerability is We next describe this impact in terms of the change in the expected outage duration. To do this, we compute the average change in outage duration conditional on a one-decile change in the socioeconomic vulnerability. Specifically, we create one synthetic dataset per county-storm in which socioeconomic vulnerability is increased by a That being said, the broad consistency of the effect of socioeconomic vulnerability—the coefficient value ranges from An SDM is appropriate in cases where the outcome in a focal county may be impacted by outcomes or characteristics of other nearby counties. Alternative approaches to spatial regression include multiple linear regression (MLR), spatial error models (SEM), and spatial autoregression models (SAR). Each of these alternative approaches can be viewed as a restriction on the parameters estimated in the SDM. The second, third, and fourth columns of the table report results from these other approaches. The second column reports results from an MLR. This specification assumes that there is no spatial correlation among counties, i.e. In Fig. .75. See .We next demonstrate the robustness of our results in a series of models with varying county-level selection criteria and covariates included in the model. The results are presented in Table In Models 5 through 8, we estimate the impact of each SVI theme individually. When socioeconomic vulnerability is the only SVI theme included in the model, the coefficient value declines to In our final set of analyses, we explore storm-level heterogeneity in the effect of socioeconomic vulnerability on expected outage duration. Our results are presented in Table One possible source of heterogeneity indicated in Table Using data on large-scale power outages induced by eight major hurricanes that affected nine states in the Southeast United States, our analysis finds that communities with more socioeconomic vulnerability experience longer-duration power outages after controlling for the direct impact of the storm. In contrast, the other three SVI themes—Household characteristics vulnerability, Racial & ethnic minority status vulnerability and Housing type & transportation vulnerability—do not exhibit a statistically significant relationship with outage duration. The affected service regions across the hurricanes account for roughly one-tenth of the United States in terms of size and one-twelfth in terms of population. Thus, we feel confident that our results are not driven by a single storm, state, or utility.Our results point to the necessity of reexamining commonly used policies for disaster recovery, infrastructure investment, and poststorm resource allocation. Adjusting storm-recovery priorities so that communities for whom prolonged failures are more disruptive are recovered relatively sooner is one possible intervention, but also one that could come at the cost of longer duration outages overall. Alternative approaches include making the grid more robust and households in economically and socially vulnerable communities more resilient to storm-caused power failures . AdditioThe study also speaks to the need for more detailed and granular data on power outages to be made available over large spatiotemporal scales for both researchers and practitioners. In particular, more granular data on communities and households measured over extended time periods is necessary to dig deeper into the mechanisms that lead socioeconomically vulnerable communities to experience longer outages, to analyze the negative impact of these outages on economically and socially vulnerable households, and to design appropriate policy interventions. Standard models of the negative impact of natural disasters evaluate risk as a function of (1) the likelihood of a threat occurring, (2) the extent of harm conditional on an event occurring, and (3) the ability for a household to diminish the effect of the hazard . While oTo the extent there is a tradeoff between recovering those communities who can least afford extended power outages and recovering as many households as possible, these data would also permit researchers and policymakers to better quantify those tradeoffs and then design interventions that achieve an optimal balance. Even better would be for decision makers to integrate real-time information about the vulnerability of households when prioritizing recovery decisions. These data would permit utilities to allocate limited resources in a manner that minimizes economic cost—e.g. by prioritizing smaller communities that lack access to backup power and the resources to evacuate prior to a storm over larger ones that have backup power or who have evacuated—rather than seeking to minimizing the aggregate outage length.Given the growing frequency and severity of damaging weather events resulting from climate change , 49, we pgad295_Supplementary_DataClick here for additional data file.


Interventions such as advance care planning (ACP), technology, or access to euthanasia may increase the sense of control over the end of life. In people with advanced dementia, the loss of cognitive and physical function limits the ability to control care. To date, little is known about the acceptability of these interventions from the perspective of persons with dementia and others involved. This study will examine the cross-cultural acceptability, and factors associated with acceptability, of four end-of-life interventions in dementia which contain an element of striving for control. Also, we report on the development and pilot testing of animation video vignettes that explain the interventions in a standardized manner.Cross-sectional mixed-methods vignette study. We assess acceptability of two ACP approaches, technology use at the end of life and euthanasia in persons with dementia, their family caregivers and physicians in six countries . We aim to include 80 participants per country, 50 physicians, 15 persons with dementia, and 15 family caregivers. After viewing each animation video, participants are interviewed about acceptability of the intervention. We will examine differences in acceptability between group and country and explore other potentially associated factors including variables indicating life view, personality, view on dementia and demographics. In the pilot study, participants commented on the understandability and clarity of the vignettes and instruments. Based on their feedback, the scripts of the animation videos were clarified, simplified and adapted to being less slanted in a specific direction.In the pilot study, the persons with dementia, their family caregivers and other older adults found the adapted animation videos and instruments understandable, acceptable, feasible, and not burdensome. The CONT-END acceptability study will provide insight into cross-cultural acceptability of interventions in dementia care from the perspective of important stakeholders. This can help to better align interventions with preferences. The study will also result in a more fundamental understanding as to how and when having control at the end of life in dementia is perceived as beneficial or perhaps harmful.The CONT-END acceptability study was originally registered at the Netherlands Trial Register (NL7985) at 31 August, 2019, and can be found on the International Clinical Trials Registry Platform. The central theme in what is regarded as a good death in western countries, is control . AttemptPalliative care assumes that anticipating and preparing for the end of life is beneficial , 3 and aDespite many barriers to initiating ACP with persons with dementia , 9, someWhile ACP may provide some control over future decisions, there are interventions at the end of life that may provide more sense of control. At one extreme, people choosing assisted dying or euthanasia can dictate the time, place and manner of their death. Since 2002, Dutch law has regulated euthanasia with the Termination of Life on Request and Assisted Suicide Act, which legalized the ending of life by physicians at the request of patients suffering unbearably without hope of relief. The same year, Belgium adopted a law on euthanasia that is largely similar to the Dutch law . Canada The debate on legalizing euthanasia and PAS is controversial. Complete consensus seems to be unachievable due to incompatible normative frameworks that clash . DiffereTechnological advances in medicine imply patients, family caregivers and physicians need to make increasingly difficult end-of-life decisions. The growing use of technology in healthcare raises new questions such as, if, when and how the use of technological aids can affect the dying process. For example, distressing symptoms are common at the end of life in persons with dementia . PatientTo optimize care for persons with dementia, physicians need to understand differing attitudes toward end-of-life care and which factors to consider when discussing end-of-life decisions with persons with dementia and families from diverse backgrounds. Acceptability of interventions that increase control may vary by life view and personality. Control may be helpful in some cases. Early research in psychology for example, found that beliefs about having (some) control promote adjustment with life-threatening disease , 30. WitIn this study, the perspectives of persons with dementia, their family caregivers, and physicians in six countries  will provide insight into the cross-cultural acceptability in dementia care of two ACP approaches, the use of monitoring technology at the end of life, and euthanasia.The primary objective is to investigate the acceptability of the four interventions . The secondary objectives include examining differences in acceptability between groups and countries, and to explore associations between acceptability and other participant characteristics . We use open-ended questions in the interviews to examine qualitatively possible ambiguity regarding being in control through the interventions and in what situations and why the participants feel the interventions are or are not acceptable.The Attempts to CONTrol the END of life in people with dementia (CONT-END) acceptability study was originally registered at the Netherlands Trial Register (NL7985) at 31 August, 2019, and can be found on the International Clinical Trials Registry Platform. The study has a cross-sectional mixed-methods design with participants evaluating intervention vignettes and completing a survey. The vignette scripts, storyboards and early versions of the animation videos were pilot-tested between March and June 2020. Data for the CONT-END acceptability study are collected in the Netherlands, US, Germany, Switzerland, Japan and Israel. The study will be conducted according to the principles of the Declaration of Helsinki .An independent Ethics Advisory Committee was installed as a requirement of the funder, which included representatives from most participating countries in the study, including one member of the Alzheimer Association, to ensure that ethical issues that may arise are also treated in a manner that is sensitive to the international differences. The main remit is to review documents and to monitor the project’s progress from an ethics point of view. The Ethics Advisory Committee members do not receive compensation for their time and are not otherwise involved in the study.The interventions offer different levels of control and their acceptability may vary between countries, groups and individuals. The countries in this study were selected based on literature about large differences in end-of-life care, access to means to exercise control and norms regarding autonomy, technology and sanctity of life –45.First, there may be differences in acceptability of the ACP interventions between countries. This is based on literature about patient autonomy versus relational autonomy or influence of the family or professional caregiver on end-of-life decision making, and legalisation of assisted suicide and not euthanasia in Switzerland and US states . PhysicSecond, inhabitants of technology-minded countries with aggressive life-prolonging treatment and infrequent withholding of treatment at the end of life to allow a “natural course” might be most in favour for using technology in the dying. By contrast, in the Netherlands, less aggressive care is common in dementia at the end of life (e.g. low antibiotic use and invasive rehydration) –50, as iThird, a number of publications , 44 haveFor the acceptability of the interventions per group, we expect that the ACP intervention with detailed advance treatment orders will be most often acceptable and euthanasia least often acceptable in physicians. No hypotheses on acceptability rated by persons with dementia compared to the other groups are formulated because not enough is known about their views on this matter to formulate specific hypotheses. With regard to acceptability by country, we hypothesize that the ACP intervention with detailed advance treatment orders will be most often acceptable in countries where patients have high autonomy in decision making about medical procedures and care, and where people may feel they need a defence against medical overtreatment, while sanctity of life is not necessarily a dominant principle . Technology for symptom monitoring when unable to self-report, such as use of cameras in the dying phase, is expected to be most often acceptable in technology-minded countries . Euthanasia may be most often acceptable in countries that have euthanasia or PAS regulation already in place for a while (in particular the Netherlands and Switzerland) and the least acceptable in countries where ending life is highly controversial .For the explorative analyses, we expect demographics, variables indicating life view such as religion, view on dementia, attitudes regarding life-prolonging treatment and death and dying, and variables indicating personality such as coping strategy to be associated with acceptability of the interventions. These aspects of life view and personality are selected because they may relate to control. In explaining diversity in acceptability of ACP, individual differences may be more important than differences between countries and respondent groups , with tWe initially aimed to include a total of 900 participants from six countries , comprising 300 persons with (early) dementia, 300 family caregivers and 300 physicians. From each country, we planned to recruit 50 dyads of persons with dementia and their family caregivers, and 50 physicians. Recruitment procedures for persons with dementia, their family caregivers and physicians are adapted for each participating country in close collaboration with our local partners. We amended the participant target due to difficulty recruiting persons with dementia and family caregivers (see paragraph ‘Adjustments to protocol’).We work with healthcare professionals, primarily physicians working in memory clinics and hospitals, to recruit dyads of a person with dementia and their family caregiver. We also recruit via general practitioners (GPs) and dementia case managers. When persons with dementia visit their physician, the physician will offer an information package to eligible participants. Participants can then: (a) directly contact the research team, or (b) inform their physician about their decision. The physician will then ask for permission to forward the contact information of the pair to the research team.For the recruitment of the physicians, the study is announced via relevant webpages and newsletters of local professional networks and educational institutions. The researchers also directly contact physicians who are already in their professional network by email to inform them about the study. The researchers send physicians who are interested an information package about the study and call them to explain the study in more depth and to schedule an appointment for the assessment.The inclusion criteria for the person with dementia are: (1) has a diagnosis of irreversible dementia established by a physician; (2) has been informed about and is aware of their diagnosis; (3) has a family caregiver who is willing to participate in the study; (4) has decision-making capacity and is able to communicate through sufficient memory and language; (5) is able to understand and sign the consent form; (6) has adequate vision and hearing (can be achieved by using corrective lenses and hearing aid if required); and (7) consents to participate.There is no formal capacity test to avoid feelings of failure if that would result in denying participation. We rely on the clinician’s estimation of whether people have capacity to decide to participate in the study and are able to do so. If needed, we provide the referring clinicians with three relevant items of the Dementia Severity Rating Scale to aid clinical judgement of the capacity to give meaningful responses in the interview . For theFamily caregivers can participate if (1) they are willing and able to participate in the study; (2) the person with dementia they care for is willing and able to participate; (3) are ≥ 18 years old. Physicians can participate if they practice a specialty that includes provision of end-of-life care for persons with dementia. Depending on the country, the specialty could be primary care physicians such as GPs, elderly care physicians, geriatricians, geriatric psychiatrists, neurologists, and palliative care physicians.The study setting differs for the person with dementia and their family caregiver versus physicians. Ideally, the assessment with the person with dementia and their family caregiver takes place at the local research site, at their home or the practice of their healthcare professional. This can be at a memory clinic, hospital, or their physician’s practice. The assessment with the physicians will take place at their office or online via videocall.Participation in the study consists of a one-time assessment of 60 (physicians) to 90 min (person with dementia and family caregiver). During the assessment, the participants view four animation videos (range duration 1:53 to 4:51 min depending on the intervention and language). After each video, they are interviewed. The order of the two ACP-videos and the Technology video is randomized by an independent statistician. Due to the potential sensitivity of the topic, the Euthanasia video is shown last. The participants also complete a brief survey with items about attitudes concerning the end of life, views on dementia, decision-making, coping, and demographic information. Table The in-person assessment with the person with dementia and their family caregiver is be conducted by two researchers or one researcher and a volunteer. Volunteers and translators are trained by the research team in advance. After finishing the assessment, the pair is debriefed and receives information about what to do if they feel distressed afterwards related to the assessment.The number of participants is determined by the primary objective of the trial (acceptability). We will use logistic regression analyses and before the COVID-pandemic, we aimed at a total of 6 (countries) x 3 groups) x 50 = 900 respondents for sufficient power according to the 10 events per variable rule of thumb, for a minimum acceptability or non-acceptability rate of 10%. Therefore, with percentages of 10% and up, power would suffice to assess differences between 6 countries and 3 respondent groups. Testing of associations with other characteristics, i.e. life view and demographic and personality characteristics, is exploratory. Also see paragraph ‘Adjustments to protocol’.Due to COVID-19 hitting the world in the beginning of 2020, the start of the data collection was postponed to July 2020 and is extended till 2023.The COVID restrictions caused severe delays in the data collection. Healthcare providers were hesitant to join the study both as a participant and to assist in the recruitment of persons with dementia and their family caregivers due to the increased workload and wanting to protect their patients. Therefore, adjustments were made to the protocol. The recruitment strategies for persons with dementia and family caregivers were expanded to recruiting through dementia cafes and social media. In the US, an online service of patients who have volunteered to participate in research studies (Research Match) and electronic resources were used to identify additional persons with dementia. When identified from the electronic record, their physician was asked if it is acceptable to contact the patients and caregivers. A telephone screening script was developed to check whether the person with dementia and family caregiver met our inclusion criteria.After completing the data collection of the Dutch and US physicians, and after interviewing 15 dyads of person with dementia and family caregiver in the Netherlands, we decided to reduce the number of interviews to 15 per country per group. This was because 50 dyads was no longer considered feasible within the remaining study time and because we found data saturation in the Dutch data was reached after 12–15 interviews . For phyFor the adjusted protocol a new power calculation was performed. We will use logistic regression analyses and expect that collecting physician data (n = 50) in a total of 6 (countries) results in 300 physician respondents. Power depends strongly on the type of intervention as this has varied, so far in data collected in the Netherlands, the US and Japan, from acceptable for almost all (advance care planning interventions) to acceptable for closely around half. According to the 10 events per variable rule of thumb, for 7 variables, with 300 respondents, 70 events suffice for acceptability in ratios close to half of respondents, but would not suffice for interventions that are (not) acceptable for the large majority of the respondents. However, examining associations with acceptability is less relevant for interventions which are endorsed or rejected by the great majority.The primary outcome is acceptability of the interventions, assessed during the interview. The two primary acceptability measures are:  whether The secondary outcomes will be assessed using the survey. Table strongly disagree  health care is to preserve my [his/her] life as long as possible, even if that requires treatments that may cause pain or discomfort using a scale ranging from strongly agree [strongly disagree [Don’t know [what you think your relative would probably want for themselves, what you want for your relative, what you think the physician of your relative wants for themselves, and don’t know.The family caregiver and person with dementia are asked to indicate the extent to which they (dis)agree with the following statement: ly agree  to strondisagree . Don’t kn’t know  is also n’t know . The famDementia is a disease you can die from [Dementia is a normal part of the ageing process [strongly agree [strongly disagree [Don’t know [Palliative care applies from the time of diagnosis to the stage of severe dementia using similar response categories [Illness cognition refers to the dementia. All three groups are asked to rate the extent they agree with two statements: die from , 37 and  process , 74 usinly agree  to strondisagree  and Don’n’t know . Physicitegories .Illness perception also refers to the dementia. The person with dementia is asked to rate four selected items of Brief Illness Perception Questionnaire (IPQ-B) –78 that self and one that includes the word other, that overlap to different degrees. Family caregivers are invited to select the pair that best describes their relationship with the person with dementia.Inclusion of other in the self (IOS) was assessed using the IOS Scale . This isdoesn’t apply at all [completely applies [Locus of control  is measured using the 4-item locus of control scale (IE-4) . The itey at all  to compl applies . Higher not at all (0) to nearly every day [To assess possible depression in the person with dementia and their family caregiver, the 2-item Patient Health Questionnaire depression module (PHQ-2)  is used.very day . The timHave you ever accompanied a member of your family or friend suffering from advanced dementia at the end of their life is used to measure personal experience with dementia [yes [no (0).The item dementia . The itetia [yes  or no  to 7 (prepared as much as possible) to allow for greater precision [The family caregiver is asked about their preparedness for the end of life of their relative using the item ir death . We adjurecision .Demographic information includes age, gender, educational level, country of birth, religious background, worked in healthcare, relation to the person with dementia, living situation of the person with dementia, and work status of the family caregiver. The family caregiver provides the demographic information about the person with dementia. For physicians, we also ask details about their work experience; specialty, additional palliative training, work setting, years of experience with dementia care .Finally, the members of the CONT-END acceptability study research team are asked to fill in a questionnaire about their own attitudes and views regarding the study and acceptability of the four interventions to increase transparency and their reflective awareness. This will be done at the beginning and after the data collection.The pilot testing of the items for the survey was conducted in the Netherlands. During a face-to-face visit, the survey for people with dementia was read out loud to one person with dementia . Her family caregiver  examined the survey for family caregivers. Six people aged over 65 years  received the digital version of the survey for family caregivers. One of them  also evaluated the survey for people with dementia digitally. The participants were asked to indicate whether the items were easy to understand and whether they were confronting. Most items were considered clear and not confronting. Items from validated questionnaires were not adjusted despite occasional comments from the participants. The time and effort needed to fill in the survey was also acceptable. Some participants commented that it was difficult to choose one option when they had a nuanced view. Minor adjustments were made in the instructions and response options .With a professional media production group, Knowledge Media Research Centre, we developed video vignettes to explain each intervention in a standardized manner, aiming at a neutral stance, not slanted to either acceptance or non-acceptance. We choose animation videos to support understanding with visual and audio cues. Each video includes a brief introduction, an example and a summary of the main aspects of the intervention. To facilitate orientation, each video has its own colour. Further, a mnemonic for each video in the form of a hand-out with screenshots summarizes the content of the animation video for the persons with dementia and their family caregivers. The handout about euthanasia is supplemented with a sheet explaining local rules and explanation of differences with locally better-known PAS or palliative sedation.The animation videos were developed iteratively navigating the following steps: step 1, developing the scripts; step 2, reviewing, pilot-testing and refining the scripts; step 3, reviewing, pilot-testing and refining the animation videos; step 4, translating and adapting the animation videos into other languages.Step 1: Developing the scripts. The initial scripts of the animation videos were developed in English. The scripts were written with the goals in mind that they should be applicable in all six countries and understandable for all three groups of participants in this study.Step 2: Reviewing, pilot-testing and refining the scripts. The initial scripts were reviewed by the CONT-END research team, consisting of an elderly care physician, GP, epidemiologist, communication expert, psychologists, and anthropologist. Next, the partners from the other countries were consulted on whether cultural adjustments were needed. This resulted in minor changes, for example, to replace “euthanasia” in the American and German context with “termination of life on demand” and “Aktive Sterbehilfe”. The independent international Ethics Advisory Committee reviewed the scripts as well. For the euthanasia video, they suggested emphasizing the hypothetical nature of the video to avoid misunderstanding in countries where active euthanasia is illegal. All feedback was discussed within the research team and adjustments were made to the scripts.The scripts were then translated into Dutch following the forward-backward technique and read out loud during home visits to four pairs of persons with early dementia  and their family caregivers . The family caregivers were the partner or adult children of the persons with dementia. The participants were recruited through GPs. Participants were asked to comment on whether the scripts were easy to understand, neutral, and whether they were confronting. Based on the feedback from the participants, the scripts were thoroughly revised; the language and plot of the videos were simplified, overly positive words, such as “valuable”, were changed into neutral words and the difference between the two ACP interventions was clarified. The English scripts were adjusted accordingly.Step 3: Reviewing, pilot-testing and refining the animation videos. Based on the updated scripts, Dutch and English animation videos were developed and produced by a team of experts from Knowledge Media Research Centre and a freelance animation artist. The Dutch animation videos were pilot-tested digitally due to COVID-19 related restrictive measures. Eight Dutch participants  with experience with dementia or an age above 65 viewed the animation videos. They were recruited through the Regional Older people Advisory Board connected to the Leiden University Medical Center (LUMC) and via the researchers’ network. In general, the participants found the videos clear and easy to follow. Some participants pointed out that the videos gave the impression that all discomfort could be detected by the technology, and that there were no obstacles for euthanasia once all criteria are met. Potentially confronting elements in the videos were also discussed, for example, the animation of an inflamed lung reminded some people of a COVID19-infection.The English version of the euthanasia animation video was reviewed by the Ethics Advisory Committee. They suggested adding hand-outs and making the euthanasia procedure more clear for non-Dutch viewers. The English technology video was presented at the Alzheimer’s Association International Conference 2020  to collehttps://www.webfx.com/tools/read-able/check.php). The results suggested that almost all of the updated scripts (rated as grade 9 to 10) were more easily readable than the initial versions (grade 10 to 13). The updated script about technology had an average level of grade 9 and should be easily understood by 14 to 15 year-olds. The other three updated video scripts were rated as grade 10, which should be easily understood by 15 to 16 year-olds.Before and after the pilot-testing, readability tests were performed for the scripts with an online tool  from each country to check whether anything in the scripts was too confrontational or difficult.  adjustments in wordings were made when necessary. The Dutch research team and the local partners provided feedback on the timing of the animation videos and approved of the final versions.Descriptive statistics will be used to present the acceptability of the four interventions. The internal consistency of the scales will be calculated using Cronbach’s alpha. Descriptive statistics will be calculated to describe the demographics of the respondent groups per country.Do not know’ as a response option is often ignored and excluded from the denominator. A dichotomous variable will be create with a denominator of ‘acceptable versus not acceptable plus do not know’. The analyses will be unadjusted and adjusted for the most important life view or personality parameter . We will explore associations between acceptability and participant characteristics  and personality , depression, medical decision making, professional or personal experience with dementia, physician’s comfort with end-of-life conversations, and caregiver burden, and life view . For this, we will use stepwise backward regression analyses. The analyses will be done with and without adjustment for country and group .We will use logistic regression analyses with acceptability of the intervention as the dependent variable to examine differences in acceptability between group and countries. ‘Qualitative data from the interviews will be used to map possible ambiguity regarding being in control through the interventions, and as to why and in what situation the participant feels the interventions are acceptable. A content analysis regarding acceptability of the interventions will be conducted. Additionally, across all interviews, we will conduct a thematic analysis on perceptions of control. Data collection and data analysis will be executed iteratively. Coding is supported by the software program ATLAS.ti.To protect participant privacy, the data will receive a unique identification code with linkage keys to be stored securely separately from the data. Names and other information that could directly identify the participant are therefore omitted. As long as it is necessary to trace data to an individual participant, the participant identification code list per country will be maintained to enable linking the data to a particular participant. This will be until the data has been fully cleaned and no new cleaning issues have arisen.Participants can choose to fill in the survey digitally or on paper. We will use a secure certified online program for the digital questionnaires, Castor . The data from the paper survey will be entered in the online program by the researcher. We will subject 10% of the data to a random audit by a second researcher to test the accuracy of quantitative data entry of the paper survey and forms. The audio files of the interviews will be deleted after they have been transcribed and the transcripts have been checked. Data will be entered and stored using a secure data server. To allow for cross-national comparison, the study will be performed in non-EU countries according to the same protocol that is acceptable for use in the EU countries.The findings will be submitted to relevant peer-reviewed scientific journals and national and international conferences within the field. We will share the results with key stakeholders involved in both homecare and long-term care of persons with dementia to help improve clinical practice. The animation videos are available from the PI upon reasonable request after conclusion of the data collection.In this study examined the perspectives of persons with dementia, their family caregivers and physicians in six countries  to provide insight into the cross-cultural acceptability in dementia care of two ACP approaches, the use of monitoring technology at the end of life, and euthanasia. We anticipated and experienced practical and operational issues in conducting the study. First, due to COVID-19 restrictive measures, more assessments with physicians will be conducted online than initially anticipated. The online assessment offers more flexibility, possibly lowering the threshold for physicians to participate in the study and allowing the research teams to collect data simultaneously in multiple countries. While the COVID-19 pandemic may make it difficult to find physicians who have time to participate in a study, it also highlights the importance of timely ACP and monitoring distress signals at the end of life, possibly motivating physicians to share their opinions about these interventions. Second, we strive to conduct the assessments with the person with dementia and their family caregiver in person. It could be that the person and family caregiver are reluctant to receive visitors, even if allowed. The online option with these groups will also be offered as a last resort option after consultation with the local institutional review board and based on the judgement of the family caregiver if this would be a feasible option for their relative. Third, the recruitment of persons with dementia matching our inclusion criteria may be challenging in countries where dementia is generally diagnosed in a late stage of the disease.The study limits professional caregivers’ perceptions to those of physicians and nurse practitioners with medical responsibilities whereas nurses have a role in providing these interventions as well. Further, data will not be collected simultaneously in all countries and groups; as a result of the sequential cross-sectional design, we cannot adjust for possible trends over time.Strengths of this study include the cross-cultural aspect, comparing the perspectives of persons with dementia, family caregivers, and physicians, the sample size, mixed-method design, and initiative to increase the researchers’ transparency and their reflective awareness. The animation videos were developed using input of international experts, have been pilot-tested, and have been reviewed and approved by an independent Ethics Advisory Committee. This study will contribute to a more fundamental understanding of how acceptable a range of interventions differing in level of control offered is, and more generally, as to how and when having control at the end of life in dementia is perceived as beneficial. This facilitates aligning interventions with preferences and will help improve dementia care.