Ehmt1±) expresses anxiety, autistic-like traits, and aberrant social interactions with non-cagemates. To investigate how Ehmt1± mice behave with unfamiliar conspecifics, we allowed adult, male animals to freely interact for 10 min in a neutral, novel environment within a host-visitor setting. In trials where the Ehmt1± mice were hosts, there were defensive and offensive behaviors. Our key finding was that Ehmt1± mice displayed defensive postures, attacking and biting; in contrast, wild-type (WT) interacting with other WT did not enact such behaviors. Further, if there was a fight between an Ehmt1± and a WT mouse, the Ehmt1± animal was the most aggressive and always initiated these behaviors.Kleefstra syndrome in humans is characterized by a general delay in development, intellectual disability and autistic features. The mouse model of this disease (The online version contains supplementary material available at 10.1007/s10071-023-01757-2. EHMT1) gene  c57bl/6j background] and ten male Ehmt1± mice were part of this experiment. A power calculation to estimate sample size was not done a priori, since this was a novel experiment and the outcome was not predicted. Animals were bred in-house, 16–20 weeks of age at the start of behavioral training, group housed in heterogenous genotype groups  and had ad libitum access to food and water. Mice were maintained on a 12 h/12 h light/dark cycle and tested during the light period. In compliance with Dutch law and Institutional regulations, all animal procedures were approved by the Centrale Commissie Dierproeven (CCD) and conducted in accordance with the Experiments on Animal Act. Project number 2016–014 and protocol number 2016–014-030, approved by the national CCD and local animal welfare body at Radboud University, The Netherlands.Ten male Ehmt1±), and the second cohort of three cages with seven animals  .All animals were extensively habituated to the experimenters by handling for a period of two weeks before habituation to the experimental environment. By the end of the second week, the animals freely climbed upon the experimenters’ hands and showed no sign of distress when picked up by the experimenters. Pick-ups were performed by the tail until the third day of handling, from there on animals were picked up by cupping  made of lacquered wood, with no deliberate cues in sight. Habituation was composed of two sessions, in the first of which all animals from the same cage were placed together in the box for 30 min. In the following session, each animal was left to freely roam or explore on its own for ten minutes. The next time the animal would enter the box would be during the experimental phase.Two boxes were used simultaneously in the behavioral room, each box had distinctive colored floors, and every day the cues surrounding and inside the box were changed, meaning that there were two new boxes daily. Pairs of mice would be placed randomly into either of the boxes, and no mouse would ever re-enter the same environment. Cues were composed of everyday materials  and were attached to the walls inside of the maze in a two-dimensional manner. Walls surrounding the box also were equipped with cues, which were bulkier, to provide three-dimensional cues. Additionally, each novel environment was paired with a particular smell, provided by a cotton pad with scented oil glued within the box, out of the animal’s reach. The smells used were: sandalwood, lavender, vanilla, English rose, jasmine, honeydew, strawberry, blueberry, blue water and musk. All pairs interacting on the same experimental day were cued to the same smell.Video recordings were achieved with a Logitech HD Webcam C270 clamped onto the ceiling of the experimental room. Light level in the room was ~ 35 lx.Before the beginning of each trial, the floor of the box was thoroughly cleaned with 70% ethanol. The trial began by placing a mouse, the host, in the experimental environment and leaving them to roam freely. Each mouse had already been habituated to the experimental room and to the empty experimental box. At the 20-min mark, a non-cagemate, the visitor, was introduced to the environment, and the host-visitor pair were left to interact for ten minutes Fig. A. This sThe task used in this research is adapted from Avale et al.  for all measures between observers. Behaviors were classified visually, and the three types of behaviors were: sitting, wall and cue exploration, spatial exploration and social interaction. Sitting was defined as when the animal sat grooming or sitting still. Cue and wall exploration was defined as smelling, touching or actively looking into the direction of cues in case they were out of reach. Spatial exploration was defined when the animal was moving throughout the arena and not exploring cues nor sitting. Social interaction was defined as when one or both of the animals were touching or smelling each other.In the case of trials where there were defensive or offensive behaviors, a defensive-offensive scale was used per individual. The scale had 4 levels, with 0 being no defense, 1 if the animal stands on their hind paws and/or rattles its tail, 2 when the animals engage in a fight, and 3 when the fight reaches a point where one mouse emits a distress vocalization. In this case, the offender is scored with 3 while the offended animal depending on its behavior, is scored from 0 to 2 . Once an animal in a trial reached scored 3, the host-visitor pair were separated by the experimenter and the trial was terminated, to avoid stress and harm to the animals.In case the trials were terminated, the time at which the trial was stopped was noted, and the percentages of behaviors were calculated out of the total time of the trial.Statistical analysis was run with each trial as the sample. Analysis was repeated for each animal as the sample in supplementary materials. Since there were trials terminated early, the values used for analysis are percentages of the total time spent in the trial.Ehmt1± vs. WT) and role (host or visitor) as the between-subject variable. Data concerning social interaction over sessions were analyzed using repeated-measures ANOVA with genotype (Ehmt1± vs. WT) and session  as the between-subject variables. Data concerning social interaction over sessions for a single genotype were analyzed using univariate analysis with a session as the between-subject variable since not all subjects completed all sessions. Data concerning interaction time in trials with defensive and offensive behaviors and those without were analyzed using independent sample t tests. Posterior analysis was performed using independent sample t tests.All behavioral data were analyzed using IBM SPSS. Data concerning exploratory behavior were analyzed using repeated-measures ANOVAs with time spent in different behaviors as the within-subject variable and genotype , and every Ehmt1± animal was part of at least one trial with DO-behaviors. In previous studies using the original version of the task, no antisocial behaviors had been reported among WTs  . The percentage of time spent in social interaction , and there seemed to be an additive effect where there was a linear change from two wild-types to mixed interactions, to finally two Ehmt1± spending more time interacting. The latency until the first social encounter showed an opposite trend .First, we analyze the trials with no DO-behaviors, which were 10 min long, summarized in the blue square in Fig. Ehmt1± hosts, and statistical analysis showed an effect of the genotype of the host . When analyzing the time spent interacting over consecutive trials only for Ehmt1± hosts, there was a significant decrease over time , while when performing the same analysis for WT hosts, no differences could be seen across sessions .Each animal experienced a maximum of one trial per day, either as a host or a visitor, and on the following days they could perform the task again until every animal experienced the role of host and visitor at least once. To analyze the effect of repeating the task and if their behavior changed over time, we evaluated the time spent by each host engaging in social interaction, split for consecutive trials Fig. E. A trenEhmt1± hosts had longer interaction times and shorter latencies until the first social interaction. Over repeated instances of performing the task, the time spent in social interaction decreased for Ehmt1± hosts.Overall, in trials with no DO-behaviors, trials with Ehmt1± host . Social interaction in these trials was divided into DO-behaviors and interaction without DO-behaviors. The time spent posturing (standing on hind legs), tail rattling, biting and fighting was scored for each individual of the pairing, as well as every instance of DO-behavior , with Ehmt1± animals enacting more DO-behaviors.Next, we analyze the trials where there were DO-behaviors, which only happened when there was an Ehmt1± animals defensive-offensive levels were similar for host and visitor, but when there is an Ehmt1±–WT pairing, the Ehmt1± was always the biggest offender. The initiator of the offense was also identified in all such interactions , while in Ehmt1±—WT pairings, it was always the Ehmt1± animal who initiated the offense.Continuing with trials that had DO-behaviors, the latency until the first DO-behavior was not different depending on the genotype of the visitor Fig. F. IncreaEhmt1± animals were hosts. In Ehmt1±—WT pairings, the Ehmt1± mice spent longer in DO-behaviors, had a higher count of DOB and always initiated the offense, while WTs only postured or rattled their tails. In Ehmt1±—Ehmt1± interactions, the visitor spent longer in DOB than the host, but there was no difference in the count of DO behaviors. Both hosts and visitors were likely to initiate an offense, and both roles reached the highest level in our defensive-offensive scale.In sum, DO-behaviors were only observed when Ehmt1± mice in social paradigms , while others do Supplementary file2 (EPS 2253 KB)Below is the link to the electronic supplementary material.


In Germany, only about 10% of patients with alcohol use disorder (AUD) are treated by the professional help system. “The First 30 Days without Alcohol”, an interactive e-health intervention, was developed to support people with “alcohol problems” to abstain from alcohol. The aim of this study was to examine the feasibility of the approach, the program’s target group, if and why it is effective. In March 2022 an email was sent to all users who had completed the program. A link to a web-based survey regarding the target group’s characteristics, its alcohol-use patterns, former attempts to change the problematic drinking behavior and experience with the program was introduced. The Alcohol Use Disorders Identification Test (AUDIT) was used prior and post intervention. A total of 718 participants completed the questionnaire. Of these, 99.2% suffered from AUD; 81.6% of participants were females, and about one third reported some form of psychiatric comorbidity; 46.6% did not use any additional help or assistance apart from the program; 78.3% reported to be abstinent after participation in the 30-day program, and the data show a significant AUDIT score reduction. Primary e-health interventions may contribute to the established addiction-help system. The intervention seems to reach predominantly highly educated and high-functioning females because of their characteristics. In Germany, according to the criteria of the Alcohol Use Disorder Identification Test (AUDIT), problematic alcohol consumption is present in 17.6% of the adult population, while 3.1% are alcohol dependent and another 2.8% have been diagnosed with alcohol abuse ,5. Even Web-based, electronic health interventions (e-interventions) are heterogenous with specific types of intervention and may play a crucial role in intervening in alcohol use and especially in AUD ,10. In rA novel approach is the establishment of abstinence-oriented interactive tools to address people with alcohol use problems with specific characteristics . RegardiAnother study used asynchronized as well as synchronized chats with a counselor for a duration of ten weeks and found significant effects . A recen“The First 30 Days without Alcohol” (30-day program) is one of the most frequently used e-interventions in the field of alcohol treatment among German-speaking people. It was developed in 2019 by Nathalie Stüben who was suffering from alcohol addiction, overcame it without using the professional addiction care system and started to publish web content about alcohol, AUD and abstinence. The online program consists of two parts: (1) cost-free information about addiction and abstinence via newsletters, Instagram, podcasts, YouTube and TikTok, and (2) the two paid online programs, “The First 30 Days without Alcohol” (30-day program) and the subsequent program “Stabilize Abstinence”. The programs support people with “drinking problems”—from risky drinking up to alcohol addiction—in living without alcohol. According to the primary goal of the current S3 guidelines , the 30-The present study aims at examining the target group’s characteristics, its alcohol-use patterns, their former attempts to change the problematic drinking behavior and whether the program is effective as well as which parts of the program’s design make it effective. The characteristics of the target group included sociodemographic data and physical as well as psychological comorbid disorders. The latter is of interest because alcohol use disorder is associated with various mental disorders, such as affective disorders, anxiety disorders or attention deficit hyperactivity disorder (ADHD) ,31. It wThe 30-day program has been online since October 2019. On the 27 March 2022, a one-time email went out to everyone who had completed the program by then, introducing a link leading to a web-based survey questionnaire on the domain “oamn.jetzt”. The questionnaire offered multiple choice questions regarding the target group’s characteristics, alcohol-use patterns, former attempts to change the problematic drinking behavior, and experience with the program. In addition, the Alcohol Use Disorders Identification Test (AUDIT) was used prior and post intervention. The survey was closed two weeks later. Data were collected using the tool “Typeform”. Prior to participation, participants were informed about aims, contents and background of the study as well as about anonymous data handling and the voluntary character of participation.Initially, independent data were collected . Then, participants were asked about smoking behavior, physician’s diagnosis of any psychiatric disorder and whether abstinence reduced symptoms of the above-mentioned disorder. After that, the Alcohol Use Disorders Identification Test (AUDIT) as a WHO-recommended tool to assess severity of alcohol use  was usedSPSS Statistics Version 28.0.1.0 was used for statistical analysis.n = 2943). The questionnaire was accessed by 1515 participants (51.5%). The questionnaire was started by n = 1019 participants (34.6%) and submitted by n = 746 (25.3%) participants. N = 718 agreed to data use for scientific evaluation leading to a completion rate of 24.4% with an average completion time of 15.47 min.The call for participation was sent to all users of the 30-day program  and highly educated . In sum, 32.2% (n = 174) were smokers, 20.8% (n = 149) had never smoked, 55.0% (n = 395) quit in the past. Participants were 49 years old ; the youngest was 23, the oldest 78. The vast majority were female  had not been diagnosed with any psychiatric disorder (except substance use); 32.2% (n = 231) suffered from any psychiatric disorder. Regarding those who stated that they have any psychiatric disorder, 52.8% (n = 180) reported depression, 22.9% (n = 78) anxiety disorder(s), 12.9% (n = 44) eating disorders, 8.8% (n = 30) post-traumatic stress disorder (PTSD) and 2.6% (n = 9) attention deficit/hyperactivity disorder (ADHD).The majority  had not been (completely) abstinent; 50.2% (n = 116) stated that symptoms were significantly reduced; 10.8% (n = 25) reported that all symptoms disappeared; 16.5% (n = 38) reported that symptoms were unchanged; and 11.3% (n = 26) could not decide.Regarding remission of symptoms of the above-mentioned psychiatric disorders during abstinence, participants indicated that 10.4% (n = 562), while 29.7% (n = 213) were abstinent for 0–3 months, 21.3% (n = 153) for 4–6 months, 13% (n = 93) for 7–12 months and 14.3% (n = 103) for over 12 months. However, 21.7% (n = 156) had not quit yet.When participating in the survey, the vast majority indicated having quit drinking completely  started the program during the last 3 months, 44.4% (n = 319) before more than 3 months ago but less than 1 year and 24.7% (n = 177) before more than 1 year.Moreover, 30.9% .Regarding the mean outcome values, the total AUDIT score was 22.6 (SD = 6.56) before participating in the 30-day program. After having completed the program, the AUDIT score was significantly reduced to a mean of 3.26 (SD = 6.19) (The most significant results were the reduction of the frequency of drinking (means before and after: 3.58 vs. 0.64), the amount of drinks (2.12 vs. 0.29) and the frequency of drinking more than six drinks (2.80 vs. 0.39). n = 136), TV , print and online articles , search engines such as Google  and the above-mentioned podcast . Other types of media  and recommendations  were rather infrequent ways of becoming aware of the 30-day program.The majority of participants knew about the existence of the 30-day program via YouTube , the possibility to stay at home (not to go out)  or to integrate the 30-day program with everyday life , a feeling of “mismatch” between oneself and the professional addiction help system , the opportunity to start “right now” , increased awareness around having an alcohol problem  and a personal recommendation of the program .There were multiple reasons for deciding to participate in the 30-day program such as a positive attitude towards future abstinence  “enjoyed” the program, 36.1% (n = 259) stated that they “really enjoyed” the program; others could not decide or did not enjoy the program.Out of all participants, 44.6% (n = 10) stated to have learned nothing. All other participants stated to have learned that abstinence can be considered as a kind of benefit , to be not alone with the alcohol problem , the important role of alcohol in one’s own life , to change their way of thinking , a new strategy for abstinence  and to understand oneself in a better way .Learning effects were stated to be high in general: Only 0.4% (Specific components of the 30-day program were considered to be helpful. These results are shown in n = 183) or almost all  of the required tasks; 13.5% (n = 97) only watched the program’s videos and read the respective texts and only 1.1% (n = 8) did not use the provided material.Most of the participants had completed all  or “positive changes” , and only 6.3% (n = 41) recognized no or nearly no or even negative changes. For specific changes in their different aspects of life, see Nearly all participants recognized “pronounced positive changes”  or “significantly easier”  than expected to quit drinking for the majority of all participants. However, 16.3% (n = 117), respectively, had not quit completely when answering the questions.Using the 30-day program, it was “easier”  experienced lapses or relapses after having started the program, as presented in For alcohol-dependent subjects, the question of lapses and relapses is a highly important aspect that was assessed in the survey, too. Of the subjects, 23.4% (n = 402) did not use any additional help or assistance. Some used the second program “Stabilize Abstinence”  or sought additional help from a psychotherapist , a physician , an addiction counseling center , a self-help group , other online offers/programs .To abstain from drinking, nearly half of all participants .A significant part of participants stated that they would recommend the 30-day program to others  of 2943 participants started the detailed questionnaire, about half of the users assessed the questionnaire and 718 (24.4%) submitted data indicating a major interest of participants in providing relevant data.p < 0.01) after having finished the program.Of these, 99.2% suffered from AUD as indicated by an AUDIT score of 8 or higher. The mean AUDIT score of 22.61 (SD = 6.6) when entering the program was significantly reduced to a mean of 3.26 (SD = 6.19) . The majority of those who quit alcohol use completely with the help of the 30-day program appreciated the positive way of thinking about abstinence followed by the decentralized possibilities to use the 30-day program as well as the personal communication style combined with learning tools about alcohol and the possibilities of interaction. The majority  enjoyed using the program and evaluated it to be a real profit for them. However, (re-)lapses occurred during the 30-day program as well as after having finished the program. Another significant difference relates to the number of drinks consumed before and after the program respectively treatment, which mostly improved . Few were unchanged , or worsened .For decades, therapeutic options for alcohol dependence have been dominated by self-help strategies. Meanwhile, there is a plethora of studies, reviews and meta-analyses about therapeutics ,34,35. AIn spite of the broad range of therapeutic options, only about 10% of alcohol dependent patients can be reached by these options  and the In contrast to the easy way of providing  information with web-based interventions, interaction is more difficult but crucial regarding effectiveness . NeverthToday, there are many more web-based interventions than in the past; these interventions are increasingly analyzed and evaluated ,42,43,44The main characteristics of web-based interventions are that it is a low threshold to use these interventions, they offer permanent availability and they provide the possibility to adopt an active role in one’s own (pathologic) pattern of alcohol use. These aspects may have strengthened digital interventions during the COVID-19 pandemic and its lockdowns due to the unavailability of any  services. Beyond that, most recent web-based interventions such as the 30-day program enable interaction with others and feedback. However, there may remain a paucity of “real” therapeutic empathy. Nevertheless, web-based interventions in the field of AUD apparently have a promising future. This future will probably not comprise a “pure” digitalization of existing therapeutic interventions but developing, new types of interventions and materials. Of course, there is an epidemic need and a broad interest.There are some limitations of this study to be discussed. This study has to be viewed as a proof-of-concept study integrating 718 participants out of 2943 users of the 30-day program. As in other anonymous web-based studies, generalizability of findings can be questioned. Furthermore, web-based surveys do not allow control of the sample regarding participation (participation bias) which must be considered when interpreting the results; this is valid for personal characteristics of participants as well as their attitudes, their success of abstinence, tendency to minimize the problem, tendency of socially desirable answers and further aspects. However, it can be assumed that all users of the 30-day program identified a problem with their drinking pattern. This may lead to more reliable answers concerning alcohol consumption. Beyond that, the high degree of privacy may strengthen participants’ honesty. Another limitation of the study is that the program is not accessible to everyone, as one has to pay for the program. This limits the representativeness of the sample of people with AUD by excluding those who do not have the financial resources. In addition, it is believed that people who spend money on such a program are more likely to be among the motivated. Motivation is a key factor in successful abstinence and may be a prerequisite for program effectiveness. At the same time, the financial investment may have increased the motivation to implement the program.Overall, these preliminary data indicate that many people who were not attracted by the professional addiction help system may profit from digital online interventions such as the 30-day program. However, the long-term effects of such interventions are not yet clear. Therefore, long-term studies including control groups are necessary to further explore the benefits of digital online interventions.In conclusion, the present study shows that the interactive web-based program “The First 30 Days Without Alcohol” has a positive effect on reducing AUD symptoms. Most participants were abstinent after the program. Specifically, women appeared to be attracted to the interventions presented. Due to the low-threshold and anonymous offer, people with AUD can be reached and supported who have not yet arrived in the established addiction support system. The results give the first and many promising indications of the effectiveness of the program. Based on this, randomized controlled trials should be conducted to examine these initial efficacy study results.


In comparison with the control group, the experimental group showed significantly greater post-intervention changes in the CIST score, PFT and RPT parameters, static balance, and Y-balance anterior (p < 0.05). Conclusions: The senior musical program enhanced older women’s cognitive, respiratory, and physical functions and promoted a sense of accomplishment and self-satisfaction.Background: We aimed to investigate the effects of a community-based senior musical program on the cognitive and physical functions in older women. Method: Older women aged ≥65 years participating in a program at a community welfare center were randomized to experimental (n = 17) or control (n = 17) groups. The control group participated in singing and yoga classes offered at the welfare center, while the experimental group participated in a senior musical program consisting of vocal training, dancing, and breathing training. The effects of the 12-week program  and the intergroup differences in outcomes were compared using the cognitive impairment screening test (CIST), pulmonary function test (PFT), respiratory muscle pressure test (RPT), and static and dynamic balance tests. Result: The experimental group showed significant post-intervention changes in CIST scores, cardiorespiratory parameters, and static and dynamic balance ( In 2021, the Republic of Korea was designated as an aged society with the older adult population reaching 16.5% of the total population owing to improved standards of living and advances in healthcare technology. At this pace, the country is projected to become a super-aged society with 20.3% of its population being older adults by 2025 ; an; an25]; The purpose, procedure, and method of the study were explained to all participants, and only those who voluntarily consented to participate were enrolled. This study was approved by the bioethics committee of Daejeon University and is registered in the WHO International Clinical Trials Registry Platform (KCT0007769).This study is a preliminary study. This study used a two-group pre-test and post-test study design. Sample size was determined using the G*power program , and with reference to the main effect size (d) of 1.11 reported by Kim et al. , signifiThe control group participated in singing and yoga classes offered at the welfare center. The singing class was led by an instructor, and the participants sang along to songs with recorded music playing in the background. A song was chosen every week for repeat practice until the participants could sing along without looking at the lyrics. The yoga class was led by an instructor, and the difficulty level was progressively increased over the weeks. Both the singing and yoga classes were conducted for 12 weeks .The experimental group underwent a senior musical program designed as a purposeful and motivational program that comprehensively enhances cognitive, respiratory, and musculoskeletal functions . With reThe effects of the community-based health-promoting programs for older adults were compared using the CIST, pulmonary function test (PFT), respiratory pressure test (RPT), and the static and dynamic balance tests. One participant in the experimental group and one participant in the control group withdrew from the study midway due to personal reasons, so data from a total of 16 participants in each group were analyzed. After the 12-week program, the control group was offered the same musical program provided to the experimental group. The study design is illustrated in The CIST was developed by the Korean Ministry of Health and Welfare to address the limitations associated with the repeated use of existing cognitive impairment screening tools in the long term. It can screen for cognitive impairment and measure cognitive function in a relatively brief period of time (approximately 10 min), and cognitive impairment can be determined according to the participant’s age and education level . The CISIn this study, we used the PFT to assess pulmonary function . The PFT2O). The peak values of the pressure recorded during three forced inhalations and exhalations were recorded as the maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP), respectively.The effects of the intervention program on respiratory muscle strength were measured using RPT . The preThe effects of the intervention program on the participants’ static balance were quantitatively analyzed using a Wii balance board . The WBB is an affordable and portable force plate that can be used with the Balancia software to measure body sway by quantifying path length, velocity, and 95% area of the center of pressure (CoP). It shows high concurrent validity in comparison with a force plate (intraclass correlation coefficient (ICC) = 0.94) and is widely used in various clinical studies due to its portability and ease of use. With reference to the method used in a previous study on older adults, the participants were instructed to maintain a static standing position for 20 s with their eyes closed and then open, with their feet shoulder-width apart. The average value of three measurements was recorded .Dynamic balance was tested using the Y-balance test. The Y-balance test is a tool used to assess dynamic balance by measuring the maximum distance a person can extend one leg to the anterior, posterior lateral (PL), and posterior medial (PM) directions from a marked Y line while maintaining balance with their dominant leg. It is a widely used clinical tool with a high reliability (ICC range: 0.85 to 0.93) .p < 0.05.The collected data were entered into a Microsoft Excel sheet and analyzed using the IBM SPSS Win ver. 25.0. The data were presented using descriptive statistics, namely mean and standard deviation, and normality of data was tested using the Shapiro–Wilk test. Homogeneity of participants’ general characteristics and baseline outcome measures was analyzed with an independent t-test, and changes in the outcome measures after the intervention in comparison with the baseline within each group were analyzed with paired t-tests. The statistical differences in the intervention period between the two groups were analyzed with an independent-samples t-test. The statistical significance (α) was set at p < 0.05; The two groups did not show significant differences in their CIST score at the baseline, and only the experimental group showed a significant change in the CIST score after the intervention (p < 0.05). In contrast, the control group only showed a significant change in MVV (p < 0.05). Furthermore, the experimental and control groups showed significant differences in FVC, FEV1, and MIP . In addition, the control group showed significant changes in velocity with eyes open (EO), path length with eyes closed (EC), and Area 95% EO after the intervention (p < 0.05). The experimental group showed significantly greater post-intervention changes than the control group in all parameters of the static balance test . The control group showed significant changes only in the Y-balance test anterior value (p < 0.05). The two groups showed significant differences in the Y-balance test anterior and Y-balance test posterior lateral values .This study aimed to develop a senior musical program that can comprehensively promote respiratory and musculoskeletal functions in older adults and investigate its effects on older women’s cognitive, respiratory, and musculoskeletal functions. The results showed that the senior musical program positively improved older women’s cognitive and respiratory functions and their static and dynamic balance (p < 0.05). We speculate that a dual task involving saying verbal lines and dancing simultaneously led to a greater activation of the cerebral cortex, thereby helping to improve cognitive functions.Cognitive decline leads to dementia in older adults, thereby tremendously impairing their own and their family’s quality of life . In a stp < 0.05). As for the RPT, the experimental group showed a 29.9% improvement in MIP (effect size 0.94) (p < 0.05). The potential motivation and sense of fulfillment experienced by the participants in the senior musical program may have contributed to their voluntary practice of the program’s exercises outside of the prescribed intervention, subsequently resulting in improved respiratory function. Nevertheless, no significant changes were observed in MEP after the intervention (effect size = 0.58), suggesting that the senior musical program had a limited impact on expiratory muscle strength because the activity involves singing while breathing in.To analyze the effects of the senior musical program on respiratory function, we examined the changes in the PFT and RPT scores. Eley and Gorman  administp < 0.05). As for dynamic balance, the experimental group showed a 5.9% improvement in the Y-balance test anterior, 6.2% improvement in the Y-balance test PL, and 4.5% improvement in the Y-balance test PM values (p < 0.05). The improved balance ability observed in order women participants of the musical program may be due to the continuous dancing and singing required by the program, as well as the participants’ baseline respiratory function and low lower extremity muscle strength. The participants’ increased attention to balance during the program may have contributed to the observed outcomes.Falls caused by weakened lower-extremity muscles have been identified as a major cause of death among older adults. Thus, balance, which is based on muscle strength, is an important component in the quality of life of older adults . WallmanThis study had a few limitations that may impact the validity of the study. First, since the participants were allowed to participate in other programs offered at other welfare centers, it is possible that these programs also influenced the participants’ physical and cognitive functions. Second, the participants were recruited without regard to their income level and education level, so there were no different levels of difficulty available. In addition, the CIST evaluation tool is an evaluation tool developed according to the situation in Korea, and it must be changed to another cognitive function evaluation tool to apply it to other countries. Third, no follow-up assessments were performed, which precluded evaluations of the long-term effects. Fourth, as this study is a preliminary study, it is necessary to closely analyze the intervention effect through follow-up studies. Further research is needed to address these limitations and provide evidence to support the efficacy of senior musical programs.This study aimed to develop and evaluate the effects of a senior musical program that may prevent physical and cognitive functional decline in older women. Our results showed that the senior musical program had positive effects on older women’s physical and cognitive functions. We recommend community welfare centers to offer this senior musical program to older women and encourage further follow-up studies to build on these findings.


The aim of this paper is to highlight the key lessons learned from Australia’s successful program to eradicate bovine tuberculosis (TB) over a 27-year period from 1970 when the Brucellosis and Tuberculosis Eradication Campaign commenced, through to when TB freedom was declared on 31 December 1997.As well as discussing the key elements of the national program and its success factors, the author documents a number of case studies and reflects on personal experiences in the far north-west of the state of Queensland during the very difficult latter phases of the program from the mid 1980s and subsequently as State program leader. The late 1980’s was a crucial time in the program leading up to a target declaration of Impending Freedom from TB. Australia eradicated bovine tuberculosis (TB) over a 27-year period from 1970 when the Brucellosis and Tuberculosis Eradication Campaign (BTEC) commenced, through to when TB freedom was declared on 31 December 1997 . The oriThe key elements of this approximately AUD$1 billion program have been well documented , 4. The In 1987 the author was transferred as Divisional Veterinary Officer to the Mount Isa Veterinary Division in the state of Queensland Fig. , one of The late 1980’s was a crucial time in the program leading up to a target declaration of Impending Freedom from TB by 1 January 1990, which required meeting the criteria for declaration . These cIn the Mount Isa Division and many other regions across the north of Australia, a number of challenges were faced to achieve eradication. Firstly, a significant number of infected premises remained and although the TB prevalence had been reduced to relatively low levels after many years of effort, much needed to be achieved over a short period of time. This was exacerbated by the relatively short cattle management season dictated by weather. That is, the summer months were too hot to work cattle, plus inaccessibility during the wet season, meant that cattle could only be mustered once or twice per year for operations such as tuberculin testing. Consequently, cattle were often relatively wild and lack of infrastructure, particularly fences, on some properties meant that in some parts of the region the cattle were essentially feral. All of this combined meant that it was difficult to achieve 100 percent musters (rounding up) of cattle for testing and/or depopulation. To overcome the latter issue, two key measures were utilised. Firstly, a mustering subsidy was paid to owners to cover the additional costs of achieving close to 100 percent musters, compared with a normal ‘commercial muster’ (which may have been only 80–90 percent). Secondly, paddocks were inspected by stock inspectors in helicopters to confirm the efficiency of the muster. Any unmustered cattle that were found were generally shot. The region also featured some large areas with feral cattle populations that had to be controlled and/or depopulated.The mechanism to achieve eradication at a property level was an approved property program (APP) for each of these large cattle stations, tailored to accommodate individual circumstances. The APP was a legal agreement between the property owner and the government agency, and included: property details and it’s TB history; a summary of the eradication program for the coming year and any problems anticipated; the program details, which generally was organised by epidemiological group and/or paddock/area on the property and included animal identification requirements, whether the group was to be tested or depopulated or a combination of both; inspection requirements; movements of cattle within the property; their disease status progression; assistance measures that would apply; and any other general program conditions.A key issue was to recognise the limitations of the tuberculin test. The test used was the single intradermal caudal fold test, as it was the only one that was practical to use under the circumstances. The gamma interferon test was used late in the program, although it did present practical difficulties and the TB prevalence was so low by this time that it was virtually impossible to judge its value. The sensitivity of the single caudal fold test was at-best 70 percent , althougTo Illustrate how the program worked on the ground, three case studies are presented.This was a large (approximately 90 km by 110 km) cattle station towards the south of the region. It had a carrying capacity of around 30,000 head and was divided into multiple paddocks. Management of such an enterprise is complex, with the annual mustering program having to be carefully orchestrated. This property had a long history of infection, primarily in the western parts but had reached a confirmed free one status (CF1—three whole herd clear tests at least 6 months apart) by 1986, through a program of TB testing and targeted depopulation. However, after a change in ownership, TB was detected in again in 1987 in three animals consigned to the abattoir. An analysis was conducted of the internal epidemiological relationships between groups of cattle on the property, which led to an intensive program of testing and targeted depopulation (either on an age or paddock basis). Overall, 17 TB infected animals were detected between 1987 and 1989, with all infected groups being depopulated. The remaining groups had regained CF1 status through testing by the end of 1989, with approximately 20,000 head remaining. Further whole herd monitoring tests were required in subsequent years, with no further infection detected.This was a much smaller property (approximately 27 km by 10 km), but was situated in very rough country in the hills to the north of the city of Mount Isa. The property had never had TB detected at abattoir, but a number of neighbouring properties had a history of infection and this property had never been tested. To organise the required testing, an initial meeting was held with the owner and he was asked, as was normal, to provide or draw a map of the property showing all relevant management features. How a testing program would be managed would then be discussed. A property map usually showed the boundaries of the property, internal paddock fences, stock handling yards etc. In this case, the owner took a piece of paper and started drawing wiggly lines and each of the lines had names. After some consternation, it was realised that he was drawing gullies . In this rough country, property boundaries and fences had little meaning. His cattle lived and grazed in gullies and the country was too dry and rugged for them to live anywhere else for most of the year. Once this was understood, a testing program was able to be formulated in conjunction with the neighbours. Mustering occurred on an area basis, with cattle held in holding paddocks while tested. Mustered areas were inspected by helicopter, with any unmustered cattle shot. No TB was found. However, this example is provided to demonstrate the need to be flexible and adapt to individual circumstances.This example relates to a very large area of about 10,000 square kilometres that in the mid 1980s was largely undeveloped from a cattle production perspective. That is, there were very few stock fences, access roads and cattle handling facilities, despite there being eight land owners. It was referred to as the ‘Nicholson Area’, bound by the Nicholson river to the south, the Northern Territory border to the west and the Gulf of Carpentaria to the north Fig. . Cattle The approach taken was to initially construct a number of ‘strategic’ fences using program funds to break the area into more manageable sections Fig. . These wThe second purpose of the strategic fences was to facilitate area depopulation. There became a point where the mustering of cattle from the ‘outside areas’ became uneconomic. That is, the cost of mustering was greater than the value of animals mustered. At this point, the country was formally ‘handed over’ to the Department, where upon a series of large-scale depopulation operations were conducted over a one to two year period, with all remaining cattle shot from helicopters. This was a large logistical exercise, facilitated by the presence of the strategic fences. Similar operations were conducted in other parts of northern Australia.Through the methods described above, the Mount Isa Division achieved Impending Free status at the end of 1989, as did a number of other similar administrative regions. This was just one of a series of progressive area status changes that drove progress at the national level over time Fig. . In geneAs mentioned earlier, the Standard Definitions and Rules  specifieA key driver for action by cattle owners was the control of cattle movements. Figure Another very important element of BTEC was the government – industry partnership that was established formally in 1984 with establishment of the national BTEC Committee . InitialAnother mechanism established in some states was Ministerial BTEC advisors. These were people nominated by industry and who were given a brief to be able to visit the various administrative regions, review progress and provide advice on any problem areas. For example, they would sometimes visit a ‘problem property’ with the local Divisional Veterinary Officer to provide valuable advice and assistance to help resolve on-the-ground issues. It is interesting to note that the author observed that the industry representatives were often tougher on their constituents than the government employed staff.One of the changes to the program influenced by industry involvement was a greater suite of assistance measures to reduce the financial impact of APPs on affected producers. These included market value compensation for animals ordered to be destroyed or depopulated; a mustering subsidy to help cover the additional cost of achieving close to 100 percent musters ; a freight subsidy to help cover the cost of freighting replacement stock back to the property; and low interest loans for property improvements such as fences and cattle handing facilities. Taxation concessions were negotiated with the Taxation Department to allow averaging of income over a number of years when large groups were depopulated, and financial counsellors were also made available.Despite all of the above measures that were used to encourage people to effectively implement property programs, there was the occasional non-complying producer. In these cases, State jurisdictions had the powers within their legislation to take legal action. This occurred on a number of occasions, including Court rulings that enabled the Department to complete the required eradication actions.Towards the end of BTEC, some innovative methods were implemented to overcome particular problems. This included targeted depopulation of infected, feral water buffalo in local geographical areas based on field surveillance, and the ‘Judas cow’ technique. The latter was developed to deal with areas where it was difficult to find all animals within an area for depopulation, for example, because of very dense vegetation . The tecBTEC underpinned Australia’s animal health system for many years. Post-BTEC there have been a number of ongoing legacies of the program. The property improvements in the northern industry that were required to achieve eradication have largely persisted, meaning that the beef cattle industry became much more modern and productive. The infrastructure improvements allowed better management of cattle, including use of improved genetics, controlled mating and culling of poor performers, all leading to improved productivity. The partnership approach between government and industry has persisted and is now an imbedded feature of Australia’s biosecurity system. For example, Animal Health Australia (AHA) is a formal industry – government partnership. It is a not-for-profit public company with 34 government and industry members that coordinates a significant number of national animal health programs . One mecFollowing declaration of tuberculosis freedom on 31 December 1997, BTEC concluded and was replaced by the Tuberculosis Freedom Assurance Program and a granuloma submission program, with a major focus on enhancing detection at abattoirs of any remaining residual TB infection . Figure This stringent approach is illustrated by the handling of the last officially recognised primary case of TB in cattle which was detected in 2000 , 14. ThiA similar process was followed on all other breakdown properties following declaration of Impending Freedom, often involving depopulation of the entire herd. An incentive program was subsequently introduced to encourage accelerated turn-off to abattoir of any remaining cattle on these properties that had not been depopulated, thus providing further confidence that the disease had been eradicated.This paper highlights a number of key design features of the overall Australian program that led to its success. Foremost, there was commitment from both government and industry, with clear and agreed outcomes and targets. This was supported by robust program planning and management, which included timelines and measures of progress. These aspects were supported by appropriate funding through a cost shared model. There were agreed, national technical standards that all jurisdictions implemented for national consistency (including laboratory support) and these worked hand in hand with strict controls, particularly around animal testing, movement controls based on herd and area status and targeted depopulation of infected cohorts. These controls had a solid legal backing. A very strong surveillance system to identify infected herds was in place, with a particular emphasis on abattoir monitoring. This required an effective cattle tracing system. Finally, a suite of assistance measures was in place to minimise the financial impact on individual producers.Across all of these success factors there was an over-arching culture of persistence and being prepared to be tough where required. Another intangible success factor was possibly the Australian cultural tendency to respect our institutions and laws. This was highlighted in a recent Australian survey, despite an image of Australia that is perhaps the opposite .


Suicide is a major public health issue globally. The World Health Organization has called for nations to create comprehensive national suicide prevention strategies including multisectoral collaboration, awareness raising, advocacy and capacity building. The workplace provides opportunity and structure for suicide prevention programs. However, many of these programs are poorly documented and evaluated. The MATES in Construction (MATES) program is a multimodal workplace-based suicide prevention program designed for and by the construction industry. This systematic review examined the available evidence for the effectiveness of the MATES program and is reported according to PRISMA guidelines. A literature search resulted in the inclusion of 12 peer-reviewed articles published between January 2010 and February 2023 containing primary data of evaluations of MATES. There was evidence of the effectiveness of the MATES program in improving mental health and suicide prevention literacy, helping intentions and reducing stigma. The results highlighted the importance of worker-to-worker peer approaches with workers consistently stating that supervisors were the least trusted resources for mental health and suicide concerns. Favourable results were found in relation to reduced suicide risk in the construction industry. The evidence base for MATES is limited in terms of causal inference with very few controlled evaluations and no experimental studies having been conducted to date. Improved understanding of how the program motivates volunteers, their experiences and research on the longer-term impacts of the program on the industry is required. The study found some support for the MATES ‘Outrage, Hope, Action’ Model of engaging men in collective action preventing suicide.MATES demonstrates the efficacy for a focus on help offering over help seeking in male suicide prevention.The findings from this study have wider applications in providing health promotion to male-dominated populations.The World Health Organization (WHO) has stated that suicide and suicide behaviours are a critical public health issue . Globalland socio-cultural determinants, engage men through ‘doing’, use language acceptable to men, and change norms through peer engagement  and supports a network of 21,888 ‘Connectors’, workers volunteering to be the connection point between workers in distress and support resources and 2889 ‘ASIST workers’, workers volunteering to be a support resource for colleagues in distress across the Australian construction industry . MATES iThe MATES program logic model describes how program outputs are expected to generate program outcomes  includinThe systematic review for this study followed the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA)  were carried out among samples of construction workers (n = 7) used quantitative survey methods  and a comparison group (n = 355), there was a significant, favourable post-training improvement in responses to five questions that were not observed in the non-intervention group (p ≤ 0.01) suggesting a positive impact of the training on mental health and suicide prevention literacy and stigma , using similar pre–post-survey instruments, demonstrated improvement in suicide prevention literacy and decreased stigma in pre-GAT to immediately post-GAT testing  the study found that there was no significant difference between the modality of delivery (GAT vs MAT). While there was a significant improvement in suicide literacy and stigma reduction from pre- to post-training, most of this effect was lost by the 3 months follow-up. However, help-offering intention, a core objective of the MATES program, did maintain a significant improvement from T1 to T3 (p ≤ 0.001).One study (n = 649), 6 months  and 18 months  post-GAT training. Participants showed significant improvements over the 18 months in attitudes to public- and self-stigma, disagreeing with a statement that they would be treated differently by friends  or colleagues  if they knew about them having a mental health condition. The same was not observed for structural stigma [referring to policies, procedures and cultural norms that restrict the opportunities of those with mental illness (p = 0.07).Sayers et al. examined outcomes from a MATES intervention in two coal mines  (p < 0.001) while men had a significantly greater improvement from pre- to post-training responses (p = 0.01)  while those who did not have lived experience of a suicide attempt had a more desirable change in responses recognizing the industry’s role in suicide prevention (p = 0.001) . After training participants agreed that they could save lives in their workplace (99%), knew where to get help and support (99%) and they felt prepared to have discussions about suicide (98%). Important for program diffusion, 99% of participants intended to tell someone about the MATES program (p ≤ 0.001). The emotional well-being of the participants was also improved from pre- to post-training  and felt the Connector training provided them with the right awareness and skills to be confident in the role (Hope and Action). Connectors felt that it was important that MATES was an inherent part of their industry and their workplace. They found the MATES model simple to engage with and created a movement for suicide prevention by building both passion and camaraderie.A qualitative analysis . One study also found that this improvement was maintained for the MATES-related resources, MATES worker/Connector (p < 0.001) and Helpline (p = 0.01) longitudinally over 3 months , family members (p = 0.05), friends (p = 0.02), colleagues (p < 0.01), employee assistance programs (p < 0.01) and psychologists (p = 0.04)   increased from 11% in 2011 to 22% in 2021, and referrals from unions increased from 14% in 2011 to 20% in 2021 (1.‘Suicide in the Construction Industry is Reduced’Three studies (p = 0.386) against a slight increase for other employed males . The authors noted these national trends would most likely be attributable to a range of general population initiatives over this period but also construction-specific initiatives including the MATES program.A recent study  over employer-structured resources such as Employee Assistance Programs and supervisors or professional mental health resources. Findings also suggest that MATES led to increased help-seeking intentions from MATES-specific resources such as Connectors and the MATES helpline and that this increase was maintained over time. These findings provide some, although limited, support for the effectiveness of the MATES ‘Outrage, Hope, Action’ Model in engaging construction workers in suicide prevention. Finally, studies found some evidence that MATES has had a positive impact on suicide rates and relative suicide risk in the construction industry.Previous workplace suicide prevention systematic reviews have focussed on specific industries (Previous reviews of workplace programs described in the peer reviewed and grey literature found that very few programs were well articulated in the literature and even fewer evaluated . The MATet al. identified 13 studies evaluating suicide intervention programs targeting protective or emergency services (Witt services . This isWitt et al. identified that most workplace programs focussed on secondary and tertiary-level prevention activities with only a few programs considering work environment factors . While tWorker engagement and collective action are central to the MATES program . We founA limitation of the available evidence of the MATES program is the lack of analysis of the role of masculine norms. The impact of masculinity on suicide risk and in suicide prevention is complex and cannot be explained by lack of help seeking alone . The genThis study highlights the complexity of the MATES program logic model, and that further research is required to fully assess the effectiveness of the MATES program. The published evidence to date was limited by the lack of experimental designs as well as a deep qualitative documentation of how the program functions on worksites. For future research, a focus on medium-term outcomes such as improvement to individual and site resilience, reduction in stigmatizing behaviours, improved interpersonal relationships, worker ownership and extensions to the MATES program on sites and the creations of cross-industry alliances for better mental health and suicide prevention is required. From a broad public health perspective, it is significant that very limited evidence exists on the effectiveness of the MATES ‘Outrage, Hope, Action’ Model for diffusion of the MATES program.This review has a number of strengths. It demonstrates the utility of an articulated MATES program logic model in framing and interpreting evaluation findings, and that further research is required to fully assess the impacts of the MATES program. It has applied a systematic approach following PRISMA guidelines to maximize transparency and reproducibility. Included studies generally had very high participation rates as data were collected as an integrated part of delivering the program, in particular the training elements of the program which target a minimum of 80% of all workers on site. This is the first review of the peer-reviewed evaluation research on the MATES program, providing a relatively detailed portrayal of a single program, complementing other reviews combining findings across workplace programs.This review has several limitations. While restriction to peer-reviewed literature optimized the scientific quality of the included papers, this approach may also create a risk of publication bias. The variety of measures used in included studies precluded a meta-analysis, thus requiring a narrative synthesis of findings. We also note limitations in terms of generalizability, given that all included studies were conducted in Australia.While the MATES program is well documented in the literature and has a published program logic model, evaluation research on the MATES program to date has focussed on near- to medium-term outcomes, often with low causal inference research designs. While the current evidence is favourable, future research should prioritize higher causal inference studies and more emphasis on longer-term outcomes. From a broader public health perspective, further evaluation of the implementation and effectiveness of the MATES ‘Outrage, Hope, Action’ engagement model may inform strategies for the diffusion of MATES and other suicide prevention programs.daad082_suppl_Supplementary_MaterialClick here for additional data file.


Program synthesis is the mechanised construction of software. One of the main difficulties is the efficient exploration of the very large solution space, and tools often require a user-provided syntactic restriction of the search space. While useful in general, such syntactic restrictions provide little help for the generation of programs that contain non-trivial constants, unless the user is able to provide the constants in advance. This is a fundamentally difficult task for state-of-the-art synthesisers. We propose a new approach to the synthesis of programs with non-trivial constants that combines the strengths of a counterexample-guided inductive synthesiser with those of a theory solver, exploring the solution space more efficiently without relying on user guidance. We call this approach CEGIS( Program synthesis  is the pSyntax-Guided Program Synthesis (SyGuS) [In full generality, program synthesis is an exceptionally difficult problem, and thus, the research community has explored pragmatic restrictions. One particularly successful direction is  (SyGuS) . The keyUnfortunately, it is difficult to provide the syntactic template in many practical applications. A very obvious exemplar of the limits of the syntax-guided approach are programs that require non-trivial constants. In such a scenario, the syntax-guided approach requires that the user provides the exact value of the constants in the solution.x to the next highest power of two. If we refer to the function computed by the program as f(x), then the specification can be written asf(x) to be a power of two, the others require it to be the next highest. A possible solution for this is given by the following C program:For illustration, let’s consider a user who wants to synthesise a program that rounds up a given 32-bit unsigned number It is improbable that the user knows that the constants in the solution are exactly 1, 2, 4, 8, 16, and thus, she will be unable to effectively restrict the solution space. As a result, synthesisers are very likely to enumerate possible combinations of constants, which is highly inefficient.In this paper we propose a new approach to the synthesis of programs with non-trivial constants that combines the strengths of a counterexample-guided inductive synthesiser with those of a solver for a first-order theory in order to perform a more efficient exploration of the solution space, without relying on user guidance. Our inspiration for this proposal is CDCL(ument}T) , 31, 39 Similarly, we attempt to separate reasoning about a program’s structure and its constants. For this purpose, we propose a new algorithm called CounterExample-Guided Inductive Synthesis variable elimination  and one As a case study, we present an integration of CEGIS, The input specification provided to a program synthesiser is of the formcounterexamples provided by a verification oracle, that is, concrete input values CounterExample-Guided Inductive Synthesis (CEGIS) is a popular approach to program synthesis. It is an iterative process that maintains at all times a candidate program I of all possible inputs. The candidate program I of inputs passed to the synthesiser, and the loop repeats.The CEGIS process is illustrated in Figure The methods used in the synthesis and verification blocks vary in different CEGIS implementations. We give details of the algorithms used in CVC4 in Sect. To improve the performance of the traditional CEGIS process, we have devised an extension of it, CEGIS. The standard CDCL algorithm, comprising Decide, Boolean Constraint Propagation (BCP), Analyze-Conflict and BackTrack components as illustrated in Figure F has been found. Otherwise, a constraint over the Boolean variables in Decide, and the process repeats.Given a formula entclass1pt{minimaIn the very first SMT solvers, the SAT solver first obtained a full assignment to the Boolean variables that comprise the abstraction of the input. Subsequently, the theory solver would determine whether or not this assignment was satisfiable according to the background theory. If not, the next Boolean assignment was then checked. Such SMT solvers were prone to enumerating all possible candidate solutions at the Boolean level in the worst case. The key improvement in CDCL where if then else.For illustration, let’s consider the trivial problem of synthesising a function In order to make the synthesis task even simpler, we are going to assume that we know a part of this solution, namely we know that it must be of the form Synthesis engines can be used as reasoning engines in program analysers, and constants are important for this application. In such a case, the synthesised program computes the program proof of interest   and EUSoProving termination Next, let’s look at the following terminating program:R is a ranking function, i.e., an injective function that has a well-founded set D with order Its termination argument can be encoded as the following formula, where Proving non-termination One way of proving non-termination is by finding a recurrence set, i.e., a nonempty set of states S such that for each state ent}s′∈S . As an ei and j will overflow and be reset to 0 in subsequent loop iterations. The corresponding recurrence set S has to satisfy the following formula of bitvector arithmetic, which encodes that S must be reachable from an initial state and, for each state in S, at least one successor must be in S. Note that, as the program is deterministic, all successors of a state in S must be in S.For bit-vectors, the initial state Bug finding Next, let’s look at the buggy example below, where we increment x and y in each loop iteration, maintaining the same initial difference of 10 between them. Consequently, the assertion at line 6 fails.danger invariant [D must hold in some initial state, be inductive with respect to the transition relation and, on exit from the loop, imply the negation of the assertion:D-state — thus we are in the situation where the danger invariant denotes either an assertion violation or the presence of a recurrence set.We can prove that this program has a bug by finding a nvariant , which cR proving that the loop does terminate making the assertion at line 6 reachable.D and R require non-trivial constants.If we want to prove only an assertion violation, an additional part of the danger invariant is a ranking function In this section, we describe the architecture of CEGIS(To explain the main ideas behind CEGIS(Candidate solution) Using the notation from Sect. candidate solution of  P then The set mentclass2pt{minimCandidate solution skeleton) Given a candidate solution skeleton of  Given a candidate solution skeleton generalised candidatei-th hole  A candidate solution finalised solution if the formula  Given the example in Sect. The CEGIS architecture (enclosed in a dotted rectangle with the label “CEGIS”) generates the candidate solution constant removal. Subsequently, Deduction attempts to find a constraint over The theory solver (enclosed in a dashed rectangle with the label “Theory Solver”) obtains the skeleton This constraint is propagated back to CEGIS. Whenever there is no valuation of The CEGIS be the formula that is obtained by eliminating Let Given that For the current skeleton The specification mination ) work onmination , 43. As x from x fromWe recall the example in Sect. For our second variant of a theory solver, we make use of an off-the-shelf SMT solver that can solve first-order formulae with quantifiers. This approach is more general than the one described in Sect. Recall that our goal is to obtain a constraint The formula passed to the SMT solver is still a non-trivial formula containing an alternating quantifier, except now both quantifier prefixes are first-order, that is quantify over domain values not over functions. It would not be uncommon for an SMT solver to take substantially longer to solve this formula than the synthesis step of CEGIS takes. To avoid that, we impose a heuristically chosen timeout of 2 s on the verification step. If the solver exceeds the timeout, CEGIS background theory. Concretely, CVC4’s background theory is extended with mentclass2pt{minimmentclass2pt{minimsmart) enumeration, which allows for numerous optimisations [fast) enumeration [hybrid approach combining smart and fast enumeration [Depending on the structure of the synthesis problem, CVC4 uses different strategies for generating candidates solutions. It either applies a constraint-based .For example, consider the candidate solution We compared CEGIS. This makes CEGIS a prime candidate for incremental SAT solving. We implemented incremental solving in the synthesis block of CEGIS.Benchmarks We selected a set of bitvector benchmarks from the Syntax-Guided Synthesis (SyGuS) competition [petition  and a sepetition . The selpetition , a variapetition .grammar or the template) provided in the SyGuS benchmarks generally contain all the necessary non-trivial constants, we completely removed the grammars from these benchmarks. Removing just the non-trivial constants and keeping the rest of the grammar (with the only constants being 0 and 1) would have made the problem much more difficult, as the constants would have had to be incrementally constructed by applying the operators available to 0 and 1.Since the syntactic restrictions  [A well-known application of CEGIS is program sketching , 42, whe (SyGuS)  requiresAnother very active area of program synthesis are component-based approaches , 24, 32.Heuristics for constant synthesis are presented in , where tRegarding the use of SMT solvers in program synthesis, they are frequently employed as oracles. By contrast, Reynolds et al.  present We proposed CEGIS(in this paper, we evaluated CEGIS(mentclasspt{minima


Lifestyle modification programs, such as cardiac rehabilitation, may reduce atrial fibrillation (AF) burden and improve quality of life (QOL), but remain unproven. The objective of this pilot study was to assess feasibility, acceptability, and preliminary effectiveness of an exercise and nutrition-based cardiac rehabilitation-like program for AF patients.We enrolled overweight adults aged ≥ 30 years with symptomatic AF in a 12-week cardiac lifestyle group program, including 6 virtual and 6 in-person visits. All visits included discussion and education about nutrition, exercise, and behavior modification. In-person visits included supervised aerobic exercise and strength training. Outcomes at baseline and 12 weeks included feasibility of participation, acceptability, change in weight and BMI, and changes in survey-based AF burden, symptoms, and QOL.2); 9 (82%) completed the program. Patients attended an average of 9.7 (81%) visits (Range: 6–11). Mean weight loss was 9.1 pounds (Range: 0–16); mean BMI decrease was 1.4 kg/m2 (Range: 0–2.6). Patients found the program helpful overall: all reported making diet and exercise changes during the program. Compared to baseline, patients reported decreased AF burden  and symptom  scores at the conclusion of the program. Patients also reported increased QOL overall From 84 invitees, 11 (13.1%) were enrolled (mean age 64; baseline BMI 38 kg/mParticipation in a cardiac rehab-like program was feasible and acceptable for overweight patients with symptomatic AF. Results suggest preliminary effectiveness of the program for reducing AF burden and symptoms and increasing QOL. We plan to conduct a future pragmatic randomized trial of patients with symptomatic, paroxysmal AF to a cardiac lifestyle program compared to usual care. In this trial, we will examine the effectiveness of the intervention on decreasing AF burden and symptoms, as well as how well the benefits of the intervention persist over a 12-month period.2) adults aged ≥ 30 years with symptomatic paroxysmal AF seen by an electrophysiologist at Massachusetts General Hospital. Patients were excluded if asymptomatic, scheduled for catheter ablation, or if their physician did not think they could participate in an exercise program. Potentially eligible patients were identified from an electronic health record query. Research staff conducted an initial chart review to remove those not eligible, and final eligibility was confirmed by the treating physician.Eligible patients were overweight or obese , the proportion of patients who completed the program, and the proportion of eligible patients who expressed interest in participating. Acceptability was assessed by survey following completion of the program and included questions about satisfaction with the program overall and with specific program components.6, and quality of life (QOL)7. AF burden and symptoms was assessed at baseline and follow-up by survey using the Atrial Fibrillation Severity Scale (AFSS),6 and quality of life was assessed with the AF Effect on Quality-Of-Life Questionnaire (AFEQT).7 Changes in outcomes from baseline were evaluated with paired sample t-tests. The sample size goal was 10–12 patients. The research protocol was approved by the Mass General Brigham Institutional Review Board. Participants provided written informed consent to participate.Secondary preliminary effectiveness outcomes included changes from baseline in weight, BMI, survey-based AF burden and symptoms2 (Range: 29.9–48.9 kg/m2), and 8 (72%) were anticoagulated at baseline. Of 11 enrollees, 9 (82%) completed the program and all study surveys. Among those who completed the program, the mean number of visits attended was 9.7 of 12 (81%) .Among 96 potentially eligible patients, 12 (13%) were excluded by their physician. Among 84 patients sent recruitment letters, 33 (39%) expressed interest in the program, 32 (38%) declined participation, 19 (12%) were never reached by phone, and 11 (13%) enrolled . RecruitPatients found the program helpful overall, and all reported making diet and exercise changes . Patient2 . Compared to baseline, patients reported decreased AF burden  and symptom  scores at the conclusion of the program. Patients also reported increased QOL overall  and for all QOL subscales: symptoms , daily activities , treatment concerns  ; mean BMI decreased 1.4 kg/m= 0.004) .Prior to conducting a large-scale pragmatic trial of an exercise and nutrition-based cardiac lifestyle modification program for secondary prevention of AF, this pilot study demonstrated that participation in a lifestyle modification program was feasible and acceptable for overweight and obese patients with symptomatic AF. Importantly, results suggest preliminary effectiveness of the program for reducing AF burden and symptoms and increasing QOL.5 Randomized studies examining the impact of lifestyle modification and cardiac rehabilitation on secondary prevention of AF have been limited in size and duration, with few evaluating sustainability.8 The ACTIVE-AF randomized trial demonstrated that a tailored aerobic-based exercise program reduced AF symptom severity and improved maintenance of sinus rhythm.9 These benefits were achieved in the absence of weight loss. Other studies have reported decreased AF burden and symptoms with aggressive risk factor reduction, including weight loss.11 Interventions evaluating the benefits of interventions that include both exercise and nutrition components warrant further investigation. Our pilot trial demonstrated feasibility and preliminary effectiveness of a hybrid, health clinic and virtual home-based, intervention to promote lifestyle modification related to both exercise and nutrition for secondary prevention of AF. Such a model may increase participation and be more sustainable than an entirely facility-based approach.12 Future research should evaluate the efficacy of a hybrid-based exercise and nutrition-based program for AF related  and clinical  endpoints in a multi-site, adequately powered clinical trial.There is growing evidence that lifestyle modifications have a significant impact on management of AF.There was significant interest in study participation among eligible patients. More than half the patients reached by phone expressed interest in participating in the study and we quickly met our sample size goal. Among our 11 enrolled subjects, there was good retention with 9 completing the full 12-week program.Our sample size of 11 enrolled subjects is small. Available funding for this pilot study was not significant enough to expand capacity of this clinical program. While our sample did have adequate representation of women (n = 5 of 11), we did not have an ethnically or racially diverse sample and did not have information about educational attainment or income. Additionally, we were unable to evaluate long-term sustainability of changes in diet and/or exercise beyond the 12-week program, or maintaining improvements in AF burden/symptoms and QOL. However, evaluating sustainability is a goal of the larger trial.This study demonstrates that enrolling overweight and obese patients with symptomatic AF in an exercise and nutrition-based cardiac lifestyle modification program for secondary prevention of AF is both acceptable to patients and feasible. An adequately powered pragmatic randomized trial comparing such a program to usual care appears possible.