Background: The initial injury burden from incident TBI is significantly amplified by recurrent TBI (rTBI). Unfortunately, research assessing the accuracy to conduct rTBI surveillance is not available. Accurate surveillance information on recurrent injuries is needed to justify the allocation of resources to rTBI prevention and to conduct high quality epidemiological research on interventions that mitigate this injury burden. This study evaluates the accuracy of administrative health data (AHD) surveillance case definitions for rTBI and estimates the 1-year rTBI incidence adjusted for measurement error.Methods: A 25% random sample of AHD for Montreal residents from 2000 to 2014 was used in this study. Four widely used TBI surveillance case definitions, based on the International Classification of Disease and on radiological exams of the head, were applied to ascertain suspected rTBI cases. Bayesian latent class models were used to estimate the accuracy of each case definition and the 1-year rTBI measurement-error-adjusted incidence without relying on a gold standard rTBI definition that does not exist, across children (<18 years), adults (18-64 years), and elderly (> =65 years).Results: The adjusted 1-year rTBI incidence was 4.48  per 100 person-years across all age groups, as opposed to a crude estimate of 8.03  per 100 person-years. Patients with higher severity index TBI had a significantly higher incidence of rTBI compared to patients with lower severity index TBI. The case definition that identified patients undergoing a radiological examination of the head in the context of any traumatic injury was the most sensitive across children [0.46 ], adults [0.79 ], and elderly [0.87 ]. The most specific case definition was the discharge abstract database in children [0.99 ], and emergency room visits claims in adults/elderly [0.99 ]. Median time to rTBI was the shortest in adults (75 days) and the longest in children (120 days).Conclusion: Conducting accurate surveillance and valid epidemiological research for rTBI using AHD is feasible when measurement error is accounted for. Traumatic brain injury (TBI) leads to significant disability and economic burden in populations across the globe , 2. A brWithin a 1-year period after an index TBI, recurrent TBI (rTBI) affects 5-10% of individuals . These rAdministrative health data are a widely available resource for conducting surveillance , 18, 19.We used a prospective cohort design to ascertain cases of rTBI in cohorts of index TBI patients, stratified by index injury severity and age group . Index TBI patients were identified using a previous latent class analysis that predicted the probability of individuals having an index TBI based on widely-used TBI case definitions in administrative health data  of Montreal from 2000 to 2014 to identify incident and recurrent TBI events. The cohort is dynamic with membership maintained to represent a 25% random sample of the CMA of Montreal population. Administrative health data from the Régie de l'Assurance-Maladie du Québec (RAMQ) were used for the analysis . These dTo carry over the uncertainty from our original analysis on index TBI to the present analysis, we predicted 1,000 cohorts of index TBI patients using our original Bayesian latent class model on incident TBI . These pWe estimated the incidence of rTBI over a 1-year period, using the person-time contribution of the 1,000 predicted index TBI cohorts until 1-year follow-up, censoring from the cohort, or meeting the case definition of a suspected rTBI surveillance case definition.We applied four widely used ICD-based surveillance case definitions for administrative health data to identify suspected rTBI cases  4, 19, , 19, 25.4 = 16) response patterns of positive case definitions based on whether they met these case definitions at least 7 days after their index TBI and up to 365 days after it. We included this temporal constraint since in our previous analysis on incident cases, we had placed a constraint that all claims had to occur within 7 days of the earliest claim for the combination of case definitions to be attributed to the incident TBI. Therefore, all case definitions that were met within the first 7 days after an incident TBI were assumed to be related to the incident event. In our previous analysis on incident TBI, we excluded prevalent cases of TBI by identifying patients that met our TBI case definitions from 1998 to 2000 and excluding them from the follow-up cohort.Patients had 1 of 16  since we only had sufficient degrees of freedom to conduct such an analysis without having to use informative prior information, which is not available in the literature . BrieflyWhen using latent class analysis, we assume that the multiple case definitions used in the model are conditionally independent given disease status. We verified model fit, and in turn that this assumption was not violated, by conducting posterior predictive checks that assessed the probability that the observed agreement between pairs of case definitions were greater than their predicted agreement  22, 35), 3522, 3We assessed the crude median time to rTBI using the date of the first positive case definition as the time of recurrent injury. We also estimated an adjusted median time to rTBI which adjusted for the probability that an individual was a true incident TBI and rTBI case .All analyses were conducted in Just Another Gibbs Sampler (JAGS) called from R. Convergence diagnostics were performed by assessing traceplots and the Gelman-Rubin statistic (<1.1). The parameters were sampled from their posterior distribution using three parallel chains of Markov chain Monte Carlo simulations with 20,000 iterations and a burn-in of 5,000 iterations by specifying the likelihood and prior distributions of each one for the Gibbs sampler. 95% credible intervals and medians were reported from the highest posterior densities. We placed constraints on the incidence parameter, the specificity parameters, and two of the sensitivity parameters (ER claims and discharge abstract database) in the form of non-informative prior information. This was completed to help with model convergence across the 1,000 latent class analyses we conducted for each incident TBI cohort that was predicted and to avoid label switching, which can occur in latent class analysis . The repWe allowed our constraints (prior information) to vary within plausible ranges to assess whether these priors had an impact on the conclusions of the primary analysis . FinallyIn From 2000 to 2014, there were 7,532 suspected rTBI cases within 1 year of their incident event. The crude 1-year rTBI incidence was 8.03  per 100 person-years. The measurement error-adjusted rTBI incidence from the Bayesian latent class analysis was lower [4.48  per 100 person-years]. The adjusted median time to recurrence was more delayed across all age groups than the crude estimate . There wThe rTBI incidence was most elevated for the elderly population  and the lowest in children . When comparing male and female incidence across the entire population of incident TBI patients, female sex was associated with a higher incidence of rTBI. However, male sex was associated with a higher incidence of rTBI compared to female sex when individually assessing the incidence of rTBI in children and adults. In addition, the incidence of rTBI between males and females was similar in the elderly. Patients with a “most severe” index TBI had a significantly higher incidence of rTBI in comparison to patients with a “mildest/more severe” index TBI, across all age groups .The most sensitive rTBI case definition was based on a radiological examination with a diagnosis of trauma and the least sensitive was based on the DAD, except for the elderly where the outpatient claims were the least sensitive. In children, the case definition based on the DAD was the most specific, whereas in adults and the elderly it was the emergency room physician claim. The least specific case definition in children was the ER claim. The DAD and radiological examination case definition had the highest PPV in children. In contrast, in adults the radiological examination and in the elderly the ER claim had the highest PPV, respectively . As showModel fit across the three age groups was deemed appropriate based on posterior predictive checks and sensitivity analyses where prior information was varied within plausible ranges . More spCrude rTBI incidence decreased across all three age groups when we excluded all suspected rTBI claims in the first 30 days after the incident TBI . For eacThe impact of rTBI on the overall TBI burden has been overlooked in the general population , 16. ThiThere has been a considerable amount of research on the methodology used to conduct incident TBI surveillance , 25, 37.A wide variation in the estimates of rTBI incidence in the general population has been reported, due to heterogenous surveillance methods used . CompariThe rTBI incidence we reported in adults and the elderly was higher than in children, which is in keeping with previous studies demonstrating that increasing age is a risk factor for rTBI , 45. TheAs for index TBI, the incidence of rTBI varies by age and sex. The incidence of recurrence increases with increasing age , 45. In We also observed that the adjusted rTBI incidence for children and adults was significantly different than the crude rTBI incidence in these age groups. However, in the elderly the crude rTBI and adjusted rTBI incidence were similar. Although we cannot conclude why the latter was observed, one hypothesis is that elderly patients are more likely to be frail and require longer hospitalizations or rehabilitation after an incident TBI. As such, early claims after an incident TBI may not occur since these patients do not have follow-up appointments recorded in administrative health data while they are hospitalized. Thus, false rTBI claims that are actually follow-ups are less likely in the elderly population. Our sensitivity analysis where we restrict our analysis to use TBI claims 30 days after an initial TBI supports this argument, since the crude rTBI incidence was the least reduced for the elderly cohort when completing this sensitivity analysis.Our study emphasized that index TBI severity is an important determinant of rTBI. Patients with a “most severe” index TBI had a significantly higher incidence of a recurrent injury compared to patients with milder injuries. However, the precision of estimates varied widely across the three age groups. Previous studies have reported similar findings, although the magnitude of association was smaller than in the present study , 47, 48.The performance of the surveillance case definitions also varied by index TBI severity. We demonstrated that among the cohort of patients with a “mildest/more severe” index TBI, sensitivity was highest for case definitions based on emergency department physician claims and radiological examinations. In contrast, for patients with a “most severe” index TBI, the DAD and radiological examinations case definitions tended to have the highest sensitivity. Moreover, the specificity and PPV of the DAD and radiological examinations case definitions were higher in patients with a “mildest/more severe” index TBI compared to a “most severe” index TBI. A possible explanation for these findings is that patients with a higher severity index TBI are more likely to obtain follow-up imaging for their index injury and may be readmitted to a rehabilitation center where a new DAD entry is entered, which leads to more false positives. In short, the variability in how the case definitions perform by age group and index TBI severity is important for stakeholders in surveillance and epidemiological research who may be investigating the incidence of rTBI in specific TBI subpopulations.Assessing the time-to-recurrence of rTBI is important as it defines a window of opportunity during which interventions may help mitigate the risk of rTBI. We identified that the median time to recurrence varied from 75 to 120 days, depending on the age group, which is in keeping with previous research . Our stuClearly, more research is necessary to identify strategies to reduce the risk of rTBI, which tends to occur within the first few months post-index injury. The accuracy of case definitions to identify rTBI is important to consider when conducting epidemiological research. By using the methods and results from this study, investigators have the tools to construct cohorts of index TBI patients, assess their outcome of rTBI accurately, and thereafter make valid inferences regarding the association between interventions and rTBI. For example, preliminary research on the impact of treating patients in a specialized neurotrauma center as opposed to a non-specialized center, for equally severe injuries, is associated with a lower risk of rTBI . FurtherOur study has limitations that should be considered. First, we used administrative health data from a single jurisdiction, which may limit the generalizability of the results across other health regions. Nonetheless, administrative data tend to be similar across jurisdictions and extensive research on TBI epidemiology demonstrates that TBI epidemiological characteristics are consistent across the developed word . Second,Recurrent TBI is an important contributor to the overall population burden of TBI. Administrative health data can be used to conduct accurate and efficient rTBI surveillance by adjusting for measurement error. The methods and results from this study provide stakeholders in rTBI with tools and information to justify the allocation of resources toward prevention and care for rTBI. They can also inform and enable epidemiological research that investigates strategies to reduce the rTBI burden and thereby help address the overall TBI burden.oliver.lasry@mcgill.ca.The data analyzed in this study is subject to the following licenses/restrictions: The dataset used are Quebec's (RAMQ) administrative health data that cannot be publicly shared. Requests to access these datasets should be directed to Oliver Lasry, This study was reviewed and approved by the Institutional Review Board of McGill University's Faculty of Medicine. Written informed consent from the participants' legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.OL devised the research questions, conceptualized the study design, planned and executed the statistical analysis, interpreted the results, and drafted the final manuscript. ND helped design the statistical plan, reviewed the analysis, and critically reviewed the final manuscript. JM helped with designing the study and establishing the case definitions used, in addition to critically reviewing the final manuscript. DB helped with designing the study, reviewing the statistical plan, and critically reviewed the final manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


There have been limited reports on crime prevention policies by local governments in Japan, which is one of the safest countries in the world. This article reviews crime prevention policies in Adachi Ward, which used to have the highest crime rates in Tokyo. The government of Adachi Ward introduced the “Beautiful Windows Movement” (BWM) in 2008. Based on BWM, Adachi Ward implemented various programs and interventions based on two different aspects: the aspect of preventing minor crimes and disorder in partnership with the police referring to the Broken Windows Theory and the aspect of literally making the Ward beautiful in cooperation with citizen volunteers. After 11 years of implementing BWM, the number of recorded crimes in Adachi Ward declined the most in Tokyo and residents’ sense of security improved significantly. This case study highlights the advantage of the duality of BWM to both reduce crimes and improve residents’ sense of security.The online version contains supplementary material available at 10.1057/s41300-021-00118-w. Local governments take responsibility for planning and delivery of crime prevention due to their ability to mobilize local resources; to build partnerships, and to understand local problems . BWM was influenced by the Broken Windows Theory (Wilson and Kelling Since the end of World War II (when the authorities began to record crime) to the 1990s, the number of crimes in Japan ranged between 1.3 and 1.5 million per year. During the same period, the population of Japan increased steadily from 72 to 123 million. Crime began to surge in the late 1990s and reached a peak of 2.85 million per year in 2002. Similarly, the number of crimes recorded in Tokyo had been stable in the range of 200,000 to 250,000 per year from the 1960s to the 1980s; it increased sharply in the late 1990s and exceeded 300,000 in 2002.In the USA, the “Broken Windows Theory” was proposed as an explanation of the progress of disorder in the community. If a broken window is left unattended, another window will then be torn, eventually ruining the entire building, the entire community. In this way, if a small violation is left untreated, a sense of disorder is gradually created, which leads to a large deterioration of public security. In New York City, USA, in order to restore public security, police cracked down on small violations and took steps to erase subway graffiti. While these are just a part of the improvement of a social environment where crime is unlikely to occur, the crime situation in the city has dramatically improved under these efforts  and related ministries in Japan issued a document urging municipalities to develop crime-resistant communities based on crime prevention through environmental design (CPTED) . Prefectural police departments are set up in each prefecture under the supervision of the NPA, and the MPD has jurisdiction over Tokyo. Adachi Ward has a population of 693,411 (fifth among the 23 Wards) and comprises of 356,641 households . The population of Adachi Ward has been increasing due to strong development pressures, especially after the opening of two new train lines, the Tsukuba Express and the Nippori-Toneri Liner in 2005 and 2008, respectively.The Ward had the greatest number of recorded crimes in central Tokyo for four consecutive years from 2006 to 2009. Considering the relatively large area and population among the 23 wards, the number of cases in Adachi Ward was not large. Nevertheless, the Ward’s image suffered both locally and regionally. Yayoi Kondo, the female mayor of Adachi Ward since 2007, strongly felt the need to change the “image” of the area. She pointed out that “Adachi Ward is said to be a “dangerous town” [and that] a woman cannot walk even in the daytime. Some people have such an image without having been to Adachi Ward. However, it is also true that Adachi Ward has had the greatest number of crimes among the 23 wards for the fourth consecutive year” Kondo . A year Since 2008, the government of Adachi Ward in cooperation with the local community, the police, and other related organizations, has been working to develop the BWM, which aims to create a beautiful, livable city, safe from crime. BWM is influenced by the broken windows theory and its applications in New York City; it is a unique movement that aims to deter crime by giving the impression of “a beautiful town” , which introduced various crime countermeasures, such as the organizing of crime prevention volunteers and the redesign of roads and parks to conform with basic crime prevention principles (Table A1). The plan stated that CPTED would be applied to roads, parks, and residential developments. Based on the plan incorporating CPTED as well as the Broken Windows Theory, Adachi Ward aimed to create a safer city through the cooperation of crime prevention volunteers formed by local people, schools, and shop owners’ associations, as well as the four police stations in the Ward , and literally making the Ward beautiful in cooperation with citizen volunteers (the sun). BWM is reasonable in that it tries to improve the image of the ward focusing on crimes and disorders that could be "warning signals" Innes .As already stated, the model designed to study crime prevention in Adachi Ward is based on (1) crime prevention measures in partnership with the police and (2) crime prevention measures in cooperation with citizen volunteers. The government of Adachi Ward hoped that the combination of the two would reduce the number of recorded crimes and improve the image of the area and the sense of security. We selected as representatives of the category of “crime prevention measures in partnership with the police” the following: measures against bicycle theft and the installation of CCTVs. We focused on measures against bicycle thefts because they represented the highest proportion of crime; the Ward viewed reduction in bicycle theft, which directly links to the reduction in total number of crimes, as a way to dispel the negative image of the Ward Kondo . As descWhat interventions and programs exist in Adachi Ward based on BWM?To what extent are these programs and interventions responsive to crime problems and citizens’ sense of security?The two key research questions of this study are:Through answering these research questions, this article examines the usefulness of BWM derived from the Broken Widows Windows Theory by conducting a case study of Adachi Ward. As already mentioned, to date there has been a limited focus on crime prevention measures at the local government level in Japan. This study will contribute to crime prevention policy research by adding a case study of a Japanese local government, which used to have high crime rates (according to Japanese standards).The research methods adopted for this study include the following: (1) interviews with Ward staff and executives; (2) crime data analysis; and (3) analysis of policy documents. One of the authors has been an advisor of Adachi Ward on crime matters since 2010 and exchanges opinions with the staff of the Risk Management section of the Ward almost monthly. Moreover, the author attends BWM Promotion Strategy Meetings and crime prevention events where he meets the mayor and executives of the Adachi Ward. In addition, in the “neighborhoods that promote the prevention of crime” project, he has joined the Community Development Section of the Ward and participates in workshops with local residents about three times a year.In the crime data analysis section of this article, we use two sets of data. The first is the recorded number of crimes recorded by the MPD. The second is the citizens’ sense of security since 2007, one year before BWM started. Sense of security has been measured in questionnaire surveys conducted by the Adachi Ward every summer among 3,000 randomly selected citizens aged 20 and over (response rate: 53.0% in 2019). The director of the Risk Management section (temporarily transferred from MPD) has cooperated with the data collection.In order to rectify the crime situation and improve the image of the Ward, the local government and the Community Safety Department of the MPD published the “Protocol Promoting the Restoration of Security” on December 21, 2009 (Table A2). This helped to strengthen the relationship between MPD and the Adachi Ward. It was the first time that the MPD, which has jurisdiction over the entire Metropolitan Tokyo, published such a protocol with a specific municipality, suggesting that the MPD was also concerned with the crime situation in Adachi Ward. Centering on the BWM, the Ward has taken measures such as strengthening crime prevention patrols and expanding activities for citizens’ awareness on crime prevention with the cooperation of the MPD and the four police stations in the ward. Based on the protocol, MPD shared crime information with the Ward for the first time as a municipality. For example, the Ward opened a “Crime Map” on the website to inform where crimes had been occurring in order to enhance citizens’ awareness and deter crimes (Adachi Ward Operation “Aijo (with affection) Lock”: The staff locks unlocked bicycles without owners’ permission in public parking lots and large commercial facilities a few times a month. The bike owners ask the staff for the lock number, unlock it, and get the lock for free.“Gacchiri (firm) Lock” campaign: The staff exchanges weak bike locks with strong ones for free a few times a year on occasions such as festivals where many people gather (Adachi Ward Youth volunteers for bike-theft prevention: High school students and other young volunteers inform their colleagues that they should lock bicycles and that bicycle theft is a crime (because approximately one-third of the victims are teenagers) twice a year in spring and autumn. For example, 56 bike locks were replaced in a public residential estate where bicycle thefts occurred frequently in October 2020.Ordinance on safe use of bicycles: An ordinance which prohibits leaving bicycles in designated areas such as around railway stations and requires users to lock or take other appropriate measures (revised in January 2018).Adachi Ward has been focusing on prevention of bicycle theft because it occupies approximately one-third of recorded crimes in the Ward. The following are the examples of countermeasures against bicycle thefts:In addition to these, the Ward carries out various programs and interventions collaborating with the police stations and crime prevention volunteers.While the first action plan (2010) included the installation of CCTVs in streets and in public facilities, subsequent plans added installation around elementary schools and in parks. The Tokyo Metropolitan Government actually urged municipalities to install CCTVs in anticipation of the Tokyo 2020 Olympic and Paralympic Games; however, Adachi Ward focused more on CCTVs than other municipalities in Tokyo. The Ward has installed 670 CCTVs in public spaces, especially in local parks, around elementary schools, and busy commercial areas (as of April 2019). Originally, these CCTVs had been set up and managed by each section of the Ward, such as the road section and the park section. As it took up to 10 days to provide information to the police, the system was changed and only one section manages CCTVs. Currently, information is provided on the same day or 2 days after the police makes a request. Responses to breakdowns of CCTVs have also been speeded up, and strategic installation based on the distribution of existing CCTVs has become possible. In addition, 1160 CCTVs have been installed by NHAs in residential and local commercial areas with the subsidy of the Ward. The Ward subsidizes 95% of the installation cost and part of the operation cost; the subsidy amounts to approximately 81 million yen per year.Crime volunteer patrols, “Streets with flowers project,” and certification of neighborhoods are discussed in this section. While aiming at crime prevention, all of them improve the sense of security through developing social capital.Besides crime prevention patrols by private security services entrusted by the Ward, crime prevention volunteers (CPVs) patrol their neighborhood. Residents’ voluntary crime prevention activities in Japan are generally carried out in each neighborhood by members of NHAs, parents and teachers’ associations (PTAs), and other local stakeholders. According to police, 4,500 citizens in 170 groups were registered as CPVs in Adachi Ward (as of the end of 2019).Activities of CPVs are diverse, including patrol (on foot and using blue-light cars), cleaning neighborhoods, planting flowers, checking risky places, watching out for children walking to/from school, conducting activities to prevent fraud to elderly, and so on. These actions raise residents’ awareness that they have to keep their neighborhoods safe by themselves. The Ward supports them providing tools used in crime prevention activities and volunteer insurance. The Ward also provides financial support for CPVs that conduct patrol more than twice a month to watch for children walking to/from school. The support is up to 100,000 yen per group for buying equipment such as vests, jackets, armbands, clappers, flashlights, and flags . Physical offenses against children are concentrated during this time, and CPVs are expected to prevent such offenses and improve the sense of security . However, despite the changes, in a general sense residents view security as “Good” or “Bad.” As shown in Fig. This study reported the implementation of various crime prevention measures based on BWM, which resulted in a reduction of crimes and the improvement of citizens’ sense of security in Adachi Ward. Crime prevention measures involved two different types; (1) those in partnership with the police and (2) those to make the Ward beautiful in cooperation with citizen volunteers. The first directly reduced the number of crimes, which improved citizens’ sense of security. It can be said that the strategy of focusing on measures against minor crimes, especially bicycle theft which decreased by 10 pp more than the average of all 23 wards, seems to have worked well. At the same time, it is difficult to quantify and connect various measures with results. This is also apparent from the results of annual surveys, which overall are positive but specifically vary. Still, the large decrease in the number of crimes and the release from the stigma of Adachi being “the worst among the 23 Wards” certainly contributed to the improvement of citizens’ sense of security.The activities in cooperation with citizen volunteers, which enriched social capital in the neighborhood, contributed to the decrease in the number of crimes, and improved citizens’ sense of security Below is the link to the electronic supplementary material.


Learning through a 360° virtual reality (VR) or 2D video represents an alternative way to learn a complex medical education task. However, there is currently no consensus on how best to assess the effects of different learning materials on cognitive load estimates, heart rate variability (HRV), outcomes, and experience in learning history taking and physical examination (H&P) skills.The aim of this study was to investigate how learning materials  impact learning outcomes and experience through changes in cognitive load estimates and HRV for learning H&P skills.P value of <.01.This pilot system–design study included 32 undergraduate medical students at an academic teaching hospital. The students were randomly assigned, with a 1:1 allocation, to a 360° VR video group or a 2D video group, matched by age, sex, and cognitive style. The contents of both videos were different with regard to visual angle and self-determination. Learning outcomes were evaluated using the Milestone reporting form. Subjective and objective cognitive loads were estimated using the Paas Cognitive Load Scale, the National Aeronautics and Space Administration Task Load Index, and secondary-task reaction time. Cardiac autonomic function was assessed using HRV measurements. Learning experience was assessed using the AttrakDiff2 questionnaire and qualitative feedback. Statistical significance was accepted at a two-sided P=.04). The reaction time at the 10th minute in the 360° VR video group was significantly higher than that in the 2D video group (P<.001). Multiple logistic regression models of the overall cohort showed that the 360° VR video module was independently and positively associated with a reaction time at the 10th minute of ≥3.6 seconds  and a Milestone level of ≥3 . However, a reaction time at the 10th minute of ≥3.6 seconds was not related to a Milestone level of ≥3. A low-frequency to high-frequency ratio between the 5th and 10th minute of ≥1.43 seemed to be inversely associated with a hedonic stimulation score of ≥2.0  after adjusting for video module. The main qualitative feedback indicated that the 360° VR video module was fun but caused mild dizziness, whereas the 2D video module was easy to follow but tedious.All 32 participants received the intended intervention. The sample consisted of 20 (63%) males and 12 (38%) females, with a median age of 24 (IQR 23-25) years. The 360° VR video group seemed to have a higher Milestone level than the 2D video group (Our preliminary results showed that 360° VR video learning may be associated with a better Milestone level than 2D video learning, and that this did not seem to be related to cognitive load estimates or HRV indexes in the novice learners. Of note, an increase in sympathovagal balance may have been associated with a lower hedonic stimulation score, which may have met the learners’ needs and prompted learning through the different video modules.ClinicalTrials.gov NCT03501641; https://clinicaltrials.gov/ct2/show/NCT03501641 From premedical students to practicing physicians, competency-based medical education (CBME) has been applied in the design, implementation, and evaluation of medical education programs according to competency-based outcomes . CBME foCBME is used to improve graduates’ competency levels, ensuring they are skillful and qualified in all critical areas of their occupation. To this end, CBME emphasizes the use and importance of simulation-based training, which considers patient safety and for which real-life opportunities are limited . This coVR consists of a computer-generated 3D simulation in which the user both explores and manipulates the contents of the environment to learn and assess clinical knowledge and skills . VR provHowever, transferring practical skills to a clinical setting using a criterion-based training program with VR simulators is difficult . In addiEstimations of cognitive load and specific load types are still challenging based on current cognitive load theory ,27. For VR immersion, especially containing stressful content, can evoke acute stress reactions accompanied by autonomic dysfunction . Heart rThis study aimed (1) to evaluate differences between two learning materials  in the subjective and objective cognitive loads, autonomic function, outcome, and learning experience while students were learning H&P skills and (2) to study how learning materials  impact learning outcomes through the changes in cognitive load and HRV. The initial hypotheses were that (1) subjective and objective cognitive loads and autonomic function would be changed while using different learning materials and (2) learners with higher learning outcomes and experience would have different cognitive load and autonomic function during the learning tasks than those with lower learning outcomes and experience.Therefore, we used cognitive questionnaires immediately after completing a video learning module to assess subjective cognitive load. We also used secondary-task reaction time and HRV to objectively estimate the dynamic changes of cognitive load and cardiac autonomic function during a video module for providing ongoing feedback to improve video learning. Subsequently, we used the Milestone report form to evaluate the real-patient H&P. The Milestones have been designed according to the grounding principles of CBME and have become a significant formative component of the current accreditation model of graduate medical education . AlthougWe conducted a prospective, randomized controlled, pilot system–design study from June 1 to October 30, 2018, at an academic teaching hospital . The Institutional Review Board of the Chang Gung Medical Foundation approved this study (No. 201601821B0), and we conducted all procedures in compliance with the Declaration of Helsinki 1975. We informed the participants about the aims of the study and then obtained written informed consent from them. We registered the entire study proposal at ClinicalTrials.gov NCT03501641). 1641. 50]We used analysis, design, development, implementation, and evaluation models  to desigThis module was developed to arbitrarily review the immersive 3D 360° VR video through a head-mounted display . The useThe 2D video was played in a fixed 120° focused field of view through the same head-mounted display . The useA convenience sampling approach was used, and 32 consecutive volunteers were recruited during the study period. The inclusion criteria were as follows: (1) aged >20 years and (2) novices in ORL-HNS . The exclusion criteria were as follows: (1) contraindications for using VR, such as pregnancy, hypertension, motion sickness, inner ear infections, claustrophobia, recent surgery, pre-existing binocular vision abnormalities, heart disorders, or epilepsy, and (2) declining to participate. All of the volunteers had at least a basic level of computer literacy and could use VR headsets and controllers after instruction. We used the 25-item Group Embedded Figures Test (GEFT) (score range 0-18) to assess the participants’ cognitive style . The GEFThe participants were blinded to the purpose of the study during recruitment to minimize preparation bias. After the participants had provided consent and completed the GEFT, we randomly assigned them, with a 1:1 allocation, to the 360° VR video group and the 2D video group, matched by age, sex, and cognitive style . The RanAfter randomization, the participants reviewed their allocated video through a head-mounted display in the same space for 10 minutes. To reduce the effect of the head-mounted display on learning experience, both groups used the same VR device . We explained the functionality of the VR device to the participants before the intervention. In the 360° VR video group, the learners arbitrarily reviewed the instructor’s demonstrations and responses from standard patients and other medical staff from a first-person perspective in an immersive 360° environment . In the We used five different face-to-face assessments, including the Paas-CLS and the NASA-TLX for subjectively estimating the cognitive load, the Milestone for assessing the learning outcomes, and the AttrakDiff2 questionnaire and anonymous qualitative feedback for determining the learning experience. There was one objective estimate of cognitive load using the secondary-task performance and one measurement of cardiac autonomic function using HRV monitoring.We used the Paas-CLS  to estimThe NASA-TLX questionnaire is a subjective assessment of cognitive load . This inSecondary-task performance has been shown to be sensitive in estimating intrinsic cognitive load among novices engaged in simulation-based learning . As the HRV has been shown to be an objective estimation of learners’ cognitive load in a learning environment ,62. For The Milestones have been used to assess the development of resident physicians in key dimensions of the elements of physician competency in otolaryngology since 2004 . In thisThe AttrakDiff2 questionnaire was developed to reliably evaluate the acceptance of technical innovations . It asseEach participant in this study provided anonymous feedback about their experience of the module used.The primary outcome measure of this study was the Milestone level after completing the video learning module. The secondary outcomes were the AttrakDiff2 questionnaire scales.U test was used to calculate a sample size of 16 in each group . For a block size of 8, we decided to enroll a total of 32 students to show the difference in the Milestone level.The sample size was estimated using primary outcome effects (the Milestone) based on a priori study . A two-tailed Wilcoxon-Mann-Whitney U test, or the Fisher exact test as appropriate. Effect sizes were calculated using the Hodges-Lehmann method for the Mann-Whiney U test and the Wilcoxon signed-rank test, or odds ratios for the Fisher exact test. The Spearman correlation test was used to analyze relationships between variables of interest. The Bonferroni correction was used to adjust P values because of the increased risk of a type I error when conducting multiple statistical tests at the same time [P values were two‐sided, and statistical significance was accepted at P<.01. Statistical analyses were performed using G*Power software , Prism for Windows , and SPSS Statistics for Windows .The D’Agostino-Pearson omnibus normality test showed that most of the continuous variables were nonnormally distributed, and they were presented as median and IQR. Differences between groups were analyzed using the Wilcoxon signed-rank test, the Mann-Whitney ame time . ContinuA total of 32 volunteers were recruited, of which 20 (63%) were males and 12 (38%) were females. The median age was 24 (IQR 23-25) years. There were 3 (9%) field-dependent and 29 (91%) field-independent participants. P=.001) after 10 minutes of video instruction  than the reference value of “10” before and after the Bonferroni correction  but comparable to the reaction time at baseline. In contrast, the reaction time at the 5th minute was equal to the reaction time at baseline after the Bonferroni correction. In the 360° VR video group, the reaction time at the 10th minute was significantly higher than the reaction time at the 5th minute (corrected P=.003) and the reaction time at baseline (corrected P=.006). Still, the reaction time at the 5th minute and the reaction time at baseline were comparable (P<.001), even though differences in the reaction time at the 5th minute and reaction time at baseline were not statistically significant.In the overall cohort , the reamparable , upper. Differences across the RR at 5 to 10 minutes, RR at 0 to 5 minutes, and RR at baseline were not statistically significant in the overall cohort, the 360° VR video group, and the 2D video group, respectively. Furthermore, the RR at 5 to 10 minutes, RR at 0 to 5 minutes, and RR at baseline were comparable between both groups . DiffereP<.001) after 10 minutes of video instruction. Although the Milestone level of the 360° VR video group  was higher than that of the 2D video group , the difference did not reach statistical significance   than the reference value of “1”  , lower.P<.01, after 10 minutes of video instruction  and “good for physical examinations” . Qualitative feedback from the 2D video group emphasized that they found the 2D video module “easy to follow”  and “highly efficient” .Out of 16 participants in the 360° VR video group, 3 (19%) reported that it caused “mild VR dizziness.” Notably, the 2D video learners said that the module was “tedious”  and that there was “no interaction” .This study’s main findings highlighted the complexities of cognitive load estimations and HRV indexes inherent in developing and evaluating 360° VR and 2D video learning. Our results showed that video learning resulted in a higher total cognitive load and mental demand and prolonged the reaction time at the 10th minute; however, video learning also enhanced a Milestone level of H&P skills with positive learning experiences. Using the same head-mounted display, both the 360° VR and 2D videos were efficient learning methods with positive learning experiences for novice learners. Notably, the 360° VR video learners demonstrated a higher Milestone level of H&P in actual patients with SDB than the 2D video learners. Although both video modules produced comparable total cognitive load and subscales, the 360° VR video learners had a more prolonged reaction time at the 10th minute than the 2D video learners.Interestingly, in the second portion of the video, the 360° VR video learners had a longer reaction time than the baseline data. These findings suggested that the immersive 360° VR video could reduce secondary-task performance without increasing subjective cognitive loads. Furthermore, the elevated LF/HF ratio at 0 to 5 minutes correlated with a reduced hedonic stimulation scale. Combined with qualitative feedback, we found that the students seemed to consume more cognitive resources to fit the immersive 360° VR video than the 2D video learning. This preliminary study suggests that the immersive 360° VR video might lead to a better Milestone level than the 2D video, which seemed to be unrelated to cognitive load estimates and HRV indexes in novice learners.This study used quantitative and qualitative measures and methods to evaluate different video learning materials and showed its potential clinical applicability for learning H&P skills. However, several limitations should be addressed. First, this study needs external validation due to the small sample size. Although H&P is one of the essential training topics for undergraduate medical students, our outcomes may not be generalizable to junior residents who already have basic knowledge, skills, and attitudes. Second, assessments of the learner’s performance in the workplace, such as the Mini Clinical Evaluation Exercise, were not included in this study. Third, there were several significant associations between variables of interest in this study. However, the potential relationships between video module, cognitive load, and HRV might be underestimated using such stringent criteria for multiple tests . AccordiOur results indicate that both 360° VR and 2D video learning modules can increase H&P competency. Traditionally, students learn clinical skills, such as H&P, from clinical teachers. Instructional videos offer an excellent pedagogical approach to enhance medical students’ clinical competencies and self-confidence levels ,75. MoreImmersive 360° VR videos allow for a virtual experience where learners can improve their competencies by experiencing all of the sights and sounds of teaching clinics and responses from the patients, families, and medical staff from a first-person perspective. When working memory and information processing capacities are limited, 360° VR video learning can trigger a higher cognitive load or stress than conventional 2D video learning. In this study, 360° VR video learning might reduce participants’ attention toward the secondary task without changing subjective cognitive load estimates and HRV indexes regardless of the learning outcome. Therefore, the quality of 360° VR video learning modules still needs to be improved concerning reducing objective cognitive load.Approximately 25% of our volunteers reported high vibration, out-of-focus blur, eye fatigue, and motion sickness in the preparation phase of the 360° VR video production. A literature review revealed that immersive 360° VR video might induce 3D visual fatigue  and visuIn contrast, the 2D video learners did not report these problems while using the same head-mounted display. Although the participants might have an adequate cognitive function to overcome the impaired attention for obtaining the H&P competence, the instructors need to design a 360° VR video with less distraction and lower cognitive load. A motion capture unit to synchronize vestibular response and visual information may reduce motion sickness , and furInterestingly, the elevated LF/HF ratio at 5 to 10 minutes seemed to be associated with lower hedonic stimulation. Since these cognitive load estimates were not related to Milestone level, they could be used to improve the quality of video learning. For example, the virtual environment sustained the increased LF/HF ratio and acted as a stimulatory driver for cardiac autonomic activity after mental stress . TherefoThis study applied the adaptive EMD method and the well-behaved Hilbert transform technique to process the nonstationary electrocardiogram signals ,64. ImpoOur preliminary results suggested that 360° VR video learning may result in a better H&P performance despite causing a more prolonged secondary-task reaction time than 2D video learning. Furthermore, the increased LF/HF ratio was associated with lower acceptance of video learning. Qualitative evaluation reflected varying benefits and faults between the 360° VR and 2D videos. Consequently, the students seemed to consume more cognitive resources to fit the immersive 360° VR video than 2D video learning. Without cognitive overload, the undergraduate medical students could adjust their mental efficiency to handle the decreased cognitive reserve when learning through the 360° VR video module. This study indicates that the ubiquitous and diverse roles of multimodal cognitive load estimations and HRV measures in video learning may function as part of an integrated CBME curriculum. Further research is necessary to assess their effects on other performance outcomes.


Surgical patients frequently seek information from digital sources, particularly before common operations such as laparoscopic cholecystectomy (LC). YouTube provides a large amount of free educational content; however, it lacks regulation or peer review. To inform patient education, we evaluated the quality of YouTube videos on LC.  We searched YouTube with the phrase “laparoscopic cholecystectomy.” Two authors independently rated quality of the first 50 videos retrieved using the JAMA, Health on the Net (HON), and DISCERN scoring systems. Data collected for each video included total views, time since upload, video length, total comments, and percentage positivity . Interobserver reliability was assessed using an intraclass correlation coefficient (ICC). Association between quality and video characteristics was tested.  Mean video quality scores were poor, scoring 1.9/4 for JAMA, 2.0/5.0 for DISCERN, and 4.9/8.0 for HON. There was good interobserver reliability with an ICC of 0.78, 0.81, and 0.74, respectively. Median number of views was 21,789 . Videos were mostly published by private corporations. No video characteristic demonstrated significant association with video quality.  YouTube videos for LC are of low quality and insufficient for patient education. Treating surgeons should advise of the website's limitations and direct patients to trusted sources of information. Use of the Internet by patients seeking health information is ubiquitous. Patients turn to information on the Internet both before seeking help from a professional and also after or as a second opinion . In partIn the midst of the coronavirus disease 2019 (COVID-19) pandemic, social and physical distancing recommendations there have been rapidly increase in the use of telehealth solutions . In thisPrevious studies have characterised the quality of YouTube videos for patient education prior to surgery and found them to be poor , 6. A liWe adapted methods outlined by Ovenden and Brooks . A YouTuFor each video, we extracted data for search results, date of publication, length, number of views, number of comments, and number of ‘likes' and ‘dislikes' and assigned an authorship category. We defined ‘positivity' as the ratio of video ‘likes' to the sum of ‘likes' and ‘dislikes' expressed as a percentage.Two authors (JNH and JGK) independently watched and scored each video against three previously validated scoring systems: the Journal of the American Medical Association (JAMA) , Health Prior to video scoring, the authors had a discussion regarding what would be considered the ideal video and how points would be awarded. The scoring process was then undertaken independently.t-tests were used to test for relationships between scores assigned and video characteristics. All statistical analysis was performed with IBM SPSS ver. 27 .We tested interobserver reliability with an intraclass correlation (ICC) analysis and then used the mean score from both observers for further analysis. Linear regression or Student's Of the 50 videos analysed, 26 (52%) were authored by surgeons, 10 (20%) by healthcare or education companies, and 7 (14%) by hospitals or universities, and in 7 cases (14%), video authorship fell outside these categories or was unclear. Five videos were authored by the same surgeon and 2 videos by the same healthcare or education company. Extracted data regarding video characteristics are outlined in There was good interobserver reliability for all three scoring systems with ICC values 0.78, 0.81, and 0.74 for JAMA, DISCERN, and HON scores, respectively. The mean (+/− SD) video quality as measured by each score was 1.9/4.0 (±0.7), 2.0/5.0 (±0.6), and 4.9/8.0 (±0.9) for JAMA, DISCERN, and HON, respectively. There was a statistically significant correlation between video quality as measured by each score and as measured by both other scores. This is demonstrated in p < 0.001, Pearson's correlation). There was a correlation between video rank in search results and number of views  and comments  but no correlation between video rank and quality as measured by each score.There was no significant association between any video characteristics and video quality as measured by any of the three scoring systems. There was a positive correlation between the number of views and number of comments  and complementarity (15%). For DISCERN, relevance (62%) and discussion of risks (24%) were the highest and lowest scoring categories.The quality of YouTube videos on laparoscopic cholecystectomy for patient education is suboptimal when assessed by the JAMA, DISCERN, and HON scoring systems. There was good intraclass correlation between scorers for each of these systems. This video series contained a higher proportion of videos produced by surgeons and, significantly, no patient testimonial videos. This is in contrast to the series of videos Ovenden and Brooks obtained on anterior cervical discectomy which included nearly 50% patient testimonials . The reaThere was no correlation in our series between high video quality and the number of views. While YouTube's algorithm for search recommendations remains an unknown black box , it is nThe management of surgical systems has been modified considerably at many points during the current COVID-19 pandemic . Recent Patient education before operations such as laparoscopic cholecystectomy typically consists of pamphlets and verbal information provided by the surgeon and nurses during a preadmission consultation . While oApproaches to surgical intervention have evolved rapidly over time . AlthougThis study has multiple limitations. Primarily, we only analysed the first 50 search results obtained from YouTube. However, this amount was selected pragmatically, as it is within the scope of retrieved videos which the usual searcher would be most likely to view. YouTube was the only platform used in this study, potentially limiting the generalisability of our results to other online health information sources. “Laparoscopic cholecystectomy” was the only search term, and there may be higher-quality videos for patient education available by searching “gallbladder operation,” for example. Five of the 50 videos were posted by the same surgeon and 2 by the same company, and this may further limit the generalisability of our results. This is a limitation inherent in YouTube's search algorithm, however, and these same videos could be presented to a patient who made the same search. There will always be an inherent level of subjectivity to qualitative assessments of these forms of videos; however, we sought to mitigate this limitation and ensure reliability of results through the use of three separate validated scoring methods. Within the scoring tools, certain items required knowledge of the intervention, alternative treatment approaches, and effectiveness within overall shared decision making between the patient and clinician. At the time of this study, the two authors who scored the videos were a surgical resident medical officer and final-year medical student, respectively, and, thus, did not have a specialist level of knowledge of laparoscopic cholecystectomy. To mitigate potential bias, we selected scoring tools that have been validated and do not require specialist knowledge or help to be used .Surgeons should be aware that the quality of information their patients may have accessed regarding laparoscopic cholecystectomy online is suboptimal. This is even more important when, with the uptake of telehealth experienced along with the COVID-19 pandemic and the rise of digital health, patients may turn increasingly to sources of information other than their treating surgeon.


Mixtures of neuroactive substances occurring at low concentrations can induce adverse neurological effects in humans and organisms in the environment. Therefore, there is a need to develop new screening tools to detect these chemicals. Measurement of behavior or motor effects in rodents and fish are usually performed to assess potential neurotoxicity for risk assessment. However, due to pain and stress inflicted on these animals, the scientific community is advocating for new alternative methods based on the 3R principle . As a result, the behavior measurement of early stages of zebrafish embryos such as locomotor response, photomotor response and spontaneous tail coiling are considered as a valid alternative to adult animal testing. In this study, we developed a workflow to investigate the spontaneous tail coiling (STC) of zebrafish embryos and to accurately measure the STC effect in the KNIME software. We validated the STC protocol with 3 substances  which have different mechanisms of action. The KNIME workflow combined with easy and cost-effective method of video acquisition makes this STC protocol a valuable method for neurotoxicity testing.  Specifications TableThe spontaneous tail coiling (STC) represents the earliest motor activity observed in the developing neural network of zebrafish embryos. It is assumed to be mediated by the innervation of the muscle by the primary motor neurons, which are first present at around 17 hpf ,11,13. TAdult zebrafish (OBI and WIK strains) were obtained from a local commercial breeder and crossed to obtain a hybrid strain . Fish were cultured under 14 h light/10 h dark photoperiod in 120 L aquaria. Spawning trays were placed in the tanks on the afternoon 4–6 h before the end of the light cycle. The following day, lights were automatically switched on at 8am to initiate the spawning and eggs were collected at 9am. In order to remove dirt and debris, the eggs were washed several times with ISO water. After washing, fertilized eggs between 2 and 3 hpf were selected under a stereomicroscope. Twenty embryos were exposed to 20 mL of test chemical in 40 mL glass petri-dish  and covered with a glass lid to prevent evaporation or cross-contamination. Glass dishes were incubated at 28 °C till the next day. Exposure was conducted with 14 glass dishes representing 7 concentrations and 2 replicates including the negative and positive control . The gla(1)2·2H2O, 20 mM MgSO4·7H2O, 31 mM NaHCO3, 3.1 mM KCl]ISO water was prepared according to ISO 7346–3 (1996) [80 mM CaCl(2)Chemical stock solutions were prepared a day before in ISO water or were already standing on the bench when prepared in dimethyl sulfoxide (DMSO). The stock solution was diluted to give lower concentrations in 50 mL standard volumetric flasks.(3)The glass petri-dishes were labeled with the necessary experiment information according to the number of treatments and replicates(4)Twenty fertilized embryos (2–3 hpf) were selected and transferred into each labeled dish. Embryos were transferred into the dishes systematically i.e. first replicate for all treatments starting from lowest to highest concentration were filled and followed by the second replicate. This system models the video acquisition format see . This en(5)The selected embryos were exposed to each chemical concentration and ISO water as negative control. Water was first removed using a pipette and 20 mL of the respective exposure solution was added into the dishes. A solvent control should be used when solvents are used to prepare the chemical solution.(6)The dishes were covered and Incubated at 28 °C overnight.Specific procedure:On the next day, the microscope and camera were setup for video acquisition. The embryos were removed from the incubator and allowed to acclimatize at room temperature for at least 30 min. The acclimatization period aimed to ensure a constant measuring temperature since the microscope was not contained within an incubator. We found in a previous study (1)The computer screen, camera (Olympus DP21) and stereomicroscope (Olympus SZX7) were turned-on. Light source was from a LED illumination base of the microscope.(2)The magnification of the microscope was set to 0.8X and the background base was tuned to dark background to create a contrast against the transparent embryos.(3)Camera settings were ISO = 400; shutter speed = 1/80, image size = 400 × 300 pixels and image resolution = 1600 × 1200 pixels. Other types of camera including a mobile phone camera may be used to collect videos if quality requirements are met.(4)Embryos at ≈ 24–25 h post fertilization were removed from the incubator and equilibrated at room temperature for at least 30 min.(5)Embryos were assessed for developmental malformations and lethality under the stereomicroscope. Deformed or dead embryos were removed or separated. Number of removed embryos were recorded in a data sheet.(6)All normal embryos were clustered to the center by slightly swirling the dish and forceps were used to improve the clustering when required. Embryos were placed side by side and not super imposed on each other a.Fig. 2A(7)Embryos were videotaped for 1 min using a stop clock. Embryos could be monitored or observed during video acquisition via the computer screen. It is important to keep the table holding the camera still during video recording.(8)Video acquisition was completed within a period of ≈ 30 min in order to avoid confounding effects of developmental stage within an experiment i.e. 2 min per dish or 28 min for 7 treatments and 2 replicates.(9)A second chemical exposure may be conducted in parallel by following the same procedure as for the first chemical i.e. preparation of chemical solutions, embryo selection may be conducted simultaneously but video acquisition should be performed in blocks of independent experiments.(10)The videos were stored in a mobile drive and transferred to a local or cloud drive for further analysis.Specific procedure:The workflow  computesThe workflow requires video recordings in AVI format as input and iterates over all video files in the selected folder. The video files are converted to stacks of images using the FFmpeg tool (2016) at a sample rate of 120 frames per minute. The program is executed by using the external tool node in KNIME®. The individual embryos in the image are detected by applying a threshold for conversion to binary images. Briefly, for each frame a median filter is applied to smooth the image and the background is subtracted using the ImageJ macro node (SubstractBackground function). Then a threshold is automatically set and applied using a variable node. The threshold is based on the mean pixel intensity of all frames, but it can be adjusted depending on the characteristics of the video files. The image with the applied threshold should display embryos completely filled in white and the background in black b. Then iSubsequently the variance of gray values of embryo labels of two successive images is compared to identify movements. Therefore, a lag column is created and the difference of pixel across each video frame stamp is calculated using the image calculator node. Then a threshold is applied and the variance in pixel is extracted using the image segment features node for each labeled embryo. This threshold was set by verifying the concordance between the final KNIME® output and the visual count of the STCs.Embryo labels between subsequent frames were associated using the centroid of the label. Because embryos may slightly move between each frame, a distance of 15 pixels was allowed between label centroids of individual frames.Finally the frequency of movements of each embryo is analyzed by iterating over each label and using as input the pixel variance over all the frames. An increase in variance indicates tail coiling. Therefore during the time series, peaks representing tail coilings were identified using the function ‘findpeaks’ of the R package ‘quantmod’ Note that we included a metanode (“Check for error”) after the “position binner” metanode. This node serves as an internal control to detect when there is an error during the image analysis, for example in case that embryo were not correctly identified and labeled. That would require to repeat the analysis of the specific video by adjusting the first threshold value  or correcting the maximum distance of centroid allowed between individual frames.https://youtu.be/wgJN71zTvRw(1)https://www.knime.com/downloads) and install on your PC.Download KNIME ((2)Also download the STC workflow and ffmpeg software from KNIME hub and import it into your KNIME software. Open the KNIME software and set the workspace to your preferred folder.(3)Install all necessary KNIME extensions  for the STC workflow and restart KNIME.(4)Configure ffmpeg software by setting up the path to its location on your PC using the bin folder as the end of the path.(5)Open R software and install the required packages . If necessary, change the file path of R to the correct location. R error messages can be diagnosed by clicking Eval script in KNIME and then installing the missing packages(6)The video file or folder containing the video files to analyze should be inserted in the KNIME workspace folder, use the Explorer browser node to select the folder containing the video. Alternatively, you can use the List files node to select folders outside of the workspace folder. Specific video files from the folder can be selected using the row filter node next to list files node.(7)The workflow can be executed by clicking the double green arrow in the top menu to start the loop.(8)The workflow creates a folder with the same name as the video file analyzed which contains the stack of images generated. After the analysis they should be removed to save disk space.(9)(a)Frames per minute can be changed in the ffmpeg component configuration and in the Frequency analysis component configuration. Default is set to 120 frames per minute. Both configurations should have the same frame rate for a correct analysis.(b)R parameters for threshold and smoothing can be changed in the Frequency analysis component configuration. Default is set to 0.003 and 0.1 for threshold and smoothing respectively.(c)Global threshold for detecting embryo can be changed by subtracting or adding a number in the Threshold component configuration. This controls the global threshold node.Changing KNIME parameters:More details on how to implement the workflow are shown in the youtube video: Data was obtained from the KNIME workflow as the number of STCs per minute or STC frequency for one embryo. Inspect the peaks: A possible correction protocol could be to visually inspect the peaks for errors e.g. by comparing unsmoothed and smoothed peaks . IrregulSuspect peaks: Suspected peaks should be verified using the annotated label of the embryo to locate and check embryo movement in the original video . The useThe STC frequency of the individual embryos, the mean of all embryos, the STC peaks and the annotated embryos are compiled as results within an output Excel file from the KNIME workflow. An example Excel file and corresponding video is given in the supplementary information (SI Excel file 1 and video 1). The mean STC frequency (3.3 ± 0.85/min) for untreated embryos varied between independent experiments . To obta50 – the concentration at which the percentage STC is half-maximum relative to the untreated embryos. Hypothesis testing may also be used when sufficient technical replicates are tested. Shapiro test and Bartlett test could be used to check for normality and homogeneity of variance, respectively. In case normality of the data is not met, non-parametric test such Kruskal-Wallis or Dunnet tests could be used to test for statistical differences between treatment groups. Statistical difference was considered when the p-value < 0.05.To determine the actual effect of a chemical, it is possible to analyze the data using concentration-response modeling or hypothesis testing. We performed concentration-response modeling to estimate the ECThe STC test as devised in this study can be used to screen neuroactive chemicals based on the hyper and hypoactivity response of zebrafish embryos. In addition, the STC test may also be used to screen non-neuroactive substances assuming that behavior endpoints are usually more sensitive than lethality. The STC test method described in the current paper have already been applied to screen a range of 18 test chemicals with different modes of action 50 of 0.055 µM. Four other studies reported hypoactivity for abamectin in the STC test but the reported lowest observed effect concentrations (LOEC) were higher than the EC50 found in the current study [Abamectin is an avermectin insecticide expected to cause hypoactivity by activating Gamma aminobutyric acid-gated chloride channel. Abamectin induced hypoactivity in the STC test at an ECnt study ,9,15,17.50 and EC10 of 0.32 and 0.05 µM respectively and this is consistent (the EC10) with the LOEC of 0.03 µM reported by Weichert et al. Chlorpyrifos-oxon is a metabolite of chlopyrifos which is an organophosphate insecticide. It acts by inhibiting acetylcholinesterase enzyme which breaks down acetylcholine, and therefore keeps the nicotinic acetylcholine receptors open for sodium ions to flow into the cell leading to an action potential and hence potential hyperactivity. In our study, chlorpyrifos-oxon induced hyperactivity in the STC test at an ECPyraclostrobin is a fungicide and expected to not impact on the STC due to its classification as a narcotic or baseline toxic in quantitative structure and activity relationship (QSAR) for zebrafish In this paper, we described a protocol for measuring spontaneous tail coiling in zebrafish embryos. First, we gave exhaustive guidelines on how to conduct the experiment based on optimized experimental parameters. Second, we detailed how to automatically analyze the collected video recordings in a workflow with the open source KNIME software. Third, we then validated the described method using three chemicals with different modes of action. The STC test can now be used for the assessment of neuro  toxicity and testing of both neuro and non-neuroactive compounds. This automated analysis in KNIME provides an easier way to analyze STC over the laborious manual counting in Supplementary material and/or Additional information:SI Excel file 1 – Result output of the STC analysis in KNIME. Sheet 1 (“default”) contains embryo identification labels, total embryos analyzed and threshold of analysis. Sheet 2 (“Raw data”) contains the STC peaks, peak number for each embryo and STC frequency.SI Video 1 – Video recording of 20 embryos which was analyzed in KNIME to give the result output in SI Excel file 1.Co-submissions are papers that have been submitted alongside an original research paper accepted for publication by another Elsevier journalCo-SubmissionNTT_106918The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.


To examine the moderating effect of older adults’ history of drinking problems on the relationship between their baseline alcohol consumption and risk of dementia and cognitive impairment, no dementia (CIND) 18 years later.n = 4421) was analyzed to demonstrate how older adults’ baseline membership in one of six drinking categories  predicts dementia and CIND 18 years later.A longitudinal Health and Retirement Study cohort . Similar patterns obtained for the prediction of CIND.For older adults, consuming alcohol at levels within validated guidelines for low-risk drinking may offer moderate long-term protection from dementia and CIND, but this effect is diminished by having a history of drinking problems. Efforts to predict and prevent dementia and CIND should focus on older adults’ history of drinking problems in addition to how much alcohol they consume. Almost 6 million Americans live with Alzheimer’s Disease and related dementias (ADRD), and more than one-third of U.S. adults over age 70 experience cognitive difficulties that fall short of dementia but significantly interfere with their daily functioning ) –4. Prevaquantity of alcohol that older adults consume and the degree of their cognitive impairment. Although findings in this area are not completely consistent, they suggest overall that there is a “U”- or “inverted J” - shaped relationship between how much alcohol older adults consume and their subsequent risk of dementia and impaired cognitive function, wherein risk is least among “moderate” drinkers, and highest among non- and “heavy” drinkers ) This study had several strengths, including a large sample size, a longitudinal design featuring an 18-year follow-up interval, and use of validated classification systems to assess alcohol consumption levels and cognitive function outcomes. However, it also had limitations. The HRS measure of history of drinking problems is completed only once, when participants first enter the study, comprises only four items, and indicates only whether participants have “ever” experienced the items. Accordingly, it is not possible to infer the time of onset, duration, or severity of participants’ drinking problems over the life course. The outside-guideline drinking group was small, which may have diminished the likelihood of our detecting effects of membership in this group on cognitive function outcomes. Moreover, although our research design has the benefit of temporal precedence between predictive and outcome variables, it does not demonstrate a causal link between alcohol consumption and cognitive function. Although we controlled for key sociodemographic and health factors, there may be other variables associated with alcohol use and cognitive function that were uncontrolled and account for the associations we found between participants’ initial drinking behaviors and subsequent cognitive function. Finally, the 18-year longitudinal cohort studied here was subject to selective survival and other attrition processes that must be considered in interpreting the findings . Our finand a signature drinking behavior associated with history of drinking problems, the practice of clustering many drinks within single drinking occasions, a behavior known to be increasing among older adults in the U.S. throughout the past decade [For older adults, consuming alcohol at levels within validated guidelines for low-risk drinking may offer some long-term protection from dementia and CIND, but this effect is diminished by having a history of drinking problems. This finding has potential public health significance. It reinforces previous findings , 53 showt decade , 55. Cli


Ulcerative colitis (UC) is an inflammatory disorder, and almost one-third of UC patients ultimately undergo surgical interventions because of complications or refractory disease. Current restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the standard intervention for severe chronic UC with refractory disease. Several complications associated with this procedure can occur, including anastomotic leak, sepsis, and pouch ischemia. The most frequent long-term complication is pouchitis, an idiopathic inflammatory condition involving the ileal pouch. Presentations may vary but include stool frequency, urgency, incontinence, fatigue, malaise, and fever, less commonly bloody stools. We report a case of ileal pouchitis in a young patient, two years after proctocolectomy with IPAA responsive to antibiotic treatment. Our case supports that imaging studies like flexible sigmoidoscopy are necessary to rule out other disorders in patients with pouchitis. Pouchitis is an inflammatory disorder and a common complication of ileal pouch-anal anastomosis (IPAA), in patients with ulcerative colitis (UC) and familial adenomatous polyposis (FAP) ,2. The uA 25-year-old female presented with a one-week history of abdominal pain and watery diarrhea. She had a past medical history of papillary thyroid carcinoma with complete thyroidectomy, UC status post colectomy with IPAA (J-pouch). Her pain was most intense in the left lower abdominal quadrant and only relieved by heating pads. She stated an increased frequency of abdominal bowel movements (her regular bowel movements were four/day). She denied any environmental exposures, dietary changes, fevers, chills but stated malaise. The patient was initially placed nil per oral and started on intravenous fluids for dehydration. Her laboratory works up for inflammatory markers, and routine workup was negative, including thyroid panel. Her stool osmolality was 309 mOsm/kg, consistent with secretory diarrhea and abdominopelvic CT scan revealed J-pouch thickening without evidence of bowel obstruction, ascites, adenopathy, or pneumoperitoneum. The Clostridium difficile toxin was negative and stool culture failed to grow anything. Due to her history of UC and surgical intervention, she underwent flexible sigmoidoscopy with biopsy by gastroenterology and was noted to have a patchy area of mild erythematous mucosa Figure . A tentaThe patient was started on ciprofloxacin and metronidazole and discharged with a follow-up in the clinic. Her biopsy later revealed severe acute inflammation and degenerative changes without adenomatous dysplasia or malignancy. She received ten days of ciprofloxacin 500 mg twice a day and metronidazole 500 mg twice a day with resolutions of symptoms.Pouchitis can present with various clinical manifestations, and patients can have an acute or chronic presentation. The spectrum of presentation ranges from increase stool frequency, urgency, abdominal pain, and fecal incontinence. Patients may have associated pelvic or cramping abdominal pain that may not be relieved by a bowel movement. Despite a lack of bloody bowel movements, pouchitis can result in iron deficiency anemia ,8. In caIleal pouch endoscopy with biopsy is primarily performed for evaluation in case of a suspected cause of pouchitis. Endoscopically, a clinician may notice erythema (as in our case), erosion or ulceration of mucosa, and increased friability . TypicalIn the case of refractory pouchitis, it may be essential to repeat biopsy to exclude any concurrent infection. Blood tests to rule out primary sclerosing cholangitis and stool specimen for Clostridium difficile should also be obtained. Refractory pouchitis is the leading cause for pouch failure, ending in pouch excision or permanent ileostomy. A chronically inflamed pouch can increase the risk of cellular dysplasia or cancer ,15. Due Pouchitis is the most prevalent long-term unfavorable sequela of IPAA after restorative proctocolectomy. The natural history of pouchitis is poorly understood. Pouchitis has a wide range of clinical presentations, disease course, and the prognosis is often good. The key to appropriately manage pouchitis is an accurate diagnosis and its classification. It is important to consider the cost-effectiveness of diagnostic interventions as well. Treatment of pouchitis is mainly antibiotic-based. Maintenance of remission in antibiotic-dependent pouchitis and management of antibiotic-refractory pouchitis is a challenge. Secondary causes for refractory pouchitis should be excluded.