Functional disability is a significant problem after natural disasters. Musculoskeletal pain is reported to increase after disasters, which can cause functional disability among survivors. However, the effects of musculoskeletal pain on functional decline after natural disasters are unclear. The present study aimed to examine the association between musculoskeletal pain and new-onset poor physical function among elderly survivors after the Great East Japan Earthquake.A longitudinal study was conducted on survivors aged ≥65 years at three and 4 years after the Great East Japan Earthquake. A total of 747 persons were included in this study. Physical function was assessed using the Kihon Checklist. New-onset poor physical function was defined as low physical function not present at 3 years but present at 4 years after the disaster. Knee, hand or foot, low back, shoulder, and neck pain was assessed using a self-reported questionnaire and was defined as musculoskeletal pain. Musculoskeletal pain at 3 years after the disaster was categorized according to the number of pain regions . Multiple logistic regression analyses were performed to calculate the odds ratio (OR) and 95% confidence interval (95% CI) for new-onset poor physical function due to musculoskeletal pain.p for trend = 0.003).The incidence of new-onset poor physical function was 14.9%. New-onset poor physical function was significantly associated with musculoskeletal pain. Compared with “0” musculoskeletal pain region, the adjusted ORs (95% CI) were 1.39 (0.75–2.58) and 2.69 (1.52–4.77) in “1” and “≥ 2” musculoskeletal pain regions, respectively (Musculoskeletal pain is associated with new-onset poor physical function among elderly survivors after the Great East Japan Earthquake. Monitoring musculoskeletal pain is important to prevent physical function decline after natural disasters. Functional disability is a significant problem after natural disasters, especially among elderly survivors . The GreThe present study aimed to examine the association between musculoskeletal pain and new-onset poor physical function among elderly survivors in the recovery period after the GEJE.n = 6396). Altogether, there were 2853 (44.6%) participants. Among those, 1400 were aged 65 years and over. We excluded participants who already had poor physical function (n = 474) or for whom data on physical function were missing (n = 29). Study participants were followed up at 4 years after the disaster. The follow-up rate in this period was 85.1% (763/897); 16 persons were excluded due to missing data on physical function. Finally, 747 persons were analyzed in this study  who were registered in the Residential Registry of Ogatsu and Oshika districts and who participated in the previous survey in the Wakabayashi Ward were recruited , which is a self-reported questionnaire consisting of five yes/no questions. New-onset poor physical function was defined as poor physical function that was absent at 3 years but present at 4 years after the disaster. The questions were as follows: “Can you climb stairs without holding onto a handrail or wall?,” “Can you get up from a chair without grabbing something?,” “Are you able to walk for about 15 minutes?,” “Have you fallen in the past year?,” and “Are you very worried about falling?” . Each neMusculoskeletal pain at 4 years after the disaster was evaluated using self-reported questionnaires based on the Comprehensive Survey of Living Conditions . The queThe following variables were considered as covariates according to a previous report : sex, agn = 456], or ≥ 75 [n = 291] years), and ORs and 95% CIs for new-onset poor physical function were assessed in the same manner. SPSS version 24.0  was used for all analyses and differences at p < 0.05 were considered statistically significant.Variables are presented as frequencies and percentages (%). Crude and multiple logistic regression analyses were performed to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) for new-onset poor physical function according to musculoskeletal pain at 3 years after the disaster. Variables used in the analysis were sex, age (< 75 or ≥ 75 years), body mass index , living areas , smoking habits , drinking habits , chronic conditions , working status , and walking time per day  (Model 1). Furthermore, variables related to disasters, such as living environment , subjective economic hardship , psychological distress , sleep disturbance , and social isolation , were added (Model 2). The ORs and 95% CIs for new-onset poor physical function according to each musculoskeletal pain region were also evaluated. Moreover, we divided the participants into two subgroups according to age  for new-onset poor physical function were 2.63 1.04–6.63) for “1” pain region and 2.74 (1.16–6.48) for “≥ 2” pain regions in the age < 75 group (p for trend = 0.031) and were 1.06 (0.40–2.81) for “1” pain region and 2.99 (1.28–6.96) for “≥ 2” pain regions in the age ≥ 75 group (p for trend = 0.029) . Additionally, adjusted for living status, subjective economic hardship, psychological distress, sleep disturbance, and social isolation (Model 2).OR Odds Ratio, CI Confidence Interval.Adjusted for sex, age, body mass index, living area, smoking habits, drinking habits, chronic conditions, working status, walking time, living status, subjective economic hardship, psychological distress, sleep disturbance, and social isolation.OR odds ratio, CI confidence interval.Adjusted for sex, body mass index, living area, smoking habits, drinking habits, chronic conditions, working status, walking time, living status, subjective economic hardship, psychological distress, sleep disturbance, and social isolation.OR odds ratio, CI confidence interval.This study showed that musculoskeletal pain is associated with new-onset poor physical function among elderly survivors in the recovery period of the GEJE. There have been some reports of functional disabilities after natural disasters , 10, 14.The prevalence of new-onset poor physical function among survivors aged ≥75 years was approximately twice the rate of that among survivors aged < 75 years. Functional decline was more common in older survivors, which is in accordance with the former report after the GEJE . In the This study has several limitations. First, the questionnaires and informed consent forms were mailed and the response rate was not high. The people who responded might have been in better health than those who did not respond, which could affect the results. Second, musculoskeletal pain and physical function were assessed in only two periods and changes in other periods were unknown. Third, musculoskeletal pain was assessed using self-reported questionnaires based on the Comprehensive Survey of Living Conditions. Although this survey is widely accepted in Japan, the reliability and validity of this method were not evaluated in this study. Furthermore, the questionnaires included five pain sites but did not include other musculoskeletal pains such as hip or elbow pain. Because these pains could have also led to physical function decline, this might have affected the results. In addition, the degree of pain was not assessed. Finally, this study did not include a control group, because the disaster struck a vast area of Japan.Musculoskeletal pain is associated with new-onset poor physical function among elderly survivors in the recovery period after the GEJE. Monitoring musculoskeletal pain is important to prevent physical function decline after natural disasters.


N = 175), loneliness predicted preferences for larger interpersonal distance within intimate space net gender, objective social isolation, anxiety, depressive symptomatology, and marital status. In Study 2 (N = 405), we replicated these results, and mediation analyses indicated that measures of social closeness could not adequately explain our findings. These studies provide compelling evidence that loneliness predicts preferences for larger interpersonal distance within intimate space, consistent with predictions from the evolutionary model of loneliness.Loneliness is thought to serve as an adaptive signal indicating the need to repair or replace salutary social connections. Accordingly, loneliness may influence preferences for interpersonal distance. If loneliness simply motivates a desire to socially reconnect, then loneliness may be associated with a preference for smaller interpersonal distances. According to the evolutionary model of loneliness, however, loneliness also signals an inadequacy of mutual aid and protection, augmenting self-preservation motives. If loneliness both increases the motivation to reconnect and increases the motivation for self-protection, then the resulting approach-avoidance conflict should produce a preference for larger interpersonal distance, at least within intimate  space. Here, we report two survey-based studies of participants’ preferences for interpersonal distance to distinguish between these competing hypotheses. In Study 1 ( Loneliness, defined as a discrepancy between one’s desired and achieved levels of social connectedness , has beeThe extant research on interpersonal distance, originally derived from Hall’s theory of proxemics, suggests that various factors can influence people’s preferences. For instance, preferences for interpersonal distance are strongly influenced both by feelings of social closeness , with prSome gender differences in interpersonal distance have also been identified. For instance, females have been found to prefer smaller interpersonal distances than males , but HesIn the evolutionary model of loneliness, Cacioppo and colleagues –20 depicHowever, Cacioppo and colleagues’ evolutionary model additionally holds that loneliness is associated with a set of motivational, behavioral and cognitive adjustments related to short-term self-preservation ,19. AmonIf loneliness simply motivates a desire to socially reconnect, then it should be associated with a motivation to approach, producing a preference for smaller interpersonal distance ,35. HoweTo distinguish between our two competing hypotheses, we measured participants’ preferences for interpersonal distance within three regions of personal space that correspond to the three facets of loneliness: (1) intimate space–the personal space in which an individual is comfortable interacting with intimate others such as partners; (2) relational space–the personal space in which an individual is comfortable interacting with relational others such as friends; and (3) collective space–the personal space in which an individual is comfortable interacting with others who share a social identity . We haveMage = 44.0 years, age range: 19–83 years), due to the small numbers of respondents from any given foreign country and previously detailed cultural differences in preferences for interpersonal distance  circle were to be sitting or standing next to you, how close would that individual have to get to make you feel uncomfortable?” The response scale was ordinal, with response options of, “No distance would make me feel uncomfortable,” “1–9 inches would begin to feel uncomfortable,” “10–25 inches would begin to feel uncomfortable,” “2.5 feet would begin to feel uncomfortable,” “5 feet would begin to feel uncomfortable,” “More than 5 feet would begin to feel uncomfortable,” “I have no one in my ______  circle,” and “Prefer not to answer” . ResponsTo validate that participants understood these personal spaces, we asked participants to select the relationship types of individuals with whom they preferred to interact in each space, as well as how many individuals they included in each. For the intimate and relational spaces, options included “Romantic Partner,” “Grand Parent(s),” “Mother,” “Father,” “Brother(s),” “Sister(s),” “Best Friend(s),” or “Other.” For the collective space, which is primarily related to collective identities and groups as opposed to individuals , options2 = 6.46, p = .011). Table B in The relationship types specified for each personal space suggested that the participants understood the distinctions among the personal spaces when expressing their preferences for interpersonal distance. For instance, “Best Friend(s)” (61.5%) and “Romantic Partner” (59.6%) were among the most cited relationship types included in intimate space. “Best Friend(s)” (71.8%) and various family members, including “Brother(s)” (29.5%), “Mother” (25.0%), “Father” (25.0%), and “Sister(s)” (24.4%), were the most commonly cited types for relational space. Finally, “Professional Association(s)” (57.7%) and “Club(s)” (38.5%) were the most commonly cited group types for collective space. Across personal spaces, the only relationship type that differed between lonelier and less lonely participants (median split) was “Romantic Partner” within the intimate space. 51.4% of lonelier individuals included this relationship type, compared to 70.9% of less lonely individuals (χα = .88), reverse coding where necessary so that higher scores corresponded to greater loneliness .Loneliness was assessed using a 9-item version of the revised UCLA Loneliness Scale . An examMarital/cohabitation status was quantified by coding a participant as married/cohabiting if the participant was legally married, in a civil union, or cohabiting. A participant was coded as non-married/not cohabiting if the participant was single, divorced, separated, or widowed. By this criterion 52.6% of participants were considered married/cohabiting. Marriage and female gender predict smaller interpersonal distances  circle on average?” Responses were made using a sliding-bar type question in Qualtrics, with ticks from “Least Close” (0) to “Closest” (10). “Strangers” was omitted as a target for these ratings due to potential confusion about what was meant by feelings of closeness toward this group. We also gauged the participants’ preference for social closeness with members of each personal space. This measure was implemented for each personal space by asking participants, “Considering your level of closeness to members of your _____  circle, would you prefer to have:” Responses were made on a 5-point scale, from “Much less closeness” (-2) to “Much more closeness” (2). This item was also omitted for strangers.We also implemented the IOS scale to pictorially measure participants’ feelings of self-other overlap. This scale was implemented by asking participants to “Please select the picture below that best describes your relationship with members of your _____  circle on average:” Response options included a series of seven standard pairs of circles which overlap to greater or lesser degrees. This question was omitted for strangers.To assess feelings of behavioral closeness with others, we measured the participants’ frequency of contact with members of each personal space by asking, “How often do you have contact  with members of your ______  circle on average?” Responses were made on a Likert-type scale from “Very Rarely” (1) to “Very Often” (5). We also asked participants about their preferences for more or less contact with members of their personal spaces: “Considering your amount of contact with your ______  circle, would you prefer to have:” Responses were made on a Likert-type scale from “Much less contact” (-2) to “Much more contact” (2). These items were omitted for strangers.To address our first aim, we used the final model identified by stepwise selection in Study 1, and we applied the proportional odds mixed model to determine the association between loneliness and preferences for interpersonal distance. Notably, to assure that the use of an ordinal measure of interpersonal distance preference did not somehow bias our results, we also included a sliding scale, continuous measure of interpersonal distance in Study 2. With this continuous measure, we obtained results that were consistent with those obtained using our primary ordinal measure in both studies 1 and 2  using the same stepwise model selection procedure as implemented in Study 1. This allowed us to separately test the proportional odds assumption for each measure, and to test for interactions with personal space. Only measures that met the criterion of statistical significance were included in the final model for Study 2 and served as potential mediators in subsequent analyses. As noted above, social closeness was not measured in relation to strangers to avoid confusion about what was meant by social closeness. Consequently, for mediation analyses, the collective personal space served as the reference category, rather than strangers. A full description of the model selection steps and relevant statistics are provided in Table F in NDE) and the natural indirect effect [NIE, or ACME, “represents the causal effect of the treatment on the outcome that can be attributed to the treatment-induced change in the mediator” when the treatment variable itself is held constant [Mediation was investigated using a non-parametric simulation-based method for proportional odds models ,70, witht effect . The NIEconstant . This apconstant ,73,74 anconstant . Importaconstant . For furM = 1.42, SD = .77), relational space , collective space , and stranger . Importantly, we found that lonelier participants again preferred significantly larger interpersonal distances within intimate space , whereas loneliness was not associated with interpersonal distance preferences within relational  or collective space . The gender effect noted in Study 1 also replicated, with males preferring significantly larger interpersonal distances than females across social dimensions . As in Study 1, the model was significant compared to an intercept-only model (χ2 (8) = 1329.10, p < .001; McFadden R2 = .31; adjusted McFadden R2 = .31), with McFadden’s R2 and Count R2 both indicating an excellent fit . Coefficient estimates, standard errors, and odds ratios for all predictors in the model are displayed in We began by testing the consistency and replicability of the optimal model identified in Study 1 here in our larger Study 2 sample. Consistent with Study 1, preferences for interpersonal distance increased markedly from proximal to distal personal space dimensions: intimate space , but no association was noted within relational space . Notably, the small reduction in effect size and corresponding change in p-level for the former effect may reflect the use of collective space rather than strangers as the reference category for this analysis. Despite the association between loneliness and interpersonal distance preference within intimate space being marginally significant in the presence of putative mediators, the overall loneliness*personal space interaction remained significant (Likelihood-ratio drop-test: χ2 (2) = 9.21, p = .01).Stepwise model selection produced an optimal model consisting of the following predictors: (1) personal space dimension, (2) loneliness, (3) a personal space*loneliness interaction, (4) gender, (5) social closeness, (6) social closeness preference, (7) a personal space*social closeness preference interaction, (8) frequency of contact preference, and (9) self-other overlap. Because social closeness was not measured in regards to strangers , collective space served as the reference category for the personal space dimension variable in this regression model. Largely consistent with the Study 1 model, lonelier participants were marginally more likely to prefer larger interpersonal distances within intimate space . The model as a whole was significant compared to an intercept-only model (χ2 (16) = 821.44, p < .001; McFadden R2 = .27; adjusted McFadden R2 = .26), with McFadden’s R2 and Count R2 both indicating an excellent fit . Regression results are shown in In contrast to previous analyses, loneliness exhibited a significant main effect in this model, predicting preferences for larger interpersonal distance across personal space dimensions (NIE-Q) across levels of interpersonal distance preference and gender. The NIE-Q was not statistically significant for any measure of social closeness: (a) social closeness preference , (b) frequency of contact preference , (c) social closeness , or (d) the IOS  , (b) closeness preference , (c) frequency of contact preference , or (d) the IOS . The right column of Next, we formally tested whether any measure of social closeness significantly mediated the association between loneliness and preference for interpersonal distance within intimate space. We separately examined each measure of social closeness as a putative primary mediator, utilizing an analysis strategy that allows a primary mediator to also act via indirect effects transferred through secondary mediators, in this case, other social closeness measures  see Sec. We perfp = .11) . AdditioCross-validation of the model developed in Study 1 confirmed the association between loneliness and a preference for larger interpersonal distance within intimate space. Although measures of social closeness did significantly predict interpersonal distance preferences, no measure significantly mediated the association between loneliness and the preference for larger interpersonal distance within intimate space. Analyses showed that the natural direct effect of loneliness on interpersonal distance preference within intimate space  called the immediate body-buffer zone. Horowitz and colleagues (1964) found that this body-buffer zone was smaller with nonthreatening objects than with persons, and that compared to healthy controls, this immediate body-buffer zone was larger for schizophrenia patients, whom the authors characterized as “notorious for interpersonal withdrawal and avoidance” . NotablyOur results are also notable in light of recent neuroimaging studies investigating both loneliness and the regulation of interpersonal distance. Our recent resting-state fMRI study identified a putative neural mechanism for tonic hypervigilance for social threats in loneliness. Specifically, we found that lonelier participants exhibited elevated functional connectivity within the cingulo-opercular network, which is known from prior literature to be involved in the maintenance of tonic alertness . Future The current results were based on participants’ rated responses to vignettes, rather than behavioral responses to interpersonal space violations. Measures of interpersonal distance such as the Comfortable Interpersonal Distance scale , which iIt should also be noted that the present results are correlational, and further studies will be needed to establish the causal direction of the association between loneliness and interpersonal distance preference. The present results, in conjunction with robust evidence of hypervigilance for social threats in loneliness and the known proximity gradients of approach-avoidance conflicts, suggest that loneliness may lead to a preference for maintaining a larger distance from intimate others. However, it is also possible that distancing oneself from intimate others, whether emotionally or physically, could lead to increased loneliness. Tests of causation utilizing longitudinal cross-lagged panel analyses or strong experimental manipulations of loneliness are thus warranted to evaluate these alternatives. We hope that the present study lays the groundwork for such potential future investigations.In sum, across human history, not only have humans survived and prospered by banding together to provide companionship, mutual protection and assistance, but a chief threat to a person’s reproductive success and survival has come from other humans. The same objective social relationship  can be perceived as caring and protective or as exploitive and threatening, based on a host of factors including an individual’s prior experiences with, attributed intentions toward, and inferred goals of others. According to Cacioppo and colleagues’ evolutionary model, the brain is the key organ for forming, monitoring, maintaining, repairing, and replacing salutary connections with others, and the perception of being socially isolated, even when around others, triggers the aversive state of loneliness, which is part of the biological warning machinery that alerts us to threats to our social body –20. AmonS1 FileFigure A. Odds ratios and associated 95% Wald confidence intervals (reported as “OR (5th percentile– 95th percentile)” for each predictor in the Study 2 replication of the final model obtained from step-wise selection in Study 1. Negative odds ratios indicate preferences for smaller interpersonal distances, whereas positive odds ratios indicate preferences for larger interpersonal distances. Strangers served as the reference category for the social dimension variable. +: p < .10, *: p < .05, **: p < .01, and ***: p < .001, respectively. Figure B. Probability of intimate interpersonal distance within each category  as a function of standardized UCLA loneliness score (x-axis), with effects averaged across genders. Probabilities and confidence intervals represent predictions derived from a proportional odds mixed model utilizing meta-analytically combined coefficient estimates across studies 1 and 2. Probabilities on the dotted line at x = 0 represent the baseline probabilities for no effect of loneliness. Figure C. Odds ratios and associated 95% confidence intervals (reported as “OR (5th percentile– 95th percentile)” for each predictor in the final model obtained from step-wise selection with putative mediators in Study 2, extended to the group of individuals specified by participants as members of their intimate, relational, and collective social dimensions. “Closeness 1|2,” “Closeness 2|3,” and “Closeness 3|4” represent the nominal effects of closeness on each respective cumulative probability of the ordinal outcome Click here for additional data file.S1 Survey(PDF)Click here for additional data file.S2 Survey(PDF)Click here for additional data file.


The methodology is based on the measurement of electric potential variation resulting from chemical reactions between wine polyphenols and a free radical mediator M• as source of oxidants. Total antioxidant activity as estimated by the PAOT-Liquid® activity was 6.8 fold higher in red wines (n = 14) when compared to rosé (n = 3) and white (n = 3) wines bought in a commercial market. Moreover, PAOT-Liquid® activity was highly correlated with total polyphenols content (TPC) of all wines  and the classical DPPH  assay which is often used for evaluating antioxidant capacity of food matrices .Polyphenol compounds present in high quantity in wines are well-known to have potent cardio-protective properties through several biological mechanisms including antioxidant activity. A large number of methods have been developed for evaluating the antioxidant capacity of food matrices. Most of them have, however, the disadvantage of being time consuming and require specific analytical protocols and devices. In the present study, we present the electrochemical PAOT -Liquid A large number of studies have evidenced that oxidative stress plays a key role in the development of several pathologies including cardiovascular, neurological and inflammatory diseases, cancer and diabetes . Jones h® technology which is able to measure the total antioxidant capacity of wine, and indirectly their total polyphenol content (TPC), thanks to a fast electrochemical application. Repartition of polyphenols in natural foods is as follows: fruits (41%), fresh vegetables (11%), dry vegetables 8%) and processed products such as fruit juices, cocoa, coffee, green tea, olive oil but also red wine (33%). Over the past decade, the health effects of moderate red wine consumption (125 mL glass) by reducing risk of developing cancer and cardiovascular diseases have been the matter of many studies (for a review see references % and pro). HoweveAntioxidants gallic acid (GA), catechin (C), epicatechin (EC), epigallocatechin gallate (EGCG), epigallocatechin (EGC), gallocatechin (GC), myricetin, quercetin, kaempherol, naringin, hesperdin methyl calcone, cyanidin chloride, delphinidin chloride, pelargordin chloride, free radical 2,2-diphenyl-1-picryhydrazyl (DPPH) and Trolox (T) were all purchased from Sigma, Nancy and Lyon, France. Folin’s reagent, methanol and sodium carbonate have been supplied by WWR International, Fontenay-sous-Bois, France. Wines including 14 red, 3 rosé and 3 white produced in five different countries have been bought in a commercial market in Belgium.w/v) was added. The mixture was heated at 100 °C for 1 min. After cooling, the absorbance at 750 nm was measured. Using gallic acid (GA) as a standard, results were expressed as mg gallic acid equivalents/par liter (GAE) L−1.Total polyphenols content was determined by the Folin–Ciocalteu method . Appropr−1.Antioxidant capacity of wines was determined by the DPPH  assay as initially described by Tadolini et al. . All com® Technology is a method allowing total antioxidant capacity determination in various matrices, such as raw materials and processed food products, cosmetic and medicinal preparations, biological fluids or plant extracts [® Technology is actually the subject of a patent application filing . Thanks to the robust and easily transportable device shown on •). Two microelectrodes, one being the working electrode and the second one the reference electrode, were then immersed in the medium. After addition of 20 μL of pure antioxidants  or wine samples, PAOT-liquid® activity was estimated by registering electrochemical potential modifications in the reaction medium (due to changes in the concentration of oxidized/reduced forms of the mediator M• during reaction with antioxidants as AOX (oxidized mediator M• + AOX -→ reduced mediator M + oxidized AOX) [•. Results were calculated according to the following formula:EPcontrol0 was the electrochemical potential at time 0 and EPproduct10 the electrochemical potential obtained after 10 min registration in presence of tested antioxidants or wine samples. Gallic acid was used as a standard and results were expressed as mg gallic acid equivalents (GAE) L−1.PAOT  Liquidextracts . The PAOzed AOX) . Figure ® activity of main polyphenols, more particularly those of the flavonoid family, which can be found in wines. Tested at a concentration of 1 mM, myricetin belonging to the flavonol family exhibited the highest PAOT-Liquid® activity (677.78 mg (GAE) L−1) when compared to quercetin (560.4 mg (GAE) L−1) and kaempferol (404.56 mg (GAE) L−1). In the anthocyanins family, cyanidin had the best score (512.54 mg (GAE) L−1) in front of delphinidin and pelargordinin. Both EC (730.2 mg (GAE) L−1) and EGCG (613.11 mg (GAE) L−1) from the favano-3-ol subgroup were among all tested molecules those having the highest antioxidant capacity. For comparison, Trolox which is the antioxidant reference used in most in vitro assays, had only a value of 544.16 mg (GAE) L−1. At least, both naringin (53.28 mg (GAE) L−1) and hesperidin methyl calcone (51.85 mg (GAE) L−1) from the flavanone group presented a score which was largely below those of all other tested flavonoids.−1) was clearly found in red wines when compared to rosé  L−1) and white  L−1) wines. As suggested daily allowance in total polyphenols is around 1000 mg [−1 (wine 3). A total of 5/14 red wines had a TPC higher than 2000 mg (GAE) L−1 . Three of them  were multi-varietal while the two other ones were mono-varietal . By contrast, 9/14 wines  had values between 1278 and 2000 mg (GAE) L−1. Six of them  were mono- or bi-varietal and three multi-varietal . Statistical analysis revealed, however, that there was not significant difference between the mean value in TPC of mono or bi and multi varietal wines (1733 ± 125.6 mg (GAE) L−1, n = 8 vs. 1864 ± 164.5 mg (GAE) L−1, n = 6; p = 0.57).As shown in  1000 mg , the conp < 0.0001) between TPC and PAOT-Liquid® activity. The deep shift between red wines and rosé and white ones was confirmed. Among red wines, two different groups were identified as for TPC: wines 1, 3, 4, 10, 11, 13, 14 vs. wines 2, 5, 6, 7, 8, 9, 12. As shown on ® activity and DPPH assay  or TPC and DPPH assay .® Technology can be classified in the SET category since this electrochemical assay directly estimates the antioxidant capacity via the electric potential shift due to changes in the concentration of oxidized/reduced forms of the free radical mediator (M•) during reaction with antioxidants. Moreover, the use of microelectrodes for registering current changes from reaction between the oxidant mediator M• and antioxidants rendered the method very sensitive.A large number of methods have been developed to determine the in vitro antioxidant capacity of food matrices. They include two major groups: assays based on single electron transfer reaction (SET), in which the redox reaction between the antioxidant and the oxidant is measured by the change in the oxidant’s color, as an indicator of the end of the reaction; and assays based on hydrogen atom transfer reaction (HAT), in which there is a competitive reaction between the antioxidant and the substrate (probe) for the free radicals. SET methods are Trolox Equivalent Antioxidant Capacity (TEAC) assay, Ferric Reducing Ability (FRAP) assay, Copper Reduction (CUPRAC) assay, and, finally, 2,2-diphenyl-1-picrylhydrazyl radical scavenging capacity (DPPH) assay which is the most popular. HAT assays include the crocin bleaching assay, the total peroxyl radical trapping antioxidant parameter (TRAP) assay, and overall, the Oxygen Radical Absorbance Capacity (ORAC) assay. Advantages and disadvantages of all these methods have been discussed in detail in a previous paper of us . The PAO® Technology was perfectly able to evaluate the antioxidant capacity of molecules present in wines such as polyphenols from the flavonoids family. The relationship between PAOT-Liquid® activity and the structure of these compounds can be even evidenced. The basal chemical structure for all flavonoids is constituted of a benzene A ring linked to an oxidized heterocyclic C ring substituted in position 2 by another benzene B ring. In the flavanone family, two phenolic (–OH) groups are present on ring A in positions 5 and 7, one on the ring C in position 4 while ring B is respectively substituted by 1, 2 and 3 –OH groups respectively in case of kaempferol (position 4′), quercetin (positions 3′ and 4′) and myricetin . ® activity logically increased with the number of antioxidant –OH groups on ring B, myricetin having so the highest value in front of quercetin and kaempferol.As shown in n = 9), EGCG has, as expected, one of the highest PAOT-Liquid® activity. It is instructive to note that both isomers of catechin and epicatechin have a higher antioxidant activity than the original form.In the flavanol-3-ol family, benzene A rings possess two –OH groups on positions 5 and 7 while one –OH group is present on the heterocycle C ring on position 3. Ring B is substituted with 2 –OH groups in case of catechin and its isomer epicatechin (EC) on positions 4′ and 5′. Gallocatechin (GC) and epigallocatechin (EGC) have another –OH group on position 3′. When compared to GC, the chemical structure of epigallocatechingallate (EGCG) has the –OH group on the heterocyclic C ring substituted by a gallate group constituted of a benzene ring having 3 –OH groups. Due its large number of –OH groups , 2 (positions 3′ and 4′) and 3  –OH groups. According to its number of antioxidant –OH groups, pelagornidin has the lowest PAOT-LiquidMolecules from the flavanone family are characterized by the presence of one –OH group on ring A (position 5) and another one on ring C (position 4′). In the case of naringin and hesperidin methyl calcone, the –OH group on ring B (position 7) is substituted by a rutinose moiety, resulting in an important loss in the antioxidant capacity.−1 against only 265 ± 65 for rosé and 221 ± 28 for white wines. These results are in agreement with literature data [n = 5) or below (n = 9) 2000 mg (GAE) L−1. However, we did not observe significant difference in TPC between red wines constituted of mono-, bi- or multi-varietals as also reported by Paixao et al. [ure data ,19. Amon® activity and TPC of wines were highly correlated . Other authors using electrochemical detection with laccase biosensor [® activity provided such strong evidence that the majority of the antioxidant activity was attributed to the polyphenolic compounds in such beverages. In a recent study [A shown in iosensor , poly when compared to more expensive tests performed in specialized laboratory analysis. Of interest is to note that the PAOT-Liquid® Technology can also be used for determining antioxidant capacity of other types of non-alcoholic beverages, such as orange juices or plant extracts, as already described by us [Due to the strong correlation between antioxidant activity determined by the PAOT-Liquided by us .


This study explored the influence of healthy vending contracts (HVC) on the nutritional quality of vending machine products in 46 Canadian publicly funded recreation and sport facilities. A quasi-experimental comparison design was used to examine the difference in nutritional quality of snack and beverage vending machine products at baseline (December 2015–May 2016) and 18-month follow-up. Staff Surveys assessed facility contract type  and vending machine audits identified product nutritional quality. Products were categorized by provincial guidelines as Do Not Sell (DNS), Sell Sometimes (SS) or Sell Most (SM). ANOVA compared categories cross-sectionally  and repeated measures ANOVA compared them longitudinally .p = 0.001; snack: 55% vs 85%, p < 0.001), higher SS  and higher SM Products . Longitudinally, facilities with consistent HVC or that changed to HVC showed greater decreases in DNS products over time (p < 0.050).Approximately one quarter of contracts (24% beverage and 28% snack) had health stipulations at baseline or follow-up. Cross-sectionally, facilities with HVC at any time period had significantly lower percentage DNS (beverage: 56% vs 73%, Although less healthy products were still highly prevalent, facilities with HVC or that changed to HVC had fewer unhealthy products available in their vending machines over time compared to those without HVCs. Healthy vending contracts appear to be an effective change strategy. •Healthy vending contracts are associated with healthier vending product profiles.•Healthy vending contracts improved the ‘healthiness’ of the products sold in vending machines.•Healthy vending contracts appear to improve the food environment of recreational and sport facilities.•Unhealthy foods remain prevalent in recreational and sport facilities even when healthy vending contracts are in place. This isIn Canada, unhealthy food environments are commonplace in public facilities , includiFood and beverage policy has strong potential to improve unhealthy food environments . In addiIncorporating health stipulations into vending machine contracts  may be a viable facility-level policy option for several reasons. First, contracts are a direct and legal means through which modifications to vending machine products may be promoted . The fooExpanding the evidence-base on healthy food procurement policies in Canada  and prom22.1A non-equivalent quasi-experimental comparison design was used to address the research objectives. The study was conducted using data from the broader Eat, Play, Live (EPL) trial: a natural experiment with an embedded randomized comparison trial examining the impact of provincial nutrition guidelines and capacity-building on food environments in publicly funded recreation and sport facilities . Data us2.2Ethical approval for this research was provided by the Research Ethics Boards at the University of Victoria and University of British Columbia (Harmonized # BC 15-196), the University of Alberta (#Pro00058096), the University of Waterloo (#20913) and Dalhousie University (#2015-3637).2.3Forty-nine publicly funded recreation and sport facilities across four Canadian provinces; British Columbia (n = 14), Alberta (n = 11), Ontario (n = 17), and Nova Scotia (n = 7) participated in the EPL trial. As previously outlined , they we2.4Surveys to assess contract status (condition) were administered and standardized vending product nutrition quality audits  were con2.4.1Staff representatives completed questionnaires administered by the research team via e-mail or telephone when e-mail response was slow. Questions asked if a vending contract existed, what type of product they targeted  and if they had a health stipulation . Other health stipulations included specifying the proportion of products that must be ‘healthy’ or ‘unhealthy’ and whether someone was assigned to monitor adherence to the healthfulness of vending products. Survey responses were used to classify contracts; if they included health stipulations they were classified as healthy (HVC) and if they did not they were conventional.2.4.2We employed a four-step standardized vending machine audit procedure with previously established inter-rater reliability (test-retest and inter-rater reliability ≥0.88) . Step 1.www.healthlinkbc.ca). The final counts for each category were converted into percentages to account for variability in the number of slots between vending machines.Although provincial guideline nutrient profiling systems differ across jurisdictions, they offer moderate to good agreement on product nutritional quality and similar policy outcomes . The Bri2.5Statistical Package for the Social Sciences (SPSS Version 22.0 [IBM Inc]) was used for all analysis.2.5.1Vending data from facilities with a HVC at either T1 or T2 were compared with data from the remaining facilities with a conventional contract using a one-way ANOVA. A facility's data was only used once in the analysis and HVC data taken from the period first reported. Data was classified as missing if staff representatives were unsure of contract health stipulations at T1 and T2.2.5.2Longitudinal analyses examined changes in availability of healthier vending products over time and whether this differed by condition. There were four comparison conditions including: 1) facilities that reported a conventional contract or no contract at both T1 and T2, 2) facilities that reported a HVC at both T1 and T2, 3) facilities that reported a conventional contract or no contract at T1 and a HVC at T2, and 4) facilities that reported unknown at T1 and a HVC at T2. The number of facilities in each condition for beverage and snack vending machines is reported in Six Repeated Measures Mixed ANOVAs were conducted to assess whether there were time and time by condition effects for percentage of DNS, SS or SM products across both beverage and snack vending machines. Assumptions of independence of observations and normalcy were met. To account for the assumption of sphericity, the Greenhouse-Geisser condition was used. Multiple post-hoc comparisons were performed using a Bonferroni correction to explore the significant effect of contract type.33.1The final sample size was 62 beverage and 43 snack vending contracts within the 46 participating facilities. Approximately a quarter of facilities had HVCs. 3.2Fifteen contracts were reported as ‘up for renewal’ during the 18-month EPL trial at T1. As displayed in 3.2.1F  = 17.169, p < 0.001, partial eta2 = 0.290 and a significant interaction between time and contract type, F  = 4.491, p = 0.008, partial eta2 = 0.243. For the SS beverage condition, there was a significant main effect for time, F  = 4.192, p = 0.047, partial eta2 = 0.091 but no significant interaction between time and contract type, F  = 1.801, p = 0.162, partial eta2 = 0.114. For the SM beverage condition, a significant main effect for time, F  = 20.430, p < 0.001, partial eta2 = 0.327 and a significant interaction between time and contract type, F  = 7.358, p < 0.001, partial eta2 = 0.345. The differences in the percentage of DNS and SM beverages between T1 and T2 were not consistent across all categories of contract change.For the DNS beverage condition, there was a significant main effect for time, The post-hoc testing see  showed t3.2.2F  = 32.117, p < 0.001, partial eta2 = 0.493 and a significant interaction between time and contract type, F  = 6.185, p = 0.002, partial eta2 = 0.360. Similarly, for the SS snack condition, a significant main effect for time, F  = 20.539, p < 0.001, partial eta2 = 0.384 and a significant interaction between time and contract type, F  = 3.717, p = 0.021, partial eta2 = 0.253 was found and for the SM snack condition, also a significant main effect for time, F  = 22.224, p < 0.001, partial eta2 = 0.402 and a significant interaction between time and contract type, F  = 5.940, p = 0.002, partial eta2 = 0.351. This indicates that there was a difference in the percentage of all product categories between T1 and T2; like beverages however, this difference was not consistent across all categories of contract change.For the DNS snack condition, there was a significant main effect for time, The post-hoc testing see  showed s4Current public health goals to promote healthy eating among children necessitate improving the food environments in the settings where children spend their time . This inVending machine contracts with health stipulations (HVCs) may be an effective policy tool  to improWe used both a cross-sectional and longitudinal analysis to explore whether nutritional quality of products differed in facilities with HVCs or that changed over to HVC between T1 and T2. Cross-sectional findings showed a greater availability of healthier vending machine products in facilities with a HVC at either time period. The longitudinal analysis supported the cross-sectional results and illuminated a plausible causal pathway. Vending product quality increased positively over time in facilities that had a consistent HVC (at T1 and T2) or introduced a HVC between T1 and T2 compared to those facilities with conventional contracts. We discuss our findings in the context of the literature and strengths and limitations of the research following.4.1Although the majority of facilities in this study reported having a vending contract, only a small number of the contracts met the HVC criteria and only a few facilities added health stipulations to their contracts over the 18-month EPL intervention period. This is not surprising considering that some of the facilities were EPL comparison sites that were asked not to make changes and evidence indicates that changing contracts may take longer than the study time frame depending on contract renewal dates .Cross-sectional analyses showed that facilities with HVCs had better availability of healthy beverage and snack vending products. Further, longitudinal findings showed that facilities that had a consistent HVC or changed to a HVC had significant improvements in the nutritional quality of vending products over time compared to those that did not. Our findings reinforce the positive association between HVCs and availability of healthier products found in other settings , as wellThe most substantial improvements in the nutritional quality of vending machine products between T1 and T2 were the reduced availability of the least healthy (DNS) snack and beverage products. This corresponds with research in the health services setting linking a HVC with greater reductions in availability of unhealthy products , and sug4.2An inevitable limitation of HVCs as a form of policy is their temporary nature which does not ensure sustainability and could be especially problematic without sufficient time to actualize positive change. This was one of the issues cited following discontinuation of Denmark's enforced tax paid on saturated fat content in food after 1 year which negated time for “incremental health effects to accumulate and become practically significant” . It may Nevertheless, the impermanence of vending contracts also allows for renewals which have previously been used to improve the health of food and beverages in public settings  includin4.3Caution should be used when interpreting the findings of this study based on the limitations of its real world non-equivalent quasi-experimental comparison design. These designs do not control for a number of threats to validity including history, maturation or selection bias and interaction among these. It is also likely that only those facilities interested in changing their food environment participated which introduces issues of sampling bias. However, it should be noted that even among facilities that volunteered, having a HVC or changing to a HVC was not frequent. Also mentionable is that this analysis only addresses the outcomes of a HVC, and not factors that influenced adoption and implementation. A related limitation is the small number of facilities with HVCs, which increased the likelihood that a true difference may have been missed . FurtherStrengths of this study include the ‘real world context’ in which it was implemented, it's use of both cross-sectional and longitudinal analysis to explore the influence of HVCs, as well as the use of data from multiple provinces which supports the generalizability of our findings across jurisdictions.5Our findings add to a growing literature base and establish a causal pathway between HVCs and the availability of healthier food and beverage vending products specifically in recreation and sport facilities, which may over time influence social norms. This research supports the importance of facility-level policy in the form of HVCs to achieving guideline implementation in Canadian and other jurisdictions. A substantive finding was the relatively short-time frame to achieve change in facilities that either maintained a HVC or changed to a HVC; a facility-level action. These are notable findings considering the limited resources and barriers governments face in the food and beverage policy field .Unfortunately, it is also important to note how far off the ‘ideal’ facilities remained. Vending audits indicated no facilities met the BC provincial guidelines  of 50% SSFLK, RH, LCM, DLO, KR, PJN designed the overall Eat, Play, Live study, obtained funding and oversaw ongoing implementation; RP, SC and DT collected and entered all of the data; CL and PJN formulated the research questions and designed the sub-study; CL, DT and TM analysed the data; CL drafted the manuscript; and all authors revised the manuscript.


Natural (N) and artificial (A) domains are the most obvious and traditional distinctions in categorization. The distinct event-related potential (ERP) responses for N and A domains have not yet been examined during category-based inferences. In this study, the differences between ERP inference parameters within N and A domains were measured during inductive decision processing, while controlling the premise−conclusion similarity and premise typicality between those two domains. Twenty-two adults were asked to make a decision on whether a conclusion was definitely weak, possibly weak, possibly strong, or definitely strong, based on a premise. The behavioral results showed that semantic inferences within the N domain shared similar inductive strength, similar “correct” response rates, and similar reaction times with that within the A domain. However, the ERP results showed that semantic inferences elicited smaller frontal-distributed N400 (FN400) amplitudes within the N domain than within the A domain, which suggested that knowledge of the ontological domain of a category affects category-based inferences, and underlaid the increased categorical coherence and homogeneity in the N as compared to the A categories. Therefore, we have distinguished the cognitive course of semantic inferences between N and A domains.Category-based inferences allow inductions about novel properties based on categorical memberships ( People can use their categorical knowledge to generalize novel properties from categorical examples, termed category-based inferences. For example, hearing that “All trout [premise category] have novel property X [premise property]”, one may infer that “all fish [conclusion category] would have novel property X [conclusion property]”, because trout belongs to the fish category. This type of inference has various names in the literature, including category-based induction, categorical induction, property induction, feature induction, and induction projection3.Categories are essential for human conceptual organization. A central function of categorization is making predictionse.g., animal), and the categories in the A domain include produced or manufactured objects 5. Researchers suggest that the N and A domains are distinct in the nature of their ontology11. The categories in the N domain are generally tightly structured, coherent, and share many similarities . In contrast, the categories in the A domain are typically more loosely structured, less homogeneous, and share fewer important features .One of the most obvious and traditional distinctions in categorization is between the natural (N) and artificial (A) domains. The categories in the N domain include naturally occurring objects 12.However, few studies have directly compared the differences between N and A domains during category-based inferences14, while few studies have matched the typicality of premise categories between the N and A domains when comparing inferences within these two kinds of categories. Moreover, several theories have suggested that category-based inferences are driven by similarities between premises and conclusions, termed similarity-based models of category-based inferences18. According to these models, if the degree of similarity between the premise and conclusion under the N and A domain are similar, then the inference decision in both domains would be similar. This hypothesis is supported by Badger and Shapiro4. They found that children’s inferences did not vary by domains while controlling for perceptual similarity across those two domains. However, Badger and Shapiro4 did not test whether or not adults have similar pattern to children in their study.However, most previous studies have not matched categories between the N and A domain during inferring. For example, some studies have found that the degree of typicality of premise categories affected inferences19. Although previous studies have measured the ERP responses to semantic category-based inferences24, inferences within the N and the A domains were not directly compared. In the present study, the semantic categories of both the N and A domains were considered. Participants were asked to decide whether a conclusion was definitely weak, possible weak, possible strong, or definitely strong, based on a premise.The present study therefore aimed to compare adults’ inferences within the N and A domains after matching the degree of premise-conclusion similarity and the degree of premise typicality between them, by using event-related potentials (ERPs). ERPs can uncover cognitive processes in the brain with high temporal sensitivity19. More specifically, we predicted that the semantic categories from the N domain would elicit smaller FN400 amplitudes than those from the A domain when making inferences. FN400 is a negative deflection at 200–600 ms, with frontal scalp distribution. Previous ERP studies found that the amplitudes of FN400 were influenced by various factors during sematic category-based inferences25. The attenuated FN400 amplitudes were associated with elevated conceptual priming28. Inferences within the N domain would therefore elicit smaller N400 amplitudes than those within the A domain because of the enhanced conceptual priming produced by increased categorical coherence and homogeneity in the N compared to the A domain.Behavioral and ERP responses to the conclusions were recorded and analyzed. As the similarity-based models suggested, we predicted that no significant behavior response differences would be found because the degree of premise typicality and premise-conclusion similarity between the two domains were matched in the present study. However, we predicted that the differences on ERP results would appear, as the ERP measurements are more sensitive to processing differences than behavioral dataThis study was approved by the ethics review board at the Faculty of Psychology, Southwest University, Chongqing, China. Written informed consent was obtained from all participants. The methods were carried out in accordance with the relevant guidelines and regulations.SD]: 1.45; 14 women) were recruited for the ERP study. All participants were right-handed, had normal or corrected-to-normal eyesight, and had no neurological disorders. Prior to the formal ERP experiment, 35 undergraduates  evaluated the degree of experimental items’ familiarity, 35 undergraduates  evaluated the degree of experimental items’ typicality, and another 24 undergraduates  evaluated the degree of similarity between each item and its superordinate category. The evaluators did not participate in the ERP study.Twenty-two paid undergraduates  as blank properties, to reduce the influence of background knowledge15. Similar to previous studies20, a category and a property were presented simultaneously, linked by a blank space to indicate that the category had this novel property .Two types of premise category domains were used: the N and the A domains. The novel properties were presented by a capital letter and an Arabic number . For incongruent conclusions, the conclusion categories excluded the premise categories . The premises and conclusions shared the same properties in each trial. Therefore, there were four sub-conditions: congruent conclusions with a natural premise category (N+), congruent conclusions with an artificial premise category (A+), incongruent conclusions with a natural premise category (N−), and incongruent conclusions with an artificial premise category (A−). Similar to previous studies20, both the conclusion categories and conclusion properties were presented simultaneously, with a question mark (?) to ask participants to judge the inference strength of the conclusions, based on a 4-point Likert scale.Two types of conclusion conditions were also involved: congruent (+) and incongruent (−) conclusions. For congruent conclusions, the conclusion categories included the premise categories  and four A  categories, and these eight superordinate categories were used as the conclusion categories, and were presented in Chinese characters. Therefore, there were 48 trials for each sub-condition, resulting in a total of 192 trials in the formal experiment. An additional 20 trials  were used for training and did not appear in the formal experiment.31. To match the repetition times, for premise categories, every 12 basic level categories came from one superordinate level category. As a result, the N category items involved 12 kinds of vegetables, 12 kinds of birds, 12 kinds of fruits, and 12 kinds of mammals; the A category items involved 12 kinds of tools, 12 kinds of clothing, 12 kinds of furniture, and 12 kinds of appliances. Each premise category appeared twice. For conclusion categories, each superordinate category  appeared 24 times: 12 times for congruent condition, and 12 times for incongruent condition. Moreover, we checked the characters’ frequencies  in the formal experiment against the Corpus Word list (www.cncorpus.org), and found no significant differences between those two domains .Previous studies have shown that the repetitions and frequencies of words affected N400 amplitudesSD = 0.38], range: 3.10−4.95; A: 4.08 [SD = 0.51], range: 3.55 – 4.84; F  = 1.38, p = 0.25). The degree of typicality of the premise categories was evaluated on a 6-point Likert scale . For example, participants were instructed to “please judge the degree to which you think that apples are typical of fruit on a 5-point Likert scale; 1 represents least typical, and 5 represents most typical”. The typicality for the two types of stimuli were not statistically significantly different .Before the ERP experiment, the familiarity and typicality of stimuli were evaluated. Participants were required to determine the degree to which they were familiar with the premise category words based on a 5-point Likert scale . For example, participants were instructed to “please judge the degree to which you are familiar with the word ‘apple’ on a 5-point Likert scale; 1 represents least familiar, and 5 represents most familiar”. The familiarity differences between N and A stimuli were not significant  as well as under incongruent conclusions .Moreover, the degree of global similarity between each item and its superordinate category was evaluated on a 7-point Likert scale . For example, participants were instructed to “please judge the degree to which you think that apples are globally similar to fruit on a 7-point scale; 1 represents least similar, and 7 represents most similar”. The global similarities of the two types of stimuli were also not statistically significantly different between items and their superordinate categories, under congruent conclusions . After the premise, the conclusions  were presented. Participants were asked to infer the inductive strength of the conclusion based on the premise, by pressing four different number keys representing definitely weak, possibly weak, possibly strong, and definitely strong responses, as accurately and quickly as possible. The experimental trials were divided into four blocks, and were presented randomly. Participants were allowed to rest for 60 s after completing each block. Moreover, to counterbalance key pressing across participants, 11 participants were instructed that 1 was “definitely weak”, 2 was “possibly weak”, 3 was “possibly strong”, and 4 was “definitely strong”, while the other 11 participants were instructed that 1 was “definitely strong”, 2 was “possibly strong”, 3 was “possibly weak”, and 4 was “definitely weak”.Figure 32 and ERPLAB toolboxes33. EEG data were filtered using IIR-Butterworth filters with half-power cutoffs at 0.1 and 30 Hz (roll-off = 12 dB/oct)19. Independent component analysis (ICA) was subsequently performed to correct components associated with eye movements and eye-blinks. Then, the ICA-corrected EEG data were re-referenced to the average of the left and right mastoids19.An electroencephalogram (EEG) was recorded from 64 electrode sites across the scalp using a Neuroscan cap  with Ag/AgCl electrodes while participants responded to the conclusions. The electrodes were positioned according to the International 10–20 system. A ground electrode was placed at the middle of FPz and Fz. The recording was referenced to an electrode between Cz and CPz. A vertical electrooculogram (EOG) was recorded supra- and infra-orbitally at the left eye; and the horizontal EOG was recorded from the left versus the right orbital rim. The EEG and EOG were amplified using a SynAmps2 amplifier (Neuroscan) and digitized in a 500-Hz sample size. The EEG and EOG were amplified with a band-pass filter from 0.05 to 200 Hz in AC mode. All interelectrode impedances were maintained below 5 kΩ. Off-line analyses were performed in MATLAB  using the EEGLAB19, with a window-width of 200 ms, a window step of 100 ms, and a threshold of 65 μV. This resulted in 36.82 trials (SD: 5.03) for N+, 38.27 trials (SD: 5.17) for N−, 37.45 trials (SD: 4.65) for A+, and 37.68 trials (SD: 5.75) for A− conditions. There was no significant difference among the number of trials under four conditions.The epochs were segmented time-locked to the conclusions. The “definitely strong” and “possibly strong” responses to congruent conclusions, and the “definitely weak” responses and “possibly weak” responses to incongruent conclusions were identified as “correct” responses. Only “correct” responses were overlapped and averaged. Each epoch was 1200 ms, including a 200-ms pre-stimulus baseline correction. Trials were excluded as noise by using peak-to-peak amplitude sliding window methodBehavioral and ERP responses to the conclusions were analyzed. Two-factor repeated-measures analyses of variances (ANOVAs) were used to analyze the response strength, “correct” response rates, and reaction times of “correct” responses. The factors were domains (N or A) and congruencies (+ or −). For the response strength, the “definitely weak” response was defined as a score of 1, the “possibly weak” response was defined as a score of 2, the “possibly strong” response was defined as a score of 3, and the “definitely strong” response was defined as a score of 4.34 and visual observation, the F3, F1, Fz, F2, F4, FC3, FC1, FCz, FC2, FC4, C3, C1, Cz, C2, and C4 electrode sites at the fronto-central region were selected, and the mean amplitudes of FN400 were measured in a 250–450-ms time-window after conclusion onset. To illustrate relatively precise temporal courses, data analysis was executed for each 50 ms. Moreover, to increase the statistical strength, and to reduce false effects35, these electrodes were collapsed by averaging. The 2-factor repeated-measures ANOVAs were used to analyze the mean amplitudes of FN400. The factors were domains (N or A) and congruencies (+ or −). For all analyses, the p-values of F tests were corrected for deviations using the Greenhouse–Geisser method, and post-hoc multiple comparisons were performed by the Bonferroni procedure. For the analysis of the mean amplitudes of FN400 at 250–450-ms, the p-values were corrected using the false discovery rate for multiple comparisons .Figure F  = 3.19, p = 0.09, η2p = 0.13) suggests that N arguments had similar response scores to A arguments. A significant main effect of congruencies  suggests that the response scores under congruent conclusions were greater than those under incongruent conclusions. The interaction of domains and congruencies did not reach significance .Figure F  < 1, p = 0.85, η2p < 0.01; RT: F  < 1, p = 0.88, η2p < 0.01) and congruencies  were not significant. The interactions between domains and congruencies also did not reach significance . Altogether, inferences within the N and A domain categories had similar response strengths , “correct” response rates , and reaction times for correct responses .For both “correct” response rates and reaction times of “correct” responses, the main effects of domains 58.However, the ERP parameter differences between inferences for N and A categories did not provide strong evidence for the conceptual representation hypotheses. Whether semantic memory representations of N and A categories are supported by single or multiple cortical systems is debatedet al.63 suggested that ERP parameter differences between N and A categories may not reflect modality specificity, but variability or homogeneity in those two categories, as suggested by the present study. However, other studies have suggested that N400 differences between N and A categories support modality-specific hypotheses48. By this logic, the significant FN400 amplitude differences between N and A categories in our study provide further evidence for modality-specific hypotheses of conceptual representations. Therefore, a limitation of our study is that it did not provide strong evidence for either amodal or modality-specific conceptual representation hypotheses. More research is needed on this issue.Ković The present study contributed to the elucidation of the complex differential processes underlying semantic inferences within N and A domains. The behavioral results showed that semantic inferences within N and A domains shared similar inference strength “correct” response rates, and reaction times after matching the degree of premise–conclusion similarity and the degree of premise typicality between the two domains. However, the ERP results showed that differences existed during semantic inferences within the N and A domain. The N domain elicited smaller FN400 amplitudes than the A domain, suggesting a role for increased categorical coherence and homogeneity in the N domain, as compared to the A domain, during semantic inferences.


Background and objectives: Maximal heart rate (HRmax) is an important training and testing tool, especially in the context of evaluating intensity in exercise prescription; however, few studies have examined the validity of prediction equations of HRmax in physically active female adolescents and the role of maturation level. Therefore, the aim of the present study was to examine the differences between measured and predicted HRmax in a sample of physically active female adolescents. Materials and Methods: Seventy-one selected volleyball players  performed a 20 m shuttle run endurance test, and the actual HRmax was compared with Tanaka HRmax (‘208 − 0.7 × age’) and Fox HRmax (‘220 − age’). Results: A large main effect of assessment method on HRmax was found  with Fox overestimating actual HRmax by 6.8 bpm  and Tanaka underestimating actual HRmax by −2.6 bpm . The more matured participants had similar actual HRmax , difference Fox − actual HRmax , and difference Tanaka − actual HRmax  to the less matured participants. Conclusions: These findings suggest that age-based prediction equations of HRmax developed in adult populations should be applied with caution in physically active female adolescents, and Tanaka should be preferred instead of the Fox equation. An accumax) . Thus, tmax might be measured directly through a graded exercise test (GXT) till exhaustion, whereas indirectly it might be calculated using an age-based equation [max; ‘220 − age’) [max; ‘208 − 0.7 × age’) [HRequation . Occasio − age’)  and Tana × age’)  —might b × age’)  and adolmax has enhanced our understanding of the practical applications of these equations, the role of maturation as a covariate has not been considered adequately so far by the existing literature, where two relevant studies were found [Although the existing research on the validity of age-based predicted HRre found ,10. Howere found , whereasre found , it woulFor the purpose of the study, a sample of convenience consisting of 71 selected female adolescent volleyball players was retrospectively analyzed. Participants were members of volleyball clubs from Attiki, i.e., the wider geographical area of Athens, and were selected by the national teams’ coaches to be considered as members of national teams. Inclusion criteria were the absence of any known pain or injury that would prevent participants from exercise testing. Parents or guardians of participants provided informed consent prior to exercise testing. The study was approved by the local institutional review board . All procedures adhered to the 2013 revision of the Declaration of Helsinki.max was recorded as the peak HR during SRT. SRT started at 8.5 km/h, and speed increased by 0.5 km/h every minute till exhaustion [max was predicted using Fox HRmax (‘220 − age’) [Exercise testing was performed in two sessions separated by a week. Anthropometric characteristics were recorded in the first session in an exercise physiology laboratory, and a 20 m shuttle run test (SRT)  was donehaustion . During  − age’)  and Tanap = 0.05. Data were tested for normality using the Kolmogorov-Smirnov test and visual inspection of Q-Q plots and were expressed as mean and standard deviations of the mean (SD). A one-way repeated measures analysis of variance (ANOVA) examined differences between actual, Fox and Tanaka HRmax. Despite potential limitations , this statistical approach was used previously by studies on differences between actual and age-based predicted equations [ŋ2 ≤ 0.06), medium (0.06 < ŋ2 ≤ 0.14) and large (ŋ2 > 0.14) [max were examined using Bland–Altman analysis. The relationship of actual HRmax and age was tested by Pearson’s product–moment correlation coefficient (r). The magnitude of r was interpreted as very small (r < 0.1), small (0.1 ≤ r < 0.3), moderate (0.3 ≤ r < 0.5), large (0.5 ≤ r < 0.7), very large (0.7 ≤ r < 0.9), nearly perfect (0.9 ≤ r < 1) and perfect (r = 1) [t-test examined differences between less  and more matured participants . The classification of participants into these two groups relied on the split technique, which—without neglecting its drawbacks—has been a common practice in clinical research [t-test was evaluated using Cohen’s d, which was considered as trivial (d ≤ 0.2), small (0.2 < d ≤ 0.6), moderate (0.6 < d ≤ 1.2), large (1.2 < d ≤ 2.0) or very large (d > 2.0) [max) by maturation level  and IBM SPSS v. 23.0 . Significance was set at quations ,15 and w > 0.14) . The acc (r = 1) . A t-tesresearch . The magd > 2.0) . Complimon level , regresson level  and mixeon level . p < 0.05), whereas no difference in body mass index (BMI) and SRT between the two maturation groups was observed. The actual and predicted HRmax can be seen in max was shown between the maturation groups (p > 0.05). The more matured participants had similar actual HRmax , difference Fox − actual HRmax  and difference Tanaka − actual HRmax  to the less matured participants. No relationship was observed of actual HRmax with chronological age or ΔAPHV , with Fox overestimating by 6.8 bpm  and Tanaka underestimating actual HRmax by −2.6 bpm   . The Bla1, −0.1)  show thamax in physically active female adolescents. The main findings were that (a) Fox’s ‘220 − age’ overestimated actual HRmax by ~7 bpm, (b) Tanaka’s ‘208 − 0.7 × age’ underestimated actual HRmax by ~3 bpm, (c) a large amount of individual variation was observed in both prediction equations, and (d) no variation of these findings was observed by maturation. Tanaka underestimated HRmax less than Fox overestimated, and the notion that the former provided a better estimate of actual HRmax than Fox was in agreement with the existing literature in adolescents [max was related to several factors, such as HR at rest  [max) [The present study examined the application of two popular age-based prediction equations of HRlescents , and thie HRmax)  and bodyx) [max) .max with chronological or biological age was not surprising and should be attributed to the small range (<3 years) of chronological age of participants (11.7–14.6 years). Previous studies [max and chronological age, covered a chronological range of many decades. Furthermore, growth-related differences in HR might be linked to maturation of sympathetic-parasympathetic neural regulation and the role of circulating modulators [max than their younger counterparts due to their larger accumulated training experience. This assumption relied on the suggestion that aerobic training would result in chronic adaptations, such as plasma volume expansion and alteration of the electrophysiology of the sinoatrial node [max by 6 bpm, and detraining and tapering increased HRmax by 6 bpm, whereas athletes had lower HRmax than sedentary individuals by 8 bpm [max by age might also be attributed to the nature of volleyball training practiced by participants, which should not be considered aerobic training.The lack of correlation of actual HR 11.7–14. years. P studies ,20, whicdulators ,22. In aial node . A meta-by 8 bpm . The lacmax, considering that an age-related decline in HRmax was more striking after puberty with a rate of ~0.7 bpm per year [With regards to the role of maturation, no difference in the validity of age-based prediction equations was observed between the two maturation groups. The research hypothesis was that the more matured group would have lower actual HRper year . Prepubeper year . The lacmax was elicited during a field GXT. Thus, caution would be needed to generalize the findings in a laboratory setting. It was acknowledged that laboratory criteria of achieving maximal performance  [max than a laboratory GXT on treadmill ergometer, likely due to the more natural running patterns observed in the former than in the latter case [max in physically active adolescents. Considering the importance of exercise intensity when prescribing exercise programs [max, its use should be contraindicated when there is high exercise intensity and, consequently, increased risk of overtraining, whereas Tanaka should be avoided in prescribing low exercise intensity, since an underestimation of actual HRmax would result in a training program of inadequate exercise intensity to induce the desired physiological adaptations. Another limitation of the findings of the present study was the sample size, which was relatively small due to the specific characteristics of participants . Future studies should not only use larger sample size, but also recruit participants with a larger range of maturity status, e.g., from pre-pubescence to post-pubescence.A limitation of this study was that actual HRlactate)  were notter case . A strenprograms , the finmax developed in adult populations should be applied with caution in physically active female adolescents. In the context of testing and training, practitioners would be advised to choose an age-based prediction equation considering the risks of overestimation and underestimation of actual HRmax. Tanaka equation provided more accurate values than Fox equation.Based on these findings, it is suggested that age-based prediction equations of HR


Extracellular matrix (ECM) molecules are responsible for structural and biochemical support, as well as for regulation of molecular signalling and tissue repair in many organ structures, including the pancreas. In pancreatic islets, collagen type IV and VI, and laminins are the most abundant molecules, but other ECM molecules are also present. The ECM interacts with specific combinations of integrin α/β heterodimers on islet cells and guides many cellular processes. More specifically, some ECM molecules are involved in beta cell survival, function and insulin production, while others can fine tune the susceptibility of islet cells to cytokines. Further, some ECM induce release of growth factors to facilitate tissue repair. During enzymatic isolation of islets for transplantation, the ECM is damaged, impacting islet function. However, restoration of the ECM in human islets (for example by adding ECM to the interior of immunoprotective capsules) has been shown to enhance islet function. Here, we provide current insight into the role of ECM molecules in islet function and discuss the clinical potential of ECM manipulation to enhance pancreatic islet function and survival.The online version of this article (10.1007/s00125-017-4524-8) contains a slideset of the figures for download, which is available to authorised users. Type 1 diabetes is an autoimmune disorder leading to the destruction of insulin-producing beta cells. Current clinically available methods of insulin replacement cannot prevent the occurrence of frequent hypoglycaemia and diabetic complications , 3 and tIslets are conventionally transplanted by infusion into the liver via the portal vein. This procedure is clinically effective in type 1 diabetes  but isleRecently, the importance of the extracellular matrix (ECM) in islet transplantation has been recognised , 15, 16,Here, we provide a summary of the types of ECM molecules that are normally expressed in the islet, followed by a discussion of the current knowledge on the contribution made by ECM to the function of islets and other organs. This knowledge will facilitate the future design of islet ECM complexes applicable for islet transplantation. We conclude by discussing the current experimental proof of principle of improving islet function by supplementation with specific ECM components in immuno-isolating islet grafts.ECM molecules play an important role in guiding proliferation, differentiation and migration of cells, starting as early as embryogenesis , 33. TheCollagens are the most abundant protein in organisms and are usually divided into fibrillar and nonfibrillar structures , 43. OveCollagens VI and IV are located at the islet–exocrine interface and islet basement membrane and regulate fibronectin assembly by restraining cell–fibronectin interactions –48. CollCombinations of collagens and polymeric biomaterials or other ECM molecules have been incorporated into transplanted grafts to create matrices with desired mechanical properties . For exa4β1, α5β1 and α9β1 integrins and with Ig superfamily cell-surface counter receptors, such as vascular cell adhesion molecule 1 (VCAM-1) [Fibronectin, a multifunctional component of ECM, facilitates cell attachment and cellular spreading by direct interaction with cells , 54. The(VCAM-1) . One sug(VCAM-1) . However(VCAM-1) , 59.Pdx1 and Pax6 [5β1 integrin and increase matrix production and cell viability in isolated islets [Fibronectin regulates several processes in islets via interaction with islet integrin and non-integrin receptors. It improves islet and beta cell function and, through transcriptional upregulation of the anti-apoptotic protein B cell lymphoma 2 (Bcl-2), has been demonstrated to enhance islet survival , 16, 60.and Pax6 . Further6 integrins in the developing pancreas and promote islet function in vitro [1, β1 and γ1 chains) is the primary isoform present in the developing mouse pancreas [5, β1, and γ1 isoform [4, β1 and γ1 chains) and -laminin-511 have been found to be essential for beta cell proliferation and insulin transcription [Laminins are heterotrimeric glycoproteins composed of α, β and γ polypeptide chains joined by disulfide bonds . The spein vitro . Lamininpancreas , 65. How isoform . In humacription .1 chains [1 chain [In terms of distribution, laminin-332 has been found to be present near the glucagon producing alpha cell , whilst 1 chains –73. Othe[1 chain , 70, 71.[1 chain . Further[1 chain . They al[1 chain .Glycosaminoglycans (GAGs) are linear sugar chains consisting of repeating units of disaccharides, hexosamine  and uronic acid . Except GAGs, particularly HSPGs, may also be involved in islet amyloid formation and cellular dysfunction . For exavβ1, which is known to be important for the function of transplanted islets [vβ3 integrin expression, which prevents beta cell apoptosis [Fibrin, a complex matrix formed by polymerisation of fibrinogen, plays an important role in homeostasis and tissue repair . Althougd islets . In vitrd islets , 80, 81.poptosis . Thus, fpoptosis , 87.4 and α5 were found to be essential for normal beta cell adhesion, proliferation and insulin secretion [As mentioned, combinations of ECM molecules play an important role in cell proliferation, differentiation and migration , 33 and,ecretion . On the ecretion .IIbβ3 and αvβ3 integrin in the β subunit N-terminus [As mentioned above, ECM molecules convert their signal into a biological response via ligation to cellular receptors, such as integrins  and non-terminus , 93, 94.terminus . Ligatioterminus , 95. Indterminus , 16, 95.The potency of manipulating ECM to achieve beneficial effects on pancreatic islet function is demonstrated by the stimulation of interactions between integrins and the ECM that modulate the expression of fibroblast growth factor receptor-1 (FGFR1) in beta cells, a receptor that regulates pathways involved in beta cell survival and function . HoweverSome believe that changes in ECM composition and ECM interaction with cells act as a morphogenetic language that is precisely interpreted by cells . The senIn addition to adding ECM molecules, modulation or improvement of cellular function can be achieved by adding ECM-modulating MMPs, which carry out multiple functions, such as lysis of susceptible intracellular proteins in subcellular compartments . A multi3, α5, αv, α6, β1, β3 and β5 integrin components have been reported in adult pancreatic islets [3, α5, α6 and β1 integrin in fetal pancreatic tissue [3, αv, α6, β1 and β5 integrin subunits in endocrine pancreas cells [v, β1, β4, and β7, can crosstalk with growth factor receptors like EGF receptor (EGFR) [1 subunit is of special interest for cell transplantation and tissue engineering since it has been shown to be important in maintaining stem cell function in several organs, including islets [Since integrins connect ECM molecules with the cytoskeleton via adapters, such as talin , and inic islets , 117, α3c tissue , 119 andas cells . Figure as cells . Some inr (EGFR) . The β1 g islets , 123.Fig6β1 is involved in the transduction of a matrix signal that modulates beta cell function and enhances insulin secretion [3β1 integrin include fibronectin, laminin, collagen I and collagen IV, yet only collagens I and IV promote rat INS-1 cell viability and proliferation [vβ3 binds tenascin C, which is a glycoprotein linked to promotion of tumour progression [vβ1, αvβ5, and α1β1, suggesting that many of these integrins are localised in or on beta cells and that α1, αv and β1 integrins might be important for creating and maintaining islet architecture. These interactions between ECM and integrins can induce both intracellular and extracellular processes [Islet integrins can be stimulated via different ECM molecules Table . For exaecretion  and thatecretion . In otheferation . Additiogression  whilst, gression , 68. Furgression  found throcesses . Intracerocesses  and, hen1-dependent interactions [In addition to its direct interaction with cells, the ECM can serve as a reservoir for immune-active signalling molecules, such as cytokines and growth factors , 105, thractions .Proteoglycans are the major ECM component involved in immune signalling. Further, perlecan and agrin , 131, loOther matrix molecules, such as laminin-332, can mediate the synthesis of TGF-β1 and TNF-α . MoreoveThe efficacy of cytokines can also depend on ECM molecules as co-receptors, or on ECM receptors molecules, such as integrins . For exaHuman islets are currently isolated by application of enzyme mixtures, which contain collagenase, neutral protease, trypsin and clostripain . As mentA possible strategy for enhancing the functional survival of islets is to add specific ECM molecules before transplantation. Recent studies have demonstrated that collagen IV and laminin sequences, such as RGD, LRE and PDSGR, have positive effects on the function of isolated human islets , 16, 23.In an attempt to enhance the survival of encapsulated pancreatic islets in alginate-based microcapsules, we investigated the impact of single ECM molecules and combinations of ECM molecules. We used bioactive sequences of ECM molecules instead of full proteins as they can be produced synthetically and are associated with fewer variations than ECM components from biological origin. An interesting observation was that not all ECM components had beneficial effects and effects vary depending on the concentration of ECM components. For example, excessively high concentrations of collagen IV had detrimental effects on GSIS , 6; whilOverall, it is clear that the manipulation of ECM may promote successful islet transplantation. However, there are still many questions left to be answered with regard to the type of ECM molecules that are beneficial for islet graft survival. To facilitate a response to these questions, however, we must first elucidate the mechanisms by which these ECM molecules enhance the survival and function of pancreatic islets. Importantly, these finding may aid with the development of future treatments for type 1 diabetes that will help to improve the life expectancy and quality of patients with type 1 diabetes.ESM(PPTX 901 kb)


A dielectric anomaly induced by doping has been observed at about 340 K in chlorine-doped diisopropylammonium bromide. The dielectric anomaly has a switchable behaviour, which indicates potential applications on switches and sensors. Temperature-dependent Raman spectrum, X-ray diffraction and differential scanning calorimetry do not show any anomaly around the dielectric anomaly temperature, which prove that the dielectric anomaly does not come from structure phase transition and has no specific heat variety. It is assumed that this dielectric anomaly can be attributed to the freezing of ferroelectric domain walls induced by the pinning of point defects. Ferroelectrics usually feature a switchable spontaneous electric polarization and have good piezoelectric performance . Relaxor to 0.6% –12, ther to 0.6% . Researc3  [3 [3 [3  [2PbCl4 [Recently, a series of simple molecular ferroelectrics have been found, such as diisopropylammonium bromide (DIPAB) –18, diis= Cl,Br) ,26,  [3 , (cyclopr) [3 [3 ,  ,30,  and high Curie temperature, Tc , which possesses ferroelectric properties comparable to those of BaTiO3. Ferroelectric DIPAC and DIPAB have similar crystal structure (P21) and similar structure phase transition (P21 → P21/m). So, the two materials can form solid solution single crystal at any ratio. This is similar to that of relaxor-based ferroelectric single crystals which have large piezoelectric coefficients and large subsequent strain levels. We have studied the chlorine-doped DIPAB (DIPAB-C) single crystal in the earlier work [Diisopropylammonium chloride (DIPAC)  and DIPAier work . It is f2.6H16NBrx1−Clx, DIPAB-C) was grown by slow evaporation of methanol solution containing 1 mol diisopropylamine, x mol hydrochloric acid and (1 − x) mol hydrobromic acid (x = 0–1). The element contents were measured using a CHN elemental analyser (Heraeus CHN-O-Rapid). DSC measurements of single crystals were recorded by using a NETZSCH DSC 200F3 in the temperature range of 300–453 K. The complex permittivity was measured using a Tonghui TH2828A LCR meter. Variable temperature powder X-ray diffraction (PXRD) was performed on a Bruker D8 Advance X-ray diffractometer. Raman spectra were taken using a Horiba Jobin Yvon HR800 spectrometer system with a 488 nm laser line from an air-cooled Ar-ion laser.The single crystal of chlorine-doped DIPAB (C3.6H16NBr0.76Cl0.24 (DIPAB-C1) as an example to analyse in the following.Chlorine content in the single crystal of DIPAC was determined by the carbon mass fraction measured by a combustion method using a CHN elemental analyser . The act1, similar to that of pure DIPAB. But the structure of the as-grown crystal of DIPAB-C is P212121, which is non-ferroelectric. Room temperature ferroelectric DIPAB-C could be acquired by heating the samples above the first phase transition temperature at about 420 K due to the irreversible phase transition. The following measurements were all performed on the ferroelectric samples.The structure of ferroelectric DIPAB-C is P2−1. ɛ = ɛ′ − iɛ″, where ɛ″ is the imaginary part) at the frequency range from 500 Hz to 1000 KHz. The real part (ɛ′) of the complex dielectric is shown in figure 1a and the imaginary part (ɛ″) is shown in figure 1b. Two dielectric anomalies can be seen in c), which belongs to the ferroelectric–paraelectric phase transition. At 412 K, DIPAB-C1 undergoes a structure phase transition from P21 to P21/m. In the vicinity of Tc, the temperature-dependent dielectric constant along the polar axis follows the Curie–Weiss law of ferroelectric materials parametrized as ɛ′ = C/(T − T0), as shown by the linear relationship between reciprocal dielectric constant and temperature in electronic supplementary material, figure S2.The dielectric constant of DIPAB-C1 was measured in the heating cycle with the heating rate of 2 K min1), which is not found in the pure DIPAB and has not been reported in the previous literature. The dielectric anomaly has a switchable behaviour, which indicates potential applications on switches and sensors. Both the real part ɛ′ and the imaginary part ɛ″ of the complex dielectric display slow step-like dielectric anomaly. When heating across T1, the dielectric frequency dispersion has an abrupt increase, characterizing an abrupt increase of relaxation time phase transition. Furthermore, above T1, the frequency dispersion of ɛ′ and ɛ″ enhance with the increase of temperature, indicating the relaxation time decrease with the increasing temperature. Below T1, the frequency dispersion keeps almost constant, indicating the relaxation time is independent of temperature. Simply speaking, the relaxation time keeps constant below T1, increases abruptly at T1 and increases slowly above T1.It is interesting for us to find another slow step-like dielectric anomaly at about 340 K  and Bragg equation 2dsinθ = n * λ, we can calculate the variance of the plane space d along (100) direction against temperature. The calculated coefficient of thermal expansion α is 60 × 10−6 K−1, which is just half of that of polyvinylidene fluoride (PVDF). The large thermal expansion coefficient indicates DIPAB-C1 is as soft as polymer, illustrating DIPAB-C possesses potential electrostriction application [Temperature-dependent PXRD measurements of DIPAB-C1 samples were performed from 303 to 373 K to examine the structure change during the dielectric anomaly happening at Tperature  inset. Tlication .Figure a shows the Raman spectra measured from 303 to 373 K. The intensity of the Raman peaks in figure 4a do not appear to abruptly change. Some typical peaks' positions shifts according to that of 303 K are shown in figure 4b. There are no apparent abrupt shifts at about 340 K. The chosen Raman peak positions almost show a linear variation with temperature. The temperature-dependent Raman spectrum proves the lattice vibrations are not affected by the dielectric anomaly at T1. Raman spectrum results deepen the conclusion that the dielectric anomaly does not belong to a structure phase transition.In order to understand the mechanism and dynamics of the phase transitions, we performed Raman measurements as a function of temperature , which iFigure 41 is not structure phase transition. Then what is responsible for the dielectric anomaly? One reasonable explanation may be the freezing of ferroelectric domains at low temperature induced by the defects in DIPAB-C1. It has been reported that ferroelectric domains in some ferroelectric materials normally froze at low temperature [1, the relaxation time will be long so that it is difficult to establish relaxation polarization and only instantaneous polarization is in operation. This could easily explain why the dielectric constant hardly changes with temperature and have less frequency dispersion below T1. Once the ferroelectric domains unfreeze at high temperature, the relaxation time will decrease with the increase of temperature, which behaves as that the frequency dispersion increase with the temperature increasing.From DSC, PXRD and Raman measurements, we have reached a conclusion that the dielectric anomaly at Tperature ,36, whicx is low, the change ratio of the dielectric constant is small around T1. Electronic supplementary material, figures S3–S6 show the dielectric constant curves when x = 0.024, 0.062, 0.41 and 0.60. The dielectric constant increases at 500 Hz by 7.6%, 25%, 521%, 428% and 160% in the vicinity of T1 when x = 0.024, 0.062, 0.24, 0.41 and 0.60, respectively. Therefore, the dielectric anomaly is closely related with the doping content. At low doping level, the defects density will increase with the doping content increase. The increased doping level will make freezing process more clear. It is worth noting that defects exist in pure DIPAB single crystals unavoidably, so the freezing process of ferroelectric domains exists unavoidably. This may explain that it is hard for the spontaneous polarization in DIPAB to flip through eternal applied electric field at low temperature.In addition, when the doping chlorine content 4.A dielectric anomaly was found at 340 K in the chlorine-doped DIPAB, which does not appear in pure DIPAB. Relaxation modes are different near the dielectric anomaly temperature. Above the dielectric anomaly temperature, the dielectric frequency dispersion is larger, and below the dielectric anomaly temperature, the dielectric frequency dispersion is less. DSC, PXRD and Raman spectrum measurements show the dielectric anomaly does not come from structure phase transition and has no specific heat variety. The freezing of ferroelectric domains at low temperature may be responsible for the dielectric anomaly. The dielectric anomaly was induced by doping in DIPAB.