In recent years, automatic sleep staging methods have achieved competitive performance using electroencephalography (EEG) signals. However, the acquisition of EEG signals is cumbersome and inconvenient. Therefore, we propose a novel sleep staging approach using electrooculogram (EOG) signals, which are more convenient to acquire than the EEG. A two-scale convolutional neural network first extracts epoch-wise temporary-equivalent features from raw EOG signals. A recurrent neural network then captures the long-term sequential information. The proposed method was validated on 101 full-night sleep data from two open-access databases, the montreal archive of sleep studies and Sleep-EDF, achieving an overall accuracy of 81.2 and 76.3%, respectively. The results are comparable to those models trained with EEG signals. In addition, comparisons with six state-of-the-art methods further demonstrate the effectiveness of the proposed approach. Overall, this study provides a new avenue for sleep monitoring. Sleep-stage classification plays an essential role in sleep quality assessment and sleep disorder diagnosis. According to the american academy of sleep medicine (AASM), sleep stages can be categorized into five stages: wake, N1, N2, N3, and rapid-eye-movement (REM) . Sleep tNumerous machine learning-based methods for automatic sleep staging have been proposed. Most studies use EEG signals as the primary modality . CardiorIn contrast, the Cardiorespiratory and movement signals are convenient to acquire . HoweverConsidering the trade-off between feasibility and accuracy, we found that the EOG is a potential modality for sleep staging. First, EOG recordings can reflect eye activity, which is a crucial indicator for recognizing non-REM and REM stages. Second, EOG signals are typically contaminated with EEG signals. As shown in The contributions of this paper are as follows.(1)A novel sequential hierarchical neural network for sleep-stage classification using single-channel EOG signals is proposed to balance the complexity of data acquisition and accuracy of data analysis.(2)To achieve competitiveness in sleep staging classification, the characteristic and temporal information within successive sleep epochs of EOG signal are explored.(3)The proposed method is validated by comparing it with six existing state-of-the-art approaches.The main context of this study is as follows. Section “Materials and Methods” details the methodology. The experimental process is described in section “Experiments.” The results are presented in section “Results,” and section “Discussion” discusses the experimental results and model analysis. The last section summarizes this study.The overall workflow of the proposed approach is shown in The classification performance of the existing machine learning method primarily depends on feature engineering. However, extracting task-relevant features is challenging and complicated. In contrast, CNN-based approaches have powerful abilities of feature learning and have achieved high accuracy in many studies . InspireSeveral stage-switch criteria and temporal relations  exist inBiGRU and softmax represent Bi-GRU and softmax layer, respectively. F, h, and R denote features learned by feature learning, Bi-GRU, and the final predicted classification probabilities, respectively.where, Sleep datasets suffer from class imbalance problems (CIPs). Several studies have attempted to address CIPs by oversampling minority class samples . Such apAs shown in For evaluating the performance of the proposed model, 101 full-night sleep data from the montreal archive of sleep studies (MASS) database  and Slee−6, while the learning rate for the sequence learning parts was set to 10−4. In addition, we employed a heuristic gradient clipping approach to avoid the gradient explosion problem. We used a couple of improved techniques, including ℓ−2 regularization, dropout technique , which empirically indicated a higher accuracy. The weights of the pre-trained feature learning parts were fine-tuned with a learning rate of 10echnique , and focechnique , to imprechnique . The hypThe experiments were conducted under two protocols: the 5-class-task protocol and the 4-class-task protocol. In the first protocol, sleep stages were categorized into five classes, which was consistent with the staging criteria of AASM. In the second protocol, sleep stages were reformulated as stage Wake, Light, Deep, and REM, in which class Deep contains stage N1 and N2 defined in AASM. This criterion is practical for clinical applications as N1 is exceptionally scarce in sleep recordings. In both protocols, we used a leave-one-subject-out (LOSO) validation to evaluate the performance of the trained model. The overall accuracy (Acc.), F1-score (F1), Cohen’s kappa coefficient (κ), as well as precision, and recall are reported in this study.The overall performance of the proposed approach is presented in According to the confusion matrix in We compared the proposed model with six state-of-the-art sleep staging approaches as described below:Compared to the proposed method, method 1, method 2, method 3, and method 4 are based on handcrafted features, which highly depend on the expertise knowledge. These features are partly explainable. However, a suboptimal feature set may lead to information loss. Thus the performance of methods using handcrafted features often inferior to those using feature-learning-based methods. In contrast, method 5 uses an end-to-end CNN model to learn compact and discriminative features from raw EEG signals. The sequential information is derived from five consecutive epochs. However, the model does not take long-term sequential information into account. Method 6 shares a similar concept with the proposed method using CNN modules and LSTM to extract time-invariant features and sequential information, respectively. However, the proposed method uses residual blocks on both CNN branches to reserve the learning capacity for shallow parts of the network. In addition, we proposed a data augmentation method to address sleep CIPs.For fair comparisons, all the above models were trained using the MASS database on the same hardware platform. The hyperparameters were kept consistent with their original settings. LOSO validation was used for performance evaluation.To take a glimpse into how network components impact model performance, we conducted ablation studies. In particular, we analyzed and compared the performance of the proposed network in different settings: (1) dropping sequential learning parts; (2) without pre-training step; (3) replacing two-scale CNN with MobileNetV2  for reprThe results of ablation studies are summarized in In this study, we proposed a novel automatic sleep staging network using single-channel EOG. The basis of using single-channel EOG signals for sleep staging is that EOG signals are typically multi-source, which mainly consist of frontal and ocular EEG activity, as well as eye muscle EMG activity. Many studies have exploited automatic sleep staging methods using single-channel EEG, achieving state-of-the-art performance. EOG signals, which contain rich information from EEG, are promisingly ideal alternatives as the primary modality to train sleep staging models. Moreover, EOG signals are generally convenient to acquire due to the ease of electrode placement. Thus EOG-based sleep staging approaches can promisingly provide a solution for long-term and home-based sleep monitoring.To exploit the feasibility of using single-channel EOG to classify sleep stages. We develop a network to capture sleep patterns from raw EOG signals. The network consists of two parts, feature learning, and sequential learning parts. The weights of the network are optimized under a two-step training protocol. In the first step, the feature learning part is pre-trained to learn time-invariant features from raw EOG signals. In the second step, the sequential learning part of the network is trained to capture inner-epoch temporary information, and the weights of the feature learning part are fine-tuned. The experimental results on two publicly available databases indicate that the proposed methods can achieve comparable performance in comparison with methods using EEG. This indicates the feasibility of using single-channel EOG as the primary modality for sleep staging.According to the analysis of six state-of-the-art sleep staging methods, using the same method, models trained with EEG can invariably outperform models trained with EOG signals. The rationale is that EEG patterns provide the dominant information for interpreting EEG recordings both for human sleep technicians and intelligence algorithms. With single-channel EOG, the proposed network has achieved the best results with an accuracy of 81.2% among all the methods. Consequently, the accuracy obtained from EOG-trained models can match that obtained from EEG-trained models with only marginal accuracy inferiority (1.9%).The high accuracy is partly attributed to the topology of the networks, which is designed to match the characteristics of EOG signals, partly attributed to the two-step training protocol. To be specific, in the first step, the feature learning part of the network is pre-trained using class-balanced training sets, which are generated by our proposed data augmentation methods. The data augmentation method is inspired by the large-scale image recognition tasks in computer vision. Analog to images, morphological transformation on EOG signals can produce new samples with new patterns from origin signals, thus can improve the robustness of the trained models. The results of ablation studies suggest that all the components in the proposed network play essential roles in sleep staging. The performance of trained models drops when deprecating two-scale CNN, Bi-GRU, or two-step training protocols. Besides, we also tested several variants of the proposed network, including a network using MobileNetV2 to take the place of the proposed two-scale CNNs and a network using a transformer for sequential learning instead of proposed Bi-GRU cells. The results show that these variants can hardly further obtain performance gains but lead to performance degeneration.Although the proposed method has achieved promising performance using single-channel EOG, several improvements are required in future works:(1)In this study, all sleep recordings for model validation are from healthy subjects. Staging sleep recordings from patients with sleep disorders is considered to be more challenging. In future works, we plan to test the proposed methods on a larger population with different health conditions.(2)For long-term sleep monitoring, the convenience of signal acquisition is a crucial factor, highly influencing usability and acceptance. Besides PSG and EOG signals can also be acquired by eye masks , glasses(3)Sleep data from different cohorts generally suffer from data mismatch issues. Models trained using data from one database typically perform poorly on other databases. We plan to improve the generalization of the proposed method with several techniques such as transfer learning and meta-learning in our future work.https://massdb.herokuapp.com/en/ and https://www.ahajournals.org/doi/full/10.1161/01.cir.101.23.e215.Publicly available datasets were analyzed in this study. This data can be found here: CS, JF, CC, and WC: conceptualization and methodology. CS and JF: data curation. CC and WC: funding acquisition and supervision. CS: investigation and software. WC: project administration. CS and CC: writing-original draft. JF, CC, ML, and WC: writing-review and editing. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Tracts with median housing age values before 1975 with a poverty level of 20% or more were considered to be neighborhoods with a high risk of exposure to deteriorating lead-based paint. We estimated multilevel models to examine the relationship between neighborhood housing age/poverty level and each dependent variable . The odds of adverse birth outcomes were significantly higher for mothers living in high-poverty neighborhoods with median housing built before the lead-based paint ban. Increased awareness of—and improved methods of alleviating— ubiquitous lead-based paint exposure in Texas may be necessary interventions for positive developmental trajectories of children. Allocating federal funds for place-based interventions, including universal lead paint mitigation, in older, high-poverty neighborhoods may reduce the disproportionate risk of adverse birth outcomes. The purpose of this study was to determine whether housing age in combination with neighborhood poverty, as a proxy for fetal exposure to heavy metal lead, is associated with adverse birth outcomes. We linked population-level birth certificate data for Black, Hispanic, White and Other women, stratified by nativity, from 2009–2011 in Texas ( Negative birth outcomes in the United States of America are common and consequential. In 2018, 1 out of every 10 infants was born preterm (less than 37 weeks), and 1 in 12 exhibited low birth weights . In receResearchers have investigated a number of potential causes for negative birth outcomes. Maternal infection, hypertension, pre-eclampsia, maternal stress, and multiple pregnancies are significant predictors of preterm birth and low birth weight, though this list is non-exhaustive ,7. Of inInhalation of lead from leaded gasoline was the primary source of elevated blood lead levels in the past, but exposure via gasoline plummeted after the U.S. ban on leaded gasoline . CurrentAlthough there is an indistinct relationship between many environmental metals and adverse birth outcomes, that is not the case for the relationship between lead exposure and adverse birth outcomes ,19,20. TDespite the relationships between ubiquitous lead exposure and adverse birth outcomes, studies looking at lead exposure from house paint have become less common since the ban on lead-based paint in the mid-1970s . HoweverHypothesis 1 (H1).Living in an older, high-poverty neighborhood increases the odds of preterm birth, low birth weight, and small-for-gestational age compared to living in a newer and/or low poverty neighborhood in Texas.Hypothesis 2 (H2).High-poverty neighborhoods with median housing built before the lead-based paint ban will be concentrated in rural areas.Hypothesis 3 (H3).The urban/rural status of a census tract will significantly moderate the relationship between at-risk neighborhoods and the odds of preterm birth, low birth weight, and small-for-gestational age.Hypothesis 4 (H4).There will be racial/ethnic disparities, extenuated by nativity status, in the prevalence of preterm birth, low birth weight, and small-for-gestational age for Black and Hispanic women compared to White women.In this study, we use population-level data from Texas to document associations between living in pre-1975 housing and high-poverty neighborhoods and negative birth outcomes. Furthermore, we present geospatial information on these neighborhoods. Our study is the first to link negative birth outcomes in Texas using comprehensive birth certificate data linked to geographic census tract-level housing and poverty data, and to examine racial/ethnic groups by nativity.n = 1,128,679) [n = 1,040,642).We obtained restricted individual-level birth certificate data from natality files for all singleton births to non-Hispanic Black, Hispanic, non-Hispanic Other, and non-Hispanic White women from 2009–2011 in Texas 128,679) . To arri,679 . ToCensus tract-level median housing age data were obtained from the American Community Survey, 2007–2011, and census tract-level poverty data were obtained from the American Community Survey, 2006–2010 ,30. TracWe linked individual-level birth certificate data to census tract-level data and ERS Rural–Urban Continuum Codes based on residential geocodes, provided with the birth certificate data from the Department of State Health Services. These mothers lived in 99.0% of census tracts in Texas , with an average of 200 mothers per tract (range = 1–1873). Nearly 97% of the census tracts had at least 30 births, indicating substantial clustering by census tract.Our dependent variables were preterm birth, low birth weight, and small-for-gestational age. The three dependent variables were each binary coded into 0 and 1, with 1 indicating the presence of preterm birth, low birth weight, or small-for-gestational age. Preterm birth was defined as fewer than 37 weeks gestation, low birth weight was defined as <2500 g, and small-for-gestational age was defined as <10th percentile of birth weight-for-gestational age using published national reference guidelines . Other iThe median housing age at the tract level was first coded into a dichotomous variable, with 1 as a median age before 1975 and 0 as a median age of 1975 or after. Next, census tract poverty level, representing the percentage of census tract residents living below the federal poverty line, was divided using the American Community Survey cutoff score for census tracts designated as “poverty areas”  . Then, tUrban and rural status for neighborhood tracts was created from the ERS Rural–Urban Continuum Codes for counties across Texas. The county codes are available in three metropolitan groupings  and six non-metropolitan groupings , resulting in a nine-part county classification. Census tracts were matched with their corresponding counties and then the codes were dichotomized into metropolitan and non-metropolitan based on the two metropolitan and non-metropolitan groupings provided by ERS. Tracts coded as 1 were considered urban (comprised of the three metropolitan codes) and tracts coded as 0 were considered rural (comprised of the six non-metropolitan codes).00 = 0.04 to 0.05, p < 0.0001). Although the ICCs are low, high clustering and significant variance between neighborhoods implied that our decision to use multilevel modeling was appropriate. The confidence level was set at 95% (p < 0.05) to determine the statistical significance. We first examined the distribution of the variables and prevalence of the dependent variables  overall and by individual-level characteristics and neighborhood-level housing age with and without poverty level. Next, we examined preterm birth stratified by housing age/poverty level and race/ethnicity/nativity. Finally, we estimated three sets of hierarchical generalized linear models (HGLM) to examine the relationship between neighborhood housing age and each dependent variable. Multilevel models were built sequentially: (a) bivariate models, (b) a demographic model, (c) a full model, and (d) an interaction model. The HGLM was estimated using Laplace based on a binomial distribution and logit link function which allowed us to assess model fit by examining the change in the negative two log-likelihood (-2LL) between models and comparing AIC and BIC values [The pseudo intra-class correlations (ICC) were 1.1–1.5%, depending on the birth outcome, and the variances between neighborhoods were all significant . Stratified by nativity status, about 33% of births were to U.S.-born White mothers and about 10% were to U.S.-born Black mothers. There were very few births to immigrant Black or White women and 80% of births to “Other” race/ethnicity were immigrants (and likely to be mostly women of Asian descent given Texas demographics). About 58% of the births were to unmarried women, and about 40% were first births. About 52% of the women had a high school degree or less education, and approximately 22% were college graduates. About 15% of the births were missing father’s education, and about 46% of the fathers had a high school degree or less education. About 39% of the women started prenatal care after the first trimester  or had no prenatal care, 66% of them lived in neighborhoods classified as urban, about 32% of them lived in neighborhoods where the median age of housing was before 1975, about 39% of them lived in neighborhoods where the poverty level was 20% or higher, and about 20% of them lived in neighborhoods where the median age of housing was before 1975 and the poverty level was 20% or higher .Ten percent of births were classified as preterm birth, 7% were low birth weight, and 11% were small-for-gestational age. The prevalence of adverse birth outcomes was highest for 11-to-19-years-old mothers, Black U.S.-born mothers, unmarried mothers, parents who were less educated (or missing information on father’s education), mothers with delayed or no prenatal care, mothers living in rural neighborhoods, mothers living in neighborhoods with older housing, mothers living in neighborhoods with a poverty level of 20% or higher, and mothers living in at-risk neighborhoods (both older housing and a poverty level of 20% or higher). The prevalence of adverse birth outcomes was lowest among White immigrant mothers, married mothers, parents who were college graduates, mothers without delayed/no prenatal care, mothers living in urban neighborhoods, mothers living in neighborhoods with newer housing (1975 or newer), mothers living in neighborhoods with a poverty level less than 20%, and mothers living in neighborhoods with newer housing and/or a poverty level less than 20%. The lowest prevalence of adverse birth outcomes differed among age groups, with preterm birth and low birth weight being lowest for 20-to-34-years-old mothers, and small-for-gestational age being lowest for mothers aged 35 or higher. The prevalence of birth outcomes varied by parity status where preterm birth was most prevalent for mothers with five or more births, whereas low birth weight and small-for-gestational age were most prevalent for mothers with their first births.In support of the primary hypothesis, the odds of giving birth to a preterm, low-birth-weight, or small-for-gestational-age infant were all significantly higher for Texas mothers living in areas with greater concentrations of housing built before the ban on lead-based paint with high neighborhood poverty from 2009 to 2011. Individual-level sociodemographic characteristics explained much of the variation in the odds of experiencing negative birth outcomes, especially mothers’ race/ethnicity/nativity, but could not fully diminish the association between living in an at-risk neighborhood and inauspicious births.Many studies document the relationship between heavy metal lead and increased risk of adverse birth outcomes ,20,21,22The secondary hypothesis, that Texas rural areas would have more at-risk neighborhoods than urban neighborhoods, was not supported by the study results. Instead, across the state of Texas, high-poverty neighborhoods with median housing built before the ban on lead-based paint (at-risk neighborhoods) were concentrated in urban census tracts. This coincides with previous literature on other states. For example, one study in South Carolina found a higher prevalence of blood lead levels in urban areas and that older housing age is a major factor in increasing blood lead levels . In thisThe third hypothesis, that the urban/rural status of a census tract would moderate the relationship between at-risk neighborhoods and the odds of the adverse birth outcomes, was not supported. These study findings may indicate that older, high-poverty neighborhoods have higher risk regardless of urban/rural status, or perhaps that other structural patterns exist. The geospatial analysis of at-risk neighborhoods often matched maps of historically redlined neighborhoods in major Texas cities. Given that historical redlining is associated with higher rates of preterm birth in cities such as New York City , the potIn support of the final hypothesis, U.S.-born Black mothers had the highest risk for all of the adverse birth outcomes compared to U.S.-born White mothers, and U.S.-born Hispanic women also had higher risk compared to U.S.-born White mothers; these findings add support to a growing body of literature that highlights structural racism as a key determinant in birth outcomes . Racial Since a large portion  of the population resided in at-risk neighborhoods, the primary implication is support for place-based interventions that reduce poverty and inequalities in the built environment, particularly for high poverty neighborhoods with median housing age built before the ban on lead-based paint. First, further examination of environmental factors, including the presence of lead-based paint, lead-contaminated water, pollution, and other known correlates of adverse birth outcomes can identify the best points of intervention for the individual at-risk neighborhoods ,18,52. ORehabilitation efforts have been implemented across cities in the U.S.A. to decrease exposure to lead . For exaThe racial/ethnic/nativity disparities in adverse birth outcomes and the overlap of urban at-risk neighborhoods with historically redlined neighborhoods may indicate that funding for place-based interventions should especially be allocated to older, high-poverty communities of color. In Texas, addressing structural racism in low-income historically redlined neighborhoods may mean allocating funding to mitigate existing environmental injustices linked to adverse birth outcomes, including air pollution, and lead-contaminated water . FurtherOther pathways, such as risks associated with structural racism  , may alsCurrently, the regulatory body in charge of monitoring lead levels in the U.S.A. is the Environmental Protection Agency, which directs its lead-monitoring and enforcement efforts through its office of Enforcement and Compliance Assurance. Most of the strength of the agency and office is exercised through the Lead Renovation, Repair, and Painting rule (LRRP) , which rWhile notifying potential residents of the presence of lead and regulating building renovations may lessen some lead exposure, these sources of mitigation will mostly benefit individuals and families who possess the resources to have choices when deciding where to live, and those who can afford to live in renovated properties. Ideally, federal funds would be set aside to institute a universal lead paint testing program for older buildings and to properly contain the lead in affected buildings.This study is limited by short-term, cross-sectional, census-tract level housing and poverty data, as well as a limited set of socioeconomic factors. Longitudinal studies using individual-level housing characteristic indicators are needed to obtain more precise estimates of the association between living in pre-lead-ban housing and adverse birth outcomes. Despite these limitations, this study is bolstered by a large, population-level sample of over 1 million births; utilization of all eligible birth certificate data in Texas; comparison by nativity for Hispanic, Black, and White mother subgroups; objective measures of birth outcomes from the birth certificate data; objective rather than subjective median housing age and poverty level for census tracts; an appropriate multilevel modeling strategy; and fairly recent data.This study adds to the evidence that housing age in combination with neighborhood poverty is still a significant predictor of adverse birth outcomes; areas with older median housing ages and high poverty appear to be most at risk of these birth disparities. More broadly, findings identify older housing and high-poverty neighborhoods as potential structural determinants of adverse birth outcomes. Additionally, structural racism likely plays an important factor as U.S.-born Black and Hispanic women face disproportionate odds of these adverse birth outcomes compared to U.S.-born White women. Furthermore, poor families, families living in high-poverty neighborhoods, residents in older neighborhoods within urban or historically segregated areas, U.S.-born Black and Hispanic mothers, and those subject to other choice-limiting vulnerabilities will likely continue to face disproportionate rates of adverse birth outcomes without place-based interventions.This study points to the need for increased awareness of the prevalence of lead-based paint in older, high-poverty neighborhoods in Texas and broadly across the U.S.A. Despite the ban on lead-based paint, the measure of risk of exposure to lead was associated with increased adverse birth outcomes. Integrated surveillance of housing characteristics, neighborhood poverty, sociodemographic characteristics of mothers, and birth outcomes will be critical for future investigations of whether living in low-income neighborhoods and older housing plays a lasting role in children’s developmental trajectories.


Emotional dysregulation is of great cause for concern because it is associated with severe outcomes. Currently, the identification of youths with signs of emotional and behavioral dysregulation is obtained through the assessment of a Dysregulation Profile (DP), including the Strengths and Difficulties Questionnaire-DP (SDQ-DP). Despite its increasingly frequent use in research, studies exploring the SDQ-DP properties are still limited, and no study with Italian samples is currently available. The current study aimed to explore the psychometric properties of the SDQ-DP parent-report and its association with difficulties in the school context in a sample of 332 Italian early adolescents. Results showed that the SDQ-DP parent-report is a single-factor measure with good internal consistency. Also, in both males and females, the SDQ-DP parent-report was associated with higher teacher-reported Internalizing  and Externalizing Problems  and lower Prosocial Behavior. This study added further evidence about the utility of the SDQ-DP in the assessment, prevention, and treatment of emotional dysregulation. A considerable number of early adolescents present a complex picture of co-occurring emotional, behavioral, and cognitive dysregulation, causing significant adjustment problems ,2,3. UsuThis index is associated with self-regulatory problems in multiple domains and represents a risk marker for psychiatric problems and youths’ poor adjustment . The DP,A specific DP score based on the Strengths and Difficulties Questionnaire (SDQ)  has alsoThe SDQ-DP, as defined by Holtmann et al. , represeFurthermore, early adolescence is a period of transition with significant biological, physical, mental, and social changes and challenges; thus, the evaluation of a screening measure of dysregulation might be particularly important for early adolescents to identify youths at risk for developing psychopathological symptoms . In thisThe SDQ-DP, as described above, has been validated to screen the DP in a clinical setting . The SDQSD = 0.64). Eighty-six students (25.90%) were 6th graders, while 246 (74.10%) were 7th graders.The sample was collected in schools located in the northeast of Italy. It included 332  middle school Italian students aged 10–14 years old .Strengths and Difficulties Questionnaire: The SDQ  is a 25-School grades: School grades were derived from class assignments, and scores ranged from 0 to 10 (with ten being the best mark). Teachers reported the mean grade of all school subjects for each student. n = 10). Incomplete variables were imputed under fully conditional specification, using the default setting “Impute Missing Data Values (Multiple Imputation)” available on SPSS. The statistical tests were run on IBM SPSS Statistics for Windows, Version 26.0  unless otherwise stated. The percentage of missing values across all the variables varied between 0% and 14.7%. Overall, 8.07% of the values were incomplete. Missing data were imputed using multiple imputations (χ2) statistic, a comparative fit index (CFI), a Tucker–Lewis index (TLI), and a root mean square error of approximation (RMSEA). We interpreted TLI and CFI values ≥ 0.90 as acceptable and ≥0.95 as excellent, and RMSEA values ≤ 0.08 as acceptable and ≤0.06 as excellent ) and Externalizing Problems , Prosocial Behavior , nor school grades .The moderation models showed that gender did not moderate the associations between the SDQ-DP parent-report and teacher-reported Internalizing  and Externalizing Problems , and negatively associated with Prosocial Behavior .Further analyses revealed that, in both males and females, the SDQ-DP parent-report was positively associated with teacher-reported Internalizing  ,27.The growing awareness about the long-term consequences that emotional dysregulation can yield has made it necessary for the development of new tools to measure it reliably and identify those youths at greater risk for adverse outcomes.The first tool to be used for assessing emotional dysregulation was the CBCL-DP. More recently, an equivalent DP based on the items of the SDQ parent-report has been developed . Both dyHowever, it is important to highlight that studies evaluating the SDQ-DP reliability are still limited, and, currently, no studies have explored its psychometric properties in Italian samples. The current study fits within this field of research and aims to test the factor structure and internal consistency of the SDQ-DP parent-report in a community sample of Italian early adolescents. χ2, CFI, TLI, RMSEA) indicated that a single-factor model fit our data. Besides, in contrast to previous studies [Results showed that, in our sample, the SDQ-DP parent-report reliably assessed a single construct. The goodness-of-fit indices  in moderating the association between the SDQ-DP parent-report and the studied outcomes. However, previous studies showed that the SDQ-DP was not associated with differences in several socio-demographic characteristics—see for instance . FinallyOverall, our results showed that the SDQ-DP parent-report is a reliable measure of emotional and behavioral dysregulation in a sample of Italian early adolescents. We also found that more than 14% of the students met the criteria for the SDQ-DP, whose scores were associated with more significant difficulties in the school context. These results highlight the importance of finding proper tools to identify youths at greater risk for severe outcomes, and promptly address their difficulties and prevent them from heading towards the most unfavorable pathways . At the


The number of colleges and universities with smoke- or tobacco-free campus policies has been increasing. The effects of campus smoking policies on overall sentiment, particularly among young adult populations, are more difficult to assess owing to the changing tobacco and e-cigarette product landscape and differential attitudes toward policy implementation and enforcement.The goal of the study was to retrospectively assess the campus climate toward tobacco use by comparing tweets from California universities with and those without smoke- or tobacco-free campus policies.Geolocated Twitter posts from 2015 were collected using the Twitter public application programming interface in combination with cloud computing services on Amazon Web Services. Posts were filtered for tobacco products and behavior-related keywords. A total of 42,877,339 posts were collected from 2015, with 2837 originating from a University of California or California State University system campus, and 758 of these manually verified as being about smoking. Chi-square tests were conducted to determine if there were significant differences in tweet user sentiments between campuses that were smoke- or tobacco-free  compared to those that were not. A separate content analysis of tweets included in chi-square tests was conducted to identify major themes by campus smoking policy status.P=.03). Higher positive sentiment on campuses without a smoke- or tobacco-free campus policy may have been driven by general comments about one’s own smoking behavior and comments about smoking as a general behavior. Positive sentiment tweets originating from campuses without a smoke- or tobacco-free policy had greater variation in tweet type, which may have also contributed to differences in sentiment among universities.The percentage of positive sentiment tweets toward tobacco use was higher on campuses without a smoke- or tobacco-free campus policy than on campuses with a smoke- or tobacco-free campus policy (76.7% vs 66.4%, Our study introduces preliminary data suggesting that campus smoke- and tobacco-free policies are associated with a reduction in positive sentiment toward smoking. However, continued expressions and intentions to smoke and reports of one’s own smoking among Twitter users suggest a need for more research to better understand the dynamics between implementation of smoke- and tobacco-free policies and resulting tobacco behavioral sentiment. The number of colleges and universities with smoke- or tobacco-free campus policies has been increasing -4. As ofThe effects of campus smoking policies on overall sentiment, particularly among young adults, are more difficult to assess given the changing tobacco and e-cigarette product landscape and differential attitudes toward policy implementation and enforcement. Geolocating social media posts to specific spatiotemporal areas allows for comparison of in situ smoking-related attitudes and behaviors, including between campuses with and without smoke- or tobacco-free campuses. Hence, geolocation information available from publicly available social media Twitter posts represents an opportunity to garner infoveillance-generated insights retrospective to the policy implementation periods.Public 4-year universities in California provide a unique comparison for assessing tobacco-related attitudes and behaviors during policy implementation. The state has two public 4-year university systems, the University of California (UC) and California State University (CSU). As of January 2014, a systemwide tobacco-free policy went into effect on all UC campuses prohibiting tobacco use, including e-cigarettes, on campus grounds . The CSUGeolocated Twitter posts from 2015, a year after which the UC system had enacted its systemwide tobacco-free policy and prior to enactment in the CSU system, were used to conduct a retrospective analysis of smoking-themed tweets geofenced from UC and CSU campuses (one CSU campus—Fullerton—enacted its own smokefree policy effective August 2013). Data collection was conducted using the Twitter public application programming interface in combination with cloud computing services on Amazon Web Services. Data were filtered for messages that included geospatial coordinates enabled by users. These data were collected in JSON format and stored in a relational database, with information on the date and time of the post, hyperlink to the original tweet, text of the tweet, and geospatial coordinates.bidis, cigarette, cigarettes, cigarillos, cigars, ciggie, class, dip, e-cig, hookah, huqqa, joint, JUUL, kreteks, Marlboro, Newport, njoy, pipe, roll-up, shag, smoke, smoking, snuff, snus, tobacco, vape, vaped, vapejuice, vaper, vapes, vapine, vapor, waterpipe, waxpen, or weed. Keywords were selected and adopted on the basis of prior studies [Posts were selected for further analysis if they included any of the following keywords associated with tobacco products and behavior:  studies ,16 and bTweets that included these keywords were then further filtered to identify those physically originating  from CSU or UC campuses using base maps of these schools available from the Stanford Prevention Research Center , which tHuman annotators manually assessed posts relating to the study theme corresponding to user-generated tobacco products or related behavior, for face validity. Human annotators were trained in tobacco research and have participated in prior research infoveillance research ,19. PostA separate content analysis of tweets with smoking-related sentiment was conducted by the first author to identify central themes . Tweets P=.03). A total of 42,877,339 posts with smoking-related keywords were collected from 2015, with 2837 originating from a UC or CSU system campus, and 758 of these manually verified as being associated with user-generated smoking behavior discussions. Among Twitter posts for which positive or negative sentiment was identified (396 posts from 286 unique users), 66.4% (n=89) of posts originating from smoke- and tobacco-free campuses had a positive sentiment toward tobacco products compared to 76.7% (n=201) of posts originating from campuses without smoke- or tobacco-free campus policies  may have yielded additional user sentiment after policy implementation. Another limitation is the constrained contextual information available in some tweets , found mainly among tweets expressing an intention to smoke, which may have referred to marijuana and not tobacco products. We also did not restrict our data set to one tweet per user, though a user expressing negative or positive sentiment may be more likely to have a similar sentiment in other tweets they post. The rationale for this approach included the detection of both second- and first-hand accounts of smoking behavior, which could relate to multiple smoking behavior instances and the possibility that this could lead to possible underestimation of expressed sentiment toward alleged violations of campus smoking bans. Finally, this is an ecological study assessing the relationship between a survey of smoking-related social media posts from college campuses and the policies on those campuses. Associations uncovered in this study may not apply to individuals, and the effect of college policies on sentiment should be further investigated in studies with a breadth of individual participants whose selection is representative of the campus population.Among Twitter users in California public universities, the overall sentiment toward tobacco products and use is high, although positive sentiment is higher on campuses without smoke- or tobacco-free campus policies. Smoke- and tobacco-free policy initiatives, including implementation, may help reduce positive sentiment toward smoking on college campuses and should be strengthened to maximally increase their impact.


Intravenous infusion of lidocaine (IVF-Lido) during the perioperative period is an option to accelerate bowel function recovery after major colorectal surgery. However, previous meta-analyses have shown inconsistent conclusions. Recent randomized controlled trials (RCTs) have been reported after the publication of a previous meta-analysis.We conducted an updated and comprehensive meta-analysis to determine the effects of IVF-Lido on time to first flatus and defecation after major colorectal surgery.We performed a systematic review according to the Preferred Reporting Items for the Systematic Reviews and Meta-Analysis Protocols 2020 guideline. Only RCTs were included. The revised Cochrane risk-of-bias tool was chosen for appraisal. Meta-analysis with meta-regression and trial sequential analysis was carried out. The Doi plot was presented to evaluate publication bias. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology was executed to evaluate the certainty of evidence (CoE).Thirteen RCTs with 696 participants were enrolled. IVF-Lido significantly decreased the time to first flatus  and first defecation . Trial sequential analysis yielded identical results and ampleness of required information sizes. No obviousness in publication bias was detected, and the CoE in GRADE was low in both outcomes. Meta-regression showed that a significantly shorter time to the first defecation was associated with studies with more improvement in pain control in comparison of two groups and better-improved analgesia in the control group.We discretionarily suggest the use of IVF-Lido on postoperative bowel function recovery following major colorectal surgery. Beyond the analgesic effects, IVF-Lido might have additional benefits when postoperative pain relief has already been achieved. Considering the high heterogeneity in this updated meta-analysis, more RCTs are needed.https://inplasy.com/inplasy-2020-7-0023/, INPLASY [202070023]. With the current popularity of enhanced recovery after surgery (ERAS) in the colorectal surgery field, many aspects of perioperative interventions have been proposed to accelerate patients' bowel function recovery . IntraveWhen randomized controlled trials involving a broad spectrum of intra-abdominal procedures and other surgeries were selected for meta-analysis, uncertain results on the beneficial effects of IVF-Lido on postoperative pain control or bowel function recovery were obtained in the recent Cochrane Database of Systematic Reviews . When we10.37766/inplasy2020.7.0023). The protocol was updated, and changes were recorded until 25 July 2021.This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA) 2020 guideline and the Cochrane Handbook –29 and fThe structured search strategy was developed by a librarian author (Fang CJ), and results were retrieved from seven databases, namely, Embase, MEDLINE, Cochrane CENTRAL, Scopus, China National Knowledge Infrastructure, Index to Taiwan Periodical Literature System, and WHO International Clinical Trials Registry Platform (ICTRP) with no language restrictions until 25 July 2021. Reference lists of relevant articles and conference abstracts were reviewed to identify additional studies.The two key concepts “colorectal surgery” and “lidocaine,” along with their synonyms (42 free-text terms plus truncation symbols when appropriate) and controlled vocabulary (19 MeSH terms and 22 Emtree terms), were used. Two independent authors (Chen PC and Fang CJ) examined the titles and abstracts of these studies. Then, the full texts of relevant studies were retrieved. The inclusion criteria were as follows: (1) RCTs that involved patients undergoing major colorectal surgery, (2) intervention and control groups treated with IVF-Lido and IVF-saline, respectively, and (3) the primary outcome consists of the bowel function recovery under IVF-Lido, including the time to first flatus passage and the time to the first defecation after surgery. Non-RCTs were not enrolled to avoid confounding and selection bias.Data were extracted from eligible studies included by two authors (Chen PC and Fang CJ). The extracted data included first author, publication year, country of the study, source of funding number of patients, procedure type, IVF-Lido dosage in intervention groups, drugs for maintenance of general anesthesia, additional uses of perioperative analgesics, outcomes of bowel function recovery, and visual pain analog scores (VAS) or numerical rating scales (NRS). The RoB was independently assessed by two authors (Lai PC and Huang YT) by using the RoB tool 2.0 for RCTs (30). Divergences were resolved by consensus.2) statistics. A priori power of the meta-analysis was calculated by the R package “dmetar” with the random-effects model  version 5.3 . Continuous variables were pooled as mean difference (MD) with 95% confidence intervals (CIs). A random-effects model was chosen for the meta-analysis. Subgroup analyses were further performed based on the overall RoB of enrolled RCTs based on the requirement of AMSTAR2. Heterogeneities among studies were evaluated using the I-square (Its model .2). The TSA result was presented as MD and α-spending-adjusted CI.When a meta-analysis using sparse data, type I errors may occur due to low methodological quality, outcome measure bias, publication bias, small trial bias, or random errors. The use of TSA provides more information on the precision and uncertainty of meta-analysis results . TSA wasSensitivity analysis is a methodology to deal with ranges of values for decisions that were unclear . Sensitihttp://www.gradepro.org).Not only to yield the statistical results but also to state the level of evidence becomes an essential presentation in the research of evidence-based medicine . We asseThe initial literature search identified 2,298 potentially eligible articles, among which 13 studies were finally enrolled in our meta-analysis . These 1Each domain and the overall RoB of included RCTs are shown in 2 = 85%, 2 = 78%, Pooled effects of IVF-Lido from all the enrolled RCTs yielded significant shortening in time to first flatus [MD = −6.03 h, 95% CI: , I2 = 55%, 2 = 84%, 2 = 78.1%, p = 0.03), indicating discordant results between RCTs with low/some-concerned and high overall RoB , Irall RoB . The poo2 = 78%, 2 = 0%, P = 0.66) between RCTs with low/some-concerned and high overall RoB  Irall RoB . When al2 = 30 and 1% in time to first flatus and defecation, respectively) was presented in both endpoints of the non-Asian group. In contrast, high heterogeneity  was observed in both endpoints of the Asian group. The pooled estimates in time to first flatus were similar between two groups , but the pooled estimates in time to the first defecation were much shorter in the non-Asian group . It is worth noting that four out of six Asian studies were rated as high overall RoB.We also divided the included studies into Asian and non-Asian groups because near half (six in thirteen) of the enrolled studies were conducted in Asia. Significant shortening in time to first flatus  and defe2 values of 91 and 85% in time to first flatus and defecation, respectively. We further determined the strength of evidence in RCTs only with low or some-concerned overall RoB by using TSA. The Z curves in the study endpoints of time to first flatus  might lead to different wound sizes and influence the analgesic effects of IVF-Lido, we analyzed the data by using “surgical type” as a covariant. The results showed that the mean differences in time to first flatus  and defeIn comparison with the previous three meta-analyses investigating the effects of IVF-Lido for bowel function recovery after major colorectal surgery in recent 2 years, our updated meta-analysis focused on a high-quality systematic review appraised by AMSTAR2  17–19).–19.17–19While following the appraisal criteria described by Chalmers and Jadad  or the oAfter major colorectal surgery, reducing the pain triggered by a combination of neural and inflammatory pathways facilitates bowel functional recovery . AlthougDespite these controversies, the results from our meta-regression demonstrated a positive correlation of faster bowel function recovery associated with more VAS/NRS improvement by IVF-Lido, especially in time to the first defecation. Traditionally, meta-regression is conducted when a meta-analysis under consideration of power has more than 10 studies, but this rule is not strict , 38. We Surprisingly, in the enrolled RCTs, the beneficial effects persisted for many hours or even days after infusion, which raised a question on the pure analgesic effect of IVF-Lido on bowel function recovery , 39. TheIn short, the results from our meta-regression indicate that IVF-Lido might play a multifaceted role in bowel function recovery, including analgesic effect, but other mechanisms  should also be considered. Theoretically, using IVF-Lido in a higher dose and a longer duration fashion might augment the shortening of bowel function recovery time through anti-inflammation and improved analgesic effects. However, physicians should always consider the adverse effects (AEs) and toxicity. Regarding the occurrence of AEs during IVF-Lido, only two of the included RCTs were mentioned in this study , 15. No In this updated meta-analysis with an enrolment of 13 RCTs, perioperative IVF-Lido significantly decreased the time to first flatus and first defecation after major colorectal surgery. Based on low CoE rated by GRADE methodology, we discretionarily suggest the perioperative use of IVF-Lido in patients undergoing major colorectal surgery for improved postoperative bowel function recovery. Analgesic effects of lidocaine may contribute to the recovery of bowel function from the observation of meta-regression. Additional administration of IVF-Lido in patients with the well-controlled analgesia by other strategies remarkably enhanced the speed of intestinal motility after major colorectal surgery, as depicted in meta-regression. Considering the high heterogeneity, more high-quality RCTs should be conducted to provide complete information for the ERAS society of major colorectal surgery.The original contributions presented in the study are included in the article/P-CC: conceptualization and drafting. PL and YH: methodology, software, formal analysis, and visualization. C-JF, C-HL, and P-CC: validation. P-CC and C-JF: searching and data extraction. C-HL: writing-review and editing. All authors have read and agreed to the published version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The locus coeruleus (LC), a small brainstem nucleus, is the primary source of the neuromodulator norepinephrine (NE) in the brain. The LC receives input from widespread brain regions, and projects throughout the forebrain, brainstem, cerebellum, and spinal cord. LC neurons release NE to control arousal, but also in the context of a variety of sensory-motor and behavioral functions. Despite its brain-wide effects, much about the role of LC-NE in behavior and the circuits controlling LC activity is unknown. New evidence suggests that the modular input-output organization of the LC could enable transient, task-specific modulation of distinct brain regions. Future work must further assess whether this spatial modularity coincides with functional differences in LC-NE subpopulations acting at specific times, and how such spatiotemporal specificity might influence learned behaviors. Here, we summarize the state of the field and present new ideas on the role of LC-NE in learned behaviors. Norepinephrine (NE) is one of the four main neuromodulators in the brain, exerting widespread influence over almost all cortical and subcortical brain regions. Neurons in the locus coeruleus (LC) release NE to regulate baseline arousal and to facilitate a variety of sensory-motor and behavioral functions . DysfuncDespite its brain-wide effects and established involvement in CNS disorders, much about even the normal function of the LC-NE system in the brain remains unknown. For example, the conditions under which LC-NE neurons are transiently activated and the modes of NE action during learned behaviors are poorly understood, especially in comparison to other neuromodulatory systems, such as dopamine . There aDespite its small number of neurons [∼3,000 neurons in the rodent brain  and ∼50,Norepinephrine neuronal bodies make up a dense LC “core,” with LC-NE dendrites extending into a pericoeruleus “shell” region. The pericoerulear region also contains GABAergic (LC-GABA), glutamatergic, neuropeptide-S-expressing, and cholinergic neurons . WhetherWhether the other neuronal subtypes in the LC shell – e.g., glutamatergic, neuropeptide-S-expressing, or cholinergic – form direct connections with LC-NE neurons, or play a role in shaping LC-NE activity, remains unknown. However, these neuronal subtypes are predominantly active during wakefulness , indicatOne of the strongest behavioral correlates of LC-NE activity is its link with vigilance states. LC-NE neurons are silent during REM sleep, display low levels of activity during non-REM sleep, and are most active during wakefulness . ManipulThe link between LC-NE activity and arousal is likely relevant for explaining the role of LC-NE in learned behaviors during wakefulness. LC activation tightly correlates with pupil size and arousal level in mice , monkeysin vivo in awake behaving animals. Finally, defining the function of LC-NE activity as a global broadcast system of arousal might be too simplistic for understanding its role in learned behavior, as we discuss later with the emergence of modular functional data in the LC-NE system.Arousal alters attention by suppressing low-salience stimuli while enhancing responses to highly salient or goal-directed information; accordingly, LC-NE is also thought to be critically involved in regulating attention through its brain-wide release . Older aThe role of LC-NE neurons extends beyond arousal, attention, and anxiety. Recordings or pharmacological manipulations of phasic NE activity suggest a dual involvement in behavior and cognition. First, LC activation is critical for sustained attention, as its phasic activity correlates with behavioral responses in learned behaviors . Non-tarIn addition to its role in facilitating behavioral execution, LC activation is critically involved in learning and memory. LC projections to the hippocampus, amygdala, and PFC influence spatial learning and memory formation . For exaOne mechanism by which LC-NE activity could enable learning is through encoding of environmental novelty. In naïve animals, electrophysiological measurements show that LC activity increases in response to novel or salient stimuli , and thiIt has been widely observed that LC dynamics correlate with fluctuations in pupil diameter, both in human and animal studies . Many stTwo predominating theories attempt to explain the role of the LC in sensory-motor behavior: the adaptive gain theory  and the Though these theories of gain-modulation and network reset are not mutually exclusive, neither alone can fully explain the role of LC-NE in the brain, and little progress has been made in either refining or unifying them in the past 15 years. Recent technological advances and increased tool availability enabling precise measurements and manipulations of LC spiking activity in awake behaving mice present a means of evaluating these theories or advancing alternative proposals. Future studies on the role of LC-NE in learned behavior will require well-designed behavioral experiments to address these dual functions, while also considering the heterogeneous nature of LC activity and potential for spatial modularity of outputs.One way to reconcile the divergent roles for LC-NE activity is suggested by recent evidence of spatial modularity within the LC-NE neuronal population . HistoriOur current understanding of the LC-NE circuitry suggests at least partially distinct populations of LC-NE neurons with respect to their projection targets and functional organization . These dThe suggestion of a modular input-output organization in the LC raises the question of whether LC-NE subpopulations exhibit different molecular signatures that could confer different functional properties. Again, though the LC has often been considered a homogenous nucleus, there is evidence to suggest that LC-NE neurons are a molecularly heterogeneous population. For example, though all LC neurons contain NE, separable subpopulations also contain other neuropeptides, such as Neuropeptide Y, galanin, and cocaine-and-amphetamine-regulated transcripts , 2005. TLocal integration of NE release by targets is an important way by which the activity of single LC neurons exhibiting multiple task components, with projections to multiple areas, can nonetheless be utilized for separate functions. Due to different NE receptor expression throughout the cortex , heterogUnderstanding the complex role of LC-NE signals in facilitating distinct aspects of behavior will require understanding the timescales on which LC-NE neurons are activated, how this activity affects performance in a learned behavior, and how these LC-NE signals are used by target regions to facilitate behavioral responses and learning. As in human studies manipulating the discriminability of a target, a learned behavior for studying LC-NE in model systems should incorporate different levels of sensory uncertainty. Thus, a task dependent on trial-history that incorporates sensory uncertainty and necessitates a goal-directed behavioral choice would enable a more unified understanding of the role of LC-NE in learned behaviors. Another important goal for the field is developing an understanding of how NE interacts with other neuromodulators to modulate brain states and behaviors. An established task that can be used across neuromodulatory systems would be well-suited for this goal. For example, in the cholinergic system, an auditory go/no-go task was used to show that cholinergic neurons encode reinforcement surprise, and that these responses scale with uncertainty . Using vDespite the diverse roles of the LC in regulating arousal, attention, and facilitating more complex behaviors, our understanding of this nucleus is quite limited. Recent studies, however, are changing our understanding of the LC. What was formerly considered a homogenous nucleus exerting global, uniform influence over its many diverse target regions, is now suggested to be a heterogenous population of NE releasing cells, potentially exhibiting both spatial and temporal modularity that govern its function. These observations, combined with a rapidly expanding neuroscience toolkit, enable updating of existing theories, or potentially forming new ones, to explain the roles of LC-NE in learned behaviors.VB-P and GD wrote the initial draft. VB-P made all figures. All authors discussed the content and commented on the text and figures.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Humor is a main ingredient of interpersonal relationships. Two sets of psychopathological traits known for their devastating impact on interpersonal relationships are psychopathy and narcissism. The current study was developed to provide a fine-grained analysis of the relationship between four humor styles  and both psychopathic and narcissistic traits. Specifically, it addresses how humor styles relate to the three psychopathy subfactors (following the triarchic model) and four subfactors of grandiose narcissism.N = 177.Self-report measures in a non-clinical male sample Multiple regression analyses revealed psychopathic and narcissistic traits’ relation to using both benign and injurious humor. Subfactor analyses showed that aggressive and self-defeating humor were mostly associated with impulsivity and entitlement, while dominance levels actuated the use of humor to cope with stress. The cold-heartedness component of psychopathy proved to be particularly humorless, setting it aside as a distinctively disturbing psychopathic subfactor.Humor strongly colors the interpersonal style of both psychopathic and narcissistic personalities. Differential components of both personality types inform on the possible underlying motivations that drive the use of distinct styles of humor. This implies that psychopathic and narcissistic traits could potentially be lowered through the alternation of humor styles. Humor is an essential component of interpersonal communication. Earlier research framed humor as an adaptive trait enhancing one’s physical and psychological health . Later, The current study focusses on humor at its relationship with two personality constellations that strongly impact interpersonal relationships: psychopathy and narcissism. Psychopathy is characterized by deficits in emotional function and antisocial behavior. Narcissism primarily reflects a cognitive-affective preoccupation with the self. Communalities in both of these sets of traits are a self-centered focus, and the tendency to place one’s needs above those of others. Consequently, familial, parenting, romantic, and professional relationships of people with increased levels of psychopathy or narcissism are often characterized by high stress levels, low commitment, conflicts, and counter productivity e.g., . Excessigetting ahead or getting along. A similar distinction is between an agentic versus a communal focus, with the first referring to power and achievement, and the latter to one’s sense of belonging and relationships with others . Additionally, narcissistic traits have been linked to both positive humor styles . Aside fh others . Both psh others . Humor ch others  and happh others , and narh others  and optih others , these th others . Both reh others  and narch others , as asseAlthough our knowledge about the humor correlates of psychopathy and narcissism are vastly improving, three questions remain unaddressed. First, none of the previous studies addressed the triarchic psychopathy components. To address this lacuna, the current study will be the first in the humor area assessing psychopathy with the Psychopathic Personality Inventory-Revised (PPI-R) . Second,N = 177 male participants recruited at Maastricht University. The average age was 28.08 years, SD = 12.56, 18–68. Only males were included to avoid confounding gender or floor effects because males tend to demonstrate higher levels of psychopathic traits  to 7 . The HSQ has displayed adequate internal consistencies for each of the subscales ranging from α = 0.76 to 0.83 for both the English and the Dutch version (Humor styles were assessed using the 32-item Humor Style Questionnaire (HSQ) , which m version . Further version . The HSQ version . The HSQfalse to 4 = true). Total PPI scores reflect a global index of psychopathy and includes eight subscales. Factor analytic studies revealed a three-factor conceptualization: fearless-dominance (FD), self-centered impulsivity (SCI), and cold-heartedness (Cold) . According to Grandiose narcissism was assessed with the 37-item Narcissistic Personality Inventory (NPI) . The iteParticipants were recruited using flyer advertisement and convenience sampling. Following written consent, questionnaires were administered on a computer and presented in a random order. Native Dutch participants conducted the study in Dutch, and other participants conducted the study in English. After completing the research, the participants were debriefed, thanked, and either received course credits or a financial compensation. This study was approved by the ethics committee of Maastricht University, reference numbers 114_06_05_2012, 2014_04_28_08_42_15, and 145_07_10_2014.All analyses were conducted using SPSS version 24 . Correla1.Descriptive statistics and correlation analyses can be seen in Affiliative humor was positively correlated with all psychopathic variables except for PPI-R-Cold. Self-enhancing humor was significantly associated with PPI-R-total and PPI-R-FD. Self-defeating humor was positively correlated with PPI-R-SCI and negatively with PPI-R-Cold. Aggressive humor exhibited positive significant relations with PPI-R-total and PPI-R-SCI .F = 15.61, p < 0.001, R2 = 0.21), self-enhancing , self-defeating , and aggressive humor . Affiliative humor was significantly positively predicted by PPI-R-FD and PPI-R-SCI, and negatively by PPI-R-Cold. PPI-R-FD was the only positive significant predictor of self-enhancing humor. Self-defeating humor was significantly positively associated with PPI-R-SCI and negatively with PPI-R-Cold. PPI-R-SCI was a significantly positively related to aggressive humor , in which NPI-SEA served as the positive predictor. Self-enhancing humor revealed a significant model  and was significantly positively predicted by NPI-SUA. The models for self-defeating  and aggressive humor  were significant, and NPI-EE positively and significantly predicted both these humor styles  psychopathy and grandiose narcissism. Overall, psychopathic and narcissistic traits related to various benign and injurious humor styles, directed toward others and the self.Regarding the first study aim, as expected, total psychopathy scores showed to relate to affiliate, self-enhancing, and aggressive humor in a positive, and largely medium-strong, way. The link between psychopathy and aggressive humor styles is in line with the fact that excessive aggression levels are reflected in several psychopathy criteria , and witRegarding the second study aim, global grandiose narcissism scores displayed a positive relationship with all humor styles. The expected relationship with affiliative and aggressive humor was of medium effect size, while the self-directed humor styles represented small effects. In-depth analyses of the different subscales of narcissism revealed that two subscales drove the use of benign humor styles. Specifically, self-absorption/self-admiration traits predisposed to using humor to bond with others , and superiority and arrogance traits increased the inclination to cope with difficult situations through humor . In contrast, the exploitative and entitlement scale can be considered the most maladaptive aspect of narcissism, related to increased use of both injurious humor styles. There has been abundant empirical evidence linking narcissism to aggression, for example, through ego-threat . SimilarStrengths of the current study include the investigation of how humor relates to the triarchic components of psychopathy and stricter analyses of the differential subfactors of psychopathy and narcissism. In addition, this is the first study on humor tendencies using a European sample, which might be relevant given the cultural differences in the meaning and expression of humor . LimitatThe current study highlights the importance of humor in two of the most devastating types of psychopathologic traits. The fact that both sets of traits have shown to be linked to benign humor styles comes with potential societal implications. First, the link with affiliative humor shows that both psychopathic and narcissistic traits are related to an intact, and even superior use of humor to create interpersonal bonds. Therefore, humor could have the potential to serve as a tool to strengthen and repair interpersonal relationships in people with elevated psychopathic and narcissistic traits—this is especially conceivable in case they would be able to succeed in simultaneously lowering their use of aggressive humor. Second, encouraging self-enhancing humor could potentially be beneficial because it has shown to be effective in coping with stress . In sharTaken together, the current, fine-grained analyses of psychopathic and narcissistic (sub)traits evidenced that humor is a frequent and important correlate of both these personality constellations. The two injurious humor styles  were mostly associated with impulsivity and entitlement. Dominance levels seemed to actuate the use of humor as a stress-coping method. Using humor for affiliative means was linked to a broader range of psychopathic and narcissistic traits. The cold-heartedness component of psychopathy clearly lacks humor which, again, stresses its particularly disturbing nature.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by The Ethics Review Committee Psychology and Neuroscience (ERCPN). Written informed consent to participate in this study was provided by the participants.JL was responsible for study conceptualization and data collection. JL and VF were responsible for data preparation, data analysis, and report writing. Both authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


To investigate the significance of echocardiography combined with N-terminal pro-B-type natriuretic peptide (NT-pro BNP) levels in the evaluation and prognosis of diastolic heart failure (DHF).  Clinical data were collected from 168 patients with DHF. Serum levels of NT-pro BNP were first measured by ELISA. Meanwhile, the echocardiography was used to examine left ventricular end-diastolic diameter (LVEDD), left ventricular diameter (LVD), and other parameters. Multivariate logistic regression analysis was performed for variables in heart failure assessment grade or poor prognosis. Finally, the predictive ability for New York Heart Association (NYHA) class as well as prognosis was assessed by ROC curves. E/Ea) and serum NT-pro BNP level was risk factors for NYHA class and prognosis. However, LVEF, LVEDD, and flow propagation velocity (Vp) can be a benefit condition. In addition, ROC curve showed that echocardiography combined with NT-pro BNP content had higher accuracy in NYHA class and prognostic assessment of DHF than applied separately.  NT-pro BNP was the overexpression in the serum of patients with DHF. And the degree of elevation was related to NYHA class, while NT-pro BNP levels were significantly higher in the P-MACE group than in the N-MACE group. According to the multivariate logistic regression analysis, the ratio of peak velocity of left atrial early diastolic blood flow to early diastolic peak velocity of mitral annulus ( The diagnosis of echocardiography combined with NT-pro BNP levels has the potential to distinguish the NYHA class in heart function of patients with DHF and determine the prognosis of patients. Chronic heart failure (CHF) is a clinical syndrome of ventricular filling dysfunction and ejection dysfunction which caused by the cardiac structural damage and functional disturbances due to the various factors. Cardiac blood supply in CHF patients cannot meet the metabolic needs of other organs of the body . AccordiE/A) [DHF is also called heart failure with preserved ejection fraction (HFPEF). Its pathogenesis is due to the increased myocardial stiffness and slowed diastolic velocity, resulting in ventricular relaxation dysfunction or ventricular stiffness increasing, ultimately leading to abnormal ventricular filling and insufficient returned blood volume . MoreoveE/A) . This meIn recent years, N-terminal pro-B-type natriuretic peptide (NT-pro BNP) as an inactive brain-type natriuretic peptide (BNP) in ventricular cell analysis , it has Collected 168 patients with DHF visited our hospital from January 2016 to March 2019. All the collected patients complied the European Society of Cardiology (ESC) diagnostic criteria for DHF in 2007. According to the New York Heart Association (NYHA) cardiac function classification criteria, patients with DHF were divided into three subgroups: mildly symptomatic patients (NYHA II), moderately symptomatic (NYHA III), and severely symptomatic (NYHA IV). According to whether they had adverse cardiovascular events (MACE) during 1-year follow-up, patients with DHF were divided into major adverse cardiovascular event (MACE) group (P-MACE) and no MACE group (N-MACE). The control group was composed of healthy volunteers with normal heart function and left ventricular ejection fraction (LVEF) ≥ 50% and without severe heart disease and clinical symptoms of heart failure in the same issue. All subjects volunteered to participate in this study and were informed and consented.Inclusion criteria are as follows: meet the ESC diagnostic criteria for DHF in 2007 , have ty5 mL venous blood was collected from all subjects at fasting state and centrifuged at 3000 r/min for 10 min at 4°C. The supernatant was removed in a new centrifuge tube and stored at -80°C. The level of NT-pro BNP in serum was detected strictly according to the steps in the package insert of NT-pro BNP ELISA assay kit.Use Philips IE Elite Color Doppler ultrasound diagnostic instrument with 2-4 MHz frequency probe. Transthoracic ultrasonography was performed with the patient in the left lateral decubitus position, and the probe was closely attached to the sternum and apical regions of the subject to obtain two-dimensional and color Doppler flow images of the left ventricular long and short axis, apical long axis, apical four-chamber, and two-chamber views.E value), and interventricular septum thickness (IVS) were measured on the left ventricular long-axis view. (2) Left ventricular ejection fraction (LVEF), flow propagation velocity (Vp), peak early diastolic velocity of mitral annulus (Ea), and E/Ea value were measured in apical four-chamber view and two-chamber view.They recorded the following parameters: (1) left ventricular end-diastolic diameter (LVEDD), left ventricular diameter (LVD), left atrial diameter (LAD), peak early diastolic blood flow velocity . Used multivariate logistic regression analysis analyzes potential risk factors for variables with statistically significant differences in heart failure assessment grades  and variables with statistically significant differences in prognosis . ROC curves were plotted to calculate the area under the curve (AUC) and judge the predictive ability of echocardiography and NT-pro BNP single or combined application for the poor prognosis of DHF. Differences were considered statistically significant at P < 0.05.The data were analyzed by P < 0.05). However, there were no significant differences in age, gender, smoking history, and triglyceride (TG) levels between the two groups (P > 0.05).The basic information of all subjects was shown in Supplementary Table P < 0.05). This result illustrated that serum NT-pro BNP levels were significantly increased in patients with DHF, and that the more severe the DHF grade, the more significant the increase in NT-pro BNP levels. In addition, we divided the patients into the P-MACE group (n = 87) and N-MACE group (n = 81) according to whether MACE occurred. ELISA results showed that the serum NT-pro BNP level in the P-MACE group was significantly increased than that in the N-MACE group (P < 0.05).The results of ELISA showed that the levels of serum NT-pro BNP in patients with DHF were significantly increased compared with the control group, and the higher levels of NYHA class, the NT-pro BNP level also increased P < 0.05.CE group P < 0.05.E/Ea were significantly increased in patients with DHF, while the values of LVEDD, LAD, LVEF, and Vp were significantly lower (P < 0.05). Cardiac parameters were further compared across NYHA class in patients with DHF. It was found that the values of LVD, IVS, and E/Ea were significantly higher in the NYHA IV and NYHA III group than in the NYHA II group and higher in NYHA IV than in the NYHA III group. The values of LEVDD, LAD, LVEF, and Vp were significantly lower in the NYHA IV group compared with the NYHA II group , while the differences in LVD and LAD values between the two groups were not statistically significant (P > 0.05).We then compared the differences in cardiac parameters between patients in the N-MACE and P-MACE groups. As shown in E/Ea and the level of NT-pro BNP serum could be risk factors for NYHA class. LVEF, LVEDD, and Vp could be favorable factors for NYHA class .Multivariate logistic regression analysis was performed on variables with statistically significant prognosis. The results showed that The diagnostic value of echocardiography and NT-pro BNP levels for NYHA class or prognosis was assessed by the ROC curve analysis. Echocardiography combined with NT-pro BNP had higher accuracy in identifying NYHA III (AUC: 0.771) and NYHA IV (AUC: 0.985) than echocardiography or NT-pro BNP level assessment alone Figures . In addiBNP and NT-pro BNP are significance in the diagnosis of heart failure, and they also have auxiliary value in evaluating the severity and prognosis of heart failure. NT-pro BNP is decomposed from BNP released by myocardial cells. It has the characteristics of stable chemical structure, small difference among individuals, and long half-life which has more clinical value than BNP. Nowadays, NT-pro BNP plays an important role in the diagnosis, classification, and treatment of chronic heart failure, and some studies have applied it to the prognosis of heart failure . Some stE/Ea > 8, LVEDP > 15 mmHg, and LVEF > 50%. The results of other studies showed that the decrease of LVEDD, Vp, and LVEF was the factor of DHF produced [E/Ea values of DHF patients were significantly increased, and the LVEF, LAD, LVEDD, and Vp values were significantly decreased. At the same time, compared with the N-MACE group, IVS and E/Ea in the P-MACE group were significantly increased, while LVEF, LVEDD, and Vp were significantly decreased. These results indicate that echocardiography can evaluate the classification and prognosis of DHF through E/Ea, LVEDP, LVEF, and other indicators, but there was no statistical significance of difference in IVS, LVEF, and LVEDD between NYHA III and NYHA IV subgroups, indicating that echocardiography cannot clarify the standard difference between NYHA III and NYHA IV. Through multiple factor logistic regression analysis, further found that E/Ea is a risk factor for NYHA class and MACE in DHF patients, while LVEF, LVEDD, and Vp are favorable factors. Although previous studies have shown that E/Ea value is the gold standard for DHF evaluation and prognosis judgment [E/Ea due to the measurement of E and Ea in different cycles and different load states and the instability of E and Ea in DHF patients; moreover, the measurement repeatability of LVEDD, Vp, and LVEF is poor, which is not conducive to clinical development. Therefore, this study considered use echocardiography combined with NT-pro BNP level to evaluate DHF and prognosis.Among them, the main judgment indexes of DHF determined by Doppler ultrasound include produced , 19. Othproduced . The resjudgment , it is dWith the development of recombinant protein technology, in clinic, the detection results of NT-pro BNP are more stable and reliable, and the operation of NT-pro BNP is more convenient, which can avoid the deviation of echocardiography caused by different operation. At the same time, the detection results of NT-pro BNP can make up for the shortcomings of echocardiography, such as the unclear standard difference between NYHA III and NYHA IV. Echocardiography can provide the information of cardiac cavity size and wall thickness, which can avoid the deviation of NT-pro BNP content as the standard caused by gender or renal function. Therefore, in clinical practice, echocardiography and NT-pro BNP are often used in combination to diagnose diseases. The research shows that echocardiography combined with NT-pro BNP can be used to diagnose percutaneous transvenous mitral commissurotomy , subclinIn conclusion, echocardiography combined with NT-pro BNP level has the potential to distinguish the NYHA class of DHF patients and judge the prognosis of DHF patients. However, in this study, the cases collected by a single medical institution are limited in region and number of cases, which cannot fully represent all DHF patients. Therefore, it is still need a further research to better illustrate the diagnostic value of echocardiography combined with NT-pro BNP.


The prevalence of kidney failure is increasing globally. Most of these patients will require life-sustaining dialysis at a substantial cost to the health care system. Assisted peritoneal dialysis (PD) and assisted home hemodialysis (HD) are potential alternatives to in-center HD and have demonstrated equivalent outcomes with respect to mortality and morbidity. We aim to describe the costs associated with assisted continuous cycling PD (CCPD) and assisted home HD.Cost minimization model.Adult incident maintenance dialysis patients in Manitoba, Canada.Full- and partial-assist home HD and CCPD. Full-assist modalities were defined as nurse-assisted dialysis setup and takedown performed by a health care aide, whereas partial-assist modalities only included nurse-assisted setup. Additionally, full-assist home HD was evaluated under a complete care scenario with the inclusion of a health care aide remaining with the patient throughout the duration of treatment.Annual per-patient maintenance and training costs related to assisted and self-care home HD and CCPD, presented in 2019 Canadian dollars.This model took the perspective of the Canadian public health payer using a 1-year time frame.Annual total per-patient maintenance (and training) costs by modality were the following: full-assist CCPD, $75.717 ; partial-assist CCPD, $67,765 ; full-assist home HD, $47,862 ($301); partial-assist home HD, $44,650 ; and full-assist home HD (complete care), $64,659 ($301).This model did not account for costs taken from the societal perspective or costs related to PD failure and modality switching. Additionally, this analysis reflects only costs experienced by a single center.Assisted home-based dialysis modalities are viable treatment options for patients from a cost perspective. Future studies to consider graduation rates to full self-care from assisted dialysis and the cost implications of respite care are needed.  Providing dialysis care to patients with kidney failure is costly for the health system. Performing dialysis in the patient’s home has been shown to cost less in comparison to care provided in the hospital, yet many patients are unable to perform the self-care required. In this study, we provide the yearly cost of providing dialysis in the patient’s home with the assistance of trained caregivers on both a partial and fully assisted basis. Costs such as staffing, dialysis supplies, dialysis machines, utilities, and training were included. The cost model showed that both partial and fully assisted dialysis care offer cost savings when compared with dialysis care provided in the hospital.Transplantation is the optimal treatment for kidney failure from both quality-of-life and cost perspectives.The provision of dialysis care for patients with ESKD imposes high cost burdens on health care systems due to its resource-intensive nature. In the United States, yearly health care spending on dialysis patients is on average $90.6 thousand per patient.,,,,Assisted home peritoneal dialysis (PD) and assisted home HD are alternative care options suitable for patients who are unable or unwilling to perform self-care in home. Assisted PD programs in European countries such as France and Belgium are already well established, demonstrating acceptable quality-of-life and equivalent clinical outcomes in terms of peritonitis, technique survival, and hospital readmissions.The purpose of our study is to provide a descriptive yearly cost analysis of assisted home-based dialysis modalities for patients with kidney failure at varying levels of assistance.Following the methods outlined in Beaudry et alFurthermore, we build on the original model by incorporating home assistance–specific human resource expenditures related to transportation, parking, and cellular telephones to project the costs borne over time associated with full and partial nurse-assisted CCPD and thrice-weekly conventional home HD. Full-assist CCPD and home HD include a licensed practical nurse performing patient setup, with takedown duties performed by a health care aide. Partial-assist CCPD and home HD include nurse-assisted setup only. Additionally, full-assist home HD was evaluated with the inclusion of a health care aide remaining with the patient throughout the duration of treatment (4 hours) along with performing patient takedown (complete-assist scenario). Scenario descriptions can be found in Modality-specific training costs are incorporated explicitly to understand the impact of this up-front investment on total cost minimization. CCPD and CAPD training times were averaged between modalities to account for potential patient graduation from CCPD to CAPD. Added human resource–related expenditures and model inputs were sourced from the Manitoba Renal Program’s administrative data and in consultation with nurse managers in the Seven Oaks General Hospital dialysis program.The primary outcome considered was the 1-year maintenance cost of providing dialysis care in Manitoba. Secondary outcomes included training costs encompassing all costs related to direct human resources, benefits, relief hours, and vacation time, as well as the time to reach cost neutrality when comparing modalities. Cost neutrality points represent the points in time at which the most cost-effective modality changes. Moreover, when modalities require an investment in patient training, the model provides estimates for the time-to-payoff–associated costs, given possible alternative modalities.As sensitivity analysis, in-center HD yearly maintenance costs were varied by ±25% to determine new cost-neutrality points between modalities. Scenario analyses were performed by increasing the dialysis care schedule for home HD patients from 3 to 3.5 times per week. Additionally, we examined the per-patient annual cost by modality in a model in which all assisted home dialysis tasks performed by a licensed practical nurse were instead done by a health care aide. Outcomes are presented in real 2019 Canadian dollars on a per-patient per-year basis.Model outputs overlaid in The annual maintenance cost of delivering daily full-assist CCPD inclusive of direct labor, consumables, and capital totalled $75,717 per patient, with initial training costs of $301. When considering partial-assist CCPD, the yearly per-patient maintenance costs are reduced to $67,765, with initial training costs of $4,385. In comparison, the annual maintenance costs of self-administered CCPD totaled $48,132, with associated training costs of $7,919. The marked cost premium for assisted CCPD over standard self-administered PD is attributed to a significantly higher labor requirement (inclusive of benefits and vacation and relief), with premiums of $36,387 . This premium is reduced to $19,632 when considering partial-assist CCPD. The annual maintenance and initial training costs associated with self-care CAPD amounted to $36,265 and $7,919 per patient, respectively.Annual maintenance cost per patient associated with full-assist thrice-weekly home HD using a conventional HD machine was estimated at $47,862, with associated training costs of $301. Maintenance costs for partial-assist home HD were $44,650 per patient per year, with an initial training cost of $14,813. Considering the complete-care scenario in which the health care aide remains throughout the duration of treatment, the annual maintenance cost per patient was $64,695, with training costs of $301. Self-care home HD annual maintenance and initial training costs were re-estimated from the previous cost model and totaled $36,618 and $25,486 per patient, respectively.Considering graduation from assisted to self-care dialysis, this model estimates a cost-savings of $27,585 per year when patients graduate from full-assist CCPD to its self-care alternative (excluding training costs). These cost savings are reduced to $19,632 per year when considering graduation from partial-assist CCPD to self-care CCPD. Inclusive of training costs, economic gains are still realized within the first year. Graduation from full, partial, and complete care assisted home HD modalities to self-care home HD translates to a cost savings of $11,244, $8,031, and $28,077 per patient per year (excluding training costs). Inclusive of training costs, graduating from complete care assisted home HD to its self-care alternative is the only scenario in which cost savings are realized within the first year.Cost-neutrality points representing the time in which cost savings are realized between modalities are presented in Sensitivity analysis considering a 25% reduction in the cost of in-center HD increased months required to achieve cost savings for self-care CAPD and CCPD to 6.41 and 37.74 months, respectively. Partial- and full-assist CCPD modalities were more costly at all points in this scenario. Under similar circumstances, the months required to achieve cost neutrality between self-care, full-assist, and partial-assist home HD versus in-center HD increased to 20.85, 0.65, and 27.43 months, respectively. Complete care assisted HD did not achieve cost-neutrality at any point when in-center costs were reduced by 25%. In contrast, when in-center HD costs were increased by 25%, all modalities achieved cost savings at varying time points.With respect to patient graduation from full- and partial-assisted PD to self-care PD, this model estimates a cost savings of $36,387 and $19,632 per patient per year, respectively. For CCPD patients, this translates to an annual cost savings of $19,283 per patient when compared with in-center HD and $31,150 per patient for CAPD patients (excluding training costs). Patients graduating from assisted home HD to self-care conventional home HD can reduce annual per-patient costs by $31,201 in comparison to in-center HD (excluding training costs).Scenario analysis results considering an increase in home HD schedules are presented in Using a cost-minimization approach, we have established a model that includes all direct maintenance and training costs associated with assisted home dialysis modalities from a health care payer’s perspective. This model estimates that assisted thrice-weekly home HD, regardless of scenario, offers cost savings relative to in-center HD. Nevertheless, under the complete-care scenario, the difference between annual maintenance costs compared with in-center HD is the least distinct. Moreover, full- and complete care assisted home HD scenarios are less costly than self-care home HD in the short term (~10 months) due to differences in initial patient training costs. As such, they are optimal treatment options from a cost-savings perspective for patients expected to require dialysis for a limited time who are unable to perform full self-care.,Whereas this model estimates the costs associated with full-assist PD to exceed those of in-center HD, other publicly funded jurisdictions have reported similar costs between the 2 modalities.Economic gains may be realized from patients graduating from assisted modalities to full self-care. Although specific rates of graduation from assisted to full self-care are unknown in this population, research from 1 large Canadian assisted-dialysis study found graduation rates to full self-care or family-assisted care of 38%, with a median modality switch time of 31 days.Conversely, economic disincentives such as utility costs may decrease the attractiveness of home-based modalities for patients in programs in which such costs are not covered. Although these costs are relatively minimal compared with overall costs ($404 per annum for water and $78 per annum for electricity), they may deter patients from home modalities in view of the inverse relationship between income and incidence of ESKD.Although assisted modalities become less attractive economically as the frequency of treatment increases, we have shown that costs per patient can be reduced when staffing models are adjusted to use less costly labor. Evidence from a Canadian pilot project demonstrated that safe and adequate care can be delivered when using health care aide equivalents to perform assisted dialysis.,,Assisted home modalities have been shown to offer similar outcomes to dialysis delivered in-center with respect to all-cause hospitalizations, all-cause infections, and mortality rates.,There are other potential cost synergies that may be possible with the expansion of assisted home dialysis programs. Increased capacity to support respite care for patients who normally perform full self-care PD may be beneficial because it has shown to be cost minimizing for failing self-care patients.,Dialysis care in rural and remote areas can be costly in comparison to care in an urban setting.Our model has many strengths. First, this analysis uses a previously validated costing model based on actual program expenditures by the British Columbia Renal Agency to estimate direct human resources.Our study has several important limitations. First, we do not account for costs taken from the societal perspective, including all home utilities, transportation, patients’ opportunity costs, or caregiver burden. Second, the results of the study reflect the costs experienced by only a single center, and heterogeneity between programs and the relative size of home dialysis programs may have a substantial influence on cost-related outcomes. As such, findings should be adapted to local circumstances and patient mix when necessary. Last, costs related to PD failure and modality switching, such as hospitalization and surgery, are not factored into calculations of cost neutrality. Although this may result in increased costs over simply initiating and maintaining in-center HD, previous research has demonstrated that patients who transition from PD to HD experience costs that are similar and not in excess to those experienced by patients who receive in-center HD as a sole modality.Dialysis therapy is a resource-intensive and costly treatment for patients with kidney failure. Assisted home-based modalities can offer similar or reduced costs in comparison to in-center HD and should be considered, particularly in programs with a high proportion of individuals relocating for in-center care. Further research is needed to determine graduation rates to full self-care, as well as costs associated with respite care, with more detailed models evaluating the impact on the entire trajectory of patient treatment with dialysis.