The theoretical explanation of human problems is derived from the complex interplay of psychological, social, economic, political, and physical factors.This study examined the roles of behavioral health  and social environment  and mental health  in predicting insomnia in adolescents in an ecological perspective.Approximately 6445 high school students in Taiwan were administered an anonymous self-report survey. Hierarchical multiple regression was performed to examine how multidimensional social environment, behavioral health, and mental health factors were associated with insomnia in adolescents.p < 0.001), whereas family support (β = −0.06), school connectedness (β = −0.05), and favorable neighborhood (β = −0.10) were negatively associated with insomnia (p < 0.001). Sex did not predict insomnia, but age was positively associated with insomnia . Among all predictors of insomnia in the study, mental health factors, especially depression, play a major role on insomnia among adolescents, and is as much important as social environment factors.The prevalence rate of insomnia in the sample was 30%. The results indicated that alcohol abuse (β = 0.04), suicidality (β = 0.06), depression (β = 0.29), anxiety (β = 0.14), and ADHD (β = 0.11) were positively associated with insomnia  and psychological symptoms were associated with insomnia in adolescents when the demographic variables (sex and age) were controlled and provided valuable information and evidence for clinicians, social workers, and health professionals who provide support to adolescents with insomnia. Applying an ecological approach in practice can aid in understanding at individual, family, school, and community levels and in identifying the strengths and weaknesses of their interactions with each other.This perspective enables practitioners in effectively treating problems and addressing the needs of the various levels, including the individual, family, school, and the broader community. Thus, prevention and intervention of insomnia in adolescents should focus on multidimensional risk and protective factors, including mental health, behavioral health, and social environment, in the context of an ecological system. MoreoveConsidering the person-in-environment perspective, it is important to understand an individual and individual behavior in light of the environment contexts in which that person lives and acts. Thus, in addition to mental health , the current study also examined the roles of behavioral health  and social environment  simultaneously in predicting insomnia in adolescents. First, regarding behavioral health, alcohol abuse and suicidality are potential barriers to good sleep and risk factors for insomnia. Concerning alcohol abuse, studies have found that chronic alcoholic exposure can cause sleep disruptions, which is manifested by increasing sleep-onset latency and wakefulness . In addin = 39,590) indicated that perceived neighborhood safety is negatively associated with insomnia symptoms and poor sleep quality in the past 30 days , social environment , and mental health  to determine their association with insomnia in adolescents in the context of an ecological system. Concordant with previous research, we hypothesized that alcohol abuse, suicidality, depression, anxiety, and ADHD would be the risk factors for insomnia in adolescents, after control for sex and age. By contrast, family support, school connectedness, and conducive neighborhood would be the preventive factors associated with insomnia.The participants in this study were enrolled from the 2009 Project for the Health of Children and Adolescents in Southern Taiwan, a research program studying the mental health status of children and adolescents living in four counties and three metropolitan areas in southern Taiwan . In 2009This study was approved by the Institutional Review Board (IRB) of Kaohsiung Medical University before sampling and data collection. The research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside of the research context. And, the data were recorded in a manner that individuals cannot be identified in the anonymous survey. The waiver of written parental consent form did not adversely affect the rights and welfare of the subjects and was approved by IRB. The passive parental consent was used. Prior to the administration of the survey, parents/guardians of all student participants received written notice letter that their child would be recruited to participate in the study and explaining the study purpose and procedure, emphasizing the voluntary and confidential nature of the study. Parents were given the opportunity to exclude their daughter/son from participation in the study and asked to respond within 3 days. Students took the letter home for their parents or guardians, who were given a choice to call the researchers, write in the school communications book, or ask their children to directly, all convey to their refusal for their children to join the study. In addition, the students were given the liberty to refuse participation in this study by returning blank questionnaires along with those from other students.n = 76) was conducted to ensure adequate reliability of all research instruments by performing a 2-week test–retest reliability.Based on the ecological system theory, we included three layers of social environment as predictors in the study: family support, school connectedness, and favorable neighborhood. We assessed the students’ experiences with insomnia, mental health , behavioral health , and social environment  by using the self-reported surveys. A pilot study (p < 0.001).The 8-item Athens Insomnia Scale (AIS-8) was used to assess the severity of subjective insomnia over the preceding month . The iteThe 20-item Mandarin-Chinese version of the Center for Epidemiological Studies-Depression (CES-D) Scale was used to assess the frequency of depressive symptoms in the previous week . Each itWe used the Taiwanese Version of the Multidimensional Anxiety Scale for Children (MASC-T) to assess the participants’ self-reported anxiety symptoms . The MASAn 18-item self-report ADHD scale was modified from the Vanderbilt ADHD Diagnostic Parent Rating Scale  and reprThe 5-item alcohol abuse scale was adapted from the CRAFFT substance abuse screening test to assess problematic alcohol use in adolescents . We remop < 0.001)  . The CroThe 5-item Chinese version of the Family APGAR Index  was applThe level of connectedness to school was assessed based on five statements: “I enjoy my school life,” “I get along well with my teachers,” “I get along well with my schoolmates,” “I feel that I am popular,” and “I feel no interest to interact with friends or schoolmates (revise coded).” The participants scored the items on a 4-point Likert scale from 0 to 3, with a higher score indicating more agreement with the statements. To make the interpretation easier, we reverse-coded these items and calculated the sum score. After recoding, a higher score indicating a higher level of school connectedness. The mean score was calculated. The Cronbach’s alpha was 0.68.The 8-item favorable living environment scale was adapted from the Taiwanese Quality of Life Questionnaire for Adolescents  to assesStatistical analysis was performed using the SPSS Statistical Package for Windows, version 24. First, descriptive statistics were used to assess the distribution of adolescents’ insomnia, behavioral health , social environment , and mental health  based on the ecological system theory. Second, we conducted correlational analyses using the Pearson coefficient of correlation to illustrate interrelationships between each of the variables. Third, we performed hierarchical regression to examine the effects of behavioral health, social environment, and mental health on insomnia in adolescents, after control for age and sex.Overall, 6445 participants completed the research questionnaires without withdrawal, of which 52% were girls and 48% were boys. r = 0.52). As the collinearity statistics  were all within accepted limits, the result indicated that multicollinearity was not a concern  = 61.18, p < 0.001 and accounted for 2% of the variance in insomnia. Introducing two behavioral health and three social environmental variables significantly explained an additional 22% of the variance in insomnia and this change in R2 was significant, F = 371.98, p < 0.001. Finally, the addition of three mental health variables to the regression model explained an additional 12% of the variance in insomnia and this change in R2 was also significant, F = 403.69, p < 0.001 . Taken together, in the final model, these demographic, behavioral health variables, social environment variables, and mental health variables significantly explained 36% of the variance in insomnia. The sum of square was 345.71 and the sum of square error was 610.86. A Mallow’s Cp value (Cp = 11) that was close to the number of predictors plus the constant indicated that the model produced relatively precise and unbiased estimates. The regression coefficients indicated that alcohol abuse (β = 0.04), suicidality (β = 0.06), depression (β = 0.29), anxiety (β = 0.14), and ADHD (β = 0.11) were positively associated with insomnia (p < 0.001), whereas family support (β = −0.06), school connectedness (β = −0.05), and favorable neighborhood (β = −0.10) were negatively associated with insomnia (p < 0.001). Therefore, adolescents who reported higher levels of alcohol abuse, suicidality, depression, anxiety, and ADHD were more likely to have insomnia. In contrast, adolescents who perceived higher levels of family support, school connectedness, and favorable neighborhood were less likely to have insomnia. Sex did not predict insomnia. Age was positively associated with insomnia . Older adolescents reported more insomnia than younger adolescents. Among all predictors of insomnia in the study, mental health factors, especially depression, play a major role on insomnia among adolescents, and is as much important as social environment factors. When applying stepwise elimination approach, depression was the best predictor that accounted for the most of the variance in insomnia , followed by ADHD and favorable neighborhood, and school connectedness accounted for the least of the variance in insomnia.The results showed that adolescents’ sex and age significantly contributed to the regression model, The present study extends the previous research regarding the impact of behavioral and mental health and social environment on insomnia in adolescents. This study addressed the increasing problems of insomnia in adolescents and added to the fund of knowledge by analyzing how multidimensional factors contribute to insomnia in adolescents at individual, family, school, and community levels in the ecological system. The results supported our hypotheses. First, we found empirical support that adolescent alcohol abuse and suicidality were positively associated with insomnia, after control for age, sex, and other factors. Second, we revealed that family support, school connectedness, and favorable neighborhood were negatively associated with adolescent insomnia, after control for demographics and other covariates. Third, we found that mental health problems such as depression, anxiety, and ADHD were positively associated with insomnia when controlling the demographics and other covariates. Both the behavioral health and social environment variables and the mental health variables explained the significant variance in the model.Regarding behavioral health problems, the study confirmed the relationship between alcohol abuse and insomnia among adolescents in Taiwan – concordant with previous research on adult samples . AdolescConsidering that behavioral and mental health problems were the risk factors for insomnia, we examined the potential preventive factors in the three social environment levels that were related to low insomnia levels. This relationship has not been explored much previously. We hypothesized three preventive factors in the context of family, school, and community to represent the social environment in the ecological system. The results supported the hypotheses that higher family support, school connectedness, and a conducive neighborhood contributed to low risk of insomnia among adolescents. Based on the stress-buffering model, social support protected individuals from the negative psychological consequences of a wide range of stressful events that can help reduce insomnia . Family A strength of our study is the use of an ecological perspective to examine the roles of mental health and multidimensional psychosocial determinants, such as behavioral health  and social environment , in insomnia in adolescents. Holistic thinking can provide a paradigm to understand how various systems and their interactions can contribute to an individual’s problem and behavior. Another strength is the large size of the study sample. By contrast, a limitation of the study is its cross-sectional design that can only draw conclusions regarding the correlation between the study variables and not interpret the cause-and-effect. Moreover, some of the variables may have a reciprocal relationship with insomnia. For example, depression predicts insomnia, whereas insomnia also predicts depression. Future research may be warranted to examine the reciprocal relationships between the psychosocial variables and insomnia and identify patterns of a negative cycle.The study provides valuable information and evidence for clinicians, social workers, and health professionals providing support to adolescents with insomnia. Applying an ecological approach in practice aids in understanding the issues at individual, family, school, and community levels and identify the strengths and weaknesses of the interactions between them. This perspective allows the practitioner to effectively treat problems and address the needs of the various levels, including the individual, family, school, and the broader community. The prevention and intervention of insomnia in the adolescents should focus on multidimensional risks and preventive factors, including mental health, behavioral health, and social environment in the context of an ecological system.The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.This study was approved by the IRB of Kaohsiung Medical University before sampling and data collection. Before conducting the study, we prepared a leaflet explaining the study purpose and procedure, emphasizing the voluntary and confidential nature of the study. Students took the leaflets home for their parents or guardians, who were given a choice to call the researchers, write in the school communications book, or ask their children to directly, all convey to their refusal for their children to join the study. In addition, the students were given the liberty to refuse participation in this study by returning blank questionnaires along with those from other students.Y-PH: conceptualization, methodology, software, validation, formal analysis, investigation, resources, data curation, writing – original draft preparation, review and editing, and visualization. W-HL and C-FY: conceptualization, validation, investigation, resources, data curation, review and editing, supervision, project administration, and funding acquisition.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.


Despite improvements in treatment for rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (axSpA), several key unmet needs remain, such as fatigue. The objective of this study was to describe the severity of fatigue, disease characteristics and socioeconomic factors in people with RA, PsA and axSpA.The study was designed as a cross-sectional survey collecting patient characteristics such as disease characteristics, socioeconomic factors and fatigue in people with RA, PsA and axSpA in Denmark. Respondents were consecutively recruited for the study over a six-month period in 2018 via routine visits to outpatient rheumatology clinics. Study nurses collected information on diagnosis, current disease-related treatment and disease activity from medical journals. People were invited to complete a questionnaire related to socioeconomic factors and containing the FACIT-Fatigue subscale. Descriptive statistics were analyzed using SAS.We invited 633 people to participate, and 488 (77%) completed the questionnaire. Women constituted 62% of respondents, and the mean age was 53.5 years. Respondents had on average been diagnosed between 11 and 15 years ago. Overall, 79% had no changes to their disease-related treatment during the past year, and the average disease activity as indicated by DAS28 for RA and PsA was 2.48 and 2.36, respectively, and BASDAI for axSpA was 28.40. Fatigue was present in all three diagnoses (mean: 34.31). The mean fatigue score varied from respondents answering that they suffered from no or little fatigue (mean: 45.48) to extreme fatigue (mean: 10.11). Analyses demonstrated that the respondents were not considerably different from nonrespondents, and the study population is considered representative compared with Danish RA and axSpA patients in the Danish National Rheumatology Registry, the DANBIO database.We found that the majority of the study population were fatigued (61%). They had low disease activity and few disease-related treatment changes. Fatigue is described as extreme tiredness, typically resulting from mental or physical exertion or illness . HoweverIn recent years, there has been an increased focus on fatigue and how fatigue correlates with other symptoms or conditions. According to a recent review of fatigue and RA, severe fatigue is common among individuals with RA and has a significant impact on quality of life . In addiThe prevalence of RA, PsA and axSpA varies globally. In Europe, the estimated prevalence is between 0.3% and 1% for RA , 0.001% The objective of this study was to describe the severity of fatigue, disease characteristics and socioeconomic factors in people with RA, PsA and axSpA.This study was designed as a cross-sectional study of people with RA, PsA and axSpA currently enrolled at one of Rigshospitalet’s two outpatient clinics in Glostrup and Frederiksberg, Denmark. We aimed to recruit a representative sample of people with RA, PsA and axSpA, amounting to 527 . Inclusion criteria were people 18 and older with a confirmed diagnosis of RA, PsA or axSpA; who had been enrolled at one of the two clinics for more than four weeks; who were able to read, understand and write Danish; and who signed an informed consent to participate in the study. People were consecutively recruited between January and June 2018.We developed a questionnaire, which was used by the study nurse to collect informed consent and characteristics from each respondent’s medical journal  Files. CWe developed a patient questionnaire, which was used to collect patient demographics  Files. IThis study is a part of a larger study “The impact of fatigue in patients with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis in Denmark”. Besides the abovementioned, data on work productivity, health related quality of life, sleep and depression were collected, and will be reported elsewhere (in preparation).The questionnaires were pilot-tested among five people with RA . The pilot was conducted in the same setting as the study cohort on a random day with people with RA, PsA and axSpA visiting the clinics for routine visits. The questionnaire was tested for comprehensibility, user friendliness and time consumption. As the primary part of the questionnaire was made up of validated scales, we did not test the comprehensibility of the specific scales but of the entire questionnaire, as well as the flow in the questionnaire. In general, the pilots answered within an expected time frame and found the questionnaire acceptable and understandable.People with RA, PsA or axSpA were approached by a study nurse in each clinic and enrolled in the study based on informed consent. The study nurse collected characteristics via a medical journal while the person completed a self-reported questionnaire on an iPad. If the respondent preferred to complete the questionnaire at home, the respondent was either given a link to the online questionnaire or a paper version of the questionnaire and a stamped, addressed envelope and was asked to return the questionnaire by ordinary mail. Study participation was encouraged by the study nurse for those people who agreed to participate in the survey but for some reason did not answer the questionnaire. The study was conducted with approval from the Danish Data Protection Agency (j.nr. 2012-41-1199) and approval from the Ethics Committee of the Capital Region of Denmark (Protocol 17021125). The Danish Medicines Agency was informed about the execution of the study, as per current Danish guidelines (case no. 2017071026).The questionnaires were both set up in SurveyXact, an online questionnaire collection program developed by Rambøll. The answers of those respondents choosing to complete the questionnaire on paper were entered manually into SurveyXact. Statistical analyses were conducted in SAS and Microsoft Excel. Where applicable, we applied analysis of variance and Pearson’s chi-square test to test for significant differences between groups.We invited 633 people to complete the questionnaire, and of those, 488 completed it (77% response rate). Of the 145 (23%) who did not complete the questionnaire, 18 (3%) refused to participate, 117 (18%) agreed but never started the questionnaire, and 10 (2%) partly completed the questionnaire .In total, 488 respondents completed the questionnaire . Of the 488, 60% had a diagnosis of RA, 17% a diagnosis of PsA and 23% a diagnosis of axSpA . Of all Among the newly diagnosed (0–5 years), the highest share of respondents was among those with axSpA (30%) . More thWhen analyzing the nonrespondents according to characteristics, it became evident that nonrespondents were distributed evenly across the diagnoses compared with respondents . HoweverIn Denmark, data on people with RA and axSpA currently receiving DMARDs is routinely collected at scheduled visits to rheumatology centers in the Danish National Rheumatology Registry, the DANBIO database. However, the DANBIO database do not include information on people with PsA. The data collected includes age and gender, type of treatment, and treatment changes registered by the nurse or physician as well as patient-reported data  ,29. ThisIn 2017, there were 4,788 people with RA, PsA and axSpA enrolled at the Glostrup and Frederiksberg outpatient rheumatology clinics . We targWhen comparing the study cohort with the Glostrup and Frederiksberg cohort from DANBIO 2017, the RA respondents are slightly younger than the average Glostrup and Frederiksberg cohort from 2017  . FurtherThe mean fatigue scores on the VAS were 42.16 (SD: 29.95), 49.69 (SD: 29.18) and 45.01 (SD: 29.57) for RA, PsA and axSpA, respectively. The mean VAS fatigue scores did not vary statistically significantly among the three diagnoses (p = 0.11). On the FACIT-Fatigue scale, the mean fatigue score was 34.31 (SD: 6.08), and fatigue was present in all three diagnoses . The meaIn this study, 488 respondents (77% response rate) completed the questionnaire, and fatigue was frequent in all three diagnoses . Women constituted 62% of respondents, and the mean age was 53.5 years, which is in accordance with other studies that have found that more fatigue has been reported in association with advancing age ,33 and fDespite this, the study population suffered from fatigue. We measured fatigue in two ways. On the VAS, we found a mean fatigue score of 42.16 (SD: 29.95), 49.69 (SD: 29.18) and 45.01 (SD: 29.57) for RA, PsA and axSpA, respectively. Our findings are consistent with mean fatigue scores previously documented in a cross-sectional Norwegian study  . We alsoThe study population from both disease-specific and socioeconomic perspectives was a well-functioning group of people. Also, overall, the population belonged to the active workforce (58%). This is noteworthy because a recently published study that aimed to determine factors associated with work productivity found a strong association of fatigue with all work measures as well as with daily activity impairment . This emTo date, the FACIT-Fatigue scale has been used to measure progress in fatigue in both cross-sectional and longitudinal studies. These studies have reported a minimal important difference of 3–8.3 on the FACIT-Fatigue scale from 0 to 52 .Our study has several strengths. One of the main strengths of the study is the data source for the patient characteristics, which were recorded by trained study nurses from the respondents’ medical journals. This method excludes potential recall biases seen in surveys exclusively based on patient-reported data. Another strength of the study is the recruitment method, which has ensured a high response rate. Similarly, the dropout analysis showed that the respondents were not considerably different from the nonrespondents. Finally, our study is considered representative of the Danish RA, PsA and axSpA populations.We acknowledge, however, that the study has some limitations. The study is cross-sectional and can therefore not provide any conclusions concerning causality. It can generate only hypotheses, which can be further analyzed in future prospectively conducted studies. Despite a good representation in the study cohort of both genders and age groups, the study cohort is slightly older and consists of more women than the group of nonrespondents. The same tendency is seen in other surveys . The stuScales differ in their focus, some measuring severity only and others duration and impact on a range of functions as well as different aspects of fatigue. In this study, we focused on measuring the severity of fatigue using both VAS and FACIT-Fatigue scores, which measured one aspect of fatigue  and not the multidimensional aspects of fatigue, which can be viewed as a limitation.We found that the majority of the study population was fatigued. The study cohort represents a stable group with low disease activity, few disease-related treatment changes and strong attachment to the labor market. The study cohort is considered representative, and the results warrant further analyses of how fatigue correlates with other PROs and how it differs across the diagnoses.S1 File(DOCX)Click here for additional data file.S2 File(DOCX)Click here for additional data file.S3 File(DOCX)Click here for additional data file.S4 File(DOCX)Click here for additional data file.


The arterial pulse wave (PW) is a rich source of information on cardiovascular (CV) health. It is widely measured by both consumer and clinical devices. However, the physical determinants of the PW are not yet fully understood, and the development of PW analysis algorithms is limited by a lack of PW data sets containing reference CV measurements. Our aim was to create a database of PWs simulated by a computer to span a range of CV conditions, representative of a sample of healthy adults. The typical CV properties of 25–75 yr olds were identified through a literature review. These were used as inputs to a computational model to simulate PWs for subjects of each age decade. Pressure, flow velocity, luminal area, and photoplethysmographic PWs were simulated at common measurement sites, and PW indexes were extracted. The database, containing PWs from 4,374 virtual subjects, was verified by comparing the simulated PWs and derived indexes with corresponding in vivo data. Good agreement was observed, with well-reproduced age-related changes in hemodynamic parameters and PW morphology. The utility of the database was demonstrated through case studies providing novel hemodynamic insights, in silico assessment of PW algorithms, and pilot data to inform the design of clinical PW algorithm assessments. In conclusion, the publicly available PW database is a valuable resource for understanding CV determinants of PWs and for the development and preclinical assessment of PW analysis algorithms. It is particularly useful because the exact CV properties that generated each PW are known.NEW & NOTEWORTHY First, a comprehensive literature review of changes in cardiovascular properties with age was performed. Second, an approach for simulating pulse waves (PWs) at different ages was designed and verified against in vivo data. Third, a PW database was created, and its utility was illustrated through three case studies investigating the determinants of PW indexes. Fourth, the database and tools for creating the database, analyzing PWs, and replicating the case studies are freely available. The arterial pulse wave (PW) is used for physiological assessment in both clinical medicine and consumer devices. The PW contains a wealth of information on the cardiovascular (CV) system . It is iThe PW has been the subject of much in vivo research. For instance, the physiological determinants of pulse wave velocity (PWV) and late systolic pressure augmentation have been investigated in both large observational studies , 127a anOne-dimensional (1D) computational modeling provides a complementary approach for research into the PW, as it allows PWs to be simulated under different CV conditions . Indeed,1) develop methods for simulating PWs during healthy aging, exhibiting normal physiological variation; 2) develop a method for simulating photoplethysmogram (PPG) PWs, which are widely measured by pulse oximeters and consumer devices; 3) create a database of PWs, representative of a sample from a healthy adult population, and verify it through comparison with in vivo data; 4) present case studies demonstrating the utility of the approach; and 5) make the PW database and accompanying code freely available to support further research. This builds on preliminary work , parabolic flow, and no energy losses at bifurcations. The previously described model provided four types of arterial PWs: blood flow velocity (U), luminal area (A), volume flow rate (Q = UA), and BP (P) waves. In this study, the model was extended to simulate PPG PWs by assuming that the PPG is dependent on the volume of arterial blood in a tissue. At the periphery, the PPG PW was calculated from the volume of blood stored in the terminal windkessel model. Within the arterial network, the PPG was calculated from the volume of blood stored in the arterial segment. In both cases, the PPG was calculated by normalizing the pulsatile variation in blood volume to occupy a range of 0 to 1.The nonlinear 1D equations of incompressible and axisymmetric flow in Voigt-type viscoelastic vessels were used to model blood flow, based on the physical principles of conservation of mass, momentum, and energy . Key assNumerical Model.For further details of the model, including the geometry of the arterial network and the methodology for simulating PPG PWs, see the Literature Review. The most reliable studies reporting the mean and intersubject variation of each parameter at each age were identified using the following criteria: 1) whether the reported change with age was in keeping with the consensus from the review; 2) the accuracy of the technique used to measure the parameter; and 3) the nature of the subjects studied . The typical values found for a sample of healthy adults are shown for each parameter in Literature Review.The model input parameters were adjusted to simulate PWs representative of healthy adults at each age decade from 25 to 75 yr. The parameters can be categorized as follows: cardiac, arterial, vascular bed, and blood properties. Referring to Cardiac properties were specified to the model through an inflow waveform prescribed at the aortic root shown in . The wavn = 5,209): an increase until around 55 yr in men, followed by a slight decrease until age 70 yr, and a rapid decline thereafter. The change observed in this study was small, with the mean HR varying between 67 and 76 beats/min for men. When combined with the nonlinear nature of the change, and the inclusion of older subjects in this study, this may explain why most other studies did not identify a change. This study was used to model changes in HR with age since it was population based and far larger than the others. Mean values for each age were obtained by interpolating the male data from this study using shape-preserving piecewise cubic interpolation. Values for normal variation in HR were not provided by this paper. Therefore, a standard deviation of 11 beats/min was obtained from a population study of 800 UK Biobank participants, aged 45–74 yr old , as t is time and T is the duration of a cardiac cycle.The majority of the identified articles , 132 indThe majority of the identified studies , 171 obsThere is little information in the literature on how the PFT is affected by age. A study of 82 healthy subjects, aged 21–78 yr, found no significant change in PFT with age when measured with gold standard aortic Doppler flow . SimilarQ with age). Similarly, Svedlund et al.  was used to model changes in aortic diameter with age, since it contained data from all three aortic sites, from subjects free of CV disease and medication, over a wide age range (24–73 yr), acquired using MRI. However, this study did not provide data on normal variation in aortic diameter. Therefore, normal variation was modeled using data from Agmon et al.  according to age and BP (n = 524). These relationships were then used to calculate desired values for arm and leg PWVs, corresponding to the desired aortic PWVs. Following studies . The cd was calculated as Γ=btherwise .It is difficult to assess the properties of vascular beds in vivo. Therefore, we considered changes in systemic vascular properties reported in the literature and used these to inform the expected changes in vascular bed properties.n = 623 and 200) found no change in SVR index  and SVR in men (A (The majority of articles describing variations in systemic vascular resistance (SVR) with age , 132 repR in men , 125. CoR in men , the samR in men ] to achin men  from its mean value. The resulting PWs at the carotid and radial arteries are shown in Prescribing Model Input Parameters for Different Ages Based on a Literature Review above). Second, PWs were simulated for 36 = 729 subjects at each age by changing the six identified CV properties in combination with each other by ±1 SD from their age-specific mean values. This resulted in 6 × 729 = 4,374 subjects in the database. Third, the plausibility of each subject was investigated by comparing their aortic and brachial BPs  to reference healthy values from McEniery et al.  were measured along the following paths: carotid-femoral, carotid-radial, femoral-ankle, aortic , and between the aortic root and each measurement site. PTTs were measured from pressure waves using the foot-to-foot algorithm (mod), reflection index (RI), and stiffness index (SI)].PW indexes, which are commonly measured in clinical practice or research, were extracted from PWs. First, hemodynamic parameters were extracted from flow and pressure PWs at the aortic root. SV, CO, LVET, PFT, and RFV were extracted from the flow PW. HR and maximal dP/dlgorithm , 53. PWVt on the pressure PWs; a, b, c, d, e, systolic peak, diastolic peak, dicrotic notch, and point of maximal dPPG/dt on the PPG PWs. These points were identified using the PulseAnalyse script , which analyses the PWs and their derivatives, as shown in U and maximum AP due to wave reflection, respectively , and the determinants of the indexes were assessed using the relative sensitivity index [which indicates the percent change in a PW index associated with a change in model input parameter of 1 SD from baseline (T × (SBP + DBP)], where T is the PW duration, and compliance is assumed to be proportional to mean BP . Most of the subjects with abnormally high PP had increased PWV and often had at least one of increased SV, increased MAP, and decreased large-artery diameter. The subjects with abnormally low PP had the opposite characteristics: decreased PWV and at least one of decreased SV, decreased MAP, and increased diameter. Most of the remaining subjects with abnormally high PPamp had decreased PWV and often increased HR or decreased MAP. The proportion of subjects exhibiting implausible BPs increased with age (from 3% of 25 yr olds to 32% of 75 yr olds). Only those subjects with BPs within healthy ranges were included in the following analyses.A total of 537 out of the 4,374 virtual subjects exhibited BPs outside of healthy ranges. This was predominantly due to abnormal PP (observed in 431 subjects) and abnormally high PPamp, and carotid AIx. There were marked changes in these resultant parameters with age, indicating that the different values of input parameters prescribed at each age did result in changes in PW shape, as seen in vivo.The hemodynamic characteristics of the PW database are summarized in 1) the amplitude of the secondary systolic peak in middle cerebral U PWs increased with age; 2) the augmentation in the secondary systolic peak of the carotid and ascending aorta pressure PWs increased with age; 3) the diastolic peak in the radial, digital, and femoral (not shown) pressure PWs was present for the 25 yr old and disappeared with age; 4) the diastolic peak of the finger PPG PW disappeared with age; 5) the two systolic peaks in the ear PPG merged with age.A selection of the simulated PWs are compared with PWs from the literature in left-hand plots) and simulated (right-hand plots) characteristics: aortic pressure, systolic pressure, and PPs increased with age; PPamp decreased with age; the time to the return of the reflected pressure wave (Tr) decreased with age; and pressure augmentation increased with age (AIx and AP). However, brachial PP increased with age, rather than decreasing and then increasing with age. This was because the brachial SBP was slightly lower than in the literature at ages 25 and 35 yr. Overall, these similarities indicate that the hemodynamic characteristics of the simulated PWs showed similar trends, and in most cases similar absolute values, to those reported in the literature.The hemodynamic characteristics of the simulated PWs are compared with those in the literature in A and B. The profiles demonstrate that two mechanisms influence PPamp . First, the early systolic portion was amplified in both subjects, causing SBPb to be greater than SBPa and therefore PPamp > 1. Second, late systolic aortic pressure augmentation (the increase in pressure from P1a to P2a) was higher in older subjects, increasing PPa and decreasing PPamp. The contributions of these mechanisms to PPamp for the whole database are illustrated in b/(P1a − DBPa). In contrast, the increase in late systolic aortic pressure augmentation with age (in blue) caused a decrease in PPb/(P2a − DBPa) with age. The effect of aortic pressure augmentation outweighed that of early systolic amplification, meaning PPamp decreased substantially with age, in keeping with in vivo studies  and LVET, as shown in amp observed with age was primarily due to changes in aortic pressure wave morphology.The profiles of pressure PW propagation from the aorta to the brachial artery were examined in young and elderly subjects, as shown in  studies . The datR2) values ranging from 0.66 to 0.70  virtual subjects (shown in red), indicating that these indexes may be less useful for stratifying middle-aged patients. The sensitivity analyses in the lower plots quantify the relative impact of different input parameters on the indexes. Several CV properties in addition to PWV influenced the indexes, such as HR and SV. For instance, the RI and SI both increased with large-artery diameter. Since large-artery diameter and aortic PWV both increase with age, this strengthened their correlations with aortic PWV across the age range. In contrast, the AGImod was not strongly influenced by large-artery diameter and performed better both across the age range and when considering only middle-aged subjects. This in silico assessment of PPG-derived indexes for assessing aortic stiffness indicates that 1) clinical studies should investigate performance over a small age range as well as over the entire cohort to assess the potential utility of indexes for stratifying patients; 2) the AGImod may provide best performance for stratification of middle-aged patients; and 3) indexes can also be influenced by HR and SV, indicating that it may be beneficial to assess performance when these CV properties are varied in vivo.The performance of the PPG-derived indexes for assessing aortic stiffness is shown in  to 0.70 A. This iThe performance of the CO algorithms is shown in In this study, we developed and verified an approach for simulating PWs representative of a sample of healthy adults. 1D numerical modeling was used to simulate PWs for virtual subjects of different ages, where the input parameters were based on normal values and ranges of CV properties obtained from a comprehensive review of previous studies. The simulated PWs exhibited similar changes with age to those reported in in vivo studies, including changes in PW shape and in hemodynamic parameters derived from PWs. The utility of this approach for gaining novel insights into hemodynamics and PW indexes was demonstrated through three case studies. The approach for simulating PWs, the resulting PW database, and the accompanying code are valuable resources for future in silico studies of hemodynamics and PW indexes.We used 1D modeling combined with a comprehensive review of CV changes with age to simulate PWs around the body for healthy subjects of different ages. The use of 1D modeling allowed us to simulate PWs at a range of common measurement sites, similar to previous studies , 169, inA  mostly had combinations of CV properties that would be expected to produce high PP; e.g., due to increased SV and/or decreased arterial compliance , whereas the accuracy of BP-derived indexes for tracking changes in CO was influenced by MAP and CO itself. These findings indicate that future studies of these indexes should assess their performance during changes in these properties. In addition, the performance of some indexes for assessing aortic stiffness was reduced when only considering subjects of a certain age. Whereas previous in vivo studies have provided valuable results across a wide age range , 164, th1) the reasons for differences in the performance of different PWV measurement paths for assessing aortic PWV (2) the CV properties that influence a transfer function relating peripheral to central pressure (3) the strengths and weaknesses of physiological measurement devices (1) the determinants of central PP (2) the influence of CV properties on forward and backward pressure waveform morphology  the pressure , 150; an devices , 156. Montral PP ; and 2) rphology . We expeIn the future, this approach may form a basis for creating hemodynamic digital twins: simulations of an individual’s hemodynamics using input parameters obtained from their physiological measurements . This woendnote at the end of this article.This article is accompanied by resources to enable other researchers to use this approach for simulating PWs. First, the PW database is freely available to download . Second,We have designed and verified an approach for simulating PWs representative of healthy adults of different ages. A computational model of the arterial system was used to simulate several types of PWs at common measurement sites for 4,374 virtual subjects. Simulations were performed for subjects of different ages by adjusting model input parameters in line with typical CV parameters for each age obtained from a comprehensive literature review. The resulting database of PWs exhibited similar age-related changes in hemodynamic parameters and PW morphology to those in previous in vivo studies. We demonstrated the utility of the approach through case studies, which provided novel insights into the hemodynamic determinants of PWs and provided pilot data to inform clinical studies of PW algorithms. The database is freely available and is a valuable resource for future research.This work was supported by the British Heart Foundation [PG/15/104/31913], the Wellcome Engineering and Physical Sciences Research Council (EPSRC) Centre for Medical Engineering at King’s College London [WT 203148/Z/16/Z], and the King’s College London and Imperial College London EPSRC Centre for Doctoral Training in Medical Imaging [EP/L015226/1] funding for J.M.H. The authors acknowledge financial support from the Department of Health through the National Institute for Health Research (NIHR) Cardiovascular MedTech Co-operative at Guy’s and St. Thomas’ National Health Service Foundation Trust (GSTT).The views expressed are those of the authors and not necessarily those of the British Heart Foundation, Wellcome Trust, EPSRC, NIHR, or GSTT.No conflicts of interest, financial or otherwise, are declared by the author(s).P.H.C., J.M.H., S.V., Y.L., P.C., and J.A. conceived and designed research; P.H.C. and J.A. performed experiments; P.H.C. analyzed data; P.H.C., S.V., Y.L., P.C., and J.A. interpreted results of experiments; P.H.C. and J.A. prepared figures; P.H.C., P.C., and J.A. drafted manuscript; P.H.C., J.M.H., S.V., Y.L., P.C., and J.A. edited and revised manuscript; P.H.C., J.M.H., S.V., Y.L., P.C., and J.A. approved final version of manuscript.https://doi.org/10.5281/zenodo.3374476. These materials are not a part of this manuscript, and have not undergone peer review by the American Physiological Society (APS). APS and the journal editors take no responsibility for these materials, for the website address, or for any links to or from it.At the request of the authors, readers are herein alerted to the fact that additional materials related to this manuscript may be found at


Over the last few decades, Cesarean section (CS) rates have increased significantly worldwide particularly in Iran. Classification methods including logistic regression (LR), random forest (RF) and artificial neural network (ANN) were used to identify factors related to CS among primipars.This cross-sectional study included 2120 primipars who gave singleton birth in Tehran, Iran between 6 and 21 July 2015. To identify factor associated with CS, the classification methods were compared in terms of sensitivity, specificity, and accuracy.The CS rate was 72.1%. Mother’s age, SES, BMI, baby’s head circumference and infant weight were the most important determinant variables for CS as identified by the ANN method which had the highest accuracy (0.70). The association of RF predictions and observed values was 0.36 (kappa).The ANN method had the best performance that classified CS delivery compared to the RF and LR methods. The ANN method might be used as an appropriate method for such data. Cesarean section (CS) is “one of the most commonly performed surgeries in obstetric practice” . In mostThe CS has some complications for the mother and infant. Common maternal complication includes bleeding, infection, postpartum hemorrhage, wound infection, endometritis –9. Some Classification methods are a set of data mining techniques used to predict group membership for new cases. A variety of classification methods have been introduced such as logistic regression (LR), random forest (RF), artificial neural network (ANN), support vector machines (SVM), decision tree (DR), k-nearest neighbor, and boosting. , 15. LotSelecting the applied classification method is very important so that accurate classifications can lead to accurate predictions. Among different classification approaches, LR is well known and utilized due to its ease of use and interpretation. However, RF is preferable when a large number of covariates and factors are available and used. ANN as a non-linear, flexible, and general tool can detect complex nonlinear relationships between dependent and independent variables , 20.According to the increasing rate of CS and its adverse consequences for the mother and child, it is important to diagnose and predict the CS delivery.Therefore, we aimed to determine the rate of CS among primipars in Tehran, Iran, and identify factors related to it using different classification methods including LR, RF and ANN. Furthermore, this study investigates the performance of these classification methods for CS data.This cross-sectional study was conducted on 2120 primiparas referred to hospitals across Tehran Province, Iran affiliated to one of these four universities, Tehran University of Medical Sciences, Shahid Beheshti University of Medical Sciences, Iran University of Medical Sciences and Islamic Azad University, from 6–21 July 2015.This study was approved by the Ethics Committee of Royan Institute, Tehran, Iran (Code: IR. ACECR. Royan.REC.1395.43). The purpose of the study and confidentiality of the data were explained verbally to the pregnant women by midwives and nurses before data collection. Moreover, written informed consent was obtained from all participants before completing the questionnaires.2), infant sex , infant weight (g), infant height (cm), baby’s head circumference (cm), type of pregnancy , history of abortion , history of stillbirth , preeclampsia , use of assisted reproductive technology  and type of delivery . The criterion for preeclampsia was having a blood pressure reading of more than 140/90 millimeters of mercury (mmHg) and the presence of an excess of proteins in the urine (proteinuria). A principal component analysis was performed on checklists that pertained to home appliances and digital goods to determine the SES of each family.For data collection, a checklist containing mother’s demographic information, obstetrical data and newborn’s information, was used. The checklists were filled out through direct interview with mothers and reviewing their cases in delivery room by a nurse or a trained obstetrician, which it included information such as mother’s age (years), mother’s education (academic، non-academic), father’s education (academic، non-academic), mother’s occupation , socio-economic status (SES), body mass index  and R . To perform the classification methods and to validate the results, the test and training samples were composed randomly among cases. The results derived from the training sample (70% of cases) was then evaluated by utilizing the test sample (30% of cases). In this paper, LR, RF, and ANN were used for data analysis.LR is one of the most common applied classification methods in medical data analysis when the response variable is dichotomous. The model can be written as:ix′ s are the covariates to classify the response and the iβ′ s are the regression coefficients. The term, In this model the ANN is an information processing method. This tool is based on human brain performance. Multilayer perceptron (MLP) is frequently used among several ANN approaches. The MLP is a combination of input, output, and hidden layers with nodes in each layer. The data is transformed between the layers through an activation function and using a degree of non-linearity. Input layer consists of all risk factors affecting the output layer (CS) with two nodes as the possible outcomes. To find the best performance of the network, a complicated non-linear mapping between input and output layers is found using the number of nodes determined empirically in the hidden layer .RF is a collection of classification and regression trees. The trees are built by a replacement sampling of the main dataset. An “out-of-bag” sample consists of the rest of data and evaluates the performance of the trees. The trees create nodes using variables that assess the occurrence of CS and a random subset of covariates is chosen at the nodes. Selection of a covariate to split node into consequent nodes is determined by a covariate which causes the largest decrease in the Gini impurity criterion. In other words, low Gini (i.e. higher decrease in Gini) shows a main role of predictor to split and classify the response variable. Therefore, the mean decrease Gini is high as well as mean decrease accuracy. After an iteration history, the final nodes contain only cases assigned to the same classes. Averaging predictions made by lots of trees allows prediction for a case at random forest . MoreoveTo check the adequacy of the models, indices such as sensitivity, specificity, diagnostic accuracy (DA), positive predictive value (PPV), negative predictive value (NPV), and the area under curve (AUC) were calculated using the observed data as the gold standard. To find the amount of agreement between the observed and predicted values, Kappa statistic was calculated.Of 2120 pregnancies, 591 (27.9%) were vaginal and 1529 (72.1%) were CS. The unadjusted comparison of demographic variables between the two groups of vaginal and CS is shown in P<0.001). Academic education resulted as a significant factor for choosing CS so that 65.3% of non-academic mothers and 81.8% of academic mothers preferred CS delivery (P<0.001). Housewife mothers (81.8%) were significantly less interested in CS in comparison to employed (69.3%). The socio-economic score was higher in the cesarean group (P<0.001). The body mass index for mother in the vaginal group was 0.99 less than CS (P<0.001). Babies’ head circumference in vaginal deliveries was lower than CS (P<0.001). A larger percentage of vaginal deliveries had no preeclampsia as well as no ART in comparison to CS . However, infant sex (P=0.887), weight (P=0.729) and height (P=0.866) as well as type of pregnancy (P=0.381), history of abortion (P=0.452) and stillbirth (P=0.294) were statistically the same for the two groups.Mothers in vaginal group were significantly younger than CS  so that older mothers were more interested in CS. Adjusted for other variables, a higher score of SES and BMI resulted in more preference of cesarean so that the odds of CS was 0.751 and 0.956, respectively. One centimeter increase in head circumference raised the likelihood CS by 15.3 percent.After LR model section using the training dataset and determining the most important variables using stepwise method, the resulted model was evaluated through the test set . The resThe mean decreases Gini and mean decrease accuracy of independent variables are shown in The best ANN among several models included one hidden layer with six hidden nodes, two output, and 24 input nodes. Hyperbolic tangent and softmax were the activation functions for hidden and output layers, respectively. The importance of the variables is shown in The efficiency and accuracy of the three performed methods are compared and shown in This study aimed to determine the factors related to CS. The rate of cesarean section in Iran was higher than the rate in other countries and the one reported by world health organization . The ratUnadjusted analysis showed a significant association between CS and independent variables. However, after adjusting the effects, mother’s age, SES, BMI, baby’s head circumference and infant weight were found as the most important and affective variables on CS. In a study to investigate socioeconomic factors on CS rates, a higher SES causes higher rate of CS was found . This maThree classification methods were performed and compared in this study. The chosen methods were based on generalized linear models, nonlinear dependency of the response variable to the predictors and non-parametric approaches. According to the highest accuracy as well as highest association of predicted and observed values for the CS, the ANN method outperformed in comparison to LR and RF. ANN methods perform non-linear statistical models and can be used to classify a case into a dichotomous response variable. Although complex computations are required for ANN, non-linear types of associations can be checked. This method is able to detect the interactions among several predictor variables . RF apprThe rate of CS is considerably high in Iran which needs significant improvement in mothers’ education, psychological interventions to modify the attitude to CS, improving the quality of vaginal delivery services and eliminating the fear and anxiety of mothers about vaginal delivery. Moreover, ANN classification method was resulted as the best approach to classify a new case into CS based on its determinant factors such as baby’s head circumference, SES, BMI, infant weight and height.Ethical issues  have been completely observed by the authors.


Law no. 281, enacted by the Italian Parliament in 1991, was the first that aimed at managing urban free-roaming cats living in colonies, without killing and/or moving them from their site. It had been anticipated by the Lazio Regional Law no. 63/1988 and subsequently refined by the Lazio Regional Law no. 34/1997. These laws introduced: (i) the cats' right to live free and safe; (ii) the compulsory neutering of cats by the Veterinary Services of the Local Health Unit; (iii) the institutionalization of cat caretakers. Within this context, this paper intends to evaluate the effects of the application of the Italian laws on management of urban free-roaming cats for the years 1988 to 2018. To this end, some indicators have been built and applied to our activity data: number of censused colonies and number of cats; number of stable colonies due to neutering; number of hygiene and sanitary notifications; number of notifications to check cat welfare; number of bites by unowned free-roaming cats; number of notifications of cat poisoning. The number of citizens' requests for institutional interventions by public veterinary services in cat colonies management and, accordingly, the detection of cat colonies yet unknown, seem to confirm the interest of people to control the cat colonies in Rome in a humanitarian way, as evidenced in our data. This fact/phenomenon should be analyzed in its multiple dimensions, also including the many changes and social unrests which have affected the human-cat relationship in the last 30 years. With regard to the evolutionary trend in global thinking and advocacy about unowned urban cat management, as Italian stakeholders, we were born on the right side of the world: in fact, it was back in 1991 that the Italian Parliament passed the first law (no. 281 /1991) that aimed at managing urban free-roaming cats living in colonies, without killing and/or moving them from their site. It had been anticipated by the Lazio Regional Law no. 63/1988 and subsequently refined by the Lazio Regional Law no. 34/1997. Thus, when Sheilah Robertson published her review  origin ; (ii) dependence on/independence from food supplied by human beings; (iii) socialization status to human beings , 3. To aIn order to evaluate the effects of 30 years of protectionist legislation, 7 indicators of our Local Health Unit activity have been constructed . ActivitThe evaluation period ranges from 10 to 30 years see ; furtherSince 2008, the Ministerial Ordinance, and subsequent additions and modifications, has focused on animal poisoning. In the 10 years from 2008 to 2018, a database has been created on the various causes of death, with special attention to cases of poisoning. In fact, public and private veterinarians, police and private citizens can bring the dead bodies of animals and/or the suspected poisoned baits found in our territory see  for our Laboratory diagnoses were made by the Experimental Zoo-Prophylactic Institute of Latium and Tuscany Regions, in Rome, at the Chartered Institute which represents the National Reference Center for forensic veterinary medicine. The Institute routinely performs gross necropsy, histopathology, chemical testing and toxicology screening. The toxin tested is established based on the lesions found during autopsy. The following toxins are included: anticoagulants, pesticides, metaldehyde, strychnine, and zinc phosphide.The total number of censused colonies composed of unowned cats (from 1988) was 1,878 in 2017, 89 of which have gone extinct. Since 2001, the number of new registered colonies of cats has increased, to reach a peak in 2011 , 3; afteOur Unit receives hygiene and sanitary notifications related to all animals in the urban environment, limited to the jurisdiction of Local Health Unit Rome 3 see . The notOur Local Health Unit is also notified of any animal bite reports or claims filed for the whole city of Rome. In 10 years, out of 4,600, 143 were filed over domestic cat bites and only 6 over unowned cat bites.Finally, in 10 years (2008–2017), we received 74 notifications of suspected cat poisoning, 21 of which were positive . The substances most commonly used were rodenticides (anticoagulants) (no. = 9), molluscicide (neurotoxic) (no. = 8) and a mixture of them (no. = 4). Since the above substances were found in edible baits near the dead body of the cats and in the dead cats' stomachs, it is highly probable that it was deliberate poisoning. In fact, the Italian laws forbid using these substances in public places; thus, if a poisoned meat ball is found in a public park, it is evident that it was deliberately put there to eliminate some animals.The other causes of death were traffic accidents, predation by dogs and/or wild animals, infectious diseases and chronic silent diseases.The first result reported here is the fact that in Rome the dynamic of cat populations has been monitored for 30 years, fulfilling the obligations of law, unlike many countries where unowned free-roaming urban cats are rarely quantified . TherefoThe 2006 survey on 103 colonies of free-roaming unowned cats in Rome, based on the data gathered up to 2000 , the undeniable fact is that 204 cat colonies are entirely composed of neutered cats and this makes them stable. Since some abandonment rate, although low, should be presumed along the years, the data seem to confirm the positive effect of the institutionalized management of cats by registered cat caretakers. In fact, few immigrated cats have replaced the dead or adopted cats. The demographic control put into action by TNR is the first step to a responsible management of unowned cat colonies. When a member of our research group (E.N.) started studying unowned free-roaming cat behavior in 1978, before the Italian laws on neutering were passed and no unowned cats were neutered yet, a slight constant increase in the number of cats was recorded throughout the years. The problem, however, was not only the increase in the number of cats, but rather the reason as to why such an increase was not as massive as expected: as a matter of fact, there was mass infant mortality Furthermore, if we consider the number of notifications from citizens asking for the control of unowned cats' welfare in the last 10 years , there is evidence that Roman citizens are increasingly concerned for cat welfare. One of the concurrent causes of this trend could be the educational campaign on urban animals addressed to citizens.Interestingly, in Rome, Toxoplasmosis sero-prevalence greatly decreased between 1991 and 2013. In fact, in 1990–1991 the sero-prevalence was 50.4% (IC 95% range 41–60%) .The different rate of Toxoplasmosis sero-prevalence registered after about 2 decades is mainly attributable to the common practice of feeding cats (unowned and/or pets) with industrial food rather than with home leftovers and/or meat remnants from butchers. But data are still scarce, and more extensive studies will have to be carried out before formulating any conclusion.The number of cat bite reports also deserves some comment: in 10 years, only 6 out of 4,600 reports were registered regarding non owned free-roaming cats. These numbers suggest why cats, unlike dogs, are not feared for their bites and aggressiveness. In fact, even when non owned, cats are not aggressive (with few exceptions) and people do not fear them. As the data discussed here have shown, the reports notified to our Unit from citizens complaining about hygienic and sanitary problems of the environment due to non owned cats, although still rare (on average 4.7 hygienic and sanitary notifications per year), were much more frequent than non owned cats bite reports (on average 0.6 bites per year).Finally, although poisoning is not so frequent, it requires monitoring. Since 2008, thanks to the specific Ministerial ordinance enactment, and to other national laws against animal abuse, the attention of public bodies and private citizens has increased. This has resulted in a parallel increase in the number of reports filed. Of course, abuse and poisoning occurred also before 2008, but they were not notified. This is further evidence that institutionalized cat caretakers have become more sensitive and keener to know the causes of sudden cat deaths, mainly in order to prevent them and thus protect unowned free-roaming cats.In conclusion, notwithstanding the fact that evidence from other parts of Italy point to still growing concerns for unowned free-roaming cat diffusion in terms of human health, animal welfare and social costs , in our The results of this survey suggest that an evolution in the relationship between humans and cats has taken place in Italy, prompting the shift from demographic control to the adoption of a more sensitive attitude toward cat welfare.Lazio Regional Law no. 34 issued on 21/10/1997. Tutela degli animali di affezione e prevenzione del randagismo. Suppl. ord. no. 3, Bollettino ufficiale della Regione Lazio no. 30, 30 ottobre 1997.a Serie Speciale - Regioni n.36 del 09/09/1989.Lazio Regional Law no. 63, issued on 09/09/1988. Istituzione anagrafe canina e protezione degli animali. GU 3Ministerial Ordinance 18th December 2008, and subsequent additions and modifications. Norme sul divieto di utilizzo e di detenzione di esche o di bocconi avvelenati. GU Serie Generale no.13 17/01/2009.National Law no. 833, issued on 23/12/1978. Istituzione del Servizio Sanitario Nazionale. GU Serie Generale n. 360 del 28-12-1978–Suppl. Ordinario.National Law no. 281, issued on 14/08/1991. Legge quadro in materia di animali di affezione e prevenzione del randagismo. Gazzetta Ufficiale no. 203, 30 August 1991.National Law no. 189, come out 20/07/2004. Disposizioni concernenti il divieto di maltrattamento degli animali nonché di impiego degli stessi in combattimenti clandestini o competizioni non autorizzate. G.U. no. 178 of 31/07/2004.We did not need an institutional or governmental permission to carry on the study since it was an observational study and the neutering falls in good veterinary practice allowed by the National and International Laws.Neither euthanasia, or any kind of animal sacrifice, was part of the study.EN, LiM, and AF contributed conception and design of the study. LiM, LaM, SV, RP, LL, FP and AF organized the database. EN wrote the first draft of the manuscript. All authors contributed to manuscript revision, read 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.


Background: This study investigates insomnia as a partial mediator in the relationship between personality and symptoms of anxiety and depression.Methods: The study is based on partly longitudinal data from the ongoing cohort study “Survey of Shift work, Sleep, and Health” (SUSSH) among Norwegian nurses, a survey examining the work situation and health status of Norwegian nurses measured with annual questionnaires. The present study uses data collected in 2012 (Wave 4), 2013 (Wave 5), and 2014 (Wave 6). The final sample at Wave 6 consisted of 2002 participants, of which 91% were females. The questionnaires included items measuring, among others, demographic variables, work time schedule, insomnia , personality (Mini-IPIP) and anxiety and depression .Results: Extraversion and conscientiousness had no significant direct or indirect association with insomnia, anxiety or depression. Neuroticism and insomnia had direct associations to future symptoms of anxiety and depression. Insomnia was also a significant partial mediator of the relationship between both neuroticism and anxiety, and neuroticism and depression, meaning that neuroticism had an indirect relation to symptoms of anxiety and depression through insomnia. When adjusting for previous symptoms of anxiety and depression at Wave 5, insomnia was no longer a significant mediator between neuroticism and anxiety, and only marginally mediated the relationship between neuroticism and depression.Conclusion: The results showed that insomnia may act as a mediator between neuroticism and symptoms of anxiety and depression, but the indirect relationship between neuroticism and anxiety and depression through insomnia is considerably weaker than the direct association. Hence, the mediating effect of insomnia should be interpreted with caution. The sample mainly consisted of female nurses, and the generalizability of the findings to male dominated occupations is limited. Findings from the present study highlight the importance of an integrated approach and strengthen the understanding of how personality and psychopathology are connected. Anxiety and depression are two of the most common health problems in today’s society . The rolThe relationship between personality and psychopathology is complex. Several models trying to elucidate this relationship include the pathoplastic model , the spectrum model , and the more common etiological model where personality is assumed to contribute to the onset of mental disorders . In agrePersonality seems to influence subjective quality and timing of sleep, but not necessarily sleep duration . IndividPersonality traits may as such act as protective or predisposing, as well as perpetuating factors for insomnia , which iIn addition to direct associations, certain personality traits may influence anxiety and depression through their impact on insomnia. Individuals with high scores on neuroticism have an increased risk for experiencing symptoms of insomnia compared to low-scorers , therebyWe argue that these relationships are especially important to investigate among nurses. Nurses are at particular risk of developing anxiety, depression and sleep problems, as they face several physical and emotional challenges in terms of high work load , shift wConclusions about the complex relationships between sleep disturbances, anxiety and depression has previously been somewhat difficult to draw due to small and heterogenic samples and an overreliance on cross-sectional studies. Tracing paths between personality and anxiety and depression through potential mediators can help explain the processes involved in the onset and course of mood disorders. This can have implications for treatment and identifying individuals at risk for psychopathology  and for The present study investigates insomnia as a mediating factor between personality and anxiety and depression using a partly longitudinal design. The use of longitudinal data answers the call for more comprehensive research on the relationship between personality traits, anxiety and depression , includi1.Neuroticism will be positively related to future symptoms of insomnia, whereas extraversion and conscientiousness will be negatively related to future symptoms of insomnia.2.Neuroticism and insomnia will be positively related to future symptoms of anxiety and depression, whereas extraversion and conscientiousness will be negatively related to future symptoms of anxiety and depression.3.Insomnia will partially mediate the relationship between personality and future symptoms of anxiety and depression, also when controlling for previous symptoms of anxiety and depression.The present study is based on longitudinal data from the ongoing cohort study “Survey of Shift work, Sleep and Health” (SUSSH) among Norwegian nurses. This survey examines the work situation and health status of Norwegian nurses measured annually. The first wave of data collection was conducted in 2008–2009 (Wave 1), with subsequent data collection taking place annually starting from 2010 (Wave 2). The present study uses data collected in 2012 , 2013 , and 2014 , respectively.The project was approved by the Regional Committee for Medical Research Ethics (REK) of Western Norway . Informed written consent was obtained from all who participated in the study.N = 6000) comprised of five strata, each containing 1200 nurses maintaining at least a 50% work position, was randomly selected from the member register of the NNO. The criteria for the different strata were time elapsed since graduation, in this case 0–11 months (stratum 1), 1–3 years (stratum 2), 3.1–6 years (stratum 3), 6.1–9 years (stratum 4), and 9.1–12 years (stratum 5). The nurses were invited to participate in the SUSSH survey and received the baseline SUSSH questionnaire in the period November 2008 to March 2009. The nurses received paper formatted questionnaires by postal mail and sent them back by prepaid return envelopes. Up to two reminders were sent to nurses who did not respond. A total of 600 invitations were returned due to unknown addresses, which resulted in 5,400 invited nurses of whom 2,059 nurses (response rate: 38%) returned the baseline SUSSH questionnaire. The instruments included in each questionnaire varied. However, many were repeated in each wave.Nurses were enrolled from the member registry of the Norwegian Nurses Organization (NNO). To be eligible for SUSSH, nurses had to be registered in NNO and work at least half-time. A survey sample (SD = 8.3). Of the 1668 participants who answered the specific question at Wave 6, 331 (20%) worked daytime only, 534 (32%) worked both evening and daytime, 108 (7%) night time only, 620 (37%) worked rotating shift , and 68 (4%) had other work time schedules with both day and night time. For each wave, the same nurses who replied at the first wave were invited to participate again. For Wave 4 the response rate was 76% (N = 2172), in Wave 5 the response rate was 69% (N = 1923), and lastly 71% in Wave 6 (N = 2002).The sample at Wave 6 consisted of 1815 (91%) females and 174 (9%) men. The mean age was 38 years (The questionnaires included items measuring (among others) demographic variables, work time schedule, insomnia, personality, anxiety, and depression.Personality was assessed at Wave 4 using a Norwegian version of the Mini-IPIP, a 20-item short form of the 50-item International Personality Item Pool-Five-Factor Model measure . The scaThe Bergen Insomnia Scale (BIS)  containsAnxiety and depression were assessed at Wave 5 and 6 with the Hospital Anxiety and Depression Scale (HADS) . The insmedsem command in Stata  analysis with maximum likelihood including missing values estimation (MLMV). The analysis for each outcome  included all observed and latent variables in a single step. A correlation between the residuals of the endogenous latent variables anxiety and depression was included, making the model equivalent to multivariate regression. The in Stata  estimatein Stata . The medincluded , as was t-tests with Bonferroni correction for family wise error rate , and both were moderately correlated with insomnia . Neuroticism had moderate to strong correlations to insomnia , anxiety , and depression .The relationship between the variables, means and standard deviations are presented in 2 = 2373.43, p < 0.001. The root mean squared error of approximation (RMSEA) was 0.04, 90% CI . Values below 0.08 are considered acceptable fit, while values below 0.05 are considered good fit. The comparative fit index (CFI) and the Tucker-Lewis index (TLI) is recommended to be at or above 0.90 in order to indicate acceptable model fit (The model fit was χodel fit . In thisp < 0.001), anxiety , and depression . Extraversion and conscientiousness measured at Wave 4 were not significant predictors of the endogenous variables measured at Wave 6. Older individuals were more prone to depression , but not anxiety, while men were slightly more prone to anxiety compared to women . Insomnia had a significant direct relation to both anxiety  and depression . Insomnia also partially mediated a proportion the relationship between neuroticism and anxiety and depression. In addition to the direct association, neuroticism had an indirect association to anxiety  and depression  through insomnia. Thus, 11% of the relationship between neuroticism and anxiety, and 22% of the relationship between neuroticism and depression was explained by insomnia. The residuals of anxiety and depression were strongly associated with each other , meaning that the two endogenous variables shared about 30% of their variance that was not already explained by the exogenous variables.The structural model showing the direct and indirect relations is presented in p = 0.001), but still significant. The direct relation between insomnia and anxiety (β = 0.01), and the indirect relation between neuroticism and anxiety through insomnia (β = 0.01) was no longer significant. The direct relation between neuroticism and depression , between insomnia and depression  and the indirect relation between neuroticism and depression through insomnia  was considerably weakened, but still significant. In all, 18% of the relationships between neuroticism and depression was mediated by insomnia in the adjusted model. The fit statistics of this model indicated poorer fit than the unadjusted model, RMSEA = 0.04, 90% CI , CFI = 0.84, TLI = 0.83, χ2 = 6608.65, p < 0.001. The stability coefficient (r) of HADS A (anxiety) and HADS D (depression) between Wave 5 and Wave 6 were 0.71 and 0.64, respectively (p < 0.001).When adjusting for earlier symptoms of anxiety and depression at Wave 5 (anxiety and depression were not assessed at Wave 4 in the current study), several changes in the structural model were observed. The direct relation between neuroticism and anxiety was reduced . In large-scale surveys, short inventories are preferred, although few items often come with the cost of reduced internal consistency , as obseOur findings highlight the importance of an integrated approach to research on the topic, and the need for taking bidirectional and circular relations into account. The extensive research on nurses, especially related to sleep, health, and shift work  reflectsWe found a direct relationship between neuroticism and insomnia, anxiety and depression in line with previous studies. In addition, the present study demonstrated an indirect relationship between neuroticism and anxiety and depression through the association between neuroticism and insomnia. However, when adjusting for previous symptoms of anxiety and depression, insomnia still partly mediated the relationship between neuroticism and future symptoms of depression, but not anxiety. No significant relationships were found between conscientiousness, extraversion and symptoms of anxiety and depression. In sum, the results indicate that among the Five Factor Model personality traits, only neuroticism seemed to be a predictor for anxiety and depression in the present study. However, as the sample mainly consisted of female nurses, generalization to other and more male dominated professions is challenging. In conclusion, insomnia may act as a partial mediator between neuroticism and anxiety and depression, but the direct relation between neuroticism and anxiety and depression is considerably stronger than the indirect association through insomnia.The project was approved by the Regional Committee for Medical Research Ethics (REK) of Western Norway .IS-L and TS conceived the present idea. TS was in charge of the overall execution and planning of the present study, contributed to all parts of the article and wrote the first draft of the manuscript, edited all drafts, and developed the introduction, hypotheses, methods, and discussion together with IS-L and EL. HK performed the statistical analyses and wrote the first draft of the results. EL and IS-L contributed to all parts of the study, the introduction and discussion in particular, and edited all drafts. SP, BB, SW, and BM designed the SUSSH-study, collected the data, and edited the drafts of the manuscript. All authors contributed to the final work and revisions on 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.


A broad line of research has conceptualized personality based on the interaction of two aspects: interpersonal relatedness and self-definition. This theoretical corpus understands these functions as two poles according to the patterns of interaction and relevance in personality. Additionally, the exacerbation of one of these poles generates a psychopathological model that identifies three types of depressive experience: anaclitic, introjective, or mixed pattern. Understanding the lack of interest as a key symptom of depression, this experiment evaluates a relation for anhedonia and the polarities model configuration using an empirical and experimental protocol. We tested 177 individuals using the Beck Depression Inventory (BDI) subscale for anhedonia and a visual discrimination task with a specific reward system, which was implemented to study reinforcement sensitivity. Participants were classified into four groups by the polarities of experience model. The subscale's results showed that individuals with an introjective character exhibited an enhanced anhedonic symptomatology but no co-occurrence of this evidence on the experimental protocol. These results empirically support the two polarities of the depressive personality model and raise new questions regarding how to experimentally test this relation. Blatt's  PolaritiFurthermore, there is a significant body of evidence about the lack of interest in positive experiences (anhedonia) in depression, which is an essential component of many diagnoses , 13. It Considering the important clinical and theoretical contributions of the POE model, little has been studied experimentally . In thisSD: 1.65, 106 women). As an important exclusion criterion, we did not select participants with self-reported symptoms of depression . Each participant completed one experimental session and received $7 USD. Informed consent forms were signed, and the guidelines of the Code of Ethics of the World Medical Association—Declaration of Helsinki were completely followed. The ethics committees of the Universidad del Desarrollo, Pontificia Universidad Católica de Chile, and the Universidad de La Frontera approved the study at all stages.One hundred seventy-seven undergraduate students participated in the study . Additionally, each of the participants answered the BDI to confirm the presence of self-reported depression symptomatology. In addition, the BDI's anhedonia and melancholia subscales were used for analysis. These subscales were built according to Pizzagalli et al.  with theRegarding the experimental manipulation Figure , particiRichcorrect denotes the trials in which the participant responded correctly to the condition that had an enhanced reinforcement. On the other hand, Leancorrect considered the trials in which the participant responded correctly to the diminished reinforced condition. Richincorrect and Leanincorrect refer to the trials in which the participant performed erroneously for each of the rewarded condition.Behavioral performance was analyzed using the signal-detection theory by calculating both response biases (Log-B) toward the more frequently rewarded stimulus , 19. AddF = 10.51, p < 0.01, η2 = 0.15]. Post-hoc comparisons (Bonferroni) revealed that the normal group presented significant melancholia differences with all the other groups  = 5.64, p < 0.01, η2 = 0.08, Figure SE = 0.32, p < 0.01, normal vs. mixed AI ΔM = – 0.98, SE = 0.30, p < 0.01 Bonferroni). This first result confirms our hypothesis, indicating that introjective individuals, our group of interest, differ from the normal characterization in terms of anhedonia. In the same line, the anaclitic group as introjective's counterpart does not differ in anhedonia from the normal group.First, to determine the POE categories, the DEQ was analyzed by extracting Dependency and Self-criticism factors. The categorization limits used to determine the POE groups follow the standard literature criterion . The samF = 42.85 p < 0.01]; however, no interaction is observed between this factor and the POE Group (p = 0.34), which allows us to rule out the possibility that the anhedonia variability reported above is simply explained by the level of depression in general.Finally, to rule out the possibility that our results could be interpreted simply as depression in the participants, i.e., a confounding effect of depression on anhedonia, we repeated the analysis considering six levels of depression . For thiF = 81.41, p < 0.01, ηp2 = 0.19 Greenhouse-Geisser corrected] and Condition  without any interaction among these three factors  or with the POE main effect group (p > 0.17). Regarding performance, a significant main effect of POE group  and an interaction between Blocks and Condition  were observed. Post-hoc analysis (Bonferroni) showed significant differences between the anaclitic and normal groups . No other effects were found . In sum, results show that all groups improved their RTs through the task. Regarding the performance, only the anaclitic individuals showed POE group differences, improving their performance differentially through the Blocks of the task.Results related to the experimental task show that there are no differences between POE groups' reward responsiveness and no diminished sensitivity to reinforcement in introjective individuals. Measurement of performance followed a similar pattern. First, Response Time (RT) and the mean Error Rate were analyzed using a repeated measures ANOVA with Blocks  as within factors. POE groups  and Condition (rich and lean) were considered as between factors. We also included all possible interactions. Participants were considered the random factor. Before the analysis, mean RTs were log-transformed, and Error Rate was arcsine-transformed to approximate normal distribution. Regarding RTs, results indicated a significant main effect of Blocks  with a difference between POE groups  but without interaction between these factors (p = 0.75). In the same line, ANOVA on Response Bias again showed only a significant main effect of Block . No other effects were found . Interestingly, through a linear regression, we could not show a relationship of this measure with the level of anhedonia (ps > 0.78) or with the level of depression (ps > 0.83). Consistent with the performance analysis (Error rate and RTs), Discrimination (Log-D), and Response Bias (Log-B) scores mainly increased as a function of Blocks. POE configurations were not significantly different in terms of reinforcement sensitivity  and Response Bias (Log-B). The former denotes the subject's capacity to differentiate the two stimuli of the task (long or short mouth), and the latter represents the tendency to be impacted by the task reinforcement program. To test this, a repeated-measures ANOVA was run on Log-D and Log-B with factors of Blocks, POE group, and their interaction. Results for Discriminability showed a significant main effect of Blocks . In thiHowever, the results related to the questionnaires did follow the direction of our hypothesis, having significant differences particularly for introjective individuals on BDI's anhedonia subscale. Moreover, if sensitivity to reinforcement was analyzed just between introjective and normal individuals, some incipient evidence appears to support this distinction. Undoubtedly, more and better evidence is needed to settle this question.In conclusion, all these results could be considered preliminary evidence suggesting a potential difficulty experienced by introjective subjects in being stimulated by positive cues. The understanding of the POE has been wider than merely that of the perspective of psychopathology; however, the intensity of the depressive experience undoubtedly has clinical repercussions that manifest in mood and in its behavioral correlation. The anhedonia as part of the depressive constellation allows us to differentiate how the loss of interest is a symptom strained by one of the polarities of the experience.JS, CM, and MK conceived and designed the experiments. JS performed the experiments. JS and AV-C analyzed the data. JS, AV-C, MK, and CM wrote the paper.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.