Background: Autism spectrum disorder (ASD) often co-exists with attention deficit/hyperactivity disorder (ADHD), which may aggravate functional impairment. However, it is unclear how comorbid ADHD symptoms influence the adaptive behavior and social interaction deficits of children with ASD.Methods: The study enrolled 340 children (ranging from 2 to 14 years) with ASD, with comorbid ASD and ADHD, or with typical development (TD). A psychological evaluation involving adaptive behavior and social function was conducted using the Vineland Adaptive Behavior Scale, Second Edition (VABS-II) and the Social Responsiveness Scale (SRS).Results: There was a high prevalence of ADHD symptoms (46.6%) in children with ASD, and children with ASD + ADHD presented the worse profile of ASD symptoms. The ASD + ADHD group had higher scores on VABS and lower scores on SRS in comparison with the ASD alone group and TD group. The regression analysis revealed that ASD symptoms and ADHD symptoms were significantly associated with greater impairments in adaptive behavior and social function. The ADHD symptoms were responsible for an additional 0.8% of the variance in adaptive behavior, and 9.5% of the variance in social function.Conclusions: More severe ASD symptoms and greater impairment in adaptive function and social ability were found in children with ASD and comorbid ADHD, highlighting the need to identify ADHD comorbidities early on in children with ASD and to reduce their negative impact on functioning. Autism spectrum disorders (ASD) are behaviorally defined as neurodevelopmental disabilities, which are characterized by deficits in reciprocal social interaction and communication as well as by restricted, repetitive patterns of behavior or interests , 2. ReceDiagnostic and Statistical Manual for Mental Disorders, Fifth Edition (DSM-5) in 2013, clinicians are able to make a diagnosis of ADHD in the context of ASD. This has led to increasing interest in the overlap of the clinical presentations of ASD and ADHD symptoms. Epidemiological studies have identified that the comorbidity rate of ADHD in ASD ranges from 14 to 70% in different countries  had ever received an ADHD diagnosis . Accordi.4% had eountries . To dateountries –14.Adaptive behavior and social function are the most important measures in evaluating functioning in ASD. Adaptive behavior refers to the ability to perform the daily activities required for individual and social sufficiency , and is Therefore, this study aims at clarifying the effect of ADHD symptoms in the context of ASD on adaptive behaviors and social function, and to analyze the independent effects of the ADHD symptoms on functional impairment in ASD children. We hypothesized that the children and adolescents with comorbid ASD and ADHD may exhibit more severe autism symptomatology, lower adaptive skills, and poor social function. Here, the present study recruited a case-control sample of children and adolescents (2–14 years old) with confirmed ASD, ASD with ADHD, and TD. This study would provide a more comprehensive understanding of the functional impairments in ASD with comorbid ADHD, and offer basic evidence for the development of personalized treatment training programs for individuals with ASD comorbidities.This cross-sectional study included 340 children, ranging from 2 to 14 years, who were consecutively recruited from the general public and the Child Developmental and Behavior Center of Harbin Medical University, Harbin, China. Diagnosis of ASD and/or ADHD was based on two independent specialist clinicians from our research team using the diagnostic criteria specified in DSM-5. The current gold standard for ASD diagnosis is based on clinical observation, substantiated by standardized testing of the patient with the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS). Diagnoses of ADHD were also confirmed by using the Vanderbilt ADHD Parent Rating Scale (VADPRS). Exclusion criteria included (1) neurodevelopmental disorders of known etiology , (2) significant sensory or motor impairment, and (3) serious chronic diseases. The neurodevelopmental histories and mental states of the typical development (TD) group were also evaluated and confirmed by neuropediatric specialists. The sample description and scores on primary measures were showed in All participants recruited for the purpose of the research received oral feedback and a written summary of the results of evaluation without any payment. Caregivers provided written informed consent and children provided assent if possible. The procedures related to this study were approved by the Institutional Review Board of Harbin Medical University.In this study, all psychologists or trainees involved in administering the measurement protocols had established research reliability. Participants were evaluated using the ADI-R, ADOS, VAPRS, Vineland Adaptive Behavior Scale; Second Edition (VABS-II), Social Responsiveness Scale (SRS), Childhood Autism Rating Scale (CARS), Autism Behavior Checklist (ABC) and a cognitive assessment. Due to applicability, cooperativity and compliance from patients and their guardians, some cases did not complete all above examinations. Multiple assessments were available for many cases in this corpus. However, only the most recent assessment was retained for each case.The ADI-R  is a semThe ADOS  is an inThe Childhood Autism Rating Scale (CARS)  was use The ABC  was fillThe VADPRS was scored using the National Institute for Children s Health Quality s criteria, and consists of 45 statements on children s behaviors, 9 of which correspond with behaviors included in the Diagnostic and Statistical Manual of Mental Disorders for the predominately inattentive subtype of ADHD and 9 to the hyperactive/impulsive subtype. Higher scores reflect more severe of problem behavior of children with ADHD. This questionnaire had good reliability and validity , 27, andThe VABS-II, is a measure of adaptive behavior based on parent interview with validity and reliability from birth to adulthood, and commonly incorporated in assessments for ASD. The VABS yields domain scores in the areas of communication, daily living skills, socialization, and motor skills, as well as an overall adaptive behavior composite. Lower scores indicated greater impairment of adaptive behavior. The VABS-II has demonstrated strong reliability and validity . In the The SRS  is a 65-M = 100 and SD = 15. In this study, we use the full scale IQ as an indicator of IQ.The Wechsler Preschool and Primary Scales of Intelligence  or Wechst-tests or one-way analyses of variance (ANOVA), followed by post-hoc Welch two-sample t-test and Least-significant (LSD). To non-normal distribution of data, multiple comparisons among three groups were conducted by Kruskal-Wallis H test and differences between two groups were assessed by Mann-Whitney U-test for post-hoc analysis. Pearson's chi-squared test was used to compare gender composition between groups. Linear regression model with enter method (VABS and SRS) as outcome variable was conducted to test the associations of potential explanatory variables. The demographics  as covariates were entered into the first block, followed by ASD diagnosis in the second block and ADHD diagnosis in the third block. The model R2 is reported as interpretation of the meaning of such individual coefficients is limited by multicollinearity. Significance level was set at p < 0.05 (two-tailed). SPSS Version 21.0  was used for all statistical analyses.Comparisons between groups were examined, as appropriate, by means of independent samples F = 0.149; p = 0.862 and χ2 = 4.533; p = 0.104). However, IQ was significantly different among the groups , and the post-hoc analyses showed that IQ was significantly lower in the ASD + ADHD group, compared with the TD group (p < 0.001) and the ASD group (p < 0.013). Meanwhile, there was significantly lower IQ in the ASD group, compared with the TD group (p < 0.001).Overall, the 340 children in our study included 293 boys and 47 girls with a mean age of 5.85 ± 2.65 years: 134 children with ASD (ASD group), 117 children with ASD and ADHD (ASD + ADHD group) and 89 with typical development (TD group). The ADHD comorbidity rate was 46.6% in the children with ASD. As shown in t = −3.052; p = 0.003), ADOS , and ABC . However, the scores for the CARS were not significantly different between the two groups  (The ASD + ADHD group had higher scores than the ASD group in the ADI-R (= 0.694) .2 = 84.932; p < 0.001), Daily living skills , Socialization , Motor skills , and the Composite scale   . The posTD group .F = 15.872; p < 0.001), social cognition , reciprocal social interaction , social motivation , autistic mannerisms , and SRS total scale   . Subsequs domain .2 value increased by 0.8% , which was statistically significant. The ASD diagnosis  and ADHD diagnosis  were negatively correlated with the VABS-II score. For the SRS, when the ASD diagnosis variable was added alone (model 2), it explained 9.6% of the variance in the SRS scores; when the ADHD diagnosis variable was further added (model 3), the R2 value increased by 9.5% , which was statistically significant. The ASD diagnosis  and ADHD diagnosis  were significantly positively correlated with the SRS score.After controlling for demographic confounders , for VABS-II, when the ASD diagnosis variable was added (model 2), 7.3% of the variance was explained by ASD diagnosis; when the ADHD diagnosis variable was further added (model 3), the RIn this population-based case-control study, we found a high prevalence of ADHD symptoms (46.6%) in children with ASD. Children with ASD + ADHD exhibited more severe ASD traits, and a greater degree of weakness in adaptive profile and social function. Moreover, ADHD symptoms could aggravate the impairment of adaptive behavior and social function in individuals with ASD.Previous research , 33 has In extrapolating from the current data, children with ASD + ADHD had worse performance in adaptive behaviors than children with only ASD and children with TD, which were noted in the communication, daily living skills, socialization and motor skills subdomains, and in the VABS composite. The findings of the present study were in line with previous reports and provide supportive evidence that ADHD symptoms have an impact on adaptive behaviors , 34. AvnA large-scale population-based study demonstrated that ASD symptoms explained 18% of the variance in adaptive behavior, while the same variables were responsible for 14% of the variance in social function . This stOne potential explanation for the findings is that symptoms of comorbidity will confuse the diagnosis of ASD, so that when ASD is diagnosed, the symptoms are more severe and the function is more impaired than in other children of the same age. For example, a study from the National Survey of Children's Health found that ~20% of 1,500 U.S. children aged 2–17 years with parent-reported ASD were initially given a diagnosis of ADHD, and were diagnosed with ASD three years later than children without ADHD concerns , compareIn addition, it is well-known that the SRS and VABS assessment outcomes are affected by the individual characteristics of children, such as age, gender and cognitive level . The EurThere are some limitations to the current research. First, we did not enroll children with only ADHD in the analysis, and the study could have benefited from comparisons with the ADHD population. Second, there is a selection bias in our research. On the one hand, all participants involved in this study were from Heilongjiang Province, on the other hand, fewer older children are recruited, so it is difficult to extrapolate the results to the general population. Finally, whether the children with ASD and ADHD received medical treatment for ADHD was not taken into account. For a more detailed understanding of the changes of adaptive function and social function in ASD, a longitudinal study is needed to explore further the differentiated executive strategies required in the interventions designed for children with ASD and ADHD.In summary, our results indicate that, for individuals with ASD who are diagnosed with ADHD, the characteristics of the comorbidity made their ASD symptoms more severe, and exacerbated their deficits in adaptive function and social ability. In light of the these findings, it is important to identify ADHD comorbidities early on in children with ASD, and to explore effective medical and behavioral interventions to reduce the impact of ADHD symptoms, thereby hopefully leading to improved functioning.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by Harbin Medical University. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin. Written informed consent was obtained from the individual(s), and minor(s)' legal guardian/next of kin, for the publication of any potentially identifiable images or data included in this article.MZ and CS conceived and designed the research. YL, LW, SX, SP, and JZ performed clinical assessment. YL analyzed the data and wrote the paper. CS and MZ contributed reagents, materials, and analysis tools. 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.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.


Light-emitting diodes (LED) are widely employed in display applications and lighting systems. Further research on LED that incorporates carbon nanostructures and metal nanoparticles exhibiting surface plasmon resonance has demonstrated a significant improvement in device performance. These devices offer lower turn-on voltages, higher external quantum efficiencies, and luminance. De facto, plasmonic nanoparticles, such as Au and Ag have boosted the luminance of red, green, and blue emissions. When combined with carbon nanostructures they additionally offer new possibilities towards lightweight and flexible devices with better thermal management. This review surveys the diverse possibilities to combine various inorganic, organic, and carbon nanostructures along with plasmonic nanoparticles. Such combinations would allow an enhancement in the overall properties of LED. Nanomaterials have engendered the miniaturization of devices, bringing about advances in a variety of fields, such as biomedicine, environmental technologies, optoelectronics, and photocatalysis –2. In paInorganic LED consist of inorganic semiconductor materials in the active region, for example thin films of GaAs that emit in the red to near-infrared >700 nm) region . Ga-base00 nm regOrganic light-emitting diodes (OLED) possess several interesting properties and are therefore gaining popularity . Their lSeveral methods have been proposed to tune the properties of LED. To that end, multiwall carbon nanotubes (MWNT) and single-wall carbon nanotubes (SWNT) have been applied to various layers in LED, such as the emissive layer (EML), the hole transport layers (HTL), the electron transport layers (ETL), the cathode, and the anode –21. EnhaI–V) characteristics. A list of various abbreviations employed in this review is available in This manuscript reviews the effect of carbon nanostructures, such as carbon nanodots, carbon nanotubes (CNT), and graphene (GR) towards producing cost-effective and efficient LED. A second strategy consisting of enhancing the optical and electrical properties of LED via SPR of MNP is also surveyed. The LED covered in this review include inorganic LED, OLED, inorganic/organic LED, and HyLED. The feasibility of incorporating GR and CNT in large-scale devices is also discussed. Even though plasmonic nanoparticles (NP) are a developing field, their applications are nonetheless promising. The effect of these nanostructures on the performance of LED when included in individual layers  is analyzed. Subsequently, various characteristics of LED containing carbon nanostructures and plasmonic NP are discussed in terms of EQE, internal quantum efficiency, luminance, EL, and current–voltage  with a high electrical conductivity and a high transparency ranging from the UV to the red region. Additionally, it should also be cost-effective and producible on a large scale. For this purpose, transparent conducting oxides (TCO), such as thin films of In studied –34. The trations . Althougtrations .I–V results in Carbon-based nanostructures play a dual role at the anode. Light-emitting diodes are self-heating, current-sensitive, and luminously intensive light sources. They are also highly dependent on ambient temperatures. The lifetime of LED, in particular OLED, is on an average reduced by 30–50% for each 10 °C rise in temperature. Further, self-heating in LED causes degradation of the active region, which further affects the efficiency and the operational lifetime of LED. Therefore, in order to obtain adequate performances from LED, proper thermal management of the device is required. In this regard, graphene at the anode tends to alleviate self-heating issues as it disperses the heat away from the active layer. This in turn also reduces the thermal resistance between the device layers –38. Furt2 and 1.4 cd/A, respectively, at a turn-on voltage of 6.6 V. These values are however not as satisfactory as the ITO-based device: 6000 cd/m2 and 1.9 cd/A at a turn-on voltage of 6.2 V. One reason for lower SWNT device performance is associated with its lower transmittance of 44% compared to 90% of ITO. A higher transmittance is nonetheless possible by optimizing the interface between HTL and SWNT via a parylene layer, which tends to increase the transparency of SWNT. Guo et al. also reported an increase of about 40% in the EL intensity under a 5 mA current injection at room temperature in AlGaInP LED, after the deposition of graphene onto the anode or the GaP surface . Other cThe anode can be supplemented with various metal nanostructures for improved performance. 3 + DCM/Alq3/LiF/Al red LED. The SPR absorption of Au nanorods and nanospheres were approx. 650 and 520 nm, respectively. Therefore, Au nanorods were able to enhance the red emission from the LED with an EQE of 6.8 × 10−4 at 10 V compared to the device with Au nanospheres (EQE = 2.4 × 10−4).Equivalent to Ag, SPR of AuNP can also be applied to the anode in order to enhance the overall EL of the LED. Both of these MNP tend to increase the quantum efficiency of the LED. However, owing to the differences in the ranges of their SPR energies, different emission wavelengths are enhanced. In general, SPR of AgNP favors the quantum efficiency of the blue emission. On the other hand, Tanaka et al. reported that the SPR of AuNP positively influences the quantum efficiency of the red emission . In addiIn addition to the shape of AuNP, their size also influences the performance of LED. To that end, AuNP of diameters 2 and 5 nm were combined with CNT and deposited onto a p-GaN-based anode in a multiquantum-well LED . The EL Based on the data listed in The optimization of charge carrier injection also consists of reducing the driving voltage of the LED. For achieving this, holes should be readily injected from the high-work-function anode surface , while the electrons should be injected from the low-work-function metal cathode surface. Therefore, HTL should possess excellent charge mobility and maintain morphological stability. Moreover, it should have an appropriate highest occupied molecular level (HOMO), ensuring a low energy barrier for hole injection from the anode into the EML. A suitable lowest unoccupied molecular level (LUMO) should be capable of blocking electron injection from the EML to the HTL. Thus, HTL play a very important role in OLED and HyLED.3/Li:Al . Th. Th2 sheThe performance parameters of OLED, for example, turn-on voltage, operating voltage, current/power efficiency, and lifetime are strongly dependent on the physical parameters of the cathode material . A catho3 EML. Carbon nanomaterials, such as graphene and SWNT present interesting alternatives to overcome the drawbacks of metal and metal nanocomposite cathodes in OLED. Klain et al. have reported one possibility by doping graphene with n-type Ca [I–V characteristics of the device with Ca-doped graphene/Alq3/Ag manifest a two-fold increase in current (at 2 V bias) as compared to only graphene. Similarly, Chang et al. have doped graphene with n-type CsF or Cs2CO3 on a SiO2 substrate, thus reducing the work function of graphene from 4.4 to 3.2 eV, which was used to fabricate blue light-emitting OLED with maximum brightness of 1034 cd/m2 [There are a few examples where plasmonic NP are used at the cathode to enhance the overall emission of the LED. Plasmonic AgNP have been inserted in Al (150 nm)/LiF (1 nm) cathode layer and a PL enhancement was observed . In fact-type Ca . The 1 n34 cd/m2 . On the 34 cd/m2 . However2, ZnO, SnO2 in combination with Ag, Au, and PtNP has shown increment in the luminance and reduction in the operating voltages of the devices.This article has provided an overview of the combination of various nanostructures that enhance the overall properties of various types of LED. In particular, CNT and MNP exhibiting SPR improve several characteristics of LED, such as lower turn-on voltages, higher EQE, and high luminance. The versatility of these nanomaterials lies in the fact that they can be accommodated into one or several layers of the LED. For example, carbon-based nanostructures can be added to the anode, hole injection, and transport layers as well as the EML. On the other hand, SWNT are still being tested as a viable cathode material. Depending upon the layer, these carbon-based nanostructures are able to enhance current spread, injection, and recombination lifetime values. Similarly, plasmonic NP, such as Au and Ag clearly enhance LED properties and can be integrated in all the layers of the device structure. Furthermore, incorporation of metal oxides, such as TiOFor several decades, inorganic LED based on III–V group semiconductors  have been extensively studied and improved. More than 50% EQE for AlGaInP (red) and InGaN/GaN (blue/green) emitters has already been achieved with a future possibility of reaching up to 80%. Moreover, achievement in the device stability of up to 20000 h is remarkable for inorganic LED. However, these inorganic LED have poor color quality and they are fabricated with rare, costly, and non-flexible materials, which hinder their wide scale applications in wearables and display technologies. In addition, the self-heating of such structures is unavoidable. Carbon nanotubes and plasmonic NP exhibiting SPR have shown their superiority in enhancing the color quality of these inorganic LED by enhancing the PL, EL, current efficiency, and density. Moreover, graphene and SWNT incorporated into the anode have opened opportunities for thermal management in flexible inorganic LED.3 and derived version of PPV polymer, whereas QD based on Cd, Zn, Se, and S are mainly used for QLED. Both technologies have many advantages over traditional inorganic LED and liquid crystal displays in terms of low power consumption, wider view angle, higher resolution and cost-effectiveness. However, device degradation is common in both OLED and QLED due to charge accumulation in the layers. In the case of red QLED, HTL is rather stable and the device degradation rate is therefore low. On the other hand, in the blue QLED, their poor lifetime is caused by the quicker degradation of ETL. A similar degradation in OLED has also been observed but mainly in the HTL; the poor hole injection ability of polymers is also a cause for concern. From a commercial point of view, the present OLED displays are expensive as compared to QLED displays consisting of Cd-based QD. Graphene and CNT could be viable options in slowing or circumventing the degradation of HIL in OLED and QLED when combined with polymer nanocomposites.Currently, OLED and QLED are dominating the display market. Light sources in OLED mainly consist of Alq2 could also include a graphene oxide HIL, in which a luminance of 56000 cd/m2 has been reported in such OLED. Doped ZnO in the ETL is also a suitable candidate for high-luminance blue OLED. Since the degradation of these nanocomposites is relatively slow as compared to pure CNT, they could therefore provide a workable pathway to enhance the lifetime of the blue QLED. Moreover, due to the localized SPR of AgNP the brightness of blue QLED can also be improved significantly. Enhancement of the red luminescence has been possible by the addition of AuNP. Enhancing the green luminescence has not been widely studied in OLED and QLED. However, AgNP has the potential to enhance the green emission through the engineering of its shape and size in order to modify their SPR properties.In order to enhance the color purity of the OLED-based displays, SWNT combined with an emissive polymer tend to increase the luminance of the device and thereby achieve a higher color saturation. Nevertheless, SWNT display an emission spectrum with full width at half maximum of approximately 30 nm, which is very close to the color saturation of QLED displays (≈25 nm). The blue/green emission from InGaN LED, ZnO NP, and OLED is enhanced through the SPR effect of AgNP, which in turn could counteract the high external luminance. Thus, the low brightness and short operation lifetime of blue QLED could be improved by using CNT–polymer or CNT–metal oxide nanocomposites as ETL and incorporating AgNP in this layer. Further strategies to counteract the outdoor luminance of 7000 cd/mOLED- and QLED-based displays are commercially available. Nonetheless, cost-effective and better quality displays are constantly being developed. The combination of various polymers with inorganic components or HyLED could very well fulfill the future needs of the display and lighting market. Even though HyLED is commercially available for lighting applications, further work still needs to be carried out in order to implement them in display technologies. Nevertheless, a combination of organic, inorganic, carbon nanostructures, and plasmonic NP could very well pave the way for future display technologies.


To evaluate the reliability and validity of the short version six-item Quality of Life Scale (QOLS-6) and the consistency of subject-proxy data in a case-control psychological autopsy study on elderly suicide in rural China.A two-stage stratified cluster sampling method was used to select research sites. We used self-administered questionnaires to collect proxy-based information from informants and subject-based information from living comparisons.A total of 242 pairs of suicide cases and living comparisons were selected in our research. Subject-proxy consistency for QOLS-6 was good (Intraclass correlation coefficient (ICC) was 0.688) in living controls. Good internal consistency of QOLS-6 was validated by Cronbach’s α being greater than 0.6 among suicide cases and living comparisons. The mean scores of quality of life were lower among suicide cases than living controls. Quality of life was negatively correlated with depression, loneliness, hopelessness, impulsiveness and stressful life events, while it was positively correlated with activities of daily living and family function.QOLS-6 has good reliability and validity, which can be used for assessing quality of life among Chinese rural older adults. It is shorter and easier than any other scale for measuring quality of life and can be used as a screening tool in future studies. The World Health Organization defines quality of life as an individual’s perception of their position in life in the context of their culture and value systems. It is affected in a complex way by the person’s physic, psychology, level of independence, social relationships, and environment .Quality of life includes a person’s physical health, psychological state, and social relationships. According to the definition of healthy, quality of life can be considered a reflection of the health status. Some researchers found that quality of life is one of the critical factors leading to suicidal behavior .As the population aging process accelerates, we should pay more attention to quality of life among the elderly to ensure that their life is worth living. The elderly’s income may be reduced due to loss of work, and the living environment also undergoes certain changes. With advancing age, the elderly begin to develop chronic diseases, face reduced income, and lose some connection with their networks. These will inevitably cause declines in their quality of life.The population aged 60 or older reached 900 million worldwide . In ChinThere are many well-developed scales used to measure quality of life, such as WHOQOL-100, WHOQOL-BREF, EQ-5D, SF-36, and so on . Howeverper capita of 31 provinces in mainland China  was always the person who lived with a suicide case or living comparison, whereas the second informant  usually didn’t lived with them. Interviews with informants of living comparisons were conducted as soon as comparisons and their informants were identified, while interviews with informants of suicide cases were conducted in a schedule of 2–6 months after death. Each informant was interviewed separately by one trained interviewer. The average interview time was 90 min. The content of the interview with the informants was to reflect the situation of the target person (suicide case or living control) rather than the informants. The information of a suicide case was obtained from the description of two corresponding informants. Besides, the information of a living control was obtained by himself as well as the corresponding informants. Thus, the information obtained from the living control themselves was also called the gold standard. Questionnaires are almost the same between informants and living controls themselves, the questionnaire of informants is interviewed for information of the target person (a suicide case or a living comparison) but not informants. A total of 242 suicides and 242 living controls were investigated in this study. Informed consent was obtained from participants in this study by signing the informed consent form prior to the interview. The participants of suicide case group were the informants of suicide cases, but those of living control group were living controls and their informants. This study was approved by the Human Research Ethics Committees of Shandong University , Central South University , and Guangxi Medical University .A two-stage stratified cluster sampling was used to select research sites. Firstly, according to the GDP nd China , 3 proviThere were some discrepancies and differences from two informants for a target person, thus the information needed to be integrated. For the demographic characteristics, the information provided by the first informant was more reliable than those from second informant. If the target person has behaviors that increase the risk of suicide, this answer of informant should be adopted. Because when one of the two informants observed targeting behavior, it may exist.Demographic data such as sex, age, education level, family income, marital status, employment status, and living arrangements were collected. Education level included below primary school, primary school and above primary school. Based on 33 and 66 percentiles, family annual income in Chinese yuan (CNY) was divided into three groups: <3,600 yuan, 3,600–10,000 yuan and >10,000 yuan. For marital status, people who were married and living with the spouse or cohabiting were classified as “stable marital status”, while people with another marital status  were classified as “unstable marital status”. Being left-behind is defined as all adult family members who have been away from home for at least 10 months and had visited the elderly no more than twice in the nearly 12 months prior to death/investigation.Quality of Life scale (QOLS-6)  developeGeriatric Depression Scale (GDS) , ChineseDescriptive analysis, McNemar’s test, paired t-test, Wilcoxon signed-rank test were used to compare demographic characteristics. Intraclass correlation coefficient (ICC) was used to evaluate the agreement between proxy-based data from informants and subject-based data from living controls (gold standard). Exploratory factor analysis was used to analyze structural validity of QOLS-6. Concurrent validity of QOLS-6 were examined by using Spearman’s correlation analysis between QOLS-6 and other related scales.P values were two-sided, and P values < 0.05 were considered statistically significant.Statistical analysis was performed by using SPSS 23.0 for Windows . All reported P < 0.001).A total of 242 elderly suicide cases and 242 living comparisons were investigated. As shown in Cronbach’s α of suicide cases and living controls was 0.641 and 0.782, respectively, which indicated that the internal consistency of QOLS-6 was good.The consistency between gold standards and proxy information among living controls is shown in χ2 = 365.350, P < 0.001 for suicide victims and KMO = 0.737, χ2 = 449.878, P < 0.001 for living comparisons. This study was appropriate for exploratory factor analysis to discuss the factors structure, because both groups have KMO > 0.600 and P < 0.05.Data on suicide cases and living controls of QOLS-6 were performed using the Kaiser–Meyer–Olkin (KMO) measure of sampling adequacy and Bartlett’s spherical test. The results of this study were KMO = 0.659, Two common factors were extracted using exploratory factor analysis. The cumulative variance percentage of these two factors was 65.847% for suicide victims and 69.032% for living comparisons. Scree plots of exploratory factor analysis of suicide cases and living controls are shown in The concurrent validity of QOLS-6 were examined using Spearman’s correlation coefficients between scores of QOLS-6 and other related scales. As shown in P < 0.001).As shown in This study was designed to assess the reliability and validity of QOLS-6 through psychological autopsy among elderly suicide cases and controls in rural China. The scale reported in this study provides a useful and practical tool much needed for research on older adults. It evaluates quality of life in three dimensions: physical, mental, and social well-being. The result showed that QOLS-6 had good reliability and validity among Chinese rural older adults. This instrument is simple to use and well accepted by rural residents or others with a minimum of primary school education.It is important to use a reliable scale to measure quality of life for suicide prevention. Poor quality of life is associated with increased risk of suicide . By contThe short version of the QOL scale has good reliability, and proxy data are reliable for evaluating the quality of life of the target population. The ICC between gold standard and informants is greater than 0.6, which indicates that the quality of life obtained through proxy data is reliable. This result is consistent with other studies . ICC valMoreover, the scale has good construct validity. Two factors were found for the suicide and control groups, which could be defined as the internal and external components, respectively. The internal components mainly reflect the physical, psychological, economic, and working conditions, while the external components are mainly related to relationships with family or others. The items which the factor loading concentrated on were consistent both in suicide and comparison cases, which indicated that the scale’s structural validity was acceptable.The scale has good concurrent validity. Older adults with depression, loneliness, hopelessness, impulsiveness, or low family function have a poor quality of life. Previous studies indicate that depression is associated with quality of life, and people with good quality of life suffer less from depressive symptoms . SimilarThis scale has practical significance for clinical work. Through above analysis, we can know that quality of life is related to suicide and various other mental health problems . Therefore, we can use it to predict and prevent the risk of suicide and other mental health problems.There are some limitations to this study. There is information bias in both the suicide cases and living controls, while the case-control design can minimize the impact of information bias. In this study, we used living comparisons as the gold standard to assess the validity of their informants’ reports. Informants in suicide group may be in grief and reported information may be affected. This study adjusted and matched the age, sex, and living location to identify potential risk factors, which meant that we could not consider the potential interaction between these factors and other potential risk factors. Men and women are very different in their communications and interpersonal interactions. Thus, we may miss a key potential element when not comparing results for men and women. In addition, with the rural elderly as the study objects in this study, further research should be carried out in other groups, and more other risk factors should be considered.In conclusion, QOLS-6 scale has good reliability and validity for assessing quality of life among older adults in China. It is shorter and easier than any other scale for measuring quality of life and could be used as a screening tool in future studies. With changes in the medical models, future research should pay more attention to mental and social factors. In addition to the components of physical and psychological health, the scale also explains quality of life from a social perspective, which is more conducive to comprehensive assessment of quality of life. As our study focuses on Chinese rural older adults, we recommend that future studies should be conducted on different age groups in various populations to further evaluate the validity and reliability of QOLS-6. Quality of life showed the potential to identify the elderly who may be at risk of suicide, but the mechanism of effect on suicide may need to be carried out in follow-up research.10.7717/peerj.12396/supp-1Supplemental Information 1The data of each scale related to the analysis of this article and the data of each item of the quality of life scale.Click here for additional data file.10.7717/peerj.12396/supp-2Supplemental Information 2Click here for additional data file.10.7717/peerj.12396/supp-3Supplemental Information 3Click here for additional data file.


Blood eosinophils are considered a biomarker for the treatment of chronic obstructive pulmonary disease (COPD). Population-based studies are needed to better understand the determinants of the blood eosinophil count (BEC) in individuals with and without COPD.1/FVC < 0.7. For the pre-specified outcomes related to BEC, the first 35 COPD and 35 non-COPD subjects were consecutively recruited in 12 of the participating centres with the objective of analysing 400 individuals in each group. Baseline BEC and its association with demographic, clinical and functional variables were analysed.EPISCAN II is a multicentre, cross-sectional, population-based epidemiological study aimed at investigating the prevalence and determinants of COPD in Spain. Study subjects were randomly selected from the general population, and COPD was defined by a post-bronchodilator FEVA total of 326 COPD and 399 non-COPD subjects were included in the analysis. The mean age (standard deviation [SD]) was 63.2 years (11.0), 46.3% were male, and 27.6% were active smokers. BEC was significantly higher in individuals with COPD . In a stepwise multivariate model, being male, active smoker and having a previous diagnosis of asthma were independently associated with having a higher BEC.This population-based study estimated the distribution of eosinophils in the healthy adult population and concluded that COPD patients have a significantly higher BEC. Male sex, active smoking and concomitant asthma were significantly associated with a higher BEC. Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with multiple phenotypes and endotypes, which may be associated with different prognoses and response to treatment , 2. One In order to better understand the role of blood eosinophils as a biomarker in COPD it is important to generate new data about the distribution of blood eosinophil values in healthy adult populations and different groups of patients with COPD according to different phenotypes, degree of severity and treatments. While the distribution of blood eosinophils has been examined in several United States , 14 or NEPISCAN II is a population-based, epidemiological study the main objective of which was to investigate the prevalence and determinants of COPD in all autonomous communities in Spain . One of EPISCAN II is a national, multicentre, cross-sectional, population-based epidemiological study the main objective of which was to investigate the prevalence of COPD in Spain. The full protocol, the fieldwork and all the methods have been described previously , 20. Brihttps://clinicaltrials.gov (NCT03028207) and at www.gsk-clinicalstudyregister.com/study/205932.The study was approved by the ethics committees of each of the participating centres, and all participants provided informed consent. The EPISCAN II protocol is registered at 1/FVC) ratio < 0.7. The study population was divided into two cohorts, depending on the results of the post-bronchodilator spirometry: patients with COPD (FEV1/FVC < 0.7) and non-COPD individuals (FEV1/FVC ≥ 0.7). Symptoms were assessed by the COPD Assessment Test (CAT) questionnaire. Physical activity was measured by the Yale Physical Activity Questionnaire (YPAS) validated for the Spanish population and the elderly population. This questionnaire reflects the amount, frequency, and intensity of physical activity that can be used to estimate the effects of physical activity as a continuous parameter, even at the low levels of activity that might be expected in COPD patients  and higher percentages of airway wall area in both primary and secondary bronchi (both p < 0.0001)  and median 150 cells/μL. BECs were significantly higher in individuals with COPD  vs. 160 cells/μL ; p = 0.0003). The distribution of blood eosinophils in both groups of subjects is depicted in Fig. The differences in BEC according to CT scan parameters did not achieve statistical significance Table . This anFigure A stepwise multivariate model was developed with the following variables: age, sex, body mass index, smoking, previous diagnosis of asthma, COPD, CAT scores, FEV1 (%), DLCO (%), YPAS score, 6MWD, exacerbations, ICS treatment, platelets, fibrinogen, CRP, emphysema (% fixed threshold), and airway wall area . Only five variables had a p value < 0.10 in the final model, with three being significant at a level of < 0.05. Being male, active smoker, and having a previous diagnosis of asthma were significantly and independently associated with a higher BEC Table .Table 3MGiven the potential for BEC as a biomarker in COPD , 11, 30,Since the EPISCAN II was a population-based epidemiological study, it is important to note that the majority of our population of COPD patients had mild disease, with 56% of GOLD stage I, and 75% were undiagnosed and untreated .. [The mean BEC in non-COPD subjects was 160 cells/μL, which was significantly lower than the mean count in COPD patients (192 cells/μL). The concentrations observed in our population of non-COPD individuals were intermediate compared to those observed in an Austrian population described by Hartl et al.  with a g. , and the. . However. [. [1(%) of 82% and 56% males in our population. Actually, some of these characteristics have been associated with BEC; in our study, male sex, active smoking, previous history of asthma and impaired FEV1(%) were significantly and independently associated with a higher BEC. Moreover, in previous studies, male sex [1(%) indicating higher levels in more severe disease.Our data replicate previous results showing a significantly higher BEC in subjects with COPD compared with non-COPD controls. In the previously mentioned study by Kolsum et al. , the mea. . A previ. , with 28.  found a . [. , 8, 30 cmale sex , 17, actmale sex  and asthmale sex , 17 havemale sex , 17. OurInterestingly, we did not observe any significant association between blood eosinophils and exacerbations or ICS treatment, probably due to the characteristics of our population which was mainly made up of mild and untreated patients. Our results concur with those of a previous large database study in patients at low risk of exacerbations in Primary Care that did not observe any influence of treatment with ICS on BEC, and no association was found between blood eosinophils and the frequency of exacerbations .. [1(%) of 43%. In contrast, there was an underrepresentation of patients with moderate and severe COPD in our sample, and the mean percent emphysema area was 10% in our COPD patients. A recent Canadian study described that patients with COPD and an elevated BEC had thickened central airway walls and a reduction in the total number of visible airways, indicating airway remodelling [Blood eosinophils were not associated with percent airway wall area for either the central or peripheral airways. Apparently, there was a trend towards a higher BEC in patients with COPD and more emphysema on CT, but the differences were not significant. On the contrary, Papaioannou et al.  found thodelling . More stOur study has several limitations, since it was a population-based study of the general population, patients identified with COPD were predominantly mild, undiagnosed and paucisymptomatic, with underrepresentation of patients with other degrees of severity. However, despite these characteristics, there were clear and significant differences in their characteristics compared with non-COPD individuals, including a significantly higher concentration of blood eosinophils. The cross-sectional design did not allow evaluation of the possible prognostic value of BEC for outcomes such as exacerbations. However, the design of the study had the strength to allow the analysis of an unselected population of COPD and non-COPD individuals from all geographic areas of Spain. Finally, we did not systematically assess the presence of possible causes of hypereosinophilia, although they have a low prevalence in the general population.1(%) are significantly associated with a higher BEC.The results of our population-based study provide an estimate of the distribution of eosinophils in the healthy adult population in Spain and has demonstrated that COPD patients, even with milder stages, have a significantly higher BEC. In addition to COPD, male sex, active smoking, the presence of asthma and a worse FEV


Background: Treatment of mentally disordered offenders (MDOs) is challenging as their behavior and clinical conditions can be traced to a complex constellation of major mental disorders, substance use and antisocial lifestyle. Finding subgroups of these offenders, which could guide treatment and risk assessment, is desirable. There are few long-term, prospective studies of risk factors for persistent criminal behavior among MDOs.Aims: The aims are (1) to provide a map of lifetime criminality in MDOs, (2) to identify subgroups of offenders, and (3), if such clusters exist, to test whether they differ in lifetime criminality and patterns of negative events during in-patient treatment.Methods: Background data on all offenders from the Malmö University Hospital catchment area sentenced to forensic psychiatric in-patient treatment 1999–2005 (n = 125) was collected. Data on negative events during treatment  from date of admittance until discharge or until June 30, 2008 was gathered. Court decisions for 118 of the cohort-individuals were collected from the 1st of January 1973 until December 31, 2013. We used hierarchical cluster analysis to identify subgroups and MANOVA-analysis to examine differences between these clusters on lifetime criminality variables and negative events. A MANCOVA was used to control for time in treatment.Results: The cohort was sentenced to a total of 3,380 crimes (944 violent) during the study period. Median age at first crime was 20 years (range 15–72), and at first violent crime 27 years (range 15–72). A subgroup (n = 26) was characterized by childhood adversities, neurodevelopmental disorders and later substance use disorders and was more often associated with substance-related crimes, financial crimes and lower age at first crime. During treatment, this cluster showed higher rates of substance use and threats. When controlling for treatment time, no differences in negative events were found.Conclusions: This study replicated findings from prison populations of the existence of a more criminally persistent phenotype characterized by early-onset neurodevelopmental and behavior disorders, childhood adversities and later substance use disorders. We did not find this cluster of variables to be related to negative events during inpatient treatment when controlling for length of stay. Pathways to delinquent behavior, and for some, to a lifelong antisocial lifestyle have interested researchers for decades –3 as theTo explore the emergence of criminal career patterns, the developmental taxonomic theory in its original outline  posits tThe previously identified heightened risk of violent behavior associated with schizophrenia and other psychotic disorders have in later studies emerged as magnified by comorbid SUD –27, but Prerequisites for a sentence to in-patient forensic psychiatric treatment in Sweden is the presence of a severe mental disorder calling for such treatment and that the crime was committed under its influence, and that the crime is severe enough to warrant a prison sentence. As a group, Swedish forensic psychiatric patients share many similarities. The majority are men of which about two thirds suffer from schizophrenia, almost all have had contact with psychiatric health services prior to their sentence and it is usually a violent crime that leads to forensic psychiatric treatment . In a prThe aims of the present study are; (1) to map lifetime criminality in a total cohort of persons sentenced to forensic psychiatric treatment and to describe different criminal patterns, (2) to determine if forensic psychiatric patients constitute of clinically distinct groups of offenders based on lifetime clinical and background characteristics in this population, and (3), if such clusters exist, to test whether they differ in variations of lifetime criminality and patterns of negative events during inpatient treatment.n = 36, 29%) had a first-degree relative with a mental disorder of some kind and another third  had been in contact with child- and adolescent psychiatric care when young. The paper further delved into risk prediction of relapse in criminality during a 10-year follow-up based on clinical and background data, where one finding was that patients with a restriction order was less likely to relapse into criminality. Lastly, Delfin et al. have described the incremental effects of neuroimaging data on risk prediction  who were sentenced to forensic psychiatric in-patient treatment during 1999–2005. The group is nationally representative as it includes all consecutively sentenced individuals who at the time of the forensic psychiatric treatment belonged to the catchment area of the Skåne University Hospital, Malmö, which was demographically typical for all of Sweden at the time of the study. The cohort has been portrayed in greater detail in three previous papers; in a previous study by Andreasson et al. , the medediction  based onn = 97, 78 %) or a Forensic Psychiatric Screening Report (FPSR)  prior to sentencing. Detailed descriptions of the Swedish criminal system and the forensic psychiatric treatment have previously been published  , suicide attempts, and diagnostics of mental disorders including NDD, were gathered from the FPIs and FPSRs in accordance with a structured protocol. The variables were chosen as they either explicitly or indirectly were proxies of previously described risk factors of criminal behavior. At the time of the original forensic investigations, the Diagnostic and Statistical Manual of Mental Disorders 4th Edition , financial crimes (including fraud and counterfeit), drug- and alcohol-related crimes and minor offenses (most commonly damage to other people's property).absconding , substance use , threats  and violent behavior . The data includes threat and violent events with both staff and patients as recipients. An event was registered in the database if it had been affirmed in the hospital files.Data on length of stay have previously been described in depth . By usinIn-patient treatment time was defined as time from when the court decision gained legal force until discharge or until 30th of June 2008, the end-point of the aforementioned study .To assess the risk of renewed criminal behavior and psychopathic personality traits, HCR-20  and the The PCL:SV screens for psychopathic personality traits and is a 12-item rating scale which is highly correlated with the 20-item full version , 57. TheOnly individuals who underwent a full FPI were assessed with the HCR-20 and PCL:SV. In most cases this was done by the FPI team but in 25 cases the assessments were made retrospectively by the research team based on the information gathered from the FPI files and from extensive file and register reviews in each case. Previous studies have shown that it is possible to reliable assess psychopathy  and riskAll analyses were conducted using version 25.0 of the SPSS . Due to 2-tests and Fisher's exact test when any cell count was less than five. Mann-Whitney U-test was used for continuous variables as data was not normally distributed. All statistics were calculated using anonymized data, using two-tailed p-values. To measure effect size, Phi scores for χ2-tests and r for Mann Whitney U tests are presented. According to Cohen's model , being placed in social custody or a youth institution before the age of 18, and being diagnosed with a NDD, SUD, psychotic disorder or a personality disorder. Ward's method  was usedhoc analysis to determine what would be considered a statistically significant p-value. The continuous variables included in the MANOVA analyses were converted to z-scores in order to illustrate the distribution of the means of the variables in linear diagrams. Statistical analyses were performed using the SPSS 25.0.One-way between-groups multivariate analysis of variance (MANOVA) was chosen to investigate cluster differences in variables of lifetime criminality and in negative events during in-patient treatment. Preliminary assumption testing was conducted to check for normality, linearity, univariate and multivariate outliers, homogeneity of variance-covariance matrices, and multicollinearity. Since the variables exhibited a non-linear relationship, all continuous data were transformed in accordance with the natural logarithm and as such used in the subsequent analyses. Eventually, two MANOVAs were performed. The first one to investigate cluster differences in lifetime criminality variables grouped as violent crimes and non-violent crimes, where the latter were further sub-categorized according to the headings of the Swedish penal code into theft and shoplifting crimes, traffic-related crimes, financial crimes, drug- and alcohol related crimes, and minor offense, and finally, age at first crime registered at courts. The second one to investigate negative events during in-patient treatment in the forensic psychiatric hospital defined as number of substance use events, absconding, violent events, and threats. To further explore the data, three one-way multivariate analyses of covariance (MANCOVA) were performed. As extensions of the MANOVA of lifetime criminality, age at the time of the FPI and time from initiating in-patient treatment at the index-crime until end of study or death, were entered as co-variates in two separate MANCOVAs. By extending data on negative events during in-patient treatment, length of stay was used as the co-variate in the third MANCOVA. In all the inferential statistical procedures, a Bonferroni correction was made as a post-The study was approved by the regional ethical review board in Lund (64/2007 and 2014/911). All data were anonymised using coded files, and the key code was kept separate from the study material and database. Since it is register-based and it would not be possible to contact most participants due to the length of time that has passed after finishing treatment informed consent was not considered necessary. The fact that contact could pose a risk to vulnerable subjects with mental health and/or legal problems was also considered in the ethical approval. When applying for the second ethical approval, the ethical board requested that the authors of this study announced the planned register study in mainstream media. The announcement went out in the two largest newspapers in the Malmö and Gothenburg area in the beginning of 2015.The total number of crimes found in sentences committed by the cohort from the beginning of registries at the 1st of January 1973 until endpoint of study at December 31, 2013 was 3380 . Five individuals (4 %) had committed only one crime during the study period and for 16 individuals (14 %) the index crime was their first registered offense. The median age at first crime was 20 years (range 15–72 years). Of the non-violent crimes, thefts or shopliftings were most common followed by traffic offenses, drug- and alcohol related crimes, financial crimes and fraud, and lastly other minor crimes.The total number of committed violent crimes in the cohort was 944 . The median age at first convicted violent crime was 27 years (range 15–72 years). Eight individuals (7%) had not been convicted of a violent crime. Eight individuals (7%) had been convicted of some form of lethal violent crimes  and 14 individuals (12%) had committed arson. Ten individuals (8%) had committed in total 37 sexual crimes . Four of these individuals (3%) had committed sexual crimes against children.n = 26, 28%) was grouped in cluster 1 and the rest, 67 individuals (72%), in cluster 2. Individuals in cluster 1 were more likely to have childhood onset problems or adversities, such as having a first degree relative with SUD, not having finished primary school, having contact with CAP, being placed in social custody or a youth institution before the age of 18, and having NDD. Presence of SUDs was also more prevalent among those in cluster 1.Two clusters, 1 and 2, were identified based on background and clinical data, see p < 0.001), and they also had higher HCR-20 scores compared with cluster 2, both on total scores  and on historical scores (p < 0.01).In F  = 2.46, p = 0.024; Wilks' Lambda = 0.832; partial eta squared = 0.168. When the results for the dependent variables were considered separately, two variables reached statistical significance, using a Bonferroni adjusted alpha level of 0.007; lifetime number of financial crimes, F  = 12.03, p = 0.001, partial eta squared = 0.117, and number of alcohol or drug-related crimes, F  = 8.85, p = 0.004, partial eta squared = 0.089. An inspection of the mean scores indicated that individuals of cluster 1 were more often convicted of financial crimes compared to those in cluster 2 (mean (M) = 3.42, standard deviation (SD) = 3.44 vs. M = 1.22, SD = 1.98), and of alcohol or drug-related crimes .The criminal careers differed between the two clusters that were identified. There was a statistically significant difference in a MANOVA between clusters 1 and 2 on the combined dependent variables covering criminality in a lifetime perspective, F  = 2.93, p = 0.009, partial eta squared 0.196, Wilks' Lambda = 0.804. When the results for the dependent variables were considered separately, only one variable reached statistical significance, using a Bonferroni adjusted alpha level of 0.007; age at first crime, F  = 109.82, p = 0.000, partial eta squared = 0.550.To further test the validity of the identified clusters, two MANCOVAs were made. First, age at the time of the FPI was added as a co-variate. There was a statistically significant difference between the clusters on the combined dependent variables after controlling for age at the time of the FPI, F  = 0.701, p = 0.671, partial eta squared 0.055.A second MANCOVA was made by entering time from initiating in-patient treatment at the index-crime until end of study or death, as a co-variate. There was no statistically significant difference between the clusters on the combined dependent variables, A MANOVA was also performed to investigate cluster differences in negative-events during in-patient treatment at the forensic psychiatric hospital. In the analysis, four dependent variables were included: absconding, substance use, threats or violence during in-patient treatment. As in the first MANOVA, the independent variable was the two clusters.F  = 2.57, p = 0.044, Wilks' Lambda = 0.896; partial eta squared = 0.104. When the results for the dependent variables were considered separately, the only difference to reach statistical significance using a Bonferroni adjusted alpha level of 0.0125, was number of events of substance use during in-treatment time, F  = 7.36, p = 0.008, partial eta squared 0.075. Here individuals in cluster 1 were more often involved in using drugs or alcohol during in-patient treatment time .There was a statistically significant difference between clusters 1 and 2 on the combined dependent variables, F  = 1.78, p = 0.106, partial eta squared 0.085].However, when length of stay was added as a co-variate in a MANCOVA, there was no statistically significant difference between the clusters on the combined dependent variables [This study of a nationally representative total cohort of MDOs sentenced to forensic psychiatric treatment had as a first aim to map lifetime criminality. The study individuals were markedly crime burdened as 96% had been sentenced for at least two crimes during their lifetime and as the median number of crimes during the lifetime was 16.5. Added to this, official crime registry data does not include the full extent of all committed crimes, only those that have led to a sentencing. It is therefore a fair assumption that there is a large quantity of criminal behavior not reported in this study and that the cohort as a whole could be described as having various forms of persistent criminal careers. Previous studies of life course patterns of criminal behavior have shown that a long criminal career is associated with low age at first committed crime , a findiin-utero exposure to alcohol and toxins and childhood adverse experiences such as familial psychopathology, maltreatment and neglect are potential risk factors for conduct disorder , though the latter statistical significance ceased when controlling for length of stay. A criminal lifestyle and SUD go hand in hand as crime may be a necessity in order to sustain a misuse of drugs and/or alcohol. Though we could not replicate three clusters exhibiting the criminal trajectories Hodgins proposed, the findings of the current study are in concordance with studies suggesting two subgroups of early and late starters . Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.HK, BH, HA, and TN designed the study. HK collected the data and took the lead in writing the manuscript in close collaboration with and under supervision of BH. TN and BH supervised the statistical analyses made by HK. All authors provided critical feedback and helped shape the analysis, research and full 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.


Cyber-victimization, tobacco and alcohol use are all prominent public health problems among adolescents throughout the world. Against this background, this study examined the association between cyber-victimization and tobacco and alcohol use, as well as the moderating role of deviant peer affiliation and the potential age differences among elementary, middle, and high school students. A survey conducted among 1488 school students  found that cyber-victimization was positively correlated with tobacco and alcohol use among students of all stages. However, the moderating mechanism was different. Among elementary school students, deviant peer affiliation played a positive moderating role. For individuals with high deviant peer affiliation, this association was stronger. Among middle school students, the moderating role of deviant peer affiliation was insignificant. Among high school students, deviant peer affiliation played a negative moderating role; this association was significant for individuals with low deviant peer affiliation. The results of this study clarify the relationship between cyber-victimization and tobacco and alcohol use by examining the moderating role of deviant peer affiliation and age differences, providing intervention guidance for reducing the negative influences of cyber-victimization on children and adolescents with respect their use of tobacco and alcohol. In our current information society, the internet has become a significant environmental factor influencing the development of children and adolescents. Cyber-victimization refers to the phenomenon whereby an individual is repeatedly bullied by other individuals or groups using electronic communication tools . This isSubstance use is a prominent public health concern among children and adolescents. In China, it specifically refers to the use of tobacco and alcohol  . AlthougIn addition, as one of the main socialization agents, peers  represent a significant factor capable of influencing the problem behaviors of children and adolescents ,11. FurtSmoking and drinking among children and adolescents have always been serious social concerns, and their influencing factors have been widely explored. It was found that stressful life events in one’s social environment associated with one’s family, school, and peers are important incentives for substance use . In the According to general strain theory , negativAt the same time, peers also play an important role in the development and adaptation of children and adolescents ,24. In pRegarding the association between cyber-victimization and tobacco and alcohol use, affiliating with deviant peers may make victims develop a positive attitude regarding problem behaviors . After bIn addition, cyber-victimization and its association with internalizing and externalizing problems may be different for children and adolescents in different development periods. Firstly, regarding cyber-victimization, the rate of cyber-victimization an individual experiencing varies by grades. It increases from 6.4% in the sixth grade to 11.6% in the tenth grade, and then decreases again to 7.8% in the twelfth grade . At the Deviant peer affiliation, then, also has different shapes of developmental trajectories ,26,32. TIn conclusion, this study aims to examine the association between cyber-victimization and tobacco and alcohol use, as well as the moderating role of deviant peer affiliation. The potential age differences among elementary, middle, and high school students were also investigated.n = 76), regular answers (n = 38), and over 30% of survey items were not answered (n = 5) were removed. The final usable sample consisted of 1488 students (52.6% boys), including 702 elementary school students , 318 middle school students , and 468 high school students .Participants were recruited from two elementary schools , two middle schools (grades seven and eight) and two high schools (grades ten and eleven) in central China with the approval of the school authority and the Academic Committee for Scientific Research at the first author’s university. Through convenience sampling, a total of 1607 students participated in this study voluntarily. Surveys with a lack of gender and age information  on each of the six items, with higher scores indicating a higher frequency of cyber-victimization. In this study, the Cronbach’s alpha of this scale was 0.92 in the total sample and 0.94, 0.88, and 0.92 in the elementary, middle, and high school student samples, respectively.The E-Victimization Scale (E-VS)  was adopnone, 5 = almost all), with higher scores indicating more deviant peer affiliation. In this study, the Cronbach’s alpha of this scale was 0.84 in the total sample and 0.84, 0.86, and 0.84 in the elementary, middle, and high school student samples, respectively.The Chinese version of the deviant peer affiliation scale  was adopNever to 6 = 20–30 days (or 1 = Never to 6 = 10 or more cigarettes/glasses per day), with higher scores representing heavier tobacco and alcohol use. In this study, the Cronbach’s alpha of this scale was 0.83 in the total sample and 0.90, 0.81, and 0.79 in the elementary, middle, and high school student samples, respectively.The Chinese version of the tobacco and alcohol use scale  was usedThis study was approved by the Ethical Committee for Scientific Research at the researchers’ affiliated institution. The ethical values required in research with human beings, the fundamental principles included in the Helsinki Declaration , and the regulations of the education management department were followed. At the same time, all the participants and their parents were informed of the principles of the study, and parental consent for the children’s participation in the study was also obtained.http://www.afhayes.com, accessed on 11 February 2021) for SPSS (Model 1), suggested by Hayes [All of the statistical analyses were conducted with the SPSS 23.0. First, the descriptive statistics and correlational analyses were calculated. Then, the PROCESS macro . The interaction of cyber-victimization and deviant peer affiliation was also significantly associated with tobacco and alcohol use , indicating the significant moderating effect of deviant peer affiliation. Then, a simple slope test was conducted. As shown in simpleβ = 0.22, p < 0.001) than lower deviant peer affiliation . Thus, Hypothesis 2 was supported among elementary school students.The SPSS macro-Process (Model 1) was further conducted to test the moderating effect of deviant peer affiliation. As previous studies had indicated that gender was closely associated with both cyber-victimization and substance use , this waRegarding middle school students, neither cyber-victimization nor the interaction between cyber-victimization and deviant peer affiliation were significantly associated with tobacco and alcohol use. Thus, Hypothesis 2 was not supported among middle school students.β = −0.10, p < 0.01), indicating the significant moderating effect of deviant peer affiliation. Then, a simple slope test was conducted. As shown in simpleβ = 0.13, p = 0.04), but was non-significant for high school students with higher deviant peer affiliation . This finding is contrary to the moderation’s direction of deviant peer affiliation in Hypothesis 2.Lastly, among high school students, the association between cyber-victimization and tobacco and alcohol use was non-significant, while the interaction between cyber-victimization and deviant peer affiliation was significantly associated with tobacco and alcohol use , and the correlation between deviant peer affiliation and tobacco and alcohol use was also significantly stronger among high school students . Although the moderating effect of deviant peer affiliation was not the “cumulative risk” effect we hypothesized among high school students, it is particularly troubling since the negative effect of cyber-victimization and deviant peer affiliation on high school students’ tobacco and alcohol use is more similar to a model in which “one trades and the other grows”.In this study, although we did not find the moderating role of deviant peer affiliation in the association between cyber-victimization and tobacco and alcohol use among middle school students, it was found that this association was moderated by deviant peer affiliation among high school students. To our surprise, and contrary to our hypothesis, for high school students with high deviant peer affiliation, the association between cyber-victimization and tobacco and alcohol use was non-significant. For those with low deviant peer affiliation, the association between cyber-victimization and tobacco and alcohol use was positively significant. This result demonstrates that deviant peer affiliation did not amplify the adverse effect of cyber-victimization on high school students’ tobacco and alcohol use. Instead, it “weakened” the association between cyber-victimization and tobacco and alcohol use. This may be related to the gradual increase of peer effect during adolescence . For high school students in adolescence, with the increasing time spent with peers, peer relationships become the primary social context that influences social development and peer influence is stronger . AccordiSeveral limitations should be acknowledged. Firstly, a cross-sectional design cannot draw causality. Particularly, some studies using longitudinal data have shown the causal relationship between cyber-victimization and tobacco and alcohol use ,20, but The findings also have some implications. Theoretically, from the perspective of a peer context, this study further clarifies the boundary condition of the relationship between cyber-victimization and tobacco and alcohol use and also clarifies age differences. This deepens our understanding of the outcomes of cyber-victimization on children and adolescents and also contributes to revealing the underlying mechanism of cyber-victimization and tobacco and alcohol use. Practically, cyber-victimization, as a kind of negative experience in online interpersonal interaction, can induce children and adolescents’ offline problem behaviors. Therefore, children and adolescents themselves should use the internet healthily, learn to identify the security risks of information online, and timely ask parents or teachers to seek a reasonable way to deal with problems such as bullying. Moreover, parents should monitor children’s online behavior and teach them to know and deal with cyber-victimization; educators should carry out internet literacy and network security education, and cultivate students’ social skills and scientific interpersonal communication methods; and online media should develop information filtering and blocking functions to warn and block minors’ harmful information with intimidation and threats, so as to prevent bullying perpetration and bullying victimization. At the same time, parents and educators should also pay attention to the offline peer interaction of children and adolescents, especially to prevent them from interacting with delinquents. In addition, the differences among elementary, middle, and high school students should also be noticed so that educators can teach students in accordance with their aptitude in practical work.To sum up, this study found that cyber-victimization was positively correlated with tobacco and alcohol use among elementary, middle, and high school students, and this relation was influenced by deviant peer affiliation. Among elementary school students, deviant peer affiliation positively moderated this relation. Among middle school students, deviant peer affiliation had no significant moderating role. And, lastly, among high school students, deviant peer affiliation negatively moderated this relation.


Over-the-counter (OTC) medicine is defined as safe and effective for the general public to use, without seeking therapy from a health professional. As primary social media and internet users, university and college students are more likely to be exposed to unverified sources of health information. This study aims to assess the knowledge, attitudes, and behaviour of students at institutions of higher learning in Brunei with regard to the safe use of OTC medicines. A cross-sectional study was performed using a self-administered online questionnaire, adapted from the literature with additional information from the United States Food and Drug Administration (FDA) on the educational resources in understanding OTC medicine for consumers. The questionnaire consisted of 4 sections: demographic information, knowledge of OTC medicines, attitudes, and practice. Descriptive and inferential statistics were used for data analysis. A total of 335 students returned a completed questionnaire. The students had a mean knowledge score of 7.1 out of 9, with more than half (53.4%) having good knowledge (knowledge score > 7), and only a small percentage (5.7%) with poor knowledge. Almost all of the students (99.7%) had a positive attitude toward OTC medicine use. Few of the students practiced improper habits in terms of OTC medicine use, such as not reading the instructions or taking more than the recommended dose. Awareness of proper OTC medicine use among students in institutions of higher learning is necessary to prevent the rise of inappropriate user practices. Over-the-counter (OTC) medicines are therapeutic products that pharmacies or retail outlets sell directly to consumers, unlike prescription medicines, which can only be dispensed based on a physician’s valid prescription . OTC medGlobally, inappropriate self-medication with OTC medicines has increased and is recognized as a public concern . Misuse Several studies have shown that university students lack knowledge of OTC medicine use and have poor attitudes toward proper medicine handling and safe use ,14. PoorAccording to 2018 data presented by the Substance Abuse and Mental Health Services Administration, it is estimated that 6.5% of people aged 18 to 25 years old have misused OTC cough and cold medicines containing dextromethorphan (DXM) in their lifetime . When a Across Southeast Asia, self-medication practice for OTC medicine use is common. The various economic classes and healthcare systems in Vietnam, Singapore, and Thailand have reported high prevalence rates of self-medication with OTC medicines ,18,19. IBrunei Darussalam is a small country with a population of 453,600, according to 2020 estimates . The couTo the best of our knowledge, there is no documented Bruneian study assessing the use of OTC medicines. A survey targeting the younger population, especially those undergoing university or college education, will be helpful, because they are the primary users of social media and so are most likely to be exposed to unverified sources of health information. Furthermore, such a survey is needed because it may benefit public health policymakers and local health authorities as baseline data for future health promotion and intervention. Therefore, this study aimed to examine the safe use of OTC medication by determining the knowledge, attitudes, and behaviour with regard to OTC medications among the students in Brunei’s institutions of higher learning.This is a cross-sectional online survey conducted from March to April 2021 involving all students enrolled in all public institutions of higher learning in Brunei Darussalam. There are six such institutions, namely: Universiti Brunei Darussalam (UBD), Universiti Teknologi Brunei (UTB), Universiti Islam Sultan Sharif Ali (UNISSA), Kolej Universiti Pergururan Ugama Seri Begawan (KUPU SB), Politeknik Brunei (PB), and Institute of Brunei Technical Education (IBTE). Full-time or part-time students enrolling in any of these institutions in Brunei Darussalam, 18 years old or above, and either Bruneian citizens or permanent residents, were eligible to participate. The study questionnaire was adapted from a survey conducted by Tesfamariam et al. . AdditioThe final questionnaire consisted of four sections with a total of 38 questions: seven questions on demographic data, nine questions on knowledge, eight questions on attitude, and 14 questions on practice . The knoThe online survey was distributed to all students at all public institutions of higher learning through email invitations sent to the students’ official email addresses at the participating universities and colleges. The email list was collated by the assistant registrars, with the email invitation consisting of an online survey link and a participant information sheet. An email reminder was sent following a two-week interval to increase the response. Sampling was not necessary because all eligible participants were invited and were therefore given a chance to participate.p value of <0.05 was considered statistically significant.Data collected were summarized using descriptive statistics for the percentages, frequencies, median, and mean. Chi-square and Fisher’s exact tests were used to analyse the association between the demographic data and knowledge. R version 4.0.4 software and Microsoft Excel version 2019 were used for data analysis ,28. A p The Joint Research Ethics Committee of the PAPRSB Institute of Health Sciences, Universiti Brunei Darussalam, granted full approval for this study (UBD/PAPRSBIHSREC/2020/135). Additionally, the data collected remained anonymous, and confidentiality was strictly maintained. A written consent form was provided by asking respondents to tick an option at the beginning of the online survey. Participation was on a voluntary basis. The face validity of the online questionnaire was assessed by a pharmacist, an epidemiology/biostatistics lecturer, and a physician from the PAPRSB Institute of Health Sciences, Universiti Brunei Darussalam, for readability, length, and relevance. A pretest was also conducted among 38 students, after which the responses were used to finalize the questionnaire. The internal consistency of the final questionnaire was determined using Cronbach’s alpha coefficient. Cronbach’s alpha values for the knowledge, attitude, and practice sections were 0.74, 0.73, and 0.73, respectively.A total of 335 respondents returned the completed questionnaire. The median age of the respondents was 22.0 years . The characteristics of the respondents are displayed in p = 0.028) and course of study , but not in terms of nationality or year of study. There was a statistically significant difference of knowledge scores between students on health science-related and non-health science-related courses (p < 0.001).More than half of the respondents (53.4%) had good knowledge of the use of OTC medicine, with a mean total knowledge score of 7.1 out of 9 . StudentA health science-related course is defined as students who are health science majors studying health and disease in the human body, such as medicine, dentistry, pharmacy, biomedical, and nursing. A non-health science-related course is defined as students who are not health science majors studying health and disease in the human body, such as engineering, IT, religion, finance, design, and art.Almost all respondents indicated a positive attitude toward the use of OTC medicine . Most agThe respondents depend on various sources of information before purchasing suitable OTC medicine, such as family members (84.5%), the Internet (66.6%), friends (62.1%), a pharmacist (37.0%), a doctor (35.8%), and social media (15.8%) . Their rA few (9.9%) of the respondents experienced adverse effects from OTC medicine . In addiMost respondents always read the instructions on the medicine’s label before use (64.2%), check the expiry date (71.3%), and store the OTC drug in a cool, dry place or as stated on the label (60.0%). If the OTC medicine showed a change in shape, colour, or odour, 92.5% would immediately discard it.This study assessed the safe use of OTC medicine and determined the knowledge, attitudes, and practice around OTC medicine among students from public institutions of higher learning in Brunei Darussalam.p = 0.028). There was also a significant difference between the knowledge of OTC medicine according to the course of study (p < 0.001). Health science-related students with a higher education level are more familiar with the clinical practice and medications, which improves their knowledge of OTC medicine use. Upper-year health science-related students have a better understanding of medications and self-medication since they are more exposed to the drugs than lower-year students. The finding of this study is similar to that from another study in Northwest Ethiopia, where fifth year students were found to be more likely to practice self-medication [In this study, there was a significant difference between knowledge of OTC medicines depending on the academic degree  reported having experienced adverse effects, while 17.7% did not know if they had ever experienced them.Inappropriate practices of self-medication in developing countries have increased due to a lack of knowledge, inadequate medical information exposure, and confusing or unclear product labelling on different medicines ,45. BefoStudents are considered active participants in OTC medication as their knowledge influences drug use and the overall safety of drug use. Proper and appropriate self-medication practice can positively impact the individual and the healthcare system by saving lives from an acute ailment, reducing the waiting time in hospitals or clinics, reducing morbidity and decreasing healthcare costs.This study has several limitations. Firstly, the questionnaire can be further improved to ensure it is more appropriate and relevant to the topic. One main reason is that the questionnaire was challenging to construct, and there were no comprehensive tools for testing the knowledge aspect available for this study. Secondly, the intentional misreporting of behaviours by respondents may confound the survey results or hide inappropriate behaviour. Hence, the responses to the questionnaire may not reflect the actual attitudes or behaviours of the respondents. Thirdly, as the practice segment of the questionnaire was embedded with recall questions on OTC medicine use, recall bias is likely to occur. Lastly, the male to female ratio was 25:75 in this study and 41:59 for overall higher institutions of learning in Brunei, indicating a potential oversampling of females in our study . This coStudents from institutions of higher learning in Brunei generally have a good level of knowledge and positive attitudes toward OTC drug use. There are still some gaps around inappropriate practices with OTC medicine, especially concerning reading of medication labels, checking of expiry dates and storage. However, only a minority of respondents have such inappropriate habits. Increased awareness of the proper use of OTC medicine among students in institutions of higher learning is necessary to prevent the rise of improper practices in OTC medicine use.