To investigate the preoperative body composition, metabolic characteristics, and postoperative changes in patients with active acromegaly and analyze the effects of gender and age.  We included 36 patients with untreated acromegaly and 37 patients with nonfunctional pituitary adenomas. Adipose tissue (AT), the visceral fat index (VFI), sclerotin, protein, skeletal muscle, total body water (TBW), intracellular water (ICW), and extracellular water (ECW) were measured using bioelectrical impedance analysis (BIA). Total energy expenditure (TEE) and basal metabolism (BM) were measured with a cardiopulmonary and metabolic analyzer (CMA). Tricep skinfold thickness (TST), bicep circumference, waistline, hipline, and calf circumference were measured with a skinfold caliper and tape. These indices were measured before surgery and 3 months and 1 year after surgery.  Overall, AT, VFI, and TST were lower, whereas sclerotin, protein, skeletal muscle, TBW, ICW, ECW, TEE, and BM were higher in acromegaly patients. Postoperatively, TST rose initially and then decreased, the waistline increased, and sclerotin, skeletal muscle, TEE, and BM decreased. Changes in these indices differed with gender and age in unique patterns.  Body composition and metabolism in acromegaly patients changed after surgery, and gender and age influenced these changes. Acromegaly is mostly caused by a growth hormone- (GH-) secreting pituitary adenoma, resulting in excess GH and insulin-like growth factor 1 (IGF-1) and thus overgrowth of soft tissue and bone . AlthougSeveral studies have focused on body composition and metabolic changes in patients with acromegaly. Moller et al. and O'Sullivan et al. demonstrated that the total energy expenditure (TEE) and basal metabolism (BM) were increased in patients with acromegaly compared with the general population , 6. FredThe most commonly used methods to measure bone mass, AT, lean body mass (LBM), and body water are MRI, DXA, and isotopic dilution , 12. HowStudies evaluating body composition using the BIA method are rare. Postoperative changes and trends in TEE and BM are unclear. Additionally, whether body composition and metabolism are the same at 3 months and 1 year after surgery is unknown. The effect of age on body composition and metabolism in patients with acromegaly is ambiguous. Thus, this study aimed to prospectively evaluate the preoperative characteristics of body composition and metabolism in patients with untreated acromegaly using BCA and a cardiopulmonary and metabolic analyzer (CMA) to determine the extent of postoperative changes between follow-up at 3 months and 1 year after surgery, and to explore the different effects of age and gender on body composition and metabolism in patients with acromegaly.This study consecutively enrolled patients with acromegaly admitted to the Department of Neurosurgery at Peking Union Medical College Hospital  from June 2015 to June 2016 into the experimental group. Each year, approximately 140 patients with acromegaly and over 500 patients with nonfunctional pituitary adenomas were admitted to PUMCH and underwent pituitary tumor resection. The inclusion criteria were as follows: (1) adult patients who presented characteristic clinical manifestations of acromegaly , 18; (2)Informed consent was obtained from each patient prior to enrollment. This study was approved by the Ethics Committee of PUMCH at the Chinese Academy of Medical Sciences and Peking Union Medical College.All subjects completed a medical history record, physical examination, hormone assays  for GH, and other hormone assays), contrast-enhanced MRI of the sellar region, and routine preoperative examinations. Body composition and metabolic measurements were performed for all subjects 1 day before surgery in the Department of Parenteral and Enteral Nutrition of PUMCH. Female participants were required to complete the measurement on days when they were not menstruating. The gender, age, height (to within 0.1 cm), body weight (to within 0.1 kg), BMI, disease duration, and past medical history were recorded before surgery. The disease duration was defined as the interval from the onset of symptoms related to acromegaly to a definitive diagnosis. After excluding the contraindications, all of the patients underwent a transsphenoidal pituitary tumor resection, recovered smoothly, and were discharged 3 days after the operation. Histopathology of the paraffin-embedded tissues and immunohistochemical pathology confirmed the diagnosis of pituitary adenoma.Patients with acromegaly were followed-up at 3 months and 1 year after surgery in the outpatient service. Acromegaly-related symptoms, pituitary hormones, and pituitary images were recorded. If the patients did not meet the biochemical cure standard, including the presence of residual tumors or neogenetic tumors, and had high GH and IGF-1 levels, we reevaluated their conditions and prepared an optimized treatment. These patients did not undergo body composition and metabolism reassessments. Body composition and metabolism were retested in patients who were cured at the follow-up.μIU/ml), T3 (0.66–1.92 ng/ml), T4 (4.3–12.5 μg/dl), ACTH (0–46 pg/ml), cortisol (4–22.3 μg/dl), testosterone (1.75–7.81 ng/ml), and prolactin (0–30 ng/ml). Normal reference ranges of FSH, LH, estradiol, and progestin changed with patients' menstrual cycles.Serum hormones were collected in the Neurosurgery Ward at 6 a.m. after an eight-hour fasting period and sent to the Department of Laboratory Medicine. The OGTT for GH was collected at five time intervals as follows: before, 30 min after, 60 min after, 120 min after, and 180 min after glucose administration. The GH level was measured using an IMMULITE 2000 analyzer with a chemiluminescence assay . The IGF-1 level was measured with a chemiluminescence assay  using the same analyzer. The age-related IGF-1 reference ranges at PUMCH were as follows : 21–25 yHypogonadotropic hypogonadism was characterized by both low gonadal hormones and the presentation of infertility, low libido, or sparse pubic hair. The levels of FSH and LH could be within the normal range or lower. The diagnostic criteria of secondary hypothyroidism included the manifestation of hypothyroidism, a low T3 or T4 level, and low/normal TSH. Adrenal insufficiency was defined as the presentation of weakness and anorexia, low cortisol, and low/normal ACTH.Contrast-enhanced MRI for the sella was performed using the same machine  in the Department of Radiology. The diagnostic radiological presentation for a pituitary adenoma is a solid mass in the sella presented as hypointense on T1-weighted imaging and hyperintense on T2-weighted imaging and an unremarkable reinforcement of the mass.The somatometry indices include tricep skinfold thickness (TST), bicep circumference, waistline, hipline, and calf circumference. The measurement point for the TST is the midpoint between the acromion and the olecranon on the side of the dominant hand. The researcher held the skin and subcutaneous tissue with the thumb, index finger, and middle finger of the left hand and measured the thickness using a skinfold caliper that was accurate to 0.1 mm. The measurement point/plane of the bicep circumference, calf circumference, waistline, and hipline was defined as the midpoint between the acromion and the olecranon on the side of the dominant hand, the plane of the maximal calf circumference, the midpoint between the inferior costal margin and the peak of the iliac crest, and the plane of the maximal hipline, respectively. These measurements were taken three times with a tape and were accurate to 0.1 cm.Body composition was measured using a BCA  with the BIA method; the indices used included total AT, the visceral fat index (VFI), sclerotin, protein, skeletal muscle, total body water (TBW), intracellular water (ICW), and extracellular water (ECW). Sclerotin indicated the total bone substance of the patients. The basic working principle of the BIA was Ohm's law. A small amount of current was released, and the abovementioned indices were analyzed based on the resistance in different parts of the body , 14. TheThe body metabolism was measured with a CMA ; the indices used were the TEE and BM. The patients were required to fast for 12 hours, and smoking was prohibited for 2 hours. The indoor temperature was set at 25 degrees centigrade, and the test cabinet was kept quiet. The patient was placed in a supine position on the test bed with a shield covering the head. The CMA determined the body energy expenditure by calculating the oxygen consumption and carbon dioxide output. Data from the first five minutes were discarded to obtain a more accurate result. The entire process took approximately 20 minutes, and patient movements were prohibited during the test.t-test, whereas variables lacking normal distributions were assessed using the Mann–Whitney U test. Enumeration data were compared with the χ2 test. Statistical significance was defined as p < 0.05.We conducted the statistical analysis using the SPSS Statistics software  and drafted histograms using the Origin software . Patients in the experimental and control groups were divided into subgroups based on gender and age (>40 years and ≤40 years). Quantitative data were shown as the mean ± standard deviation (SD), and enumeration data were shown as note Levene's test was used to evaluate distributions for the quantitative data; data with normal distributions were assessed using a 2 (SD = 2.7), and the disease duration (DD) was 89.3 months (range from 12 to 276 months). The morbidity due to hypertension was 25%, and to diabetes was 8.3%. A total of 37 patients were enrolled in the control group , with an average age of 43.0 years (SD = 12.9), BMI of 24.8 kg/m2 (SD = 4.0), and DD of 27.2 months (range from 1 to 84 months). A total of 8.3% of the patients in the control group were complicated with hypertension and 2.8% with diabetes. The statistical analysis indicated that no significant differences in these indices occurred between the two groups. The GH and IGF-1 levels were significantly increased in the patients with acromegaly and in the subgroup comparisons. Other pituitary hormones exhibited normal reference levels.Enrolled patients were strictly selected from all admitted patients according to the inclusion criteria. The clinical characteristics of the enrolled patients are presented in p = 0.005). Invasiveness (Knosp classification > 2) was observed in 25.0% of the patients (9/36) in the experimental group and 29.7% of the patients in the control group (11/37).Sella MRI showed that the typical radiological characteristics of the tumors were hypointensity on T1-weighted images, hyperintensity on T2-weighted images, and decreased contrast enhancement compared to the surrounding normal pituitary tissue. The average maximum diameter of the tumor in patients with acromegaly was significantly smaller than that in the controls , and 16 patients were followed-up at 1 year (10 men and 6 women) after transsphenoidal surgery.During the first 3 postoperative months, we identified 2 patients with hypothyroidism, 5 patients with transient adrenal insufficiency (one week after surgery), and 3 patients with hypogonadism. Hormone substitution was applied to help these patients maintain normal pituitary function. At 1 year after surgery, the thyroid function of the 2 patients with hypothyroidism was normal, and euthyrox was withdrawn. Two of the 3 patients with hypogonadotropic hypogonadism recovered to normal gonadal hormone levels without gonadal hormone substitution. Another patient was newly diagnosed with hypogonadism at the 1-year follow-up and subsequently received hormone substitution.p = 0.007) and the TST was thinner , whereas the bicep circumference, calf circumference, waistline, and hipline revealed no differences. Elements of the body frame, including sclerotin , protein , and the skeletal muscle mass , were significantly larger in the patients with acromegaly. TBW was larger , and its constituents, ICW  and ECW , were both larger in the patients with acromegaly. BM  was significantly elevated in the patients with acromegaly.The AT was lower in the patients with acromegaly than in the controls. In acromegaly patients, the VFI was lower , ECW (p = 0.009), sclerotin (p = 0.041), protein (p = 0.040), and skeletal muscle (p = 0.024) were larger than those in the female controls, total AT did not decrease, the AT distribution did not change, and TEE and BM did not increase. Patients with acromegaly aged > 40 years had a lower VFI (p = 0.038) and higher skeletal muscle (p = 0.031) and ECW (p = 0.033) values than those aged > 40 years among the controls, whereas other body composition and metabolic characteristics changed inconspicuously.In the subgroup analysis , the difAmong the patients with acromegaly, the body composition and metabolic changes in those who were biochemically cured during the postoperative period are presented in Tables As presented in The sclerotin and skeletal muscle mass decreased during the postoperative period in the patients with acromegaly. The decreases were not significant at 3 months after surgery, but they were significantly decreased at 1 year after surgery in both the male and female groups. The protein levels in all four subgroups did not change after surgery.The TEE and BM decreased to different extents in the patients with acromegaly during the postoperative period. The decrease was significant at the 1-year follow-up, but it was not significant at the 3-month follow-up, especially in the female patients and the patients aged ≤ 40 years.This study examined the preoperative body composition characteristics and postoperative changes in acromegaly patients using the BIA method and analyzed the surgical effect on changes in metabolism. The preoperative body composition and metabolic characteristics and the postoperative changes in patients with acromegaly presented unique and complex patterns. The total AT, VFI, and TST were decreased preoperatively in the patients with acromegaly and rose again after surgery to different extents. The bicep circumference, calf circumference, waistline, and hipline did not differ from the controls before surgery. However, these measurements all slightly increased postoperatively, and the increase in the waistline in the males and patients aged > 40 years was significant. The TBW, including the ECW and ICW, was higher in the patients with acromegaly before surgery, but the ECW increased 3 months after surgery instead of decreasing. The sclerotin, protein, skeletal muscle, TEE, and BM were higher in the acromegaly patients preoperatively and declined after surgery. Interestingly, gender and age played different roles in influencing the body composition and metabolism. The changes in body composition and metabolism also differed during the different postoperative periods.Excess GH and IGF-1 can both influence fat metabolism, whereas the effects of GH predominately promote fat breakdown . GH may In this study, gender differences apparently influenced the changes in AT in acromegaly patients. The total AT, VFI, and TST were decreased in the male patients with acromegaly before surgery, whereas the decreases were not significant in the females. Estrogen can inhibit the GH to IGF-1 conversion process in the liver and then slow down lipolysis by suppressing the fat oxidation process , 22. ThiThe bicep circumference, calf circumference, waistline, and hipline of the patients with acromegaly accorded with those of the controls regardless of gender and age. This phenomenon indicated that apart from enlarged fingers, toes, and facial changes, the body shape did not obviously change in the patients with acromegaly. This finding might be the comprehensive outcome of decreased body fat and increased sclerotin and skeletal muscle. Although the bicep circumference, calf circumference, waistline, and hipline in the male patients had a tendency for a moderate increase, only the increase in the waistline in the males was significant 1 year after surgery.One essential element of the material basis of body anabolism is water. Excess GH in patients with acromegaly accelerates the retention of water and sodium to ensure the normal proceeding of boosted anabolism , 24. TheThe effect of excess GH on the acceleration of anabolism results in an increase in the LBM in untreated acromegaly, and the LBM decreases with the decline in GH , 26–29. The BM has been reported to be slightly increased in patients with acromegaly and in patients receiving GH replacement therapy . An elevIn conclusion, the body composition , body metabolism (TEE and BM), and postoperative changes in patients with acromegaly presented interesting and unique patterns. The BIA method can systematically and comprehensively evaluate these changes. The characteristics can help to perform better preoperative assessments and to assuage patients' doubts and improve their quality of life. The mechanism underlying gender-specific and age-related body composition and metabolic characteristic changes during the pre- and postoperative periods is still ambiguous and needs to be verified.


P = 0.044), and was not associated with reduced recurrence-free survival (RFS) in pre-menopausal patients with early-stage endometrial cancer . Preservation of the ovaries appears to be a safe option with significant benefit for this low risk population after a thorough preoperative evaluation and extensive intraoperative exploration.We searched Medline, Embase, Cochrane library, the Chinese Biomedicine Literature Database, the Chinese Scientific Journal Full-text Database, the Chinese Journal Full-text Database, and the Wanfang Database to collect observational studies on the effects of ovary-saving surgery in comparison to bilateral salpingo-oophorectomy (BSO) in young patients with early-stage endometrial cancer (EC). The literature search included studies up to March 2017, and 10 retrospective cohort studies met our selection criteria. Random and fixed effect models revealed that ovarian preservation (OP) was associated with better overall survival (OS) (hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.57–0.99,  EC is primarily a disease of postmenopausal women, but 25% of patients are premenopausal . The incThe search strategy generated 792 citations, of which 43 were potentially relevant and retrieved for assessment Figure . Of thesThe clinical characteristics of all patients and methodological qualities from the 10 articles are summarized in Table P = 0.044 Figure I2 = 0.0%, P = 0.737) . Of the four studies, one from China contained a small number of patients with non-endometrioid histological type. When only the three studies that were restricted to patients with endometrioid adenocarcinoma were considered in the analysis the HR of OS was of a similar magnitude .Four studies from the USA, Korea, and China compared OS between the BSO group and the OP group in 10716 patients (9376/1340) expressed as HR , 17, 19.) Figure  and no eP = 0.648 Figure I2 = 50.3%, P = 0.156). Funnel plot showed that there might be publication bias .Two studies compared RFS between the two arms in 567 patients 366/201) , 17. Ran66/201 , I2 = 0.00%, P = 0.647) did not show any significant benefit in the BSO group over the OP group with respect to RFS   with no statistically significant heterogeneity detected between studies .Only two studies reported data on HR of RFS, and these data were too sparse to be pooled. We extracted data to calculate a pooled RR and 95% CI. Similarly, for seven studies with 1024 patients enrolled 706/318) , 16–18,  , 16–18,) Figure . There wSince no prospective study on this issue has been designed and a randomized controlled trial is unlikely in the near future owing to the anticipated difficulty in patient recruitment, the results of this study carry weight. This meta-analysis, which included over 10,000 cases from the USA, Korea, and China, demonstrates that OP significantly improves the OS  and does not adversely impact RFS  of young patients with early-stage EC. Although this study cannot conclusively refute or support the safety of OP with regard to risk of EC recurrence (RR), it is noteworthy that, in this low risk population, the absolute recurrence rate (4.09%) was low. Patients who receive surgery with ovarian conservation might take a 2.1 fold risk of recurrence, but in the long run they will benefit and have a higher OS probability.Two previous systematic reviews have examined the survival benefit of ovarian conservation in endometrial carcinoma , 42. BotAs the proportion of young women diagnosed with EC has been rising over time, it has become increasingly important to reach consensus on the practice of OP. Between 1983 and 2012, approximately 15% of patients diagnosed with stage I type I EC were under the age of 50 and were forced to make a difficult choice on whether or not to receive an oophorectomy , 7, 24. The second concern stems from the possibility that continued estrogen production by the ovaries may stimulate residual endometrial tumor cells. Four retrospective studies have looked at the issue of estrogen replacement therapy (ERT) after surgical treatment of early-stage endometrial adenocarcinoma, and all of them show no significant increase in recurrences or deaths caused by EC in the ERT group –29. A prIt has been suggested that surgical menopause can cause adverse long-term effects in bone, heart, and neurologic health as well as quality of life. Additionally, it eliminates the fertility of young nulliparous women completely , 31, 32.Although current guidelines recommend oophorectomy for all women with EC, mounting data suggests that it may be time to reevaluate these recommendations and consider more individualized treatment, especially for early-stage young patients. In an observation study of Lee et al, seven of the 175 EC patients had documented recurrence, and all seven recurrences had risk factors, namely, non-endometrioid histology, deep myometrial invasion, cervical stromal invasion, and inadequate adjuvant treatment . YoshinoIn regard to the limitations of this study, first, all the studies enrolled in the meta-analysis were retrospective data, and some did not have a sufficient follow-up period due to missing data in the medical records. Despite the recognized limitations of observational data, all of the studies in our analysis are high quality according to NOS, and it is unlikely that a randomized controlled trial of oophorectomy compared with ovarian conservation will ever be performed. Second, as in any observational study, a number of unmeasured confounders may have influenced the allocation of treatment. We lack data on family history, the presence of inherited genetic abnormalities such as Lynch syndrome, body mass index, the gross appearance of the ovaries at the choice to perform oophorectomy, and the status of adjuvant treatment. Third, the consequences of surgical menopause in young women, such as cardiovascular disease, osteoporosis, and quality of life, such as hot flushes and genital tract atrophy, were not evaluated. Fourth, publication bias might exist due to the small number of studies that were included for each outcome, although the assessment of publication bias showed no statistically significant asymmetry. Fifth, although we collected data from China to calculate in our study, these data were not population-based, which might lead to selection bias. Finally, some of the patients had ovaries saved incidentally because they were not diagnosed as having EC preoperatively, while others were diagnosed with EC preoperatively and were willing to conserve their ovaries with informed consent. OP is more like to be performed when a clinician encounters a favorable case and a younger patient. Thus, selection bias should have been controlled in order to compare the survival outcomes of the two groups.In summary, this meta-analysis demonstrates that OP significantly improves the OS and does not significantly decrease RFS of young patients with early-stage EC. OP is a reasonable option in some young women with low risk EC after a thorough preoperative evaluation and an extensive intraoperative exploration. Further larger trials to evaluate the safety of OP for low risk EC patients  with adequate survival data, cardiovascular disease, osteoporosis, and quality of life measured, especially from Asia, are warranted.This systematic review and meta-analysis is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement and was registered at International Prospective Register of Systematic Reviews (number CRD42017054306). We identified observational studies by searching Medline (from 1950), Embase (from 1980), Cochrane library (from 1996), the Chinese Biomedicine Literature Database (from 1978), the Chinese Scientific Journal Full-text Database (from 1989), the Chinese Journal Full-text Database (from 1994), and the Wanfang Database (from 1980). The search strategy included terms for endometrial cancer , patient age , tumor stage , and treatment (ovarian conservation and OP). The literature search was performed up to March 2017. The full electronic search strategy for Medline can be found in the appendix (Supplementary Appendix 1). We hand searched abstract books of conference proceedings between 2010 and 2016 to identify potentially eligible studies. The reference lists of all identified relevant studies were used to carry out a recursive search of the literature.Retrieved articles had to meet the following inclusion criteria: (1) Patients who underwent hysterectomy and were diagnosed with Stage I or II endometrial carcinoma; (2) premenopausal or under the age of 50; (3) original articles comparing the OS and/or RFS between the group treated with ovarian preservation surgery (OP group) and the group that received BSO (BSO group); and (4) only studies published in English or Chinese were included. This age cutoff of 50 years was chosen based on mean age of spontaneous menopause in the North American and Chinese populations , 37.The following were the exclusion criteria: (1) Uterine sarcomas and metastatic tumors to the uterus were excluded. (2) Patients with EC that coexisted with other malignant tumors were excluded. (3) Articles without full-text or articles without extractable data to calculate were excluded. (4) The study year, study centers, and study periods were investigated and overlapping articles were excluded.Two authors (P.J. and Y.Z) independently examined the titles and abstracts of all articles, and excluded those going beyond the selection criteria. Any discrepancy in their opinions was discussed to reach an agreement.Two reviewers independently extracted data on to an Excel spreadsheet (Microsoft for Mac 2011) as survival outcomes . In addition we extracted the following clinical data for each trial: country, period of observation, patient age, tumor stage, the grade and histology of tumor, and duration of follow-up.No prospective study on this issue has been designed, thus only observational studies were included in the meta-analysis. To evaluate the quality of the studies, two reviewers (P.J. and Y.Z) assessed studies according to the NOS  for obseP < 0.05 was considered to be statistically significant. For too few studies expressing RFS outcomes as HR, we also extracted data to calculate a pooled RR and 95% CI. Study-to-study variation was assessed using the Higgins I2 test, which measured the proportion of the total variation across the studies [P-value < 0.1 or I2 > 25% [a priori according to patient age and histology type.The results of this study were expressed as a pooled HR and 95% CI. A value of  studies . When siI2 > 25% ) was notWe used STATA 12.0  to generate forest plots of pooled HR, RR, and risk differences for outcomes with 95% CI. The Egger and Begg tests were used to assess funnel plots for evidence of publication bias .


A Principal Components Analysis, which was directly tested with a Confirmatory Factor Analysis, confirmed the proposed three-factor model resulting in 14 final items. Reliability analyses demonstrated high internal consistency of the scales. Furthermore, the scales showed high convergent validity, as they were positively correlated with related scales of the Interpersonal Reactivity Index  completed the newly developed Empathy Questionnaire for Children and Adolescents (EmQue-CA) that was tested on reliability, construct validity, convergent validity, and concurrent validity. The EmQue-CA aims to assess empathy using the following scales: ty Index . With re Empathy, the ability to share and understand emotional states of others , has a lUp until now, validated questionnaires that have been most commonly used with child and adolescent populations are the Interpersonal Reactivity Index IRI;  and the affective empathy: a scale that measures the extent to which the child/adolescent feels for the emotional state of the suffering person, (2) cognitive empathy: a scale that measures the extent to which the child/adolescent understands why the other person is in distress, and (3) intention to comfort: a scale that measures the extent to which the child/adolescent is inclined to actually help or support the suffering person.Moreover, existing empathy questionnaires are mainly focused on assessing sharing feelings of others , and undN = 1250). To test the intended three-factor structure of the questionnaire, the total sample was divided in two, where a Principal Component Analysis (PCA) was conducted on the first half and a Confirmatory Factor Analysis (CFA) was conducted on the second half of the sample. For concurrent validity, the associations of the EmQue-CA scales with related concepts were examined. We expected that adolescents who scored high on affective empathy had more awareness of what happened in their body following emotional situations. Understanding what is happening in your own body makes it easier to distinguish your emotions from those of someone else, which is expected to promote feelings of empathy and to prevent personal distress  to conform to cultural norms with regard to performing specific gender roles . Hill anM age = 13.25; SD = 1.67; 50% girls; see Table 1 for the descriptive statistics). The complete sample is a combination of five subsamples, which did not differ in study variables or demographic composition (see Supplementary Table Table 2 for an overview). To get a clear overview, we classified ethnic background by continent (the Netherlands excepted). All participants were recruited from local elementary and high schools with different levels of education, including preparatory schools for vocational secondary education and university.Thousand two hundred and fifty children and adolescents aged 10–15 participated in the current study  measuring the extent to which one feels for the emotion of another person, (2) cognitive empathy  measuring the extent to which one understands why another person is in distress, and (3) intention to comfort  measuring the extent to which one is also inclined to actually help or support a person in need. Participants were asked to rate to what extent the description was true for them on a 3-point scale: (1) not true, (2) somewhat true, and (3) true  (3) true . All queN = 160; hereafter referred to as affective empathy), and perspective taking . Both scales contained six items; each item was rated on a 5-point Likert scale with (0) completely untrue, (1) not quite true, (2) in between, (3) quite true and (4) completely true. All questions were (re) scored such that higher scores reflected higher empathy. Mean scores were calculated per scale. See Table 3 for Cronbach’s alphas.Two scales of the IRI  were obtN = 117): differentiating emotions , bodily awareness of emotions  and attending to others’ emotions . All items were answered on a 3-point scale with (1) not true, (2) sometimes true, (3) often true. Mean scores were calculated per scale and higher scores indicated better abilities in differentiating own emotions, higher bodily arousal in response to own emotions, and higher attendance to others’ emotional states. See Table 3 for Cronbach’s alphas.Three scales of the well validated EAQ were included in a subsample of this study ; N = 117N = 862) containing 28 items assessing positive  and negative friendship quality . Participants were asked to indicate how much each item was true for their relationship with their best friend on a 5-point Likert scale ranging from (1) not true to (5) completely true. Considering the strong links between positive friendship quality and empathy . Mean scores were calculated and higher scores indicated higher relationship quality. See Table 3 for Cronbach’s alphas.We used an adapted version of the FQS ; N = 862 empathy , we inclbullying was assessed using the well-validated OB/VQ (N = 907). Participants were asked to indicate how often they engaged in different acts of bullying in the last 6 months on a 5-point scale with answers varying from (0) I haven’t bullied other children to (4) several times a week. Mean scores of the six bullying items were used; higher scores indicated more engagement in bullying behavior. See Table 3 for Cronbach’s alphas.Self-reported ed OB/VQ ; N = 907In order to assess the construct validity of the EmQue-CA, we randomly split the total sample in two. The first half of the sample was used to examine the factor structure by conducting Principal component analyses (PCA), using SPSS version 23. To determine the number of factors to be retained parallel analysis was used . In paraOn the second half of the sample a Confirmatory factor analysis was conducted to test the final model as derived by the previous PCA, using EQS version 6.3. All items were hypothesized to load on their key factor; no cross-loadings or error covariances were allowed. Goodness of fit was evaluated using the following cut-off criteria: CFI > 0.90, RMSEA < 0.08, SRMR < 0.08 , 1999.Furthermore, the inter-factor correlations were computed to demonstrate diversity between the scales, and Cronbach’s alphas were computed to examine construct consistencies. Next, we examined the associations between the scales of the EmQue-CA with the scales of the IRI to determine convergent validity. The concurrent validity of the EmQue-CA was also tested, for which we examined the associations between the EmQue-CA scales with emotion awareness, friendship quality, and bullying behavior. Finally, we applied Fisher r-to-Z transformation to calculate a value of Z to assess the significant differences between boys and girls for the correlations between the scales of the EmQue-CA with the scales of the IRI, EAQ, FQS, OB/VQ, and age.χ2= 2596.94, df = 210, p < 0.001), confirming suitability of the data for PCA.A PCA on all 21 items was performed using the first half of the sample. The Kaiser-Meyer-Olkin (KMO) measure was 0.82, which indicated adequate sampling. In addition, KMO values for individual items had sampling adequacy coefficients ranging from 0.51 to 0.90, which are all above the acceptable limit of 0.5 . BartletTo extract the suitable number of factors, an initial PCA analysis was conducted. The parallel analysis indicated that four factors should be retained. The four factors together explained 43.38% of the total variance. In the subsequent four-factor PCA with rotation, four items were excluded since loadings on all factors were <0.40 . Exploring the content of the items within the factors it was noted that three factors clearly represented the three hypothesized theoretical constructs: (1) affective empathy (six items), cognitive empathy (three items), and intention to comfort (five items). The fourth factor consisted of three theoretically unrelated items  and were therefore removed from further analysis, resulting in retaining three factors.χ2= 1839.64, df = 91, p < 0.001) all indicated that data was adequate for PCA. Parallel analysis indicated a 3-factor solution. The three factors combined explained 48.35% of the total variance. Following rotation, all items loaded on the intended factor; the following analyses were thus performed with the newly formed three scales. See Table 4 for a complete list of all items and factor loadings.Subsequently, another PCA was performed with the 14 final items. The overall KMO measure (0.80), the KMO values for individual items (range = 0.74–0.89), and Bartlett’s Test of sphericity  = 230.59, p < 0.001; SRMR = 0.055; CFI = 0.912; RMSEA = 0.058, 90% C.I. = 0.050, 0.067]. Standardized factor loadings ranged from 0.450 to 0.861. Thus, the three-factor model based on the final set of 14 items was retained (see Table 4).The final model obtained with PCA was directly tested with a CFA, using the second half of the sample. Given that Mardia’s normalized coefficient (13.21) indicated substantial multivariate kurtosis, analyses were based on the robust Satorra-Bentler affective empathy 0.70, cognitive empathy 0.70, and intention to comfort 0.74 (see Table 3). The mean scores in Table 3 show that girls scored higher on affective empathy, cognitive empathy, and intention to comfort. Correlations between all three scales were significant, but still below 0.38 indicating that there was no collinearity (see Table 5). The correlations remained significant when analyzed separately per age group (see Table 1 for more information about the age groups). Additionally, the affective and cognitive empathy scales of the EmQue-CA correlated positively with the respective IRI scales (see Table 5). Table 3 also presents the means of all included constructs separately for boys and girls. Boys and girls differed significantly on all measures, except for differentiating emotions. Girls scored higher on all empathy measures, attending to others’ emotions and friendship quality; boys reported significantly higher levels of bodily awareness of emotions and bullying than girls.Cronbach’s alphas of the three scales of the EmQue-CA indicated good internal consistencies  for the Table 5). The results showed a negative correlation between affective empathy and differentiating emotions, and a negative correlation between affective empathy and bodily awareness of emotions and intention to comfort and bodily awareness of emotions. Affective empathy and cognitive empathy were both related positively to higher scores on the EAQ scale attending to others’ emotions. When we examined the relationships of the EmQue-CA scales with indices of social functioning, we found that friendship quality correlated positively with affective empathy, and intention to comfort. Bullying, on the other hand, correlated negatively with all three scales of the EmQue-CA. All correlations remained significant after controlling for age.To examine the concurrent validity of the EmQue-CA, we tested the relationship between the EmQue-CA scales and related constructs . Additionally, results showed a significant gender difference in the correlation between affective empathy and differentiating emotions , and between intention to comfort and attending to others’ emotions ; in both cases, the correlations were only significant for boys.To test for gender differences regarding the strengths of the relationships  between scales of the EmQue-CA and other variables in this study, we applied Fisher r-to-Z transformation. The correlation between z. These analyses showed a significant gender difference for the link between affective empathy and age , cognitive empathy and age , and intention to comfort and age . Girls showed a positive relationship between age and affective empathy  and cognitive empathy , whereas there was a negative relationship for boys between age and affective empathy  and cognitive empathy . Moreover, boys showed a negative correlation between age and intention to comfort ; an effect that was absent in girls.We tested for gender differences in the correlations of the EmQue-CA scales and age by applying Fisher r-to-Z transformation to calculate a value of In this study, we examined the construct, convergent, and concurrent validity of the EmQue-CA, a newly developed empathy questionnaire for children and adolescents. The EmQue-CA aims to assess affective- and cognitive empathy and the tendency to care for another’s welfare as a result of empathy. The outcomes of this study confirm a three-factor structure within the EmQue-CA. Moreover, the three identified scales show good internal consistencies, as well as the expected relationships with another validated empathy measure , and related constructs of emotion awareness and differentiation (as assessed by the EAQ), and social functioning .The negative correlations of the affective empathy scale and the intention to comfort scale of the EmQue-CA with the scale bodily awareness of emotions of the EAQ were as expected. Children and adolescents who focused more on other people’s distress  and who had a stronger tendency to help others  were more focused on their own internal state as assessed by bodily awareness of emotions. This is in line with prior findings showing that being aware of your own emotions and the emotions of others is related to reporting less depressive symptoms . OverallThis could be explained by gender differences in affective empathy as proved by several experiments using different neurophysiological measures  divergent social behaviors may be related to delayed or lacking development of one or more components of empathy. For example, several studies have denoted the possibility of higher levels of affective empathy combined with lower levels of cognitive empathy in children and adolescents with Autism Spectrum Disorder (ASD) . The disTaken together, the EmQue-CA presents a significant contribution to the literature on empathy and intention to comfort in children and adolescents. Specifically, the scale assessing intention to comfort presents a valuable addition to existing questionnaires measuring empathy. Examining intention to comfort is particularly important during childhood and adolescence, as prosocial behavior is crucial for adaptive socio-emotional functioning. We demonstrate here that the three scales of the EmQue-CA show differential links with age and gender and thus contribute uniquely to the assessment of empathy. Future studies should further employ the EmQue-CA to unravel how empathy and intention to comfort contribute to psychosocial functioning, as these concepts are of great importance in forming and maintaining social relationships across childhood and adolescence.This study was carried out in accordance with the recommendations of APA guidelines, with informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the Ethics Committee of Leiden University.Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work: SO, CR, EB, and BG. Drafting the work or revising it critically for important intellectual content: SO, CR, EC, and BG. Final approval of the version to be published: SO, CR, EB, EC, and BG. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: SO, CR, EB, EC, and BG.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: In order to search for effective control and prevention measures, the status of metal pollution in Ningbo, China was investigated. Methods: Nine of the most common contaminating metals including lead (Pb), cadmium (Cd), copper (Cu), iron (Fe), manganese (Mn), chromium (Cr), nickel (Ni), zinc (Zn), and mercury (Hg) in samples of vegetables, rice, soil, irrigation water, and human hair were detected using inductively coupled plasma-mass spectrometry (ICP-MS). Three different districts including industrial, suburban and rural areas in Ningbo were studied through a stratified random sample method. Results: (1) Among all of the detected vegetable samples, Cd exceeded the standard limit rates in industrial, suburban and rural areas as high as 43.9%, 27.5% and 5.0%, respectively; indicating the severity of Cd pollution in Ningbo. (2) The pollution index (PI) of Cd and Zn in soil  suggests that soil is slightly polluted by Cd and Zn. Among all samples, metal contamination levels in soil were all relatively high. (3) A positive correlation was found between the concentrations of Pb, Cd and Cu in vegetables and soil; Pb, Cu, Cr and Ni in vegetables and irrigation water, as well as, Cu and Ni in rice and irrigation water; and, (4) Higher Pb and Cd concentrations were found in student scalp hair in both industrial and suburban areas compared to rural areas. (5) Hg and Pb that are found in human scalp hair may be more easily absorbed from food than any of the other metals. Conclusions: In general, certain harmful metal pollutions were detected in both industrial and suburban areas of Ningbo in China. Rapid industrialization in China has resulted in serious environmental pollution. Among the different types of pollutions, metal pollution is considered to be one of the major environmental issues . NumerouAfter entering the human body, it is difficult for metals to be completely metabolized. They may accumulate in soft tissues or in the bones, causing toxic effects ,10,11. ITherefore, the following objectives are included in the present study: (1) investigate the status of the nine most common contaminating metals, including lead (Pb), cadmium (Cd), copper (Cu), iron (Fe), manganese (Mn), chromium (Cr), nickel (Ni), zinc (Zn), and mercury (Hg) from industrial, suburban and rural areas in Ningbo; (2) analyze the relationship between concentrations of selected metals in vegetables, rice, soil, irrigation water, and student scalp hair and search for an effective way to control and prevent these environmental pollutions; and, (3) provide some insights into metals accumulation in the agricultural ecosystem and human tissue to serve as a basis for comparison to other regions both in China and worldwide.The Ningbo area is an important coastal industrial city which is located on a typical flat alluvial plain in the Yangtze River Delta region  . BecauseThree different districts including industrial, suburban and rural areas in Ningbo were studied by a stratified random sample method. The industrial and suburban areas were assumed to be possible severe contaminated areas, and the rural area was set as possibly none or a slightly contaminated area. The downtown area was not included in this study due to the uncertainty where the consumed vegetables or rice was produced, but the industrial and suburban areas are normally consumed from local produced vegetables and rice. One town or one street in each area was selected for sampling . Ten samples of greens, radish, cabbage, celery, and soil were collected from the farmlands located around the residential houses. The collected rice samples were produced in the local farmland, as well as, water samples used to irrigate these farmlands. Rice samples were not collected from suburban areas, because most residents in the suburban area purchase rice from other provinces or abroad. Hair samples were obtained from the local school students who had stayed in the sampling regions for more than five years. A total of 399 students  were selected to participate in this study, . All of the students were given an informed consent (written) for inclusion before they participated in the study. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of the Ningbo University Ethics Committee No. AEWC-2013-115) on 19 June 2013. Only the first 2.0 cm of hair proximal to the scalp was used for analysis [13-115 on3-HCl-HF in a test tube [3-H2O2-H2O at 130 °C until no residue remained in the solution. The digested samples were cooled at room temperature and diluted to 25 mL with de-ionized distilled water for further analysis. Food samples were oven-dried at 105 °C for 1 h and then at 70 °C until constant weight. Then, food samples were comminuted using a pulverizer and sieved through a nylon sieve with 100 meshes. Approximately 0.2 g food powder was digested by using 3 mL HNO3 at 100 ± 5 °C until no residue remained. All of the samples were treated and analyzed according to the national standard method GB/T5009-2003 [Soil samples (approximately 500 g) were collected from the farmland surface (10–20 cm deep) and air-dried in the laboratory. Soil samples (0.25 g) were digested with a 6 mL acid mixture of 1:1:1 HNOest tube . The mix009-2003 . All the009-2003 . The acc009-2003 .iC is the metal concentration of the sample, and iS is the pollution threshold of i, the equation applies for the chemical that was given the national hygienic standard.The food samples included 120 vegetable samples and 20 rice simples, the environmental samples included 30 soil samples and 30 irrigation water samples. The pollution levels of metals in food and environmental samples were evaluated using the pollution index (PI), (Equation (1)) ;(1)PI=ChC and eC are the total metal concentrations in hair samples and corresponding food and environmental samples, respectively [The bioaccumulation factor (BAF) of each metal was used to assess the transfer of metals from food and environment to hair. It can be calculated as:ectively .t-test and correlation analysis were used. The statistical significance levels were set at p < 0.001, p < 0.01 and p < 0.05.Statistical analysis was performed using SPSS V17.0 software  for Windows. Data of metal of food and environment are normal distribution, hair samples are log-normal distribution (One-Sample Kolmogorov-Smirnov Test), the median and percentile were used in hair samples data as statistics description. ANOVA Dunnett, q’ = 0.038, p = 0.01), Cu , Cr , and Ni  contained in four kinds of vegetables in the suburban area were significantly higher than that of the rural area; whereas, the average concentrations of Pb , Cr , Ni , and Hg  in the industrial area were significantly higher than that of the rural area.q’ = 0.016, p = 0.017) and Cr  in the suburban area were significantly higher than that of the rural area.In the greens, the concentrations of Cd  in the industrial area and Cd  and Cu  in the suburban area were significantly higher than that of the rural area.In the radish, the concentrations of Mn  in the industrial area was significantly higher than that of the rural area.In the cabbage, only the concentration of Hg , Cu  and Cr  in the industrial area and the concentrations of Cu  and Cr  in the suburban area were significantly higher than that of the rural area.In the celery, the concentrations of Pb , Cr  and Ni  in the rice in the industrial area were significantly higher, whereas Zn  was significantly lower, than that of the rural area.q’ = 0.110, p = 0.016) and industrial  areas were significantly higher than that of the rural areas.q’ = 0.053, p = 0.041) and Mn  in the industrial area and Cu  and Mn  in the suburban areas were significantly higher than that in the rural areas.The descriptive statistics of the pollution index (PI) of metal concentrations in food and the environment is presented in r = 0.793, p < 0.01), Cd  and Cu  in vegetables and soil. Pb , Cu , Cr , and Ni  in vegetables were correlated with that in irrigation water. Cu  and Ni  in rice were correlated with that in irrigation water.q’ = 0.296, p < 0.001), Cd , Fe , and Zn  in student hair in industrial areas and the concentrations of Pb , Cd  and Fe  in student hair in suburban areas were all significantly high. When compared to rural areas, the concentrations of Cu , Cr , Ni , and Hg  in student hair in industrial areas and the concentrations of Mn , Ni , and Zn  in student hair in suburban areas were all significantly low. Furthermore, in order to investigate the correlation between the studied metal concentrations recorded in the scalp hair, the Pearson’s correlation coefficient was calculated and is shown in The bioaccumulation factor (BAF) of metals in the hair, food, and environmental samples is shown in In this study, we found that the average concentrations of Cd, Cu, Cr, and Ni in four evaluated vegetables in the suburban area of Ningbo, China were significantly higher than in the rural area. However, in the industrial area, the average concentrations of Pb, Cr, Ni, and Hg were significantly higher than the rural area. The amount of Cd in the four evaluated vegetables in suburban, industrial and rural area samples reached 43.9%, 27.5%, and 5.0%, respectively, exceeding the standard limit. Rice produced in the industrial area had more Cu, Cr, and Ni contamination than that of the rural area. These results indicate that metal pollution in the suburban and industrial areas were more serious than in the rural area, especially Cd pollution, due to the dramatically increased industrial operations and rapid urban expansion in the past three decades in Ningbo. In addition, the relatively high PI of Cd in vegetables also indicated Cd contamination. The dynamic uptake of metals varies at different growth points for different vegetables [In soil samples, we found only the Hg concentrations in both suburban and industrial areas were significantly higher than in the rural area . Pb, Cd,Our results are in agreement with the conclusion of Briki et al. a higher level of metal contaminations exists in suburban and industrial areas than that of rural areas , except The biological monitoring of metal pollution for human exposure is of optimal interest for researchers . As a stvia the environment-food-human system. Eliminating metals in the environment is the basic method to reduce metal levels in the hair. The correlation analysis showed that the six metals  in the hair of the students were positively correlated with each other. It can be seen from a correlation among various trace metals that there exists a mutual dependence of these metals in the environment, which is probably due to their similar chemical nature [In our study, though median concentrations of Pb, Cd, and Hg in student hair were all within the reference concentration range reported previously, the concentrations of Pb, Cd in industrial and suburban areas were all significantly higher than rural areas. The bioaccumulation factor (BAF) of Pb and Hg in the hair samples from vegetables, rice was relatively high, reflecting that metals accumulated in the students’ bodies mainly originated from food. Soil had the largest BAF for Hg, indicating that Hg were more easily absorbed by the hair l nature . Many ofPb, Cd, and Hg are nonessential elements, which are widely distributed at low levels in the environment , In thisFurther studies should focus on the following issues:(1) More studies concerning the relationship between metals concentrations in human tissue and food should be conducted. (2) More reference of metals in body tissue should be studied and updated frequently, especially for children. (3) Every element in the food chain should be used to investigate the dynamic uptake of metals.In general, we found that metal pollution in the suburban and industrial areas was more serious than that in the rural areas; among all the detected vegetable samples, Cd rates exceeds the standard limit and is higher in the industrial and suburban areas when compared to the rural areas. Thus, Cd pollution in Ningbo is a serious one; Higher Pb and Cd concentrations were found in student hair in both industrial and suburban areas compared to rural areas. In conclusion, certain harmful metal pollutions were detected in both industrial and suburban areas of Ningbo in China.


A multimedia fugacity model with spatially resolved environmental phases at an urban scale was developed. In this model, the key parameter, organic matter, was replaced with black carbon (BC) and applied to simulate the distributions of phenanthrene (Phe), pyrene (Pyr) and benzo[α]pyrene (BaP) in Nanjing, China. Based on the estimated emissions and measured inflows of air and water, the Phe, Pyr and BaP concentrations in different environment media were calculated under steady-state assumptions. The original model (OC-Model), BC-inclusive model  and improved model (BC-Model) were validated by comparing observed and predicted Phe, Pyr and BaP concentrations. Our results suggested that lighter polycyclic aromatic hydrocarbons (PAHs) were more affected by BC substitution than their heavier counterparts. We advocate the utilization of sorption with BC in future multimedia fate models for lighter PAHs based on the comparison of the calculated and observed values from measured and published sources. The spatial distributions of the Phe, Pyr and BaP concentrations in all phases were rationally mapped based on the calculated concentrations from the BC-Model, indicating that soil was the dominant sink of PAHs in terrestrial systems, while sediment was the dominant sink of PAHs in aquatic systems. The United States Environmental Protection Agency (US EPA) has identified 16 PAHs as priority pollutants, and these PAHs are also listed in the 1998 protocols on persistent organic pollutants under long-range transboundary air pollution3. Therefore, investigating the fate of PAHs in multimedia environments is very important to assess their ecological and human health risk. However, due to the complicacy of the chemicals and the paucity of systematic regional monitoring data for various environmental phases, predicting the fate and distribution of environmental multimedia has become an essential step in linking emission sources, environmental distribution, and human exposure4. Among various multimedia fate models, the fugacity model has been developed and applied to predict the fate of organic chemicals5.Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants that are carcinogenic and mutagenic to humans and toxic to all living organisms7. One important assumption of fugacity models is that the bulk phases are completely mixed with the homogeneous concentrations of the modeled chemical10. Recently, 69 surface soil samples from Nanjing were measured for PAHs, and a fairly large variation was found among the sampling locations1. Thus, relatively large uncertainty resulted from ignoring the spatial variation, and no valuable information was obtained on the spatial distribution of the modeled chemicals5. Multimedia models with regional segments have been conducted in several studies, but few have been attempted at an urban scale11.Fugacity models are based on the fugacity concept, whereby the fugacity of a compound in a specific environmental phase is directly related to its concentration by means of the fugacity capacity of the phase12. An increasing number of studies have indicated that black carbon (BC) leads to enhanced sorption of planar and aromatic organic compounds15. The formation process of BC is similar to PAHs, as the two compounds are both formed by fossil fuel combustion ; part of their formation results from the combustion of biomass 16. BC consists of the combustion-derived carbon fraction, including residues, of initial fuel (char) as well as highly condensed carbonaceous products (soot)17, which are ubiquitous in the environment. The fraction of BC to total organic carbon (TOC) ranges from 5–18% in sediment samples around the world18, but most PAHs are bound to the BC fraction19. Generally, BC contents are approximately 1–15% of the TOC, and therefore, in several cases, BC can be expected to more strongly contribute to overall sorption than all the other organic matter constituents16. Prevedouros et al.12 developed a BC-inclusive multimedia model for predicting the fate of organics and found that lighter PAHs were more affected by BC inclusion than their heavier counterparts.Multimedia fugacity models assume that organic matter is entirely responsible for the capacity of solids to sorb organic chemicals. However, increasing evidence has suggested that the existing organic matter partitioning paradigm is not sufficient to explain the sorption to environmental solids of hydrophobic organic contaminants that can obtain a planar configuration20, which included developing and evaluating a spatially resolved solution. We compared the simulated results among the original model (OC-Model), BC-inclusive model 12, and BC-substituted model (BC-Model), which assumed that BC is entirely responsible for the capacity of solids to sorb organic chemicals, to determine the best model to simulate the environmental distribution of PAHs in Nanjing, China. Air, vegetation, water, soil, sediment, and organic film (“pure” film plus particles are covered on impervious surfaces) were included in the model20. The model was based on the steady-state, level III fugacity model of Mackay21, and the spatially distributed emissions of PAHs in the Nanjing urban areas from January 2012 – December 2013 were estimated and then used as the representative data for contemporary emissions. This study should provide a useful tool for modeling the distribution of PAHs in urban environments.Based on the above analysis, this study attempted to improve the multimedia urban model (MUM) structure23. The study region was divided into 36 grid cells (4 km × 4 km). Each grid cell was constructed with six connected phases representing air, water, soil, sediment, vegetation, and organic film. Figure Nanjing was selected as a prototype city. The city is an ancient capital of six dynasties with a history of more than 2500 years and a profound cultural background. As a main port along the Yangtze River, Nanjing is a complex industrial base dominated by electronics, automobile, and chemical industries. Each environmental medium in Nanjing has been heavily contaminated by many types of pollutants, including PAHsf, Pa), fugacity capacity , and transfer rate coefficients , were employed in this model to describe the environmental distribution and fate processes. Z is specific to the properties of the contaminant and the environmental media. D represents the inter-media transport and transformation processes, including diffusion, advection, and degradation, and is related to the chemical transfer flux. The concentration of the contaminant within a phase  is a product of f and Z. The original and developed Z values for each phase are listed in the Supporting Information  and KBC-A (BC-air partition coefficient) of the three chemicals were derived from Prevedouros et al.2. The physical-chemical properties of Phe, Pyr and BaP are shown in Table 25. The soil BC contents were determined by the method described by He and Zhang26 using a Heraeus CHN-O-Rapid elemental analyzer . The SOM and soil BC content results for each grid in the study area are shown in Table et al.27. The content of BC in water suspended particulates was obtained from Huang and Zhang28. The concentration of BC in sediment was derived from Huang and Zhang29.The parameters used in the model calculations include various environmental parameters, physical-chemical properties of Phe, Pyr and BaP, and flux matrixes among various media. Most of the data were obtained from the literature or from the model default value30. The external source concentrations of PAHs in the air and validation data were measured using polyurethane foam passive air samplers deployed throughout the city for a 3 month period in 2014. Twenty water samples were collected from rivers and lakes in the Nanjing urban areas to explore the external source concentrations of PAHs and to construct validation data. The advections in water and air for each grid in the study area are shown in Table 31. Parameter values for the study area summarized in Tables The air and water flows were described by matrixes of flow rates for their inter-regional movements. Airflow rates were calculated from the annual mean wind speedIn this study, seven major sources were considered: coking production, primary aluminum production, transport petroleum combustion, non-transport petroleum combustion, industrial coal combustion, domestic coal combustion, and biomass burning. However, biomass burning, such as straw and fire wood burning, has rarely occurred in recent years in our research area. Primary aluminum is also not produced in the Nanjing urban areas, and domestic coal combustion has been replaced by coal gas and natural gas in these urban areas. Therefore, only four sources were considered in this research: transport petroleum combustion, non-transport petroleum combustion, industrial coal combustion, and coking production. The emissions from these sources were then distributed across the grid cells in the model for the gridded region.et al.32 found that the consumption of transport petroleum, non-transport petroleum and industrial coal linearly correlated with secondary plus tertiary GDPs (GDP23). Energy consumption data on a provincial scale as well as data of the county and street level during January 2012 – December 2013 were collected from yearbooks38. The main coking production data were collected from official published sources38. Thus, the energy consumption for each street was estimated, the data were integrated into each grid using a Geographic Information System, and the emissions were calculated using the emission factors39. Figure The emission estimates in our study were based at the urban street level (known as the township level division in China), but no energy consumption data were available at this level. Zhang Xi (i is the index of the input variable) denotes the input parameter of the model, Y denotes the output of the model when the test parameter is adjusted ± 10%, and Δ refers to perturbations.Sensitivity analysis is an important methodology used to test the sensitivity of the model to parameter changes and identify the most influential parameters for the model output. In this research, sensitivity analysis was performed for all the inputs parameters. Each parameter was individually adjusted by ± 10%, and the sensitivity coefficient (S) was calculated by the following formula:g(r) is the random variable, f(r) is the distribution density function, and <g> is the mathematical expectation of g(r). The approximate formula can be converted into:37. The values of the key input parameters were randomly selected within their respective probability distributions. The Monte Carlo simulations were repeatedly run 10000 times using Oracle Crystal Ball to obtain the distribution of the output.Monte Carlo simulations were performed to evaluate the overall uncertainty of predictions based on the probability distributions of the input parameters. This method computes results based on repeated random sampling and statistical analysis. The model can be formulated as follows:Two procedures were used to test the validity of the model. One procedure assessed the calculated predictions by comparing the observations and predictions of the PAH concentrations in the bulk phase . The other compared the prediction results among the BC-Model, dual C-Model and OC-Model.41. The independently measured mean Phe concentrations were 591.4 ng/g and 5.05 ng/g for vegetation and sediment, respectively, compared to 627.00 ng/g and 1.18 ng/g for the BC-Model, 1.63 ng/g and 0.5 ng/g for the dual C-Model, and 1.62 ng/g and 0.1 ng/g for the OC-Model, respectively. Obviously, the prediction results of the Phe concentrations in the BC-Model were closer to the observed values from the published sources. Unfortunately, measured data on organic film are not available. The calculated mean concentrations in the organic film decreased in the following order: BC-Model (−0.97 log mol/m3) > OC-Model (−1.67 log mol/m3) > dual C-Model (−2.51 log mol/m3).As shown in Fig. 41, the absolute differences between the calculated and measured mean concentrations in vegetation fell within 1 log-unit, but the difference was greater than 1 log-unit in the sediment phase. In all cases, the difference between the modeled concentrations of the BC-Model, dual C-Model and OC-Model fell within 0.5 log-unit for BaP. Compared to the observed values, almost no difference in BaP modeled concentration was observed in the air phase. The average difference between the calculated and measured concentrations fell within 0.5 and 0.1 log-units for BaP in water and soil, respectively, which are acceptable for this type of study. The calculated BaP concentration results in the other phases are illustrated in the Supporting Information (Fig. 41, the absolute differences between the calculated and measured mean concentrations in vegetation and sediment are both approximately 0.5 log-unit. The scatter plots of predicted versus observed values are illustrated in Fig. Additionally, no difference in the Pyr concentrations in the air phase among the three models was found, and the predicted values versus the observed values were similar. In the water phase, the distribution of the calculated Pyr concentration was similar to that of the Phe concentration. In the soil phase, the calculated Pyr concentrations in the OC-Model and dual C-Model were the same but lower than the calculated value in the BC-Model, which was closer to the measured values in the most grids. However, their concentration differences fell within 1 log-unit. The calculated Pyr concentration results in the other phases are illustrated in Fig. ion Fig. . Compareet al.42, which indicated that lighter PAHs were more affected by BC inclusion than their heavier counterparts in all cases. In this study, we simulated the distributions and inventories of Phe, Pyr and BaP using the BC-Model, which provided more accurate simulations compared to the observed values from measured and published sources. The predicated results are as follows.Based on the results of the abovementioned analysis, the BC-Model did not cause any considerable variations to the air levels and water levels of the grids containing PAHs from external water sources when simulating the fate of PAHs. However, the BC-Model caused increases in other environmental phase concentrations related to increase solid partitioning, except for BaP. In other words, the difference of the calculated concentration decreased with an increasing molecular weight of PAH in the three models. Our results are similar to the findings of Prevedouros The spatial distributions of the Phe, Pyr and BaP concentrations in all phases were mapped based on the calculated results. As shown in Figs The model predictions for the inventory in each grid are shown in Tables 43. Segment 27 was selected as an example for the sensitivity and uncertainty analyses. The sensitivities and uncertainties of the modeled concentrations in all the phases to the input parameters of Phe, Pyr and BaP in the OC-Model, dual C-Model and BC-Model were analyzed. The Supporting Information (Tables As no differences in the source, distribution and contribution of the input parameters were observed between different segments, the sensitivity and uncertainty analysis results in one cell could be representative on the entire regionn Tables –S16 shown Tables –S19. TheIn this study, a spatially resolved MUM model was developed. The key parameter, organic carbon, was displaced with BC, and model predictions were validated by comparing the observations and predictions of PAH concentrations. Our results suggested that lighter PAHs were more affected by BC substitution than their heavier counterparts. Based on the comparison of the calculated and observed values from measured and published sources, we advocate the utilization of sorption with BC in future multimedia fate models for lighter PAHs. The spatial distributions of the Phe, Pyr and BaP concentrations in all phases were rationally mapped based on the calculated concentrations of the BC-Mode, indicating that soil was the dominant sink of PAHs in terrestrial systems, while sediment was the dominant sink of PAHs in aquatic systems.Supporting information


The present study extended traditional nation-based research on person–culture–fit to the regional level. First, we examined the geographical distribution of Big Five personality traits in Switzerland. Across the 26 Swiss cantons, unique patterns were observed for all traits. For Extraversion and Neuroticism clear language divides emerged between the French- and Italian-speaking South-West vs. the German-speaking North-East. Second, multilevel modeling demonstrated that person–environment–fit in Big Five, composed of elevation , scatter (differences in mean variances) and shape (Pearson correlations between individual and cantonal profiles across all traits; Furr,  The world we live in offers an overwhelming economic, political, cultural, social and climatic diversity , a national panel study that collects annual data on a large, stratified, random sample of Swiss residents  was used to investigate whether person–environment–fit was associated with subjective well-being. Given its manifold downstream consequences, e.g., for health, longevity, social relationships and fertility, subjective wellbeing has evolved into a vibrant field Diener, , which iSD = 19.16), which is consistent with prior research if one bears in mind that minors were not included in the current study  to wave 17 (2015) of the SHP (described below) were used. Given the data collection conventions of the SHP, inter alia, the dataset contains minors from 14 to 17 years of age. Recognizing that personality is usually not yet fully developed and rather prone to drastic changes during one's youth , which oversees the SHP, agreeing to legal and ethical conditions that apply to the use of the data for research purposes .r = 0.08 (agreeableness), r = 0.26 (conscientiousness), r = 0.36 (extraversion), r = 0.36 (neuroticism), and r = 0.21 (openness to experience), which is consistent with prior published research featuring personality data from the SHP  of each Big Five trait was computed. Next, these variances were averaged to calculate a mean variance for each profile. Thereafter, the absolute difference between the mean variance of the respective individual's profile and the profile of their canton of residence was calculated and labeled as scatter Furr, , 2010. TShape was derived via a Pearson correlation on the construct level  between the respective individual and the corresponding canton of residence Furr, , 2010. FTaken together, a good fit would be composed of high shape (high correlation and thus resemblance between the profiles under comparison), as well as low elevation  and low scatter (less difference in variance and henceforth greater similarity).For our main analyses, all indices were based on the construct level . However, all indices were also calculated on the item level  and employed in a robustness check as reported in the Results section.In keeping with the research questions outlined in the introduction, the analysis procedure is two-pronged: First, based on the aggregate Big Five traits, heat maps were created to locate and visualize the geographical distribution of personality across cantons . Second, multi-level modeling (MLM) was applied to investigate whether canton-level person–environment–fit in personality predicts subjective wellbeing fluctuations with individuals as unit of analysis.To visualize their spatial distribution across Switzerland, canton-level Big Five scores had to be calculated. To that end, every participant who had completed the BFI-10 at some point was considered. Canton of residence in the year of Big Five assessment determined the respective canton to which participants' Big Five scores were attributed. After exclusion of minors, 7,767 participants remained. As is customary in geographical psychology, the cantons' Big Five personality profiles were derived by aggregating the scores of all inhabitants of the respective cantons  and henceforth considered prone to bias. The maps displayed in Figure  Pisati, . Mirrori Pisati, , unique As can be seen in Figure Figure Whereas Agreeableness and Conscientiousness showed somewhat fragmented and inconsistent geographical patterns as outlined above, a very clear-cut divide exists for Extraversion. Hereby, Extraversion is highest among the German-speaking eastern cantons i.e., Appenzell Outer Rhodes, Schaffhausen, Schwyz, St. Gallen, Thurgovia, suggesting that large proportions of residents in this part of the country were sociable, energetic and talkative. Meanwhile, the lowest levels of Extraversion are all found in southwestern Switzerland, i.e., French-speaking Fribourg, Geneva, Neuchâtel, Valais, Vaud and the Italian-speaking Ticino, thus indicating that residents of these cantons tended to be introverted, reserved and quiet.Clear patterns were found when mapping out geographical variation in Neuroticism, with the data producing a nearly inverse mirror image of the Extraversion map. As such, comparatively low concentrations were located in the German-speaking Eastern cantons of Appenzell Outer Rhodes, Schaffhausen, St. Gallen, suggesting that inhabitants of these areas were contented, self-confident and emotionally stable. High concentrations of Neuroticism appeared primarily in the French-speaking Western part of the country  and the Italian-speaking Ticino, suggesting that people living in these regions were comparatively moody, tense and depressed.Lastly, Figure Harnessing the longitudinal structure of the panel data, the impact of the three person–environment–fit indices on the development of various indicators of subjective wellbeing  was examined. As it yielded the best trade-off between sample size, availability of fit indices and length of observational timeframe, 2012 (wave 14) was set as base year. For the Big Five, which are not available longitudinally, a cumulative canton-level person–environment–fit was computed with data from 2009 (wave 11) to 2011 wave 13). Again, canton of residence in the year of Big Five assessment determined the respective canton to which participants' Big Five scores were attributed. Mirroring the foregoing mapping approach, six cantons whose personality profiles were calculated from <50 people  were excluded from analysis. Table . Again, When examining within-person variability in psychological states, multilevel modeling (MLM) is usually the method of choice Nezlek, . In the Following Nezlek , we firsxtmixed command in Stata 14.1. The results are displayed in Table 2-statistics, model degrees of freedom and N (Level 1) as well as N (Level 2) and N (Level 3) are presented. All models were significant . Moreover, in all four cases the three-level model offered a significantly better fit to the data than a single level model .Turning to the test of our hypothesis, we then fitted multilevel models for all four dependent variables, using the In keeping with the guidelines assembled by Nezlek  in the r(higher person–environment–fit predicts increased subjective wellbeing) mixed results were found, even though the findings for every fit index  in isolation were consistent. In accordance with our assumptions Big Five shape similarity significantly predicted higher life satisfaction (β = 0.134*), enhanced satisfaction with personal relationships (β = 0.117*), stronger positive affect (β = 0.222*) as well as reduced negative affect (β = −0.235*). Meanwhile, failing to support our hypothesis, Big Five elevation did not emerge as significant predictor of subjective wellbeing. Lastly, in clear conflict with our expectations, Big Five scatter consistently predicted subjective wellbeing in the opposite direction of our predictions. As such, higher scatter, which is indicative of decreased fit, was significantly related to elevated life satisfaction (β = 0.137*), greater satisfaction with personal relationships (β = 0.166*), more positive affect (β = 0.127*) and less negative affect (β = −0.145*).As can be seen in Table To ensure the validity of the findings, a series of robustness checks was applied. First, in recognition of the hierarchical structure of personality, McCrae  has arguSecond, Wood and Furr  have poiper se would produce the observed effects.We tried to account for the NDC by removing the Big Five trait that is most likely to be confounded with desirability, i.e., Neuroticism from our model. Neuroticism is evidently the least desirable of the Big Five traits , concordant with our hypothesis  and higher negative affect (β = 0.022*), which conforms to our original fit hypothesis.However, more noteworthy deviations from the original findings occurred when removing Neuroticism from the fit indices, as becomes apparent in Table n = 50 to include cantons in the MLM might not be conservative enough. Thus, in order to rule out that this decision may have affected our outcomes, we varied the cutoff-value and reran the model, setting a minimum cell size of 200 for inclusion in the model. As a result, the number of cantons that were included at Level 3 shrunk to 13. Again, as can be seen in Table *) and Model 3  where Big Five elevation emerged as significant predictor in line with our original expectations.Third and last, one might argue that the cutoff-value of Taken together, the present analysis yielded mixed results with respect to our hypothesis. More specifically, the findings offered strong empirical evidence in favor of the positive impact of shape, with the effects holding up through a series of various robustness checks, thus inspiring confidence in their validity. In contrast, while the few occasions when elevation emerged as statistically significant predictor pointed in the hypothesized direction, in the vast majority of cases it yielded null findings, thus failing to provide much support for our predictions. Intriguingly, all scatter predictors produced effects in the opposite direction of those predicted, except for one robustness check, when Neuroticism was removed from the Big Five fit indices  there is considerable regional variation in personality traits across the 26 cantons of Switzerland, and (2) canton-level person–environment–fit predicts various indicators of subjective wellbeing. However, the findings are not as clear and straightforward as this summary suggests. Therefore, in the following paragraphs the present results are discussed in detail.M = 52.29, SD = 9.34) and Italy  were higher than in Germany . Likewise, the reversed pattern was found for Extraversion which was considerably higher in Germany  than in France  and marginally higher than in Italy . This finding hints at potentially meaningful cultural interaction effects in border regions and offers an interesting avenue for future research.First, exploring the geographical distribution of Big Five personality traits yielded an intriguing pattern. Agreeableness, Conscientiousness and Openness showed variation that mirrored prior research  and elevation  pointed to the existence of non-linear effects. Although preliminary these findings suggest that fit is not necessarily a matter of sameness and deserves increased attention as it appears to be a much more complex phenomenon than previously assumed.At the same time, the notion of supplementary vs. complementary fit and optimal distinctiveness Brewer,  may not In light of these considerations, we tentatively draw the following conclusions: First, the study of cultural differences at the regional level offers a fruitful addition to traditional nation-based approaches to culture . Although great care was taken by the responsible researchers at the Swiss Centre of Expertise in the Social Sciences FORS to ensure equivalence by using established measures with solid psychometric properties and thoroughly validated translations whenever possible, one might raise concerns about measurement invariance. However, prior research in cultural psychology has undertaken extensive comparisons across various multilingual cohorts : 8.57%, wave 12 (2010): 6.87%, wave 13 (2011): 6.39%, wave 14 (2012): 7.84%, wave 15 (2013): 5.83%, wave 16 (2014): 5.48%, wave 17 (2015): 5.85%). This finding is consistent with representative statistics for Switzerland as a whole, where 75% of all intra-national residential mobility takes place within the same canton . Said use for the current research has been explicitly approved by the Swiss Centre of Expertise in the Social Sciences (FORS), after ethical and legal conditions had been met by our research team upon signing a bilateral contract in accordance with the data distribution policy of FORS and the SHP. The Swiss Household Panel itself was carried out in accordance with the recommendations of the Research Commission of the University of Neuchâtel. The protocol was approved by the Research Commission of the University of Neuchâtel. All subjects had been provided with written informed consent in accordance with the Declaration of Helsinki and also gave verbal consent as the data collection was conducted via telephone interviews.FG and PR: contributed conception and design of the study; FG: organized the database; TE and FG: performed the statistical analysis; FG: wrote the first draft of the manuscript; TE and PR: critically revised the manuscript. All authors have read and approved the final 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.


The relative abundance of DPPC was clearly lower in NSCLC sputum than in control, and the relative abundances of phosphatidylglycerol and phosphatidylglycerolphosphate were higher in NSCLC sputum than in control. The detection of changes in sputum lipids with ND-EESI-MS may be a noninvasive, radiation-free, relatively inexpensive, repeatable, and efficient method for diagnosis of NSCLC.Non–small cell lung cancer (NSCLC) is a leading cause of cancer mortality worldwide, and early diagnosis needs to be improved. We examined whether neutral desorption extractive electrospray ionization mass spectrometry (ND-EESI-MS) could be used to detect sputum lipids expression changes to enable earlier diagnosis. Overall, 167 NSCLC patients and 140 controls were enrolled. The main peaks in the sputum of patients with NSCLC patients differed from controls , and the signals were not associated with pathological type, TNM stage or smoking history. The relative abundance of peaks at m/z734, m/ z756, m/z772, m/z782, m/z798 and m/z803 reliably distinguished NSCLC sputum from control. Collision-induced dissociation confirmed that m/z734, m/z756, and m/z772 represented [DPPC + H] Lung cancer is a leading cause of cancer death in both men and women world wide . There aIn many pulmonary diseases , sputum examination is a valuable tool for disease diagnosis. The sputum has been the target for the discovery of noninvasive biomarkers to diagnose NSCLC because it contains airway epithelial cells, and molecular alterations identified in sputum are most likely to reflect tumor-associated changes . However+ was higher in normal tissue than in cancerous tissue Pulmonary surfactants are produced by type II alveolar epithelial cells (AT II cells) that are a type of lung stem cell. There is evidence that the occurrence of lung cancer is closely related to mutation in these cells . In our In conclusion, we have shown that using ND-EESI-MS in combination with PCA can facilitate the discovery of different lipids, including DPPC, PG, and PGP, in sputum, and that DPPC, PG, and PGP may be useful potential biomarkers of NSCLC. This difference in lipids in sputum can be used to noninvasively predict and assess the occurrence of NSCLC. The method could improve the rate of the early detection of NSCLC and thus improve the survival time of these patients.This study was approved by the Medical Ethics Committee of the Hospital Institutional Review Board of the Second Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China. All clinical investigations were conducted according to the principles expressed in the Declaration of Helsinki.For this study we used a LTQ-XL mass spectrometer . Methanol  was obtained from Tedia Company Inc., Fairfeild, OH, USA, and acetic acid from Xilong Chemical Company, Shantou, People's Republic of China. The deionized water was homemade. Sputum samples were obtained from the Second Affiliated Hospital of Nanchang University.−1 by a pump, ionized by a high voltage of +3.5 kV, and atomized by a N2 gas flow of 1.2–1.6 MPa. A gentle N2 gas flow of 0.4–0.6 MPa was then driven into the desorption liquid  to form a N2/methanol/acetic acid gas flow as the neutral desorption airflow, which was used to bring the interior analytes of the sputum to the ionization region. The interior analytes of sputum were charged continuously when it met the ionizing solvent  comprised 43 healthy individuals and 97 patients with other  lung diseases attending hospital during the same period; the latter included 39 patients with COPD, 33 patients with bronchiectasis, and 25 patients with pneumonia or other bacterial pulmonary diseases. None of these patients had any type of cancer. The median age of the controls was 54 years .All hospitalized patients were enrolled in this study from March 2015 to May 2016 if they had a diagnosis of NSCLC (confirmed by pathology), no other accompanying malignancies, no other lung diseases, and no history of preoperative chemotherapy or radiotherapy. In total, 167 NSCLC patients were enrolled in this study. The median age of the participants was 59.5 years . There were 87 adenocarcinomas, 75 squamous cell carcinomas, and 5 large cell lung carcinomas in this group. According to the latest lung cancer staging system, 13 patients had stage I disease, 26 had stage Ib disease, 51 had stage IIa disease, 47 had stage IIb disease, 21 had stage IIIa disease, and 9 had stage IIIb disease. The control group  database . PCA of the mass spectral fingerprint data was processed using MATLAB, version 7.11 . PCA transforms the original measured variables into new uncorrelated variables called principal components. The first component describes most of the variation in the data. The second principal component is orthogonal and covers much of the remaining variation. Analyzed data were then standardized to account for the different magnitudes, so that the responses and parameters contributed equally to the data set variance and to the principal component calculation. The ions intensity of differential ions were selected and imported into MS Excel 2013 , and the curve was produced in Origin 9.0 .