Disruptive behavior disorders and psychopathic traits in adolescents:Empathy-related responses to witnessing animal distress

Cruelty to animals is a symptom of conduct disorder and associated with psychopathic traits in childhood. One of the factors thought to contribute to animal cruelty is reduced empathy and concern for the well-being of animals. A first aim of this study was to examine empathy towards animals in distress in male adolescents with disruptive behavior disorders (DBD) and high or low psychopathic traits, and normal controls (NC). Psychopathic traits were assessed by the Antisocial Process Screening Device (APSD). Respondents were exposed to a short film clip depicting a baby bear in distress. Heart rate (HR) responses were monitored during film exposure. Afterwards, respondents were asked to report the emotions they had observed and experienced. Contrary to expectations based on research on human empathy, no group differences were found in empathy-related responses to witnessing animal distress. Both DBD groups and normal controls observed equal levels of distress in the baby bear, experienced as much empathy and sympathy, and showed similar levels of HR reduction during the most dramatic scene. Results suggest that empathy for humans does not generalize to animals, and vice versa. A second aim was to examine the associations between empathy-related responses and the broad concept of psychopathy as well as its dimensions. The relationships were different and for the most part reversed in the NC and DBD groups. Group proved to be an important moderating factor, indicating that results obtained within a sample of healthy adolescents do not generalize to adolescents with DBD, and vice versa

The Neurovegetative Complaints Questionnaire in the Maastricht Aging Study: psychometric properties and normative data

Hoogenhout, E. M., Van der Elst, W., De Groot, R. H. M., Van Boxtel, M. P. J., & Jolles, J. (2010). The neurovegetative complaints questionnaire in the Maastricht aging study: Psychometric properties and normative data. Aging and Mental Health, 14(5), 613-23.Neurovegetative and somatic symptoms (such as headaches, heart palpitations, and dizziness) have a high prevalence. These symptoms are often indicative for ‘masked depression’ or ‘depression without sadness’, especially in older adults. At present, no instrument exists that enables the assessment of these symptoms. The current study presents a questionnaire that assesses neurovegetative and somatic complaints, as well as reactive emotional complaints: the ‘Neurovegetative Complaints Questionnaire’ (NCQ). The factor structure, internal consistency, and validity of the NCQ were evaluated in a large sample of 1,105 healthy subjects aged 24-81 years from the Maastricht Aging Study. The effects of age, gender and educational level on the NCQ measures were established to provide demographically corrected normative data. Two constructs underlay the responses to the NCQ items, i.e., the Neurovegetative/Somatic and Reactive/Emotional complaints factors (eigenvalues were 4.63 and 1.65 respectively, 33.0 % of the variance was explained, Pearson’s r between both factors equalled .448). Internal consistency of both scales was acceptable (i.e. Cronbach’s α = .74 and .71, respectively) and convergent validity was sufficient (Pearson’s r = |.387 - .499|). Females and older participants were characterized by more Neurovegetative/ Somatic and Reactive/Emotional complaints compared to males and younger people. Demographically corrected regression-based norms were provided for use in research and clinical settings. The NCQ is a psychometrically sound questionnaire that is specifically aimed at assessing neurovegetative/somatic and reactive/emotional complaints, symptoms that often are indicative for a ‘masked depression’

The complex associations between early childhood adversity, heart rate variability, cluster B personality disorders, and aggression

Early childhood adversity can cause an imbalance in the autonomic function, which may in turn lead to the development of trauma-spectrum disorders and aggressive behavior later in life. In the present study, we investigated the complex associations between early adversity, heart rate variability (HRV), cluster B personality disorders, and self-reported aggressive behavior in a group of 50 male forensic inpatients (M age = 41.16; SD = 10.72). Structural Equation Modeling analysis revealed that patients with cluster B personality disorders were more likely to have adverse early childhood experiences and reduced sympathetic dominance in response to a threat than patients without cluster B personality disorders. In addition, HRV and cluster B personality disorders did not significantly mediate the association between early childhood adversity and self-reported aggressive behavior. These findings are important for clinical practice to facilitate specific treatment programs for those affected

Testing elementary and secondary school students’ ability to perform historical perspective taking: the constructing of valid and reliable measure instruments

Historical reasoning competencies play an important role in history education. However, valid and reliable large-scale measurement instruments to assess these competencies are scarce. This study considers two instruments for measuring students’ ability to perform historical perspective taking (HPT) as a historical reasoning competency. The instruments have been tested for validity and reliability among 1,270 Dutch upper elementary and secondary school students, ranging in age from 10 to 17 years. One instrument offers effective validity and reliability and can map HPT performance among a large and heterogeneous student population. The results show that even upper elementary school students are capable of performing HPT. However, as students age, their ability to perform HPT increases. Differences regarding the ability to perform HPT were also found between educational levels. Pre-university students performed HPT more successfully compared to students at lower educational levels. The results of this study can be used to gain insight into the construct of HPT and into how historical reasoning competencies such as HPT can be measured. Furthermore, the results provide insight into how differences between students, such as age and educational levels, influence the performance of HPT

Teaching Historical Contextualization:The Construction of a Reliable Observation Instrument

Since the 1970s, many observation instruments have been constructed to map teachers’ general pedagogic competencies. However, few of these instruments focus on teachers’ subject-specific competencies. This study presents the development of the Framework for Analyzing the Teaching of Historical Contextualization (FAT-HC). This high-inference observation instrument focuses on history teachers’ competency in promoting historical contextualization in classrooms. The results of the study demonstrate the instrument’s content validity. Generalizability studies were conducted to further assess the instrument’s dimensionality and reliability by decomposing the instrument’s variance. A large proportion of the variance was explained by differences between observed teachers, and a small proportion of the variance was explained by lessons and observers, demonstrating the instrument’s reliability. Furthermore, a decision study was conducted to determine the optimal number of observers and lessons needed for a reliable scoring design. The developed instrument could be used to gain greater insight into history teachers’ subject-specific competencies and to focus teacher professionalization on teachers’ specific needs

Promoting historical contextualization: the development and testing of a pedagogy

The aim of this explorative study was to develop and test a pedagogy aimed at promoting students’ ability to perform historical contextualization. Teaching historical contextualization was conceptualized in terms of four pedagogical design principles: (1) making students aware of the consequences of a present-oriented perspective when examining the past, (2) enhancing the reconstruction of a historical context, (3) enhancing the use of the historical context to explain historical phenomena and (4) enhancing historical empathy. The effectiveness of these principles was explored in a lesson unit focusing on the seventeenth and eighteenth centuries. In a quasi-experimental pre-test–post-test design with experimental and control conditions, the effects of the pedagogy on 15- and 16-year-old students’ ability to perform historical contextualization were examined (n = 131). The results indicated that students in the experimental condition significantly improved their ability to perform historical contextualization compared to students in the control condition. These findings could be used to help teachers and other educational professionals design and implement historical contextualization tasks and instructions

Students’ historical contextualization and the cold war

This exploratory study presents an example of how a historical contextualization framework can be used to develop and implement a lesson unit on Cold War events. The effects of the lesson unit on students’ ability to perform historical contextualization are explored in a quasi-experimental pre-test–post-test design with an experimental (n = 96) and a control (n = 73) condition. The students’ answers on a historical contextualization test were analysed. The results indicate that students in the experimental condition increased their ability to perform historical contextualization and displayed less present-oriented perspectives in their answers compared to students in the control condition

Exposure-toxicity relationship of cabozantinib in patients with renal cell cancer and salivary gland cancer

Cabozantinib is registered in fixed 60 mg dose. However, 46% to 62% of patients in the registration studies needed a dose reduction due to toxicity. Improved clinical efficacy has been observed in renal cell carcinoma patients (RCC) with a cabozantinib exposure greater than 750 μg/L. In our study we explored the cabozantinib exposure in patients with different tumour types. We included RCC patients from routine care and salivary gland carcinoma (SGC) patients from a phase II study with ≥1 measured C min at steady-state. The geometric mean (GM) C min at the starting dose, at 40 mg and at best tolerated dose (BTD) were compared between both tumour types. Forty-seven patients were included. All SGC patients (n = 22) started with 60 mg, while 52% of RCC patients started with 40 mg. GM C min at the start dose was 1456 μg/L (95% CI: 1185-1789) vs 682 μg/L (95% CI: 572-812) (P <.001) for SGC and RCC patients, respectively. When dose-normalised to 40 mg, SGC patients had a significantly higher cabozantinib exposure compared to RCC patients (C min 971 μg/L [95% CI: 790-1193] vs 669 μg/L [95% CI: 568-788]) (P =.005). Dose reductions due to toxicity were needed in 91% and 60% of SGC and RCC patients, respectively. Median BTD was between 20 to 30 mg for SGC and 40 mg for RCC patients. GM C min at BTD were comparable between the SGC and the RCC group, 694 μg/L (95% CI: 584-824) vs 583 μg/L (95% CI: 496-671) (P =.1). The observed cabozantinib exposure at BTD of approximately 600 μg/L is below the previously proposed target. Surprisingly, a comparable exposure at BTD was reached at different dosages of cabozantinib for SGC patients compared to RCC patients Further research is warranted to identify the optimal exposure and starting dose to balance efficacy and toxicity

Excessive toxicity of cabozantinib in a phase II study in patients with recurrent and/or metastatic salivary gland cancer

AIM: Because the tyrosine kinases c-MET and vascular endothelial growth factor receptors (VEGFR) are often overexpressed in salivary gland cancer (SGC), this study evaluated the efficacy and safety of cabozantinib in patients with recurrent/metastatic (R/M) SGC. PATIENTS AND METHODS: A single-centre phase II study was conducted. Patients with immunohistochemical c-MET-positive R/M SGC were included in three cohorts: adenoid cystic carcinoma (ACC); salivary duct carcinoma (SDC) and other miscellaneous SGCs. No prior systemic treatments were required. Patients started cabozantinib 60 mg once daily. The primary outcome was the objective response rate (ORR). Secondary outcomes included survival, safety and quality of life. Per Simon-two-stage design, depending on efficacy, a maximum of 43 patients would be included. RESULTS: In total, 25 patients were included until premature closure owing to severe toxicity. Six patients (24%) had grade 3-5 wound complications, occurring at a median of 7.1 months on cabozantinib treatment (range 2.1-12.6). Remarkably, four of these six patients developed this complication in the area prior exposed to high-dose radiotherapy. Other grade ≥3 adverse events in >1 patient were hypertension (20%), diarrhoea (8%) and dehydration (8%). Twenty-one patients were evaluable for response; 1/15 ACC (ORR: 7%); 1/4 SDC and 0/2 patients with other miscellaneous SGC responded. Median progression-free survival was 9.4 months (95% confidence interval [CI] 7.4-11.4 months), 7.2 months (95%CI 0.0-15.1) and 6.9 months (95%CI 0.0-15.1), respectively. CONCLUSION: This study showed too many severe cabozantinib-associated wound complications in patients with SGC, especially in prior irradiated areas. Therefore, the study closed prematurely. The efficacy in the limited number of evaluable patients was low to moderate. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov: NCT03729297

Serum Iron Parameters, HFE C282Y Genotype, and Cognitive Performance in Older Adults: Results From the FACIT Study

Although iron homeostasis is essential for brain functioning, the effects of iron levels on cognitive performance in older individuals have scarcely been investigated. In the present study, serum iron parameters and hemochromatosis (HFE) C282Y genotype were determined in 818 older individuals who participated in a 3-year randomized, placebo-controlled double-blind trial examining the effects of folic acid on carotid intima-media thickness. All participants had slightly elevated homocysteine levels and were vitamin B12 replete. Cognitive functioning was assessed at baseline and after 3 years by means of a neuropsychological test battery. At baseline, increased serum ferritin was associated with decreased sensorimotor speed, complex speed, and information-processing speed and increased serum iron was associated with decreased sensorimotor speed. Cognitive performance over 3 years was not associated with HFE C282Y genotype or iron parameters. In conclusion, serum iron parameters do not show a straightforward relationship with cognitive functioning, although elevated iron levels may decrease cognitive speed in older individuals susceptible to cognitive impairmen