Screening for affective dysregulation in school-aged children: relationship with comprehensive measures of affective dysregulation and related mental disorders

Affective dysregulation (AD) is characterized by irritability, severe temper outbursts, anger, and unpredictable mood swings, and is typically classified as a transdiagnostic entity. A reliable and valid measure is needed to adequately identify children at risk of AD. This study sought to validate a parent-rated screening questionnaire, which is part of the comprehensive Diagnostic Tool for Affective Dysregulation in Children (DADYS-Screen), by analyzing relationships with comprehensive measures of AD and related mental disorders in a community sample of children with and without AD. The sample comprised 1114 children aged 8–12 years and their parents. We used clinical, parent, and child ratings for our analyses. Across all raters, the DADYS-Screen showed large correlations with comprehensive measures of AD. As expected, correlations were stronger for measures of externalizing symptoms than for measures of internalizing symptoms. Moreover, we found negative associations with emotion regulation strategies and health-related quality of life. In receiver operating characteristic (ROC) analyses, the DADYS-Screen adequately identified children with AD and provided an optimal cut-off. We conclude that the DADYS-Screen appears to be a reliable and valid measure to identify school-aged children at risk of AD

Impact of the COVID-19 pandemic on children with and without affective dysregulation and their families

Analyzing COVID-19-related stress in children with affective dysregulation (AD) seems especially interesting, as these children typically show heightened reactivity to potential stressors and an increased use of maladaptive emotion regulation strategies. Children in out-of-home care often show similar characteristics to those with AD. Since COVID-19 has led to interruptions in psychotherapy for children with mental health problems and to potentially reduced resources to implement treatment strategies in daily life in families or in out-of-home care, these children might show a particularly strong increase in stress levels. In this study, 512 families of children without AD and 269 families of children with AD reported on COVID-19-related stress. The sample comprised screened community, clinical, and out-of-home care samples. Sociodemographic factors, characteristics of child and caregiver before the pandemic, and perceived change in external conditions due to the pandemic were examined as potential risk or protective factors. Interestingly, only small differences emerged between families of children with and without AD or between subsamples: families of children with AD and families in out-of-home care were affected slightly more, but in few domains. Improvements and deteriorations in treatment-related effects balanced each other out. Overall, the most stable and strongest risk factor for COVID-19-related stress was perceived negative change in external conditions—particularly family conditions and leisure options. Additionally, caregiver characteristics emerged as risk factors across most models. Actions to support families during the pandemic should, therefore, facilitate external conditions and focus on caregiver characteristic to reduce familial COVID-19-related stress. Trial registration: German Clinical Trials Register (DRKS), ADOPT Online: DRKS00014963 registered 27 June 2018, ADOPT Treatment: DRKS00013317 registered 27 September 2018, ADOPT Institution: DRKS00014581 registered 04 July 2018

Biomarkers in Liquid Biopsies for Prediction of Early Liver Metastases in Pancreatic Cancer

Individualized diagnostics approaches in modern cancer therapy require predictive and prognostic biomarkers that are easily accessible and stratify patients for optimal and individualized treatment. Pancreatic ductal adenocarcinoma (PDAC) is still a life-threatening disease mainly because of its late diagnosis in advanced stages or rapid progress even in patients with curative resection of the primary tumor. Moreover, patients with liver metastases exhibit an even worse prognosis. Hence, this retrospective multi-center study aims to identify biomarkers in perioperative serum of PDAC patients predicting early liver metastasis. A highly sensitive biomarker analysis was performed using two different methodological approaches. Olink® analysis, which was also used to validate LEGENDplexTM results, identified significant differences in proteins involved in chemotaxis and migration of immune cells as well as cell growth in serum of patients with early versus late onset of liver metastasis. Further studies with larger cohorts are required to validate these findings for clinical translation

Simulation of the interaction of galactic cosmic-ray protons with meteoroids : on the production of radionuclides in thick gabbro and iron targets irradiated isotropically with 1.6 GeV protons

Thick spherical targets made of gabbro (R = 25 cm) and of steel (R = 10 cm) were irradiated isotropically with 1.6 GeV protons at the Saturne synchrotron at Laboratoire National Saturne (LNS)/CEN Saclay in order to simulate the interaction in space of galactic cosmic-ray (GCR) protons with stony and iron meteoroids. Proton fluences of 1.32 x 10(14) cm(-2) and 2.45 x 10(14) cm(-2) were received by the gabbro and iron sphere, respectively, which corresponds to cosmic-ray exposure ages of about 1.6 and 3.0 Ma. Both artificial meteoroids contained large numbers of high-purity target foils of up to 28 elements at different depths. In these individual target foils, elementary production rates of radionuclides and rare gas isotopes were measured by x- and gamma-spectrometry, by low-level counting, accelerator mass spectrometry (AMS), and by conventional rare gas mass spectrometry. Also samples of the gabbro itself were analyzed. Up to now, for each of the experiments, similar to 500 target-product combinations were investigated of which the results for radionuclides are presented here. The experimental production rates show a wide range of depth profiles reflecting the differences between low-, medium-, and high-energy products. The influence of the stony and iron matrices on the production of secondary particles and on particle transport, in general, and consequently on the production rates is clearly exhibited by the phenomenology of the production rates as well as by a detailed theoretical analysis. Theoretical production rates were calculated in an a priori way by folding depth-dependent spectra of primary and secondary protons and secondary neutrons calculated by Monte Carlo techniques with the excitation functions of the underlying nuclear reactions. Discrepancies of up to a factor of 2 between the experimental and a priori calculated depth profiles are attributed to the poor quality of the mostly theoretical neutron excitation functions. Improved neutron excitation functions were obtained by least-squares deconvolution techniques from experimental thick-target production rates of up to five thick-target experiments in which isotropic irradiations were performed. A posteriori calculations using the adjusted neutron cross sections describe the measured depth profiles of all these simulation experiments within 9%. The thus validated model calculations provide a basis for reliable physical model calculations of the production rates of cosmogenic nuclides in stony and iron meteorites as well as in lunar samples and terrestrial materials

Simulation of the interaction of galactic cosmic-ray protons with meteoroids : on the production of radionuclides in thick gabbro and iron targets irradiated isotropically with 1.6 GeV protons

Thick spherical targets made of gabbro (R = 25 cm) and of steel (R = 10 cm) were irradiated isotropically with 1.6 GeV protons at the Saturne synchrotron at Laboratoire National Saturne (LNS)/CEN Saclay in order to simulate the interaction in space of galactic cosmic-ray (GCR) protons with stony and iron meteoroids. Proton fluences of 1.32 x 10(14) cm(-2) and 2.45 x 10(14) cm(-2) were received by the gabbro and iron sphere, respectively, which corresponds to cosmic-ray exposure ages of about 1.6 and 3.0 Ma. Both artificial meteoroids contained large numbers of high-purity target foils of up to 28 elements at different depths. In these individual target foils, elementary production rates of radionuclides and rare gas isotopes were measured by x- and gamma-spectrometry, by low-level counting, accelerator mass spectrometry (AMS), and by conventional rare gas mass spectrometry. Also samples of the gabbro itself were analyzed. Up to now, for each of the experiments, similar to 500 target-product combinations were investigated of which the results for radionuclides are presented here. The experimental production rates show a wide range of depth profiles reflecting the differences between low-, medium-, and high-energy products. The influence of the stony and iron matrices on the production of secondary particles and on particle transport, in general, and consequently on the production rates is clearly exhibited by the phenomenology of the production rates as well as by a detailed theoretical analysis. Theoretical production rates were calculated in an a priori way by folding depth-dependent spectra of primary and secondary protons and secondary neutrons calculated by Monte Carlo techniques with the excitation functions of the underlying nuclear reactions. Discrepancies of up to a factor of 2 between the experimental and a priori calculated depth profiles are attributed to the poor quality of the mostly theoretical neutron excitation functions. Improved neutron excitation functions were obtained by least-squares deconvolution techniques from experimental thick-target production rates of up to five thick-target experiments in which isotropic irradiations were performed. A posteriori calculations using the adjusted neutron cross sections describe the measured depth profiles of all these simulation experiments within 9%. The thus validated model calculations provide a basis for reliable physical model calculations of the production rates of cosmogenic nuclides in stony and iron meteorites as well as in lunar samples and terrestrial materials