General Psychopathology and Dysregulation Profile in a Longitudinal Community Sample: Stability, Antecedents and Outcomes.

The general factor of psychopathology (GP, or p factor) and the Dysregulation Profile (DP) are two conceptually similar, but independently developed approaches to understand psychopathology. GP and DP models and their stability, antecedents and outcomes are studied in a longitudinal sample of 1073 children (49.8% female). GP and DP models were estimated at ages 8 and 14 years using the parent-reported Child Behavior Checklist (CBCL) and Youth Self Report (YSR). Early childhood antecedents and adolescent outcomes were derived using a multi-method multi-informant approach. Results showed that the general GP and DP had similar key symptoms and were similarly related to early-childhood antecedents (e.g., lower effortful control, higher maternal depression) and adolescent outcomes (e.g., reduced academic functioning, poorer mental health). This study demonstrates that GP and DP are highly similar constructs in middle childhood and adolescence, both describing a general vulnerability for psychopathology with (emotional) dysregulation at its core. Scientific integration of these approaches could lead to a better understanding of the structure, antecedents and outcomes of psychopathology

The Dysregulation Profile in middle childhood and adolescence across reporters: factor structure, measurement invariance, and links with self-harm and suicidal ideation

Recently, a phenotype of severe dysregulation, the Dysregulation Profile (DP), has been identified. DP consists of elevated scores on the Anxious/Depressed (AD), Aggressive Behavior (AGG) and Attention Problems (AP) scales of the Child Behavior Checklist (CBCL), Teacher Report Form (TRF), or Youth Self Report (YSR). A drawback in current research is that DP has been conceptualized and operationalized in different manners and research on the factor structure of DP is lacking. Therefore, we examined the factor structure of DP across

Патентная система как метод налогового регулирования малого бизнеса

В современной рыночной экономике малый бизнес играет важную роль. Но существование малого бизнеса практически невозможно без активной поддержки со стороны государства, которая должна заключаться в разработке различных программ содействия малому бизнесу, в том числе формирование льготной налоговой политики, направленной на стимулирование его развития. В настоящей работе дана характеристика новой патентной системы налогообложения, введенной в действие с 2013 г., проанализированы ее основные отличия от действующих специальных налоговых режимов. Сделан вывод о том, что новая патентная система как метод налогового регулирования малого бизнеса требует существенной доработки

Effects of oral meal feeding on whole body protein breakdown and protein synthesis in cachectic pancreatic cancer patients

Background: Pancreatic cancer is often accompanied by cachexia, a syndrome of severe weight loss and muscle wasting. A suboptimal response to nutritional support may further aggravate cachexia, yet the influence of nutrition on protein kinetics in cachectic patients is poorly understood. Methods: Eight cachectic pancreatic cancer patients and seven control patients received a primed continuous intravenous infusion of l‐[ring‐2H5]phenylalanine and l‐[3,3‐2H2]tyrosine for 8 h and ingested sips of water with l‐[1‐13C]phenylalanine every 30 min. After 4 h, oral feeding was started. Whole body protein breakdown, protein synthesis, and net protein balance were calculated. Results are given as median with interquartile range. Results: Baseline protein breakdown and protein synthesis were higher in cachectic patients compared with the controls (breakdown: 67.1 (48.1–79.6) vs. 45.8 (42.6–46.3) µmol/kg lean body mass/h, P = 0.049; and synthesis: 63.0 (44.3–75.6) vs. 41.8 (37.6–42.5) µmol/kg lean body mass/h, P = 0.021). During feeding, protein breakdown decreased significantly to 45.5 (26.9–51.1) µmol/kg lean body mass/h (P = 0.012) in the cachexia group and to 33.7 (17.4–37.1) µmol/kg lean body mass/h (P = 0.018) in the control group. Protein synthesis was not affected by feeding in cachectic patients: 58.4 (46.5–76.1) µmol/kg lean body mass/h, but was stimulated in controls: 47.9 (41.8–56.7) µmol/kg lean body mass/h (P = 0.018). Both groups showed a comparable positive net protein balance during feeding: cachexia: 19.7 (13.1–23.7) and control: 16.3 (13.6–25.4) µmol/kg lean body mass/h (P = 0.908). Conclusion: Cachectic pancreatic cancer patients have a higher basal protein turnover. Both cachectic patients and controls show a comparable protein anabolism during feeding, albeit through a different pattern of protein kinetics. In cachectic patients, this is primarily related to reduced protein breakdown, whereas in controls, both protein breakdown and protein synthesis alterations are involved

Networks of Depression and Anxiety Symptoms Across Development.

OBJECTIVE: Frequent co-occurrence and bidirectional longitudinal associations have led some researchers to question the boundaries between depression and anxiety. A longitudinal investigation of the interconnected symptom structure of these constructs may help determine the extent to which they are distinct, and whether this changes over development. Therefore, the present study used network analysis to examine these symptom−symptom associations developmentally from early childhood to mid-adolescence. METHOD: We analyzed data from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development (N = 1,147). Depression and anxiety symptoms were assessed on 7 occasions between ages 5 and 14 years using maternal reports. Regularized partial correlation networks were constructed at each time point, and diagnostic boundaries were explored using empirical tests of network modularity (ie, clustering of symptom nodes). Nonparametric permutation tests were used to determine whether symptoms became more associated over development, and network centrality was examined to identify developmental changes in the overall importance of specific symptoms. RESULTS: Symptoms formed highly interconnected networks, as evidenced by strong associations between depression and anxiety symptoms and a lack of distinct clustering. There was some evidence of an increase in overall connectivity as children aged. Feeling “anxious/fearful” and “unhappy/sad” were consistently the most central symptoms over development. CONCLUSION: Minimal clustering of nodes indicated no separation of depression and anxiety symptoms from early childhood through mid-adolescence. An increase in connectivity over development suggests that symptoms may reinforce each other, potentially contributing to the high levels of lifetime continuity of these disorders

The German National Registry of Primary Immunodeficiencies (2012-2017)

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment

Methotrexat-induzierte Leukenzephalopathie bei Patienten mit akuter lymphatischer Leukämie oder lymphoblastischem Non-Hodgkin-Lymphom in Abhängigkeit vom MTHFR-C677T-Status

The antifolate Methotrexate and folate metabolism is central in therapy of pediatric Acute Lymphatic Leukemia (ALL). Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme of folate metabolism, so that combination of MTX-therapy and mutation of the MTHFR gene (MTHFR C677T) might result in altered toxicity. We examined 31 children with ALL or NHL, that were treated according to GPOH ALL-BFM 95 or 98 protokoll at the pediatric department of Aachen University Hospital, regarding mucositis, leucocytes, bilirubin and transaminases. 23 of them were also examined by MRT or MRS. The relation between chronic cerebral MTX toxicity as seen on MRT and MRS and MTHFR mutation has not been examined systematically so far. 14 of our patients were wildtype, 16 heterozygous and only 1 homozygous mutated TT for MTHFR. There was no statistically significant association between MTHFR mutation and acute or chronic MTX toxicity. However such association was stated before, but only when no additional folate was given, and not if folate rescue after high-dose MTX was administered, like we did. This means a possible effect of the MTHFR mutation might be concealed by high folate doses. So, as far we know today, changing the MTX regimen is not necessary to prevent more severe MTX toxicity

Methotrexat-induzierte Leukenzephalopathie bei Patienten mit akuter lymphatischer Leukämie oder lymphoblastischem Non-Hodgkin-Lymphom in Abhängigkeit vom MTHFR-C677T-Status

The antifolate Methotrexate and folate metabolism is central in therapy of pediatric Acute Lymphatic Leukemia (ALL). Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme of folate metabolism, so that combination of MTX-therapy and mutation of the MTHFR gene (MTHFR C677T) might result in altered toxicity. We examined 31 children with ALL or NHL, that were treated according to GPOH ALL-BFM 95 or 98 protokoll at the pediatric department of Aachen University Hospital, regarding mucositis, leucocytes, bilirubin and transaminases. 23 of them were also examined by MRT or MRS. The relation between chronic cerebral MTX toxicity as seen on MRT and MRS and MTHFR mutation has not been examined systematically so far. 14 of our patients were wildtype, 16 heterozygous and only 1 homozygous mutated TT for MTHFR. There was no statistically significant association between MTHFR mutation and acute or chronic MTX toxicity. However such association was stated before, but only when no additional folate was given, and not if folate rescue after high-dose MTX was administered, like we did. This means a possible effect of the MTHFR mutation might be concealed by high folate doses. So, as far we know today, changing the MTX regimen is not necessary to prevent more severe MTX toxicity

The Dysregulation Profile in middle childhood and adolescence across reporters: factor structure, measurement invariance, and links with self-harm and suicidal ideation

Recently, a phenotype of severe dysregulation, the Dysregulation Profile (DP), has been identified. DP consists of elevated scores on the Anxious/Depressed (AD), Aggressive Behavior (AGG) and Attention Problems (AP) scales of the Child Behavior Checklist (CBCL), Teacher Report Form (TRF), or Youth Self Report (YSR). A drawback in current research is that DP has been conceptualized and operationalized in different manners and research on the factor structure of DP is lacking. Therefore, we examined the factor structure of DP across multiple reporters, measurement invariance across gender, parents, and time, as well as links between DP and self-harm and suicidal ideation. Data from a large community sample were used (N = 697), covering middle childhood (Mage = 7.90, (SD = 1.16) and adolescence (Mage = 13.93, SD = 1.14). Mothers, fathers, teachers, and youth themselves reported on children’s emotional and behavioral problems using the CBCL, TRF, and YSR. Results indicated that in middle childhood and in adolescence, a bifactor model with a general factor of Dysregulation alongside three specific factors of AD, AGG, and AP fitted best, compared to a second-order or one-factor model. The model showed good fit for mother, father, teacher, and youth reports and showed invariance across gender, parents and time. Youth, mother, and father reported Dysregulation was uniquely and positively related to adolescent-reported self-harm and suicidal ideation. The DP is best conceptualized as a broad dysregulation syndrome, which exists over and above anxiety/depression, aggression, and attention problems as specific problems. The bifactor model of DP explains the uniqueness and interrelatedness of these behavioral problems and can help explaining shared and non-shared etiology factors. The exclusive link between the general dysregulation factor and adolescents’ self-harm and suicidal ideation further established the clinical relevance of the bifactor model