Analyzing the Psychological and Social Contents of Evidence—Experimental Comparison between Guessing, Naturalistic Observation, and Systematic Analysis

To improve inferences about psychological and social evidence contained in pictures and texts, a five-step algorithm—Systematic Analysis (SA)—was devised. It combines basic principles of interpretation in forensic science, providing a comprehensive record of signs of evidence. Criminal justice professionals evaluated the usefulness of SA. Effects of applying SA were tested experimentally with 41 subjects, compared to 39 subjects observing naturally (naturalistic observation) and 47 subjects guessing intuitively intuitive guessing group. After being trained in SA, prosecutors and police detectives (N = 217) attributed it a good usefulness for criminal investigation. Subjects (graduate students) using SA found significantly more details about four test cases than those observing naturally (Cohen’s d = 0.58). Subjects who learned SA well abducted significantly better hypotheses than those who observed naturally or who guessed intuitively. Internal validity of SA was a = 0.74. Applying SA improved observation significantly and reduced confirmation bias

United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis (HaPanEU)

There have been substantial improvements in the management of chronic pancreatitis, leading to the publication of several national guidelines during recent years. In collaboration with United European Gastroenterology, the working group on 'Harmonizing diagnosis and treatment of chronic pancreatitis across Europe' (HaPanEU) developed these European guidelines using an evidence-based approach.Twelve multidisciplinary review groups performed systematic literature reviews to answer 101 predefined clinical questions. Recommendations were graded using the Grading of Recommendations Assessment, Development and Evaluation system and the answers were assessed by the entire group in a Delphi process online. The review groups presented their recommendations during the 2015 annual meeting of United European Gastroenterology. At this one-day, interactive conference, relevant remarks were voiced and overall agreement on each recommendation was quantified using plenary voting (Test and Evaluation Directorate). After a final round of adjustments based on these comments, a draft version was sent out to external reviewers.The 101 recommendations covered 12 topics related to the clinical management of chronic pancreatitis: aetiology (working party (WP)1), diagnosis of chronic pancreatitis with imaging (WP2 and WP3), diagnosis of pancreatic exocrine insufficiency (WP4), surgery in chronic pancreatitis (WP5), medical therapy (WP6), endoscopic therapy (WP7), treatment of pancreatic pseudocysts (WP8), pancreatic pain (WP9), nutrition and malnutrition (WP10), diabetes mellitus (WP11) and the natural course of the disease and quality of life (WP12). Using the Grading of Recommendations Assessment, Development and Evaluation system, 70 of the 101 (70%) recommendations were rated as 'strong' and plenary voting revealed 'strong agreement' for 99 (98%) recommendations.The 2016 HaPanEU/United European Gastroenterology guidelines provide evidence-based recommendations concerning key aspects of the medical and surgical management of chronic pancreatitis based on current available evidence. These recommendations should serve as a reference standard for existing management of the disease and as a guide for future clinical research

Zweiter Fortschrittsbericht wirtschaftswissenschaftlicher Forschungsinstitute über die wirtschaftliche Entwicklung in Ostdeutschland.

Auch im Sommer 2003 kann die Entwicklung in der ostdeutschen Wirtschaft niemanden zufrieden stellen. Zusätzlich zu allen Diskussionen um Möglichkeiten einer Belebung der Wachstumsdynamik in ganz Deutschland stellt sich deswegen die Frage, wie die Politik dem Aufbau Ost neuen Schwung geben kann. Diese Frage stellt sich umso dringender, weil die finanzpolitischen Schwierigkeiten Deutschlands die Spielräume für finanziell kostspielige Programme für die neuen Länder stark einengen. Wichtige Bestandteile der Wirtschaftspolitik für Ostdeutschland waren in den letzten Jahren die spezifische Wirtschaftsförderung (insbesondere die Investitionsförderung), für die wegen ihrer Befristung wie auch wegen EU-rechtlicher Restriktionen nach Nachfolgelösungen gesucht wird, sowie die Aktive Arbeitsmarktpolitik, die im Zuge der allgemeinen Arbeitsmarktreformen ebenfalls auf den Prüfstand gestellt worden ist. In Anbetracht der anstehenden Entscheidungen über die weitere Strategie für den Aufbau Ost hat der Bundesminister der Finanzen die mit dem so genannten Fortschrittsbericht betrauten Forschungsinstitute – das Deutsche Institut für Wirtschaftsforschung Berlin (DIW), das Institut für Arbeitsmarkt- und Berufsforschung (IAB), das Institut für Weltwirtschaft an der Universität Kiel (IfW), das Institut für Wirtschaftsforschung Halle (IWH) und das Zentrum für Europäische Wirtschaftsforschung (ZEW) – deshalb gebeten, diese beiden Politikbereiche einer näheren Analyse zu unterziehen und darauf aufbauend wirtschaftspolitische Schlussfolgerungen abzuleiten. Darüber hinaus wurden als weitere Schwerpunkte der Arbeit eine regional differenzierte Analyse der Infrastrukturausstattung in den neuen Ländern, eine Untersuchung der technologischen Leistungsfähigkeit der ostdeutschen Wirtschaft und eine Analyse der finanzpolitischen Situation der ostdeutschen Länder und Gemeinden vereinbart.Wirtschaftliche Anpassung; Wirtschaftspolitik; Wirtschaftspolitische Wirkungsanalyse; Deutschland;

Zweiter Fortschrittsbericht wirtschaftswissenschaftlicher Forschungsinstitute über die wirtschaftliche Entwicklung in Ostdeutschland

Auch im Sommer 2003 kann die Entwicklung in der ostdeutschen Wirtschaft niemanden zufrieden stellen. Zusätzlich zu allen Diskussionen um Möglichkeiten einer Belebung der Wachstumsdynamik in ganz Deutschland stellt sich deswegen die Frage, wie die Politik dem Aufbau Ost neuen Schwung geben kann. Diese Frage stellt sich umso dringender, weil die finanzpolitischen Schwierigkeiten Deutschlands die Spielräume für finanziell kostspielige Programme für die neuen Länder stark einengen. Wichtige Bestandteile der Wirtschaftspolitik für Ostdeutschland waren in den letzten Jahren die spezifische Wirtschaftsförderung (insbesondere die Investitionsförderung), für die wegen ihrer Befristung wie auch wegen EU-rechtlicher Restriktionen nach Nachfolgelösungen gesucht wird, sowie die Aktive Arbeitsmarktpolitik, die im Zuge der allgemeinen Arbeitsmarktreformen ebenfalls auf den Prüfstand gestellt worden ist. In Anbetracht der anstehenden Entscheidungen über die weitere Strategie für den Aufbau Ost hat der Bundesminister der Finanzen die mit dem so genannten Fortschrittsbericht betrauten Forschungsinstitute – das Deutsche Institut für Wirtschaftsforschung Berlin (DIW), das Institut für Arbeitsmarkt- und Berufsforschung (IAB), das Institut für Weltwirtschaft an der Universität Kiel (IfW), das Institut für Wirtschaftsforschung Halle (IWH) und das Zentrum für Europäische Wirtschaftsforschung (ZEW) – deshalb gebeten, diese beiden Politikbereiche einer näheren Analyse zu unterziehen und darauf aufbauend wirtschaftspolitische Schlussfolgerungen abzuleiten. Darüber hinaus wurden als weitere Schwerpunkte der Arbeit eine regional differenzierte Analyse der Infrastrukturausstattung in den neuen Ländern, eine Untersuchung der technologischen Leistungsfähigkeit der ostdeutschen Wirtschaft und eine Analyse der finanzpolitischen Situation der ostdeutschen Länder und Gemeinden vereinbart. --

United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis (HaPanEU)

Background:There have been substantial improvements in the management of chronic pancreatitis, leading to the publication of several national guidelines during recent years. In collaboration with United European Gastroenterology, the working group on Harmonizing diagnosis and treatment of chronic pancreatitis across Europe' (HaPanEU) developed these European guidelines using an evidence-based approach. Methods: Twelve multidisciplinary review groups performed systematic literature reviews to answer 101 predefined clinical questions. Recommendations were graded using the Grading of Recommendations Assessment, Development and Evaluation system and the answers were assessed by the entire group in a Delphi process online. The review groups presented their recommendations during the 2015 annual meeting of United European Gastroenterology. At this one-day, interactive conference, relevant remarks were voiced and overall agreement on each recommendation was quantified using plenary voting (Test and Evaluation Directorate). After a final round of adjustments based on these comments, a draft version was sent out to external reviewers. Results: The 101 recommendations covered 12 topics related to the clinical management of chronic pancreatitis: aetiology (working party (WP)1), diagnosis of chronic pancreatitis with imaging (WP2 and WP3), diagnosis of pancreatic exocrine insufficiency (WP4), surgery in chronic pancreatitis (WP5), medical therapy (WP6), endoscopic therapy (WP7), treatment of pancreatic pseudocysts (WP8), pancreatic pain (WP9), nutrition and malnutrition (WP10), diabetes mellitus (WP11) and the natural course of the disease and quality of life (WP12). Using the Grading of Recommendations Assessment, Development and Evaluation system, 70 of the 101 (70%) recommendations were rated as strong' and plenary voting revealed strong agreement' for 99 (98%) recommendations. Conclusions:The 2016 HaPanEU/United European Gastroenterology guidelines provide evidence-based recommendations concerning key aspects of the medical and surgical management of chronic pancreatitis based on current available evidence. These recommendations should serve as a reference standard for existing management of the disease and as a guide for future clinical research

Low Penetrance, Broad Resistance, and Favorable Outcome of Interleukin 12 Receptor β1 Deficiency: Medical and Immunological Implications

The clinical phenotype of interleukin 12 receptor β1 chain (IL-12Rβ1) deficiency and the function of human IL-12 in host defense remain largely unknown, due to the small number of patients reported. We now report 41 patients with complete IL-12Rβ1 deficiency from 17 countries. The only opportunistic infections observed, in 34 patients, were of childhood onset and caused by weakly virulent Salmonella or Mycobacteria (Bacille Calmette-Guérin -BCG- and environmental Mycobacteria). Three patients had clinical tuberculosis, one of whom also had salmonellosis. Unlike salmonellosis, mycobacterial infections did not recur. BCG inoculation and BCG disease were both effective against subsequent environmental mycobacteriosis, but not against salmonellosis. Excluding the probands, seven of the 12 affected siblings have remained free of case-definition opportunistic infection. Finally, only five deaths occurred in childhood, and the remaining 36 patients are alive and well. Thus, a diagnosis of IL-12Rβ1 deficiency should be considered in children with opportunistic mycobacteriosis or salmonellosis; healthy siblings of probands and selected cases of tuberculosis should also be investigated. The overall prognosis is good due to broad resistance to infection and the low penetrance and favorable outcome of infections. Unexpectedly, human IL-12 is redundant in protective immunity against most microorganisms other than Mycobacteria and Salmonella. Moreover, IL-12 is redundant for primary immunity to Mycobacteria and Salmonella in many individuals and for secondary immunity to Mycobacteria but not to Salmonella in most

Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID)

Introduction: Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin's lymphoma in a real-life clinical setting. Methods: Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators. Results: A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician's visual analogue scale; mean improvement from baseline of 12.1 mm). Conclusions: Data from this registry indicate that rituximab is a commonly employed, well-tolerated therapy with potential beneficial effects in standard of care-refractory autoimmune diseases, and support the results from other open-label, uncontrolled studies

Preventing Phosphorylation of Sterol Regulatory Element-Binding Protein 1a by MAP-Kinases Protects Mice from Fatty Liver and Visceral Obesity

The transcription factor sterol regulatory element binding protein (SREBP)-1a plays a pivotal role in lipid metabolism. Using the SREBP-1a expressing human hepatoma cell line HepG2 we have shown previously that human SREBP-1a is phosphorylated at serine 117 by ERK-mitogen-activated protein kinases (MAPK). Using a combination of cell biology and protein chemistry approach we show that SREBP-1a is also target of other MAPK-families, i.e. c-JUN N-terminal protein kinases (JNK) or p38 stress activated MAP kinases. Serine 117 is also the major phosphorylation site in SREBP-1a for JNK. In contrast to that the major phosphorylation sites of p38 MAPK family are serine 63 and threonine 426. Functional analyses reveal that phosphorylation of SREBP-1a does not alter protein/DNA interaction. The identified phosphorylation sites are specific for both kinase families also in cellular context. To provide direct evidence that phosphorylation of SREBP-1a is a regulatory principle of biological and clinical relevance, we generated transgenic mice expressing mature transcriptionally active N-terminal domain of human SREBP–1a variant lacking all identified phosphorylaton sites designed as alb-SREBP-1aΔP and wild type SREBP-1a designed as alb-SREBP-1a liver specific under control of the albumin promoter and a liver specific enhancer. In contrast to alb-SREBP–1a mice the phosphorylation–deficient mice develop no enlarged fatty livers under normocaloric conditions. Phenotypical examination reveales a massive accumulation of adipose tissue in alb-SREBP-1a but not in the phosphorylation deficient alb-SREBP-1aΔP mice. Moreover, preventing phosphorylation of SREBP-1a protects mice also from dyslipidemia. In conclusion, phosphorylation of SREBP-1a by ERK, JNK and p38 MAPK-families resembles a biological principle and plays a significant role, in vivo