Expression of Interleukin-37 in paediatric chronic inflammatory bowel disease

The function of interleukin-37 is not resolved yet. It has been shown that IL-37 suppresses colonic inflammation in mice. To gain more insight into its relevance in human disease, we investigated the expression of IL-37 in the intestine of paediatric patients with chronic inflammatory bowel disease. Intestinal biopsies were obtained from children with inflammatory bowel disease (18 Crohn’s disease (CD), 14 ulcerative colitis (UC) and 11 controls) during endoscopy and analysed for IL-37 expression by immunohistochemistry and real-time PCR. Results were correlated with immunostaining for IL-18 and IL17, mRNA levels of pro- and anti-inflammatory cytokines and clinical parameters. IL-37 protein was detected in epithelial cells and submucosal lymphoid cells of CD and UC patients as well as healthy controls. IL-37 protein expression tended to be higher with submucosal lymphoid cell infiltration of patients with CD and UC and correlated with histological severity score of inflammation. IL-18 showed a similar staining pattern to IL-37, whereas staining for IL-17 revealed distinct positive cells scattered in the submucosal layer. Messenger RNA-expression of IL-8, IL-17 and IL-10 was up-regulated in CD and UC patients. mRNA-levels of IL-18 and IL-37 were not significantly elevated compared to controls. Levels of IL-37 and IL-18 mRNA showed a positive correlation in the CD group. Furthermore, out of five isoforms, only isoform IL-37b could be detected in IBD tissue. Future studies are warranted to delineate the specific contribution of IL-37 to modulate chronic bowel inflammation in humans.Die Funktion von Interleukin 37 ist noch nicht völlig geklärt. Es konnte gezeigt werden, dass IL-37 Entzündung im Darm von Mäusen unterdrücken kann. Um mehr Einblicke in dessen Relevanz für Erkrankungen beim Menschen zu erlangen, wurde hier die Expression von IL-37 im Darm von pädiatrischen Patienten mit chronisch entzündlicher Darmerkrankung untersucht. Es wurden Gewebeproben von Kindern mit chronisch entzündlicher Darmentzündung (18 Patienten mit M.Crohn, 14 Patienten mit Colitis ulcerosa und 11 Kontrollen) während einer Darmspiegelung entnommen und auf die Expression von IL-37 mittels Immunohistochemie und real-time PCR untersucht. Die Ergebnisse wurden mit Färbungen für IL-18 und IL-17, mRNA-Level pro- und anti-entzündlicher Zytokine und klinischen Parametern korreliert. IL-37 Protein konnte in den Epithelzellen des Darms sowie den submukösen lymphathischen Zellen der Patienten mit M.Crohn und Colitis ulcerosa sowie der Kontrollpatienten nachgewiesen werden. Die Expression von IL-37-Protein war tendenziell höher bei submuköser Infiltration lymphatischer Zellen von Patienten mit M.Crohn und Colitis ulcerosa und korrelierte mit dem histologischen Schweregrad der Entzündung. IL-18 wies ein ähnliches Färbemuster wie IL-37 auf, wohingegen IL-17 nur in einzelnen Zellen in der submukösen Schicht nachzuweisen war. Die messenger-RNA-Expression von IL-8, IL-17 und IL-10 war bei Patienten mit M.Crohn und Colitis ulcerosa hochreguliert. mRNA-Spiegel von IL-18 und IL-37 waren im Vergleich zu den Kontrollen nicht signifikant erhöht. Die mRNA-Expression von IL-18 und IL-37 war im Vergleich zu den Kontrollen nicht signifikant erhöht. Von den fünf bekannten IL-37-Isoformen konnte nur Isoform b im Darm- und Lebergewebe sowie PBMC nachgewiesen werden. Weitere Studien sind nötig, um die exakte Rolle von IL-37 bei der Modulation der Immunantwort im Rahmen chronisch entzündlicher Darmerkrankungen zu beschreiben

Fecal and Urinary Adipokines as Disease Biomarkers

The use of biomarkers is of great clinical value for the diagnosis and prognosis of disease and the assessment of treatment efficacy. In this context, adipokines secreted from adipose tissue are of interest, as their elevated circulating levels are associated with a range of metabolic dysfunctions, inflammation, renal and hepatic diseases and cancers. In addition to serum, adipokines can also be detected in the urine and feces, and current experimental evidence on the analysis of fecal and urinary adipokine levels points to their potential as disease biomarkers. This includes increased urinary adiponectin, lipocalin-2, leptin and interleukin-6 (IL-6) levels in renal diseases and an association of elevated urinary chemerin as well as urinary and fecal lipocalin-2 levels with active inflammatory bowel diseases. Urinary IL-6 levels are also upregulated in rheumatoid arthritis and may become an early marker for kidney transplant rejection, while fecal IL-6 levels are increased in decompensated liver cirrhosis and acute gastroenteritis. In addition, galectin-3 levels in urine and stool may emerge as a biomarker for several cancers. With the analysis of urine and feces from patients being cost-efficient and non-invasive, the identification and utilization of adipokine levels as urinary and fecal biomarkers could become a great advantage for disease diagnosis and predicting treatment outcomes. This review article highlights data on the abundance of selected adipokines in urine and feces, underscoring their potential to serve as diagnostic and prognostic biomarkers

Comparison of macroeconomic developments in ten scenarios of energy system transformation in Germany: National and regional results

t Background: Different strategies have been proposed for transforming the energy system in Germany. To evaluate their sustainability, it is necessary to analyze their macroeconomic and distributional effects. An approach to do this analysis in an integrated consistent framework is presented here. Methods: Comparing ten energy transition scenarios with emission reduction targets by 2050 of 80% or 95%, respectively, allows evaluating a broad range of energy system transformation strategies with respect to the future technology and energy carrier mix. For this purpose, an energy system model and a macroeconometric model are combined, thus re-modeling the unified scenarios. An important extension of the model was concerned with the integration of synthetic fuels into the energy-economy model. One focus besides the overall macroeconomic assessment is the regional analysis. For this purpose, own assumptions on the regional distribution of the expansion of renewable energies were developed. Results: The effects on gross domestic product (GDP) and employment are similar on average from 2030 to 2050 across the scenarios, with most of the more ambitious scenarios showing slightly higher values for the socioeconomic variables. Employment in the construction sector shows the largest effects in most scenarios, while in the energy sector employment is lower in scenarios with high energy imports. At the regional level, the differences between scenarios are larger than at the national level. There is no clear or stable regional pattern of relative loss and profit from the very ambitious transformation, as not only renewable energy expansion varies, and hydrogen strategies enter the scene approaching 2050. Conclusions: From the relatively small differences between the scenarios, it can be concluded that, from a macroeconomic perspective, it is not decisive for the overall economy which (supply side) strategy is chosen for the transformation of the energy system. More effort needs to be put into improving assumptions and modeling approaches related to strategies for achieving the final 20% CO2 reduction, for example the increasing use of hydroge

Integrated multidimensional sustainability assessment of energy system transformation pathways

Sustainable development embraces a broad spectrum of social, economic and ecological aspects. Thus, a sustainable transformation process of energy systems is inevitably multidimensional and needs to go beyond climate impact and cost considerations. An approach for an integrated and interdisciplinary sustainability assessment of energy system transformation pathways is presented here. It first integrates energy system modeling with a multidimensional impact assessment that focuses on life cycle-based environmental and macroeconomic impacts. Then, stakeholders’ preferences with respect to defined sustainability indicators are inquired, which are finally integrated into a comparative scenario evaluation through a multi-criteria decision analysis (MCDA), all in one consistent assessment framework. As an illustrative example, this holistic approach is applied to the sustainability assessment of ten different transformation strategies for Germany. Applying multi-criteria decision analysis reveals that both ambitious (80%) and highly ambitious (95%) carbon reduction scenarios can achieve top sustainability ranks, depending on the underlying energy transformation pathways and respective scores in other sustainability dimensions. Furthermore, this research highlights an increasingly dominant contribution of energy systems’ upstream chains on total environmental impacts, reveals rather small differences in macroeconomic effects between different scenarios and identifies the transition among societal segments and climate impact minimization as the most important stakeholder preferences

Sustainability assessments of energy scenarios: citizens’ preferences for and assessments of sustainability indicators

Background: Given the multitude of scenarios on the future of our energy systems, multi-criteria assessments are increasingly called for to analyze and assess desired and undesired effects of possible pathways with regard to their environmental, economic and social sustainability. Existing studies apply elaborate lists of sustainability indicators, yet these indicators are defined and selected by experts and the relative importance of each indicator for the overall sustainability assessments is either determined by experts or is computed using mathematical functions. Target group-specific empirical data regarding citizens’ preferences for sustainability indicators as well as their reasoning behind their choices are not included in existing assessments. Approach and results: We argue that citizens’ preferences and values need to be more systematically analyzed. Next to valid and reliable data regarding diverse sets of indicators, reflections and deliberations are needed regarding what different societal actors, including citizens, consider as justified and legitimate interventions in nature and society, and what considerations they include in their own assessments. For this purpose, we present results from a discrete choice experiment. The method originated in marketing and is currently becoming a popular means to systematically analyze individuals’ preference structures for energy technology assessments. As we show in our paper, it can be fruitfully applied to study citizens’ values and weightings with regard to sustainability issues. Additionally, we present findings from six focus groups that unveil the reasons behind citizens’ preferences and choices. Conclusions: Our combined empirical methods provide main insights with strong implications for the future development and assessment of energy pathways: while environmental and climate-related effects significantly influenced citizens’ preferences for or against certain energy pathways, total systems and production costs were of far less importance to citizens than the public discourse suggests. Many scenario studies seek to optimize pathways according to total systems costs. In contrast, our findings show that the role of fairness and distributional justice in transition processes featured as a dominant theme for citizens. This adds central dimensions for future multi-criteria assessments that, so far, have been neglected by current energy systems models

Integrated Multidimensional Sustainability Assessment of Energy System Transformation Pathways

Sustainable development embraces a broad spectrum of social, economic and ecological aspects. Thus, a sustainable transformation process of energy systems is inevitably multidimensional and needs to go beyond climate impact and cost considerations. An approach for an integrated and interdisciplinary sustainability assessment of energy system transformation pathways is presented here. It first integrates energy system modeling with a multidimensional impact assessment that focuses on life cycle‐based environmental and macroeconomic impacts. Then, stakeholders’ preferences with respect to defined sustainability indicators are inquired, which are finally integrated into a comparative scenario evaluation through a multi‐criteria decision analysis (MCDA), all in one consistent assessment framework. As an illustrative example, this holistic approach is applied to the sustainability assessment of ten different transformation strategies for Germany. Applying multi‐criteria decision analysis reveals that both ambitious (80%) and highly ambitious (95%) carbon reduction scenarios can achieve top sustainability ranks, depending on the underlying energy transformation pathways and respective scores in other sustainability dimensions. Furthermore, this research highlights an increasingly dominant contribution of energy systems’ upstream chains on total environmental impacts, reveals rather small differences in macroeconomic effects between different scenarios and identifies the transition among societal segments and climate impact minimization as the most important stakeholder preferences

Sustainability assessments of energy scenarios: citizens' preferences for and assessments of sustainability indicators

Given the multitude of scenarios on the future of our energy systems, multi-criteria assessments are increasingly called for to analyze and assess desired and undesired effects of possible pathways with regard to their environmental, economic and social sustainability. Existing studies apply elaborate lists of sustainability indicators, yet these indicators are defined and selected by experts and the relative importance of each indicator for the overall sustainability assessments is either determined by experts or is computed using mathematical functions. Target group‑specific empirical data regarding citizens' preferences for sustainability indicators as well as their reasoning behind their choices are not included in existing assessments. We argue that citizens' preferences and values need to be more systematically analyzed. Next to valid and reliable data regarding diverse sets of indicators, reflections and deliberations are needed regarding what different societal actors, including citizens, consider as justified and legitimate interventions in nature and society, and what considerations they include in their own assessments. For this purpose, we present results from a discrete choice experiment. The method originated in marketing and is currently becoming a popular means to systematically analyze individuals' preference structures for energy technology assessments. As we show in our paper, it can be fruitfully applied to study citizens' values and weightings with regard to sustainability issues. Additionally, we present findings from six focus groups that unveil the reasons behind citizens preferences and choices. Our combined empirical methods provide main insights with strong implications for the future development and assessment of energy pathways: while environmental and climate-related effects significantly influenced citizens preferences for or against certain energy pathways, total systems and production costs were of far less importance to citizens than the public discourse suggests. Many scenario studies seek to optimize pathways according to total systems costs. In contrast, our findings show that the role of fairness and distributional justice in transition processes featured as a dominant theme for citizens. This adds central dimensions for future multi-criteria assessments that, so far, have been neglected by current energy systems models

Statistical Outliers and Dragon-Kings as Bose-Condensed Droplets

A theory of exceptional extreme events, characterized by their abnormal sizes compared with the rest of the distribution, is presented. Such outliers, called "dragon-kings", have been reported in the distribution of financial drawdowns, city-size distributions (e.g., Paris in France and London in the UK), in material failure, epileptic seizure intensities, and other systems. Within our theory, the large outliers are interpreted as droplets of Bose-Einstein condensate: the appearance of outliers is a natural consequence of the occurrence of Bose-Einstein condensation controlled by the relative degree of attraction, or utility, of the largest entities. For large populations, Zipf's law is recovered (except for the dragon-king outliers). The theory thus provides a parsimonious description of the possible coexistence of a power law distribution of event sizes (Zipf's law) and dragon-king outliers.Comment: Latex file, 16 pages, 1 figur

Distinct metabolomic and lipidomic profiles in serum samples of patients with primary sclerosing cholangitis

Intoduction: Identification of specific metabolome and lipidome profile of patients with primary sclerosing cholangitis (PSC) is crucial for diagnosis, targeted personalized therapy, and more accurate risk stratification. Methods: Nuclear magnetic resonance (NMR) spectroscopy revealed an altered metabolome and lipidome of 33 patients with PSC [24 patients with inflammatory bowel disease (IBD) and 9 patients without IBD] compared with 40 age-, sex-, and body mass index (BMI)-matched healthy controls (HC) as well as 64 patients with IBD and other extraintestinal manifestations (EIM) but without PSC. Results: In particular, higher concentrations of pyruvic acid and several lipoprotein subfractions were measured in PSC in comparison to HC. Of clinical relevance, a specific amino acid and lipid profile was determined in PSC compared with IBD and other EIM. Discussion: These results have the potential to improve diagnosis by differentiating PSC patients from HC and those with IBD and EIM

Aligning the Goals of Learning Analytics with its Research Scholarship: An Open Peer Commentary Approach

To promote cross-community dialogue on matters of significance within the field of learning analytics], we as editors-in- chief of the Journal of Learning Analytics have introduced a section for papers that are open to peer commentary. The first of these papers, “A LAK of Direction: Misalignment Between the Goals of Learning Analytics and its Research Scholarship” by Motz et al. (2023), appeared in the journal’s early access section in March 2023, a few days before the start of the 13th International Learning Analytics and Knowledge Conference (LAK ’23). “A LAK of Direction” takes as its starting point the definition of learning analytics used in the call for papers of the first LAK conference (LAK ’11) and used since then by the Society for Learning Analytics Research (SoLAR): “Learning analytics is the measurement, collection, analysis and reporting of data about learners and their contexts, for purposes of understanding and optimizing learning and the environments in which it occurs” (Long & Siemens, 2011, p. 24). Following the conference, an invitation to submit proposals for commentaries on the paper was released, and 12 of these proposals were accepted. This paper brings those commentaries togethe