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Acute health effects of ambient air pollution including ultrafine particles in a semi-experimental setting in young, healthy individuals
Get PDFValidation of two plasma multimetabolite signatures for patients at risk of or with suspected pancreatic ductal adenocarcinoma (METAPAC): a prospective, multicentre, investigator-masked, enrichment design, phase 4 diagnostic study
Get PDFBackground
Earlier diagnosis of pancreatic ductal adenocarcinoma is key to improving overall survival in patients with this hard-to-treat cancer. We independently validated two previously identified plasma-based metabolic signatures for exclusion of pancreatic ductal adenocarcinoma in cohorts with an increased annual risk.
Methods
The METAPAC study was a prospective, multicentre, investigator-masked, enrichment design, phase 4 trial done in 23 centres in Germany. Patients with pancreatic lesions identified by diagnostic imaging that required further diagnostic assessment were recruited and followed up for 24 months. Targeted quantitative plasma metabolite analysis was done on a liquid chromatography–tandem mass spectrometry platform. The improved metabolic (i-Metabolic) signature consisted of 12 analytes plus carbohydrate antigen (CA) 19-9, and the minimalistic metabolic (m-Metabolic) signature consisted of four analytes plus CA 19-9. The primary endpoint of the study was the exclusion of pancreatic ductal adenocarcinoma with an 85% specificity and the highest possible diagnostic accuracy. All statistical analyses were done per protocol. This study is registered with the German Clinical Trials Register (DRKS00010866).
Findings
Between Sept 9, 2016, and April 8, 2022, 1370 patients with CT-identified pancreatic lesions necessitating further diagnostic assessment were screened, of whom 1129 patients (489 with pancreatic ductal adenocarcinoma, 640 controls) were included in the primary analysis (median age 67 years [IQR 58–75]; 556 [49%] female, 572 [51%] male). The control group consisted of high-risk individuals with acute pancreatitis (11 [1%] of 1129 participants), chronic pancreatitis (113 [10%]), intraductal papillary mucinous neoplasms (232 [21%]), cystic lesions other than intraductal papillary mucinous neoplasms (271 [24%]), and metastases of extrapancreatic origin (13 [1%]). The i-Metabolic signature detected pancreatic ductal adenocarcinoma with an area under the curve (AUC) of 0·846 (95% CI 0·842–0·849), specificity of 90·4% (89·8–91·1), sensitivity of 67·5% (66·9–68·0), and balanced accuracy of 80·5% (80·2–80·8), compared with CA 19-9 alone (AUC 0·799 [0·797–0·802], p<0·0001; specificity 79·1% [78·7–79·4]; sensitivity 81·8% [81·5–82·0]; balanced accuracy 80·6% [80·4–80·9]). The m-Metabolic signature detected pancreatic ductal adenocarcinoma with an AUC of 0·846 (95% CI 0·842–0·849; p<0·0001 vs CA 19-9 alone), specificity of 93·6% (93·1–94·0), sensitivity of 59·9% (59·3–60·4), and accuracy of 79·0% (78·8–79·2). In a population of 242 individuals with new-onset diabetes (three cases of incident pancreatic ductal adenocarcinoma), the m-Metabolic signature (without CA 19-9) significantly discriminated patients with pancreatic ductal adenocarcinoma from those without (p=0·038). AUC, specificity, and sensitivity remained constant after random bootstrapping for a prevalence of pancreatic ductal adenocarcinoma between 1% and 20%.
Interpretation
Two plasma-based metabolic signatures showed significant improvement in performance compared with CA 19-9 alone in excluding pancreatic ductal adenocarcinoma in a prospective real-world cohort. These findings could offer a surveillance tool in patients with an annual risk of pancreatic ductal adenocarcinoma of 1% to reduce unnecessary invasive procedures and facilitate earlier detection of resectable disease.
Funding
Federal Ministry of Education and Research (BMBF, Germany)
Evaluationsbericht zum Public Health Filmfestival 2023 - 2024
Get PDFDer nachfolgende Bericht stellt die Evaluationsergebnisse einer Wissenschaftskommunikationsmaß-
nahme an der Ludwig-Maximilians-Universität München (LMU) dar. Die kostenlose Veranstaltungsreihe trägt den Titel „Public Health Filmfestival“. Im Rahmen des Festivals fanden 2023 und 2024 jeweils vier Filmvorführungen statt – je eine davon rein digital, im Jahr 2023 eine open air, im Jahr 2024 eine für Familien. Anschließend an die Filmvorführungen fanden Gesprächsrunden mit Fachpersonen statt, die die im Film behandelten Themen in einen Public-Health-Kontext einbetteten. Ziel
der Veranstaltungsreihe war es, das Konzept Public Health in der Öffentlichkeit sichtbarer und verständlicher zu machen. Das Festival ermutigte Teilnehmende, über das Medium Film unterschiedliche Perspektiven einzunehmen, kritisch zu reflektieren und gemeinsam mit anderen Interessierten über aktuelle Themen der öffentlichen, globalen und planetaren Gesundheit zu diskutieren.
Anhand von Online-Nachbefragungen (2023: N = 58; 2024: N = 100) wurde die Erreichung dieser Ziele untersucht, auch um daraus Erkenntnisse für die Gestaltung des nächsten Public Health Filmfestivals zu ziehen.
Insgesamt war das Publikum des PHFF mehrheitlich weiblich, gut gebildet und im Bereich Wissenschaft und Forschung tätig. 2024 wurde ein größeres und heterogeneres Publikum erreicht als 2023, was an der Wahl anderer Locations, dem verstärkten Einsatz von Social Media aber auch der Einführung einer Familienveranstaltung liegen kann.
Die Veranstaltungen wurden überwiegend positiv bewertet: Die Teilnehmenden fühlten sich gut unterhalten und gaben an, etwas gelernt zu haben. Besonders die Familienveranstaltung erhielt hohe Zustimmungswerte. Die Mehrheit der Befragten war motiviert, sich weiter zu den behandelten Themen auszutauschen, zeigte jedoch geringere Bereitschaft zur Verhaltensänderung. Die Relevanz der in den Veranstaltungen behandelten Themen wurde gesellschaftlich höher eingeschätzt als persönlich – je nach Begrifflichkeit und Konkretheit der Inhalte. Die an den Film anschließende Diskussion bietet noch Möglichkeiten zur Verbesserung: Besonders die aktive Beteiligung des Publikums sollte künftig stärker gefördert werden, da der Austausch zwischen Publikum und Wissenschaft eines der Veranstaltungsziele ist. Bezüglich der Verbreitungsmaßnahmen erwies sich die Kommunikation über Social Media, insbesondere lokale Facebook-Veranstaltungsgruppen, als effektiv
Regularity of Generalized Mean-Field G-SDEs
Get PDFWe study regularity properties of the unique solution of a mean-field G-SDE. More precisely, we consider a mean-field G-SDE with square-integrable random initial condition and establish its first and second order Fréchet differentiability in the random initial condition and specify the G-SDEs of the respective Fréchet derivatives
Vanished Institutions: The Life and Death of Europe's International Organisations – Introduction
Get PDFWhy do international organisations die? Their causes of death deserve attention and analysis. Europe in the 20th century with its plenitude of international organisations provides a rich ground for studying why some of them died, why some lived, why some were resurrected from near-death and why some survive as institutional shells, or zombies. The introduction to this special issue summarises the cases that follow in order to discern a pattern or logic of institutional death in modern European history. A pattern is elusive because causal and conditional factors are almost impossible to separate in cases of institutional death. Yet they show that, in contrast to state collapse, international organisations more often die from without – that is, for external, contextual reasons – than from within. However powerful some external factors, such as war, can be, institutional death is rarely predetermined. In one form or another international organisations possess a strong will to live
A Two-Protein Chemoreceptor Complex Regulates Oxygen Thresholds in Bacterial Magneto-Aerotaxis
Get PDFBacteria in changing environments rely on motility and sensory mechanisms to locate optimal conditions. This process depends on specialized chemoreceptors to sense environmental stimuli. Exceptionally high numbers of chemoreceptor genes are present in magnetotactic bacteria (MTB), which combine magnetic alignment via intracellular magnetic nanoparticles (magnetosomes) and oxygen sensing for a unique navigation strategy toward low-oxygen zones, called magneto-aerotaxis. However, chemoreceptors for aerotaxis in MTB have not been experimentally identified. This study examines chemoreceptors in the model MTB Magnetospirillum gryphiswaldense. Gene deletion analysis shows that M. gryphiswaldense relies on a complex and partly redundant set of chemoreceptors to sense oxygen. Within this diverse repertoire of chemoreceptors, a receptor formed by two interacting proteins is identified that plays a key role in aerotaxis. Interaction assays and microscopy confirm that both proteins interact within polar-lateral regions in the cell. Moreover, genetic, biochemical, and motility experiments demonstrate that the chemoreceptor complex promotes a cellular response away from oxygen via the redox cofactor flavin adenine dinucleotide (FAD), independent of magnetic fields. These findings provide first insights into how MTB control oxygen sensing at the molecular level, shedding light on the mechanisms underlying bacterial navigation and highly complex chemosensory systems
The role of parental attitudes, home literacy environment, and migration background in preschool children's emergent literacy skills
Get PDFDeveloping proficient literacy skills is important for school success. This study examined the link between parental attitudes towards reading and preschool children's emergent literacy skills in German, focusing on children with and without migration background. It explored whether the Home Literacy Environment (HLE) mediated this relation while controlling for child age, sex, cognitive skills, and family socioeconomic status. The study involved 500 children (Mage = 60.97 months) assessed three times across a year. The results showed that parental attitudes towards reading influenced emergent literacy skills only through the HLE. Migration background had an indirect effect, with the HLE mediating its impact on literacy development. These findings highlight the critical role of the HLE in fostering literacy skills, provide a plausible explanation for individual differences in German emergent literacy skills for children with and without migration background, and suggest that interventions targeting parental attitudes and HLE may effectively support literacy development
The effect of rhythm on inter-gestural coupling of onset and vowel gestures and predictive timing in stuttering
Get PDFIn this study we investigate articulatory timing in fluent speech production in persons who stutter (PWS) and persons who do not stutter (PWNS) by focusing on consonant–vowel (CV)-timing, which refers to the coupling of onset consonant and vowel gestures, as well as on predictive timing, which describes the synchronization of the speech onset to a rhythmic event. These two timing mechanisms are particularly interesting to investigate in relation to stuttering, given that CV-timing is especially challenging for PWS and that they exhibit differences in predictive timing related to speech-motor and manual-motor tasks, suggesting that disturbances in inter-gestural coordination and auditory-motor integration may contribute to stuttering. To shed further light on this, we examine CV-timing and predictive timing under different rhythmic conditions.
Twenty German-speaking adults (10 PWS and 10 PWNS) were recorded using electromagnetic articulography (EMA). Participants produced target words that started with a bilabial onset, followed by a vowel (/a/, /o/, or /u/) and were embedded in a carrier phrase in four different conditions: Unpaced (speaking), Tapping (speaking while concurrently tapping), Metronome (synchronizing speech to a metronome), and Metronome+Tapping (speaking to a metronome while concurrently tapping).
We found evidence for both CV-timing and predictive timing differences between PWS and PWNS. Our results suggest that in general, PWS time CV gestures closer together. However, CV-timing differences were linked to condition in an unexpected way. As to predictive timing, PWS initiated their speech later to a metronome beat than PWNS but they did not differ when timing speech to their own finger tapping, indicating that motor-pacing may stabilize the speech motor system of PWS. In the Metronome+Tapping condition, the groups appeared to rely on different rhythmic cues. While PWNS timed their speech more towards the metronome beat, PWS synchronized their speech onset closer to the finger tap. We discuss that this difference could result from differences in CV-timing. Furthermore, the potential for future research on the interplay of non-verbal and verbal motor systems and the possible benefit for the stuttering population is discussed