Multiscale Neural Operators for Solving Time-Independent PDEs

Time-independent Partial Differential Equations (PDEs) on large meshes pose significant challenges for data-driven neural PDE solvers. We introduce a novel graph rewiring technique to tackle some of these challenges, such as aggregating information across scales and on irregular meshes. Our proposed approach bridges distant nodes, enhancing the global interaction capabilities of GNNs. Our experiments on three datasets reveal that GNN-based methods set new performance standards for time-independent PDEs on irregular meshes. Finally, we show that our graph rewiring strategy boosts the performance of baseline methods, achieving state-of-the-art results in one of the tasks.Comment: The Symbiosis of Deep Learning and Differential Equations III @ NeurIPS 202

Zervixlängenmessung in Kombination mit biochemischen Markern zur Prädiktion der Frühgeburtlichkeit bei asymptomatischen Schwangeren

Das Ziel dieser Arbeit war es zu überprüfen, ob durch eine Kombination verschiedener diagnostischer Methoden eine bessere Prädiktion der Frühgeburtlichkeit gelingen kann. Auch in unserer Studie konnte eine Frühgeburtenrate von 10% bestätigt werden. Bei dem ausgewählten Patientenkollektiv handelte es sich um ein „niedrig-Risiko-Kollektiv“, dementsprechend kam es auch nur zu wenigen Frühgeburten vor der 32. SSW (0,85%). Bemerkenswert hoch war die Frühgeburtenrate mit 17% bei den Patientin-nen mit einem anamnestischen Risiko, so dass das anamnestische Risiko als wichtiger Risikofaktor bestätigt werden konnte. Wie in verschiedenen vorausgehenden Studien konnten wir in unserer Arbeit eine signifikante positive Korrelation zwischen der Zervixlänge und dem Entbindungszeitpunkt in der 19.-27. SSW und in der 28.-34. SSW aufzeigen. In der 13.-18. SSW konnte dieser Zusammenhang nicht eruiert werden, demnach ist die TVS-Messung der Zervix in diesem Schwangerschaftszeitraum zur Vorhersage einer möglichen Frühgeburt nicht geeignet. Im Verlauf kam es zu einer physiologischen Verkürzung der Zervixlänge, die schneller und ausgeprägter bei den Patientinnen mit einer Risikoanamnese verlief. Das Verteilungsmuster der Zervixlängen entsprach dem einer Gauß-Normalverteilungskurve. Bei einer Zervixlänge ≤ 30 mm konnte der durchschnittlich niedrigste Entbindungszeitpunkt in allen Gruppen bestimmt werden. Wir konnten zur Vorhersage eines erhöhten Risikos für eine Frühgeburt einen cut-off-Wert in der 19.-34. SSW von ≤ 30 mm eruieren. Das relative Risiko für eine Frühgeburt bei einer Zervixlän-ge ≤ 30 mm lag in U2 bei 5,6 und in U3 bei 4,5. Die in der Literatur beschriebene Prävalenz von 10-20% für eine bakterielle Vaginose in der Schwangerschaft konnten wir hingegen in unserer Arbeit bei einer nur geringen Anzahl diagnostizierter BV (4,5%) nicht bestätigen. Allerdings wurden durch unseren angewandten BVBlue®-Schnelltest keine Mycoplasmen erfasst. Ferner wurde in der Frühgeburtengruppe und in der Patientengruppe mit einem anamnestischen Risiko doppelt so häufig wie im Gesamtkollektiv eine BV diagnostiziert (8,5% und 8,5%). Somit wurde eine Assoziation zwischen vaginaler Infektion und Frühgeburtlichkeit, trotz niedriger Fallzahl, aufgezeigt. Ein nicht-linearer Anstieg der Speichelestriolkonzentration mit einer Zunahme der Kon-zentration bis auf über 150% konnte wie in vorangehenden Studien beobachtet werden. Es konnten keine signifikanten Unterschiede zwischen Patientinnen mit Frühgeburten, Termingeburten und Patientinnen mit einem anamnestischen Risiko festgestellt werden. Die Speichelestriolmessung zur Vorhersage einer drohenden Frühgeburt hat sich nach unseren Ergebnissen demnach nicht als geeigneter Marker erwiesen. In unserer Arbeit konnte kein Vorteil einer Kombination der Zervixlängenmessung mit Bestimmung des Estriolspiegels zur Vorhersage der Frühgeburtlichkeit festgestellt wer-den. Ein früherer Entbindungszeitpunkt bei Patientinnen mit einer kurzen Zervixlänge und einem hohen E3-Spiegel und umgekehrt konnte nicht eruiert werden. Ebenso fand sich keine Korrelation zwischen dem Nachweis einer BV und erhöhten E3-Werten. Wir konnten aber zeigen, dass bei einer kurzen Zervixlänge bei gleichzeitig bestehender BV das Risiko für eine Frühgeburt steigt, bzw. dass eine BV in der Frühschwangerschaft (13.-18. SSW) mit einer kürzeren Zervixlänge in den späteren Schwangerschaftswochen assoziiert ist. Durch diese Arbeit konnte dargestellt werden, dass die sonographische Zervixlängen-messung ein objektives Maß zur Risikobeurteilung hinsichtlich einer Frühgeburt ist. Das Vorkommen einer bakteriellen Vaginose zeigte sich doppelt so häufig bei Patientinnen die vor der 37. SSW entbanden und / oder ein anamnestisches Risiko aufwiesen. Eben-falls konnte durch eine Kombination dieser beiden Frühgeburtsmarker eine bessere Prädiktion der Frühgeburtlichkeit gelingen. Fehlende Signifikanzen in der Auswertung einzelner Untergruppen sind auf die z.T. sehr kleinen Gruppengrößen zurückzuführen

Quality and risk of bias appraisals of systematic reviews are inconsistent across reviewers and centers

© 2020 The Authors. Published by Elsevier Inc. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Objective: The objective of the study was to evaluate the inter-rater and intercenter reliability, usability, and utility of A MeaSurement Tool to Assess systematic Reviews (AMSTAR), AMSTAR 2, and Risk Of Bias In Systematic reviews (ROBIS). Study design and setting: This is a prospective evaluation using 30 systematic reviews of randomized trials, undertaken at three international centers. Results: Reviewers completed AMSTAR, AMSTAR 2, and ROBIS in median (interquartile range) 15.7 (11.3), 19.7 (12.1), and 28.7 (17.4) minutes and reached consensus in 2.6 (3.2), 4.6 (5.3), and 10.9 (10.8) minutes, respectively. Across all centers, inter-rater reliability was substantial to almost perfect for 8/11 AMSTAR, 9/16 AMSTAR 2, and 12/24 ROBIS items. Intercenter reliability was substantial to almost perfect for 6/11 AMSTAR, 12/16 AMSTAR 2, and 7/24 ROBIS items. Intercenter reliability for confidence in the results of the review or overall risk of bias was moderate (Gwet's first-order agreement coefficient (AC1) 0.58, 95% confidence intervals [CI]: 0.30 to 0.85) to substantial (AC1 0.74, 95% CI: 0.30 to 0.85) for AMSTAR 2 and poor (AC1 -0.21, 95% CI: -0.55 to 0.13) to moderate (AC1 0.56, 95% CI: 0.30 to 0.83) for ROBIS. It is not clear whether using the appraisals of any tool as an inclusion criterion would alter an overview's findings. Conclusions: Improved guidance may be needed to facilitate the consistent interpretation and application of the newer tools (especially ROBIS).info:eu-repo/semantics/publishedVersio

High dietary zinc feeding promotes persistence of multi-resistant E. coli in the swine gut

High levels of zinc oxide are used frequently as feed additive in pigs to improve gut health and growth performance and are still suggested as an alternative to antimicrobial growth promoters. However, we have recently described an increase of multi-resistant E. coli in association to zinc feeding in piglets. This previous study focused on clonal diversity of E. coli, observing the effect on multi-resistant strains by chance. To shed further light into this highly important topic and falsify our previous findings, we performed a zinc pig feeding trial where we specifically focused on in-depth analysis of antimicrobial resistant E. coli. Under controlled experimental conditions, piglets were randomly allocated to a high dietary zinc (zinc group) and a background zinc feeding group (control group). At different ages samples were taken from feces, digesta, and mucosa and absolute E. coli numbers were determined. A total of 2665 E. coli isolates were than phenotypically tested for antimicrobial resistance and results were confirmed by minimum inhibitory concentration testing for random samples. In piglets fed with high dietary zinc, we detected a substantial increase of multi-resistant E. coli in all gut habitats tested, ranging from 28.9-30.2% multi-resistant E. coli compared to 5.8-14.0% in the control group. This increase was independent of the total number of E. coli. Interestingly, the total amount of the E. coli population decreased over time. Thus, the increase of the multi-resistant E. coli populations seems to be linked with persistence of the resistant population, caused by the influence of high dietary zinc feeding. In conclusion, these findings corroborate our previous report linking high dietary zinc feeding of piglets with the occurrence of antimicrobial resistant E. coli and therefore question the feeding of high dietary zinc oxide as alternative to antimicrobial growth promoters

Variation of serum hyaluronan with activity in individuals with knee osteoarthritis

PURPOSE: Serum hyaluronan (HA) was evaluated for diurnal variation in participants with osteoarthritis (OA) of the knee. METHODS: Twenty participants with radiographic OA of at least one knee were admitted overnight to the General Clinical Research Center for serial serum sampling. Serum was obtained between 6:00 p.m. and 8:00 p.m. on Day 1 (T3) after a day of normal activity. During the night of bed rest, participants remained supine for a minimum of 5 h between the hours of 3:00 a.m. and 8:00 a.m. Blood was drawn prior to arising from bed (T0), and 1h (T1) and 4 h (T2) after arising and performing usual morning activities, including eating breakfast. During the morning, participants were encouraged to remain physically active and were not permitted to sit for more than 30 min at a time. Serum HA was measured by enzyme-linked immunosorbent assay. Results were analyzed using non-parametric Freidman's test with Dunn's post-hoc Multiple Comparison test. RESULTS: Serum levels of HA increased significantly from T0 to T1 (P < 0.01). There were no other significant changes in serum HA levels observed between any of the other time points. CONCLUSIONS: Although a rise in serum HA with activity and eating has been demonstrated previously in individuals with rheumatoid arthritis, this is the first study to demonstrate a similar rise in individuals with OA. These results suggest that serum sampling for HA in OA clinical trials should be performed more than 1h after arising in the morning and at least 1h after breaking an overnight fast

Effectiveness, cost-effectiveness and cost-benefit of a single annual professional intervention for the prevention of childhood dental caries in a remote rural Indigenous community

Background The aim of the study is to reduce the high prevalence of tooth decay in children in a remote, rural Indigenous community in Australia, by application of a single annual dental preventive intervention. The study seeks to (1) assess the effectiveness of an annual oral health preventive intervention in slowing the incidence of dental caries in children in this community, (2) identify the mediating role of known risk factors for dental caries and (3) assess the cost-effectiveness and cost-benefit of the intervention. Methods/design The intervention is novel in that most dental preventive interventions require regular re-application, which is not possible in resource constrained communities. While tooth decay is preventable, self-care and healthy habits are lacking in these communities, placing more emphasis on health services to deliver an effective dental preventive intervention. Importantly, the study will assess cost-benefit and cost-effectiveness for broader implementation across similar communities in Australia and internationally. Discussion There is an urgent need to reduce the burden of dental decay in these communities, by implementing effective, cost-effective, feasible and sustainable dental prevention programs. Expected outcomes of this study include improved oral and general health of children within the community; an understanding of the costs associated with the intervention provided, and its comparison with the costs of allowing new lesions to develop, with associated treatment costs. Findings should be generalisable to similar communities around the world. The research is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), registration number ACTRN12615000693527; date of registration: 3rd July 2015

Urethral Catheter Biofilms Reveal Plasticity in Bacterial Composition and Metabolism and Withstand Host Immune Defenses in Hypoxic Environment

Biofilms composed of multiple microorganisms colonize the surfaces of indwelling urethral catheters that are used serially by neurogenic bladder patients and cause chronic infections. Well-adapted pathogens in this niche are Escherichia coli, Proteus, and Enterococcus spp., species that cycle through adhesion and multilayered cell growth, trigger host immune responses, are starved off nutrients, and then disperse. Viable microbial foci retained in the urinary tract recolonize catheter surfaces. The molecular adaptations of bacteria in catheter biofilms (CBs) are not well-understood, promising new insights into this pathology based on host and microbial meta-omics analyses from clinical specimens. We examined catheters from nine neurogenic bladder patients longitudinally over up to 6 months. Taxonomic analyses from 16S rRNA gene sequencing and liquid chromatography–tandem mass spectrometry (LC-MS/MS)–based proteomics revealed that 95% of all catheter and corresponding urinary pellet (UP) samples contained bacteria. CB biomasses were dominated by Enterobacteriaceae spp. and often accompanied by lactic acid and anaerobic bacteria. Systemic antibiotic drug treatments of patients resulted in either transient or lasting microbial community perturbations. Neutrophil effector proteins were abundant not only in UP but also CB samples, indicating their penetration of biofilm surfaces. In the context of one patient who advanced to a kidney infection, Proteus mirabilis proteomic data suggested a combination of factors associated with this disease complication: CB biomasses were high; the bacteria produced urease alkalinizing the pH and triggering urinary salt deposition on luminal catheter surfaces; P. mirabilis utilized energy-producing respiratory systems more than in CBs from other patients. The NADH:quinone oxidoreductase II (Nqr), a Na+ translocating enzyme not operating as a proton pump, and the nitrate reductase A (Nar) equipped the pathogen with electron transport chains promoting growth under hypoxic conditions. Both P. mirabilis and E. coli featured repertoires of transition metal ion acquisition systems in response to human host-mediated iron and zinc sequestration. We discovered a new drug target, the Nqr respiratory system, whose deactivation may compromise P. mirabilis growth in a basic pH milieu. Animal models would not allow such molecular-level insights into polymicrobial biofilm metabolism and interactions because the complexity cannot be replicated

Bitter taste signaling in tracheal epithelial brush cells elicits innate immune responses to bacterial infection

Constant exposure of the airways to inhaled pathogens requires efficient early immune responses protecting against infections. How bacteria on the epithelial surface are detected and first-line protective mechanisms are initiated are not well understood. We have recently shown that tracheal brush cells (BCs) express functional taste receptors. Here we report that bitter taste signaling in murine BCs induces neurogenic inflammation. We demonstrate that BC signaling stimulates adjacent sensory nerve endings in the trachea to release the neuropeptides CGRP and substance P that mediate plasma extravasation, neutrophil recruitment, and diapedesis. Moreover, we show that bitter tasting quorum-sensing molecules from Pseudomonas aeruginosa activate tracheal BCs. BC signaling depends on the key taste transduction gene Trpm5, triggers secretion of immune mediators, among them the most abundant member of the complement system, and is needed to combat P. aeruginosa infections. Our data provide functional insight into firstline defense mechanisms against bacterial infections of the lung

Prospective Association of Daily Steps with Cardiovascular Disease: A Harmonized Meta-Analysis

Background: Taking fewer than the widely promoted “10 000 steps per day” has recently been associated with lower risk of all-cause mortality. The relationship of steps and cardiovascular disease (CVD) risk remains poorly described. A meta-analysis examining the dose–response relationship between steps per day and CVD can help inform clinical and public health guidelines. Methods: Eight prospective studies (20 152 adults [ie, ≥18 years of age]) were included with device-measured steps and participants followed for CVD events. Studies quantified steps per day and CVD events were defined as fatal and nonfatal coronary heart disease, stroke, and heart failure. Cox proportional hazards regression analyses were completed using study-specific quartiles and hazard ratios (HR) and 95% CI were meta-analyzed with inverse-variance–weighted random effects models. Results: The mean age of participants was 63.2±12.4 years and 52% were women. The mean follow-up was 6.2 years (123 209 person-years), with a total of 1523 CVD events (12.4 per 1000 participant-years) reported. There was a significant difference in the association of steps per day and CVD between older (ie, ≥60 years of age) and younger adults (ie, <60 years of age). For older adults, the HR for quartile 2 was 0.80 (95% CI, 0.69 to 0.93), 0.62 for quartile 3 (95% CI, 0.52 to 0.74), and 0.51 for quartile 4 (95% CI, 0.41 to 0.63) compared with the lowest quartile. For younger adults, the HR for quartile 2 was 0.79 (95% CI, 0.46 to 1.35), 0.90 for quartile 3 (95% CI, 0.64 to 1.25), and 0.95 for quartile 4 (95% CI, 0.61 to 1.48) compared with the lowest quartile. Restricted cubic splines demonstrated a nonlinear association whereby more steps were associated with decreased risk of CVD among older adults. Conclusions: For older adults, taking more daily steps was associated with a progressively decreased risk of CVD. Monitoring and promoting steps per day is a simple metric for clinician–patient communication and population health to reduce the risk of CVD