Process Simulation of Technical Precipitation Processes - The Influence of Mixing

This work develops and shows up methods to tackle multi-scale challenges in particle formation during precipitation crystallization. Firstly, molecular, micro- and meso-scale interactions in confined impinging jet mixers are investigated and simulatively predicted. Secondly, to build up on developed methods, macroscale as present for instance in stirred tank reactors is added to the considerations

Influence of thoracic epidural analgesia on postoperative pain relief and ileus after laparoscopic colorectal resection: Benefit with epidural analgesia

Background: Thoracic epidural analgesia (TEA) provides superior analgesia with a lower incidence of postoperative ileus when compared with systemic opiate analgesia in open colorectal surgery. However, in laparoscopic colorectal surgery the role of TEA is not well defined. This prospective observational study investigates the influence of TEA in laparoscopic colorectal resections. Methods: All patients undergoing colorectal resection between November 2004 and February 2007 were assessed for inclusion into a prospective randomized trial investigating the influence of bisacodyl on postoperative ileus. All patients treated by laparoscopic resection from this collective were eligible for the present study. Primary endpoints were use of analgesics and visual analogue scale (VAS) pain scores. Secondary endpoint concerned full gastrointestinal recovery, defined as the mean time to the occurrence of the following three events (GI-3): first flatus passed, first defecation, and first solid food tolerated. Results: 75 patients underwent laparoscopic colorectal resection, 39 in the TEA group and 36 in the non-TEA group. Patients with TEA required significantly less analgesics (metamizol median 3.0g [0-32g] versus 13.8g [0-28g] (p<0.001); opioids mean 12mg [±2.8mg standard error of mean, SEM] versus 103mg [±18.2mg SEM] (p<0.001). VAS scores were significantly lower in the TEA group (overall mean 1.67 [± 0.2 SEM] versus 2.58 [±0.2 SEM]; p=0.004). Mean time to gastrointestinal recovery (GI-3) was significantly shorter (2.96 [±0.2 SEM] days versus 3.81 [±0.3 SEM] days; p=0.025). Analysis of the subgroup of patients with laparoscopically completed resections showed corresponding results. Conclusion: TEA provides a significant benefit in terms of less analgesic consumption, better postoperative pain relief, and faster recovery of gastrointestinal function in patients undergoing laparoscopic colorectal resectio

Using GRADE Evidence to Decision frameworks to support the process of health policy-making

BACKGROUND: Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Evidence to Decision (EtD) frameworks are well-known tools that enable guideline panels to structure the process of developing recommendations and making decisions in healthcare and public health. To date, they have not regularly been used for health policy-making. This article aims to illustrate the application of the GRADE EtD frameworks in the process of nutrition-related policy-making for a European country. METHODS: Based on methodological guidance by the GRADE Working Group and the findings of our recently published scoping review, we illustrate the process of moving from evidence to recommendations, by applying the EtD frameworks to a fictitious example. Sugar-sweetened beverage (SSB) taxation based on energy density was chosen as an example application. RESULTS: A fictitious guideline panel was convened by a national nutrition association to develop a population-level recommendation on SSB taxation aiming to reduce the burden of overweight and obesity. Exemplary evidence was summarized for each EtD criterion and conclusions were drawn based on all judgements made in relation to each criterion. As a result of the high priority to reduce the burden of obesity and because of the moderate desirable effects on health outcomes, but considering scarce or varying research evidence for other EtD criteria, the panel made a conditional recommendation for SSB taxation. Decision-makers may opt for conducting a pilot study prior to implementing the policy on a national level. CONCLUSIONS: GRADE EtD frameworks can be used by guideline panels to make the process of developing recommendations in the field of health policy more systematic, transparent and comprehensible

Eddy covariance raw data processing for CO2 and energy fluxes calculation at ICOS ecosystem stations

The eddy covariance is a powerful technique to estimate the surface-atmosphere exchange of different scalars at the ecosystem scale. The EC method is central to the ecosystem component of the Integrated Carbon Observation System, a monitoring network for greenhouse gases across the European Continent. The data processing sequence applied to the collected raw data is complex, and multiple robust options for the different steps are often available. For Integrated Carbon Observation System and similar networks, the standardisation of methods is essential to avoid methodological biases and improve comparability of the results. We introduce here the steps of the processing chain applied to the eddy covariance data of Integrated Carbon Observation System stations for the estimation of final CO2, water and energy fluxes, including the calculation of their uncertainties. The selected methods are discussed against valid alternative options in tenns of suitability and respective drawbacks and advantages. The main challenge is to warrant standardised processing for all stations in spite of the large differences in e.g. ecosystem traits and site conditions. The main achievement of the Integrated Carbon Observation System eddy covariance data processing is making CO2 and energy flux results as comparable and reliable as possible, given the current micrometeorological understanding and the generally accepted state-of-the-art processing methods.Peer reviewe

Anonymität und Mobilität - Whitepaper zum Begriffs- und Domänenverständnis des Kompetenzcluster ANYMOS – Anonymisierung für vernetzte Mobilitätssysteme

In ANYMOS werden Anforderungen und Methoden für eine Anonymisierung und anschließende Auswertung von zuvor personenbezogenen Daten untersucht. Dabei wird im Kompetenzcluster die Anwendungsdomäne Mobilität betrachtet und sich auf den Personenverkehr, da durch die Mobilität von Gütern nicht immer unmittelbar personenbezogene Daten anfallen, fokussiert. Die Notwendigkeit des Kompetenzclusters ANYMOS ergibt sich daraus, dass im Mobilitätsbereich bei zahlreichen Anwendungen große Datenmengen anfallen und es aufgrund der zu erwartenden Entwicklungen zu einem weiteren Anstieg dieser Datenmenge kommen wird. Um diese Daten in Zukunft sinnvoll nutzen zu können, ohne dabei durch die Verwendung personenbezogener Daten Persönlichkeitsrechte und/oder rechtliche Vorgaben zu verletzen, muss zunächst erforscht werden, wann diese Daten gesammelt werden und inwieweit sie auch nach einer Anonymisierung noch über einen Nutzwert verfügen. Im zweiten Abschnitt des Whitepapers wird daher zunächst Anonymität beschrieben und das Spannungsfeld zwischen juristischem und technischen Begriffsverständnis erörtert. Im dritten Abschnitt erfolgt eine Strukturierung der Mobilitätsdomäne. Dadurch soll das gemeinsame Verständnis der Begrifflichkeiten und der Relevanz der verschiedenen Themenbereiche für das Kompetenzcluster ANYMOS gefördert werden. Abschließend wird ein Ausblick – auch auf die weiteren Arbeiten in ANYMOS gegeben

Amyloid pathology but not APOE ε4 status is permissive for tau-related hippocampal dysfunction

We investigated whether the impact of tau-pathology on memory performance and on hippocampal/medial temporal memory function in non-demented individuals depends on the presence of amyloid pathology, irrespective of diagnostic clinical stage. We conducted a cross-sectional analysis of the observational, multicentric DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE). Two hundred and thirty-five participants completed task functional MRI and provided CSF (92 cognitively unimpaired, 100 experiencing subjective cognitive decline and 43 with mild cognitive impairment). Presence (A+) and absence (A-) of amyloid pathology was defined by CSF amyloid-β42 (Aβ42) levels. Free recall performance in the Free and Cued Selective Reminding Test, scene recognition memory accuracy and hippocampal/medial temporal functional MRI novelty responses to scene images were related to CSF total-tau and phospho-tau levels separately for A+ and A- individuals. We found that total-tau and phospho-tau levels were negatively associated with memory performance in both tasks and with novelty responses in the hippocampus and amygdala, in interaction with Aβ42 levels. Subgroup analyses showed that these relationships were only present in A+ and remained stable when very high levels of tau (>700 pg/ml) and phospho-tau (>100 pg/ml) were excluded. These relationships were significant with diagnosis, age, education, sex, assessment site and Aβ42 levels as covariates. They also remained significant after propensity score based matching of phospho-tau levels across A+ and A- groups. After classifying this matched sample for phospho-tau pathology (T-/T+), individuals with A+/T+ were significantly more memory-impaired than A-/T+ despite the fact that both groups had the same amount of phospho-tau pathology. ApoE status (presence of the E4 allele), a known genetic risk factor for Alzheimer's disease, did not mediate the relationship between tau pathology and hippocampal function and memory performance. Thus, our data show that the presence of amyloid pathology is associated with a linear relationship between tau pathology, hippocampal dysfunction and memory impairment, although the actual severity of amyloid pathology is uncorrelated. Our data therefore indicate that the presence of amyloid pathology provides a permissive state for tau-related hippocampal dysfunction and hippocampus-dependent recognition and recall impairment. This raises the possibility that in the predementia stage of Alzheimer's disease, removing the negative impact of amyloid pathology could improve memory and hippocampal function even if the amount of tau-pathology in CSF is not changed, whereas reducing increased CSF tau-pathology in amyloid-negative individuals may not proportionally improve memory function

Improving 3D convolutional neural network comprehensibility via interactive visualization of relevance maps: Evaluation in Alzheimer's disease

Background: Although convolutional neural networks (CNN) achieve high diagnostic accuracy for detecting Alzheimer's disease (AD) dementia based on magnetic resonance imaging (MRI) scans, they are not yet applied in clinical routine. One important reason for this is a lack of model comprehensibility. Recently developed visualization methods for deriving CNN relevance maps may help to fill this gap. We investigated whether models with higher accuracy also rely more on discriminative brain regions predefined by prior knowledge. Methods: We trained a CNN for the detection of AD in N=663 T1-weighted MRI scans of patients with dementia and amnestic mild cognitive impairment (MCI) and verified the accuracy of the models via cross-validation and in three independent samples including N=1655 cases. We evaluated the association of relevance scores and hippocampus volume to validate the clinical utility of this approach. To improve model comprehensibility, we implemented an interactive visualization of 3D CNN relevance maps. Results: Across three independent datasets, group separation showed high accuracy for AD dementia vs. controls (AUC$\geq$0.92) and moderate accuracy for MCI vs. controls (AUC$\approx$0.75). Relevance maps indicated that hippocampal atrophy was considered as the most informative factor for AD detection, with additional contributions from atrophy in other cortical and subcortical regions. Relevance scores within the hippocampus were highly correlated with hippocampal volumes (Pearson's r$\approx$-0.86, p<0.001). Conclusion: The relevance maps highlighted atrophy in regions that we had hypothesized a priori. This strengthens the comprehensibility of the CNN models, which were trained in a purely data-driven manner based on the scans and diagnosis labels.Comment: 24 pages, 9 figures/tables, supplementary material, source code available on GitHu

Human BRCA1-BARD1 ubiquitin ligase activity counters chromatin barriers to DNA resection

The opposing activities of 53BP1 and BRCA1 influence pathway choice of DNA double-strand break repair. How BRCA1 counters the inhibitory effect of 53BP1 on DNA resection and homologous recombination is unknown. Here we identify the site of BRCA1-BARD1 required for priming ubiquitin transfer from E2~ubiquitin. We demonstrate that BRCA1-BARD1’s ubiquitin ligase activity is required for repositioning 53BP1 on damaged chromatin. We confirm H2A ubiquitylation by BRCA1-BARD1 and show that an H2A-ubiquitin fusion protein promotes DNA resection and repair in BARD1 deficient cells. We show BRCA1-BARD1 function in homologous recombination requires the chromatin remodeler SMARCAD1. SMARCAD1 binding to H2A-ubiquitin, optimal localization to sites of damage and activity in DNA repair requires its ubiquitin-binding CUE domains. SMARCAD1 is required for 53BP1 repositioning and the need for SMARCAD1 in Olaparib or camptothecin resistance is alleviated by 53BP1 loss. Thus BRCA1- BARD1 ligase activity and subsequent SMARCAD1-dependent chromatin remodeling are critical regulators of DNA repair

A decade of acoustic thermometry in the North Pacific Ocean

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94643/1/jgrc11250.pd