Design criteria for Indoor Positioning Systems in hospitals using technological, organizational and individual perspectives

This dissertation considers three different studies that handle Indoor Positioning Systems (IPS) in hospitals. Study 1 uses the Reasoned Action Approach by questioning hospital visitors and employees about their intention to use IPS in hospitals. Study 2 reviews IPS in hospitals. Study 3 is based on the results of the first two studies. It handles expert interviews that were conducted with different hospitals and IPS developers to evaluate the determined propositions. Then, the insights were used to conduct and evaluate experiments by testing an ultrasound-based IPS for hospitals

The parabolic p-Laplacian with fractional differentiability

We study the parabolic $p$-Laplacian system in a bounded domain. We deduce optimal convergence rates for the space-time discretization based on an implicit Euler scheme in time. Our estimates are expressed in terms of Nikolskii spaces and therefore cover situations when the (gradient of) the solution has only fractional derivatives in space and time. The main novelty is that, different to all previous results, we do not assume any coupling condition between the space and time resolution $h$ and $\tau$. The theoretical error analysis is complemented by numerical experiments.Comment: Source file for experiments included in submissio

The parabolic p-Laplacian with fractional differentiability

Breit D, Diening L, Storn J, Wichmann J. The parabolic p-Laplacian with fractional differentiability. 2020.We study the parabolic p-Laplacian system in a bounded domain. We deduce optimal convergence rates for the space-time discretization based on an implicit Euler scheme in time. Our estimates are expressed in terms of Nikolskii spaces and therefore cover situations when the (gradient of) the solution has only fractional derivatives in space and time. The main novelty is that, different to all previous results, we do not assume any coupling condition between the space and time resolution h and τ. The theoretical error analysis is complemented by numerical experiments

BOiS—Berlin Object in Scene Database: Controlled Photographic Images for Visual Search Experiments with Quantified Contextual Priors

Photographic stimuli are often used for studying human perception. To faithfully represent our natural viewing environment, these stimuli should be free of potential artifacts. If stimulus material for scientific experiments is generated from photographs that were created for a different purpose, such as advertisement or art, the scene layout and focal depth might not be typical for our visual world. For instance in advertising photos, particular objects are often centered and focused. In visual search experiments, this can lead to the so-called central viewing bias and an unwanted pre-segmentation of focused objects (Wichmann et al., 2010). Also the photographic process itself can result in artifacts, such as optical, color and geometric distortions, or introduce noise. Furthermore, some image compression methods introduce artifacts that may influence human viewing behavior. In some studies, objects are pasted into scenes using graphics editing. In this case inconsistencies in color, shading or lighting between the object and the local scene background could lead to deviations from natural viewing behavior. In order to meet the needs for publicly available stimulus material in which these artifacts are avoided, we introduce in this paper the BOiS—Berlin Object in Scene database, which provides controlled photographic stimulus material for the assessment of human visual search behavior under natural conditions. The BOiS database comprises high-resolution photographs of 130 cluttered scenes. In each scene, one particular object was chosen as search target. The scene was then photographed three times: with the target object at an expected location, at an unexpected location, or absent. Moreover, the database contains 240 different views of each target object in front of a black background. These images provide different visual cues of the target before the search is initiated. All photos were taken under controlled conditions with respect to photographic parameters and layout and were corrected for optical distortions. The BOiS database allows investigating the top-down influence of scene context, by providing contextual prior maps of each scene that quantify people's expectations to find the target object at a particular location. These maps were obtained by averaging the individual expectations of 10 subjects and can be used to model context effects on the search process. Last not least, the database includes segmentation masks of each target object in the two corresponding scene images, as well as a list of semantic information on the target object, the scene, and the two chosen locations. Moreover, we provide bottom-up saliency measures and contextual prior values at the two target object locations. While originally aimed at visual search, our database can also provide stimuli for experiments on scene viewing and object recognition, or serve as test environment for computer vision algorithms.BMBF, 01GQ0850, Bernstein Fokus Neurotechnologie - Nichtinvasive Neurotechnologie für Mensch-Maschine Interaktio

Associations between BMI and the FTO Gene Are Age Dependent: Results from the GINI and LISA Birth Cohort Studies up to Age 6 Years

Objective: The association between polymorphisms in intron 1 of the fat mass and obesity associated gene (FTO) and obesity-related traits is one of the most robust associations reported for complex traits and is established both in adults and children. However, little is known about the longitudinal dynamics of these polymorphisms on body mass index (BMI), overweight, and obesity. Methods: This study is based on the 2,732 full-term neonates of the German GINI-plus and LISA-plus birth cohorts, for whom genotyping data on the FTO variants rs1558902 (T>A) or rs9935401 (G>A) were available. Children were followed from birth up to age 6 years. Up to 9 anthropometric measurements of BMI were obtained. Fractional-Polynomial-Generalized-Estimation-Equation modeling was used to assess developmental trends and their potential dependence on genotype status. Results: We observed no evidence for BMI differences between genotypes of both variants for the first 3 years of life. However, from age 3 years onwards, we noted a higher BMI for the homozygous minor alleles carriers in comparison to the other two genotype groups. However, evidence for statistical significance was reached from the age of 4 years onwards. Conclusions: This is one of the first studies investigating in detail the development of BMI depending on FTO genotype between birth and the age of 6 years in a birth cohort not selected for the phenotype studied. We observed that the association between BMI and FTO genotype evolves gradually and becomes descriptively detectable from the age of 3 years onwards

ZBTB7A prevents RUNX1-RUNX1T1-dependent clonal expansion of human hematopoietic stem and progenitor cells

ZBTB7A is frequently mutated in acute myeloid leukemia (AML) with t(8;21) translocation. However, the oncogenic collaboration between mutated ZBTB7A and the RUNX1–RUNX1T1 fusion gene in AML t(8;21) remains unclear. Here, we investigate the role of ZBTB7A and its mutations in the context of normal and malignant hematopoiesis. We demonstrate that clinically relevant ZBTB7A mutations in AML t(8;21) lead to loss of function and result in perturbed myeloid differentiation with block of the granulocytic lineage in favor of monocytic commitment. In addition, loss of ZBTB7A increases glycolysis and hence sensitizes leukemic blasts to metabolic inhibition with 2-deoxy-d-glucose. We observed that ectopic expression of wild-type ZBTB7A prevents RUNX1-RUNX1T1-mediated clonal expansion of human CD34+ cells, whereas the outgrowth of progenitors is enabled by ZBTB7A mutation. Finally, ZBTB7A expression in t(8;21) cells lead to a cell cycle arrest that could be mimicked by inhibition of glycolysis. Our findings suggest that loss of ZBTB7A may facilitate the onset of AML t(8;21), and that RUNX1-RUNX1T1-rearranged leukemia might be treated with glycolytic inhibitors

Systematic review of models assessing the economic value of routine varicella and herpes zoster vaccination in high-income countries.

Damm O, Ultsch B, Horn J, Mikolajczyk RT, Greiner W, Wichmann O. Systematic review of models assessing the economic value of routine varicella and herpes zoster vaccination in high-income countries. BMC Public Health. 2015;15(1): 533.BACKGROUND: A systematic review was conducted to assess the cost-effectiveness of routine varicella and herpes zoster (HZ) vaccination in high-income countries estimated by modelling studies.; METHODS: A PubMed search was performed to identify relevant studies published before October 2013. Studies were included in the review if they (i) evaluated the cost-effectiveness of routine childhood or adolescent varicella vaccination and/or HZ vaccination targeting the elderly, and if they (ii) reported results for high-income countries.; RESULTS: A total of 38 model-based studies were identified that fulfilled the inclusion criteria. Routine childhood or adolescent varicella vaccination was cost-effective or cost-saving from a payer perspective and always cost-saving from a societal perspective when ignoring its potential impact on HZ incidence due to reduced or absent exogenous boosting. The inclusion of the potential impact of childhood varicella vaccination on HZ led to net quality-adjusted life-year (QALY) losses or incremental cost-effectiveness ratios exceeding commonly accepted thresholds. Additional HZ vaccination could partially mitigate this effect. Studies focusing only on the evaluation of HZ vaccination reported a wide range of results depending on the selected target age-group and the vaccine price, but most found HZ vaccination to be a cost-effective or marginally cost-effective intervention. Cost-effectiveness of HZ vaccination was strongly dependent on the age at vaccination, the price of the vaccine, the assumed duration of protection and the applied cost per QALY threshold.; CONCLUSIONS: While HZ vaccination is mostly considered cost-effective, cost-effectiveness of varicella vaccination primarily depends on the in- or exclusion of exogenous boosting in the model. As a consequence, clarification on the role of exogenous boosting is crucial for decision-making regarding varicella vaccination

Non-replication of an association of CTNNBL1 polymorphisms and obesity in a population of Central European ancestry

<p>Abstract</p> <p>Background</p> <p>A recent genome-wide association (GWA) study of U.S. Caucasians suggested that eight single nucleotide polymorphisms (SNPs) in <it>CTNNBL1 </it>are associated with obesity and increased fat mass. We analysed the respective SNPs in data from our previously published GWA for early onset obesity (case-control design), in GWA data from a population-based cohort of adults, and in an independent family-based obesity study. We investigated whether variants in <it>CTNNBL1 </it>(including rs6013029) and in three other genes (<it>SH3PXD2B</it>, <it>SLIT3 </it>and <it>FLJ42133</it>,) were associated with obesity.</p> <p>Methods</p> <p>The GWA studies were carried out using Affymetrix^®SNP Chips with approximately 500,000 markers each. In the families, SNP rs6013029 was genotyped using the TaqMan^®allelic discrimination assay. The German case-control GWA included 487 extremely obese children and adolescents and 442 healthy lean individuals. The adult GWA included 1,644 individuals from a German population-based study (KORA). The 775 independent German families consisted of extremely obese children and adolescents and their parents.</p> <p>Results</p> <p>We found no evidence for an association of the reported variants in <it>CTNNBL1 </it>with early onset obesity or increased BMI. Further, in our family-based study we found no evidence for over-transmission of the rs6013029 risk-allele T to obese children. Additionally, we found no evidence for an association of <it>SH3PXD2B</it>, <it>SLIT3 and FLJ42133 </it>variants in our two GWA samples.</p> <p>Conclusion</p> <p>We detected no confirmation of the recent association of variants in <it>CTNNBL1 </it>with obesity in a population of Central European ancestry.</p

Growth independent rhamnolipid production from glucose using the non-pathogenic Pseudomonas putida KT2440

<p>Abstract</p> <p>Background</p> <p>Rhamnolipids are potent biosurfactants with high potential for industrial applications. However, rhamnolipids are currently produced with the opportunistic pathogen <it>Pseudomonas aeruginosa </it>during growth on hydrophobic substrates such as plant oils. The heterologous production of rhamnolipids entails two essential advantages: Disconnecting the rhamnolipid biosynthesis from the complex quorum sensing regulation and the opportunity of avoiding pathogenic production strains, in particular <it>P. aeruginosa</it>. In addition, separation of rhamnolipids from fatty acids is difficult and hence costly.</p> <p>Results</p> <p>Here, the metabolic engineering of a rhamnolipid producing <it>Pseudomonas putida </it>KT2440, a strain certified as safety strain using glucose as carbon source to avoid cumbersome product purification, is reported. Notably, <it>P. putida </it>KT2440 features almost no changes in growth rate and lag-phase in the presence of high concentrations of rhamnolipids (> 90 g/L) in contrast to the industrially important bacteria <it>Bacillus subtilis, Corynebacterium glutamicum</it>, and <it>Escherichia coli. P. putida </it>KT2440 expressing the <it>rhlAB</it>-genes from <it>P. aeruginosa </it>PAO1 produces mono-rhamnolipids of <it>P. aeruginosa </it>PAO1 type (mainly C₁₀:C₁₀). The metabolic network was optimized in silico for rhamnolipid synthesis from glucose. In addition, a first genetic optimization, the removal of polyhydroxyalkanoate formation as competing pathway, was implemented. The final strain had production rates in the range of <it>P. aeruginosa </it>PAO1 at yields of about 0.15 g/g_glucosecorresponding to 32% of the theoretical optimum. What's more, rhamnolipid production was independent from biomass formation, a trait that can be exploited for high rhamnolipid production without high biomass formation.</p> <p>Conclusions</p> <p>A functional alternative to the pathogenic rhamnolipid producer <it>P. aeruginosa </it>was constructed and characterized. <it>P. putida </it>KT24C1 pVLT31_<it>rhlAB </it>featured the highest yield and titer reported from heterologous rhamnolipid producers with glucose as carbon source. Notably, rhamnolipid production was uncoupled from biomass formation, which allows optimal distribution of resources towards rhamnolipid synthesis. The results are discussed in the context of rational strain engineering by using the concepts of synthetic biology like chassis cells and orthogonality, thereby avoiding the complex regulatory programs of rhamnolipid production existing in the natural producer <it>P. aeruginosa</it>.</p