Experimental approaches to understand the role of genetic and environmental influences on the microbial community associated with "Daphnia"

Every multicellular organism on this planet is associated with a diverse community of microorganisms referred to as its microbiota. In recent years, myriads of effects resulting from this interaction have been revealed. The series of experiments condensed in this thesis aimed at investigating this relationship in more detail in planktonic crustaceans from the genus Daphnia and in particular the water flea Daphnia magna. The findings from these experiments provide important basic knowledge essential for future host-microbiota related research in this system. Part one of the thesis comprises all experiments conducted by myself. In the first chapter I reciprocally transplanted the microbiota between the two species Daphnia magna and Daphnia pulex to examine the degree of specificity in these associations and determine the effects on host fitness as a consequence thereof. We found that being associated with a foreign microbial community did not negatively affect maturity, fecundity and size in both Daphnia species, letting us speculate that the two partners did not adapt to each other. This hypothesis was further supported by the insights gained when investigating the transmission of the whole microbial community, which was the purpose of the second chapter. Compositional comparisons between maternal and offspring microbiota revealed a stable fraction of microbes that gets transmitted, neither influenced by the origin nor the diversity of the microbial community. The third chapter of the thesis aimed at assessing the stability of the Daphnia-microbiota association and to what degree established microbial communities were still modifiable. We paired and raised juveniles from three different locations (Belgium, Germany and Switzerland) in a full factorial design and compared their microbiota. We found that the microbiota is easily modifiable and that microbial communities greatly influence each other’s composition. In addition, the results allowed the conclusion that the microbiota is not genetically controlled. We further investigated this in the fourth chapter dedicated to evaluate if the homozygosity level of the host influences microbial diversity by comparing the microbiota of selfed and outcrossed animals. From the results we conclude that the host genotype has little influence on the diversity of the microbiota. Taken together, these results suggest that although microbial communities play a crucial role in Daphnia, the two partners did not adapt to one another leading us to propose a scenario of how transmission in the Daphnia-microbiota association might take place. Part two of the thesis encompasses work resulting from collaborations. In chapter five, Alexandra Mushegian tested the role of bacteria for animal functioning, showing a positive effect on embryonic development under warm temperature conditions. The goal of the last chapter, conducted by Karen Sullam, was to investigate the effect of temperature, host clone, and their interaction on host-associated microbiota. The experiment showed that the interaction of the factors affected microbial community structure while their diversity was more affected by host clonal background

Resource use and outcome in critically ill patients with hematological malignancy: a retrospective cohort study

INTRODUCTION: The paucity of data on resource use in critically ill patients with hematological malignancy and on these patients' perceived poor outcome can lead to uncertainty over the extent to which intensive care treatment is appropriate. The aim of the present study was to assess the amount of intensive care resources needed for, and the effect of treatment of, hemato-oncological patients in the intensive care unit (ICU) in comparison with a nononcological patient population with a similar degree of organ dysfunction. METHODS: A retrospective cohort study of 101 ICU admissions of 84 consecutive hemato-oncological patients and 3,808 ICU admissions of 3,478 nononcological patients over a period of 4 years was performed. RESULTS: As assessed by Therapeutic Intervention Scoring System points, resource use was higher in hemato-oncological patients than in nononcological patients (median (interquartile range), 214 (102 to 642) versus 95 (54 to 224), P < 0.0001). Severity of disease at ICU admission was a less important predictor of ICU resource use than necessity for specific treatment modalities. Hemato-oncological patients and nononcological patients with similar admission Simplified Acute Physiology Score scores had the same ICU mortality. In hemato-oncological patients, improvement of organ function within the first 48 hours of the ICU stay was the best predictor of 28-day survival. CONCLUSION: The presence of a hemato-oncological disease per se is associated with higher ICU resource use, but not with increased mortality. If withdrawal of treatment is considered, this decision should not be based on admission parameters but rather on the evolutional changes in organ dysfunctions

Swiss public health measures associated with reduced SARS-CoV-2 transmission using genome data

Genome sequences from evolving infectious pathogens allow quantification of case introductions and local transmission dynamics. We sequenced 11,357 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from Switzerland in 2020 - the sixth largest effort globally. Using a representative subset of these data, we estimated viral introductions to Switzerland and their persistence over the course of 2020. We contrasted these estimates with simple null models representing the absence of certain public health measures. We show that Switzerland's border closures de-coupled case introductions from incidence in neighboring countries. Under a simple model, we estimate an 86-98% reduction in introductions during Switzerland's strictest border closures. Furthermore, the Swiss 2020 partial lockdown roughly halved the time for sampled introductions to die out. Last, we quantified local transmission dynamics once introductions into Switzerland occurred, using a phylodynamic model. We found that transmission slowed 35-63% upon outbreak detection in summer 2020, but not in fall. This finding may indicate successful contact tracing over summer before overburdening in fall. The study highlights the added value of genome sequencing data for understanding transmission dynamics

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2

Midterm results of surgical hip dislocation for the treatment of femoroacetabular impingement

Surgical treatment of femoroacetabular impingement (FAI) includes both open and arthroscopic procedures. Encouraging results have been reported for the majority of patients after surgical hip dislocation; however, most of these reports were short term and included only small cohorts

Guideline-based indicators for adult patients with myelodysplastic syndromes.

Myelodysplastic syndromes (MDSs) represent a heterogeneous group of hematological stem cell disorders with an increasing burden on health care systems. Evidence-based MDS guidelines and recommendations (G/Rs) are published but do not necessarily translate into better quality of care if adherence is not maintained in daily clinical practice. Guideline-based indicators (GBIs) are measurable elements for the standardized assessment of quality of care and, thus far, have not been developed for adult MDS patients. To this end, we screened relevant G/Rs published between 1999 and 2018 and aggregated all available information as candidate GBIs into a formalized handbook as the basis for the subsequent consensus rating procedure. An international multidisciplinary expert panel group (EPG) of acknowledged MDS experts (n = 17), health professionals (n = 7), and patient advocates (n = 5) was appointed. The EPG feedback rates for the first and second round were 82% (23 of 28) and 96% (26 of 27), respectively. A final set of 29 GBIs for the 3 domains of diagnosis (n = 14), therapy (n = 8), and provider/infrastructural characteristics (n = 7) achieved the predefined agreement score for selection (>70%). We identified shortcomings in standardization of patient-reported outcomes, toxicity, and geriatric assessments that need to be optimized in the future. Our GBIs represent the first comprehensive consensus on measurable elements addressing best practice performance, outcomes, and structural resources. They can be used as a standardized instrument with the goal of assessing, comparing, and fostering good quality of care within clinical development cycles in the daily care of adult MDS patients

Visualization in the Einstein Year 2005: A Case Study on Explanatory and Illustrative Visualization of Relativity and Astrophysics

with relativistic and astrophysical visualization, which has been culminating in a substantial engagement for visualization in the Einstein Year 2005---the 100 anniversary of Einstein&apos;s publications on special relativity, the photoelectric effect, and Brownian motion. This paper focuses on explanatory and illustrative visualizations used to communicate aspects of the difficult theories of special and general relativity, their geometric structure, and of the related fields of cosmology and astrophysics. We discuss visualization strategies, motivated by physics education and didactics of mathematics, and describe what kind of visualization methods have proven to be useful for different types of media, such as still images in popular-science magazines, film contributions to TV shows, oral presentations, or interactive museum installations. Although our visualization tools build upon existing methods and implementations, these techniques have been improved by several novel technical contributions like image-based special relativistic rendering on GPUs, an extension of general relativistic ray tracing to manifolds described by multiple charts, GPU-based interactive visualization of gravitational light deflection, as well as planetary terrain rendering. The usefulness and effectiveness of our visualizations are demonstrated by reporting on experiences with, and feedback from, recipients of visualizations and collaborators

Quantifying SARS-CoV-2 spread in Switzerland based on genomic sequencing data

Pathogen genomes provide insights into their evolution and epidemic spread. We sequenced 1,439 SARS-CoV-2 genomes from Switzerland, representing 3-7% of all confirmed cases per week. Using these data, we demonstrate that no one lineage became dominant, pointing against evolution towards general lower virulence. On an epidemiological level, we report no evidence of cryptic transmission before the first confirmed case. We find many early viral introductions from Germany, France, and Italy and many recent introductions from Germany and France. Over the summer, we quantify the number of non-traceable infections stemming from introductions, quantify the effective reproductive number, and estimate the degree of undersampling. Our framework can be applied to quantify evolution and epidemiology in other locations or for other pathogens based on genomic data