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Background:
Contamination detection is a important step that should be carefully considered in early stages when designing and performing microbiome studies to avoid biased outcomes. Detecting and removing true contaminants is challenging, especially in low-biomass samples or in studies lacking proper controls. Interactive visualizations and analysis platforms are crucial to better guide this step, to help to identify and detect noisy patterns that could potentially be contamination. Additionally, external evidence, like aggregation of several contamination detection methods and the use of common contaminants reported in the literature, could help to discover and mitigate contamination.
Results:
We propose GRIMER, a tool that performs automated analyses and generates a portable and interactive dashboard integrating annotation, taxonomy, and metadata. It unifies several sources of evidence to help detect contamination. GRIMER is independent of quantification methods and directly analyzes contingency tables to create an interactive and offline report. Reports can be created in seconds and are accessible for nonspecialists, providing an intuitive set of charts to explore data distribution among observations and samples and its connections with external sources. Further, we compiled and used an extensive list of possible external contaminant taxa and common contaminants with 210 genera and 627 species reported in 22 published articles.
Conclusion:
GRIMER enables visual data exploration and analysis, supporting contamination detection in microbiome studies. The tool and data presented are open source and available at https://gitlab.com/dacs-hpi/grimer.
Background
The aggregation of a series of N-of-1 trials presents an innovative and efficient study design, as an alternative to traditional randomized clinical trials. Challenges for the statistical analysis arise when there is carry-over or complex dependencies of the treatment effect of interest.
Methods
In this study, we evaluate and compare methods for the analysis of aggregated N-of-1 trials in different scenarios with carry-over and complex dependencies of treatment effects on covariates. For this, we simulate data of a series of N-of-1 trials for Chronic Nonspecific Low Back Pain based on assumed causal relationships parameterized by directed acyclic graphs. In addition to existing statistical methods such as regression models, Bayesian Networks, and G-estimation, we introduce a carry-over adjusted parametric model (COAPM).
Results
The results show that all evaluated existing models have a good performance when there is no carry-over and no treatment dependence. When there is carry-over, COAPM yields unbiased and more efficient estimates while all other methods show some bias in the estimation. When there is known treatment dependence, all approaches that are capable to model it yield unbiased estimates. Finally, the efficiency of all methods decreases slightly when there are missing values, and the bias in the estimates can also increase.
Conclusions
This study presents a systematic evaluation of existing and novel approaches for the statistical analysis of a series of N-of-1 trials. We derive practical recommendations which methods may be best in which scenarios.
Die Reihe "Gesellschaften und Kulturen des sephardischen Judentums I Sephardic Societies and Cultures", herausgegeben von Prof. Dr. Sina Rauschenbach, Prof. Dr. Carsten Schapkow und Dr. Jonathan Hirsch, ist die einzige wissenschaftliche Buchreihe in Deutschland mit einem explizit sephardischen Schwerpunkt. Sie beabsichtigt, durch wegweisende Manuskripte aus dem Bereich des iberisch-sephardischen Judentums und dessen westlicher Diaspora sowie des ost-sephardischen Judentums Nordafrikas und des Nahen Ostens das bestehende Forschungsdesiderat hinsichtlich des Zeitraums vom Mittelalter bis zur Gegenwart zu schließen. Die Reihe wendet sich an Forscher:innen und Studierende der Jüdischen Studien, Judaistik und Jüdischen Theologie, Israel und Middle Eastern Studies, Geschichte, Philosophie, Kulturwissenschaft, Literaturwissenschaft sowie benachbarter Fächer.
Manuskripte sollten einem historisch-kulturwissenschaftlichen Ansatz folgen, zur Erforschung der globalen Geschichte des sephardischen Judentums in seiner ganzen Vielfalt beitragen und sich aktuellen Fragestellungen und Diskussionen widmen, die auch fachübergreifend von Interesse sind. In der Reihe erscheinen Monographien, Sammelbände sowie herausragende Dissertationen und Habilitationsschriften in deutscher und englischer Sprache.
Der Band „Minor Perspectives on Modernity beyond Europe”, der von Yael Attia, Jonathan Hirsch und Kathleen Samson herausgegeben wird, eröffnet die Reihe und stellt sephardische und andere Perspektiven religiöser und kultureller Minoritäten aus der ganzen Welt auf die Moderne dar.
Mit „Die Conversos“ von Dr. Bernhard Holl ist der zweite Band bereits erschienen. Der Autor befasst sich hierin mit den Massenkonversionen vom Judentum zum Christentum im Spanien des 15. Jahrhunderts und der Ablehnung und Diskriminierung der Konvertiten durch die christliche Mehrheit. Diese Studie zeichnet erstmals detailliert die wesentlichen Wurzeln und Inhalte der Theologie einer Gruppe von christlichen Geistlichen und Gelehrten nach, die sich dieser Mehrheit entgegenstellte und forderte, die ‚Bekehrten‘ ohne Wenn und Aber als vollwertige Christen anzusehen, und sich dabei auf Recht und Tradition der lateinischen Kirche beriefen.
Jewish Studies and Postcolonial Studies are often thought to be at odds. Both disciplines intensively debate modernity, troubling its universalist claims and showing the contradictory nature of its promises. The call to provincialize Europe allows scholars from both disciplines to think, articulate and represent modern experiences beyond Europe and engage critically with traditions of modernity across disciplines, temporalities and geographies. Mapping Sephardi and other minor perspectives on modernity from across the globe in this volume, we are presenting fascinating cases and exploring new terrain where a fruitful encounter between Jewish and Postcolonial Studies can happen.
Graphene is well-knownfor its unique combination of electricaland mechanical properties. However, its vanishing band gap limitsthe use of graphene in microelectronics. Covalent functionalizationof graphene has been a common approach to address this critical issueand introduce a band gap. In this Article, we systematically analyzethe functionalization of single-layer graphene (SLG) and bilayer graphene(BLG) with methyl (CH3) using periodic density functionaltheory (DFT) at the PBE+D3 level of theory. We also include a comparisonof methylated single-layer and bilayer graphene, as well as a discussionof different methylation options (radicalic, cationic, and anionic).For SLG, methyl coverages ranging from 1/8 to 1/1, (i.e.,the fully methylated analogue of graphane) are considered. We findthat up to a coverage theta of 1/2, graphene readily accepts CH3, with neighbor CH3 groups preferring trans positions. Above theta = 1/2, the tendency to accept further CH3 weakens and the lattice constant increases. The band gapbehaves less regularly, but overall it increases with increasing methylcoverage. Thus, methylated graphene shows potential for developingband gap-tuned microelectronics devices and may offer further functionalizationoptions. To guide in the interpretation of methylation experiments,vibrational signatures of various species are characterized by normal-modeanalysis (NMA), their vibrational density of states (VDOS), and infrared(IR) spectra, the latter two are obtained from ab initio moleculardynamics (AIMD) in combination with a velocity-velocity autocorrelationfunction (VVAF) approach.
Genomic and epigenomic determinants of heat stress-induced transcriptional memory in Arabidopsis
(2023)
Background
Transcriptional regulation is a key aspect of environmental stress responses. Heat stress induces transcriptional memory, i.e., sustained induction or enhanced re-induction of transcription, that allows plants to respond more efficiently to a recurrent HS. In light of more frequent temperature extremes due to climate change, improving heat tolerance in crop plants is an important breeding goal. However, not all heat stress-inducible genes show transcriptional memory, and it is unclear what distinguishes memory from non-memory genes. To address this issue and understand the genome and epigenome architecture of transcriptional memory after heat stress, we identify the global target genes of two key memory heat shock transcription factors, HSFA2 and HSFA3, using time course ChIP-seq.
Results
HSFA2 and HSFA3 show near identical binding patterns. In vitro and in vivo binding strength is highly correlated, indicating the importance of DNA sequence elements. In particular, genes with transcriptional memory are strongly enriched for a tripartite heat shock element, and are hallmarked by several features: low expression levels in the absence of heat stress, accessible chromatin environment, and heat stress-induced enrichment of H3K4 trimethylation. These results are confirmed by an orthogonal transcriptomic data set using both de novo clustering and an established definition of memory genes.
Conclusions
Our findings provide an integrated view of HSF-dependent transcriptional memory and shed light on its sequence and chromatin determinants, enabling the prediction and engineering of genes with transcriptional memory behavior.
Rankings have grown in importance in the last decades. This is particularly evident in, but not limited to, academia. In this paper, we propose a power analytical take on academic rankings as a transnational(izing) phenomenon. In doing so, we make two contributions. First, we develop a conceptual definition of rankings as consecratory institutions. After providing an overview of the most prominent types of rankings in the academic field and discussing the different forms they can take, we suggest that rankings operate through subjectivation, zero-sum comparisons, quantification, publication and generating a doxical belief. Second, we propose that rankings fulfil a strategic double function. As a particularly momentous consecratory institution, rankings propel power shifts in the academic field and beyond by preferring (and being pushed by) specific academic milieus, types of agents, paradigms, and strategies. As a dispositif, rankings operate at the intersection of different fields, open academic fields up for a lay audience and advance processes of transnationalization by facilitating new modes of governance for hubs of state institutions, private corporations, media corporations, and data providers. Concluding, we argue that the consecration and dispositif functions rely on some basic principles of the practical functioning of rankings.
Economic evaluation of digital therapeutic care apps for unsupervised treatment of low back pain
(2023)
Background:
Digital therapeutic care (DTC) programs are unsupervised app-based treatments that provide video exercises and educational material to patients with nonspecific low back pain during episodes of pain and functional disability. German statutory health insurance can reimburse DTC programs since 2019, but evidence on efficacy and reasonable pricing remains scarce. This paper presents a probabilistic sensitivity analysis (PSA) to evaluate the efficacy and cost-utility of a DTC app against treatment as usual (TAU) in Germany.
Objective:
The aim of this study was to perform a PSA in the form of a Monte Carlo simulation based on the deterministic base case analysis to account for model assumptions and parameter uncertainty. We also intend to explore to what extent the results in this probabilistic analysis differ from the results in the base case analysis and to what extent a shortage of outcome data concerning quality-of-life (QoL) metrics impacts the overall results.
Methods:
The PSA builds upon a state-transition Markov chain with a 4-week cycle length over a model time horizon of 3 years from a recently published deterministic cost-utility analysis. A Monte Carlo simulation with 10,000 iterations and a cohort size of 10,000 was employed to evaluate the cost-utility from a societal perspective. Quality-adjusted life years (QALYs) were derived from Veterans RAND 6-Dimension (VR-6D) and Short-Form 6-Dimension (SF-6D) single utility scores. Finally, we also simulated reducing the price for a 3-month app prescription to analyze at which price threshold DTC would result in being the dominant strategy over TAU in Germany.
Results:
The Monte Carlo simulation yielded on average a euro135.97 (a currency exchange rate of EUR euro1=US $1.069 is applicable) incremental cost and 0.004 incremental QALYs per person and year for the unsupervised DTC app strategy compared to in-person physiotherapy in Germany. The corresponding incremental cost-utility ratio (ICUR) amounts to an additional euro34,315.19 per additional QALY. DTC yielded more QALYs in 54.96% of the iterations. DTC dominates TAU in 24.04% of the iterations for QALYs. Reducing the app price in the simulation from currently euro239.96 to euro164.61 for a 3-month prescription could yield a negative ICUR and thus make DTC the dominant strategy, even though the estimated probability of DTC being more effective than TAU is only 54.96%.
Conclusions:
Decision-makers should be cautious when considering the reimbursement of DTC apps since no significant treatment effect was found, and the probability of cost-effectiveness remains below 60% even for an infinite willingness-to-pay threshold. More app-based studies involving the utilization of QoL outcome parameters are urgently needed to account for the low and limited precision of the available QoL input parameters, which are crucial to making profound recommendations concerning the cost-utility of novel apps.
In this programmatic introduction, we lay out the foundations of an approach to analyzing knowledge-based political phenomena beyond the nation state from a field perspective. We understand transnational field analysis as a research program comprising genuine theoretical and methodological assumptions. While extant research is well aware of the theoretical assumptions of transnational field analysis, there is thus far relatively little awareness of the importance of its methodological premises. Addressing this imbalanced picture, we identify five methodological principles and specify consequences for studies of transnational fields. Our approach emphasizes that performing transnational field analysis goes beyond “taking a theory to the field”; it means engaging in and reflecting upon a complex research process that simultaneously draws upon and constructs theories of fields.