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Correction to: Knowledge bases and software support for variant interpretation in precision oncology
(2021)
Precision oncology is a rapidly evolving interdisciplinary medical specialty. Comprehensive cancer panels are becoming increasingly available at pathology departments worldwide, creating the urgent need for scalable cancer variant annotation and molecularly informed treatment recommendations. A wealth of mainly academia-driven knowledge bases calls for software tools supporting the multi-step diagnostic process. We derive a comprehensive list of knowledge bases relevant for variant interpretation by a review of existing literature followed by a survey among medical experts from university hospitals in Germany. In addition, we review cancer variant interpretation tools, which integrate multiple knowledge bases. We categorize the knowledge bases along the diagnostic process in precision oncology and analyze programmatic access options as well as the integration of knowledge bases into software tools. The most commonly used knowledge bases provide good programmatic access options and have been integrated into a range of software tools. For the wider set of knowledge bases, access options vary across different parts of the diagnostic process. Programmatic access is limited for information regarding clinical classifications of variants and for therapy recommendations. The main issue for databases used for biological classification of pathogenic variants and pathway context information is the lack of standardized interfaces. There is no single cancer variant interpretation tool that integrates all identified knowledge bases. Specialized tools are available and need to be further developed for different steps in the diagnostic process.
Die automatische Informationsextraktion (IE) aus unstrukturierten Texten ermöglicht völlig neue Wege, auf relevante Informationen zuzugreifen und deren Inhalte zu analysieren, die weit über bisherige Verfahren zur Stichwort-basierten Dokumentsuche hinausgehen. Die Entwicklung von Programmen zur Extraktion von maschinenlesbaren Daten aus Texten erfordert jedoch nach wie vor die Entwicklung von domänenspezifischen Extraktionsprogrammen. Insbesondere im Bereich der Enterprise Search (der Informationssuche im Unternehmensumfeld), in dem eine große Menge von heterogenen Dokumenttypen existiert, ist es oft notwendig ad-hoc Programm-module zur Extraktion von geschäftsrelevanten Entitäten zu entwickeln, die mit generischen Modulen in monolithischen IE-Systemen kombiniert werden. Dieser Umstand ist insbesondere kritisch, da potentiell für jeden einzelnen Anwendungsfall ein von Grund auf neues IE-System entwickelt werden muss. Die vorliegende Dissertation untersucht die effiziente Entwicklung und Ausführung von IE-Systemen im Kontext der Enterprise Search und effektive Methoden zur Ausnutzung bekannter strukturierter Daten im Unternehmenskontext für die Extraktion und Identifikation von geschäftsrelevanten Entitäten in Doku-menten. Grundlage der Arbeit ist eine neuartige Plattform zur Komposition von IE-Systemen auf Basis der Beschreibung des Datenflusses zwischen generischen und anwendungsspezifischen IE-Modulen. Die Plattform unterstützt insbesondere die Entwicklung und Wiederverwendung von generischen IE-Modulen und zeichnet sich durch eine höhere Flexibilität und Ausdrucksmächtigkeit im Vergleich zu vorherigen Methoden aus. Ein in der Dissertation entwickeltes Verfahren zur Dokumentverarbeitung interpretiert den Daten-austausch zwischen IE-Modulen als Datenströme und ermöglicht damit eine weitgehende Parallelisierung von einzelnen Modulen. Die autonome Ausführung der Module führt zu einer wesentlichen Beschleu-nigung der Verarbeitung von Einzeldokumenten und verbesserten Antwortzeiten, z. B. für Extraktions-dienste. Bisherige Ansätze untersuchen lediglich die Steigerung des durchschnittlichen Dokumenten-durchsatzes durch verteilte Ausführung von Instanzen eines IE-Systems. Die Informationsextraktion im Kontext der Enterprise Search unterscheidet sich z. B. von der Extraktion aus dem World Wide Web dadurch, dass in der Regel strukturierte Referenzdaten z. B. in Form von Unternehmensdatenbanken oder Terminologien zur Verfügung stehen, die oft auch die Beziehungen von Entitäten beschreiben. Entitäten im Unternehmensumfeld haben weiterhin bestimmte Charakteristiken: Eine Klasse von relevanten Entitäten folgt bestimmten Bildungsvorschriften, die nicht immer bekannt sind, auf die aber mit Hilfe von bekannten Beispielentitäten geschlossen werden kann, so dass unbekannte Entitäten extrahiert werden können. Die Bezeichner der anderen Klasse von Entitäten haben eher umschreibenden Charakter. Die korrespondierenden Umschreibungen in Texten können variieren, wodurch eine Identifikation derartiger Entitäten oft erschwert wird. Zur effizienteren Entwicklung von IE-Systemen wird in der Dissertation ein Verfahren untersucht, das alleine anhand von Beispielentitäten effektive Reguläre Ausdrücke zur Extraktion von unbekannten Entitäten erlernt und damit den manuellen Aufwand in derartigen Anwendungsfällen minimiert. Verschiedene Generalisierungs- und Spezialisierungsheuristiken erkennen Muster auf verschiedenen Abstraktionsebenen und schaffen dadurch einen Ausgleich zwischen Genauigkeit und Vollständigkeit bei der Extraktion. Bekannte Regellernverfahren im Bereich der Informationsextraktion unterstützen die beschriebenen Problemstellungen nicht, sondern benötigen einen (annotierten) Dokumentenkorpus. Eine Methode zur Identifikation von Entitäten, die durch Graph-strukturierte Referenzdaten vordefiniert sind, wird als dritter Schwerpunkt untersucht. Es werden Verfahren konzipiert, welche über einen exakten Zeichenkettenvergleich zwischen Text und Referenzdatensatz hinausgehen und Teilübereinstimmungen und Beziehungen zwischen Entitäten zur Identifikation und Disambiguierung heranziehen. Das in der Arbeit vorgestellte Verfahren ist bisherigen Ansätzen hinsichtlich der Genauigkeit und Vollständigkeit bei der Identifikation überlegen.
Since 2002, keywords like service-oriented engineering, service-oriented computing, and service-oriented architecture have been widely used in research, education, and enterprises. These and related terms are often misunderstood or used incorrectly. To correct these misunderstandings, a deeper knowledge of the concepts, the historical backgrounds, and an overview of service-oriented architectures is demanded and given in this paper.
In the area of cardiac monitoring, the use of digitally driven technologies is on the rise. While the development of medical products is advancing rapidly, allowing for new use-cases in cardiac monitoring and other areas, regulatory and legal requirements that govern market access are often evolving slowly, sometimes creating market barriers. This article gives a brief overview of the existing clinical studies regarding the use of smart wearables in cardiac monitoring and provides insight into the main regulatory and legal aspects that need to be considered when such products are intended to be used in a health care setting. Based on this brief overview, the article elaborates on the specific requirements in the main areas of authorization/certification and reimbursement/compensation, as well as data protection and data security. Three case studies are presented as examples of specific market access procedures: the USA, Germany, and Belgium. This article concludes that, despite the differences in specific requirements, market access pathways in most countries are characterized by a number of similarities, which should be considered early on in product development. The article also elaborates on how regulatory and legal requirements are currently being adapted for digitally driven wearables and proposes an ongoing evolution of these requirements to facilitate market access for beneficial medical technology in the future.
Model transformation is one of the key tasks in model-driven engineering and relies on the efficient matching and modification of graph-based data structures; its sibling graph rewriting has been used to successfully model problems in a variety of domains. Over the last years, a wide range of graph and model transformation tools have been developed all of them with their own particular strengths and typical application domains. In this paper, we give a survey and a comparison of the model and graph transformation tools that participated at the Transformation Tool Contest 2011. The reader gains an overview of the field and its tools, based on the illustrative solutions submitted to a Hello World task, and a comparison alongside a detailed taxonomy. The article is of interest to researchers in the field of model and graph transformation, as well as to software engineers with a transformation task at hand who have to choose a tool fitting to their needs. All solutions referenced in this article provide a SHARE demo. It supported the peer-review process for the contest, and now allows the reader to test the tools online.
Because software development is increasingly expensive and timeconsuming, software reuse gains importance. Aspect-oriented software development modularizes crosscutting concerns which enables their systematic reuse. Literature provides a number of AOP patterns and best practices for developing reusable aspects based on compelling examples for concerns like tracing, transactions and persistence. However, such best practices are lacking for systematically reusing invasive aspects. In this paper, we present the ‘callback mismatch problem’. This problem arises in the context of abstraction mismatch, in which the aspect is required to issue a callback to the base application. As a consequence, the composition of invasive aspects is cumbersome to implement, difficult to maintain and impossible to reuse. We motivate this problem in a real-world example, show that it persists in the current state-of-the-art, and outline the need for advanced aspectual composition mechanisms to deal with this.
This thesis presents novel ideas and research findings for the Web of Data – a global data space spanning many so-called Linked Open Data sources. Linked Open Data adheres to a set of simple principles to allow easy access and reuse for data published on the Web. Linked Open Data is by now an established concept and many (mostly academic) publishers adopted the principles building a powerful web of structured knowledge available to everybody. However, so far, Linked Open Data does not yet play a significant role among common web technologies that currently facilitate a high-standard Web experience. In this work, we thoroughly discuss the state-of-the-art for Linked Open Data and highlight several shortcomings – some of them we tackle in the main part of this work. First, we propose a novel type of data source meta-information, namely the topics of a dataset. This information could be published with dataset descriptions and support a variety of use cases, such as data source exploration and selection. For the topic retrieval, we present an approach coined Annotated Pattern Percolation (APP), which we evaluate with respect to topics extracted from Wikipedia portals. Second, we contribute to entity linking research by presenting an optimization model for joint entity linking, showing its hardness, and proposing three heuristics implemented in the LINked Data Alignment (LINDA) system. Our first solution can exploit multi-core machines, whereas the second and third approach are designed to run in a distributed shared-nothing environment. We discuss and evaluate the properties of our approaches leading to recommendations which algorithm to use in a specific scenario. The distributed algorithms are among the first of their kind, i.e., approaches for joint entity linking in a distributed fashion. Also, we illustrate that we can tackle the entity linking problem on the very large scale with data comprising more than 100 millions of entity representations from very many sources. Finally, we approach a sub-problem of entity linking, namely the alignment of concepts. We again target a method that looks at the data in its entirety and does not neglect existing relations. Also, this concept alignment method shall execute very fast to serve as a preprocessing for further computations. Our approach, called Holistic Concept Matching (HCM), achieves the required speed through grouping the input by comparing so-called knowledge representations. Within the groups, we perform complex similarity computations, relation conclusions, and detect semantic contradictions. The quality of our result is again evaluated on a large and heterogeneous dataset from the real Web. In summary, this work contributes a set of techniques for enhancing the current state of the Web of Data. All approaches have been tested on large and heterogeneous real-world input.
Wendepunkt für Gesundheit
(2019)
In this paper, we introduce an alternative approach to Temporal Answer Set Programming that relies on a variation of Temporal Equilibrium Logic (TEL) for finite traces. This approach allows us to even out the expressiveness of TEL over infinite traces with the computational capacity of (incremental) Answer Set Programming (ASP). Also, we argue that finite traces are more natural when reasoning about action and change. As a result, our approach is readily implementable via multi-shot ASP systems and benefits from an extension of ASP's full-fledged input language with temporal operators. This includes future as well as past operators whose combination offers a rich temporal modeling language. For computation, we identify the class of temporal logic programs and prove that it constitutes a normal form for our approach. Finally, we outline two implementations, a generic one and an extension of the ASP system clingo.
Under consideration for publication in Theory and Practice of Logic Programming (TPLP)
Developing rich Web applications can be a complex job - especially when it comes to mobile device support. Web-based environments such as Lively Webwerkstatt can help developers implement such applications by making the development process more direct and interactive. Further the process of developing software is collaborative which creates the need that the development environment offers collaboration facilities. This report describes extensions of the webbased development environment Lively Webwerkstatt such that it can be used in a mobile environment. The extensions are collaboration mechanisms, user interface adaptations but as well event processing and performance measuring on mobile devices.
With the advent of big data and data lakes, data are often integrated from multiple sources. Such integrated data are often of poor quality, due to inconsistencies, errors, and so forth. One way to check the quality of data is to infer functional dependencies (fds). However, in many modern applications it might be necessary to extract properties and relationships that are not captured through fds, due to the necessity to admit exceptions, or to consider similarity rather than equality of data values. Relaxed fds (rfds) have been introduced to meet these needs, but their discovery from data adds further complexity to an already complex problem, also due to the necessity of specifying similarity and validity thresholds. We propose Domino, a new discovery algorithm for rfds that exploits the concept of dominance in order to derive similarity thresholds of attribute values while inferring rfds. An experimental evaluation on real datasets demonstrates the discovery performance and the effectiveness of the proposed algorithm.
In the smallest grammar problem, we are given a word w and we want to compute a preferably small context-free grammar G for the singleton language {w} (where the size of a grammar is the sum of the sizes of its rules, and the size of a rule is measured by the length of its right side). It is known that, for unbounded alphabets, the decision variant of this problem is NP-hard and the optimisation variant does not allow a polynomial-time approximation scheme, unless P = NP. We settle the long-standing open problem whether these hardness results also hold for the more realistic case of a constant-size alphabet. More precisely, it is shown that the smallest grammar problem remains NP-complete (and its optimisation version is APX-hard), even if the alphabet is fixed and has size of at least 17. The corresponding reduction is robust in the sense that it also works for an alternative size-measure of grammars that is commonly used in the literature (i. e., a size measure also taking the number of rules into account), and it also allows to conclude that even computing the number of rules required by a smallest grammar is a hard problem. On the other hand, if the number of nonterminals (or, equivalently, the number of rules) is bounded by a constant, then the smallest grammar problem can be solved in polynomial time, which is shown by encoding it as a problem on graphs with interval structure. However, treating the number of rules as a parameter (in terms of parameterised complexity) yields W[1]-hardness. Furthermore, we present an O(3(vertical bar w vertical bar)) exact exponential-time algorithm, based on dynamic programming. These three main questions are also investigated for 1-level grammars, i. e., grammars for which only the start rule contains nonterminals on the right side; thus, investigating the impact of the "hierarchical depth" of grammars on the complexity of the smallest grammar problem. In this regard, we obtain for 1-level grammars similar, but slightly stronger results.
Background:
Early reports indicate that AKI is common among patients with coronavirus disease 2019 (COVID-19) and associatedwith worse outcomes. However, AKI among hospitalized patients with COVID19 in the United States is not well described.
Methods:
This retrospective, observational study involved a review of data from electronic health records of patients aged >= 18 years with laboratory-confirmed COVID-19 admitted to the Mount Sinai Health System from February 27 to May 30, 2020. We describe the frequency of AKI and dialysis requirement, AKI recovery, and adjusted odds ratios (aORs) with mortality.
Results:
Of 3993 hospitalized patients with COVID-19, AKI occurred in 1835 (46%) patients; 347 (19%) of the patientswith AKI required dialysis. The proportionswith stages 1, 2, or 3 AKIwere 39%, 19%, and 42%, respectively. A total of 976 (24%) patients were admitted to intensive care, and 745 (76%) experienced AKI. Of the 435 patients with AKI and urine studies, 84% had proteinuria, 81% had hematuria, and 60% had leukocyturia. Independent predictors of severe AKI were CKD, men, and higher serum potassium at admission. In-hospital mortality was 50% among patients with AKI versus 8% among those without AKI (aOR, 9.2; 95% confidence interval, 7.5 to 11.3). Of survivors with AKI who were discharged, 35% had not recovered to baseline kidney function by the time of discharge. An additional 28 of 77 (36%) patients who had not recovered kidney function at discharge did so on posthospital follow-up.
Conclusions:
AKI is common among patients hospitalized with COVID-19 and is associated with high mortality. Of all patients with AKI, only 30% survived with recovery of kidney function by the time of discharge.
Large real-world networks typically follow a power-law degree distribution. To study such networks, numerous random graph models have been proposed. However, real-world networks are not drawn at random. Therefore, Brach et al. (27th symposium on discrete algorithms (SODA), pp 1306-1325, 2016) introduced two natural deterministic conditions: (1) a power-law upper bound on the degree distribution (PLB-U) and (2) power-law neighborhoods, that is, the degree distribution of neighbors of each vertex is also upper bounded by a power law (PLB-N). They showed that many real-world networks satisfy both properties and exploit them to design faster algorithms for a number of classical graph problems. We complement their work by showing that some well-studied random graph models exhibit both of the mentioned PLB properties. PLB-U and PLB-N hold with high probability for Chung-Lu Random Graphs and Geometric Inhomogeneous Random Graphs and almost surely for Hyperbolic Random Graphs. As a consequence, all results of Brach et al. also hold with high probability or almost surely for those random graph classes. In the second part we study three classical NP-hard optimization problems on PLB networks. It is known that on general graphs with maximum degree Delta, a greedy algorithm, which chooses nodes in the order of their degree, only achieves a Omega (ln Delta)-approximation forMinimum Vertex Cover and Minimum Dominating Set, and a Omega(Delta)-approximation forMaximum Independent Set. We prove that the PLB-U property with beta>2 suffices for the greedy approach to achieve a constant-factor approximation for all three problems. We also show that these problems are APX-hard even if PLB-U, PLB-N, and an additional power-law lower bound on the degree distribution hold. Hence, a PTAS cannot be expected unless P = NP. Furthermore, we prove that all three problems are in MAX SNP if the PLB-U property holds.
SensorHub
(2022)
Observational studies are an important tool for determining whether the findings from controlled experiments can be transferred into scenarios that are closer to subjects' real-life circumstances. A rigorous approach to observational studies involves collecting data from different sensors to comprehensively capture the situation of the subject. However, this leads to technical difficulties especially if the sensors are from different manufacturers, as multiple data collection tools have to run simultaneously. We present SensorHub, a system that can collect data from various wearable devices from different manufacturers, such as inertial measurement units, portable electrocardiographs, portable electroencephalographs, portable photoplethysmographs, and sensors for electrodermal activity. Additionally, our tool offers the possibility to include ecological momentary assessments (EMAs) in studies. Hence, SensorHub enables multimodal sensor data collection under real-world conditions and allows direct user feedback to be collected through questionnaires, enabling studies at home. In a first study with 11 participants, we successfully used SensorHub to record multiple signals with different devices and collected additional information with the help of EMAs. In addition, we evaluated SensorHub's technical capabilities in several trials with up to 21 participants recording simultaneously using multiple sensors with sampling frequencies as high as 1000 Hz. We could show that although there is a theoretical limitation to the transmissible data rate, in practice this limitation is not an issue and data loss is rare. We conclude that with modern communication protocols and with the increasingly powerful smartphones and wearables, a system like our SensorHub establishes an interoperability framework to adequately combine consumer-grade sensing hardware which enables observational studies in real life.
Patient monitoring technology has been used to guide therapy and alert staff when a vital sign leaves a predefined range in the intensive care unit (ICU) for decades. However, large amounts of technically false or clinically irrelevant alarms provoke alarm fatigue in staff leading to desensitisation towards critical alarms.
With this systematic review, we are following the Preferred Reporting Items for Systematic Reviews (PRISMA) checklist in order to summarise scientific efforts that aimed to develop IT systems to reduce alarm fatigue in ICUs. 69 peer-reviewed publications were included. The majority of publications targeted the avoidance of technically false alarms, while the remainder focused on prediction of patient deterioration or alarm presentation.
The investigated alarm types were mostly associated with heart rate or arrhythmia, followed by arterial blood pressure, oxygen saturation, and respiratory rate.
Most publications focused on the development of software solutions, some on wearables, smartphones, or headmounted displays for delivering alarms to staff.
The most commonly used statistical models were tree-based. In conclusion, we found strong evidence that alarm fatigue can be alleviated by IT-based solutions.
However, future efforts should focus more on the avoidance of clinically non-actionable alarms which could be accelerated by improving the data availability.
Detection of the QRS complex is a long-standing topic in the context of electrocardiography and many algorithms build upon the knowledge of the QRS positions. Although the first solutions to this problem were proposed in the 1970s and 1980s, there is still potential for improvements. Advancements in neural network technology made in recent years also lead to the emergence of enhanced QRS detectors based on artificial neural networks. In this work, we propose a method for assessing the certainty that is in each of the detected QRS complexes, i.e. how confident the QRS detector is that there is, in fact, a QRS complex in the position where it was detected. We further show how this metric can be utilised to distinguish correctly detected QRS complexes from false detections.
Creation, collection and retention of knowledge in digital communities is an activity that currently requires being explicitly targeted as a secure method of keeping intellectual capital growing in the digital era. In particular, we consider it relevant to analyze and evaluate the empathetic cognitive personalities and behaviors that individuals now have with the change from face-to-face communication (F2F) to computer-mediated communication (CMC) online. This document proposes a cyber-humanistic approach to enhance the traditional SECI knowledge management model. A cognitive perception is added to its cyclical process following design thinking interaction, exemplary for improvement of the method in which knowledge is continuously created, converted and shared. In building a cognitive-centered model, we specifically focus on the effective identification and response to cognitive stimulation of individuals, as they are the intellectual generators and multiplicators of knowledge in the online environment. Our target is to identify how geographically distributed-digital-organizations should align the individual's cognitive abilities to promote iteration and improve interaction as a reliable stimulant of collective intelligence. The new model focuses on analyzing the four different stages of knowledge processing, where individuals with sympathetic cognitive personalities can significantly boost knowledge creation in a virtual social system. For organizations, this means that multidisciplinary individuals can maximize their extensive potential, by externalizing their knowledge in the correct stage of the knowledge creation process, and by collaborating with their appropriate sympathetically cognitive remote peers.
Polygenic risk scores (PRS) aggregating results from genome-wide association studies are the state of the art in the prediction of susceptibility to complex traits or diseases, yet their predictive performance is limited for various reasons, not least of which is their failure to incorporate the effects of gene-gene interactions. Novel machine learning algorithms that use large amounts of data promise to find gene-gene interactions in order to build models with better predictive performance than PRS. Here, we present a data preprocessing step by using data-mining of contextual information to reduce the number of features, enabling machine learning algorithms to identify gene-gene interactions. We applied our approach to the Parkinson's Progression Markers Initiative (PPMI) dataset, an observational clinical study of 471 genotyped subjects (368 cases and 152 controls). With an AUC of 0.85 (95% CI = [0.72; 0.96]), the interaction-based prediction model outperforms the PRS (AUC of 0.58 (95% CI = [0.42; 0.81])). Furthermore, feature importance analysis of the model provided insights into the mechanism of Parkinson's disease. For instance, the model revealed an interaction of previously described drug target candidate genes TMEM175 and GAPDHP25. These results demonstrate that interaction-based machine learning models can improve genetic prediction models and might provide an answer to the missing heritability problem.
In the stable marriage problem, a set of men and a set of women are given, each of whom has a strictly ordered preference list over the acceptable agents in the opposite class. A matching is called stable if it is not blocked by any pair of agents, who mutually prefer each other to their respective partner. Ties in the preferences allow for three different definitions for a stable matching: weak, strong and super-stability. Besides this, acceptable pairs in the instance can be restricted in their ability of blocking a matching or being part of it, which again generates three categories of restrictions on acceptable pairs. Forced pairs must be in a stable matching, forbidden pairs must not appear in it, and lastly, free pairs cannot block any matching.
Our computational complexity study targets the existence of a stable solution for each of the three stability definitions, in the presence of each of the three types of restricted pairs. We solve all cases that were still open. As a byproduct, we also derive that the maximum size weakly stable matching problem is hard even in very dense graphs, which may be of independent interest.
An unceasing problem of our prevailing society is the fair division of goods. The problem of proportional cake cutting focuses on dividing a heterogeneous and divisible resource, the cake, among n players who value pieces according to their own measure function. The goal is to assign each player a not necessarily connected part of the cake that the player evaluates at least as much as her proportional share. <br /> In this article, we investigate the problem of proportional division with unequal shares, where each player is entitled to receive a predetermined portion of the cake. Our main contribution is threefold. First we present a protocol for integer demands, which delivers a proportional solution in fewer queries than all known protocols. By giving a matching lower bound, we then show that our protocol is asymptotically the fastest possible. Finally, we turn to irrational demands and solve the proportional cake cutting problem by reducing it to the same problem with integer demands only. All results remain valid in a highly general cake cutting model, which can be of independent interest.
Objective:
Hypertension has long been recognized as one of the most important predisposing factors for cardiovascular diseases and mortality.
In recent years, machine learning methods have shown potential in diagnostic and predictive approaches in chronic diseases.
Electronic health records (EHRs) have emerged as a reliable source of longitudinal data. The aim of this study is to predict the onset of hypertension using modern deep learning (DL) architectures, specifically long short-term memory (LSTM) networks, and longitudinal EHRs.
Materials and Methods:
We compare this approach to the best performing models reported from previous works, particularly XGboost, applied to aggregated features.
Our work is based on data from 233 895 adult patients from a large health system in the United States. We divided our population into 2 distinct longitudinal datasets based on the diagnosis date.
To ensure generalization to unseen data, we trained our models on the first dataset (dataset A "train and validation") using cross-validation, and then applied the models to a second dataset (dataset B "test") to assess their performance.
We also experimented with 2 different time-windows before the onset of hypertension and evaluated the impact on model performance.
Results:
With the LSTM network, we were able to achieve an area under the receiver operating characteristic curve value of 0.98 in the "train and validation" dataset A and 0.94 in the "test" dataset B for a prediction time window of 1 year. Lipid disorders, type 2 diabetes, and renal disorders are found to be associated with incident hypertension.
Conclusion:
These findings show that DL models based on temporal EHR data can improve the identification of patients at high risk of hypertension and corresponding driving factors. In the long term, this work may support identifying individuals who are at high risk for developing hypertension and facilitate earlier intervention to prevent the future development of hypertension.
FIBER
(2021)
Objectives:
The development of clinical predictive models hinges upon the availability of comprehensive clinical data. Tapping into such resources requires considerable effort from clinicians, data scientists, and engineers. Specifically, these efforts are focused on data extraction and preprocessing steps required prior to modeling, including complex database queries. A handful of software libraries exist that can reduce this complexity by building upon data standards. However, a gap remains concerning electronic health records (EHRs) stored in star schema clinical data warehouses, an approach often adopted in practice. In this article, we introduce the FlexIBle EHR Retrieval (FIBER) tool: a Python library built on top of a star schema (i2b2) clinical data warehouse that enables flexible generation of modeling-ready cohorts as data frames.
Materials and Methods:
FIBER was developed on top of a large-scale star schema EHR database which contains data from 8 million patients and over 120 million encounters. To illustrate FIBER's capabilities, we present its application by building a heart surgery patient cohort with subsequent prediction of acute kidney injury (AKI) with various machine learning models.
Results:
Using FIBER, we were able to build the heart surgery cohort (n = 12 061), identify the patients that developed AKI (n = 1005), and automatically extract relevant features (n = 774). Finally, we trained machine learning models that achieved area under the curve values of up to 0.77 for this exemplary use case.
Conclusion:
FIBER is an open-source Python library developed for extracting information from star schema clinical data warehouses and reduces time-to-modeling, helping to streamline the clinical modeling process.
Cloud computing is a model for enabling on-demand access to a shared pool of computing resources. With virtually limitless on-demand resources, a cloud environment enables the hosted Internet application to quickly cope when there is an increase in the workload. However, the overhead of provisioning resources exposes the Internet application to periods of under-provisioning and performance degradation. Moreover, the performance interference, due to the consolidation in the cloud environment, complicates the performance management of the Internet applications. In this dissertation, we propose two approaches to mitigate the impact of the resources provisioning overhead. The first approach employs control theory to scale resources vertically and cope fast with workload. This approach assumes that the provider has knowledge and control over the platform running in the virtual machines (VMs), which limits it to Platform as a Service (PaaS) and Software as a Service (SaaS) providers. The second approach is a customer-side one that deals with the horizontal scalability in an Infrastructure as a Service (IaaS) model. It addresses the trade-off problem between cost and performance with a multi-goal optimization solution. This approach finds the scale thresholds that achieve the highest performance with the lowest increase in the cost. Moreover, the second approach employs a proposed time series forecasting algorithm to scale the application proactively and avoid under-utilization periods. Furthermore, to mitigate the interference impact on the Internet application performance, we developed a system which finds and eliminates the VMs suffering from performance interference. The developed system is a light-weight solution which does not imply provider involvement. To evaluate our approaches and the designed algorithms at large-scale level, we developed a simulator called (ScaleSim). In the simulator, we implemented scalability components acting as the scalability components of Amazon EC2. The current scalability implementation in Amazon EC2 is used as a reference point for evaluating the improvement in the scalable application performance. ScaleSim is fed with realistic models of the RUBiS benchmark extracted from the real environment. The workload is generated from the access logs of the 1998 world cup website. The results show that optimizing the scalability thresholds and adopting proactive scalability can mitigate 88% of the resources provisioning overhead impact with only a 9% increase in the cost.
Phe2vec
(2021)
Robust phenotyping of patients from electronic health records (EHRs) at scale is a challenge in clinical informatics. Here, we introduce Phe2vec, an automated framework for disease phenotyping from EHRs based on unsupervised learning and assess its effectiveness against standard rule-based algorithms from Phenotype KnowledgeBase (PheKB). Phe2vec is based on pre-computing embeddings of medical concepts and patients' clinical history. Disease phenotypes are then derived from a seed concept and its neighbors in the embedding space. Patients are linked to a disease if their embedded representation is close to the disease phenotype. Comparing Phe2vec and PheKB cohorts head-to-head using chart review, Phe2vec performed on par or better in nine out of ten diseases. Differently from other approaches, it can scale to any condition and was validated against widely adopted expert-based standards. Phe2vec aims to optimize clinical informatics research by augmenting current frameworks to characterize patients by condition and derive reliable disease cohorts.
Interacting services play a key role to realize business process integration among different business partners by means of electronic message exchange. In order to provide seamless integration of these services, the messages exchanged as well as their dependencies must be well-defined. Service choreographies are a means to describe the allowed conversations. This article presents a requirements framework for service choreography languages, along which existing choreography languages are assessed. The requirements framework provides the basis for introducing the language BPEL4Chor, which extends the industry standard WS-BPEL with choreography-specific concepts. A validation is provided and integration with executable service orchestrations is discussed.
Process instantiation
(2009)
Although several process modeling languages allow one to specify processes with multiple start elements, the precise semantics of such models are often unclear, both from a pragmatic and from a theoretical point of view. This paper addresses the lack of research on this problem and introduces the CASU framework (from Creation, Activation, subscription, Unsubscription). The contribution of this framework is a systematic description of design alternatives for the specification of instantiation semantics of process modeling languages. We classify six prominent languages by the help of this framework. We validate the relevance of the CASU framework through empirical investigations involving a large set of process models from practice. Our work provides the basis for the design of new correctness criteria as well as for the formalization of Event-driven Process Chains (EPCs) and extension of the Business Process Modeling Notation (BPMN). It complements research such as the workflow patterns.
With the rise of electronic integration between organizations, the need for a precise specification of interaction behavior increases. Information systems, replacing interaction previously carried out by humans via phone, faxes and emails, require a precise specification for handling all possible situations. Such interaction behavior is described in process choreographies. While many proposals for choreography languages have already been made, most of them fall into the category of interconnection models, where the observable behavior of the different partners is described and then related via message flow. As this article will show, this modeling approach fails to support fundamental design principles of choreographies and typically leads to modeling errors. This motivates an alternative modeling style, namely interaction modeling, for overcoming these limitations. While the main concepts are independent of a concrete modeling language, iBPMN is introduced as novel interaction modeling language. Formal execution semantics are provided and a comprehensive toolset implementing the approach is presented.
3D point cloud technology facilitates the automated and highly detailed acquisition of real-world environments such as assets, sites, and countries. We present a web-based system for the interactive exploration and inspection of arbitrary large 3D point clouds. Our approach is able to render 3D point clouds with billions of points using spatial data structures and level-of-detail representations. Point-based rendering techniques and post-processing effects are provided to enable task-specific and data-specific filtering, e.g., based on semantics. A set of interaction techniques allows users to collaboratively work with the data (e.g., measuring distances and annotating). Additional value is provided by the system’s ability to display additional, context-providing geodata alongside 3D point clouds and to integrate processing and analysis operations. We have evaluated the presented techniques and in case studies and with different data sets from aerial, mobile, and terrestrial acquisition with up to 120 billion points to show their practicality and feasibility.
3D point clouds are a digital representation of our world and used in a variety of applications. They are captured with LiDAR or derived by image-matching approaches to get surface information of objects, e.g., indoor scenes, buildings, infrastructures, cities, and landscapes. We present novel interaction and visualization techniques for heterogeneous, time variant, and semantically rich 3D point clouds. Interactive and view-dependent see-through lenses are introduced as exploration tools to enhance recognition of objects, semantics, and temporal changes within 3D point cloud depictions. We also develop filtering and highlighting techniques that are used to dissolve occlusion to give context-specific insights. All techniques can be combined with an out-of-core real-time rendering system for massive 3D point clouds. We have evaluated the presented approach with 3D point clouds from different application domains. The results show the usability and how different visualization and exploration tasks can be improved for a variety of domain-specific applications.
Estimation-of-distribution algorithms (EDAs) are randomized search heuristics that create a probabilistic model of the solution space, which is updated iteratively, based on the quality of the solutions sampled according to the model. As previous works show, this iteration-based perspective can lead to erratic updates of the model, in particular, to bit-frequencies approaching a random boundary value. In order to overcome this problem, we propose a new EDA based on the classic compact genetic algorithm (cGA) that takes into account a longer history of samples and updates its model only with respect to information which it classifies as statistically significant. We prove that this significance-based cGA (sig-cGA) optimizes the commonly regarded benchmark functions OneMax (OM), LeadingOnes, and BinVal all in quasilinear time, a result shown for no other EDA or evolutionary algorithm so far. For the recently proposed stable compact genetic algorithm-an EDA that tries to prevent erratic model updates by imposing a bias to the uniformly distributed model-we prove that it optimizes OM only in a time exponential in its hypothetical population size. Similarly, we show that the convex search algorithm cannot optimize OM in polynomial time.
A simplified run time analysis of the univariate marginal distribution algorithm on LeadingOnes
(2021)
With elementary means, we prove a stronger run time guarantee for the univariate marginal distribution algorithm (UMDA) optimizing the LEADINGONES benchmark function in the desirable regime with low genetic drift. If the population size is at least quasilinear, then, with high probability, the UMDA samples the optimum in a number of iterations that is linear in the problem size divided by the logarithm of the UMDA's selection rate. This improves over the previous guarantee, obtained by Dang and Lehre (2015) via the deep level-based population method, both in terms of the run time and by demonstrating further run time gains from small selection rates. Under similar assumptions, we prove a lower bound that matches our upper bound up to constant factors.
One of the first and easy to use techniques for proving run time bounds for evolutionary algorithms is the so-called method of fitness levels by Wegener. It uses a partition of the search space into a sequence of levels which are traversed by the algorithm in increasing order, possibly skipping levels. An easy, but often strong upper bound for the run time can then be derived by adding the reciprocals of the probabilities to leave the levels (or upper bounds for these). Unfortunately, a similarly effective method for proving lower bounds has not yet been established. The strongest such method, proposed by Sudholt (2013), requires a careful choice of the viscosity parameters gamma(i), j, 0 <= i < j <= n. In this paper we present two new variants of the method, one for upper and one for lower bounds. Besides the level leaving probabilities, they only rely on the probabilities that levels are visited at all. We show that these can be computed or estimated without greater difficulties and apply our method to reprove the following known results in an easy and natural way. (i) The precise run time of the (1+1) EA on LEADINGONES. (ii) A lower bound for the run time of the (1+1) EA on ONEMAX, tight apart from an O(n) term. (iii) A lower bound for the run time of the (1+1) EA on long k-paths (which differs slightly from the previous result due to a small error in the latter). We also prove a tighter lower bound for the run time of the (1+1) EA on jump functions by showing that, regardless of the jump size, only with probability O(2(-n)) the algorithm can avoid to jump over the valley of low fitness.
While many optimization problems work with a fixed number of decision variables and thus a fixed-length representation of possible solutions, genetic programming (GP) works on variable-length representations. A naturally occurring problem is that of bloat, that is, the unnecessary growth of solution lengths, which may slow down the optimization process. So far, the mathematical runtime analysis could not deal well with bloat and required explicit assumptions limiting bloat.
In this paper, we provide the first mathematical runtime analysis of a GP algorithm that does not require any assumptions on the bloat. Previous performance guarantees were only proven conditionally for runs in which no strong bloat occurs. Together with improved analyses for the case with bloat restrictions our results show that such assumptions on the bloat are not necessary and that the algorithm is efficient without explicit bloat control mechanism.
More specifically, we analyzed the performance of the (1 + 1) GP on the two benchmark functions ORDER and MAJORITY. When using lexicographic parsimony pressure as bloat control, we show a tight runtime estimate of O(T-init + nlogn) iterations both for ORDER and MAJORITY. For the case without bloat control, the bounds O(T-init logT(i)(nit) + n(logn)(3)) and Omega(T-init + nlogn) (and Omega(T-init log T-init) for n = 1) hold for MAJORITY(1).
We contribute to the theoretical understanding of randomized search heuristics by investigating their optimization behavior on satisfiable random k-satisfiability instances both in the planted solution model and the uniform model conditional on satisfiability. Denoting the number of variables by n, our main technical result is that the simple () evolutionary algorithm with high probability finds a satisfying assignment in time when the clause-variable density is at least logarithmic. For low density instances, evolutionary algorithms seem to be less effective, and all we can show is a subexponential upper bound on the runtime for densities below . We complement these mathematical results with numerical experiments on a broader density spectrum. They indicate that, indeed, the () EA is less efficient on lower densities. Our experiments also suggest that the implicit constants hidden in our main runtime guarantee are low. Our main result extends and considerably improves the result obtained by Sutton and Neumann (Lect Notes Comput Sci 8672:942-951, 2014) in terms of runtime, minimum density, and clause length. These improvements are made possible by establishing a close fitness-distance correlation in certain parts of the search space. This approach might be of independent interest and could be useful for other average-case analyses of randomized search heuristics. While the notion of a fitness-distance correlation has been around for a long time, to the best of our knowledge, this is the first time that fitness-distance correlation is explicitly used to rigorously prove a performance statement for an evolutionary algorithm.
Duplicate detection algorithms produce clusters of database records, each cluster representing a single real-world entity. As most of these algorithms use pairwise comparisons, the resulting (transitive) clusters can be inconsistent: Not all records within a cluster are sufficiently similar to be classified as duplicate. Thus, one of many subsequent clustering algorithms can further improve the result. <br /> We explain in detail, compare, and evaluate many of these algorithms and introduce three new clustering algorithms in the specific context of duplicate detection. Two of our three new algorithms use the structure of the input graph to create consistent clusters. Our third algorithm, and many other clustering algorithms, focus on the edge weights, instead. For evaluation, in contrast to related work, we experiment on true real-world datasets, and in addition examine in great detail various pair-selection strategies used in practice. While no overall winner emerges, we are able to identify best approaches for different situations. In scenarios with larger clusters, our proposed algorithm, Extended Maximum Clique Clustering (EMCC), and Markov Clustering show the best results. EMCC especially outperforms Markov Clustering regarding the precision of the results and additionally has the advantage that it can also be used in scenarios where edge weights are not available.
Duplicate detection is the task of identifying all groups of records within a data set that represent the same real-world entity, respectively. This task is difficult, because (i) representations might differ slightly, so some similarity measure must be defined to compare pairs of records and (ii) data sets might have a high volume making a pair-wise comparison of all records infeasible. To tackle the second problem, many algorithms have been suggested that partition the data set and compare all record pairs only within each partition. One well-known such approach is the Sorted Neighborhood Method (SNM), which sorts the data according to some key and then advances a window over the data comparing only records that appear within the same window. We propose several variations of SNM that have in common a varying window size and advancement. The general intuition of such adaptive windows is that there might be regions of high similarity suggesting a larger window size and regions of lower similarity suggesting a smaller window size. We propose and thoroughly evaluate several adaption strategies, some of which are provably better than the original SNM in terms of efficiency (same results with fewer comparisons).
TPC-H continues to be the most widely used benchmark for relational OLAP systems. It poses a number of challenges, also known as "choke points", which database systems have to solve in order to achieve good benchmark results. Examples include joins across multiple tables, correlated subqueries, and correlations within the TPC-H data set. Knowing the impact of such optimizations helps in developing optimizers as well as in interpreting TPC-H results across database systems.
This paper provides a systematic analysis of choke points and their optimizations. It complements previous work on TPC-H choke points by providing a quantitative discussion of their relevance. It focuses on eleven choke points where the optimizations are beneficial independently of the database system. Of these, the flattening of subqueries and the placement of predicates have the biggest impact. Three queries (Q2, Q17, and Q21) are strongly ifluenced by the choice of an efficient query plan; three others (Q1, Q13, and Q18) are less influenced by plan optimizations and more dependent on an efficient execution engine.
From face to face
(2019)
Despite advances in the conceptualisation of facial mimicry, its role in the processing of social information is a matter of debate. In the present study, we investigated the relationship between mimicry and cognitive and emotional empathy. To assess mimicry, facial electromyography was recorded for 70 participants while they completed the Multifaceted Empathy Test, which presents complex context-embedded emotional expressions. As predicted, inter-individual differences in emotional and cognitive empathy were associated with the level of facial mimicry. For positive emotions, the intensity of the mimicry response scaled with the level of state emotional empathy. Mimicry was stronger for the emotional empathy task compared to the cognitive empathy task. The specific empathy condition could be successfully detected from facial muscle activity at the level of single individuals using machine learning techniques. These results support the view that mimicry occurs depending on the social context as a tool to affiliate and it is involved in cognitive as well as emotional empathy.
While offering significant expressive power, graph transformation systems often come with rather limited capabilities for automated analysis, particularly if systems with many possible initial graphs and large or infinite state spaces are concerned. One approach that tries to overcome these limitations is inductive invariant checking. However, the verification of inductive invariants often requires extensive knowledge about the system in question and faces the approach-inherent challenges of locality and lack of context.
To address that, this report discusses k-inductive invariant checking for graph transformation systems as a generalization of inductive invariants. The additional context acquired by taking multiple (k) steps into account is the key difference to inductive invariant checking and is often enough to establish the desired invariants without requiring the iterative development of additional properties.
To analyze possibly infinite systems in a finite fashion, we introduce a symbolic encoding for transformation traces using a restricted form of nested application conditions. As its central contribution, this report then presents a formal approach and algorithm to verify graph constraints as k-inductive invariants. We prove the approach's correctness and demonstrate its applicability by means of several examples evaluated with a prototypical implementation of our algorithm.
Graph transformation systems are a powerful formal model to capture model transformations or systems with infinite state space, among others. However, this expressive power comes at the cost of rather limited automated analysis capabilities. The general case of unbounded many initial graphs or infinite state spaces is only supported by approaches with rather limited scalability or expressiveness. In this report we improve an existing approach for the automated verification of inductive invariants for graph transformation systems. By employing partial negative application conditions to represent and check many alternative conditions in a more compact manner, we can check examples with rules and constraints of substantially higher complexity. We also substantially extend the expressive power by supporting more complex negative application conditions and provide higher accuracy by employing advanced implication checks. The improvements are evaluated and compared with another applicable tool by considering three case studies.
The correctness of model transformations is a crucial element for model-driven engineering of high quality software. In particular, behavior preservation is the most important correctness property avoiding the introduction of semantic errors during the model-driven engineering process. Behavior preservation verification techniques either show that specific properties are preserved, or more generally and complex, they show some kind of behavioral equivalence or refinement between source and target model of the transformation. Both kinds of behavior preservation verification goals have been presented with automatic tool support for the instance level, i.e. for a given source and target model specified by the model transformation. However, up until now there is no automatic verification approach available at the transformation level, i.e. for all source and target models specified by the model transformation.
In this report, we extend our results presented in [27] and outline a new sophisticated approach for the automatic verification of behavior preservation captured by bisimulation resp. simulation for model transformations specified by triple graph grammars and semantic definitions given by graph transformation rules. In particular, we show that the behavior preservation problem can be reduced to invariant checking for graph transformation and that the resulting checking problem can be addressed by our own invariant checker even for a complex example where a sequence chart is transformed into communicating automata. We further discuss today's limitations of invariant checking for graph transformation and motivate further lines of future work in this direction.
Artificial intelligence (AI) is changing fundamentally the way how IT solutions are implemented and operated across all application domains, including the geospatial domain. This contribution outlines AI-based techniques for 3D point clouds and geospatial digital twins as generic components of geospatial AI. First, we briefly reflect on the term "AI" and outline technology developments needed to apply AI to IT solutions, seen from a software engineering perspective. Next, we characterize 3D point clouds as key category of geodata and their role for creating the basis for geospatial digital twins; we explain the feasibility of machine learning (ML) and deep learning (DL) approaches for 3D point clouds. In particular, we argue that 3D point clouds can be seen as a corpus with similar properties as natural language corpora and formulate a "Naturalness Hypothesis" for 3D point clouds. In the main part, we introduce a workflow for interpreting 3D point clouds based on ML/DL approaches that derive domain-specific and application-specific semantics for 3D point clouds without having to create explicit spatial 3D models or explicit rule sets. Finally, examples are shown how ML/DL enables us to efficiently build and maintain base data for geospatial digital twins such as virtual 3D city models, indoor models, or building information models.
For interactive construction of CSG models understanding the layout of a model is essential for its efficient manipulation. To understand position and orientation of aggregated components of a CSG model, we need to realize its visible and occluded parts as a whole. Hence, transparency and enhanced outlines are key techniques to assist comprehension. We present a novel real-time rendering technique for visualizing design and spatial assembly of CSG models. As enabling technology we combine an image-space CSG rendering algorithm with blueprint rendering. Blueprint rendering applies depth peeling for extracting layers of ordered depth from polygonal models and then composes them in sorted order facilitating a clear insight of the models. We develop a solution for implementing depth peeling for CSG models considering their depth complexity. Capturing surface colors of each layer and later combining the results allows for generating order-independent transparency as one major rendering technique for CSG models. We further define visually important edges for CSG models and integrate an image-space edgeenhancement technique for detecting them in each layer. In this way, we extract visually important edges that are directly and not directly visible to outline a model’s layout. Combining edges with transparency rendering, finally, generates edge-enhanced depictions of image-based CSG models and allows us to realize their complex, spatial assembly.
Graph transformation systems have been studied extensively and applied to several areas of computer science like formal language theory, the modeling of databases, concurrent or distributed systems, and visual, logical, and functional programming. In most kinds of applications it is necessary to have the possibility of restricting the applicability of rules. This is usually done by means of application conditions. In this paper, we continue the work of extending the fundamental theory of graph transformation to the case where rules may use arbitrary (nested) application conditions. More precisely, we generalize the Embedding theorem, and we study how local confluence can be checked in this context. In particular, we define a new notion of critical pair which allows us to formulate and prove a Local Confluence Theorem for the general case of rules with nested application conditions. All our results are presented, not for a specific class of graphs, but for any arbitrary M-adhesive category, which means that our results apply to most kinds of graphical structures. We demonstrate our theory on the modeling of an elevator control by a typed graph transformation system with positive and negative application conditions.
Nested application conditions generalise the well-known negative application conditions and are important for several application domains. In this paper, we present Local Church-Rosser, Parallelism, Concurrency and Amalgamation Theorems for rules with nested application conditions in the framework of M-adhesive categories, where M-adhesive categories are slightly more general than weak adhesive high-level replacement categories. Most of the proofs are based on the corresponding statements for rules without application conditions and two shift lemmas stating that nested application conditions can be shifted over morphisms and rules.