Flexible, protokollbasierte Therapie auf Basis adaptiver Workflows

Viele medizinische Therapien basieren auf standardisierten Protokollen, z.B. Chemotherapien in der Onkologie. Die darin festgelegten Behandlungsprozesse sind stark strukturiert und sehr detailliert formuliert. So werden in typischen Chemotherapieprotokollen die Therapieschritte bis hin zu einzelnen Medikamentengaben spezifiziert. Workflow-Management-Systeme (WfMS) sind deshalb ein geeignetes Werkzeug, um die Durchführung solcher Protokolle zu unterstützen. In früheren Untersuchungen(3) wurde deutlich, dass die Therapien trotz der genauen Vorgaben einen gewissen Grad an Flexibilität besitzen. Bei einer signifikanten Anzahl von Fällen treten Ausnahmen auf, bei denen in vorgeschriebener, aber nicht im Workflow modellierter Weise vom geplanten Behandlungsverlauf abgewichen werden muss. Um Workflow-Systeme dennoch einsetzen zu können, ist es notwendig die laufenden Workflows zu adaptieren (d.h. zu verändern), um sie an die neue Therapiesituation anzupassen. Aufgrund der hohen Komplexität der Therapieprotokolle und der großen Datenmenge (10-30 Befunde pro Patient und Tag bei unterschiedlichen Protokollen) ist es außerdem notwendig, den behandelnden Arzt bei der Erkennung der Ausnahmen und der Auswahl der passenden Adaption zu unterstützen. Um das medizinische Personal von der manuellen Ausnahmebehandlung zu entlasten, ist ein System erforderlich, das Ausnahmen erkennt und durch automatische Adaptionen sicherstellt, dass laufende Therapien trotz Ausnahmen weiter durchgeführt werden können. Ein solches System ist insbesondere für den Einsatz in klinischen Studien geeignet, da dort die Protokoll-Konformität der Behandlung besonders wichtig ist. Infolge der Verbesserung der Protokoll-Konformität ist dann auch eine Erhöhung der Behandlungsqualität zu erwarten

When the path is never shortest: a reality check on shortest path biocomputation

Shortest path problems are a touchstone for evaluating the computing performance and functional range of novel computing substrates. Much has been published in recent years regarding the use of biocomputers to solve minimal path problems such as route optimisation and labyrinth navigation, but their outputs are typically difficult to reproduce and somewhat abstract in nature, suggesting that both experimental design and analysis in the field require standardising. This chapter details laboratory experimental data which probe the path finding process in two single-celled protistic model organisms, Physarum polycephalum and Paramecium caudatum, comprising a shortest path problem and labyrinth navigation, respectively. The results presented illustrate several of the key difficulties that are encountered in categorising biological behaviours in the language of computing, including biological variability, non-halting operations and adverse reactions to experimental stimuli. It is concluded that neither organism examined are able to efficiently or reproducibly solve shortest path problems in the specific experimental conditions that were tested. Data presented are contextualised with biological theory and design principles for maximising the usefulness of experimental biocomputer prototypes.Comment: To appear in: Adamatzky, A (Ed.) Shortest path solvers. From software to wetware. Springer, 201

Identification of KIF3A as a Novel Candidate Gene for Childhood Asthma Using RNA Expression and Population Allelic Frequencies Differences

Asthma is a chronic inflammatory disease with a strong genetic predisposition. A major challenge for candidate gene association studies in asthma is the selection of biologically relevant genes.Using epithelial RNA expression arrays, HapMap allele frequency variation, and the literature, we identified six possible candidate susceptibility genes for childhood asthma including ADCY2, DNAH5, KIF3A, PDE4B, PLAU, SPRR2B. To evaluate these genes, we compared the genotypes of 194 predominantly tagging SNPs in 790 asthmatic, allergic and non-allergic children. We found that SNPs in all six genes were nominally associated with asthma (p<0.05) in our discovery cohort and in three independent cohorts at either the SNP or gene level (p<0.05). Further, we determined that our selection approach was superior to random selection of genes either differentially expressed in asthmatics compared to controls (p = 0.0049) or selected based on the literature alone (p = 0.0049), substantiating the validity of our gene selection approach. Importantly, we observed that 7 of 9 SNPs in the KIF3A gene more than doubled the odds of asthma (OR = 2.3, p<0.0001) and increased the odds of allergic disease (OR = 1.8, p<0.008). Our data indicate that KIF3A rs7737031 (T-allele) has an asthma population attributable risk of 18.5%. The association between KIF3A rs7737031 and asthma was validated in 3 independent populations, further substantiating the validity of our gene selection approach.Our study demonstrates that KIF3A, a member of the kinesin superfamily of microtubule associated motors that are important in the transport of protein complexes within cilia, is a novel candidate gene for childhood asthma. Polymorphisms in KIF3A may in part be responsible for poor mucus and/or allergen clearance from the airways. Furthermore, our study provides a promising framework for the identification and evaluation of novel candidate susceptibility genes

AdaptFlow: Protocol-based Medical Treatment Using Adaptive Workflows

Objectives: In many medical domains investigator-initiated clinical trials are used to introduce new treatments and hence act as implementations of guideline-based therapies. Trial protocols contain detailed instructions to conduct the therapy and additionally specify reactions to exceptional situations (for instance an infection or a toxicity). To increase quality in health care and raise the number of patients treated according to trial protocols, a consultation system is needed that supports the handling of the complex trial therapy processes efficiently. Our objective was to design and evaluate a consultation system that should 1) observe the status of the therapies currently being applied, 2) offer automatic recognition of exceptional situations and appropriate decision support and 3) provide an automatic adaptation of affected therapy processes to handle exceptional situations. Methods: We applied a hybrid approach that combines process support for the timely and efficient execution of the therapy processes as offered by workflow management systems with a knowledge and rule base and a mechanism for dynamic workflow adaptation to change running therapy processes if induced by changed patient condition. Results and Conclusions: This approach has been implemented in the AdaptFlow prototype. We performed several evaluation studies on the practicability of the approach and the usefulness of the system. These studies show that the AdaptFlow prototype offers adequate support for the execution of real-world investigator-initiated trial protocols and is able to handle a large number of exceptions

Reference materials for measuring the size of nanoparticles

This article discusses the requirements for reference materials (RMs) for measuring the size of nanoparticles (NPs). Such RMs can be used for instrument calibration, statistical quality control or interlaboratory comparisons. They can come in the form of suspensions, powders or matrix-embedded materials [i.e. NPs integrated in a natural matrix (e.g., food, soil, or sludge)]. At present, uncertainty about the most suitable form of material, the most relevant measurands and the most useful metrological-traceability statement inhibits the production of NP RMs. In addition, the lack of validated methods and qualified laboratories to produce NP RMs present formidable challenges. Metal, inorganic and organic NPs are available, but most of them are intended to be laboratory chemicals. With the exception of latex materials, certified RMs are not available, although some metrology institutes have started to develop such materials for colloidal gold and silica particles.The financial support by the European Commission through the 7th Framework Program, Contract No. 245162, Nanoparticles in Food: Analytical methods for detection and characterization (NanoLyse) is gratefully acknowledged.Peer reviewe

Flexible, protokollbasierte Therapie auf Basis adaptiver Workflows

Viele medizinische Therapien basieren auf standardisierten Protokollen, z.B. Chemotherapien in der Onkologie. Die darin festgelegten Behandlungsprozesse sind stark strukturiert und sehr detailliert formuliert. So werden in typischen Chemotherapieprotokollen die Therapieschritte bis hin zu einzelnen Medikamentengaben spezifiziert. Workflow-Management-Systeme (WfMS) sind deshalb ein geeignetes Werkzeug, um die Durchführung solcher Protokolle zu unterstützen. In früheren Untersuchungen(3) wurde deutlich, dass die Therapien trotz der genauen Vorgaben einen gewissen Grad an Flexibilität besitzen. Bei einer signifikanten Anzahl von Fällen treten Ausnahmen auf, bei denen in vorgeschriebener, aber nicht im Workflow modellierter Weise vom geplanten Behandlungsverlauf abgewichen werden muss. Um Workflow-Systeme dennoch einsetzen zu können, ist es notwendig die laufenden Workflows zu adaptieren (d.h. zu verändern), um sie an die neue Therapiesituation anzupassen. Aufgrund der hohen Komplexität der Therapieprotokolle und der großen Datenmenge (10-30 Befunde pro Patient und Tag bei unterschiedlichen Protokollen) ist es außerdem notwendig, den behandelnden Arzt bei der Erkennung der Ausnahmen und der Auswahl der passenden Adaption zu unterstützen. Um das medizinische Personal von der manuellen Ausnahmebehandlung zu entlasten, ist ein System erforderlich, das Ausnahmen erkennt und durch automatische Adaptionen sicherstellt, dass laufende Therapien trotz Ausnahmen weiter durchgeführt werden können. Ein solches System ist insbesondere für den Einsatz in klinischen Studien geeignet, da dort die Protokoll-Konformität der Behandlung besonders wichtig ist. Infolge der Verbesserung der Protokoll-Konformität ist dann auch eine Erhöhung der Behandlungsqualität zu erwarten

AdaptFlow: Protocol-based Medical Treatment Using Adaptive Workflows

Objectives: In many medical domains investigator-initiated clinical trials are used to introduce new treatments and hence act as implementations of guideline-based therapies. Trial protocols contain detailed instructions to conduct the therapy and additionally specify reactions to exceptional situations (for instance an infection or a toxicity). To increase quality in health care and raise the number of patients treated according to trial protocols, a consultation system is needed that supports the handling of the complex trial therapy processes efficiently. Our objective was to design and evaluate a consultation system that should 1) observe the status of the therapies currently being applied, 2) offer automatic recognition of exceptional situations and appropriate decision support and 3) provide an automatic adaptation of affected therapy processes to handle exceptional situations. Methods: We applied a hybrid approach that combines process support for the timely and efficient execution of the therapy processes as offered by workflow management systems with a knowledge and rule base and a mechanism for dynamic workflow adaptation to change running therapy processes if induced by changed patient condition. Results and Conclusions: This approach has been implemented in the AdaptFlow prototype. We performed several evaluation studies on the practicability of the approach and the usefulness of the system. These studies show that the AdaptFlow prototype offers adequate support for the execution of real-world investigator-initiated trial protocols and is able to handle a large number of exceptions