Data model evolution as a basis of business process management

In this article we propose an approach to business process management which meets the demands of business process evolution. This approach allows for on-the-fy modifications of business processes. In contrast to many other approaches, we do not only concentrate onactivities to be carried out in business processes, but also on the datacreated and manipulated by these activities We propose to apply datamodel analysis and improvement strategies well-known from the information system field in the context of business process management

Pharmacological modulation of conditioned fear in the fear-potentiated startle test: a systematic review and meta-analysis of animal studies

RATIONALE AND OBJECTIVES: Fear conditioning is an important aspect in the pathophysiology of anxiety disorders. The fear-potentiated startle test is based on classical fear conditioning and over the years, a broad range of drugs have been tested in this test. Synthesis of the available data may further our understanding of the neurotransmitter systems that are involved in the expression of conditioned fear. METHODS: Following a comprehensive search in Medline and Embase, we included 68 research articles that reported on 103 drugs, covering 56 different drug classes. The systematic review was limited to studies using acute, systemic drug administration in naive animals. RESULTS: Qualitative data synthesis showed that most clinically active anxiolytics, but not serotonin-reuptake inhibitors, reduced cued fear. Anxiogenic drugs increased fear potentiation in 35% of the experiments, reduced fear potentiation in 29% of the experiments, and were without effect in 29% of the experiments. Meta-analyses could be performed for five drug classes and showed that benzodiazepines, buspirone, 5-HT 1A agonists, 5-HT 1A antagonists, and mGluR2,3 agonists reduced cued conditioned fear. The non-cued baseline startle response, which may reflect contextual anxiety, was only significantly reduced by benzodiazepines and 5-HT 1A antagonists. No associations were found between drug effects and methodological characteristics, except for strain. CONCLUSIONS: The fear-potentiated startle test appears to have moderate to high predictive validity and may serve as a valuable tool for the development of novel anxiolytics. Given the limited available data, the generally low study quality and high heterogeneity additional studies are warranted to corroborate the findings of this review

Pharmacological and methodological aspects of the separation-induced vocalization test in guinea pig pups; a systematic review and meta-analysis

The separation-induced vocalization test in guinea pig pups is one of many that has been used to screen for anxiolytic-like properties of drugs. The test is based on the cross-species phenomenon that infants emit distress calls when placed in social isolation. Here we report a systematic review and meta-analysis of pharmacological intervention in the separation-induced vocalization test in guinea pig pups. Electronic databases were searched for original research articles, yielding 32 studies that met inclusion criteria. We extracted data on pharmacological intervention, animal and methodological characteristics, and study quality indicators. Meta-analysis showed that the different drug classes in clinical use for the treatment of anxiety disorders, have comparable effects on vocalization behaviour, irrespective of their mechanism of action. Of the experimental drugs, nociception (NOP) receptor agonists proved very effective in this test. Analysis further indicated that the commonly used read-outs total number and total duration of vocalizations are equally valid. With regard to methodological characteristics, repeated testing of pups as well as selecting pups with moderate or high levels of vocalization were associated with larger treatment effects. Finally, reporting of study methodology, randomization and blinding was poor and Egger's test for small study effects showed that publication bias likely occurred. This review illustrates the value of systematic reviews and meta-analyses in improving translational value and methodological aspects of animal models. It further shows the urgent need to implement existing publication guidelines to maximize the output and impact of experimental animal studies

Teratoma Assay for Testing Pluripotency and Malignancy of Stem Cells: Insufficient Reporting and Uptake of Animal-Free Methods-A Systematic Review

Pluripotency describes the ability of stem cells to differentiate into derivatives of the three germ layers. In reporting new human pluripotent stem cell lines, their clonal derivatives or the safety of differentiated derivatives for transplantation, assessment of pluripotency is essential. Historically, the ability to form teratomas in vivo containing different somatic cell types following injection into immunodeficient mice has been regarded as functional evidence of pluripotency. In addition, the teratomas formed can be analyzed for the presence of malignant cells. However, use of this assay has been subject to scrutiny for ethical reasons on animal use and due to the lack of standardization in how it is used, therefore questioning its accuracy. In vitro alternatives for assessing pluripotency have been developed such as ScoreCard and PluriTest. However, it is unknown whether this has resulted in reduced use of the teratoma assay. Here, we systematically reviewed how the teratoma assay was reported in publications between 1998 (when the first human embryonic stem cell line was described) and 2021. Our analysis of >400 publications showed that in contrast to expectations, reporting of the teratoma assay has not improved: methods are not yet standardized, and malignancy was examined in only a relatively small percentage of assays. In addition, its use has not decreased since the implementation of the ARRIVE guidelines on reduction of animal use (2010) or the introduction of ScoreCard (2015) and PluriTest (2011). The teratoma assay is still the preferred method to assess the presence of undifferentiated cells in a differentiated cell product for transplantation since the in vitro assays alone are not generally accepted by the regulatory authorities for safety assessment. This highlights the remaining need for an in vitro assay to test malignancy of stem cells