A System Dynamics Model of Resistance to Organizational Change : The Role of Participatory Strategies

The literature on organizational change and resistance to change is contradictory. Some scholars find resistance a hindrance to successful change (traditional paradigm), whereas others find it a valuable source (modern paradigm). The objective of this study is to enhance our understanding of how resistance affects organizational change by providing a coherent system dynamics perspective. Based on interviews, expert modelling and group modelling, this inductive case study develops a causal loop diagram that displays eight interacting feedback loops to explain resistance to change and the role that participatory strategies play in addressing this. The model contributes to the theoretical debate on how resistance affects change by providing propositions that integrate the traditional and modern paradigms. When managers face decisions about when to increase, stabilize or decrease the use of participatory strategies, our findings imply to base these decisions upon currently dominating feedback loops, such as the Stress Trap or Slow Trap.(VLID)334020

High-Throughput miRNA and mRNA Sequencing of Paired Colorectal Normal, Tumor and Metastasis Tissues and Bioinformatic Modeling of miRNA-1 Therapeutic Applications

MiRNAs are discussed as diagnostic and therapeutic molecules. However, effective miRNA drug treatments with miRNAs are, so far, hampered by the complexity of the miRNA networks. To identify potential miRNA drugs in colorectal cancer, we profiled miRNA and mRNA expression in matching normal, tumor and metastasis tissues of eight patients by Illumina sequencing. We validated six miRNAs in a large tissue screen containing 16 additional tumor entities and identified miRNA-1, miRNA-129, miRNA-497 and miRNA-215 as constantly de-regulated within the majority of cancers. Of these, we investigated miRNA-1 as representative in a systems-biology simulation of cellular cancer models implemented in PyBioS and assessed the effects of depletion as well as overexpression in terms of miRNA-1 as a potential treatment option. In this system, miRNA-1 treatment reverted the disease phenotype with different effectiveness among the patients. Scoring the gene expression changes obtained through mRNA-Seq from the same patients we show that the combination of deep sequencing and systems biological modeling can help to identify patient-specific responses to miRNA treatments. We present this data as guideline for future pre-clinical assessments of new and personalized therapeutic options

Targeted high throughput sequencing in clinical cancer Settings: formaldehyde fixed-paraffin embedded (FFPE) tumor tissues, input amount and tumor heterogeneity

<p>Abstract</p> <p>Background</p> <p>Massively parallel sequencing technologies have brought an enormous increase in sequencing throughput. However, these technologies need to be further improved with regard to reproducibility and applicability to clinical samples and settings.</p> <p>Methods</p> <p>Using identification of genetic variations in prostate cancer as an example we address three crucial challenges in the field of targeted re-sequencing: Small nucleotide variation (SNV) detection in samples of formalin-fixed paraffin embedded (FFPE) tissue material, minimal amount of input sample and sampling in view of tissue heterogeneity.</p> <p>Results</p> <p>We show that FFPE tissue material can supplement for fresh frozen tissues for the detection of SNVs and that solution-based enrichment experiments can be accomplished with small amounts of DNA with only minimal effects on enrichment uniformity and data variance.</p> <p>Finally, we address the question whether the heterogeneity of a tumor is reflected by different genetic alterations, e.g. different foci of a tumor display different genomic patterns. We show that the tumor heterogeneity plays an important role for the detection of copy number variations.</p> <p>Conclusions</p> <p>The application of high throughput sequencing technologies in cancer genomics opens up a new dimension for the identification of disease mechanisms. In particular the ability to use small amounts of FFPE samples available from surgical tumor resections and histopathological examinations facilitates the collection of precious tissue materials. However, care needs to be taken in regard to the locations of the biopsies, which can have an influence on the prediction of copy number variations. Bearing these technological challenges in mind will significantly improve many large-scale sequencing studies and will - in the long term - result in a more reliable prediction of individual cancer therapies.</p

Evaluation of a new arterial pressure-based cardiac output device requiring no external calibration

<p>Abstract</p> <p>Background</p> <p>Several techniques have been discussed as alternatives to the intermittent bolus thermodilution cardiac output (CO_PAC) measurement by the pulmonary artery catheter (PAC). However, these techniques usually require a central venous line, an additional catheter, or a special calibration procedure. A new arterial pressure-based cardiac output (CO_AP) device (FloTrac™, Vigileo™; Edwards Lifesciences, Irvine, CA, USA) only requires access to the radial or femoral artery using a standard arterial catheter and does not need an external calibration. We validated this technique in critically ill patients in the intensive care unit (ICU) using CO_PACas the method of reference.</p> <p>Methods</p> <p>We studied 20 critically ill patients, aged 16 to 74 years (mean, 55.5 ± 18.8 years), who required both arterial and pulmonary artery pressure monitoring. CO_PACmeasurements were performed at least every 4 hours and calculated as the average of 3 measurements, while CO_APvalues were taken immediately at the end of bolus determinations. Accuracy of measurements was assessed by calculating the bias and limits of agreement using the method described by Bland and Altman.</p> <p>Results</p> <p>A total of 164 coupled measurements were obtained. Absolute values of CO_PACranged from 2.80 to 10.80 l/min (mean 5.93 ± 1.55 l/min). The bias and limits of agreement between CO_PACand CO_APfor unequal numbers of replicates was 0.02 ± 2.92 l/min. The percentage error between CO_PACand CO_APwas 49.3%. The bias between percentage changes in CO_PAC(ΔCO_PAC) and percentage changes in CO_AP(ΔCO_AP) for consecutive measurements was -0.70% ± 32.28%. CO_PACand CO_APshowed a Pearson correlation coefficient of 0.58 (<it>p </it>< 0.01), while the correlation coefficient between ΔCO_PACand ΔCO_APwas 0.46 (<it>p </it>< 0.01).</p> <p>Conclusion</p> <p>Although the CO_APalgorithm shows a minimal bias with CO_PACover a wide range of values in an inhomogeneous group of critically ill patients, the scattering of the data remains relative wide. Therefore, the used algorithm (V 1.03) failed to demonstrate an acceptable accuracy in comparison to the clinical standard of cardiac output determination.</p

Ortho2ExpressMatrix—a web server that interprets cross-species gene expression data by gene family information

<p>Abstract</p> <p>Background</p> <p>The study of gene families is pivotal for the understanding of gene evolution across different organisms and such phylogenetic background is often used to infer biochemical functions of genes. Modern high-throughput experiments offer the possibility to analyze the entire transcriptome of an organism; however, it is often difficult to deduct functional information from that data.</p> <p>Results</p> <p>To improve functional interpretation of gene expression we introduce Ortho2ExpressMatrix, a novel tool that integrates complex gene family information, computed from sequence similarity, with comparative gene expression profiles of two pre-selected biological objects: gene families are displayed with two-dimensional matrices. Parameters of the tool are object type (two organisms, two individuals, two tissues, etc.), type of computational gene family inference, experimental meta-data, microarray platform, gene annotation level and genome build. Family information in Ortho2ExpressMatrix bases on computationally different protein family approaches such as EnsemblCompara, InParanoid, SYSTERS and Ensembl Family. Currently, respective all-against-all associations are available for five species: human, mouse, worm, fruit fly and yeast. Additionally, microRNA expression can be examined with respect to miRBase or TargetScan families. The visualization, which is typical for Ortho2ExpressMatrix, is performed as matrix view that displays functional traits of genes (differential expression) as well as sequence similarity of protein family members (BLAST e-values) in colour codes. Such translations are intended to facilitate the user's perception of the research object.</p> <p>Conclusions</p> <p>Ortho2ExpressMatrix integrates gene family information with genome-wide expression data in order to enhance functional interpretation of high-throughput analyses on diseases, environmental factors, or genetic modification or compound treatment experiments. The tool explores differential gene expression in the light of orthology, paralogy and structure of gene families up to the point of ambiguity analyses. Results can be used for filtering and prioritization in functional genomic, biomedical and systems biology applications. The web server is freely accessible at <url>http://bioinf-data.charite.de/o2em/cgi-bin/o2em.pl</url>.</p

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Work group effectiveness. Promoting and hindering dynamics

Die Effektivität von Arbeitsgruppen ist in Organisationen, die sich in einer ständig verändernden Umwelt befinden, von großer Bedeutung. Allerdings können Arbeitsgruppen ihr volles Potential oft nicht ausschöpfen. Ein wichtiger Grund dafür liegt in unserem begrenzten Verständnis von Arbeitsgruppeneffektivität. Konkret verabsäumt es Forschung in diesem Bereich häufig, essentielle Elemente wie Zeit, Nichtlinearität und Komplexität mit zu berücksichtigen. Die Integration jener drei Faktoren in meine Doktorarbeit ermöglicht es mir, die folgende allgemeine Forschungsfrage zu beantworten: „Welche Dynamiken fördern bzw. hindern die Effektivität von Arbeitsgruppen?“. Diese Forschungsfrage wird mit Hilfe von vier individuellen Manuskripten beantwortet. Während jede dieser vier Studien das Konstrukt Arbeitsgruppeneffektivität aus einem spezifischen theoretischen Blickwinkel betrachtet, haben alle vier Studien gemeinsam, dass sie eine Prozessperspektive einnehmen und ein konkretes Prozessmodel erstellen. Abgeleitet von den insgesamt vier Prozessmodellen ergeben sich wichtige Erkenntnisse darüber, wie Arbeitsgruppeneffektivität verlässlich beeinflusst wird. Im Speziellen demonstriert diese kumulative Dissertation, dass zur Förderung von Arbeitsgruppeneffektivität das Aufrechterhalten einer Spannung von dualen Elementen wie Partizipation und Delegation, Kooperation und Nachdruck, Emotion und Ratio, Kollaboration und Instruktion entscheidend ist. Dabei zeigt diese Doktorarbeit Dynamiken auf, die das Halten einer dualen Spannung fördern bzw. hindern. Bei diesen Dynamiken handelt es sich um Rückkopplungsmechanismen, die von Natur aus Zeit, Nichtlinearität und Komplexität einbeziehen und damit Forschung im Bereich Arbeitsgruppen-effektivität weiterentwickeln. Von diesen Ergebnissen leitet diese Dissertation wichtige Implikationen für PraktikerInnen ab. Dabei erläutert die vorliegende Arbeit, dass das Halten einer dualen Spannung auf anderen Interventionen beruht, als lediglich dem Versuch, duale Elemente direkt zu manipulieren oder sie sequentiell zu fördern. Stattdessen spricht sich diese Doktorarbeit für ein simultanes Halten von dualen Elementen aus, das durch das Einnehmen einer Prozessperspektive erleichtert werden kann. Letztere ermöglicht es PraktikerInnen, vergangene komplexe, nichtlineare Gruppen-prozesse zu identifizieren, daraus Rückschlüsse auf zukünftige Interaktionen zu ziehen und davon sinnvolle Interventionen abzuleiten.Work group effectiveness is crucial for organizations encapsulated in an environment that is permanently changing. However, work group effectiveness often fails to tap its full potential. One major reason for this failure is our limited understanding of work group effectiveness. In particular, current research about work group effectiveness lacks crucial elements such as time, nonlinearity and complexity. By incorporating time, nonlinearity and complexity into my research, I am able to answer the overall research question of “Which dynamics promote work group effectiveness and which dynamics hinder work group effectiveness?”. This research question is answered by means of four individual manuscripts. While each study views work group effectiveness from a specific theoretical angle, all four studies have in common that they adopt a process ontology that enables each of them to create a specific process model. Hence, from the overall four process models, I derive important insights on how to reliably influence work group effectiveness. In particular, I find that maintaining a tension between dual elements such as participating and delegating, cooperative behavior and assertive behavior, affective utility and instrumental utility, acting with others and acting on others is of crucial importance to promote work group effectiveness. This cumulative doctoral thesis contributes to research by identifying dynamics that promote keeping a dual tension as well as dynamics that hinder keeping a dual tension. Specifically, these dynamics are feedback mechanisms that inherently incorporate issues of time, nonlinearity and complexity and thus advance research on work group effectiveness. This doctoral thesis also derives important contributions to managerial practice. In particular, establishing dual tensions implies other interventions than simply trying to directly manipulate one or both of the dual elements or suggesting some sequential focus on dual elements. Instead, this doctoral thesis argues for simultaneously upholding dual elements, which is facilitated by adopting a process ontology. The latter enables researchers and practitioners to identify past nonlinear, complex group processes, anticipate future group interactions and derive some meaningful interventions.Author Mag.a Sylvia Schweiger, MSc.Universität Linz, Dissertation, 2019(VLID)349803

Das Kognitive Inventar für Borderline-Persönlichkeitsstörung (KIB). Eine Untersuchung zur Reliabilität und Validität

Theoretischer Hintergrund: Das Kognitive Inventar der Borderline-Persönlichkeitsstörung (KIB) wurde zur Messung von störungstypischen Überzeugungen sowie assoziierten behavioralen und emotionalen Symptomen entwickelt. Fragestellung: Die psychometrischen Kennwerte des KIB wurden untersucht und ergänzen die Erkenntnisse einer Pilotstudie. Methode: Die Reliabilität, die faktorielle, konvergente, divergente und differenzielle Validität sowie die Änderungssensitivität wurden anhand von zwei klinischen (Borderline-Persönlichkeitsstörung und Achse I-Störungen; n = 150) und einer nicht-klinischen Stichprobe (n = 70) untersucht. Ergebnisse: Die Ergebnisse zeigen eine hohe Reliabilität, eine hohe konvergente Validität und eine zufriedenstellende divergente Validität. Die differenzielle Validität ist als gut und die Änderungssensitivität als zufriedenstellend zu bewerten. Schlussfolgerungen: Das KIB ermöglicht eine reliable und valide Erfassung störungstypischer Regeln und Einstellungen bei BPS. Seine Besonderheit liegt in der Berücksichtigung subjektiver Funktionen selbstschädigender Verhaltensweisen