Dynamics of Knowledge Leverage in ERP Implementation

This paper reports the results of an in-depth investigation of the knowledge management (KM) activities of an ERP implementation project within a dynamic business setting. Using a case study approach, this research examines the challenges faced by the ERP project team with respect to KM and the effectiveness of KM strategies. In addition to gaining insights into typical KM activities within the ERP project lifecycle, the research reveals that major barriers for effective KM are created by external business changes and the business process life cycle. These changes trigger a chain reaction resulting in the weak performance of key KM activities such as knowledge capture, sharing and retention. The need for a comprehensive array of KM initiatives that are capable of managing such changes by recognizing the dynamics of all three life cycles is highlighted

Towards a Definition of IT Management Sophistication in Small Firms

This paper reports the results of a study aimed at understanding and characterising IT management sophistication in small businesses. A multiple-case study approach was therefore used to explore the IT management practices of small businesses. Data collection involved four small-medium chartered accountancy (CA) firms and three IT firms closely associated with the CA industry. The case results combined with past research suggested 30 individual indicators of IT management sophistication. Further investigation of these 30 indicators yielded five underlying factors characterising IT management sophistication, namely planning, controlling, organising, leading and external expertise. The results provided a useful foundation for examining the impact of IT management sophistication on organisational performance and developing appropriate improvement strategies. Directions for future research are also discussed

Predictive Factors in OCT Analysis for Visual Outcome in Exudative AMD

Background. Reliable predictive factors for therapy outcome may enable treating physicians to counsel their patients more efficiently concerning probability of improvement or time point of discontinuation of a certain therapy. Methods. This is a retrospective analysis of 87 patients with exudative age-related macular degeneration who received three monthly intravitreal ranibizumab injections. Visual acuity before initiation of intravitreal therapy and 4–6 weeks after last intravitreal injection was compared and related to the preoperative visualisation of continuity of the outer retinal layers as assessed by OCT: external limiting membrane (ELM), inner photoreceptor segments (IPS), junction between inner and outer segments (IS/OS), and outer photoreceptor segments (OPS). Results. Visual acuity increased in 40 of 87 (46.0%) patients, it remained stable in 25 (28.7%), and 22 (25.3%) patients had decreased visual acuity four to six weeks after triple intravitreal ranibizumab injections. No statistically significant predictive value could be demonstrated for grade of continuity of outer retinal layers concerning visual acuity development. Conclusions. In our series of AMD patients, grade of continuity of outer retinal layers was not a significant predictive value for visual acuity development after triple ranibizumab injections

Generation of Antibodies Selectively Recognizing Epitopes in a Formaldehyde-Fixed Cell-Surface Antigen Using Virus-like Particle Display and Hybridoma Technology

Efficient induction of target-specific antibodies can be elicited upon immunization with highly immunogenic virus-like particles (VLPs) decorated with desired membrane-anchored target antigens (Ags). However, for example, for diagnostic purposes, monoclonal antibodies (mAbs) are required to enable the histological examination of formaldehyde-fixed paraffin-embedded (FFPE) biopsy tissue samples. Aiming at the generation of FFPE-antigen-specific mAbs and as a proof of concept (POC), we first established a simplified protocol using only formaldehyde and 90 °C heat fixation (FF90) of cells expressing the target Ag nerve growth factor receptor (NGFR). The FF90 procedure was validated using flow cytometric analysis and two mAbs recognizing either the native and FFPE-Ag or exclusively the native Ag. C-terminally truncated NGFR (trNGFR)-displaying native and FF90-treated VLPs derived from HIV-1 did not reveal distinctive changes in particle morphology using transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis. Mice were subsequently repetitively immunized with trNGFR-decorated FF90-VLPs and hybridoma technology was used to establish mAb-producing cell clones. In multiple screening rounds, nine cell clones were identified producing mAbs distinctively recognizing epitopes in FF90- and FFPE-NGFR. This POC of a new methodology should foster the future generation of mAbs selectively targeting FFPE-fixed cell-surface Ags

Absorption reconstruction improves biodistribution assessment of fluorescent nanoprobes using hybrid Fluorescence-mediated tomography

Aim: Fluorescence-mediated tomography (FMT) holds potential for accelerating diagnostic and theranostic drug development. However, for proper quantitative fluorescence reconstruction, knowledge on optical scattering and absorption, which are highly heterogeneous in different (mouse) tissues, is required. We here describe methods to assess these parameters using co-registered micro Computed Tomography (µCT) data and nonlinear whole-animal absorption reconstruction, and evaluate their importance for assessment of the biodistribution and target site accumulation of fluorophore-labeled drug delivery systems.\ud \ud Methods: Besides phantoms with varying degrees of absorption, mice bearing A431 tumors were imaged 15 min and 48 h after i.v. injection of a fluorophore-labeled polymeric drug carrier (pHPMA-Dy750) using µCT-FMT. The outer shape of mice and a scattering map were derived using automated segmentation of the µCT data. Furthermore, a 3D absorption map was reconstructed from the trans-illumination data. We determined the absorption of five interactively segmented regions (heart, liver, kidney, muscle, tumor). Since blood is the main near-infrared absorber in vivo, the absorption was also estimated from the relative blood volume (rBV), determined by contrast-enhanced µCT. We compared the reconstructed absorption with the rBV-based values and analyzed the effect of using the absorption map on the fluorescence reconstruction.\ud \ud Results: Phantom experiments demonstrated that absorption reconstruction is possible and necessary for quantitative fluorescence reconstruction. In vivo, the reconstructed absorption showed high values in strongly blood-perfused organs such as the heart, liver and kidney. The absorption values correlated strongly with the rBV-based absorption values, confirming the accuracy of the absorption reconstruction. Usage of homogenous absorption instead of the reconstructed absorption map resulted in reduced values in the heart, liver and kidney, by factors of 3.5, 2.1 and 1.4, respectively. For muscle and subcutaneous tumors, which have a much lower rBV and absorption, absorption reconstruction was less important.\ud \ud Conclusion: Quantitative whole-animal absorption reconstruction is possible and can be validated in vivo using the rBV. Usage of an absorption map is important when quantitatively assessing the biodistribution of fluorescently labeled drugs and drug delivery systems, to avoid a systematic underestimation of fluorescence in strongly absorbing organs, such as the heart, liver and kidney

Модель смешанного обучения в преподавании дисциплины "Методы получения чистых веществ"

Данная работа посвящена использованию модели смешанного обучения в преподавании дисциплины "Методы получения чистых веществ" на английском языке. Исследовались элементы смешанного обучения, стратегия организации образовательного процесса, план учебной деятельности. Подробно описаны виды учебной деятельности и подобраны формы организации процесса. Для каждого вида деятельности определены уровни таксономии Блума. Показаны преимущества модели смешанного обучения в преподавании лабораторных работ для студентов инженерной специальности

Monitoring EPR Effect Dynamics during Nanotaxane Treatment with Theranostic Polymeric Micelles

Cancer nanomedicines rely on the enhanced permeability and retention (EPR) effect for efficient target site accumulation. The EPR effect, however, is highly heterogeneous among different tumor types and cancer patients and its extent is expected to dynamically change during the course of nanochemotherapy. Here the authors set out to longitudinally study the dynamics of the EPR effect upon single- and double-dose nanotherapy with fluorophore-labeled and paclitaxel-loaded polymeric micelles. Using computed tomography-fluorescence molecular tomography imaging, it is shown that the extent of nanomedicine tumor accumulation is predictive for therapy outcome. It is also shown that the interindividual heterogeneity in EPR-based tumor accumulation significantly increases during treatment, especially for more efficient double-dose nanotaxane therapy. Furthermore, for double-dose micelle therapy, tumor accumulation significantly increased over time, from 7% injected dose per gram (ID g–1) upon the first administration to 15% ID g–1 upon the fifth administration, contributing to more efficient inhibition of tumor growth. These findings shed light on the dynamics of the EPR effect during nanomedicine treatment and they exemplify the importance of using imaging in nanomedicine treatment prediction and clinical translation

What scans we will read: imaging instrumentation trends in clinical oncology

Oncological diseases account for a significant portion of the burden on public healthcare systems with associated costs driven primarily by complex and long-lasting therapies. Through the visualization of patient-specific morphology and functional-molecular pathways, cancerous tissue can be detected and characterized non- invasively, so as to provide referring oncologists with essential information to support therapy management decisions. Following the onset of stand-alone anatomical and functional imaging, we witness a push towards integrating molecular image information through various methods, including anato-metabolic imaging (e.g., PET/ CT), advanced MRI, optical or ultrasound imaging. This perspective paper highlights a number of key technological and methodological advances in imaging instrumentation related to anatomical, functional, molecular medicine and hybrid imaging, that is understood as the hardware-based combination of complementary anatomical and molecular imaging. These include novel detector technologies for ionizing radiation used in CT and nuclear medicine imaging, and novel system developments in MRI and optical as well as opto-acoustic imaging. We will also highlight new data processing methods for improved non-invasive tissue characterization. Following a general introduction to the role of imaging in oncology patient management we introduce imaging methods with well-defined clinical applications and potential for clinical translation. For each modality, we report first on the status quo and point to perceived technological and methodological advances in a subsequent status go section. Considering the breadth and dynamics of these developments, this perspective ends with a critical reflection on where the authors, with the majority of them being imaging experts with a background in physics and engineering, believe imaging methods will be in a few years from now. Overall, methodological and technological medical imaging advances are geared towards increased image contrast, the derivation of reproducible quantitative parameters, an increase in volume sensitivity and a reduction in overall examination time. To ensure full translation to the clinic, this progress in technologies and instrumentation is complemented by progress in relevant acquisition and image-processing protocols and improved data analysis. To this end, we should accept diagnostic images as “data”, and – through the wider adoption of advanced analysis, including machine learning approaches and a “big data” concept – move to the next stage of non-invasive tumor phenotyping. The scans we will be reading in 10 years from now will likely be composed of highly diverse multi- dimensional data from multiple sources, which mandate the use of advanced and interactive visualization and analysis platforms powered by Artificial Intelligence (AI) for real-time data handling by cross-specialty clinical experts with a domain knowledge that will need to go beyond that of plain imaging

Exploiting the cancer niche: Tumor-associated macrophages and hypoxia as promising synergistic targets for nano-based therapy

The tumor microenvironment has been widely exploited as an active participant in tumor progression. Extensive reports have defined the dual role of tumor-associated macrophages (TAMs) in tumor development. The protumoral effect exerted by the M2 phenotype has been correlated with a negative outcome in most solid tumors. The high infiltration of immune cells in the hypoxic cores of advanced solid tumors leads to a chain reaction of stimuli that enhances the expression of protumoral genes, thrives tumor malignancy, and leads to the emergence of drug resistance. Many studies have shown therapeutic targeting systems, solely to TAMs or tumor hypoxia, however, novel therapeutics that target both features are still warranted. In the present review, we discuss the role of hypoxia in tumor development and the clinical outcome of hypoxia-targeted therapeutics, such as hypoxia-inducible factor (HIF-1) inhibitors and hypoxia-activated prodrugs. Furthermore, we review the state-of-the-art of macrophage-based cancer therapy. We thoroughly discuss the development of novel therapeutics that simultaneously target TAMs and tumor hypoxia. Nano-based systems have been highlighted as interesting strategies for dual modality treatments, with somewhat improved tissue extravasation. Such approach could be seen as a promising strategy to overcome drug resistance and enhance the efficacy of chemotherapy in advanced solid and metastatic tumors, especially when exploiting cell-based nanotherapies. Finally, we provide an in-depth opinion on the importance of exploiting the tumor microenvironment in cancer therapy, and how this could be translated to clinical practice

Automated Generation of Reliable Blood Velocity Parameter Maps from Contrast-Enhanced Ultrasound Data

Objectives. The purpose of this study was the automated generation and validation of parametric blood flow velocity maps, based on contrast-enhanced ultrasound (CEUS) scans. Materials and Methods. Ethical approval for animal experiments was obtained. CEUS destruction-replenishment sequences were recorded in phantoms and three different tumor xenograft mouse models. Systematic pixel binning and intensity averaging was performed to generate parameter maps of blood flow velocities with different pixel resolution. The 95% confidence interval of the mean velocity, calculated on the basis of the whole tumor segmentation, served as ground truth for the different parameter maps. Results. In flow phantoms the measured mean velocity values were only weakly influenced by the pixel resolution and correlated with real velocities (r2≥0.94,  p<0.01). In tumor xenografts, however, calculated mean velocities varied significantly (p<0.0001), depending on the parameter maps’ resolution. Pixel binning was required for all in vivo measurements to obtain reliable parameter maps and its degree depended on the tumor model. Conclusion. Systematic pixel binning allows the automated identification of optimal pixel resolutions for parametric maps, supporting textural analysis of CEUS data. This approach is independent from the ultrasound setup and can be implemented in the software of other (clinical) ultrasound devices