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"Uhl, Axel"
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Model-Driven Development in the Enterprise
For decades, model-driven development has been the perfect example of software-engineering hype. Just as bees are attracted to honey, we software engineers look for ways of simplifying our work and automating endless change cycles. Today, after many years of experimenting with MDD, mostly in limited-size scientific environments, the three ingredients of methodology, notation, and tools seem to fit and support each other. Round-trip engineering might still be some years from day-to-day practice, but simple forward engineering with MDD is readily available to software practitioners now. And it works. In this issue's column, Axel Uhl, chief development architect in SAP's Office of the CTO, looks into MDD methodologies and tool support. He shares his many practical experiences to help you master the ramp-up for your own enterprise.
Journal Article
Point: Model driven architecture is ready for prime time / Counterpoint: Agile model driven development is good enough / Responses
Uhl and Ambler offer differing opinions on whether model driven architecture is ready for prime time or if agile model driven development is good enough.
Journal Article
Towards Using Police Officers’ Business Smartphones for Contactless Fingerprint Acquisition and Enabling Fingerprint Comparison against Contact-Based Datasets
Recent developments enable biometric recognition systems to be available as mobile solutions or to be even integrated into modern smartphone devices. Thus, smartphone devices can be used as mobile fingerprint image acquisition devices, and it has become feasible to process fingerprints on these devices, which helps police authorities carry out identity verification. In this paper, we provide a comprehensive and in-depth engineering study on the different stages of the fingerprint recognition toolchain. The insights gained throughout this study serve as guidance for future work towards developing a contactless mobile fingerprint solution based on the iPhone 11, working without any additional hardware. The targeted solution will be capable of acquiring 4 fingers at once (except the thumb) in a contactless manner, automatically segmenting the fingertips, pre-processing them (including a specific enhancement), and thus enabling fingerprint comparison against contact-based datasets. For fingertip detection and segmentation, various traditional handcrafted feature-based approaches as well as deep-learning-based ones are investigated. Furthermore, a run-time analysis and first results on the biometric recognition performance are included.
Journal Article
Intraoperative radiation therapy with 50 kV x‐rays: A multi‐institutional review
This report covers clinical implementation of a low kV intraoperative radiation therapy (IORT) program with the INTRABEAM® System (Carl Zeiss Meditec AG, Jena, Germany). Based on collective user experience from eight institutions, we discuss best methods of INTRABEAM quality assurance (QA) tests, commissioning measurements, clinical workflow, treatment planning, and potential avenues for research. The guide provides pertinent background information and clinical justification for IORT. It describes the INTRABEAM system and commissioning measurements along with a TG100 risk management analysis to ensure safety and accuracy of the IORT program. Following safety checks, dosimetry measurements are performed for verification of field flatness and symmetry, x‐ray output, and depth dose. Also discussed are dose linearity checks, beam isotropy, ion chamber measurements, calibration protocols, and in‐vivo dosimetry with optically stimulated luminescence dosimeters OSLDs, and radiochromic film. Emphasis is placed on the importance of routine QA procedures (daily, monthly, and annual) performed at regular intervals for a successful IORT program. For safe and accurate dose delivery, tests of important components of IORT clinical workflow are emphasized, such as, dose prescription, pre‐treatment QA, treatment setup, safety checks, radiation surveys, and independent checks of delivered dose. Challenges associated with in‐vivo dose measurements are discussed, along with special treatment procedures and shielding requirements. The importance of treatment planning in IORT is reviewed with reference to a Monte Carlo‐based commercial treatment planning system highlighting its main features and limitations. The report concludes with suggested topics for research including CT‐based image‐guided treatment planning and improved prescription dose accuracy. We hope that this multi‐institutional report will serve as a guidance document on the clinical implementation and use of INTRABEAM IORT.
Journal Article
Impact of prophylaxis, inhibitors, and genetics on joint outcomes according to the IPSG-MRI score in hemophilia A, B and vWD type 3
Hemophilia A (HA) and hemophilia B (HB) are X-linked-bleeding disorders caused by deficiency of clotting factors VIII and IX, while von Willebrand disease (vWD) type 3 involves the lack of von Willebrand factor and FVIII. Chronic joint damage from recurrent bleeding is a serious complication.
The aim was to investigate the association of prophylactical treatment, severity of the disease and joint outcome.
In this retrospective, single-center study we evaluated joint health in 41 patients with HA, HB, and vWD type 3 who visited our outpatient clinic since 2000 using Magnetic resonance imaging (MRI) and applied the International Prophylaxis Study Group (IPSG) score. A total of 246 MRI images (knees, elbows, ankles) were analyzed in relation to disease severity, genetics, inhibitor-formation, and therapy.
Of 41 patients, 28 (68%) had severe HA or HB, 10 (24%) moderate, one (2%) mild, and two (5%) were vWD patients. 19 patients with severe HA/HB received primary prophylaxis. Inhibitors developed in 7 patients (17%), most of them had loss-of-function mutations. We observed hemophilic arthropathy in 7/39 (18%) hemophilia patients (all with severe HA/HB). Only one of the 19 patients receiving early prophylaxis developed arthropathy, in the context of inhibitor development. Minor changes (IPSG score 1-5) were observed in 20% of joints while 74% of joints showed no alterations (IPSG score 0). Only 6% of joints showed hemophilic arthropathy (IPSG score ≥ 8) with ankle joints most frequently affected (10%). Among vWD-patients, one exhibited minor changes; the other had no detectable joint damage despite vWF-inhibitor presence.
This study shows that the IPSG score is a suitable tool for assessing joint health in patients with hemophilia and vWD. Reduced joint damage was associated with early diagnosis, consistent prophylaxis, and therapy adherence.
Journal Article
Cetuximab-Induced Aseptic Meningitis in a Patient with Colorectal Cancer: A Case Report and Review of Literature
Cetuximab is a chimeric IgG1 monoclonal antibody against epidermal growth factor receptor. It is approved by the European medical agency for the treatment of RAS wild-type metastatic colorectal cancer and metastatic squamous cell cancer of the head and neck. Few cases of aseptic meningitis, primarily associated with the first administration of cetuximab in patients with squamous cell cancer, have been reported. So far, there was only 1 case in a patient with metastatic colorectal cancer. We report on a 50-year-old Caucasian patient with metastatic rectum carcinoma who suffered from headache, fever, and neck stiffness 3 h after the first administration of cetuximab (400 mg/m 2 ). CSF examination revealed an excessive pleocytosis with a white blood cell count of 2,433/µL. He was diagnosed with cetuximab-induced aseptic meningitis since clinical symptoms and CSF pleocytosis resolved within days, and further diagnostic workup revealed no infectious cause. Cetuximab-induced aseptic meningitis is a rare and severe drug reaction with predominance in treating squamous cell cancer of the head and neck. Clinical presentation and CSF findings suggest acute meningoencephalitis. In all reported cases, the course of the disease was benign and self-limited. Empiric antimicrobial and antiviral therapy are suggested until infectious causes can be ruled out. A lower dosage of cetuximab and a premedication including antihistamines and glucocorticosteroids may lower the risk of a re-occurrence if cetuximab therapy is continued.
Journal Article
Distinct Chemokine Receptor Expression Profiles in De Novo DLBCL, Transformed Follicular Lymphoma, Richter’s Trans-Formed DLBCL and Germinal Center B-Cells
Chemokine receptors and their ligands have been identified as playing an important role in the development of diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, and Richter syndrome (RS). Our aim was to investigate the different expression profiles in de novo DLBCL, transformed follicular lymphoma (tFL), and RS. Here, we profiled the mRNA expression levels of 18 chemokine receptors (CCR1–CCR9, CXCR1–CXCR7, CX3CR1 and XCR1) using RQ-PCR, as well as immunohistochemistry of seven chemokine receptors (CCR1, CCR4–CCR8 and CXCR2) in RS, de novo DLBCL, and tFL biopsy-derived tissues. Tonsil-derived germinal center B-cells (GC-B) served as non-neoplastic controls. The chemokine receptor expression profiles of de novo DLBCL and tFL substantially differed from those of GC-B, with at least 5-fold higher expression of 15 out of the 18 investigated chemokine receptors (CCR1–CCR9, CXCR1, CXCR2, CXCR6, CXCR7, CX3CR1 and XCR1) in these lymphoma subtypes. Interestingly, the de novo DLBCL and tFL exhibited at least 22-fold higher expression of CCR1, CCR5, CCR8, and CXCR6 compared with RS, whereas no significant difference in chemokine receptor expression profile was detected when comparing de novo DLBCL with tFL. Furthermore, in de novo DLBCL and tFLs, a high expression of CCR7 was associated with a poor overall survival in our study cohort, as well as in an independent patient cohort. Our data indicate that the chemokine receptor expression profile of RS differs substantially from that of de novo DLBCL and tFL. Thus, these multiple dysregulated chemokine receptors could represent novel clinical markers as diagnostic and prognostic tools. Moreover, this study highlights the relevance of chemokine signaling crosstalk in the tumor microenvironment of aggressive lymphomas.
Journal Article
The CXCR4–CXCL12-Axis Is of Prognostic Relevance in DLBCL and Its Antagonists Exert Pro-Apoptotic Effects In Vitro
In tumor cells of more than 20 different cancer types, the CXCR4-CXCL12-axis is involved in multiple key processes including proliferation, survival, migration, invasion, and metastasis. Since data on this axis in diffuse large B cell lymphoma (DLBCL) are inconsistent and limited, we comprehensively studied the CXCR4-CXCL12-axis in our DLBCL cohort as well as the effects of CXCR4 antagonists on lymphoma cell lines in vitro. In DLBCL, we observed a 140-fold higher CXCR4 expression compared to non-neoplastic controls, which was associated with poor clinical outcome. In corresponding bone marrow biopsies, we observed a correlation of CXCL12 expression and lymphoma infiltration rate as well as a reduction of CXCR4 expression in remission of bone marrow involvement after treatment. Additionally, we investigated the effects of three CXCR4 antagonists in vitro. Therefore, we used AMD3100 (Plerixafor), AMD070 (Mavorixafor), and WKI, the niacin derivative of AMD070, which we synthesized. WK1 demonstrated stronger pro-apoptotic effects than AMD070 in vitro and induced expression of pro-apoptotic genes of the BCL2-family in CXCR4-positive lymphoma cell lines. Finally, WK1 treatment resulted in the reduced expression of JNK-, ERK1/2- and NF-κB/BCR-target genes. These data indicate that the CXCR4-CXCL12-axis impacts the pathogenesis of DLBCL and represents a potential therapeutic target in aggressive lymphomas.
Journal Article