Assessing UAS Flight Testing and It's Importance for Beyond-Line-of-Sight UAS Control in Cooperation with Partnering Organizations

From the 1st of June until the 21st of August, the internship has been conducted at NASA Ames Research Center as part of the Master of Space Studies at the International Space University. The main activities consisted of doing research on UAV flight-testing and the assessing of safety with respect to Beyond-Line-Of-Sight operations. Further activities consisted of accommodating international partners and potential partners at the NASA Ames site, in order to identify mutual interest and future collaboration. Besides those activities, the report describes the planning process of the ISU Space Coast Trip to 10 different space related companies on the west-coast of California. Key words: UAS, UAV, BLOS, Ames, ISU Tri

Interobserver variation in CD30 immunohistochemistry interpretation; consequences for patient selection for targeted treatment

AimsCD30 immunohistochemistry (IHC) in malignant lymphoma is used for selection of patients in clinical trials using brentuximab vedotin, an antibody drug-conjugate targeting the CD30 molecule. For reliable implementation in daily practice and meaningful selection of patients for clinical trials, information on technical variation and interobserver reproducibility of CD30 immunohistochemistry (IHC) staining is required. Methods and resultsWe conducted a three-round reproducibility assessment of CD30 scoring for categorised frequency and intensity, including a technical validation, a live polling' pre- and post-instruction scoring round and a web-based round including individual scoring with additional IHC information to mimic daily diagnostic practice. Agreement in all three scoring rounds was poor to fair ( = 0.12-0.35 for CD30-positive tumour cell percentage and = 0.16-0.41 for staining intensity), even when allowing for one category of freedom in percentage of tumour cell positivity ( = 0.30-0.61). The first round with CD30 staining performed in five independent laboratories showed objective differences in staining intensity. In the second round, approximately half the pathologists changed their opinion on CD30 frequency after a discussion on potential pitfalls, highlighting hesitancy in decision-making. Using fictional cut-off points for percentage of tumour cell positivity, agreement was still suboptimal ( = 0.35-0.60). ConclusionsLack of agreement in cases with heterogeneous expression is shown to influence patient eligibility for treatment with brentuximab vedotin, both in clinical practice and within the context of clinical trials, and limits the potential predictive value of the relative frequency of CD30-positive neoplastic cells for clinical response

Commentary on the WHO classification of tumors of lymphoid tissues (2008): indolent B cell lymphomas

The 4th edition of the World Health Organization classification of tumors of hematopoietic and lymphoid tissues introduces many new items to the classification scheme of the so-called indolent B cell lymphomas. New proposed entities, such as splenic B cell lymphoma/leukemia, unclassifiable, splenic diffuse red pulp small B cell lymphoma, hairy cell leukemia variant, pediatric follicular lymphoma, and pediatric marginal zone lymphoma have been coined, and some definitions of established diseases, such as chronic lymphocytic leukemia or Waldenström’s macroglobulinemia have been revised. One aspect of major importance is the recent description of small clonal B cell populations, in part with a CLL phenotype, and their relationship to B-CLL. Some new subtypes or variants of follicular lymphoma with distinct clinicopathologic and/or molecular genetic characteristics have been described, including primary follicular lymphomas of the duodenum and pediatric follicular lymphomas. Furthermore, the impact of some probably early, or precursor lesions, such as follicular lymphoma in situ is discussed. Overall, we succinctly discuss the essential elements of the revisions made in the updated classification, and we identify potential opportunities for refinement of new or provisional categories in subsequent classifications

Commentary on the WHO classification of tumors of lymphoid tissues (2008): “Gray zone” lymphomas overlapping with Burkitt lymphoma or classical Hodgkin lymphoma

The 2008 WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues has introduced two new categories of high-grade B-cell lymphomas: entities in which features of diffuse large B-cell lymphoma (DLBCL) overlap with Burkitt lymphoma (DLBCL/BL) or classical Hodgkin lymphoma (DLBCL/HL). The DLBCL/BL category encompasses cases that resemble Burkitt lymphoma morphologically, but have one or more immunophenotypic or molecular genetic deviations that would exclude it from the BL category; conversely, some cases have immunophenotypic and/or genetic features of BL, but display cytologic variability unacceptable for BL. Many of the cases in the DLBCL/BL category contain a translocation of MYC as well as either BCL2 or BCL6 (so-called double-hit lymphomas) and have a very aggressive clinical behavior. The DLBCL/HL category encompasses lymphomas that exhibit the morphology of classical Hodgkin lymphoma but the immunophenotype of DLBCL, or vice versa. Most DLBCL/HL cases described present as mediastinal masses, but this category is not limited to mediastinal lymphomas. These new categories acknowledge the increasing recognition of cases that display mixed features of two well-established diseases. Whether the existence of such cases reflects shortcomings of our current diagnostic armamentarium or a true disease continuum in which such hybrid or intermediate neoplasms actually exist remains to be determined

Among B cell non-Hodgkin's lymphomas, MALT lymphomas express a unique antibody repertoire with frequent rheumatoid factor reactivity

We analyzed the structure of antigen receptors of a comprehensive panel of mature B non-Hodgkin's lymphomas (B-NHLs) by comparing, at the amino acid level, their immunoglobulin (Ig)VH-CDR3s with CDR3 sequences present in GenBank. Follicular lymphomas, diffuse large B cell lymphomas, Burkitt's lymphomas, and myelomas expressed a CDR3 repertoire comparable to that of normal B cells. Mantle cell lymphomas and B cell chronic lymphocytic leukemias (B-CLLs) expressed clearly restricted albeit different CDR3 repertoires. Lymphomas of mucosa-associated lymphoid tissues (MALTs) were unique as 8 out of 45 (18%) of gastric- and 13 out of 32 (41%) of salivary gland-MALT lymphomas expressed B cell antigen receptors with strong CDR3 homology to rheumatoid factors (RFs). Of note, the RF-CDR3 homology without exception included N-region–encoded residues in the hypermutated IgVH genes, indicating that they were stringently selected for reactivity with auto-IgG. By in vitro binding studies with 10 MALT lymphoma–derived antibodies, we showed that seven of these cases, of which four with RF-CDR3 homology, indeed possessed strong RF reactivity. Of one MALT lymphoma, functional proof for selection of subclones with high RF affinity was obtained. Interestingly, RF-CDR3 homology and t(11;18) appeared to be mutually exclusive features and RF-CDR3 homology was not encountered in any of the 19 pulmonary MALT lymphomas studied

Delineation of Chondroid Lipoma: An Immunohistochemical and Molecular Biological Analysis

Aims. Chondroid lipoma (CL) is a benign tumor that mimics a variety of soft tissue tumors and is characterized by translocation t(11;16). Here, we analyze CL and its histological mimics. Methods. CL (n = 4) was compared to a variety of histological mimics (n = 83) for morphological aspects and immunohistochemical features including cyclinD1(CCND1). Using FISH analysis, CCND1 and FUS were investigated as potential translocation partners. Results. All CLs were strongly positive for CCND1. One of 4 myoepitheliomas, CCND1, was positive. In well-differentiated lipomatous tumors and in chondrosarcomas, CCND1 was frequently expressed, but all myxoid liposarcomas were negative. FISH analysis did not give support for direct involvement of CCND1 and FUS as translocation partners. Conclusions. Chondroid lipoma is extremely rare and has several and more prevalent histological mimics. The differential diagnosis of chondroid lipomas can be unraveled using immunohistochemical and molecular support

Translocation t(11;18)(q21;q21) in gastric B‐cell lymphomas

Translocation t(11;18)(q21;q21) is the most frequent chromosomal aberration reported in gastric mucosa-associated lymphoid tissue (MALT) lymphomas. Intriguingly, this translocation has been reported only rarely in diffuse large B-cell lymphomas; it has been proposed that t(11;18)-positive tumors rarely progress to diffuse large B-cell lymphomas. We examined the frequency of chromosomal translocation t(11;18)(q21;q21) in mucosa-associated lymphoid tissue lymphoma and diffuse large B-cell lymphoma of the stomach. Paraffin-embedded tissues from patients with gastric B-cell lymphomas were selected retrospectively. The presence of the t(11;18)(q21;q21) was determined using reverse transcriptase-polymerase chain reaction and/or fluorescence in situ hybridization. beta-Actin transcript was also determined to evaluate the integrity and efficiency of RNA (cDNA) recovery from paraffin-embedded tissues. We analyzed 53 gastric B-cell lymphomas (33 diffuse large B-cell and 20 mucosa-associated lymphoid tissue) obtained from Italy, the USA, or Japan. Beta-actin transcript was amplified in 50 cases (94%), including 19 mucosa-associated lymphoid tissue and 31 diffuse large B-cell lymphomas (five with mucosa-associated lymphoid tissue components). The t(11;18) translocation was detected in 19% (6 of 31) cases with diffuse large B-cell lymphoma versus 26% (five of 19) with mucosa-associated lymphoid tissue lymphoma (P = 0.72). One of five diffuse large B-cell lymphomas with a mucosa-associated lymphoid tissue component showed the t(11;18)(q21;q21). In conclusion, translocation t(11;18)(q21;q21) was found in both mucosa-associated lymphoid tissue lymphomas and diffuse large B-cell lymphomas of the stomach at approximately equivalent frequencies; its presence does not exclude progression to diffuse large B-cell lymphoma

Identifying Audiences of E-Infrastructures - Tools for Measuring Impact

Research evaluation should take into account the intended scholarly and non-scholarly audiences of the research output. This holds too for research infrastructures, which often aim at serving a large variety of audiences. With research and research infrastructures moving to the web, new possibilities are emerging for evaluation metrics. This paper proposes a feasible indicator for measuring the scope of audiences who use web-based e-infrastructures, as well as the frequency of use. In order to apply this indicator, a method is needed for classifying visitors to e-infrastructures into relevant user categories. The paper proposes such a method, based on an inductive logic program and a Bayesian classifier. The method is tested, showing that the visitors are efficiently classified with 90% accuracy into the selected categories. Consequently, the method can be used to evaluate the use of the e-infrastructure within and outside academia

Reproducibility of Gene Expression Signatures in Diffuse Large B-Cell Lymphoma

SIMPLE SUMMARY: Multiple gene expression signatures with biological or prognostic subgroups have been published in diffuse large B-cell lymphoma (DLBCL). With exception of the cell of origin (COO) classifier, these were not validated in independent cohorts. The aim of the study was to reproduce four gene expression signatures capturing multiple biological subgroups using the NanoString platform. In addition, we aimed to identify potential associations between the signatures and portray the heterogeneity of DLBCL. We show that, in an independent cohort of clinically well-defined patients, these signatures can co-occur in the same patient and that each classifier captures a different aspect of the biological heterogenous panorama of DLBCL. Beside COO, there is clear evidence of different immune and MYC signatures. A direct comparison in our cohort showed that these signatures reflect independent biological features. More comparative studies with gene expression profiles need to be conducted to enable a further integration and to help develop new taxonomy systems for clinical utility. ABSTRACT: Multiple gene expression profiles have been identified in diffuse large B-cell lymphoma (DLBCL). Besides the cell of origin (COO) classifier, no signatures have been reproduced in independent studies or evaluated for capturing distinct aspects of DLBCL biology. We reproduced 4 signatures in 175 samples of the HOVON-84 trial on a panel of 117 genes using the NanoString platform. The four gene signatures capture the COO, MYC activity, B-cell receptor signaling, oxidative phosphorylation, and immune response. Performance of our classification algorithms were confirmed in the original datasets. We were able to validate three of the four GEP signatures. The COO algorithm resulted in 94 (54%) germinal center B-cell (GCB) type, 58 (33%) activated B-cell (ABC) type, and 23 (13%) unclassified cases. The MYC-classifier revealed 77 cases with a high MYC-activity score (44%) and this MYC-high signature was observed more frequently in ABC as compared to GCB DLBCL (68% vs. 32%, p < 0.00001). The host response (HR) signature of the consensus clustering was present in 55 (31%) patients, while the B-cell receptor signaling, and oxidative phosphorylation clusters could not be reproduced. The overlap of COO, consensus cluster and MYC activity score differentiated six gene expression clusters: GCB/MYC-high (12%), GCB/HR (16%), GCB/non-HR (27%), COO-Unclassified (13%), ABC/MYC-high (25%), and ABC/MYC-low (7%). In conclusion, the three validated signatures identify distinct subgroups based on different aspects of DLBCL biology, emphasizing that each classifier captures distinct molecular profiles

A direct comparison of natural and acoustic-radiation-force-induced cardiac mechanical waves

Natural and active shear wave elastography (SWE) are potential ultrasound-based techniques to non-invasively assess myocardial stiffness, which could improve current diagnosis of heart failure. This study aims to bridge the knowledge gap between both techniques and discuss their respective impacts on cardiac stiffness evaluation. We recorded the mechanical waves occurring after aortic and mitral valve closure (AVC, MVC) and those induced by acoustic radiation force throughout the cardiac cycle in four pigs after sternotomy. Natural SWE showed a higher feasibility than active SWE, which is an advantage for clinical application. Median propagation speeds of 2.5–4.0 m/s and 1.6–4.0 m/s were obtained after AVC and MVC, whereas ARF-based median speeds of 0.9–1.2 m/s and 2.1–3.8 m/s were reported for diastole and systole, respectively. The different wave characteristics in both methods, such as the frequency content, complicate the direct comparison of waves. Nevertheless, a good match was found in propagation speeds between natural and active SWE at the moment of valve closure, and the natural waves showed higher propagation speeds than in diastole. Furthermore, the results demonstrated that the natural waves occur in between diastole and systole identified with active SWE, and thus represent a myocardial stiffness in between relaxation and contraction