Array-based comparative genomic hybridization analysis reveals chromosomal copy number aberrations associated with clinical outcome in canine diffuse large B-cell lymphoma

Canine Diffuse Large B-cell Lymphoma (cDLBCL) is an aggressive cancer with variable clinical response. Despite recent attempts by gene expression profiling to identify the dog as a potential animal model for human DLBCL, this tumor remains biologically heterogeneous with no prognostic biomarkers to predict prognosis. The aim of this work was to identify copy number aberrations (CNAs) by high-resolution array comparative genomic hybridization (aCGH) in 12 dogs with newly diagnosed DLBCL. In a subset of these dogs, the genetic profiles at the end of therapy and at relapse were also assessed. In primary DLBCLs, 90 different genomic imbalances were counted, consisting of 46 gains and 44 losses. Two gains in chr13 were significantly correlated with clinical stage. In addition, specific regions of gains and losses were significantly associated to duration of remission. In primary DLBCLs, individual variability was found, however 14 recurrent CNAs (>30%) were identified. Losses involving IGK, IGL and IGH were always found, and gains along the length of chr13 and chr31 were often observed (>41%). In these segments, MYC, LDHB, HSF1, KIT and PDGFR alpha are annotated. At the end of therapy, dogs in remission showed four new CNAs, whereas three new CNAs were observed in dogs at relapse compared with the previous profiles. One ex novo CNA, involving TCR, was present in dogs in remission after therapy, possibly induced by the autologous vaccine. Overall, aCGH identified small CNAs associated with outcome, which, along with future expression studies, may reveal target genes relevant to cDLBCL

[OI] disk emission in the Taurus star forming region

The structure of protoplanetary disks is thought to be linked to the temperature and chemistry of their dust and gas. Whether the disk is flat or flaring depends on the amount of radiation that it absorbs at a given radius, and on the efficiency with which this is converted into thermal energy. The understanding of these heating and cooling processes is crucial to provide a reliable disk structure for the interpretation of dust continuum emission and gas line fluxes. Especially in the upper layers of the disk, where gas and dust are thermally decoupled, the infrared line emission is strictly related to the gas heating/cooling processes. We aim to study the thermal properties of the disk in the oxygen line emission region, and to investigate the relative importance of X-ray (1-120 Angstrom) and far-UV radiation (FUV, 912-2070 Angstrom) for the heating balance there. We use [OI] 63 micron line fluxes observed in a sample of protoplanetary disks of the Taurus/Auriga star forming region and compare it to the model predictions presented in our previous work. The data were obtained with the PACS instrument on board the Herschel Space Observatory as part of the Herschel Open Time Key Program GASPS (GAS in Protoplanetary diskS), published in Howard et al. (2013). Our theoretical grid of disk models can reproduce the [OI] absolute fluxes and predict a correlation between [OI] and the sum Lx+Lfuv. The data show no correlation between the [OI] line flux and the X-ray luminosity, the FUV luminosity or their sum. The data show that the FUV or X-ray radiation has no notable impact on the region where the [OI] line is formed. This is in contrast with what is predicted from our models. Possible explanations are that the disks in Taurus are less flaring than the hydrostatic models predict, and/or that other disk structure aspects that were left unchanged in our models are important. ..abridged..Comment: 9 pages, accepted for publication in A&

Transformation of canine lymphoma/leukemia to more aggressive diseases : anecdotes or reality?

Transformation is the evolution of an indolent lymphoma/leukemia to an aggressive lymphoma, typically harboring a very poor prognosis. This phenomenon is well described in humans, but underestimated in dogs although recognized as a possible evolution of indolent lymphomas/leukemias. In canine chronic leukemias, blast crisis (mainly in myeloid) and Richter syndrome (transformation into a high grade lymphoma) (mainly in B-cell lymphocytic leukemia) have been reported. Transformation is a possible event also in canine low grade lymphomas, although rare. The increased knowledge has also generated new questions and posed challenges that need to be addressed to improve outcome, including the recognition of the clinical characteristics at diagnosis associated with a higher risk of transformation in an attempt of anticipating the typical evolution

Effects of pre-analytical variables on flow cytometric diagnosis of canine lymphoma : A 3 retrospective study (2009-2015)

Flow cytometry (FC) is increasingly being used for immunophenotyping and staging of canine lymphoma. The aim of this retrospective study was to assess pre-analytical variables that might influence the diagnostic utility of FC of lymph node (LN) fine needle aspirate (FNA) specimens from dogs with lymphoproliferative diseases. The study included 987 cases with LN FNA specimens sent for immunophenotyping that were submitted to a diagnostic laboratory in Italy from 2009 to 2015. Cases were grouped into 'diagnostic' and 'non-diagnostic'. Pre-analytical factors analysed by univariate and multivariate analyses were animal-related factors (breed, age, sex, size), operator-related factors (year, season, shipping method, submitting veterinarian) and sample-related factors (type of sample material, cellular concentration, cytological smears, artefacts). The submitting veterinarian, sample material, sample cellularity and artefacts affected the likelihood of having a diagnostic sample. The availability of specimens from different sites and of cytological smears increased the odds of obtaining a diagnostic result. Major artefacts affecting diagnostic utility included poor cellularity and the presence of dead cells. Flow cytometry on LN FNA samples yielded conclusive results in more than 90% of cases with adequate sample quality and sampling conditions

Prognostic role of non-neoplastic lymphocytes in lymph node aspirates from dogs with diffuse large B-cell lymphoma treated with chemo-immunotherapy

Dogs with Diffuse Large B-Cell Lymphoma (DLBCL) benefit from the addition of active immunotherapy to traditional chemotherapy. We hypothesized that immune cells within neoplastic lymph nodes (LNs) may play a role in the tumor pathobiology and treatment response. The present study describes the composition and prognostic role of non-neoplastic lymphocytes in LNs of 59 dogs with treatment-naive DLBCL receiving chemo-immunotherapy. The percentage of small non-neoplastic cells and of CD5+, CD21+, CD4+ and CD8+ small cells was recorded via flow cytometry. CD4+/CD8+ and CD5+/large CD21+ cell ratios were calculated. The likelihood of progression significantly diminished with increasing percentage of small cells, CD5+ and CD8+ small cells, and CD5+/large CD21+ cell ratio, with decreasing CD4+/CD8+ ratio and in non-anemic dogs. Active immunotherapy is more effective in dogs with higher percentage of non-neoplastic lymphocytes at diagnosis. We lay the ground for future studies assessing the role of the immune system in the pathobiology of canine DLBCL

A retrospective study of flow cytometric characterization of suspected extranodal lymphomas in dogs

Flow cytometry (FC) is widely applied to characterize and stage nodal lymphomas in dogs because it has a short turnaround time, requires minimally invasive sampling, and allows contemporary evaluation of neoplastic cells in the primary lesion and of blood and marrow involvement. We investigated advantages and limitations of FC in suspected extranodal lymphomas in dogs. The likelihood of obtaining a suitable FC sample was significantly lower for aspirates of extranodal lesions than for lymph node aspirates. However, we noted no differences among different extranodal lesion sites. We also describe FC results for 39 samples compatible with extranodal lymphoma. A dominant population of large cells was easily identified on morphologic FC scattergrams in many cases. Phenotypic aberrancies were frequently present, mainly in T-cell lymphomas. Lymphoma cells were distinguishable from normal residual lymphocytes in >85% of cases, facilitating the quantification of putative blood and marrow involvement by FC. Despite the high percentage of non-diagnostic samples (32 of 73, >40%), we support the inclusion of FC in the diagnostic workup of suspected extranodal lymphomas in dogs, in conjunction with histopathology. Histopathology is the gold standard for diagnosing lymphoma, provides relevant information, including tissue invasion and epitheliotropism, but has a longer turnaround time

Does graphical reporting improve risk disclosure? Evidence from European banks

Purpose: This study examines the voluntary disclosure of risk-related issues, with a focus on credit risk, in graphical reporting for listed banks in the major European economies. It aims to understand if banks portray credit risk-related information in graphs accurately and whether these graphs provide incremental, rather than replicative, information. It also investigates whether credit risk-related graphs provide a fair representation of risk performance or a more favourable impression than is warranted. Design/Methodology/Approach: A graphical accuracy index was constructed. Incremental information was measured. A multi-level linear model investigated whether credit risk affects the quantity and quality of graphical credit risk disclosure. Findings: Banks used credit risk graphs to provide incremental information. They were also selective, with riskier banks less likely to use risk graphs. Banks were accurate in their graphical reporting, particularly those with high levels of credit risk. These findings can be explained within an impression management perspective taking into account human cognitive biases. Preparers of risk graphs seem to prefer selective omission over obfuscation via inaccuracy. This probably reflects the fact that individuals, and by implication annual report’s users, generally judge the provision of inaccurate information more harshly than the omission of unfavourable information. Research limitations/implications: This study provides theoretical insights by pointing out the limitations of a purely economics-based agency theory approach to impression management. Practical implications: The study suggests annual reports’ readers need to be careful about subtle forms of impression management, such as those exploiting their cognitive bias. Regulatory and professional bodies should develop guidelines to ensure neutral and comparable graphical disclosure. Originality/Value: This study provides a substantive alternative to the predominant economic perspective on impression management in corporate reporting, by incorporating a psychological perspective taking into account human cognitive biases