Diagnosis of anaplastic large-cell lymphoma in a dog using CD30 immunohistochemistry

Anaplastic large-cell lymphoma or null-cell lymphoma is a clinical entity reported in people, classified according to the unique appearance of large pleomorphic cells that express CD30. Null-cell lymphoma has also been described in dogs when neither CD3 nor CD79α is expressed by the tumor. We describe a case of lymphoma in the dog in which neoplastic cells did not express routine B- or T-lymphocyte markers on flow cytometry or immunohistochemistry; however, cells immunohistochemically labeled for CD30. The dog in our case died 5 mo after initial presentation, confirming a poor prognosis. Identification of further similar cases in dogs would provide additional prognostic information for this subset of lymphomas. CD30 may also serve as a potential therapeutic target in anaplastic large-cell lymphomas

Conformity and controversies in the diagnosis, staging and follow-up evaluation of canine nodal lymphoma: a systematic review of the last 15 years of published literature

Diagnostic methods used in the initial and post-treatment evaluation of canine lymphoma are heterogeneous and can vary within countries and institutions. Accurate reporting of clinical stage and response assessment is crucial in determining the treatment efficacy and predicting prognosis. This study comprises a systematic review of all available canine multicentric lymphoma studies published over 15 years. Data concerning diagnosis, clinical stage evaluation and response assessment procedures were extracted and compared. Sixty-three studies met the eligibility criteria. Fifty-five (87.3%) studies were non-randomized prospective or retrospective studies. The survey results also expose variations in diagnostic criteria and treatment response assessment in canine multicentric lymphoma. Variations in staging procedures performed and recorded led to an unquantifiable heterogeneity among patients in and between studies, making it difficult to compare treatment efficacies. Awareness of this inconsistency of procedure and reporting may help in the design of future clinical trials

Outcome comparison between radiation therapy and surgery as primary treatment for dogs with periarticular histiocytic sarcoma: An Italian Society of Veterinary Oncology study

Localized histiocytic sarcoma may occur as a primary lesion in periarticular tissues of large appendicular joints. Treatment options for the primary lesion include radical surgical excision, radiation therapy (RT), or both, in combination with chemotherapy for potential systemic metastases. In an effort to better characterize the time to progression (TTP) following surgical vs non-surgical approaches for periarticular histiocytic sarcoma (PAHS), a contemporary European population of affected dogs was retrospectively surveyed. Medical records were queried for newly-diagnosed PAHS cases undergoing surgery (predominantly limb amputation) or RT followed by systemic chemotherapy. Of 49 dogs, 34 underwent RT and 15 underwent surgery. All dogs received adjuvant chemotherapy. There was no statistically significant difference in TTP or overall survival between groups. The median TTP was 336 days for the operated dogs and 217 days for the irradiated dogs (P =.117). The median overall survival time was 398 days for the operated dogs and 240 days for the irradiated dogs (P =.142). On multi-variable analysis, the variables significantly associated with an increased risk of both tumour progression and tumour-related death were regional lymph node and distant metastasis at admission. Survival and local control rates following RT may be comparable to radical resection. These data may better inform shared decision-making processes between multi-disciplinary care providers and owners

AMM15: a new high-resolution NEMO configuration for operational simulation of the European north-west shelf

This paper describes the next-generation ocean forecast model for the European north-west shelf, which will become the basis of operational forecasts in 2018. This new system will provide a step change in resolution and therefore our ability to represent small-scale processes. The new model has a resolution of 1.5 km compared with a grid spacing of 7 km in the current operational system. AMM15 (Atlantic Margin Model, 1.5 km) is introduced as a new regional configuration of NEMO v3.6. Here we describe the technical details behind this configuration, with modifications appropriate for the new high-resolution domain. Results from a 30-year non-assimilative run using the AMM15 domain demonstrate the ability of this model to represent the mean state and variability of the region. Overall, there is an improvement in the representation of the mean state across the region, suggesting similar improvements may be seen in the future operational system. However, the reduction in seasonal bias is greater off-shelf than on-shelf. In the North Sea, biases are largely unchanged. Since there has been no change to the vertical resolution or parameterization schemes, performance improvements are not expected in regions where stratification is dominated by vertical processes rather than advection. This highlights the fact that increased horizontal resolution will not lead to domain-wide improvements. Further work is needed to target bias reduction across the north-west shelf region

Reverse engineering field-derived vertical distribution profiles to infer larval swimming behaviors

Biophysical models are well-used tools for predicting the dispersal of marine larvae. Larval behavior has been shown to influence dispersal, but how to incorporate behavior effectively within dispersal models remains a challenge. Mechanisms of behavior are often derived from laboratory-based studies and therefore, may not reflect behavior in situ. Here, using state-of-the-art models, we explore the movements that larvae must undertake to achieve the vertical distribution patterns observed in nature. Results suggest that behaviors are not consistent with those described under the tidally synchronized vertical migration (TVM) hypothesis. Instead, we show (i) a need for swimming speed and direction to vary over the tidal cycle and (ii) that, in some instances, larval swimming cannot explain observed vertical patterns. We argue that current methods of behavioral parameterization are limited in their capacity to replicate in situ observations of vertical distribution, which may cause dispersal error to propagate over time, due to advective differences over depth and demonstrate an alternative to laboratory-based behavioral parameterization that encompasses the range of environmental cues that may be acting on planktic organisms

Efficiency review of Austria’s social insurance and healthcare system: volume 1 – international comparisons and policy options

In 2016, the London School of Economics and Political Science (LSE Health) was engaged by the Austrian Ministry of Labour, Social Affairs and Consumer Protection to undertake an efficiency review of the country’s social insurance system (see Appendix A for the original Concept Note). The review was specifically targeted at health competencies within the social insurance system; for this reason, consideration of accident and pension insurance, as well as other forms of care covered by Federal and Länder governments, were only examined where directly applicable

The influence of tides on the North West European shelf winter residual circulation

Tides contribute to the large-scale residual circulation and mixing of shelf seas. However, tides are typically excluded from global circulation models (GCMs) so their modelled residual circulation (and mixing) in shelf seas may be systematically wrong. We focus on circulation as it is relatively unexplored, and affects shelf temperature and salinity, potentially biasing climate impact studies. Using a validated model of the North West European Shelf Seas (NWS), we show the essential role of tides in driving the residual circulation, and how this affects the NWS temperature and salinity distribution. Over most of the NWS, removing the tides increases the magnitude of residual circulation while in some regions (such as the Irish Sea) it leads to a reduction. Furthermore, we show that modelling the NWS without tides leads to a cold fresh bias in the Celtic Sea and English Channel (of >0.5°C, and >0.5 psu). This shows that NWS tidal dynamics are essential in the transport of heat and matter, and so must be included in GCMs. We explore two processes by which the tides impact the residual circulation and investigate whether these could be parameterised within non-tidal GCMs: (1) Enhancing the seabed friction to mimic the equivalent energy loss from an oscillating tidal flow; (2) Tidal Phase-driven Transport (TPT), whereby tidal asymmetry drives a net transport due to the phase between tidal-elevation and velocities (equivalent to the bolus term in oceanographic literature). To parameterise TPT, we calculate a climatology of this transport from a harmonic analysis from the tidal model and add it as an additional force in the Navier Stokes equations in the non-tidal model. We also modify the bed drag coefficient to balance the bed stress between the simulations – hypothesising that using this modified drag coefficient will simulate the effect of the tides. This tends to improve the mean and variability of the residual circulation, while the TPT improves the spatial distribution and temporal variability of the temperature and salinity. We show that our proof-of-concept parameterisation can replicate the tidally-driven impact on the residual circulation without direct simulation, thus reducing computational effort

Gene Expression Profiling of B Cell Lymphoma in Dogs Reveals Dichotomous Metabolic Signatures Distinguished by Oxidative Phosphorylation

Gene expression profiling has revealed molecular heterogeneity of diffuse large B cell lymphoma (DLBCL) in both humans and dogs. Two DLBCL subtypes based on cell of origin are generally recognized, germinal center B (GCB)-like and activated B cell (ABC)-like. A pilot study to characterize the transcriptomic phenotype of 11 dogs with multicentric BCL yielded two molecular subtypes distinguished on the basis of genes important in oxidative phosphorylation. We propose a metabolic classification of canine BCL that transcends cell of origin and shows parallels to a similar molecular phenotype in human DLBCL. We thus confirm the validity of this classification scheme across widely divergent mammalian taxa and add to the growing body of literature suggesting cellular and molecular similarities between human and canine non-Hodgkin lymphoma. Our data support a One Health approach to the study of DLBCL, including the advancement of novel therapies of relevance to both canine and human health

Dissecting the regulatory microenvironment of a large animal model of non-Hodgkin lymphoma: evidence of a negative prognostic impact of FOXP3+ T cells in canine B cell lymphoma.

The cancer microenvironment plays a pivotal role in oncogenesis, containing a number of regulatory cells that attenuate the anti-neoplastic immune response. While the negative prognostic impact of regulatory T cells (Tregs) in the context of most solid tissue tumors is well established, their role in lymphoid malignancies remains unclear. T cells expressing FOXP3 and Helios were documented in the fine needle aspirates of affected lymph nodes of dogs with spontaneous multicentric B cell lymphoma (BCL), proposed to be a model for human non-Hodgkin lymphoma. Multivariable analysis revealed that the frequency of lymph node FOXP3(+) T cells was an independent negative prognostic factor, impacting both progression-free survival (hazard ratio 1.10; p = 0.01) and overall survival (hazard ratio 1.61; p = 0.01) when comparing dogs showing higher than the median FOXP3 expression with those showing the median value of FOXP3 expression or less. Taken together, these data suggest the existence of a population of Tregs operational in canine multicentric BCL that resembles thymic Tregs, which we speculate are co-opted by the tumor from the periphery. We suggest that canine multicentric BCL represents a robust large animal model of human diffuse large BCL, showing clinical, cytological and immunophenotypic similarities with the disease in man, allowing comparative studies of immunoregulatory mechanisms.This is the published version of the manuscript. It was published in PLOS One and can be found here: http://www.plosone.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0105027&representation=PD