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

On the glueball spectrum in O(a)-improved lattice QCD

We calculate the light `glueball' mass spectrum in N_f=2 lattice QCD using a fermion action that is non-perturbatively O(a) improved. We work at lattice spacings a ~0.1 fm and with quark masses that range down to about half the strange quark mass. We find the statistical errors to be moderate and under control on relatively small ensembles. We compare our mass spectrum to that of quenched QCD at the same value of a. Whilst the tensor mass is the same (within errors), the scalar mass is significantly smaller in the dynamical lattice theory, by a factor of ~(0.84 +/- 0.03). We discuss what the observed m_q dependence of this suppression tells us about the dynamics of glueballs in QCD. We also calculate the masses of flux tubes that wind around the spatial torus, and extract the string tension from these. As we decrease the quark mass we see a small but growing vacuum expectation value for the corresponding flux tube operators. This provides clear evidence for `string breaking' and for the (expected) breaking of the associated gauge centre symmetry by sea quarks.Comment: 33pp LaTeX. Version to appear in Phys. Rev.

Literature

Literature has been proposed as a means to enrich an understanding of ethical issues within medicine and health care and as a resource in medical education. Its proponents argue for the value of understanding human suffering, and the experience of health care, through literature, rather than solely through the more abstract and analytic philosophical methods of bioethics. Literature is claimed to serve as a corrective to the rational and individualist approaches of bioethics, by drawing attention to ‘our vulnerable and interdependent human existence.’ In this essay the history of a relationship between ethics and literature is discussed, along with more recent scholarship on the ethical relevance of literature, and research focusing on the constitution of ethics as literary form. It is apparent that literature, and especially futurist writing and science fiction, has an influence on the construction and understanding of ethical issues for both specialist practitioners and the lay public. It is concluded that literature enhances understanding of ethical issues in health care and research, and the manner in which it does so needs to be better understood through the skills of literary analysis as a necessary complement to bioethical analysis

Quenched QCD with O(a) improvement: I. The spectrum of light hadrons

We present a comprehensive study of the masses of pseudoscalar and vector mesons, as well as octet and decuplet baryons computed in O(a) improved quenched lattice QCD. Results have been obtained using the non-perturbative definition of the improvement coefficient c_sw, and also its estimate in tadpole improved perturbation theory. We investigate effects of improvement on the incidence of exceptional configurations, mass splittings and the parameter J. By combining the results obtained using non-perturbative and tadpole improvement in a simultaneous continuum extrapolation we can compare our spectral data to experiment. We confirm earlier findings by the CP-PACS Collaboration that the quenched light hadron spectrum agrees with experiment at the 10% level.Comment: 36 pages, 7 postscript figures, REVTEX; typo in Table XVIII corrected; extended discussion of finite-size effects in sections III and VII; version to appear in Phys. Rev.

Characterisation of the Immunophenotype of Dogs with Primary Immune-Mediated Haemolytic Anaemia

Immune-mediated haemolytic anaemia (IMHA) is reported to be the most common autoimmune disease of dogs, resulting in significant morbidity and mortality in affected animals. Haemolysis is caused by the action of autoantibodies, but the immunological changes that result in their production have not been elucidated.To investigate the frequency of regulatory T cells (Tregs) and other lymphocyte subsets and to measure serum concentrations of cytokines and peripheral blood mononuclear cell expression of cytokine genes in dogs with IMHA, healthy dogs and dogs with inflammatory diseases.19 dogs with primary IMHA, 22 dogs with inflammatory diseases and 32 healthy control dogs.Residual EDTA-anti-coagulated blood samples were stained with fluorophore-conjugated monoclonal antibodies and analysed by flow cytometry to identify Tregs and other lymphocyte subsets. Total RNA was also extracted from peripheral blood mononuclear cells to investigate cytokine gene expression, and concentrations of serum cytokines (interleukins 2, 6 10, CXCL-8 and tumour necrosis factor α) were measured using enhanced chemiluminescent assays. Principal component analysis was used to investigate latent variables that might explain variability in the entire dataset.There was no difference in the frequency or absolute numbers of Tregs among groups, nor in the proportions of other lymphocyte subsets. The concentrations of pro-inflammatory cytokines were greater in dogs with IMHA compared to healthy controls, but the concentration of IL-10 and the expression of cytokine genes did not differ between groups. Principal component analysis identified four components that explained the majority of the variability in the dataset, which seemed to correspond to different aspects of the immune response.The immunophenotype of dogs with IMHA differed from that of dogs with inflammatory diseases and from healthy control dogs; some of these changes could suggest abnormalities in peripheral tolerance that permit development of autoimmune disease. The frequency of Tregs did not differ between groups, suggesting that deficiency in the number of these cells is not responsible for development of IMHA

Effects of non-perturbatively improved dynamical fermions in QCD at fixed lattice spacing

We present results for the static inter-quark potential, lightest glueballs, light hadron spectrum and topological susceptibility using a non-perturbatively improved action on a $16^3\times 32$ lattice at a set of values of the bare gauge coupling and bare dynamical quark mass chosen to keep the lattice size fixed in physical units ($\sim 1.7$ fm). By comparing these measurements with a matched quenched ensemble, we study the effects due to two degenerate flavours of dynamical quarks. With the greater control over residual lattice spacing effects which these methods afford, we find some evidence of charge screening and some minor effects on the light hadron spectrum over the range of quark masses studied ($M_{PS}/M_{V}\ge0.58$). More substantial differences between quenched and unquenched simulations are observed in measurements of topological quantities.Comment: 53 pages, LaTeX/RevTeX, 16 eps figures; corrected clover action expression and various typos, no results change

Lattice QCD at the physical point: Simulation and analysis details

We give details of our precise determination of the light quark masses m_{ud}=(m_u+m_d)/2 and m_s in 2+1 flavor QCD, with simulated pion masses down to 120 MeV, at five lattice spacings, and in large volumes. The details concern the action and algorithm employed, the HMC force with HEX smeared clover fermions, the choice of the scale setting procedure and of the input masses. After an overview of the simulation parameters, extensive checks of algorithmic stability, autocorrelation and (practical) ergodicity are reported. To corroborate the good scaling properties of our action, explicit tests of the scaling of hadron masses in N_f=3 QCD are carried out. Details of how we control finite volume effects through dedicated finite volume scaling runs are reported. To check consistency with SU(2) Chiral Perturbation Theory the behavior of M_\pi^2/m_{ud} and F_\pi as a function of m_{ud} is investigated. Details of how we use the RI/MOM procedure with a separate continuum limit of the running of the scalar density R_S(\mu,\mu') are given. This procedure is shown to reproduce the known value of r_0m_s in quenched QCD. Input from dispersion theory is used to split our value of m_{ud} into separate values of m_u and m_d. Finally, our procedure to quantify both systematic and statistical uncertainties is discussed.Comment: 45 page

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