Canine mast cell tumours: a review of the pathogenesis, clinical features, pathology and treatment

Mast cells (MCs) are well known for their neoplastic transformation in solitary and multiple cutaneous mast cell tumours (MCTs), as well as visceral and systemic mastocytosis. Dogs have a unique risk of developing cutaneous MCTs, and they account for 7% to 21% of all canine skin tumours. The aetiology of canine MCTs is unknown but is probably multifactorial. This article reviews up-to-date knowledge on the pathogenesis, the clinical presentation, the clinical prognostic factors, the diagnostic workup including clinical staging, cytological findings, histological findings and the various grading systems which have been evaluated based on morphology, the assessment of proliferation markers and other factors such as vessel density. Furthermore, detailed information about current treatment protocols for canine cutaneous MCTs is provided.

Magnetic resonance imaging features of an extranodal T-cell rich B-cell lymphoma in the pharyngeal mucosa in a horse

An 11-year-old Warmblood gelding was presented for inspiratory stridor and dysphagia. Based on history and clinical examination, a solitary mass localised in the oropharynx was suspected. Due to its inaccessibility and defensive behaviour of the horse, it was difficult to visualise this mass either by upper airway endoscopy or by oral examination and the conventional imaging methods (radiology and ultrasound) provided only limited information. Fine needle aspiration cytology was suggestive of lymphoma, but the exact localisation and the extent of tissue infiltration of the tumour could only be defined by magnetic resonance imaging (MRI). MRI has proved to be a very useful diagnostic tool in equine lameness investigation and, as this case illustrates, it has considerable diagnostic potential for soft tissue examination of the equine head.

Clinical and biochemical profiles suggest fibromuscular dysplasia is a systemic disease with altered TGF-β expression and connective tissue features.

Fibromuscular dysplasia (FMD) is a rare, nonatherosclerotic arterial disease for which the molecular basis is unknown. We comprehensively studied 47 subjects with FMD, including physical examination, spine magnetic resonance imaging, bone densitometry, and brain magnetic resonance angiography. Inflammatory biomarkers in plasma and transforming growth factor β (TGF-β) cytokines in patient-derived dermal fibroblasts were measured by ELISA. Arterial pathology other than medial fibrodysplasia with multifocal stenosis included cerebral aneurysm, found in 12.8% of subjects. Extra-arterial pathology included low bone density (P<0.001); early onset degenerative spine disease (95.7%); increased incidence of Chiari I malformation (6.4%) and dural ectasia (42.6%); and physical examination findings of a mild connective tissue dysplasia (95.7%). Screening for mutations causing known genetically mediated arteriopathies was unrevealing. We found elevated plasma TGF-β1 (P=0.009), TGF-β2 (P=0.004) and additional inflammatory markers, and increased TGF-β1 (P=0.0009) and TGF-β2 (P=0.0001) secretion in dermal fibroblast cell lines from subjects with FMD compared to age- and gender-matched controls. Detailed phenotyping of patients with FMD allowed us to demonstrate that FMD is a systemic disease with alterations in common with the spectrum of genetic syndromes that involve altered TGF-β signaling and offers TGF-β as a marker of FMD.

Abacavir induced T cell reactivity from drug naïve individuals shares features of allo-immune responses.

Abacavir hypersensitivity is a severe hypersensitivity reaction which occurs exclusively in carriers of the HLA-B*57∶01 allele. In vitro culture of PBMC with abacavir results in the outgrowth of abacavir-reacting CD8+ T cells, which release IFNγ and are cytotoxic. How this immune response is induced and what is recognized by these T cells is still a matter of debate. We analyzed the conditions required to develop an abacavir-dependent T cell response in vitro. The abacavir reactivity was independent of co-stimulatory signals, as neither DC maturation nor release of inflammatory cytokines were observed upon abacavir exposure. Abacavir induced T cells arose in the absence of professional APC and stemmed from naïve and memory compartments. These features are reminiscent of allo-reactivity. Screening for allo-reactivity revealed that about 5% of generated T cell clones (n = 136) from three donors were allo-reactive exclusively to the related HLA-B*58∶01. The addition of peptides which can bind to the HLA-B*57∶01-abacavir complex and to HLA-B*58∶01 during the induction phase increased the proportion of HLA-B*58∶01 allo-reactive T cell clones from 5% to 42%. In conclusion, abacavir can alter the HLA-B*57∶01-peptide complex in a way that mimics an allo-allele ('altered self-allele') and create the potential for robust T cell responses.

Lateralized processing of faces: The role of features, configurations and familiarity

We investigated the lateralized processing of featural and configural information in face recognition in two divided visual field studies. In Experiment 1, participants matched the identity of a cue face containing either featural (scrambled faces) or configural (blurred faces) information with an intact test face presented subsequently either in the right visual field (RVF) or in the left visual field (LVF). Unilateral presentation was controlled by monitoring eye movements. The results show an advantage of the left hemisphere (LH) over the right hemisphere (RH) for featural processing and a specialization of the RH for configural compared to featural processing. In Experiment 2, we focused on configural processing and its relationship to familiarity. Either learned or novel test faces were presented in the LVF or the RVF. Participants recognized learned faces better when presented in the LVF than in the RVF, suggesting that the RH has an advantage in the recognition of learned faces. Because the recognition of familiar faces relies strongly on configural information (Buttle & Raymond, 2003), we argue that the advantage of the RH over the LH in configural processing is a function of familiarity.

Classification of interstitial lung disease patterns using local DCT features and random forest.

Over the last decade, a plethora of computer-aided diagnosis (CAD) systems have been proposed aiming to improve the accuracy of the physicians in the diagnosis of interstitial lung diseases (ILD). In this study, we propose a scheme for the classification of HRCT image patches with ILD abnormalities as a basic component towards the quantification of the various ILD patterns in the lung. The feature extraction method relies on local spectral analysis using a DCT-based filter bank. After convolving the image with the filter bank, q-quantiles are computed for describing the distribution of local frequencies that characterize image texture. Then, the gray-level histogram values of the original image are added forming the final feature vector. The classification of the already described patches is done by a random forest (RF) classifier. The experimental results prove the superior performance and efficiency of the proposed approach compared against the state-of-the-art.

Magnetic resonance imaging features of sinonasal disorders in horses.

Diseases of paranasal sinuses and nasal passages in horses can be a diagnostic challenge because of the complex anatomy of the head and limitations of many diagnostic modalities. Our hypothesis was that magnetic resonance (MR) imaging would provide excellent anatomical detail and soft tissue resolution, and would be accurate in the diagnosis of diseases of the paranasal sinuses and nasal passages in horses. Fourteen horses were imaged. Inclusion criteria were lesions located to the sinuses or nasal passages that underwent MR imaging and subsequent surgical intervention and/or histopathologic examination. A low field, 0.3 tesla open magnet was used. Sequences in the standard protocol were fast spin echo T2 sagittal and transverse, spin echo T1 transverse, short-tau inversion recovery (STIR) dorsal, gradient echo 3D T1 MPR dorsal (plain and contrast enhanced), spin echo T1 fatsat (contrast enhanced). Mean scan time to complete the examination was 53 min (range 39-99 min). Lesions identified were primary or secondary sinusitis (six horses), paranasal sinus cyst (four horses), progressive ethmoid hematoma (two horses), and neoplasia (two horses). The most useful sequences were fast spin echo T2 transverse and sagittal, STIR dorsal and FE3D MPR (survey and contrast enhanced). Fluid accumulation, mucosal thickening, presence of encapsulated contents, bone deformation, and thickening were common findings observed in MR imaging. In selected horses, magnetic resonance imaging is a useful tool in diagnosing lesions of the paranasal sinuses and nasal passages.

Novel Features of the Prenatal Horn Bud Development in Cattle (Bos taurus).

Whereas the genetic background of horn growth in cattle has been studied extensively, little is known about the morphological changes in the developing fetal horn bud. In this study we histologically analyzed the development of horn buds of bovine fetuses between ~70 and ~268 days of pregnancy and compared them with biopsies taken from the frontal skin of the same fetuses. In addition we compared the samples from the wild type (horned) fetuses with samples taken from the horn bud region of age-matched genetically hornless (polled) fetuses. In summary, the horn bud with multiple layers of vacuolated keratinocytes is histologically visible early in fetal life already at around day 70 of gestation and can be easily differentiated from the much thinner epidermis of the frontal skin. However, at the gestation day (gd) 212 the epidermis above the horn bud shows a similar morphology to the epidermis of the frontal skin and the outstanding layers of vacuolated keratinocytes have disappeared. Immature hair follicles are seen in the frontal skin at gd 115 whereas hair follicles below the horn bud are not present until gd 155. Interestingly, thick nerve bundles appear in the dermis below the horn bud at gd 115. These nerve fibers grow in size over time and are prominent shortly before birth. Prominent nerve bundles are not present in the frontal skin of wild type or in polled fetuses at any time, indicating that the horn bud is a very sensitive area. The samples from the horn bud region from polled fetuses are histologically equivalent to samples taken from the frontal skin in horned species. This is the first study that presents unique histological data on bovine prenatal horn bud differentiation at different developmental stages which creates knowledge for a better understanding of recent molecular findings.

Gravitational wave background from Standard Model physics: qualitative features

Because of physical processes ranging from microscopic particle collisions to macroscopic hydrodynamic fluctuations, any plasma in thermal equilibrium emits gravitational waves. For the largest wavelengths the emission rate is proportional to the shear viscosity of the plasma. In the Standard Model at 0T > 16 GeV, the shear viscosity is dominated by the most weakly interacting particles, right-handed leptons, and is relatively large. We estimate the order of magnitude of the corresponding spectrum of gravitational waves. Even though at small frequencies (corresponding to the sub-Hz range relevant for planned observatories such as eLISA) this background is tiny compared with that from non-equilibrium sources, the total energy carried by the high-frequency part of the spectrum is non-negligible if the production continues for a long time. We suggest that this may constrain (weakly) the highest temperature of the radiation epoch. Observing the high-frequency part directly sets a very ambitious goal for future generations of GHz-range detectors.

Chow–Liu trees are sufficient predictive models for reproducing key features of functional networks of periictal EEG time-series

Seizure freedom in patients suffering from pharmacoresistant epilepsies is still not achieved in 20–30% of all cases. Hence, current therapies need to be improved, based on a more complete understanding of ictogenesis. In this respect, the analysis of functional networks derived from intracranial electroencephalographic (iEEG) data has recently become a standard tool. Functional networks however are purely descriptive models and thus are conceptually unable to predict fundamental features of iEEG time-series, e.g., in the context of therapeutical brain stimulation. In this paper we present some first steps towards overcoming the limitations of functional network analysis, by showing that its results are implied by a simple predictive model of time-sliced iEEG time-series. More specifically, we learn distinct graphical models (so called Chow–Liu (CL) trees) as models for the spatial dependencies between iEEG signals. Bayesian inference is then applied to the CL trees, allowing for an analytic derivation/prediction of functional networks, based on thresholding of the absolute value Pearson correlation coefficient (CC) matrix. Using various measures, the thus obtained networks are then compared to those which were derived in the classical way from the empirical CC-matrix. In the high threshold limit we find (a) an excellent agreement between the two networks and (b) key features of periictal networks as they have previously been reported in the literature. Apart from functional networks, both matrices are also compared element-wise, showing that the CL approach leads to a sparse representation, by setting small correlations to values close to zero while preserving the larger ones. Overall, this paper shows the validity of CL-trees as simple, spatially predictive models for periictal iEEG data. Moreover, we suggest straightforward generalizations of the CL-approach for modeling also the temporal features of iEEG signals.

Fully automatic GBM segmentation in the TCGA-GBM dataset: Prognosis and correlation with VASARI features.

Reproducible definition and quantification of imaging biomarkers is essential. We evaluated a fully automatic MR-based segmentation method by comparing it to manually defined sub-volumes by experienced radiologists in the TCGA-GBM dataset, in terms of sub-volume prognosis and association with VASARI features. MRI sets of 109 GBM patients were downloaded from the Cancer Imaging archive. GBM sub-compartments were defined manually and automatically using the Brain Tumor Image Analysis (BraTumIA). Spearman's correlation was used to evaluate the agreement with VASARI features. Prognostic significance was assessed using the C-index. Auto-segmented sub-volumes showed moderate to high agreement with manually delineated volumes (range (r): 0.4 - 0.86). Also, the auto and manual volumes showed similar correlation with VASARI features (auto r = 0.35, 0.43 and 0.36; manual r = 0.17, 0.67, 0.41, for contrast-enhancing, necrosis and edema, respectively). The auto-segmented contrast-enhancing volume and post-contrast abnormal volume showed the highest AUC (0.66, CI: 0.55-0.77 and 0.65, CI: 0.54-0.76), comparable to manually defined volumes (0.64, CI: 0.53-0.75 and 0.63, CI: 0.52-0.74, respectively). BraTumIA and manual tumor sub-compartments showed comparable performance in terms of prognosis and correlation with VASARI features. This method can enable more reproducible definition and quantification of imaging based biomarkers and has potential in high-throughput medical imaging research.