The diagnosis of bilateral primary renal paragangliomas in a cat

A 9-year-old sterilised female domestic short-hair cat was referred with a history of vomiting and anorexia of 3 months’ duration. Biochemistry, full-blood counts, thoracic radiographs, feline pancreatic-specific lipase, abdominal ultrasonography and feline immunodeficiency virus/feline leukaemia virus (FIV/FeLV) SNAP tests had been performed. Mild hypochloraemia and moderate hypokalaemia were evident on initial presentation. Abdominal ultrasonography initially revealed unilateral renal nodules on the left side. These were subjected to fine-needle aspiration and cytological evaluation. A neuroendocrine tumour was suspected, and biopsies via midline coeliotomy were taken to confirm the diagnosis. Initial histopathology diagnosed primary renal carcinomas or neuroendocrine neoplasia; however, the definitive diagnosis became renal paragangliomas after immunohistochemistry and transmission electron microscopy were performed. The cat was regularly monitored with serum biochemistry parameters, blood pressure determinations, thoracic radiographs and subsequent abdominal ultrasonography. Biochemistry, radiography and blood pressures remained normal over a 24-week follow-up period, while subsequent ultrasonography revealed tumour progression in both number and size in both kidneys. Primary neuroendocrine tumours of the kidney are frequently incorrectly diagnosed as other renal tumours such as renal cell carcinoma, mesonephric tumours or undifferentiated carcinomas. This case report highlights the importance of additional testing, including immunohistochemistry and transmission electron microscopy, to obtain a definitive diagnosis of paragangliomas.http://www.jsava.co.zaam2017Companion Animal Clinical StudiesParaclinical Science

Numerical models of irrotational binary neutron stars in general relativity

We report on general relativistic calculations of quasiequilibrium configurations of binary neutron stars in circular orbits with zero vorticity. These configurations are expected to represent realistic situations as opposed to corotating configurations. The Einstein equations are solved under the assumption of a conformally flat spatial 3-metric (Wilson-Mathews approximation). The velocity field inside the stars is computed by solving an elliptical equation for the velocity scalar potential. Results are presented for sequences of constant baryon number (evolutionary sequences). Although the central density decreases much less with the binary separation than in the corotating case, it still decreases. Thus, no tendency is found for the stars to individually collapse to black hole prior to merger.Comment: Minor corrections, improved figure, 5 pages, REVTeX, Phys. Rev. Lett. in pres

Do position and species identity of neighbours matter in 8–15-year-old post harvest mesic stands in the boreal mixedwood?

Neighbourhood competition indices (NCI), where position and species identity of neighbours are known, have been used to investigate growth and competitive interactions among adult trees. In this study, we used NCI in 8–15-year-old stands following clear-cutting in a boreal mixedwood forest of eastern Canada to improve our understanding of early successional forest dynamics. Trees of increasing diameter from the center (≥1 cm) to the edge (≥5 cm) were mapped in twenty-five circular 450m2 plots. Target trees (DBH≥1 cm) were sampled in plot center to determine their annual radial stem growth. For each species, we compared a set of growth models using either a spatially explicit NCI or a non-spatial competition index. Both types of indices estimated a species-specific competition coefficient for each pair of competitor–target species. NCI were selected as the best competition model for all target species although differences in variance explained relative to the non-spatial index were small. This likely indicates that competition occurs at the local level but that the high density and the relative uniformity of these young stands creates similar neighbourhoods for most trees in a given stand. The effective neighbourhood radius for competitors varied among species and was smaller for shade tolerant species. Intraspecific neighbours were the strongest competitors for most species. Aspen (Populus tremuloides) was a weak competitor for all species as opposed to balsam fir (Abies balsamea) which was a strong competitor in all cases. These results are in contradiction with some widely used forest policies in North America (e.g. free-to-grow standards) that consider broadleaf species, such as aspen, as the strongest competitors. For these early successional forests, the decision regarding the use of spatial or non-spatial competition indices should rest on the intended use. For even-age management, spatial indices might not justify their use in highdensity stands but they are needed for the simulation of novel harvest techniques creating complex stand structure

Quasiequilibrium sequences of synchronized and irrotational binary neutron stars in general relativity. I. Method and tests

We present a numerical method to compute quasiequilibrium configurations of close binary neutron stars in the pre-coalescing stage. A hydrodynamical treatment is performed under the assumption that the flow is either rigidly rotating or irrotational. The latter state is technically more complicated to treat than the former one (synchronized binary), but is expected to represent fairly well the late evolutionary stages of a binary neutron star system. As regards the gravitational field, an approximation of general relativity is used, which amounts to solving five of the ten Einstein equations (conformally flat spatial metric). The obtained system of partial differential equations is solved by means of a multi-domain spectral method. Two spherical coordinate systems are introduced, one centered on each star; this results in a precise description of the stellar interiors. Thanks to the multi-domain approach, this high precision is extended to the strong field regions. The computational domain covers the whole space so that exact boundary conditions are set to infinity. Extensive tests of the numerical code are performed, including comparisons with recent analytical solutions. Finally a constant baryon number sequence (evolutionary sequence) is presented in details for a polytropic equation of state with gamma=2.Comment: Minor corrections, references updated, 42 pages, 25 PostScript figures, accepted for publication in Phys. Rev.

Topological Defects and CMB anisotropies : Are the predictions reliable ?

We consider a network of topological defects which can partly decay into neutrinos, photons, baryons, or Cold Dark Matter. We find that the degree-scale amplitude of the cosmic microwave background (CMB) anisotropies as well as the shape of the matter power spectrum can be considerably modified when such a decay is taken into account. We conclude that present predictions concerning structure formation by defects might be unreliable.Comment: 14 pages, accepted for publication in PR

Is treat-to-target really working in rheumatoid arthritis? a longitudinal analysis of a cohort of patients treated in daily practice (RA BIODAM).

OBJECTIVES: To investigate whether following a treat-to-target (T2T)-strategy in daily clinical practice leads to more patients with rheumatoid arthritis (RA) meeting the remission target. METHODS: RA patients from 10 countries starting/changing conventional synthetic or biological disease-modifying anti-rheumatic drugs were assessed for disease activity every 3 months for 2 years (RA BIODAM (BIOmarkers of joint DAMage) cohort). Per visit was decided whether a patient was treated according to a T2T-strategy with 44-joint disease activity score (DAS44) remission (DAS44 <1.6) as the target. Sustained T2T was defined as T2T followed in ≥2 consecutive visits. The main outcome was the achievement of DAS44 remission at the subsequent 3-month visit. Other outcomes were remission according to 28-joint disease activity score-erythrocyte sedimentation rate (DAS28-ESR), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI) and American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean definitions. The association between T2T and remission was tested in generalised estimating equations models. RESULTS: In total 4356 visits of 571 patients (mean (SD) age: 56 (13) years, 78% female) were included. Appropriate application of T2T was found in 59% of the visits. T2T (vs no T2T) did not yield a higher likelihood of DAS44 remission 3 months later (OR (95% CI): 1.03 (0.92 to 1.16)), but sustained T2T resulted in an increased likelihood of achieving DAS44 remission (OR: 1.19 (1.03 to 1.39)). Similar results were seen with DAS28-ESR remission. For more stringent definitions (CDAI, SDAI and ACR/EULAR Boolean remission), T2T was consistently positively associated with remission (OR range: 1.16 to 1.29), and sustained T2T had a more pronounced effect on remission (OR range: 1.49 to 1.52). CONCLUSION: In daily clinical practice, the correct application of a T2T-strategy (especially sustained T2T) in patients with RA leads to higher rates of remission

℮-conome: an automated tissue counting platform of cone photoreceptors for rodent models of retinitis pigmentosa

<p>Abstract</p> <p>Background</p> <p>Retinitis pigmentosa is characterized by the sequential loss of rod and cone photoreceptors. The preservation of cones would prevent blindness due to their essential role in human vision. Rod-derived Cone Viability Factor is a thioredoxin-like protein that is secreted by rods and is involved in cone survival. To validate the activity of Rod-derived Cone Viability Factors (RdCVFs) as therapeutic agents for treating retinitis Pigmentosa, we have developed e-conome, an automated cell counting platform for retinal flat mounts of rodent models of cone degeneration. This automated quantification method allows for faster data analysis thereby accelerating translational research.</p> <p>Methods</p> <p>An inverted fluorescent microscope, motorized and coupled to a CCD camera records images of cones labeled with fluorescent peanut agglutinin lectin on flat-mounted retinas. In an average of 300 fields per retina, nine Z-planes at magnification X40 are acquired after two-stage autofocus individually for each field. The projection of the stack of 9 images is subject to a threshold, filtered to exclude aberrant images based on preset variables. The cones are identified by treating the resulting image using 13 variables empirically determined. The cone density is calculated over the 300 fields.</p> <p>Results</p> <p>The method was validated by comparison to the conventional stereological counting. The decrease in cone density in <it>rd1 </it>mouse was found to be equivalent to the decrease determined by stereological counting. We also studied the spatiotemporal pattern of the degeneration of cones in the <it>rd1 </it>mouse and show that while the reduction in cone density starts in the central part of the retina, cone degeneration progresses at the same speed over the whole retinal surface. We finally show that for mice with an inactivation of the Nucleoredoxin-like genes <it>Nxnl1 </it>or <it>Nxnl2 </it>encoding RdCVFs, the loss of cones is more pronounced in the ventral retina.</p> <p>Conclusion</p> <p>The automated platform ℮-conome used here for retinal disease is a tool that can broadly accelerate translational research for neurodegenerative diseases.</p

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN