Effects of Prolonged Intravenous Flunixin Meglumine in Healthy Dogs

This study was designed to evaluate possible side effects on liver and kidney functions and haematological indices, associated with long-term intravenous (IV) administration of flunixin meglumine in healthy dogs. For this purpose, 12 dogs were divided into 2 equal groups. Group 1 was intravenously given flunixin meglumine at the dose of 1.1 mg/kg/day for 5 days and g-roup 11 received 2.2 mg/kg/day IV for 5 days. Blood samples were withdrawn before treatment (day 0), 2 h post injection on each day of treatment and one day after the last injection for biochemical (glucose, sodium-Na, potassium-K, chloride-Cl, creatinine, urea, alkaline phosphatase-AP, alanine amino transferase-ALT and total protein) and haematological (bleeding time, coagulation time, red blood cell, white blood cell, platelet count, differential leukocyte count, haematocrit and haemoglobin) analyses. Faecal and urine samples were collected on the same days as blood samples for the presence of any abnormalities. The results revealed a significant increase in bleeding (P < 0.001) and coagulation time (P < 0.001) and a decrease in platelet count (P < 0.001) in both groups. There was also a significant increase in the concentration of Na and Cl in group 1 and an elevation in AP (P < 0.00 07 ALT (P < 0.001) and glucose (P < 0.001) in group II. Blood in urine and faeces was also evident in both groups. The results may suggest that the dose of 1.1 mg/kg IV for 5 d does not cause any significant side effects provided that no bleeding disorder exists. and the dose of 2.2 mg/kg IV for 5 d should not exceed 3 d as liver enzymes began to increase significantly afterwards

Measurement and physical interpretation of the mean motion of turbulent density patterns detected by the BES system on MAST

The mean motion of turbulent patterns detected by a two-dimensional (2D) beam emission spectroscopy (BES) diagnostic on the Mega Amp Spherical Tokamak (MAST) is determined using a cross-correlation time delay (CCTD) method. Statistical reliability of the method is studied by means of synthetic data analysis. The experimental measurements on MAST indicate that the apparent mean poloidal motion of the turbulent density patterns in the lab frame arises because the longest correlation direction of the patterns (parallel to the local background magnetic fields) is not parallel to the direction of the fastest mean plasma flows (usually toroidal when strong neutral beam injection is present). The experimental measurements are consistent with the mean motion of plasma being toroidal. The sum of all other contributions (mean poloidal plasma flow, phase velocity of the density patterns in the plasma frame, non-linear effects, etc.) to the apparent mean poloidal velocity of the density patterns is found to be negligible. These results hold in all investigated L-mode, H-mode and internal transport barrier (ITB) discharges. The one exception is a high-poloidal-beta (the ratio of the plasma pressure to the poloidal magnetic field energy density) discharge, where a large magnetic island exists. In this case BES detects very little motion. This effect is currently theoretically unexplained.Comment: 28 pages, 15 figures, submitted to PPC

Diagnostic and prognostic role of TFF3, Romo-1, NF-кB and SFRP4 as biomarkers for endometrial and ovarian cancers: a prospective observational translational study

Purpose: This study aimed to evaluate trefoil factor 3 (TFF3), secreted frizzled-related protein 4 (sFRP4), reactive oxygen species modulator 1 (Romo1) and nuclear factor kappa B (NF-κB) as diagnostic and prognostic markers of endometrial cancer (EC) and ovarian cancer (OC). Methods: Thirty-one patients with EC and 30 patients with OC undergone surgical treatment were enrolled together with 30 healthy controls in a prospective study. Commercial ELISA kits determined serum TFF-3, Romo-1, NF-кB and sFRP-4 concentrations. Results: Serum TFF-3, Romo-1 and NF-кB levels were significantly higher in patients with EC and OC than those without cancer. Regarding EC, none of the serum biomarkers differs significantly between endometrial and non-endometrioid endometrial carcinomas. Mean serum TFF-3 and NF-кB levels were significantly higher in advanced stages. Increased serum levels of TFF-3 and NF-кB were found in those with a higher grade of the disease. Regarding OC, none of the serum biomarkers differed significantly among histological subtypes. Significantly increased serum levels of NF-кB were observed in patients with advanced-stage OC than those with stage I and II diseases. No difference in serum biomarker levels was found between those who had a recurrence and those who had not. The sensibility and specificity of these four biomarkers in discriminating EC and OC from the control group showed encouraging values, although no one reached 70%. Conclusions: TFF-3, Romo-1, NF-кB and SFRP4 could represent new diagnostic and prognostic markers for OC and EC. Further studies are needed to validate our results

Analysis of Mutations in AARS2 in a Series of CSF1R-Negative Patients With Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia

IMPORTANCE: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a frequent cause of adult-onset leukodystrophy known to be caused by autosomal dominant mutations in the CSF1R (colony-stimulating factor 1) gene. The discovery that CSF1R mutations cause ALSP led to more accurate prognosis and genetic counseling for these patients in addition to increased interest in microglia as a target in neurodegeneration. However, it has been known since the discovery of the CSF1R gene that there are patients with typical clinical and radiologic evidence of ALSP who do not carry pathogenic CSF1R mutations. These patients include those in whom the pathognomonic features of axonal spheroids and pigmented microglia have been found. Achieving a genetic diagnosis in these patients is important to our understanding of this disorder. OBJECTIVE: To genetically characterize a group of patients with typical features of ALSP who do not carry CSF1R mutations. DESIGN, SETTING, AND PARTICIPANTS: In this case series study, 5 patients from 4 families were identified with clinical, radiologic, or pathologic features of ALSP in whom CSF1R mutations had been excluded previously by sequencing. Data were collected between May 2014 and September 2015 and analyzed between September 2015 and February 2016. MAIN OUTCOMES AND MEASURES: Focused exome sequencing was used to identify candidate variants. Family studies, long-range polymerase chain reaction with cloning, and complementary DNA sequencing were used to confirm pathogenicity. RESULTS: Of these 5 patients, 4 were men (80%); mean age at onset of ALSP was 29 years (range, 15-44 years). Biallelic mutations in the alanyl-transfer (t)RNA synthetase 2 (AARS2) gene were found in all 5 patients. Frameshifting and splice site mutations were common, found in 4 of 5 patients, and sequencing of complementary DNA from affected patients confirmed that the variants were loss of function. All patients presented in adulthood with prominent cognitive, neuropsychiatric, and upper motor neuron signs. Magnetic resonance imaging in all patients demonstrated a symmetric leukoencephalopathy with punctate regions of restricted diffusion, typical of ALSP. In 1 patient, brain biopsy demonstrated axonal spheroids and pigmented microglia, which are the pathognomonic signs of ALSP. CONCLUSIONS AND RELEVANCE: This work indicates that mutations in the tRNA synthetase AARS2 gene cause a recessive form of ALSP. The CSF1R and AARS2 proteins have different cellular functions but overlap in a final common pathway of neurodegeneration. This work points to novel targets for research and will lead to improved diagnostic rates in patients with adult-onset leukoencephalopathy

Novel insights into host-fungal pathogen interactions derived from live-cell imaging

Acknowledgments The authors acknowledge funding from the Wellcome Trust (080088, 086827, 075470 and 099215) including a Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377 and FP7-2007–2013 grant agreement HEALTH-F2-2010-260338–ALLFUN to NARG.Peer reviewedPublisher PD

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE

Measurement of the Z/gamma* + b-jet cross section in pp collisions at 7 TeV

The production of b jets in association with a Z/gamma* boson is studied using proton-proton collisions delivered by the LHC at a centre-of-mass energy of 7 TeV and recorded by the CMS detector. The inclusive cross section for Z/gamma* + b-jet production is measured in a sample corresponding to an integrated luminosity of 2.2 inverse femtobarns. The Z/gamma* + b-jet cross section with Z/gamma* to ll (where ll = ee or mu mu) for events with the invariant mass 60 < M(ll) < 120 GeV, at least one b jet at the hadron level with pT > 25 GeV and abs(eta) < 2.1, and a separation between the leptons and the jets of Delta R > 0.5 is found to be 5.84 +/- 0.08 (stat.) +/- 0.72 (syst.) +(0.25)/-(0.55) (theory) pb. The kinematic properties of the events are also studied and found to be in agreement with the predictions made by the MadGraph event generator with the parton shower and the hadronisation performed by PYTHIA.Comment: Submitted to the Journal of High Energy Physic