Species Preference Influences on Cattle Grazing Behaviour

Lotus corniculatus offers specific nutritional benefits to animals, but exploiting these advantages in grazing systems depends on the proportion of lotus in the feed offered and the animals\u27 preference, hence desire to select for it. To determine preference for lotus, heifers were offered free-choice in contrasting, spatially separated but adjacent monocultures of ryegrass-lotus or red clover-lotus. Following a one-week period to adjust to the species offered and their arrangement, 10 young heifers were observed at 10-minute intervals during daylight hours, and the species they were on and whether or not they were grazing was recorded. This procedure was conducted in summer (February) and autumn (May). Partial preference was determined from the proportion of time spent grazing each species. Preference for lotus was higher when the alternative species was ryegrass, than when it was red clover, in both summer (75:25 vs 53:47) and autumn (67:33 vs 54:46), although this preference for lotus in the ryegrass-lotus contrast reduced in autumn compared with that exhibited in summer. Total grazing time, which was similar for each contrast, was lower in autumn (6 hrs) than in summer (9 hrs). For the ryegrass-lotus contrast, the reduced grazing time in autumn resulted from reduced time grazing lotus, whereas on the red clover-lotus contrast they reduced grazing time equally on both species

Stage-specific action of matrix metalloproteinases influences progressive hereditary kidney disease.

BackgroundGlomerular basement membrane (GBM), a key component of the blood-filtration apparatus in the in the kidney, is formed through assembly of type IV collagen with laminins, nidogen, and sulfated proteoglycans. Mutations or deletions involving alpha3(IV), alpha4(IV), or alpha5(IV) chains of type IV collagen in the GBM have been identified as the cause for Alport syndrome in humans, a progressive hereditary kidney disease associated with deafness. The pathological mechanisms by which such mutations lead to eventual kidney failure are not completely understood.Methods and findingsWe showed that increased susceptibility of defective human Alport GBM to proteolytic degradation is mediated by three different matrix metalloproteinases (MMPs)--MMP-2, MMP-3, and MMP-9--which influence the progression of renal dysfunction in alpha3(IV)-/- mice, a model for human Alport syndrome. Genetic ablation of either MMP-2 or MMP-9, or both MMP-2 and MMP-9, led to compensatory up-regulation of other MMPs in the kidney glomerulus. Pharmacological ablation of enzymatic activity associated with multiple GBM-degrading MMPs, before the onset of proteinuria or GBM structural defects in the alpha3(IV)-/- mice, led to significant attenuation in disease progression associated with delayed proteinuria and marked extension in survival. In contrast, inhibition of MMPs after induction of proteinuria led to acceleration of disease associated with extensive interstitial fibrosis and early death of alpha3(IV)-/- mice.ConclusionsThese results suggest that preserving GBM/extracellular matrix integrity before the onset of proteinuria leads to significant disease protection, but if this window of opportunity is lost, MMP-inhibition at the later stages of Alport disease leads to accelerated glomerular and interstitial fibrosis. Our findings identify a crucial dual role for MMPs in the progression of Alport disease in alpha3(IV)-/- mice, with an early pathogenic function and a later protective action. Hence, we propose possible use of MMP-inhibitors as disease-preventive drugs for patients with Alport syndrome with identified genetic defects, before the onset of proteinuria

A Comparison of DSM-IV and DSM-5 Panel Members' Financial Associations with Industry: A Pernicious Problem Persists

Lisa Cosgrove and Sheldon Krimsky examine the new competing interest disclosure policy of the American Psychiatric Association (APA) and report that DSM panel members still have considerable financial conflicts of interest

Killing tensors in pp-wave spacetimes

The formal solution of the second order Killing tensor equations for the general pp-wave spacetime is given. The Killing tensor equations are integrated fully for some specific pp-wave spacetimes. In particular, the complete solution is given for the conformally flat plane wave spacetimes and we find that irreducible Killing tensors arise for specific classes. The maximum number of independent irreducible Killing tensors admitted by a conformally flat plane wave spacetime is shown to be six. It is shown that every pp-wave spacetime that admits an homothety will admit a Killing tensor of Koutras type and, with the exception of the singular scale-invariant plane wave spacetimes, this Killing tensor is irreducible.Comment: 18 page

Canonical Quantization of the Gowdy Model

The family of Gowdy universes with the spatial topology of a three-torus is studied both classically and quantum mechanically. Starting with the Ashtekar formulation of Lorentzian general relativity, we introduce a gauge fixing procedure to remove almost all of the non-physical degrees of freedom. In this way, we arrive at a reduced model that is subject only to one homogeneous constraint. The phase space of this model is described by means of a canonical set of elementary variables. These are two real, homogeneous variables and the Fourier coefficients for four real fields that are periodic in the angular coordinate which does not correspond to a Killing field of the Gowdy spacetimes. We also obtain the explicit expressions for the line element and reduced Hamiltonian. We then proceed to quantize the system by representing the elementary variables as linear operators acting on a vector space of analytic functionals. The inner product on that space is selected by imposing Lorentzian reality conditions. We find the quantum states annihilated by the operator that represents the homogeneous constraint of the model and construct with them the Hilbert space of physical states. Finally, we derive the general form of the quantum observables of the model.Comment: 13 pages, Revte

Stage-Specific Action of Matrix Metalloproteinases Influences Progressive Hereditary Kidney Disease

Background: Glomerular basement membrane (GBM), a key component of the blood-filtration apparatus in the in the kidney, is formed through assembly of type IV collagen with laminins, nidogen, and sulfated proteoglycans. Mutations or deletions involving $\alpha$3(IV), $\alpha$4(IV), or $\alpha$5(IV) chains of type IV collagen in the GBM have been identified as the cause for Alport syndrome in humans, a progressive hereditary kidney disease associated with deafness. The pathological mechanisms by which such mutations lead to eventual kidney failure are not completely understood. Methods and Findings: We showed that increased susceptibility of defective human Alport GBM to proteolytic degradation is mediated by three different matrix metalloproteinases (MMPs)—MMP-2, MMP-3, and MMP-9—which influence the progression of renal dysfunction in $\alpha 3(IV)^{−/−}$ mice, a model for human Alport syndrome. Genetic ablation of either MMP-2 or MMP-9, or both MMP-2 and MMP-9, led to compensatory up-regulation of other MMPs in the kidney glomerulus. Pharmacological ablation of enzymatic activity associated with multiple GBM-degrading MMPs, before the onset of proteinuria or GBM structural defects in the $\alpha 3(IV)^{−/−}$ mice, led to significant attenuation in disease progression associated with delayed proteinuria and marked extension in survival. In contrast, inhibition of MMPs after induction of proteinuria led to acceleration of disease associated with extensive interstitial fibrosis and early death of $\alpha$3(IV)−/− mice. Conclusions: These results suggest that preserving GBM/extracellular matrix integrity before the onset of proteinuria leads to significant disease protection, but if this window of opportunity is lost, MMP-inhibition at the later stages of Alport disease leads to accelerated glomerular and interstitial fibrosis. Our findings identify a crucial dual role for MMPs in the progression of Alport disease in $\alpha 3(IV)^{−/−}$ mice, with an early pathogenic function and a later protective action. Hence, we propose possible use of MMP-inhibitors as disease-preventive drugs for patients with Alport syndrome with identified genetic defects, before the onset of proteinuria

Physically Realistic Solutions to the Ernst Equation on Hyperelliptic Riemann Surfaces

We show that the class of hyperelliptic solutions to the Ernst equation (the stationary axisymmetric Einstein equations in vacuum) previously discovered by Korotkin and Neugebauer and Meinel can be derived via Riemann-Hilbert techniques. The present paper extends the discussion of the physical properties of these solutions that was begun in a Physical Review Letter, and supplies complete proofs. We identify a physically interesting subclass where the Ernst potential is everywhere regular except at a closed surface which might be identified with the surface of a body of revolution. The corresponding spacetimes are asymptotically flat and equatorially symmetric. This suggests that they could describe the exterior of an isolated body, for instance a relativistic star or a galaxy. Within this class, one has the freedom to specify a real function and a set of complex parameters which can possibly be used to solve certain boundary value problems for the Ernst equation. The solutions can have ergoregions, a Minkowskian limit and an ultrarelativistic limit where the metric approaches the extreme Kerr solution. We give explicit formulae for the potential on the axis and in the equatorial plane where the expressions simplify. Special attention is paid to the simplest non-static solutions (which are of genus two) to which the rigidly rotating dust disk belongs.Comment: 32 pages, 2 figures, uses pstricks.sty, updated version (October 7, 1998), to appear in Phys. Rev.

Imaging biomarkers of adiposity and sarcopenia as potential predictors for overall survival among patients with endometrial cancer treated with bevacizumab

Objective:To examine associations of body mass index (BMI), subcutaneous fat area (SFA) and density (SFD), visceral fat area (VFA) and density (VFD) and total psoas area (TPA) to outcomes among patients receiving chemotherapy with or without bevacizumab for advanced or recurrent endometrial cancer (EC). Methods:This was a multi-institutional, retrospective study of patients with EC treated with and without bevacizumab as part of front-line, platinum based chemotherapy. Demographics and clinical characteristics were collected. SFA, VFA, SFD, VFD, and TPA were determined from pre-treatment CT scans using a deep learning algorithm. Data was compared with overall survival (OS) and progression free survival (PFS). Results:Seventy-eight patients were analyzed. The majority were Caucasian (87.2%) with a mean BMI of 34.7 kg/m2. PFS and OS did not differ between patients with BMI, SFA, VFA, SFD, VFD, or TPA ≥ the 50th percentile compared to <50th percentile (p = 0.91, 0.45, 0.71, 0.74, 0.60, and 0.74 respectively) and (p = 0.99, 0.59, 0.14, 0.77, and 0.85 respectively). When adjusting for prognostic factors, elevated VFA trended towards shorter OS (25.1 vs 59.5 months, HR = 1.68 [0.92-3.05]).Patients receiving bevacizumab had similar OS compared to those who did not (37.6 vs 44.5 months, p = 0.409). When stratified by adiposity markers, no subset demonstrated benefit from bevacizumab. Conclusion:Obesity has been associated with increased levels of vascular endothelial growth factor (VEGF), the main target for bevacizumab therapy. Imaging measurements of VFA may provide prognostic information for patients with EC but no adiposity marker was predictive of improved response to bevacizumab

Fluoroquinolones and isoniazid-resistant tuberculosis: implications for the 2018 WHO guidance.

INTRODUCTION: 2018 World Health Organization (WHO) guidelines for the treatment of isoniazid (H)-resistant (Hr) tuberculosis recommend a four-drug regimen: rifampicin (R), ethambutol (E), pyrazinamide (Z) and levofloxacin (Lfx), with or without H ([H]RZE-Lfx). This is used once Hr is known, such that patients complete 6 months of Lfx (≥6[H]RZE-6Lfx). This cohort study assessed the impact of fluoroquinolones (Fq) on treatment effectiveness, accounting for Hr mutations and degree of phenotypic resistance. METHODS: This was a retrospective cohort study of 626 Hr tuberculosis patients notified in London, 2009-2013. Regimens were described and logistic regression undertaken of the association between regimen and negative regimen-specific outcomes (broadly, death due to tuberculosis, treatment failure or disease recurrence). RESULTS: Of 594 individuals with regimen information, 330 (55.6%) were treated with (H)RfZE (Rf=rifamycins) and 211 (35.5%) with (H)RfZE-Fq. The median overall treatment period was 11.9 months and median Z duration 2.1 months. In a univariable logistic regression model comparing (H)RfZE with and without Fqs, there was no difference in the odds of a negative regimen-specific outcome (baseline (H)RfZE, cluster-specific odds ratio 1.05 (95% CI 0.60-1.82), p=0.87; cluster NHS trust). Results varied minimally in a multivariable model. This odds ratio dropped (0.57, 95% CI 0.14-2.28) when Hr genotype was included, but this analysis lacked power (p=0.42). CONCLUSIONS: In a high-income setting, we found a 12-month (H)RfZE regimen with a short Z duration to be similarly effective for Hr tuberculosis with or without a Fq. This regimen may result in fewer adverse events than the WHO recommendations