Despite being first described 45 years ago, the existence of a distinct diabetic cardiomyopathy remains controversial. Nonetheless, it is widely accepted that the diabetic heart undergoes characteristic structural and functional changes in the absence of ischaemia and hypertension, which are independently linked to heart failure progression and are likely to underlie enhanced susceptibility to stress. A prominent feature is marked collagen accumulation linked with inflammation and extensive extracellular matrix changes, which appears to be the main factor underlying cardiac stiffness and subclinical diastolic dysfunction, estimated to occur in as many as 75% of optimally controlled diabetics. Whether this characteristic remodelling phenotype is primarily driven by microvascular dysfunction or alterations in cardiomyocyte metabolism remains unclear. Although hyperglycaemia regulates multiple pathways in the diabetic heart, increased reactive oxygen species (ROS) generation is thought to represent a central mechanism underlying associated adverse remodelling. Indeed, experimental and clinical diabetes are linked with oxidative stress which plays a key role in cardiomyopathy, while key processes underlying diabetic cardiac remodelling, such as inflammation, angiogenesis, cardiomyocyte hypertrophy and apoptosis, fibrosis and contractile dysfunction, are redox sensitive. This review will explore the relative contributions of the major ROS sources (dysfunctional nitric oxide synthase, mitochondria, xanthine oxidase, nicotinamide adenine dinucleotide phosphate oxidases) in the diabetic heart and the potential for therapeutic targeting of ROS signalling using novel pharmacological and non-pharmacological approaches to modify specific aspects of the remodelling phenotype in order to prevent and/or delay heart failure development and progression.

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BACKGROUND Heart rate follows a diurnal variation, and slow heart rhythms occur primarily at night.

MANNER‐NPK (MANure Nutrient Evaluation Routine) is a decision support tool for quantifying manure (and other organic material) crop available nutrient supply. The user‐friendly design of an earlier version of MANNER was retained, but in response to user and stakeholder feedback, additional functionality was included to underpin new and revised nitrogen (N) transformation/loss modules (covering ammonia volatilization, nitrate leaching and nitrous oxide/di‐nitrogen emissions, and organic N mineralization) and also to estimate manure phosphorus (as P2O5), potassium (as K2O), sulphur (as SO3) and magnesium (as MgO) supply. Notably, MANNER‐NPK provides N availability estimates for following crops through the mineralization of organic N. Validation of the crop available N supply estimates was undertaken by comparing predicted values with data from more than 200 field experimental measurements. For cattle, pig and poultry manures, there was good agreement (P < 0.001) between predicted and measured fertilizer N replacement values, indicating that MANNER‐NPK provides robust estimates of manure crop available N supply and N losses to the wider environment.

The paper gives the results of calorimetric measurements of the heat capacities of solid and liquid CH4 and CD4, the heats of fusion of both substances and the heat of vaporization of CD4. The results for the solids, which extend from 2.3°K to the triple points, are analyzed in some detail. In order to account for the apparent zero-point entropies of both CH4 and CD4 quantitatively, it is necessary to recognize the existence of different nuclear spin species (as with ortho and para hydrogen) and to say that, as T approaches 0°K, each species tends to occupy its lowest available molecular energy level. No conversion between the different species has been observed. The relevance of these findings to the usual applications of the third law of thermodynamics is discussed. The thermal transitions which occur in solid CH4 and CD4 (as well as in the partially deuterated methanes) have also been examined and an attempt made to correlate the thermodynamic results with information derived from other experiments (e.g., spectroscopic, neutron scattering) and from theory. While correlations are possible, the fundamental causes of the transitions can still not be established.

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Articles you may be interested inTheory of phase transitions in solid methanes. XIII. The differential neutron scattering cross section in phase II of solid CH4Theory of phase transitions in solid methanes. XI. Infrared and Raman spectra of the ν3 and ν4 modes in phase II of solid CH4 Letters to the Editor 1 HE Letters to the Editor section is subdivided into three parts entitled Communications, Comments and Errata, andNotes. These three sections are all subject to the same limitations on length. The textual malerial of each Leiter is limited to a number of words equal to 950 minus the following: (a) zoo words for each average-sized figure; (b) 50 words for each displayed equation; (c) 7

Background and purpose: Radiation-induced cardiac toxicity (RICT) remains one of the most critical dose limiting constraints in radiotherapy. Recent studies have shown higher doses to the base of the heart are associated with worse overall survival in lung cancer patients receiving radiotherapy. This work aimed to investigate the impact of sub-volume heart irradiation in a mouse model using small animal image-guided radiotherapy.Materials and Methods: C57BL/6 mice were irradiated with a single fraction of 16 Gy to the base, middle or apex of the heart using a small animal radiotherapy research platform. Cone beam CT and echocardiography were performed at baseline and at 10 week intervals until 50 weeks post-treatment. Structural and functional parameters were correlated with mean heart dose (MHD) and volume of heart receiving 5 Gy (V5).Results: All irradiated mice showed a time dependent increase in left ventricle wall thickness in diastole of ~0.2 mm detected at 10 weeks post-treatment, with the most significant and persistent changes occurring in the heart base-irradiated animals. Similarly, statistically different functional effects (p<0.01) were observed in base-irradiated animals which showed the most significant decreases compared to controls. The observed functional changes did not correlate with MHD and V5 (R 2 <0.1), indicating that whole heart dosimetry parameters do not predict physiological changes resulting from cardiac sub-volume irradiation.Conclusions: This is the first report demonstrating the structural and functional consequences of sub-volume targeting in the mouse heart and reverse translates clinical observations indicating the heart base as a critical radiosensitive region.