Doses for Laboratory Animals based on Metabolic Rate

The differences in metabolic rates (M) of different mammals often make it difficult to estimate the dose of e.g. anaesthetics from one species to another. It is well known that the mammalian metabolic rate is correlated to the body weight (W), and the relationship between body weight and metabolic rate kan be expressed using the equation:(1) M = 3.8 x W-25Using the assumption, that the dose of e.g. an anaesthetic only depends on the metabolic rate of the animal, a simple mathematic equation can be used in scaling the dose from one species to another: As an example the equation is employed for the calculation of the doses of pentobarbital for a series of different mammals of different size. The calculated doses agree well with the doses reported in the literature. The equation may be of generel usefulness for a quick calculation of a suitable dose level, when the dose level of another species is known

Magnetic tight-binding and the iron-chromium enthalpy anomaly

We describe a self consistent magnetic tight-binding theory based in an expansion of the Hohenberg-Kohn density functional to second order, about a non spin polarised reference density. We show how a first order expansion about a density having a trial input magnetic moment leads to the Stoner--Slater rigid band model. We employ a simple set of tight-binding parameters that accurately describes electronic structure and energetics, and show these to be transferable between first row transition metals and their alloys. We make a number of calculations of the electronic structure of dilute Cr impurities in Fe which we compare with results using the local spin density approximation. The rigid band model provides a powerful means for interpreting complex magnetic configurations in alloys; using this approach we are able to advance a simple and readily understood explanation for the observed anomaly in the enthalpy of mixing.Comment: Submitted to Phys Rev

Fate and transport of volatile organic compounds in glacial till and groundwater at an industrial site in Northern Ireland

Volatile organic compound (VOC) contamination of subsurface geological material and groundwater was discovered on the Nortel Monkstown industrial site, Belfast, Northern Ireland. The objectives of this study were to (1) investigate the characteristics of the geological material and its influences on contaminated groundwater flow across the site using borehole logs and hydrological evaluations, and (2) identify the contaminants and examine their distribution in the subsurface geological material and groundwater using chemical analysis. This report focuses on the eastern car park (ECP) which was a former storage area associated with trichloroethene (TCE) degreasing operations. This is where the greatest amount of volatile organic compounds (VOCs), particularly TCE, were detected. The study site is on a complex deposit of clayey glacial till with discontinuous coarser grained lenses, mainly silts, sands and gravel, which occur at 0.45-7.82 m below ground level (bgl). The lenses overall form an elongated formation that acts as a small unconfined shallow aquifer. There is a continuous low permeable stiff clayey till layer beneath the lenses that performs as an aquitard to the groundwater. Highest concentrations of VOCs, mainly TCE, in the geological material and groundwater are in these coarser lenses at similar to 4.5-7 m bgl. Highest TCE measurements at 390,000 mu g L-1 for groundwater and at 39,000 mu g kg(-1) at 5.7 m for geological material were in borehole GA19 in the coarse lens zone. It is assumed that TCE gained entrance to the subsurface near this borehole where the clayey till was thin to absent above coarse lenses which provided little retardation to the vertical migration of this dense non-aqueous phase liquid (DNAPL) into the groundwater. However, TCE is present in low concentrations in the geological material overlying the coarse lens zone. Additionally, VOCs appear to be associated with poorly drained layers and in peat < 3.0 m bgl in the ECP. Some indication of natural attenuation as VOCs degradation products vinyl chloride (VC) and dichloromethane (DCM) also occur on the site

Investing in Prevention or Paying for Recovery - Attitudes to Cyber Risk

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Broadly speaking an individual can invest time and effort to avoid becoming victim to a cyber attack and/or they can invest resource in recovering from any attack. We introduce a new game called the pre-vention and recovery game to study this trade-off. We report results from the experimental lab that allow us to categorize different approaches to risk taking. We show that many individuals appear relatively risk loving in that they invest in recovery rather than prevention. We find little difference in behavior between a gain and loss framing

Impact of rs361072 in the Phosphoinositide 3-Kinase p110β Gene on Whole-Body Glucose Metabolism and Subunit Protein Expression in Skeletal Muscle

OBJECTIVE-Phosphoinositide 3-kinase (PI3K) is a major effector in insulin signaling. rs361072, located in the promoter of the gene (PIK3CB) for the p110 beta subunit, has previously been found to be associated with homeostasis model assessment for insulin resistance (HOMA-IR) in obese subjects. The aim was to investigate the influence of rs361072 on in vivo glucose metabolism, skeletal muscle PI3K subunit protein levels, and type 2 diabetes. RESEARCH DESIGN AND METHODS-The functional role of rs361072 was studied in 196 Danish healthy adult twins. Peripheral and hepatic insulin sensitivity was assessed by a euglycemic-hyperinsulinemic clamp. Basal and insulin-stimulated biopsies were taken from the vastus lateralis muscle, and tissue p110 beta and p85 alpha proteins were measured by Western blotting. The genetic association with type 2 diabetes and quantitative metabolic traits was investigated in 9,316 Danes with glucose tolerance ranging from normal to overt type 2 diabetes. RESULTS-While hepatic insulin resistance was similar in the fasting state, carriers of the minor G allele had lower hepatic glucose output (per-allele effect: 16%, P-add = 0.004) during high physiological insulin infusion. rs361072 did not associate with insulin-stimulated peripheral glucose disposal despite a decreased muscle p85 alpha:p110 beta protein ratio (P-add = 0.03) in G allele carriers. No association with HOMA-IR or type 2 diabetes (odds ratio 1.07, P = 0.5) was identified, and obesity did not interact with rs361072 on these traits. CONCLUSIONS-Our study suggests that the minor G allele of PIK3CB rs361072 associates with decreased muscle p85 alpha:p110 beta ratio and lower hepatic glucose production at high plasma insulin levels. However, no impact on type 2 diabetes prevalence was found. Diabetes 59:1108-1112, 201

Effects of Renal Denervation on Insulin Sensitivity and Inflammatory Markers in Nondiabetic Patients with Treatment-Resistant Hypertension

Increased sympathetic activity is important in the pathogenesis of hypertension and insulin resistance. Afferent signaling from the kidneys elevates the central sympathetic drive. We investigated the effect of catheter-based renal sympathetic denervation (RDN) on glucose metabolism, inflammatory markers, and blood pressure in nondiabetic patients with treatment-resistant hypertension. Eight subjects were included in an open-labelled study. Each patient was studied before and 6 months after RDN. Endogenous glucose production was assessed by a 3-3H glucose tracer, insulin sensitivity was examined by hyperinsulinemic euglycemic clamp, hormones and inflammatory markers were analyzed, and blood pressure was measured by office blood pressure readings and 24-hour ambulatory blood pressure monitoring. Insulin sensitivity (M-value) increased nonsignificantly from 2.68 ± 0.28 to 3.07 ± 0.41 (p=0.12). A significant inverse correlation between the increase in M-value and BMI 6 months after RDN (p=0.03) was found, suggesting beneficial effects on leaner subjects. Blood pressure decreased significantly, but there were no changes in hormones, inflammatory markers, or endogenous glucose production. Our results indicate that RDN may improve insulin sensitivity in some patients with treatment-resistant hypertension, albeit confirmation of these indications of beneficial effects on leaner subjects awaits the outcome of larger randomized controlled studies