Lipase inhibition attenuates the acute inhibitory effects of oral fat on food intake in healthy subjects

The lipase inhibitor, orlistat, is used in the treatment of obesity and reduces fat absorption by about 30%. However, the mean weight loss induced by orlistat is less than expected for the degree of fat malabsorption. It was hypothesised that lipase inhibition with orlistat attenuates the suppressive effects of oral fat on subsequent energy intake in normal-weight subjects. Fourteen healthy, lean subjects (nine males, five females; aged 25 +/- 1.3 years) were studied twice, in a double-blind fashion. The subjects received a high-fat yoghurt 'preload' (males 400 g (2562 kJ); females 300 g (1923 kJ)), containing orlistat (120 mg) on one study day (and no orlistat on the other 'control' day), 30 min before ad libitum access to food and drinks; energy intake was assessed during the following 8 h. Blood samples were taken at regular intervals for the measurement of plasma cholecystokinin (CCK). Each subject performed a 3 d faecal fat collection following each study. Energy intake during the day was greater following orlistat (10,220 (SEM 928) kJ) v. control (9405 (SEM 824) kJ) (P=0.02). On both days plasma CCK increased (P<0.05) after the preload. Plasma CCK 20 min following ingestion of the preload was less after orlistat (4.1 (SEM 0.9) pmol/l) v. control (5.3 (SEM 0.9) pmol/l (P=0.028); however there was no difference in the area under the curve 0-510 min between the two study days. Fat excretion was greater following orlistat (1017 (SEM 168) kJ) v. control (484 (SEM 90) kJ) (P=0.004). In conclusion, in healthy, lean subjects the acute inhibitory effect of fat on subsequent energy intake is attenuated by orlistat and the increase in energy intake approximates the energy lost due to fat malabsorption.Deirdre O’Donovan, Christine Feinle-Bisset, Judith Wishart and Michael Horowit

Labour efficiency on-farm

End of project reportImprovements in milking efficiency have a greater influence than any other aspect of the dairy farmers work on overall farm labour inputs (Whipp, 1992). In order to facilitate the examination of milking process labour inputs, the milking process may be divided into the following three components: herding pre and post milking (transfer of cows to and from the milking parlour); milking (milking tasks / work routines within the parlour); and washing (washing of milking machine and yard). Meanwhile, within milking specifically, the number of cows milked per operator per hour is the best measure of both the performance of the operator and the milking installation (Clough, 1978). This is affected by the following three factors: the milking times of the cows, the number and arrangement of the milking units, and the operator’s work routine (Whipp, 1992). The addition of extra milking units will only increase milking performance if the operator has idle time during milking (Hansen, 1999)

An a priori investigation of astrophysical false positives in ground-based transiting planet surveys

Astrophysical false positives due to stellar eclipsing binaries pose one of the greatest challenges to ground-based surveys for transiting Hot Jupiters. We have used known properties of multiple star systems and Hot Jupiter systems to predict, a priori, the number of such false detections and the number of genuine planet detections recovered in two hypothetical but realistic ground-based transit surveys targeting fields close to the galactic plane (b~10 degrees): a shallow survey covering a magnitude range 10<V<13, and a deep survey covering a magnitude range 15<V<19. Our results are consistent with the commonly-reported experience of false detections outnumbering planet detections by a factor of ~10 in shallow surveys, while in our synthetic deep survey we find ~1-2 false detections for every planet detection. We characterize the eclipsing binary configurations that are most likely to cause false detections and find that they can be divided into three main types: (i) two dwarfs undergoing grazing transits, (ii) two dwarfs undergoing low-latitude transits in which one component has a substantially smaller radius than the other, and (iii) two eclipsing dwarfs blended with one or more physically unassociated foreground stars. We also predict that a significant fraction of Hot Jupiter detections are blended with the light from other stars, showing that care must be taken to identify the presence of any unresolved neighbors in order to obtain accurate estimates of planetary radii. This issue is likely to extend to terrestrial planet candidates in the CoRoT and Kepler transit surveys, for which neighbors of much fainter relative brightness will be important.Comment: 33 pages, 7 figures, 4 tables; To be published in The Astrophysical Journa

Future Directions in Astronomy Visualisation

Despite the large budgets spent annually on astronomical research equipment such as telescopes, instruments and supercomputers, the general trend is to analyse and view the resulting datasets using small, two-dimensional displays. We report here on alternative advanced image displays, with an emphasis on displays that we have constructed, including stereoscopic projection, multiple projector tiled displays and a digital dome. These displays can provide astronomers with new ways of exploring the terabyte and petabyte datasets that are now regularly being produced from all-sky surveys, high-resolution computer simulations, and Virtual Observatory projects. We also present a summary of the Advanced Image Displays for Astronomy (AIDA) survey which we conducted from March-May 2005, in order to raise some issues pertitent to the current and future level of use of advanced image displays.Comment: 13 pages, 2 figures, accepted for publication in PAS

Gastrointestinal tract size, total-tract digestibility, and rumen microflora in different dairy cow genotypes

peer-reviewedThe superior milk production efficiency of Jersey (JE) and Jersey × Holstein-Friesian (JE × HF) cows compared with Holstein-Friesian (HF) has been widely published. The biological differences among dairy cow genotypes, which could contribute to the milk production efficiency differences, have not been as widely studied however. A series of component studies were conducted using cows sourced from a longer-term genotype comparison study (JE, JE × HF, and HF). The objectives were to (1) determine if differences exist among genotypes regarding gastrointestinal tract (GIT) weight, (2) assess and quantify whether the genotypes tested differ in their ability to digest perennial ryegrass, and (3) examine the relative abundance of specific rumen microbial populations potentially relating to feed digestibility. Over 3 yr, the GIT weight was obtained from 33 HF, 35 JE, and 27 JE × HF nonlactating cows postslaughter. During the dry period the cows were offered a perennial ryegrass silage diet at maintenance level. The unadjusted GIT weight was heavier for the HF than for JE and JE × HF. When expressed as a proportion of body weight (BW), JE and JE × HF had a heavier GIT weight than HF. In vivo digestibility was evaluated on 16 each of JE, JE × HF, and HF lactating dairy cows. Cows were individually stalled, allowing for the total collection of feces and were offered freshly cut grass twice daily. During this time, daily milk yield, BW, and dry matter intake (DMI) were greater for HF and JE × HF than for JE; milk fat and protein concentration ranked oppositely. Daily milk solids yield did not differ among the 3 genotypes. Intake capacity, expressed as DMI per BW, tended to be different among treatments, with JE having the greatest DMI per BW, HF the lowest, and JE × HF being intermediate. Production efficiency, expressed as milk solids per DMI, was higher for JE than HF and JE × HF. Digestive efficiency, expressed as digestibility of dry matter, organic matter, N, neutral detergent fiber, and acid detergent fiber, was higher for JE than HF. In grazing cows (n = 15 per genotype) samples of rumen fluid, collected using a transesophageal sampling device, were analyzed to determine the relative abundance of rumen microbial populations of cellulolytic bacteria, protozoa, and fungi. These are critically important for fermentation of feed into short-chain fatty acids. A decrease was observed in the relative abundance of Ruminococcus flavefaciens in the JE rumen compared with HF and JE × HF. We can deduce from this study that the JE genotype has greater digestibility and a different rumen microbial population than HF. Jersey and JE × HF cows had a proportionally greater GIT weight than HF. These differences are likely to contribute to the production efficiency differences among genotypes previously reported

Cmah-dystrophin deficient mdx mice display an accelerated cardiac phenotype that is improved following peptide-PMO exon skipping treatment

Duchenne muscular dystrophy (DMD) is caused by loss of dystrophin protein, leading to progressive muscle weakness and premature death due to respiratory and/or cardiac complications. Cardiac involvement is characterized by progressive dilated cardiomyopathy, decreased fractional shortening and metabolic dysfunction involving reduced metabolism of fatty acids—the major cardiac metabolic substrate. Several mouse models have been developed to study molecular and pathological consequences of dystrophin deficiency, but do not recapitulate all aspects of human disease pathology and exhibit a mild cardiac phenotype. Here we demonstrate that Cmah (cytidine monophosphate-sialic acid hydroxylase)-deficient mdx mice (Cmah−/−;mdx) have an accelerated cardiac phenotype compared to the established mdx model. Cmah−/−;mdx mice display earlier functional deterioration, specifically a reduction in right ventricle (RV) ejection fraction and stroke volume (SV) at 12 weeks of age and decreased left ventricle diastolic volume with subsequent reduced SV compared to mdx mice by 24 weeks. They further show earlier elevation of cardiac damage markers for fibrosis (Ctgf), oxidative damage (Nox4) and haemodynamic load (Nppa). Cardiac metabolic substrate requirement was assessed using hyperpolarized magnetic resonance spectroscopy indicating increased in vivo glycolytic flux in Cmah−/−;mdx mice. Early upregulation of mitochondrial genes (Ucp3 and Cpt1) and downregulation of key glycolytic genes (Pdk1, Pdk4, Ppara), also denote disturbed cardiac metabolism and shift towards glucose utilization in Cmah−/−;mdx mice. Moreover, we show long-term treatment with peptide-conjugated exon skipping antisense oligonucleotides (20-week regimen), resulted in 20% cardiac dystrophin protein restoration and significantly improved RV cardiac function. Therefore, Cmah−/−;mdx mice represent an appropriate model for evaluating cardiac benefit of novel DMD therapeutics