Increasing fruit and vegetable intake has no effect on retinal vessel caliber in adults at high risk of developing cardiovascular disease

BACKGROUND AND AIM: Retinal vessel abnormalities are associated with cardiovascular disease (CVD) risk. To date, there are no trials investigating the effect of dietary factors on the retinal microvasculature. This study examined the dose response effect of fruit and vegetable (FV) intake on retinal vessel caliber in overweight adults at high CVD risk.

METHODS AND RESULTS: Following a 4 week washout period, participants were randomized to consume either 2 or 4 or 7 portions of FV daily for 12 weeks. Retinal vessel caliber was measured at baseline and post-intervention. A total of 62 participants completed the study. Self-reported FV intake indicated good compliance with the intervention, with serum concentrations of zeaxanthin and lutein increasing significantly across the groups in a dose-dependent manner (P for trend < 0.05). There were no significant changes in body composition, 24-h ambulatory blood pressure or fasting blood lipid profiles in response to the FV intervention. Increasing age was a significant determinant of wider retinal venules (P = 0.004) whereas baseline systolic blood pressure was a significant determinant of narrower retinal arterioles (P = 0.03). Overall, there was no evidence of any short-term dose-response effect of FV intake on retinal vessel caliber (CRAE (P = 0.92) or CRVE (P = 0.42)).

CONCLUSIONS: This study demonstrated no effect of increasing FV intake on retinal vessel caliber in overweight adults at high risk of developing primary CVD.

The persistent activity of Jupiter-family comets at 3-7 AU

We present an analysis of comet activity based on the Spitzer Space Telescope component of the Survey of the Ensemble Physical Properties of Cometary Nuclei. We show that the survey is well suited to measuring the activity of Jupiter-family comets at 3-7 AU from the Sun. Dust was detected in 33 of 89 targets (37 ± 6%), and we conclude that 21 comets (24 ± 5%) have morphologies that suggest ongoing or recent cometary activity. Our dust detections are sensitivity limited, therefore our measured activity rate is necessarily a lower limit. All comets with small perihelion distances (q <1.8 AU) are inactive in our survey, and the active comets in our sample are strongly biased to post-perihelion epochs. We introduce the quantity ɛfρ, intended to be a thermal emission counterpart to the often reported Afρ, and find that the comets with large perihelion distances likely have greater dust production rates than other comets in our survey at 3-7 AU from the Sun, indicating a bias in the discovered Jupiter-family comet population. By examining the orbital history of our survey sample, we suggest that comets perturbed to smaller perihelion distances in the past 150 yr are more likely to be active, but more study on this effect is needed.

Rapid tryptophan depletion improves decision-making cognition in healthy humans without affecting reversal learning or set shifting

Rapid tryptophan (Trp) depletion (RTD) has been reported to cause deterioration in the quality of decision making and impaired reversal learning, while leaving attentional set shifting relatively unimpaired. These findings have been attributed to a more powerful neuromodulatory effect of reduced 5-HT on ventral prefrontal cortex (PFC) than on dorsolateral PFC. In view of the limited number of reports, the aim of this study was to independently replicate these findings using the same test paradigms. Healthy human subjects without a personal or family history of affective disorder were assessed using a computerized decision making/gambling task and the CANTAB ID/ED attentional set-shifting task under Trp-depleted (n=17; nine males and eight females) or control (n=15; seven males and eight females) conditions, in a double-blind, randomized, parallel-group design. There was no significant effect of RTD on set shifting, reversal learning, risk taking, impulsivity, or subjective mood. However, RTD significantly altered decision making such that depleted subjects chose the more likely of two possible outcomes significantly more often than controls. This is in direct contrast to the previous report that subjects chose the more likely outcome significantly less often following RTD. In the terminology of that report, our result may be interpreted as improvement in the quality of decision making following RTD. This contrast between studies highlights the variability in the cognitive effects of RTD between apparently similar groups of healthy subjects, and suggests the need for future RTD studies to control for a range of personality, family history, and genetic factors that may be associated with 5-HT function.

N-terminal His(7)-modification of glucagon-like peptide-1(7-36) amide generates dipeptidyl peptidase IV-stable analogues with potent antihyperglycaemic activity

Glucagon-like peptide-1(7-36)amide (GLP-1) possesses several unique and beneficial effects for the potential treatment of type 2 diabetes. However, the rapid in-activation of GLP-1 by dipeptidyl peptidase IV (DPP IV) results in a short half-life in vivo (less than 2 min) hindering therapeutic development. In the present study, a novel His(7)-modified analogue of GLP-1, N-pyroglutamyl-GLP-1, as well as N-acetyl-GLP-1 were synthesised and tested for DPP IV stability and biological activity. Incubation of GLP-1 with either DPP IV or human plasma resulted in rapid degradation of native GLP-1 to GLP-1 (9-36),amide, while N-acetyl-GLP-1 and N-pyroglutamyl-GLP-1 were completely resistant to degradation. N-acetyl-GLP-1 and N-pyroglutamyl-GLP-1 bound to the GLP-1 receptor but had reduced affinities (IC50 values 32(.)9 and 6(.)7 nM, respectively) compared with native GLP-1 (IC50 0(.)37 nM). Similarly, both analogues stimulated cAMP production with EC50 values of 16(.)3 and 27 nM respectively compared with GLP-1 (EC50 4(.)7 nM). However, N-acetyl-GLP-1 and N-pyroglutamyl-GLP-1 exhibited potent insulinotropic activity in vitro at 5(.)6 mM glucose (P

Novel dipeptidyl peptidase IV resistant analogues of glucagon-like peptide-1(7-36)amide have preserved biological activities in vitro conferring improved glucose-lowering action in vivo

Although the incretin hormone glucagon-like peptide-1 (GLP-1) is a potent stimulator of insulin release, its rapid degradation in vivo by the enzyme dipeptidyl peptidase IV (DPP IV) greatly limits its potential for treatment of type 2 diabetes. Here, we report two novel Ala(8)-substituted analogues of GLP-1, (Abu(8))GLP-1 and (Val(8) GLP-1 which were completely resistant to inactivation by DPP IV or human plasma. (Abu(8))GLP-1 and (Val(8))GLP-1 exhibited moderate affinities (IC50: 4.76 and 81.1 nM, respectively) for the human GLP-1 receptor compared with native GLP-1 (IC50: 0.37 nM). (Abu(8))GLP-1 and (Val(8))GLP-1 dose-dependently stimulated cAMP in insulin-secreting BRIN BD11 cells with reduced potency compared with native GLP-1 (1.5- and 3.5-fold, respectively). Consistent with other mechanisms of action, the analogues showed similar, or in the case of (Val(8))GLP-1 slightly impaired insulin releasing activity in BRIN BD11 cells. Using adult obese (ob/ob) mice, (Abu(8))GLP-1 had similar glucose-lowering potency to native GLP-1 whereas the action of (Val(8))GLP-1 was enhanced by 37%. The in vivo insulin-releasing activities were similar. These data indicate that substitution of Ala(8) in GLP-1 with Abu or Val confers resistance to DPP IV inactivation and that (Val(8))GLP-1 is a particularly potent N-terminally modified GLP-1 analogue of possible use in type 2 diabetes.

3D Curvature Contrast - a geometric or brightness illusion?

Simultaneous contrast effects have been found across a wide range of visual dimensions. We describe a simultaneous contrast effect - three-dimensional curvature contrast - in which the apparent curvature of a surface defined by shading and texture information is influenced by the curvature of a surrounding surface. The effect is strong and easily measurable. We asked whether the effect depends upon the presence of contrast at the level of the internal representation of surface curvature or whether it could be better explained in terms of local changes in the apparent brightness of regions within the test patches induced by luminance transition at the borders. The experimental results suggest that, whicle these luminance-contrast-induced effects do contribute to the observed changes in perceived curvature, there are additional influences. In particular changes in perceived curvature induced by a pattern of curved patches were eliminated or considerably weakened when the inducing pattern was transformed into a photographic negative, a procedure which disrupts the apparent three-dimensional structure of the surface patches without changing their brightness contrast. This suggests a component of the illusion involves comparisons at the level of representation of surface curvature. The observation that three-dimensional curvature contrast presists when the inducing surfaces are spatially separate from the test surface suggests that shape perception involves global, as well as local, operations.

Direction repulsion goes global

When viewing two superimposed, translating sets of dots moving in different directions, one overestimates the direction difference. This phenomenon of direction repulsion is thought to be driven by inhibitory interactions between directionally tuned motion detectors [1, 2]. However, there is disagreement on where this occurs — at early stages of motion processing [1, 3], or at the later, global motion-processing stage following “pooling” of these measures [4–6]. These two stages of motion pro - cessing have been identified as occurring in area V1 and the human homolog of macaque MT/V5, respectively[7, 8]. We designed experiments in which local and global predictions of repulsion are pitted against one another. Our stimuli contained a target set of dots, moving at a uniform speed, superimposed on a “mixed-speed” distractor set. Because the perceived speed of a mixed-speed stimulus is equal to the dots’ average speed [9], a global-processing account of direction repulsion predicts that repulsion magnitude induced by a mixed-speed distractor will be indistinguishable from that induced by a single-speed distractor moving at the same mean speed. This is exactly what we found. These results provide compelling evidence that global-motion interactions play a major role in driving direction repulsion.

Reparation or retribution: an investigation into regulatory compliance in planning

It is an axiom of good planning practice that procedure is informed by up-to-date research. Consequently, it is surprising to discover that there remains a dearth of specialised planning-enforcement literature relating to theory and implementation. In this paper an evaluation is given of the effectiveness of planning enforcement in Britain by reviewing existing legislative mechanisms and strategies employed by officials. Theoretical perspectives are drawn upon to suggest how the system might be improved through attention to the structural factors underpinning it.

CCD photometry of distant comets II

R band CCD photometric observations of short period Jupiter family comets in the heliocentric region of 2.11 AU less than or equal to R-h less than or equal to 5.63 AU were performed using the 4.2 m William Herschel Telescope on La Palma in December 1998. 22 comets were targeted, including the comet- asteroid transition object 49P/Arend-Rigaux. Out of a total of ten detected comets. six were seen to display substantial outgassing (48P, 65P, 74P, 103Pt 128P, and 139P), with the remaining four comets (7P. 9P, 22P. and 49P) being stellar in appearance. Nuclear radius measurements and relative dust production rates in terms of Af rho were measured for these comets, along with upper limits for the remaining twelve undetected comets (6P, 44P, 51P, 54P, 57P: 63P, 71P, 73P, 79P, 86P, 87P, and 100P). The inactive comets had nuclear radii in the range 1.8 km less than or equal to r(N) less than or equal to 4.4 km, while upper limits for the active and undetected comets (assuming they all lay within the held of view) were between 0.6 km and 12.7 km, for an assumed albedo of 0.04. Even if one applies the previously measured maximum axis ratio of 2.6:1 and the minimum measured albedo of 0.02 to the undetected comets. their projected semi-major axes are all constrained to below 8 km. For the active comets, photometric profiles of their dust comae were measured and are consistent with those of steady state coma models.

Chemical abundances and winds of massive stars in M31: a B-type supergiant and a WC star in OB 10

We present high quality spectroscopic data for two massive stars in the OB 10 association of M31, OB 10-64 (B0 la) and OB 10-WRI (WC6). Medium resolution spectra of both stars were obtained using the ISIS spectrograph on the William Herschel Telescope. This is supplemented with Hubble Space Telescope STIS UV spectroscopy and Keck I HIRES data for OB 10-64. A non- local thermodynamic equilibrium (LTE) model atmosphere and abundance analysis for OB 10-64 is presented, indicating that this star has similar photospheric CNO, Mg and Si abundances to solar neighbourhood massive stars. A wind analysis of this early B-type supergiant reveals a mass-loss rate of (M)over dot = 1.6 x 10(-6) M-circle dot yr(-1), and v(infinity) = 1650 km s(-1). The corresponding wind momentum is in good agreement with the wind momentum-luminosity relationship found for Galactic early-B supergiants. Observations of OB 10-WRI are analysed using a non-LTE, line-blanketed code, to reveal approximate stellar parameters of log L/L-circle dot similar to 5.7, T-* - 75 kK, v(infinity) similar to 3000 km s(-1), (M)over dot/(M-circle dot yr(-1)) similar to 10(-4.3) adopting a clumped wind with a filling factor of 10 per cent. Quantitative comparisons are made with the Galactic WC6 star HD 92809 (WR23) revealing that OB 10-WR1 is 0.4 dex more luminous, though it has a much lower C/He ratio (similar to0.1 versus 0.3 for HD 92809). Our study represents the first detailed, chemical model atmosphere analysis for either a B-type supergiant or a Wolf- Rayet (WR) star in Andromeda, and shows the potential of how such studies can provide new information on the chemical evolution of galaxies and the evolution of massive stars in the local Universe.

Neostigmine antagonism of rocuronium block during anesthesia with sevoflurane, isoflurane or propofol

Purpose: To examine the influence of continuing administration of sevoflurane or isoflurane during reversal of rocuronium induced neuromuscular block with neostigmine. Methods: One hundred and twenty patients, divided into three equal groups, were randomly allocated to maintenance of anesthesia with sevoflurane, isoflurane or propofol. Neuromuscular block was induced with rocuronium and monitored using train-of-four (TOF) stimulation of the ulnar nerve and recording the force of contraction of the adductor pollicis muscle. Neostigmine was administered when the first response in TOF had recovered to 25%. At this time the volatile agent administration was stopped or propofol dosage reduced in half the patients in each group (n = 20 in each group). The times to attain TOF ratio of 0.8, and the number of patients attaining this end point within 15 min were recorded. Results: The times (mean ± SD) to recovery of the TOF ratio to 0.8 were 12.0 ± 5.5 and 6.8 ± 2.3 min in the sevoflurane continued and sevoflurane stopped groups, 9.0 ± 8.3 and 5.5 ± 3.0 min in the isoflurane continued and isoflurane stopped groups, and 5.2 ± 2.8 and 4.7 ±1.5 min in the propofol continued and propofol stopped groups (P <0.5- 01). Only 9 and 15 patients in the sevoflurane and isoflurane continued groups respectively had attained a TOF ratio of 0.8 within 15 min (P <0.001 for sevoflurane). Conclusions: The continued administration of sevoflurane, and to a smaller extent isoflurane, results in delay in attaining adequate antagonism of rocuronium induced neuromuscular block.