Retinal vessel diameters and reactivity in diabetes mellitus and/or cardiovascular disease

Background: Retinal vessel calibre and vascular dilation/constriction in response to flicker light provocation may provide a measure distinguishing patients suffering from diabetes mellitus and/or cardiovascular disease. Methods: One hundred and sixteen age and sex matched patients with diabetes mellitus (DM), cardiovascular disease (CVD) and both DM and CVD (DM+CVD) underwent systemic and intraocular pressure measurements. Retinal vessel calibres were assessed using a validated computer-based program to compute central retinal artery and vein equivalents (CRVE) from monochromatic retinal images. Vessel dilation and constriction responses to flicker light provocation were assessed by continuous retinal vessel diameter recordings. Plasma endothelial markers von Willebrand factor (vWf) and soluble E selectin (sEsel) were measured by ELISA. Results: Retinal vessel calibres were comparable across groups but CRVE correlated significantly with disease duration in DM patients (r=0.57, p<0.001). Patients suffering DM only exhibited reduced arterial vasomotion at rest and reduced arterial constriction following flicker light induced vessel dilation compared to patients with CVD and those suffering both CVD+DM (p=0.030). Patients suffering from CVD+DM exhibited significant differences between each flicker cycle in regards to arterial maximum constriction (p=0.006) and time needed to reach arterial maximum dilation (p=0.004), whereas the other two groups did not show such inconsistencies between individual flicker cycles. vWf was raised in CVD+DM compared to the other two groups (p≤0.02), whilst sEsel was raised in CVD+DM compared to DM alone (p=0.044). Conclusions: Dynamic retinal vascular calibres as obtained by continuous diameter measurements using flicker light provocation can reveal subtle differences between groups suffering from CVD with and without DM. This difference in reaction pattern and lack of arterial constriction in DM may provide a suitable marker to monitor progression

The relationship of systemic markers of renal function and vascular function with retinal blood vessel responses

Purpose: To test the hypothesis of a significant relationship between systemic markers of renal and vascular function (processes linked to cardiovascular disease and its development) and retinal microvascular function in diabetes and/or cardiovascular disease.Methods: Ocular microcirculatory function was measured in 116 patients with diabetes and/or cardiovascular disease using static and continuous retinal vessel responses to three cycles of flickering light. Endothelial function was evaluated by von Willebrand factor (vWf), endothelial microparticles and soluble E selectin, renal function by serum creatinine, creatinine clearance and estimated glomerular filtration rate (eGFR). HbA1c was used as a control index.Results: Central retinal vein equivalence and venous maximum dilation to flicker were linked to HbA1c (both p<0.05). Arterial reaction time was linked to serum creatinine (p=0.036) and eGFR (p=0.039), venous reaction time was linked to creatinine clearance (p=0.018). Creatinine clearance and eGFR were linked to arterial maximum dilatation (p<0.001 and p=0.003 respectively) and the dilatation amplitude (p=0.038 and p=0.048 respectively) responses in the third flicker cycle. Of venous responses to the first flicker cycle, HbA1c was linked to the maximum dilation response (p=0.004) and dilatation amplitude (p=0.017), vWf was linked to the maximum constriction response (p=0.016), and creatinine clearance to the baseline diameter fluctuation (p=0.029). In the second flicker cycle, dilatation amplitude was linked to serum creatinine (p=0.022). Conclusions: Several retinal blood vessel responses to flickering light are linked to glycaemia and renal function, but only one index is linked to endothelial function. Renal function must be considered when interpreting retinal vessel responses

Detection of Gamma-Ray Emission from the Starburst Galaxies M82 and NGC 253 with the Large Area Telescope on Fermi

We report the detection of high-energy gamma-ray emission from two starburst galaxies using data obtained with the Large Area Telescope on board the Fermi Gamma-ray Space Telescope. Steady point-like emission above 200 MeV has been detected at significance levels of 6.8 sigma and 4.8 sigma respectively, from sources positionally coincident with locations of the starburst galaxies M82 and NGC 253. The total fluxes of the sources are consistent with gamma-ray emission originating from the interaction of cosmic rays with local interstellar gas and radiation fields and constitute evidence for a link between massive star formation and gamma-ray emission in star-forming galaxies.Comment: Submitted to ApJ Letter

Fermi Gamma-ray Imaging of a Radio Galaxy

The Fermi Gamma-ray Space Telescope has detected the gamma-ray glow emanating from the giant radio lobes of the radio galaxy Centaurus A. The resolved gamma-ray image shows the lobes clearly separated from the central active source. In contrast to all other active galaxies detected so far in high-energy gamma-rays, the lobe flux constitutes a considerable portion (>1/2) of the total source emission. The gamma-ray emission from the lobes is interpreted as inverse Compton scattered relic radiation from the cosmic microwave background (CMB), with additional contribution at higher energies from the infrared-to-optical extragalactic background light (EBL). These measurements provide gamma-ray constraints on the magnetic field and particle energy content in radio galaxy lobes, and a promising method to probe the cosmic relic photon fields.Comment: 27 pages, includes Supplementary Online Material; corresponding authors: C.C. Cheung, Y. Fukazawa, J. Knodlseder, L. Stawar

Fermi Large Area Telescope observations of PSR J1836+5925

The discovery of the gamma-ray pulsar PSR J1836+5925, powering the formerly unidentified EGRET source 3EG J1835+5918, was one of the early accomplishments of the Fermi Large Area Telescope (LAT). Sitting 25 degrees off the Galactic plane, PSR J1836+5925 is a 173 ms pulsar with a characteristic age of 1.8 million years, a spindown luminosity of 1.1$\times10^{34}$ erg s$^{-1}$, and a large off-peak emission component, making it quite unusual among the known gamma-ray pulsar population. We present an analysis of one year of LAT data, including an updated timing solution, detailed spectral results and a long-term light curve showing no indication of variability. No evidence for a surrounding pulsar wind nebula is seen and the spectral characteristics of the off-peak emission indicate it is likely magnetospheric. Analysis of recent XMM observations of the X-ray counterpart yields a detailed characterization of its spectrum, which, like Geminga, is consistent with that of a neutron star showing evidence for both magnetospheric and thermal emission.Comment: Accepted to Astrophysical Journa

Relationship between Spatial Working Memory Performance and Diet Specialization in Two Sympatric Nectar Bats

Behavioural ecologists increasingly recognise spatial memory as one the most influential cognitive traits involved in evolutionary processes. In particular, spatial working memory (SWM), i.e. the ability of animals to store temporarily useful information for current foraging tasks, determines the foraging efficiency of individuals. As a consequence, SWM also has the potential to influence competitive abilities and to affect patterns of sympatric occurrence among closely related species. The present study aims at comparing the efficiency of SWM between generalist (Glossophaga soricina) and specialist (Leptonycteris yerbabuenae) nectarivorous bats at flowering patches. The two species differ in diet – the generalist diet including seasonally fruits and insects with nectar and pollen while the specialist diet is dominated by nectar and pollen yearlong – and in some morphological traits – the specialist being heavier and with proportionally longer rostrum than the generalist. These bats are found sympatrically within part of their range in the Neotropics. We habituated captive individuals to feed on artificial flower patches and we used infrared video recordings to monitor their ability to remember and avoid the spatial location of flowers they emptied in previous visits in the course of 15-min foraging sequences. Experiments revealed that both species rely on SWM as their foraging success attained significantly greater values than random expectations. However, the nectar specialist L. yerbabuenae was significantly more efficient at extracting nectar (+28% in foraging success), and sustained longer foraging bouts (+27% in length of efficient foraging sequences) than the generalist G. soricina. These contrasting SWM performances are discussed in relation to diet specialization and other life history traits

How well do European child-related leave policies support the caring role of fathers?

Our chapter analyses the extent to which European countries (1) recognize the caring responsibilities of fathers toward their children and (2) value fathers' caring role. To do so, we analyze the designs of individual leave policies and reflect on them by assessing available data on leave uptake by fathers in 13 European countries. Our results show that there is great variation in child-related leave designs across Europe. Our findings, in line with previous work, underscore the importance of generous individual non-transferable leave entitlements. Moreover, our findings bring forward aspects of leave designs that are rarely discussed when considering fathers' leave uptake. Our results indicate that generous non-transferable leave rights should be paired with (a) clearly defined leave periods for fathers, (b) individual entitlement to benefits, and (c) greater scope for flexibility to increase the attractiveness of child-related leave and to strengthen fathers' position when negotiating their childcare leave.</p

A change in the optical polarization associated with a gamma-ray flare in the blazar 3C 279

It is widely accepted that strong and variable radiation detected over all accessible energy bands in a number of active galaxies arises from a relativistic, Doppler-boosted jet pointing close to our line of sight. The size of the emitting zone and the location of this region relative to the central supermassive black hole are, however, poorly known, with estimates ranging from light-hours to a light-year or more. Here we report the coincidence of a gamma-ray flare with a dramatic change of optical polarization angle. This provides evidence for co-spatiality of optical and gamma-ray emission regions and indicates a highly ordered jet magnetic field. The results also require a non-axisymmetric structure of the emission zone, implying a curved trajectory for the emitting material within the jet, with the dissipation region located at a considerable distance from the black hole, at about 10^5 gravitational radii.Comment: Published in Nature issued on 18 February 2010. Corresponding authors: Masaaki Hayashida and Greg Madejsk

A phase I and pharmacokinetic study of MAG-CPT, a water-soluble polymer conjugate of camptothecin

Polymeric drug conjugates are a new and experimental class of drug delivery systems with pharmacokinetic promises. The antineoplastic drug camptothecin was linked to a water-soluble polymeric backbone (MAG-CPT) and administrated as a 30 min infusion over 3 consecutive days every 4 weeks to patients with malignant solid tumours. The objectives of our study were to determine the maximal tolerated dose, the dose-limiting toxicities, and the plasma and urine pharmacokinetics of MAG-CPT, and to document anti-tumour activity. The starting dose was 17 mg m−2 day−1. Sixteen patients received 39 courses at seven dose levels. Maximal tolerated dose was at 68 mg m−2 day−1 and dose-limiting toxicities consisted of cumulative bladder toxicity. MAG-CPT and free camptothecin were accumulated during days 1–3 and considerable amounts of MAG-CPT could still be retrieved in plasma and urine after 4–5 weeks. The half-lives of bound and free camptothecin were equal indicating that the kinetics of free camptothecin were release rate dependent. In summary, the pharmacokinetics of camptothecin were dramatically changed, showing controlled prolonged exposure of camptothecin. Haematological toxicity was relatively mild, but serious bladder toxicity was encountered which is typical for camptothecin and was found dose limiting

Molecular evidence for increased regulatory conservation during metamorphosis, and against deleterious cascading effects of hybrid breakdown in Drosophila

<p>Abstract</p> <p>Background</p> <p>Speculation regarding the importance of changes in gene regulation in determining major phylogenetic patterns continues to accrue, despite a lack of broad-scale comparative studies examining how patterns of gene expression vary during development. Comparative transcriptional profiling of adult interspecific hybrids and their parental species has uncovered widespread divergence of the mechanisms controlling gene regulation, revealing incompatibilities that are masked in comparisons between the pure species. However, this has prompted the suggestion that misexpression in adult hybrids results from the downstream cascading effects of a subset of genes improperly regulated in early development.</p> <p>Results</p> <p>We sought to determine how gene expression diverges over development, as well as test the cascade hypothesis, by profiling expression in males of <it>Drosophila melanogaster</it>, <it>D. sechellia</it>, and <it>D. simulans</it>, as well as the <it>D. simulans </it>(♀) × <it>D. sechellia </it>(♂) male F1 hybrids, at four different developmental time points (3rd instar larval, early pupal, late pupal, and newly-emerged adult). Contrary to the cascade model of misexpression, we find that there is considerable stage-specific autonomy of regulatory breakdown in hybrids, with the larval and adult stages showing significantly more hybrid misexpression as compared to the pupal stage. However, comparisons between pure species indicate that genes expressed during earlier stages of development tend to be more conserved in terms of their level of expression than those expressed during later stages, suggesting that while Von Baer's famous law applies at both the level of nucleotide sequence and expression, it may not apply necessarily to the underlying overall regulatory network, which appears to diverge over the course of ontogeny and which can only be ascertained by combining divergent genomes in species hybrids.</p> <p>Conclusion</p> <p>Our results suggest that complex integration of regulatory circuits during morphogenesis may lead to it being more refractory to divergence of underlying gene regulatory mechanisms - more than that suggested by the conservation of gene expression levels between species during earlier stages. This provides support for a 'developmental hourglass' model of divergence of gene expression in <it>Drosophila </it>resulting in a highly conserved pupal stage.</p