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Abstract Background Although peri-device leakage is frequently observed after left atrial appendage occlusion (LAAO), there is no consensus on the optimal management strategy. It is unknown whether additional plugging should be preferred over surgical exclusion of the LAA, as experience with additional plugging is limited. Case summary In this case report, we demonstrate the clinical implications of additional plugging and surgical exclusion in a 65-year-old male patient with peri-device leakage and recurrent thromboembolic events. After the recurrence of paroxysmal atrial fibrillation (AF) and a transient ischaemic attack despite adequate anticoagulation, the patient was opted for re-do pulmonary vein isolation and LAAO with a Watchman device. Due to multiple ischaemic strokes and recurrent AF in combination with significant peri-device leakage, additional plugging with a second device was performed. Post-procedurally, the patient had another ischaemic stroke and persisting peri-device leakage was observed during follow-up. Due to progressive symptoms of AF and patient’s preference to discontinue DOAC, he underwent a Cox MAZE IV procedure, including amputation of the LAA with both devices. Within six months after surgery, the patient experienced two more ischaemic events. In the following two years, the patient remained free of any cerebrovascular accidents or recurrence of AF. Discussion Additional plugging of peri-device leakage is not always successful in stroke prevention. In combination with recurrent AF, progressive symptoms, contraindication for oral anticoagulation, and patient’s preference, surgical LAA exclusion could be preferred over additional plugging.

A strong positive correlation has been found between lipid peroxidation product and vascular endothelial growth factor concentrations in the vitreous of patients with proliferative diabetic retinopathy. To establish a causal relation between diabetes-associated enhanced oxidative stress and vascular endothelial growth factor production, we evaluated two antioxidants, DL-alpha-lipoic acid and taurine, on retinal vascular endothelial growth factor protein and mRNA expression and on parameters of oxidative stress in streptozotocin-diabetic rats. Our experiments were on control rats and streptozotocin-diabetic rats with a 6-week duration of diabetes, treated with or without DL-alpha-lipoic acid (100 mg x kg(-1) x d(-1), i.p.) or taurine (1% in the diet) starting from induction of diabetes. Vascular endothelial growth factor protein in retinal homogenates was assessed by sandwich ELISA with an affinity-purified polyclonal antibody and vascular endothelial growth factor mRNA by ribonuclease protection assay. Retinal lipid peroxidation products i.e. malondialdehyde plus 4-hydroxyalkenals were quantified with N-methyl-2-phenylindole. Retinal reduced and oxidized glutathione, ascorbate, dehydroascorbate, and sorbitol pathway intermediates were measured spectrofluorometrically, and taurine by reverse-phase HPLC. Vascular endothelial growth factor protein concentration (means +/- SD) was increased in diabetic rats compared with control rats (33+/-7 vs 19+/-5 pg/mg total protein, p < 0.01) This increase was attenuated by taurine (26+/-8, p < 0.05) and prevented by DL-alpha-lipoic acid (21+/-4, p < 0.01). Vascular endothelial growth factor mRNA abundance was reduced by 1.4-fold in diabetic rats compared with control rats and this decrease was attenuated but not completely prevented by both antioxidants. Malondialdehyde plus 4-hydroxyalkenal concentration was increased in diabetic rats compared with control rats, and both antioxidants arrested accumulation of lipid peroxidation products. Taurine, reduced glutathione, oxidized glutathione, ascorbate, dehydroascorbate and sorbitol pathway intermediate concentrations as well as oxidized glutathione/reduced glutathione and dehydroascorbate/ascorbate ratios were similar in control and diabetic rats treated with or without taurine. Oxidative stress is directly involved in up regulation of vascular endothelial growth factor protein in the retina during early diabetes.

Observations of a stellar occultation by (10199) Chariklo, a minor body that orbits the Sun between Jupiter and Neptune, reveal that it has a ring system, a property previously observed only for the four giant planets of the Solar System. Tiny Chariklo has its own ring system Observations of a stellar occultation by (10199) Chariklo, a Centaur-class outer-system asteroid orbiting between Saturn and Uranus, reveal that it has a ring system, a feature previously observed only for the four giant planets. Chariklo, with a diameter of about 250 km, has two narrow and dense rings separated by a small gap, probably due to the presence of a (yet-to-be-found) kilometre-sized satellite. The discovery of these rings raises questions about the formation and dynamical evolution of planetary rings. For one thing, it seems likely that planetary rings are much more common than previously thought. Hitherto, rings have been found exclusively around the four giant planets in the Solar System 1 . Rings are natural laboratories in which to study dynamical processes analogous to those that take place during the formation of planetary systems and galaxies. Their presence also tells us about the origin and evolution of the body they encircle. Here we report observations of a multichord stellar occultation that revealed the presence of a ring system around (10199) Chariklo, which is a Centaur—that is, one of a class of small objects orbiting primarily between Jupiter and Neptune—with an equivalent radius of 124   9 kilometres (ref. 2 ). There are two dense rings, with respective widths of about 7 and 3 kilometres, optical depths of 0.4 and 0.06, and orbital radii of 391 and 405 kilometres. The present orientation of the ring is consistent with an edge-on geometry in 2008, which provides a simple explanation for the dimming 3 of the Chariklo system between 1997 and 2008, and for the gradual disappearance of ice and other absorption features in its spectrum over the same period 4 , 5 . This implies that the rings are partly composed of water ice. They may be the remnants of a debris disk, possibly confined by embedded, kilometre-sized satellites.

This presentation covers two topics. First is a basic laboratory study, designed to explore the mechanism for the phenomenon of ‘early worsening,’ in which individuals with type 1 diabetes and early to moderate retinopathy are rapidly placed on ‘tight’ blood glucose control, after which about 10% of these individuals develop a worsening of retinopathy with the appearance of multiple ‘cotton wool’ spots. Our studies on cultured retinal cells used vascular endothelial growth factor (VEGF) production as an index of cellular ischaemia. VEGF production increases substantially when cells are cultured in low oxygen, but VEGF production in these hypoxic cultures decreases when the medium contains a fivefold excess glucose concentration. Cultures with no medium glucose also show increased VEGF production. In the clinical situation, we infer from these results that retinas with early retinopathy have a reduced blood supply and are therefore relatively ischaemic, thus increasing their VEGF production. Adding glucose provides an alternative energy supply, thus reducing the demand for VEGF and hence, reducing the likelihood of ‘early worsening.’ However, reducing the glucose supply to these already compromised retinas further increases their ischaemia and, therefore, the stimulus to produce more VEGF. The second part of this presentation is a clinical exploration of possible reasons for the frequent, wide discrepancy between measured central macular thickness by optical coherence tomography (OCT) and visual acuity in eyes with diabetic macular oedema. I explore the influence of different diseases in which macular oedema appears, the presence or absence, and size, of cystoid cavities; duration of the oedema; age of the subject, different anatomic derangements including epiretinal membranes and disruptions of the photoreceptor layer, and various biochemical and physiological mechanisms.

Preference for a drug formulation is important in adherence to long-term medication for chronic illnesses such as osteoporosis. We investigated the preference for and acceptability of chewable tablet containing calcium and vitamin D (Calci Chew D₃, Nycomed) compared to that of a sachet containing calcium and vitamin D₃ (Cad, Will-Pharma). This open, randomised, cross-over trial was set up to compare the preference and acceptability of two calcium plus vitamin D₃ formulations (both with 500 mg calcium and 400/440 IU vitamin D3), given twice a day in patients with osteoporosis. Preference and acceptability were assessed by means of questionnaires. Preference was determined by asking the question, which treatment the patient preferred, and acceptability was measured by scoring five variables, using rating scales. Of the 102 patients indicating a preference for a trial medication, 67% preferred the chewable tablet, 19% the sachet with calcium and vitamin D₃, and 15% stated no preference. The significant preference for Calci Chew D₃ (p < 0.0001) was associated with higher scores for all five acceptability variables. The two formulations were tolerated equally well. A significant greater number of patients considered the chewable tablet as preferable and acceptable to the sachet, containing calcium and vitamin D₃. Trial registration: Current Controlled Trials ISRCTN18822358.

The blood vessels of the human retina do not normally grow after birth. All postnatal neovascularization in this tissue is therefore pathologic, arising as a complication of diseases such as diabetes, sickle cell disease, and retinal-vein occlusion. The new vessels lack the barrier function of the normal retinal circulation and permit extravascular leakage of blood components. Because of their extremely thin endothelium, these vessels are fragile and can easily rupture, causing hemorrhage into the vitreous cavity. New retinal vessels are surrounded by fibroblasts or glial cells that may proliferate extensively as the disease progresses. The tough, contractile bands and membranes . . .

The risk of blindness from diabetic retinopathy, the most severe ocular complication of diabetes, has greatly diminished, owing to advances in management. This review discusses the spectrum of clinical manifestations of diabetic retinopathy, with particular attention to new aspects of management. Since diabetes is common, diabetic retinopathy remains an important medical problem for affected patients and those caring for them. Diabetic retinopathy is the most severe of the several ocular complications of diabetes. Advances in treatment over the past 40 years have greatly reduced the risk of blindness from this disease, but because diabetes is so common (affecting approximately 6 percent of the U.S. population 1 ), retinopathy remains an important problem. Clinical and Histopathological Manifestations The earliest clinical signs of diabetic retinopathy are microaneurysms, small outpouchings from retinal capillaries, and dot intraretinal hemorrhages. These signs are present in nearly all persons who have had type 1 diabetes for 20 years 2 and in nearly 80 percent of those with type 2 . . .

This is the first volume to appear under the joint editorship of J.P.Hirth and F.R.N.Nabarro.While Volume 11 concentrated on the single topic of dislocations and work hardening, the present volume spreads over the whole range of the study of dislocations from the application by Kléman and his colleagues of homotopy theory to classifying.

The Cassini and Juno probes have revealed large coherent cyclonic vortices in the polar regions of Saturn and Jupiter, a dramatic contrast from the east-west banded jet structure seen at lower latitudes. Debate has centered on whether the jets are shallow, or extend to greater depths in the planetary envelope. Recent experiments and observations have demonstrated the relevance of deep convection models to a successful explanation of jet structure and cyclonic coherent vortices away from the polar regions have been simulated recently including an additional stratified shallow layer. Here we present new convective models able to produce long-lived polar vortices. Using simulation parameters relevant for giant planet atmospheres we find flow regimes that are in agreement with geostrophic turbulence (GT) theory in rotating convection for the formation of large scale coherent structures via an upscale energy transfer fully three-dimensional. Our simulations generate polar characteristics qualitatively similar to those seen by Juno and Cassini: they match the structure of cyclonic vortices seen on Jupiter; or can account for the existence of a strong polar vortex extending downwards to lower latitudes with a marked spiral morphology and the hexagonal pattern seen on Saturn. Our findings indicate that these vortices can be generated deep in the planetary interior. A transition differentiating these two polar flows regimes is described, interpreted in terms of different force balances and compared with previous shallow atmospheric models which characterised polar vortex dynamics in giant planets. In addition, the heat transport properties are investigated confirming recent scaling laws obtained in the context of reduced models of GT.

Waves in thin fluid layers are important in various stellar and planetary problems. Due to rapid rotation such systems will become oblate, with a latitudinal variation in the gravitational acceleration across the surface of the object. In the case of accreting neutron stars, rapid rotation could lead to a polar radius smaller than the equatorial radius by a factor \\(\\sim 0.8\\). We investigate how the oblateness and a changing gravitational acceleration affect different hydrodynamic modes that exist in such fluid layers through analytic approximations and numerical calculations. The wave vectors of \\(g\\)-modes and Yanai modes increase for more oblate systems compared to spherical counterparts, although the impact of variations in the changing gravitational acceleration is effectively negligible. We find that for increased oblateness, Kelvin modes show less equatorial confinement and little change in their wave vector. For \\(r\\)-modes, we find that for more oblate systems the wave vector decreases. The exact manner of these changes for the \\(r\\)-modes depends on the model for the gravitational acceleration across the surface.