Efficacy of pimobendan in the prevention of congestive heart failure or sudden death in doberman pinschers with preclinical dilated cardiomyopathy (the PROTECT study)

<p>Background: The benefit of pimobendan in delaying the progression of preclinical dilated cardiomyopathy (DCM) in Dobermans is not reported.</p> <p>Hypothesis: That chronic oral administration of pimobendan to Dobermans with preclinical DCM will delay the onset of CHF or sudden death and improve survival.</p> <p>Animals: Seventy-six client-owned Dobermans recruited at 10 centers in the UK and North America.</p> <p>Methods: The trial was a randomized, blinded, placebo-controlled, parallel group multicenter study. Dogs were allocated in a 1:1 ratio to receive pimobendan (Vetmedin capsules) or visually identical placebo.</p> <p>The composite primary endpoint was prospectively defined as either onset of CHF or sudden death. Time to death from all causes was a secondary endpoint.</p> <p>Results: The proportion of dogs reaching the primary endpoint was not significantly different between groups (P = .1). The median time to the primary endpoint (onset of CHF or sudden death) was significantly longer in the pimobendan (718 days, IQR 441–1152 days) versus the placebo group (441 days, IQR 151–641 days) (log-rank P = 0.0088). The median survival time was significantly longer in the pimobendan (623 days, IQR 491–1531 days) versus the placebo group (466 days, IQR 236–710 days) (log-rank P = .034).</p> <p>Conclusion and Clinical Importance: The administration of pimobendan to Dobermans with preclinical DCM prolongs the time to the onset of clinical signs and extends survival. Treatment of dogs in the preclinical phase of this common cardiovascular disorder with pimobendan can lead to improved outcome.</p&gt

Sedimentation record in the Konkan-Kerala Basin: implications for the evolution of the Western Ghats and the Western Indian passive margin

The Konkan and Kerala Basins constitute a major depocentre for sediment from the onshore hinterland of Western India and as such provide a valuable record of the timing and magnitude of Cenozoic denudation along the continental margin. This paper presents an analysis of sedimentation in the Konkan-Kerala Basin, coupledwith a mass balance study, and numerical modelling of flexural responses to onshore denudational unloading and o¡shore sediment loading in order to test competing conceptual models for the development of high-elevation passive margins. The Konkan-Kerala Basin contains an estimated 109,000 km<sup>3</sup>; of Cenozoic clastic sediment, a volume difficult to reconcile with the denudation of a downwarped rift flank onshore, and more consistent with denudation of an elevated rift flank. We infer from modelling of the isostatic response of the lithosphere to sediment loading offshore and denudation onshore that flexure is an important component in the development of the Western Indian Margin.There is evidence for two major pulses in sedimentation: an early phase in the Palaeocene, and a second beginning in the Pliocene. The Palaeocene increase in sedimentation can be interpreted in terms of a denudational response to the rifting between India and the Seychelles, whereas the mechanism responsible for the Pliocene pulse is more enigmatic

Geological controls on the geometry of incised-valley fills: Insights from a global dataset of late-Quaternary examples

Incised valleys that develop due to relative sea-level change are common features of continental shelves and coastal plains. Assessment of the factors that control the geometry of incised-valley fills has hitherto largely relied on conceptual, experimental or numerical models, else has been grounded on case studies of individual depositional systems. Here, a database-driven statistical analysis of 151 late-Quaternary incised-valley fills has been performed, the aim being to investigate the geological controls on their geometry. Results of this analysis have been interpreted with consideration of the role of different processes in determining the geometry of incised-valley fills through their effect on the degree and rate of river incision, and on river size and mobility. The studied incised-valley fills developed along active margins are thicker and wider, on average, than those along passive margins, suggesting that tectonic setting exerts a control on the geometry of incised-valley fills, likely through effects on relative sea-level change and river behaviour, and in relation to distinct characteristics of basin physiography, water discharge and modes of sediment delivery. Valley-fill geometry is positively correlated with the associated drainage-basin size, confirming the dominant role of water discharge. Climate is also inferred to exert a potential control on valley-fill dimensions, possibly through modulations of temperature, peak precipitation, vegetation and permafrost, which would in turn affect water discharge, rates of sediment supply and valley-margin stability. Shelves with slope breaks that are currently deeper than 120 m contain incised-valley fills that are thicker and wider, on average, than those hosted on shelves with breaks shallower than 120 m. No correlation exists between valley-fill thickness and present-day coastal-prism convexity, which is measured as the difference in gradient between lower coastal plains and inner shelves. These findings challenge some concepts embedded in sequence stratigraphic thinking, and have significant implications for analysis and improved understanding of source-to-sink sediment route-ways, and for attempting predictions of the occurrence and characteristics of hydrocarbon reservoirs

Denudational history along a transect across the Drakensberg Escarpment of southern Africa derived from apatite fission track thermochronology

The denudational history of a ∼500 km long transect across the Drakensberg Escarpment on the high-elevation passive margin of SE Africa is quantified on the basis of thermal history modeling of apatite fission track data for 15 deep borehole samples, supplemented by an additional 10 outcrop samples. A minimum of 4.5 km of denudation since formation of the margin ∼130 Myr ago is estimated for the coastal zone, with a marked Early Cretaceous episode of accelerated denudation broadly coincident with continental breakup. Samples from the Swartberg borehole (SW 1/67) located ∼30 km seaward of the present position of the Drakensberg Escarpment indicate a total depth of denudation of 3.1 ± 1.2 km since ∼91 Myr, with a phase of accelerated denudation of 2.1 ± 0.9 km at a mean rate of 95 ± 43 m/Myr between ∼91 and 69 Myr. Samples from the Ladybrand borehole (LA 1/68) west of the Lesotho Highlands indicate 1.7 ± 0.5 km of denudation since ∼78 Myr, with a phase of accelerated denudation at 82 ± 43 m/Myr from ∼78 to 64 Myr. Average denudation rates declined to about 10 m/Myr during much of the Tertiary. Although the apatite fission track data do not provide any direct constraints on the denudational history of the Lesotho Highlands, interpolation between the two boreholes, constrained by geological evidence and extrapolated in situ-produced cosmogenic 36Cl-derived denudation rate estimates, suggests a pattern of denudation compatible with numerical modeling studies of escarpment evolution involving rapid river incision seaward of a preexisting inland drainage divide. These patterns of denudation are incompatible with constant retreat of the Drakensberg Escarpment from an initial position near the present coast. We suggest that the Drakensberg Escarpment formed by rapid post-breakup river incision seaward of a preexisting drainage divide located just east of the present escarpment location and became pinned at this divide with subsequent retreat rates of only 100–200 m/Myr

The nature and occurence of silcrete, Southern Cape Province, South Africa

2.65SIGLELD:7755.01(28) / BLDSC - British Library Document Supply CentreGBUnited Kingdo