1,878 research outputs found

    Simultaneous extinction of Madagascar’s megaherbivores correlates with late Holocene human-caused landscape transformation

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    Reconstructing the dynamics and drivers of late Quaternary megafaunal extinctions requires direct radiometric date series that are assessed within probabilistic statistical frameworks. Extinction chronologies are poorly understood for many tropical regions, including Madagascar, which had a diverse, now-extinct Holocene large vertebrate fauna including a “megaherbivore” guild of endemic hippopotami and elephant birds. Madagascar's megaherbivores likely played vital roles in regulating ecosystem structure and nutrient cycling, but few direct dates are available for megaherbivore specimens identified to species level, with uncertainty over when and why different representatives of this guild disappeared. Here, we conduct a new investigation into Malagasy megaherbivore extinction dynamics, including 30 new AMS dates and 63 audited published dates. We use Gaussian-resampled inverse-weighted McInerny (GRIWM) analysis to estimate species-specific extinction dates for three elephant bird species (Aepyornis hildebrandti, Mullerornis modestus, Vorombe titan), eggshell representing Aepyornis or Vorombe, and two hippo species (Hippopotamus lemerlei, H. madagascariensis), and to estimate extinction dates for megaherbivore communities in different biomes. Megaherbivores persisted for millennia after first human arrival. Extinction date estimates vary significantly between biomes, with disappearance from dry deciduous forest over a millennium earlier than other biomes, possibly reflecting local variation in megaherbivore population densities or human pressures. However, megaherbivore communities including all elephant bird and hippo species persisted elsewhere across Madagascar until ∼1200-900 bp, when they collapsed suddenly. Extinctions are closely correlated in time with intensive conversion of forests to grassland at ∼1100-1000 bp, probably associated with a shift to agro-pastoralism and representing a radical change in sustainability of prehistoric human interactions with biodiversity

    Similarity solutions for unsteady shear-stress-driven flow of Newtonian and power-law fluids : slender rivulets and dry patches

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    Unsteady flow of a thin film of a Newtonian fluid or a non-Newtonian power-law fluid with power-law index N driven by a constant shear stress applied at the free surface, on a plane inclined at an angle α to the horizontal, is considered. Unsteady similarity solutions representing flow of slender rivulets and flow around slender dry patches are obtained. Specifically, solutions are obtained for converging sessile rivulets (0 < α < π/2) and converging dry patches in a pendent film (π/2 < α < π), as well as for diverging pendent rivulets and diverging dry patches in a sessile film. These solutions predict that at any time t, the rivulet and dry patch widen or narrow according to |x|3/2, and the film thickens or thins according to |x|, where x denotes distance down the plane, and that at any station x, the rivulet and dry patch widen or narrow like |t|−1, and the film thickens or thins like |t|−1, independent of N

    Primary ovarian cancer chemotherapy: current standards of care

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    Chemotherapy has been regarded as standard therapy for the majority of women with advanced epithelial ovarian cancer for several decades, with this role filled largely by the alkylating agents — used as monotherapy — until the mid-1980s. The activity of cisplatin in this disorder was established during the 1970s, and combinations of cisplatin and an alkylating agent were widely used during the late 1980s. However, further research prompted by continuing concerns over poor survival and tolerability led to the adoption of paclitaxel in combination with either cisplatin or carboplatin as first-line therapy in ovarian cancer during the 1990s. Most recent research has focused on further optimisation of these regimens to maximise clinical benefit while minimising toxicity, and investigations into alternative taxanes (e.g. docetaxel), other novel agents and new treatment schedules are ongoing

    Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

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    The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

    Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

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    The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

    First-line treatment for advanced ovarian cancer: paclitaxel, platinum and the evidence

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    Four large randomised trials of paclitaxel in combination with platinum against a platinum-based control treatment have now been published in full, representing around 88% (3588 out of 4057) of patients randomised into the eight known trials of this question. There is substantial heterogeneity in the results of these four trials. Four main explanations for this heterogeneity have been proposed: differences in the extent and timing of ‘crossover’ to taxanes in the control groups; differences in the types of patient included; differences in the effectiveness of the research regimens used; differences in the effectiveness of the control regimens used. In this study we examine whether any of these explanations is consistent with the pattern of results seen in these trials. Each explanation suggests that a particular characteristic of each trial was responsible for the results observed. For each explanation the trials were split into groups according to that characteristic, in order to partition the total heterogeneity into that seen ‘within’ and ‘between’ groups of trials. If a particular explanation was consistent with the pattern of results, we would expect to see relatively little heterogeneity within each group of trial results viewed in this way, with most of the heterogeneity being between groups which are dissimilar with respect to the key characteristic. Heterogeneity ‘within’ and ‘between’ groups was formally compared using the F-ratio. If any explanation appeared to be consistent with the results of the trials, it was considered whether the explanation was also consistent with other evidence available about these regimens. Only one explanation appeared to be consistent with the pattern of results seen in these trials, and that was differences in effectiveness of the control arms used in these trials. This suggests that the very positive results in favour of paclitaxel/cisplatin seen in two of the trials may have been due to the use of a suboptimal control arm. There is no direct evidence about the relative effectiveness of the control arms used in these trials, but indirect evidence is consistent with the conclusion that the cyclophosphamide/cisplatin regimen used in two of the trials may be less effective than the control regimens used in the other trials. Specific concerns about the choice of a cyclophosphamide/cisplatin control arm in the first of these trials to report were raised before the results of the other trials were known, i.e. before any heterogeneity had been observed. Further investigation of this question would be useful. In the meantime, given all of the randomised evidence on the efficacy and toxicity associated with the regimens used in these trials, we conclude that single agent carboplatin is a safe and effective first-line treatment for women with advanced ovarian cancer

    Observational evidence for the accretion-disk origin for a radio jet in an active galaxy

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    Accretion of gas onto black holes is thought to power the relativistic jets of material ejected from active galactic nuclei (AGN) and the 'microquasars' located in our Galaxy(1-3). In microquasars, superluminal radio-emitting features appear and propagate along the jet shortly after sudden decreases in the Xray fluxes(1). This establishes a direct observational link between the black hole and the jet: the X-ray dip is probably caused by the disappearance of a section of the inner accretion disk(4) as it falls past the event horizon, while the remainder of the disk section is ejected into the jet, creating the appearance of a superluminal bright spot(5). No such connection has hitherto been established for AGN, because of insufficient multi-frequency data. Here we report the results of three years of monitoring the X-ray and radio emission of the galaxy 3C120. As has been observed for microquasars, we find that dips in the X-ray emission are followed by ejections of bright superluminal knots in the radio jet. The mean time between X-ray dips appears to scale roughly with the mass of the black hole, although there are at present only a few data points.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62888/1/nature00772.pd
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