6,596 research outputs found

    Fast Ensemble Smoothing

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    Smoothing is essential to many oceanographic, meteorological and hydrological applications. The interval smoothing problem updates all desired states within a time interval using all available observations. The fixed-lag smoothing problem updates only a fixed number of states prior to the observation at current time. The fixed-lag smoothing problem is, in general, thought to be computationally faster than a fixed-interval smoother, and can be an appropriate approximation for long interval-smoothing problems. In this paper, we use an ensemble-based approach to fixed-interval and fixed-lag smoothing, and synthesize two algorithms. The first algorithm produces a linear time solution to the interval smoothing problem with a fixed factor, and the second one produces a fixed-lag solution that is independent of the lag length. Identical-twin experiments conducted with the Lorenz-95 model show that for lag lengths approximately equal to the error doubling time, or for long intervals the proposed methods can provide significant computational savings. These results suggest that ensemble methods yield both fixed-interval and fixed-lag smoothing solutions that cost little additional effort over filtering and model propagation, in the sense that in practical ensemble application the additional increment is a small fraction of either filtering or model propagation costs. We also show that fixed-interval smoothing can perform as fast as fixed-lag smoothing and may be advantageous when memory is not an issue

    Histiocytoid cardiomyopathy and microphthalmia with linear skin defects syndrome: phenotypes linked by truncating variants in NDUFB11

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    Variants in NDUFB11, which encodes a structural component of complex I of the mitochondrial respiratory chain (MRC), were recently independently reported to cause histiocytoid cardiomyopathy (histiocytoid CM) and microphthalmia with linear skin defects syndrome (MLS syndrome). Here we report an additional case of histiocytoid CM, which carries a de novo nonsense variant in NDUFB11 (ENST00000276062.8: c.262C > T; p.[Arg88*]) identified using whole-exome sequencing (WES) of a family trio. An identical variant has been previously reported in association with MLS syndrome. The case we describe here lacked the diagnostic features of MLS syndrome, but a detailed clinical comparison of the two cases revealed significant phenotypic overlap. Heterozygous variants in HCCS (which encodes an important mitochondrially targeted protein) and COX7B, which, like NDUFB11, encodes a protein of the MRC, have also previously been identified in MLS syndrome including a case with features of both MLS syndrome and histiocytoid CM. However, a systematic review of WES data from previously published histiocytoid CM cases, alongside four additional cases presented here for the first time, did not identify any variants in these genes. We conclude that NDUFB11 variants play a role in the pathogenesis of both histiocytoid CM and MLS and that these disorders are allelic (genetically related)

    An Australian longitudinal pilot study examining health determinants of cardiac outcomes 12 months post percutaneous coronary intervention

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    Background Percutaneous coronary intervention (PCI) is a very common revascularisation procedure for coronary artery disease (CAD). The purpose of this study was to evaluate cardiac outcomes, health related quality of life (HRQoL), resilience and adherence behaviours in patients who have undergone a PCI at two time points (6 and 12 months) following their procedure. Methods A longitudinal pilot study was conducted to observe the cardiac outcomes across a cohort of patients who had undergone a percutaneous coronary intervention (PCI). Participants who had undergone PCI 6 months prior were invited. Those participants who met the inclusion criteria and provided consent then completed a telephone survey (time point 1). These participants were then contacted 6 months later (i.e. 12 months post-intervention, time point 2) and the measures were repeated. Results All patients (n = 51) were recorded as being alive at time point 1. The multiple model indicated that controlling for other factors, gender was significantly associated with a linear combination of outcome measures (p = 0.004). The effect was moderate in magnitude (partial-η2 = 0.303), where males performed significantly better than females 6 months after the PCI procedure physically and with mood. Follow-up univariate ANOVAs indicated that gender differences were grounded in the scale measuring depression (PHQ9) (p = 0.005) and the physical component score of the short form measuring HRQoL (SF12-PCS) (p = 0.003). Thirteen patients were lost to follow-up between time points 1 and 2. One patient was confirmed to have passed away. The pattern of correlations between outcome measures at time point 2 revealed statistically significant negative correlation between the PHQ instrument and the resilience scale (CD-RISC) (r = -0.611; p < 0.001); and the physical component score of the SF-12 instrument (r = -0.437; p = 0.054). Conclusions Men were performing better than women in the 6 months post-PCI, particularly in the areas of mood (depression) and physical health. This pilot results indicate gender-sensitive practices are recommended particularly up to 6 months post-PCI. Any gender differences observed at 6 month appear to disappear at 12 months post-PCI. Further research into the management of mood particularly for women post-PCI is warranted. A more detailed inquiry related to access/attendance to secondary prevention is also warranted

    Tree migration-rates : narrowing the gap between inferred post-glacial rates and projected rates

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    Faster-than-expected post-glacial migration rates of trees have puzzled ecologists for a long time. In Europe, post-glacial migration is assumed to have started from the three southern European peninsulas (southern refugia), where large areas remained free of permafrost and ice at the peak of the last glaciation. However, increasing palaeobotanical evidence for the presence of isolated tree populations in more northerly microrefugia has started to change this perception. Here we use the Northern Eurasian Plant Macrofossil Database and palaeoecological literature to show that post-glacial migration rates for trees may have been substantially lower (60–260 m yr–1) than those estimated by assuming migration from southern refugia only (115–550 m yr–1), and that early-successional trees migrated faster than mid- and late-successional trees. Post-glacial migration rates are in good agreement with those recently projected for the future with a population dynamical forest succession and dispersal model, mainly for early-successional trees and under optimal conditions. Although migration estimates presented here may be conservative because of our assumption of uniform dispersal, tree migration-rates clearly need reconsideration. We suggest that small outlier populations may be a key factor in understanding past migration rates and in predicting potential future range-shifts. The importance of outlier populations in the past may have an analogy in the future, as many tree species have been planted beyond their natural ranges, with a more beneficial microclimate than their regional surroundings. Therefore, climate-change-induced range-shifts in the future might well be influenced by such microrefugia

    Embryonic Exposure to Domoic Acid Increases the Susceptibility of Zebrafish Larvae to the Chemical Convulsant Pentylenetetrazole

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    BACKGROUND: Domoic acid (DA) is a neurotoxin produced by diatoms of the genus Pseudonitzschia that targets the limbic system to induce tonic–clonic seizures and memory impairment. In utero DA exposure of mice leads to a reduction in seizure threshold to subsequent DA exposures in mid-postnatal life, and similar studies have shown neurotoxic effects in rats that were delayed until adolescence. OBJECTIVE: We used in ovo microinjection of zebrafish (Danio rerio) to characterize the effect of embryonic exposure of DA on seizure-inducing agents later in life as an alternative species model to screen environmental contaminants that might induce a fetal-originating adult disease. METHODS: Embryos were microinjected within hours of fertilization to DA concentrations ranging from 0.12 to 1.26 ng/mg egg weight. Seven days later, the larval animals were characterized for sensitivity to the chemical convulsant pentylenetetrazole (PTZ), an agent that is well-defined in laboratory rodents and, more recently, in zebrafish. RESULTS: In ovo DA exposure, most significantly at 0.4 ng/mg, reduces the latency time until first PTZ seizure in larval fish and increases the severity of seizures as determined by seizure stage and movement parameters. The interaction between in ovo DA exposure and PTZ caused seizure behaviors to individually asymptomatic doses of PTZ (1.0 and 1.25 mM) and DA (0.13 and 0.22 ng/mg). CONCLUSION: These studies demonstrate that in ovo exposure to DA reduces the threshold to chemically induced seizures in larval fish and increases the severity of seizure behavior in a manner that is consistent with in utero studies of laboratory rodents

    Genotoxic capacity of Cd/Se semiconductor quantum dots with differing surface chemistries.

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    Quantum dots (QD) have unique electronic and optical properties promoting biotechnological advances. However, our understanding of the toxicological structure-activity relationships remains limited. This study aimed to determine the biological impact of varying nanomaterial surface chemistry by assessing the interaction of QD with either a negative (carboxyl), neutral (hexadecylamine; HDA) or positive (amine) polymer coating with human lymphoblastoid TK6 cells. Following QD physico-chemical characterisation, cellular uptake was quantified by optical and electron microscopy. Cytotoxicity was evaluated and genotoxicity was characterised using the micronucleus assay (gross chromosomal damage) and the HPRT forward mutation assay (point mutagenicity). Cellular damage mechanisms were also explored, focusing on oxidative stress and mitochondrial damage. Cell uptake, cytotoxicity and genotoxicity were found to be dependent on QD surface chemistry. Carboxyl-QD demonstrated the smallest agglomerate size and greatest cellular uptake, which correlated with a dose dependent increase in cytotoxicity and genotoxicity. Amine-QD induced minimal cellular damage, while HDA-QD promoted substantial induction of cell death and genotoxicity. However, HDA-QD were not internalised by the cells and the damage they caused was most likely due to free cadmium release caused by QD dissolution. Oxidative stress and induced mitochondrial reactive oxygen species were only partially associated with cytotoxicity and genotoxicity induced by the QD, hence were not the only mechanisms of importance. Colloidal stability, nanoparticle (NP) surface chemistry, cellular uptake levels and the intrinsic characteristics of the NPs are therefore critical parameters impacting genotoxicity induced by QD

    Out of Amazonia: Late Holocene Climate Change and the Tupi-Guarani Trans-Continental Expansion

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    This is the author accepted manuscript. The final version is available from SAGE Publications via the DOI in this recordThe late Holocene expansion of the Tupi-Guarani languages from southern Amazonia to SE South America constitutes one of the largest expansions of any linguistic family in the world, spanning ~ 4000 km between latitudes 0°S and 35°S at about 2500 yr B.P. However, the underlying reasons for this expansion are a matter of debate. Here, we compare continental-scale paleoecological, paleoclimate, and archaeological datasets, to examine the role of climate change in facilitating the expansion of this forest-farming culture. Because this expansion lies within the path of the South American Low-Level Jet, the key mechanism for moisture transport across lowland South America, we were able to explore the relationship between climate change, forest expansion, and the Tupi-Guarani. Our data synthesis shows broad synchrony between late Holocene increasing precipitation and southerly expansion of both tropical forest and Guarani archaeological sites – the southernmost branch of the Tupi-Guarani. We conclude that climate change likely facilitated expansion of the Guarani forest-farming culture by increasing the area of forested landscape that they could exploit, showing a prime example of ecological opportunism.The ideas and themes developed in this paper stem from a European Research Council project ‘Pre-Columbian Amazon-Scale Transformations’ (ERC-CoG 616179) to JI. The University of Reading’s ‘Centre for Past Climate Change’ funded a writing workshop for this paper. RS was funded by an NERC ‘Scenario’ DTP PhD award. JGS was funded by a CAPES PhD scholarship (Ministry of Education, Brazil). JFC and MLC received postdoctoral funding from the University of Reading and the Arts and Humanities Research Council, respectively
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