744 research outputs found

    Evaluation of Adjunctive Mycophenolate for Large Vessel Giant Cell Arteritis

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    Funding: We are grateful to Versus Arthritis (grant 22088) and PMR/GCA Scotland for supporting our workPeer reviewedPublisher PD

    Examining affective-motivational dynamics and behavioral implications within the interpersonal context of pain

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    Emotional, motivational, and interpersonal dimensions are considered integral to pain experience but have largely been examined separately. In this focus article, we argue that an integrative theoretical account that acknowledges each of these elements is a critical next step to capture the complexity and nuance of interpersonal pain dynamics and to shape future research. The aim of this focus article is to provide a foundation for such an account by drawing upon established insights from appraisal theory of emotion, influential behavioral models, empathy/interpersonal pain research, and social psychology literature to highlight conceptual relationships, potential mechanisms of action, and avenues of inquiry that have not previously been examined in the context of pain. Specifically, we highlight the interpersonal nature of pain and the conceptual relationship between emotion and motivation in pain experience. We discuss an affective-motivational tension between self- and other-oriented goals that can arise within the interpersonal pain context, and how such dynamics may affect the nature and effectiveness of care giving behavior. We then describe the role of emotion regulation and strategies that may facilitate optimal interpersonal pain dynamics and caregiving within a multiple goal context. Finally, we outline a foundation for an integrative theoretical model and directions for future research. Perspective: Drawing upon insights from appraisal theory of emotion, empathy/interpersonal pain research, influential behavioral models, and social psychology literature, this focus article provides a foundation for an integrative affective-motivational account of interpersonal pain dynamics as a basis for theoretical and clinical advancement. (C) 2017 by the American Pain Societ

    Synchronisation of egg hatching of brown hairstreak (Thecla betulae) and budburst of blackthorn (Prunus spinosa) in a warmer future

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    Synchronisation of the phenology of insect herbivores and their larval food plant is essential for the herbivores’ fitness. The monophagous brown hairstreak (Thecla betulae) lays its eggs during summer, hibernates as an egg, and hatches in April or May in the Netherlands. Its main larval food plant blackthorn (Prunus spinosa) flowers in early spring, just before the leaves appear. As soon as the Blackthorn opens its buds, and this varies with spring temperatures, food becomes available for the brown hairstreak. However, the suitability of the leaves as food for the young caterpillars is expected to decrease rapidly. Therefore, the timing of egg hatch is an important factor for larval growth. This study evaluates food availability for brown hairstreak at different temperatures. Egg hatch and budburst were monitored from 2004 to 2008 at different sites in the Netherlands. Results showed ample food availability at all monitored temperatures and sites but the degree of synchrony varied strongly with spring temperatures. To further study the effect of temperature on synchronisation, an experiment using normal temperatures of a reference year (T) and temperatures of T + 5°C was carried out in climate chambers. At T + 5°C, both budburst and egg hatch took place about 20 days earlier and thus, on average, elevated temperature did not affect synchrony. However, the total period of budburst was 11 days longer, whereas the period of egg hatching was 3 days shorter. The implications for larval growth by the brown hairstreak under a warmer climate are considered.

    History of oceanic front development in the New Zealand sector of the Southern Ocean during the Cenozoic--a synthesis

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    The New Zealand sector of the Southern Ocean (NZSSO) has opened about the Indian-Pacific spreading ridge throughout the Cenozoic. Today the NZSSO is characterised by broad zonal belts of antarctic (cold), subantarctic (cool), and subtropical (warm) surface-water masses separated by prominent oceanic fronts: the Subtropical Front (STF) c. 43deg.S, Subantarctic Front (SAF) c. 50deg.S, and Antarctic Polar Front (AAPF) c. 60deg.S. Despite a meagre database, the broad pattern of Cenozoic evolution of these fronts is reviewed from the results of Deep Sea Drilling Project-based studies of sediment facies, microfossil assemblages and diversity, and stable isotope records, as well as from evidence in onland New Zealand Cenozoic sequences. Results are depicted schematically on seven paleogeographic maps covering the NZSSO at 10 m.y. intervals through the Cenozoic. During the Paleocene and most of the Eocene (65-35 Ma), the entire NZSSO was under the influence of warm to cool subtropical waters, with no detectable oceanic fronts. In the latest Eocene (c. 35 Ma), a proto-STF is shown separating subantarctic and subtropical waters offshore from Antarctica, near 65deg.S paleolatitude. During the earliest Oligocene, this front was displaced northwards by development of an AAPF following major global cooling and biotic turnover associated with ice sheet expansion to sea level on East Antarctica. Early Oligocene full opening (c. 31 Ma) of the Tasmanian gateway initiated vigorous proto-circum-Antarctic flow of cold/cool waters, possibly through a West Antarctic seaway linking the southern Pacific and Atlantic Oceans, including detached northwards "jetting" onto the New Zealand plateau where condensation and unconformity development was widespread in cool-water carbonate facies. Since this time, a broad tripartite division of antarctic, subantarctic, and subtropical waters has existed in the NZSSO, including possible development of a proto-SAF within the subantarctic belt. In the Early-early Middle Miocene (25-15 Ma), warm subtropical waters expanded southwards into the northern NZSSO, possibly associated with reduced ice volume on East Antarctica but particularly with restriction of the Indonesian gateway and redirection of intensified warm surface flows southwards into the Tasman Sea, as well as complete opening of the Drake gateway by 23 Ma allowing more complete decoupling of cool circum-Antarctic flow from the subtropical waters. During the late Middle-Late Miocene (15-5 Ma), both the STF and SAF proper were established in their present relative positions across and about the Campbell Plateau, respectively, accompanying renewed ice buildup on East Antarctica and formation of a permanent ice sheet on West Antarctica, as well as generally more expansive and intensified circum-Antarctic flow. The ultimate control on the history of oceanic front development in the NZSSO has been plate tectonics through its influence on the paleogeographic changes of the Australian-New Zealand-Antarctic continents and their intervening oceanic basins, the timing of opening and closing of critical seaways, the potential for submarine ridges and plateaus to exert some bathymetric control on the location of fronts, and the evolving ice budget on the Antarctic continent. The broad trends of the Cenozoic climate curve for New Zealand deduced from fossil evidence in the uplifted marine sedimentary record correspond well to the principal paleoceanographic events controlling the evolution and migration of the oceanic fronts in the NZSSO

    Telomere fusion threshold identifies a poor prognostic subset of breast cancer patients

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    Telomere dysfunction and fusion can drive genomic instability and clonal evolution in human tumours, including breast cancer. Telomere length is a critical determinant of telomere function and has been evaluated as a prognostic marker in several tumour types, but it has yet to be used in the clinical setting. Here we show that high-resolution telomere length analysis, together with a specific telomere fusion threshold, is highly prognostic for overall survival in a cohort of patients diagnosed with invasive ductal carcinoma of the breast (n = 120). The telomere fusion threshold defined a small subset of patients with an extremely poor clinical outcome, with a median survival of less than 12 months (HR = 21.4 (7.9-57.6), P < 0.0001). Furthermore, this telomere length threshold was independent of ER, PGR, HER2 status, NPI, or grade and was the dominant variable in multivariate analysis. We conclude that the fusogenic telomere length threshold provides a powerful, independent prognostic marker with clinical utility in breast cancer. Larger prospective studies are now required to determine the optimal way to incorporate high-resolution telomere length analysis into multivariate prognostic algorithms for patients diagnosed with breast cancer

    A supermatrix analysis of genomic, morphological, and paleontological data from crown Cetacea

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    <p>Abstract</p> <p>Background</p> <p>Cetacea (dolphins, porpoises, and whales) is a clade of aquatic species that includes the most massive, deepest diving, and largest brained mammals. Understanding the temporal pattern of diversification in the group as well as the evolution of cetacean anatomy and behavior requires a robust and well-resolved phylogenetic hypothesis. Although a large body of molecular data has accumulated over the past 20 years, DNA sequences of cetaceans have not been directly integrated with the rich, cetacean fossil record to reconcile discrepancies among molecular and morphological characters.</p> <p>Results</p> <p>We combined new nuclear DNA sequences, including segments of six genes (~2800 basepairs) from the functionally extinct Yangtze River dolphin, with an expanded morphological matrix and published genomic data. Diverse analyses of these data resolved the relationships of 74 taxa that represent all extant families and 11 extinct families of Cetacea. The resulting supermatrix (61,155 characters) and its sub-partitions were analyzed using parsimony methods. Bayesian and maximum likelihood (ML) searches were conducted on the molecular partition, and a molecular scaffold obtained from these searches was used to constrain a parsimony search of the morphological partition. Based on analysis of the supermatrix and model-based analyses of the molecular partition, we found overwhelming support for 15 extant clades. When extinct taxa are included, we recovered trees that are significantly correlated with the fossil record. These trees were used to reconstruct the timing of cetacean diversification and the evolution of characters shared by "river dolphins," a non-monophyletic set of species according to all of our phylogenetic analyses.</p> <p>Conclusions</p> <p>The parsimony analysis of the supermatrix and the analysis of morphology constrained to fit the ML/Bayesian molecular tree yielded broadly congruent phylogenetic hypotheses. In trees from both analyses, all Oligocene taxa included in our study fell outside crown Mysticeti and crown Odontoceti, suggesting that these two clades radiated in the late Oligocene or later, contra some recent molecular clock studies. Our trees also imply that many character states shared by river dolphins evolved in their oceanic ancestors, contradicting the hypothesis that these characters are convergent adaptations to fluvial habitats.</p
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