3,079 research outputs found

    Integrative analyses identify modulators of response to neoadjuvant aromatase inhibitors in patients with early breast cancer

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    Introduction Aromatase inhibitors (AIs) are a vital component of estrogen receptor positive (ER+) breast cancer treatment. De novo and acquired resistance, however, is common. The aims of this study were to relate patterns of copy number aberrations to molecular and proliferative response to AIs, to study differences in the patterns of copy number aberrations between breast cancer samples pre- and post-AI neoadjuvant therapy, and to identify putative biomarkers for resistance to neoadjuvant AI therapy using an integrative analysis approach. Methods Samples from 84 patients derived from two neoadjuvant AI therapy trials were subjected to copy number profiling by microarray-based comparative genomic hybridisation (aCGH, n = 84), gene expression profiling (n = 47), matched pre- and post-AI aCGH (n = 19 pairs) and Ki67-based AI-response analysis (n = 39). Results Integrative analysis of these datasets identified a set of nine genes that, when amplified, were associated with a poor response to AIs, and were significantly overexpressed when amplified, including CHKA, LRP5 and SAPS3. Functional validation in vitro, using cell lines with and without amplification of these genes (SUM44, MDA-MB134-VI, T47D and MCF7) and a model of acquired AI-resistance (MCF7-LTED) identified CHKA as a gene that when amplified modulates estrogen receptor (ER)-driven proliferation, ER/estrogen response element (ERE) transactivation, expression of ER-regulated genes and phosphorylation of V-AKT murine thymoma viral oncogene homolog 1 (AKT1). Conclusions These data provide a rationale for investigation of the role of CHKA in further models of de novo and acquired resistance to AIs, and provide proof of concept that integrative genomic analyses can identify biologically relevant modulators of AI response

    Anxiety, depression, traumatic stress and COVID-19-related anxiety in the UK general population during the COVID-19 pandemic

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    BACKGROUND: The COVID-19 pandemic has created an unprecedented global crisis, necessitating drastic changes to living conditions, social life, personal freedom and economic activity. No study has yet examined the presence of psychiatric symptoms in the UK population under similar conditions. AIMS: We investigated the prevalence of COVID-19-related anxiety, generalised anxiety, depression and trauma symptoms in the UK population during an early phase of the pandemic, and estimated associations with variables likely to influence these symptoms. METHOD: Between 23 and 28 March 2020, a quota sample of 2025 UK adults aged 18 years and older, stratified by age, gender and household income, was recruited by online survey company Qualtrics. Participants completed standardised measures of depression, generalised anxiety and trauma symptoms relating to the pandemic. Bivariate and multivariate associations were calculated for demographic and health-related variables. RESULTS: Higher levels of anxiety, depression and trauma symptoms were reported compared with previous population studies, but not dramatically so. Anxiety or depression and trauma symptoms were predicted by young age, presence of children in the home, and high estimates of personal risk. Anxiety and depression were also predicted by low income, loss of income and pre-existing health conditions in self and others. Specific anxiety about COVID-19 was greater in older participants. CONCLUSIONS: This study showed a modest increase in the prevalence of mental health problems in the early stages of the pandemic, and these problems were predicted by several specific COVID-related variables. Further similar surveys, particularly of those with children at home, are required as the pandemic progresses

    Negotiating professional and social voices in research principles and practice

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    This paper draws on work conducted for a qualitative interview based study which explores the gendered racialised and professional identifications of health and social care professionals. Participants for the project were drawn from the professional executive committees of recently formed Primary Care Trusts. The paper discusses how the feminist psychosocial methodological approach developed for the project is theoretically, practically and ethically useful in exploring the voices of those in positions of relative power in relation to both health and social care services and the social relations of gender and ethnicity. The approach draws on psychodynamic accounts of (defended) subjectivity and the feminist work of Carol Gilligan on a voice-centred relational methodology. Coupling the feminist with the psychosocial facilitates an emphasis on voice and dialogic communication between participant and researcher not always captured in psychosocial approaches which tend towards favouring the interviewer as ‘good listener’. This emphasis on dialogue is important in research contexts where prior and ongoing relationships with professional participants make it difficult and indeed undesirable for researchers to maintain silence

    Odour-mediated orientation of beetles is influenced by age, sex and morph

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    The behaviour of insects is dictated by a combination of factors and may vary considerably between individuals, but small insects are often considered en masse and thus these differences can be overlooked. For example, the cowpea bruchid Callosobruchus maculatus F. exists naturally in two adult forms: the active (flight) form for dispersal, and the inactive (flightless), more fecund but shorter-lived form. Given that these morphs show dissimilar biology, it is possible that they differ in odour-mediated orientation and yet studies of this species frequently neglect to distinguish morph type, or are carried out only on the inactive morph. Along with sex and age of individual, adult morph could be an important variable determining the biology of this and similar species, informing studies on evolution, ecology and pest management. We used an olfactometer with motion-tracking to investigate whether the olfactory behaviour and orientation of C. maculatus towards infested and uninfested cowpeas and a plant-derived repellent compound, methyl salicylate, differed between morphs or sexes. We found significant differences between the behaviour of male and female beetles and beetles of different ages, as well as interactive effects of sex, morph and age, in response to both host and repellent odours. This study demonstrates that behavioural experiments on insects should control for sex and age, while also considering differences between adult morphs where present in insect species. This finding has broad implications for fundamental entomological research, particularly when exploring the relationships between physiology, behaviour and evolutionary biology, and the application of crop protection strategies

    Functional diversity of marine ecosystems after the Late Permian mass extinction event

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    Article can be accessed from http://www.nature.com/ngeo/journal/v7/n3/full/ngeo2079.htmlThe Late Permian mass extinction event was the most severe such crisis of the past 500 million years and occurred during an episode of global warming. It is assumed to have had significant ecological impact, but its effects on marine ecosystem functioning are unknown and the patterns of marine recovery are debated. We analysed the fossil occurrences of all known Permian-Triassic benthic marine genera and assigned each to a functional group based on their inferred life habit. We show that despite the selective extinction of 62-74% of marine genera there was no significant loss of functional diversity at the global scale, and only one novel mode of life originated in the extinction aftermath. Early Triassic marine ecosystems were not as ecologically depauperate as widely assumed, which explains the absence of a Cambrian-style Triassic radiation in higher taxa. Functional diversity was, however, significantly reduced in particular regions and habitats, such as tropical reefs, and at these scales recovery varied spatially and temporally, probably driven by migration of surviving groups. Marine ecosystems did not return to their pre-extinction state, however, and radiation of previously subordinate groups such as motile, epifaunal grazers led to greater functional evenness by the Middle Triassic

    Populating a Knowledge Base with Object-Location Relations Using Distributional Semantics

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    International audienceThe paper presents an approach to extract knowledge from large text corpora, in particular knowledge that facilitates object manipulation by embodied intelligent systems that need to act in the world. As a first step, our goal is to extract the prototypical location of given objects from text corpora. We approach this task by calculating relatedness scores for objects and locations using techniques from distributional semantics. We empirically compare different methods for representing locations and objects as vectors in some geometric space, and we evaluate them with respect to a crowd-sourced gold standard in which human subjects had to rate the prototypicality of a location given an object. By applying the proposed framework on DBpedia, we are able to build a knowledge base of 931 high confidence object-locations relations in a fully automatic fashion.

    COVID‐19‐related anxiety predicts somatic symptoms in the UK population

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    This study aimed to estimate the association between anxiety associated with COVID‐19 and somatic symptoms, using data from a large, representative sample (N = 2,025) of the UK adult population. Results showed that moderate to high levels of anxiety associated with COVID‐19 were significantly associated with general somatic symptoms and in particular with gastrointestinal and fatigue symptoms. This pattern of associations remained significant after controlling for generalized anxiety disorder (GAD), pre‐existing health problems, age, gender, and income. This is the first evidence that anxiety associated with COVID‐19 makes a unique contribution to somatization, above and beyond the effect of GAD

    The Authoritarian Dynamic During the COVID-19 Pandemic: Effects on Nationalism and Anti-Immigrant Sentiment

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    Research has demonstrated that situational factors such as perceived threats to the social order activate latent authoritarianism. The deadly COVID-19 pandemic presents a rare opportunity to test whether existential threat stemming from an indiscriminate virus moderates the relationship between authoritarianism and political attitudes toward the nation and out-groups. Using data from two large nationally representative samples of adults in the United Kingdom (N = 2,025) and Republic of Ireland (N = 1,041) collected during the initial phases of strict lockdown measures in both countries, we find that the associations between right-wing authoritarianism (RWA) and (1) nationalism and (2) anti-immigrant attitudes are conditional on levels of perceived threat. As anxiety about the COVID-19 pandemic increases, so too does the effect of RWA on those political outcomes. Thus, it appears that existential threats to humanity from the COVID-19 pandemic moderate expressions of authoritarianism in society
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