432 research outputs found

    The effects of seasonal and latitudinal earth infrared radiance variations on ERBS attitude control

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    Analysis performed in the Flight Dynamics Facility by the Earth Radiation Budget Satellite (ERBS) Attitude Determination Support team illustrates the pitch attitude control motion and roll attitude errors induced by Earth infrared (IR) horizon radiance variations. IR scanner and inertial reference unit (IRU) pitch and roll flight data spanning 4 years of the ERBS mission are analyzed to illustrate the changes in the magnitude of the errors on time scales of the orbital period, months, and seasons. The analysis represents a unique opportunity to compare prelaunch estimates of radiance-induced attitude errors with flight measurements. As a consequence of this work the following additional information is obtained: an assessment of an average model of these errors and its standard deviation, a measurement to determine and verify previously proposed corrections to the current Earth IR radiance data base, and the possibility of a mean motion model derived from flight data in place of IRU data for ERBS fine attitude determination

    The New ‘Hidden Abode’: Reflections on Value and Labour in the New Economy

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    In a pivotal section of Capital, volume 1, Marx (1976: 279) notes that, in order to understand the capitalist production of value, we must descend into the ‘hidden abode of production’: the site of the labour process conducted within an employment relationship. In this paper we argue that by remaining wedded to an analysis of labour that is confined to the employment relationship, Labour Process Theory (LPT) has missed a fundamental shift in the location of value production in contemporary capitalism. We examine this shift through the work of Autonomist Marxists like Hardt and Negri, Lazaratto and Arvidsson, who offer theoretical leverage to prize open a new ‘hidden abode’ outside employment, for example in the ‘production of organization’ and in consumption. Although they can open up this new ‘hidden abode’, without LPT's fine-grained analysis of control/resistance, indeterminacy and structured antagonism, these theorists risk succumbing to empirically naive claims about the ‘new economy’. Through developing an expanded conception of a ‘new hidden abode’ of production, the paper demarcates an analytical space in which both LPT and Autonomist Marxism can expand and develop their understanding of labour and value production in today's economy. </jats:p

    Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

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    BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care

    Using derivative logic to speculate on the future of the social investment market

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    This article pries open the black box of the social impact bond (SIB), the novel financial instrument at the heart of social investment. We discover that concrete information is currently limited and our method is thus more speculative. We address the obfuscation of the nomenclature of the instrument and explore the mechanics of SIBs to suggest that they are not simple bonds but rather also bear properties akin to those associated with derivative contracts. We speculate on possible developments of the market in these bonds by considering the history of some previous financial innovations, namely, collateralized debt obligations (CDOs) underpinned by microfinance loans and the short-lived policy analysis market. Our discussion leads us to reevaluate Goodhart’s law and the ways in which it operates in relation to SIBs. We conclude by suggesting that SIBs' inherent indifference to the underlying state of the world renders them ultimately unlikely to delivery improvements in public services

    The M3 muscarinic receptor Is required for optimal adaptive immunity to Helminth and bacterial infection

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    Innate immunity is regulated by cholinergic signalling through nicotinic acetylcholine receptors. We show here that signalling through the M3 muscarinic acetylcholine receptor (M3R) plays an important role in adaptive immunity to both Nippostrongylus brasiliensis and Salmonella enterica serovar Typhimurium, as M3R-/- mice were impaired in their ability to resolve infection with either pathogen. CD4 T cell activation and cytokine production were reduced in M3R-/- mice. Immunity to secondary infection with N. brasiliensis was severely impaired, with reduced cytokine responses in M3R-/- mice accompanied by lower numbers of mucus-producing goblet cells and alternatively activated macrophages in the lungs. Ex vivo lymphocyte stimulation of cells from intact BALB/c mice infected with N. brasiliensis and S. typhimurium with muscarinic agonists resulted in enhanced production of IL-13 and IFN-γ respectively, which was blocked by an M3R-selective antagonist. Our data therefore indicate that cholinergic signalling via the M3R is essential for optimal Th1 and Th2 adaptive immunity to infection

    Super diversity and city branding: Rotterdam in perspective

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    As many other cities around the world, Rotterdam has been investing in improving its image to stimulate urban development and to attract visitors, residents and investors. In particular, during the last 15 years the municipality of Rotterdam has intensified its attempts to develop a ‘brand’ that fits the ‘new Rotterdam’, which was gradually rebuilt after destructive bombardments during the Second World War (Riezebos 2014). In 2014 Rotterdam was ranked 8th by ‘Rough Guide’ in the list of ‘Top 10 Cities to See’, whereas the ‘New York Times’ listed Rotterdam in the top 10 of 52 Places to Go. These rankings demonstrate Rotterdam’s success in repositioning itself, using the physical interior of the city as a key element in its branding strategy.</p

    Breast cancer biomarkers predict weight loss after gastric bypass surgery

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    <p>Abstract</p> <p>Background</p> <p>Obesity has long been associated with postmenopausal breast cancer risk and more recently with premenopausal breast cancer risk. We previously observed that nipple aspirate fluid (n) levels of prostate specific antigen (PSA) were associated with obesity. Serum (s) levels of adiponectin are lower in women with higher body mass index (BMI) and with breast cancer. We conducted a prospective study of obese women who underwent gastric bypass surgery to determine: 1) change in n- and s-adiponectin and nPSA after surgery and 2) if biomarker change is related to change in BMI. Samples (30-s, 28-n) and BMI were obtained from women 0, 3, 6 and 12 months after surgery.</p> <p>Findings</p> <p>There was a significant increase after surgery in pre- but not postmenopausal women at all time points in s-adiponectin and at 3 and 6 months in n-adiponectin. Low n-PSA and high s-adiponectin values were highly correlated with decrease in BMI from baseline.</p> <p>Conclusions</p> <p>Adiponectin increases locally in the breast and systemically in premenopausal women after gastric bypass. s-adiponectin in pre- and nPSA in postmenopausal women correlated with greater weight loss. This study provides preliminary evidence for biologic markers to predict weight loss after gastric bypass surgery.</p

    Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

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    INTRODUCTION Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years
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