1,653 research outputs found

    Flexible formwork technologies – a state of the art review

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    Concrete is our most widely used construction material. Worldwide consumption of cement, the strength-giving component of concrete, is estimated at 4.10 Gt per year, rising from 2.22 Gt just ten years ago [1]. This rate of consumption means that cement manufacture alone is estimated to account for 5.2 % of global carbon dioxide emissions [2].Concrete offers the opportunity to economically create structures of almost any geometry. Yet its unique fluidity is seldom capitalised upon, with concrete instead being cast into rigid, flat moulds to create unoptimised geometries that result in high material use structures with large carbon footprints. This paper will explore flexible formwork construction technologies which embrace the fluidity of concrete to facilitate the practical construction of concrete structures with complex and efficient geometries. This paper presents the current state of the art in flexible formwork technology, highlighting practical uses, research challenges and new opportunities

    Prolonged response to first-line erlotinib for advanced lung adenocarcinoma

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    A 58-year-old, non-smoking female of Philippine origin presented with painful thoracic and neck nodal relapse of lung adenocarcinoma almost 5 years after left pneumonectomy for stage II non-small-cell lung cancer. She refused conventional chemotherapy or radiation because of toxicity concerns, but agreed to oral erlotinib 150 mg/day. Within weeks, her pain was well controlled, with softening of palpable neck nodes. Repeat scans after 7 months on erlotinib showed partial response of thoracic disease and nodal metastases. This response was maintained for 11 months on erlotinib, with symptomatic progression at the original sites of relapse by 15 months. Erlotinib was well tolerated, with grade 2–3 rash, and grade 1 dry cough and diarrhoea being the only significant toxicities. Importantly, the patient was able to maintain daily activities throughout erlotinib therapy

    A demonstration of an affinity between pyrite and organic matter in a hydrothermal setting

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    One of the key-principles of the iron-sulphur world theory is to bring organic molecules close enough to interact with each other, using the surface of pyrite as a substrate in a hydrothermal setting. The present paper explores the relationship of pyrite and organic matter in a hydrothermal setting from the geological record; in hydrothermal calcite veins from Carboniferous limestones in central Ireland. Here, the organic matter is accumulated as coatings around, and through, pyrite grains. Most of the pyrite grains are euhedral-subhedral crystals, ranging in size from ca 0.1-0.5 mm in diameter, and they are scattered throughout the matrix of the vein calcite. The organic matter was deposited from a hydrothermal fluid at a temperature of at least 200°C, and gives a Raman signature of disordered carbon. This study points to an example from a hydrothermal setting in the geological record, demonstrating that pyrite can have a high potential for the concentration and accumulation of organic materials

    The risk of febrile neutropenia in patients with non-small-cell lung cancer treated with docetaxel: a systematic review and meta-analysis

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    We aimed to assess the incidence of febrile neutropenia in patients with non small cell lung cancer treated with docetaxel as second line chemotherapy by systematic review and meta-analysis of clinical studies. Published studies were retrieved and included if they considered docetaxel at the licensed dose after a previous chemotherapy regimen, and reported the proportion of patients getting FN. Meta-analysis was conducted to estimate the proportion of patients who experience one or more episodes of FN. The pooled, random effects meta-analysis estimate for the proportion of patients who experience one or more episodes of FN on docetaxel was 5.95% (95% CI 4.22–8.31) based on 13 studies, comprising 1609 patients. No significant differences were seen either between studies that permitted the use of prophylactic granulocyte colony-stimulating factors or between phase II and phase III trials

    Systematic population screening, using biomarkers and genetic testing, identifies 2.5% of the U.K. pediatric diabetes population with monogenic diabetes

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    This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.OBJECTIVE: Monogenic diabetes is rare but is an important diagnosis in pediatric diabetes clinics. These patients are often not identified as this relies on the recognition of key clinical features by an alert clinician. Biomarkers (islet autoantibodies and C-peptide) can assist in the exclusion of patients with type 1 diabetes and allow systematic testing that does not rely on clinical recognition. Our study aimed to establish the prevalence of monogenic diabetes in U.K. pediatric clinics using a systematic approach of biomarker screening and targeted genetic testing. RESEARCH DESIGN AND METHODS: We studied 808 patients (79.5% of the eligible population) <20 years of age with diabetes who were attending six pediatric clinics in South West England and Tayside, Scotland. Endogenous insulin production was measured using the urinary C-peptide creatinine ratio (UCPCR). C-peptide-positive patients (UCPCR ≥0.2 nmol/mmol) underwent islet autoantibody (GAD and IA2) testing, with patients who were autoantibody negative undergoing genetic testing for all 29 identified causes of monogenic diabetes. RESULTS: A total of 2.5% of patients (20 of 808 patients) (95% CI 1.6-3.9%) had monogenic diabetes (8 GCK, 5 HNF1A, 4 HNF4A, 1 HNF1B, 1 ABCC8, 1 INSR). The majority (17 of 20 patients) were managed without insulin treatment. A similar proportion of the population had type 2 diabetes (3.3%, 27 of 808 patients). CONCLUSIONS: This large systematic study confirms a prevalence of 2.5% of patients with monogenic diabetes who were <20 years of age in six U.K. clinics. This figure suggests that ∼50% of the estimated 875 U.K. pediatric patients with monogenic diabetes have still not received a genetic diagnosis. This biomarker screening pathway is a practical approach that can be used to identify pediatric patients who are most appropriate for genetic testing.This work presents independent research commissioned by the Health Innovation Challenge Fund, a parallel funding partnership between the Wellcome Trust and the Department of Health (grant HICF-1009-041); and was supported by the National Institute for Health Research (NIHR) Exeter Clinical Research Facility and the South West Peninsula Diabetes Research Network. M.S. is supported by the NIHR Exeter Clinical Research Facility. T.J.M. is funded by an NIHR CSO Fellowship. S.E. and A.T.H. are both Wellcome Trust Senior Investigators. E.R.P. is a Wellcome Trust New Investigator. A.T.H. is an NIHR Senior Investigator

    Binary orbits as the driver of γ-ray emission and mass ejection in classical novae

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    Classical novae are the most common astrophysical thermonuclear explosions, occurring on the surfaces of white dwarf stars accreting gas from companions in binary star systems. Novae typically expel �10,000 solar masses of material at velocities exceeding 1,000 km/s. However, the mechanism of mass ejection in novae is poorly understood, and could be dominated by the impulsive flash of the thermonuclear runaway, prolonged optically thick winds, or binary interaction with the nova envelope. Classical novae are now routinely detected in GeV gamma-rays, suggesting that relativistic particles are accelerated by strong shocks in nova ejecta. Here we present high-resolution imaging of the gamma-ray-emitting nova V959 Mon at radio wavelengths, showing that its ejecta were shaped by binary motion: some gas was expelled rapidly along the poles as a wind from the white dwarf, while denser material drifted out along the equatorial plane, propelled by orbital motion. At the interface between the equatorial and polar regions, we observe synchrotron emission indicative of shocks and relativistic particle acceleration, thereby pinpointing the location of gamma-ray production. Binary shaping of the nova ejecta and associated internal shocks are expected to be widespread among novae, explaining why many novae are gamma-ray emitters

    Targeted antitumour therapy – future perspectives

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    The advent of targeted therapy presents an unprecedented opportunity for advances in the treatment of cancer. A key challenge will be to translate the undoubted promise of targeted agents into tangible clinical benefits. Achieving this goal is likely to be dependent upon a number of factors. These include continued research to improve our understanding of the heterogeneity and complexity of the tumour microenvironment; refinement of clinical trial design to incorporate nontraditional end points such as the optimum biological dose and health-related quality of life; and the use of technological advancements in proteomics, genomics and biomarker development to better predict tumour types and patient subsets that may be particularly responsive to treatment, as well as enable a more accurate assessment of drug effect at the molecular level. In summary, the future success of targeted agents will require an integrated multidisciplinary approach involving all stakeholders

    Migraine aura: retracting particle-like waves in weakly susceptible cortex

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    Cortical spreading depression (SD) has been suggested to underlie migraine aura. Despite a precise match in speed, the spatio-temporal patterns of SD and aura symptoms on the cortical surface ordinarily differ in aspects of size and shape. We show that this mismatch is reconciled by utilizing that both pattern types bifurcate from an instability point of generic reaction-diffusion models. To classify these spatio-temporal pattern we suggest a susceptibility scale having the value [sigma]=1 at the instability point. We predict that human cortex is only weakly susceptible to SD ([sigma]&#x3c;1), and support this prediction by directly matching visual aura symptoms with anatomical landmarks using fMRI retinotopic mapping. We discuss the increased dynamical repertoire of cortical tissue close to [sigma]=1, in particular, the resulting implications on migraine pharmacology that is hitherto tested in the regime ([sigma]&#x3e;&#x3e;1), and potentially silent aura occurring below a second bifurcation point at [sigma]=0 on the susceptible scale
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