969 research outputs found

    Risks in circular business models innovation: A cross-industrial case study for composite materials

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    Circular business models (CBMs) are key enablers to implement circular economy (CE), yet they entail risks, which often discourage organisations. This work aims to explore the main risk factors perceived by the manufacturing industry in transitioning to CBMs to enable the development of appropriate risk management strategies. A cross- industrial multiple-case study research design was used to explore risk factors across seven organisations planning the transition to CBMs for composite-based products and involving three different CBM types—‘Circular Supplies’, ‘Product Life Extension’ and ‘Hybrid’. Results evidenced that risks are multi-disciplinary but are not equally per- ceived across different CBM types. Customers' perceptions of CE products, economic cycle and take-back systems were prevalent across all CBMs. Supply and technological risks were prioritised for ‘Circular Supplies’ CBM, whereas political and regulatory risks for ‘Product Life Extension’ CBM. This research contributes to the CE field by evaluating and prioritising the perceived risk factors in transitioning to CBMs and first disaggregating such risk factors according to CBM types. Critical risk patterns identified across different industries and CBM types enable mitigating actions to be prioritised

    Sedimentary context and palaeoecology of Gigantoproductus shell beds in the Mississippian Eyam Limestone Formation, Derbyshire carbonate platform, central England

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    A sedimentological study was conducted at two localities exposing the Mississippian Eyam Limestone Formation of the Derbyshire carbonate platform, UK. Ricklow Quarry comprises seven facies with diverse skeletal assemblages, representing deposition on the inner to middle ramp within open marine waters. Once-a-Week Quarry comprises four facies, dominated by crinoidal debris representing deposition on the inner ramp. Both localities expose Gigantoproductus shell beds. Palaeoecological analysis of a single shell bed from each locality enabled investigation of the rapid colonization and success of this taxon on the platform. At Ricklow Quarry, on the eastern side of a localized mud mound, both life (>72% of thin and thick-shelled brachiopods in life position) and neighbourhood assemblages are present. A low-moderate diversity community (<1.37 and <0.8 Shannon diversity index) rapidly established over relict Brigantian mud mounds. Shell beds are preluded by intervals of decreased energy that allowed larvae to settle. Once established, the dominance of thick-shelled individuals enabled baffling, potentially providing localized shelter for larvae and nearby individuals. At Once-a-Week Quarry, where no mud mound is present, only thick-shelled Gigantoproductus species and a low diversity community (<1.07 Shannon diversity index) exclusively comprising neighbourhood assemblages (37% in life position) is present. The presence of inactive mud mounds at Ricklow Quarry appears to have been the key to the success of Gigantoproductus species enabling the onset of stable communities in the shelter provided by the relict mound. Once the first palaeocommunities were established, larvae dispersed and colonized higher energy settings, such as at Once-a-Week Quarry

    H3F3A (Histone 3.3) G34W Immunohistochemistry: A Reliable Marker Defining Benign and Malignant Giant Cell Tumor of Bone

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    Giant cell tumor of bone (GCTB) is a locally aggressive subarticular tumor. Having recently reported that H3.3 G34W mutations are characteristic of this tumor type, we have now investigated the sensitivity and specificity of the anti-histone H3.3 G34W rabbit monoclonal antibody in a wide variety of tumors including histologic mimics of GCTB to assess its value as a diagnostic marker. We also determined the incidence of H3.3 G34 mutations in primary malignant bone tumors as assessed by genotype and H3.3 G34W immunostaining. A total of 3163 tumors were tested. Totally, 213/235 GCTB (90.6%) showed nuclear H3.3 p.G34W immunoreactivity. This was not the case for the rare variants, p.G34L, M, and V, which occurred most commonly in the small bones of the hands, patella, and the axial skeleton. If these sites were excluded from the analysis, H3.3 G34W expression was found in 97.8% of GCTB. Malignant bone tumors initially classified as osteosarcomas were the only other lesions (n=11) that showed G34W expression. Notably an additional 2 previously reported osteosarcomas with a p.G34R mutation were not immunoreactive for the antibody. A total of 11/13 of these malignant H3.3-mutant tumors exhibited an osteoclast-rich component: when imaging was available all but one presented at a subarticular site. We propose that subarticular primary malignant bone sarcoma with H3.3 mutations represent true malignant GCTB, even in the absence of a benign GCTB component

    Digital PCR analysis of circulating tumor DNA: a biomarker for chondrosarcoma diagnosis, prognostication, and residual disease detection

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    Conventional chondrosarcoma is the most common primary bone tumor in adults. Prognosis corresponds with tumor grade but remains variable, especially for individuals with grade (G) II disease. There are currently no biomarkers available for monitoring or prognostication of chondrosarcoma. Circulating tumor DNA (ctDNA) has recently emerged as a promising biomarker for a broad range of tumor types. To date, little has been done to study the presence of ctDNA and its potential utility in the management of sarcomas, including chondrosarcoma. In this study, we have assessed ctDNA levels in a cohort of 71 patients, 32 with sarcoma, including 29 individuals with central chondrosarcoma (CS) and 39 with locally aggressive and benign bone and soft tissue tumors, using digital PCR. In patients with CS, ctDNA was detected in pretreatment samples in 14/29 patients, which showed clear correlation with tumor grade as demonstrated by the detection of ctDNA in all patients with GIII and dedifferentiated disease (n = 6) and in 8/17 patients with GII disease, but never associated with GI CS. Notably detection of ctDNA preoperatively in GII disease was associated with a poor outcome. A total of 14 patients with CS had ctDNA levels assessed at multiple time points and in most patients there was a clear reduction following surgical removal. This research lays the foundation for larger studies to assess the utility of ctDNA for chondrosarcoma diagnosis, prognostication, early detection of residual disease and monitoring disease progression

    Effect of pitch range on dogs’ response to conspecific vs. heterospecific distress cries

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    Distress cries are emitted by many mammal species to elicit caregiving attention. Across taxa, these calls tend to share similar acoustic structures, but not necessarily frequency range, raising the question of their interspecific communicative potential. As domestic dogs are highly responsive to human emotional cues and experience stress when hearing human cries, we explore whether their responses to distress cries from human infants and puppies depend upon sharing conspecific frequency range or species-specific call characteristics. We recorded adult dogs’ responses to distress cries from puppies and human babies, emitted from a loudspeaker in a basket. The frequency of the cries was presented in both their natural range and also shifted to match the other species. Crucially, regardless of species origin, calls falling into the dog call-frequency range elicited more attention. Thus, domestic dogs’ responses depended strongly on the frequency range. Females responded both faster and more strongly than males, potentially reflecting asymmetries in parental care investment. Our results suggest that, despite domestication leading to an increased overall responsiveness to human cues, dogs still respond considerably less to calls in the natural human infant range than puppy range. Dogs appear to use a fast but inaccurate decision-making process to determine their response to distress-like vocalisations

    Glioblastoma adaptation traced through decline of an IDH1 clonal driver and macro-evolution of a double-minute chromosome

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    In a glioblastoma tumour with multi-region sequencing before and after recurrence, we find an IDH1 mutation that is clonal in the primary but lost at recurrence. We also describe the evolution of a double-minute chromosome encoding regulators of the PI3K signalling axis that dominates at recurrence, emphasizing the challenges of an evolving and dynamic oncogenic landscape for precision medicin
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