495 research outputs found

    Homotopical resolutions associated to deformable adjunctions

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    Given an adjunction connecting reasonable categories with weak equivalences, we define a new derived bar and cobar construction associated to the adjunction. This yields homotopical models of the completion and cocompletion associated to the monad and comonad of the adjunction. We discuss applications of these resolutions to spectral sequences for derived completions and Goodwillie calculus in general model categories.Comment: 22 pages; v2 is the final journal version, with expository improvements suggested by the refere

    A universal characterization of higher algebraic K-theory

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    In this paper we establish a universal characterization of higher algebraic K-theory in the setting of small stable infinity categories. Specifically, we prove that connective algebraic K-theory is the universal additive invariant, i.e., the universal functor with values in spectra which inverts Morita equivalences, preserves filtered colimits, and satisfies Waldhausen's additivity theorem. Similarly, we prove that non-connective algebraic K-theory is the universal localizing invariant, i.e., the universal functor that moreover satisfies the "Thomason-Trobaugh-Neeman" localization theorem. To prove these results, we construct and study two stable infinity categories of "noncommutative motives"; one associated to additivity and another to localization. In these stable infinity categories, Waldhausen's S. construction corresponds to the suspension functor and connective and non-connective algebraic K-theory spectra become corepresentable by the noncommutative motive of the sphere spectrum. In particular, the algebraic K-theory of every scheme, stack, and ring spectrum can be recovered from these categories of noncommutative motives. In order to work with these categories of noncommutative motives, we establish comparison theorems between the category of spectral categories localized at the Morita equivalences and the category of small idempotent-complete stable infinity categories. We also explain in detail the comparison between the infinity categorical version of Waldhausen K-theory and the classical definition. As an application of our theory, we obtain a complete classification of the natural transformations from higher algebraic K-theory to topological Hochschild homology (THH) and topological cyclic homology (TC). Notably, we obtain an elegant conceptual description of the cyclotomic trace map.Comment: Various revisions and correction

    Encouraging Literacy and Mathematics Achievement Through Study of Real Estate

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    The era of high stakes testing often puts pressure on teachers and administrators to deemphasize creative activities not perceived as directly related to improving test scores. Alternatively, the authors propose that using environmental text is essential for encouraging overall learning competencies in general and reading/writing/ and mathematical achievement in particular. The authors propose that using real estate booklets can be helpful in generating learning activities in literacy, social studies, and mathematics. In addition, integrating music and art comfortably accompanies strategies presented. Real estate booklets are colorful, rich in content, and readily available at no expense

    A Patient Activities of Daily Living Scale for Amyotrophic Lateral Sclerosis

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    Background: Motor neuron disorders are rare, progressive neurodegenerative diseases which affect multiple domains of motor function. The ability to assess function from home using an electronic medical record (EMR) would facilitate pragmatic studies. Objective: To develop a Patient Activity of Daily Living scale for Amyotrophic Lateral Sclerosis and other motor neuron disorders (PADL-ALS) to support large pragmatic trials. Methods: The Greater Plains Collaborative Clinical Data Research Network (GPC) developed and tested the feasibility of using the PADL-ALS.  We convened patient and caregiver focus groups and in-person meetings to recommend changes to the ALS Functional Rating Scale-Revised (ALSFRS-R), which clarified language and added questions about pseudobulbar affect, pain, and faith.  Feasibility was determined by conducting a survey of participants identified using EMR-computable phenotypes and returned via patient-preferred modalities. Results: Surveys were distributed to 1079 participants at nine GPC health systems.  The survey response rate was 44.4% (range 12.9-57.66%): male to female ratio 1.56; 84% self-identified as a patient with ALS.  Patient respondents used computers or tablets more frequently than caregivers responding on their behalf.  The PADL-ALS correlated to clinic-performed ALSFRS-R within 4 weeks of survey completion (n=33, rho=0.93, Kansas only).  The pseudobulbar affect question correlated to functional motor burden.  Over 80% agreed to be contacted for future research opportunities. Conclusion:  We demonstrated the feasibility of determining functional burden with the PADL-ALS using an EMR-computable phenotype.  Future directions include implementing the PADL-ALS to answer pragmatic questions about ALS care

    Responding to health inequities: Indigenous health system innovations

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    This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.Over the past decades, Indigenous communities around the world have become more vocal and mobilized to address the health inequities they experience. Many Indigenous communities we work with in Canada, Australia, Latin America, the USA, New Zealand and to a lesser extent Scandinavia have developed their own culturally-informed services, focusing on the needs of their own community members. This paper discusses Indigenous healthcare innovations from an international perspective, and showcases Indigenous health system innovations that emerged in Canada (the First Nation Health Authority) and Colombia (Anas Wayúu). These case studies serve as examples of Indigenous-led innovations that might serve as models to other communities. The analysis we present suggests that when opportunities arise, Indigenous communities can and will mobilize to develop Indigenous-led primary healthcare services that are well managed and effective at addressing health inequities. Sustainable funding and supportive policy frameworks that are harmonized across international, national and local levels are required for these organizations to achieve their full potential. In conclusion, this paper demonstrates the value of supporting Indigenous health system innovations

    Public opinion on energy crops in the landscape: considerations for the expansion of renewable energy from biomass

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    Public attitudes were assessed towards two dedicated biomass crops – Miscanthus and Short Rotation Coppice (SRC), particularly regarding their visual impacts in the landscape. Results are based on responses to photographic and computer-generated images as the crops are still relatively scarce in the landscape. A questionnaire survey indicated little public concern about potential landscape aesthetics but more concern about attendant built infrastructure. Focus group meetings and interviews indicated support for biomass end uses that bring direct benefits to local communities. Questions arise as to how well the imagery used was able to portray the true nature of these tall, dense, perennial plants but based on the responses obtained and given the caveat that there was limited personal experience of the crops, it appears unlikely that wide-scale planting of biomass crops will give rise to substantial public concern in relation to their visual impact in the landscape

    TWEAK/Fn14 signalling promotes cholangiocarcinoma niche formation and progression.

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    Background & Aims: Cholangiocarcinoma (CCA) is a cancer of the hepatic bile ducts that is rarely resectable and is associated with poor prognosis. Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) is known to signal via its receptor fibroblast growth factor-inducible 14 (Fn14) and induce cholangiocyte and myofibroblast proliferation in liver injury. We aimed to characterise its role in CCA. Methods: The expression of the TWEAK ligand and Fn14 receptor was assessed immunohistochemically and by bulk RNA and single cell transcriptomics of human liver tissue. Spatiotemporal dynamics of pathway regulation were comprehensively analysed in rat and mouse models of thioacetamide (TAA)-mediated CCA. Flow cytometry, qPCR and proteomic analyses of CCA cell lines and conditioned medium experiments with primary macrophages were performed to evaluate the downstream functions of TWEAK/Fn14. In vivo pathway manipulation was assessed via TWEAK overexpression in NICD/AKT-induced CCA or genetic Fn14 knockout during TAA-mediated carcinogenesis. Results: Our data reveal TWEAK and Fn14 overexpression in multiple human CCA cohorts, and Fn14 upregulation in early TAA-induced carcinogenesis. TWEAK regulated the secretion of factors from CC-SW-1 and SNU-1079 CCA cells, inducing polarisation of proinflammatory CD206+ macrophages. Pharmacological blocking of the TWEAK downstream target chemokine monocyte chemoattractant protein 1 (MCP-1 or CCL2) significantly reduced CCA xenograft growth, while TWEAK overexpression drove cancer-associated fibroblast proliferation and collagen deposition in the tumour niche. Genetic Fn14 ablation significantly reduced inflammatory, fibrogenic and ductular responses during carcinogenic TAA-mediated injury. Conclusion: These novel data provide evidence for the action of TWEAK/Fn14 on macrophage recruitment and phenotype, and cancer-associated fibroblast proliferation in CCA. Targeting TWEAK/Fn14 and its downstream signals may provide a means to inhibit CCA niche development and tumour growth. Lay summary: Cholangiocarcinoma is an aggressive, chemotherapy-resistant liver cancer. Interactions between tumour cells and cells that form a supportive environment for the tumour to grow are a source of this aggressiveness and resistance to chemotherapy. Herein, we describe interactions between tumour cells and their supportive environment via a chemical messenger, TWEAK and its receptor Fn14. TWEAK/Fn14 alters the recruitment and type of immune cells in tumours, increases the growth of cancer-associated fibroblasts in the tumour environment, and is a potential target to reduce tumour formation
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