895 research outputs found
Ludology as a theoretical lens for interactive works: Demonstrating the theoretical gaps in copyright analysis of interactive works
This research argues that without the appropriate category or lexicon to address interactive creations and with their assessment by analogy, interactive creations are improperly protected by copyright. They are over-under protected, their infringement decisions incoherent, inconsistent, and are protected in ways which entirely overlook their distinct and unique characteristics as an expressive medium. Drawing the boundaries of protection already proves difficult for copyright, owing to flaws and shortcomings with its principles and subject matter categorization. Which in part is why copyright struggles to protect interactive creations. However, it is contended that interactive creations present further difficulties which emerge by virtue of their interactivity. It is argued that this interactivity leads them to present significant practical and conceptual questions which copyright is ill equipped to answer. And whilst the existing academic commentary does highlight the challenges facing interactive creations, it does not do so in a way that meaningfully or specifically addresses interactive creations as a distinct medium, nor does it consider their unique qualities. To that end, this thesis argues that video game scholarship presents a helpful foundation for understanding how a more accurate ontology for interactive works might be constructed. It is contended that video game studies and ludology, can provide insights on what these neglected qualities are, as well as potential frameworks and vocabulary for more appropriately understanding and structuring these concepts. Arguing that ludology and the concepts proposed by the ludologist Frasca provide a clearer analytical lens for assessing the distinct and novel expressive capabilities of the medium. Concluding that copyright must re-evaluate its scope and purpose to better accommodate the subject matter it seeks to protect
The Anthropocene monument:on relating geological and human time
In the Parthenon frieze, the time of mortals and the time of gods seem to merge. Dipesh Chakrabarty has argued that with the advent of the Anthropocene the times of human history and of the Earth are similarly coming together. Are humans entering the ‘monumental time’ of the Earth, to stand alongside the Olympian gods of the other geological forces? In this paper I first look at the cultural shifts leading to the modern idea of separate human and Earth histories. I examine the changing use of monuments to mediate between human and other temporalities. I explore the use of ‘stratigraphic sections’ as natural monuments to mark transitions between the major time units of Earth history, and the erection of intentional monuments nearby. I suggest that the Anthropocene, as a geological epoch-in-the-making, may challenge the whole system of monumental semiotics used to stabilise our way of thinking about deep time
An ontology for strongly sustainable business models: Defining an enterprise framework compatible with natural and social science
Business is increasingly employing sustainability practices, aiming to improve environmental and social responsibility while maintaining and improving profitability. For many organizations, profit-oriented business models are a major constraint impeding progress in sustainability. A formally defined ontology, a model definition, for profit-oriented business models has been employed globally for several years. However, no equivalent ontology is available in research or practice that enables the description of strongly sustainable business models, as validated by ecological economics and derived from natural, social, and system sciences. We present a framework of strongly sustainable business model propositions and principles as findings from a transdisciplinary review of the literature. A comparative analysis was performed between the framework and the Osterwalder profit-oriented ontology for business models. We introduce an ontology that enables the description of successful strongly sustainable business models that resolves weaknesses and includes functionally necessary relationships
HDAC inhibitor confers radiosensitivity to prostate stem-like cells
Background: Radiotherapy can be an effective treatment for prostate cancer, but radiorecurrent tumours do develop. Considering prostate cancer heterogeneity, we hypothesised that primitive stem-like cells may constitute the radiation-resistant fraction.
Methods: Primary cultures were derived from patients undergoing resection for prostate cancer or benign prostatic hyperplasia. After short-term culture, three populations of cells were sorted, reflecting the prostate epithelial hierarchy, namely stem-like cells (SCs, α2β1integrinhi/CD133+), transit-amplifying (TA, α2β1integrinhi/CD133−) and committed basal (CB, α2β1integrinlo) cells. Radiosensitivity was measured by colony-forming efficiency (CFE) and DNA damage by comet assay and DNA damage foci quantification. Immunofluorescence and flow cytometry were used to measure heterochromatin. The HDAC (histone deacetylase) inhibitor Trichostatin A was used as a radiosensitiser.
Results: Stem-like cells had increased CFE post irradiation compared with the more differentiated cells (TA and CB). The SC population sustained fewer lethal double-strand breaks than either TA or CB cells, which correlated with SCs being less proliferative and having increased levels of heterochromatin. Finally, treatment with an HDAC inhibitor sensitised the SCs to radiation.
Interpretation: Prostate SCs are more radioresistant than more differentiated cell populations. We suggest that the primitive cells survive radiation therapy and that pre-treatment with HDAC inhibitors may sensitise this resistant fraction
Clinical Features, Treatment, and Outcome in 102 Adult and Pediatric Patients with Localized High-Grade Synovial Sarcoma
Background. There remains controversy on the routine use of chemotherapy in localized SS. Methods. The records of 87 adult (AP) and 15 pediatric (PP) patients with localized SS diagnosed between 1986 and 2007 at 2 centres in Toronto were reviewed. Results. Median age for AP and PP was 37.6 (range 15–76) and 14 (range 0.4–18) years, respectively. 65 (64%) patients had large tumours (>5 cm). All patients underwent en bloc surgical resection resulting in 94 (92.2%) negative and 8 (7.8%) microscopically positive surgical margins. 72 (82.8%) AP and 8 (53%) PP received radiotherapy. Chemotherapy was
administered to 12 (13.8%) AP and 13 (87%) PP. 10 AP and 5 PP were evaluable for response to
neoadjuvant chemotherapy, with response rate of 10% and 40%, respectively. 5-year EFS and OS was
69.3 ± 4.8% and 80.3 ± 4.3%, respectively, and was similar for AP and PP, In patients with tumors >5 cm, in whom chemotherapy might be considered most appropriate, relapse occurred in 9/19 (47%) with
chemotherapy, compared to 17/46 (37%) In those without. Conclusions. Patients with localized SS have a
good chance of cure with surgery and RT. Evidence for a well-defined role of chemotherapy to improve
survival In localized SS remains elusive
Human CEACAM1 is targeted by a Streptococcus pyogenes adhesin implicated in puerperal sepsis pathogenesis
Life-threatening bacterial infections in women after childbirth, known as puerperal sepsis, resulted in classical epidemics and remain a global health problem. While outbreaks of puerperal sepsis have been ascribed to Streptococcus pyogenes, little is known about disease mechanisms. Here, we show that the bacterial R28 protein, which is epidemiologically associated with outbreaks of puerperal sepsis, specifically targets the human receptor CEACAM1. This interaction triggers events that would favor development of puerperal sepsis, including adhesion to cervical cells, suppression of epithelial wound repair and subversion of innate immune responses. High-resolution structural analysis showed that an R28 domain with IgI3-like fold binds to the N-terminal domain of CEACAM1. Together, these findings demonstrate that a single adhesin-receptor interaction can drive the pathogenesis of bacterial sepsis and provide molecular insights into the pathogenesis of one of the most important infectious diseases in medical history
Planned surgery in the COVID-19 pandemic: a prospective cohort study from Nottingham
PurposeGlobally planned surgical procedures have been deferred during the current COVID-19 pandemic. The study aimed to report the outcomes of planned urgent and cancer cases during the current pandemic using a multi-disciplinary prioritisation group.MethodsA prospective cohort study of patients having urgent or cancer surgery at a NHS Trust from 1st March to 30th April 2020 who had been prioritised by a multi-disciplinary COVID Surgery group. Rates of post-operative PCR positive and suspected COVID-19 infections within 30 days, 30-day mortality and any death related to COVID-19 are reported.ResultsOverall 597 patients underwent surgery with a median age of 65 years (interquartile range (IQR) 54–74 years). Of these, 86.1% (514/597) had a current cancer diagnosis. During the period, 60.8% (363/597) of patients had surgery at the NHS Trust whilst 39.2% (234/597) had surgery at Independent Sector hospitals. The incidence of COVID-19 in the East Midlands was 193.7 per 100,000 population during the study period. In the 30 days following surgery, 1.3% (8/597) of patients tested positive for COVID-19 with all cases at the NHS site. Overall 30-day mortality was 0.7% (4/597). Following a PCR positive COVID-19 diagnosis, mortality was 25.0% (2/8). Including both PCR positive and suspected cases, 3.0% (18/597) developed COVID-19 infection with 1.3% at the independent site compared to 4.1% at the NHS Trust (p=0.047).ConclusionsRates of COVID-19 infection in the post-operative period were low especially in the Independent Sector site. Mortality following a post-operative diagnosis of COVID-19 was high
A rare case of giant leiomyosarcoma in a filarial scrotum: a case report
Giant leiomyosarcoma of scrotum is a rare tumour. A case of scrotum leiomyosarcoma is presented in a 67 year old patient with scrotal filariasis which was managed successfully with total scrotectomy with bilateral orchidectomy, degloved penis reconstructed with rotation advancement supra pubic fasciocutaneous flap. We made a literature search proving the rarity of this lesion type. Only 36 cases have been described and the first case in a filarial scrotu
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