Primary Sources on Copyright revisited: a copyright history webinar on Papal Privileges and the Stationers' Register

This working paper presents an edited transcript of a copyright history webinar held on 15 December 2021, marking 15 years since the conception of the Primary Sources on Copyright (1450-1900) 1 digital archive. Giles Bergel (University of Oxford) and Ian Gadd (Bath Spa University) introduce Stationers’ Register Online (SRO)2 – a new resource that digitises the entries for the literary, musical and artistic works made in the Registers of the Stationers’ Company of London3 between 1557 and 1640. Jane Ginsburg (Columbia Law School) presents a new section on Vatican sources which she (and her team of Latinists) contributed to the Primary Sources digital archive, edited by Lionel Bently (University of Cambridge) and Martin Kretschmer (CREATe, University of Glasgow). The project presentations were followed by a panel discussion, joined by Elena Cooper (CREATe, University of Glasgow) and Neil Netanel (University of California at Los Angeles), two of the national editors of Primary Sources on Copyright. This working paper offers a reference point of wider interest. What should be the ambitions of a primary sources project? Can the history of copyright law be re-written? What is the role of history for policy

Protection from inflammatory organ damage in a murine model of hemophagocytic lymphohistiocytosis using treatment with IL-18 binding protein

Hemophagocytic lymphohistiocytosis (HLH) is a life threatening condition due to the association of an infectious agent with lymphocyte cytotoxicity defects, either of congenital genetic origin in children or presumably acquired in adults. In HLH patients, an excess of lymphocyte or macrophage cytokines, such as IFN-gamma and TN Fu is present in serum. In animal models of the disease, IFN-gamma and INF-alpha have been shown to play a central pathogenic role. In humans, unusually high concentrations of IL-18, an inducer of IFN-gamma, and INF-alpha have been reported, and are associated with an imbalance between IL-18 and its natural inhibitor IL18 binding protein (IL18BP) resulting in an excess of free IL18 Here we studied whether IL-18B P could reduce disease severity in an animal model of HLH. Mouse cytomegalovirus infection in perforin-1 knock out mice induced a lethal condition similar to human HLH characterized by cytopenia with marked inflammatory lesions in the liver and spleen as well as the presence of hemophagocytosis in bone marrow. IL-18B P treatment decreased hemophagocytosis and reversed liver as well as spleen damage. IL-18BP treatment also reduced both IFN-gamma and TNF-alpha production by CD8+ T and NK cells, as well as Fas ligand expression on NK cell surface. These data suggest that IL-18B P is beneficial in an animal model of HLH and in combination with anti infectious therapy may be a promising strategy to treat HLH patients

Moxetumomab pasudotox in heavily pre-treated patients with relapsed/refractory hairy cell leukemia (HCL): long-term follow-up from the pivotal trial

Background Moxetumomab pasudotox is a recombinant CD22-targeting immunotoxin. Here, we present the long-term follow-up analysis of the pivotal, multicenter, open-label trial (NCT01829711) of moxetumomab pasudotox in patients with relapsed/refractory (R/R) hairy cell leukemia (HCL). Methods Eligible patients had received ≥ 2 prior systemic therapies, including ≥ 2 purine nucleoside analogs (PNAs), or ≥ 1 PNA followed by rituximab or a BRAF inhibitor. Patients received 40 µg/kg moxetumomab pasudotox intravenously on Days 1, 3, and 5 of each 28-day cycle for up to six cycles. Disease response and minimal residual disease (MRD) status were determined by blinded independent central review. The primary endpoint was durable complete response (CR), defined as achieving CR with hematologic remission (HR, blood counts for CR) lasting > 180 days. Results Eighty adult patients were treated with moxetumomab pasudotox and 63% completed six cycles. Patients had received a median of three lines of prior systemic therapy; 49% were PNA-refractory, and 38% were unfit for PNA retreatment. At a median follow-up of 24.6 months, the durable CR rate (CR with HR > 180 days) was 36% (29 patients; 95% confidence interval: 26–48%); CR with HR ≥ 360 days was 33%, and overall CR was 41%. Twenty-seven complete responders (82%) were MRD-negative (34% of all patients). CR lasting ≥ 60 months was 61%, and the median progression-free survival without the loss of HR was 71.7 months. Hemolytic uremic and capillary leak syndromes were each reported in ≤ 10% of patients, and ≤ 5% had grade 3–4 events; these events were generally reversible. No treatment-related deaths were reported. Conclusions Moxetumomab pasudotox resulted in a high rate of durable responses and MRD negativity in heavily pre-treated patients with HCL, with a manageable safety profile. Thus, it represents a new and viable treatment option for patients with R/R HCL, who currently lack adequate therapy.publishedVersio

Crop Updates 2002 - Weeds

This session covers fifty eight papers from different authors: 1. INTRODUCTION Vanessa Stewart, DEPARTMENT OF AGRICULTURE INTEGRATED WEED MANAGEMENT IWM system studies / demonstration sites 2. Major outcomes from IWM demonstration sites, Alexandra Douglas Department of Agriculture 3. Integrated weed management: Katanning, Alexandra Douglas Department of Agriculture 4. Integrated weed management: Merredin, Vanessa Stewart Department of Agriculture 5. Long term resistance site: Get ryegrass numbers low and keep them low! Peter Newman and Glen Adams Department of Agriculture 6. Using pastures to manage ryegrass populations, Andrew Blake and Natalie Lauritsen Department of Agriculture Weed biology and competition 7. Understanding the weed seed bank life if important agricultural weeds, Sally Peltzer and Paul Matson Department of Agriculture 8. Consequence of radish competition on lupin nutrients in wheat-lupin rotation, Abul Hashem and Nerys Wilkins Department of Agriculture 9. Consequence of ryegrass competition on lupin nutrients in a wheat-lupin rotation, Abul Hashem and Nerys Wilkins Department of Agriculture 10. Brome grass too competitive for early sown wheat in a dry year at Mullewa, Peter Newman and Glenn Adam Department of Agriculture Crop establishment and weed management 11. Seeding rate, row spacing and herbicides for weed control, David Minkey Department of Agriculture 12. Effect of different seeding methods on wheat and ryegrass, Abul Hashem, Glen Riethmuller and Nerys Wilkins Department of Agriculture 13. Role of tillage implements and trifluralin on the effectiveness of the autumn tickle for stimulating annual ryegrass emergence, Tim Cusack1, Kathryn Steadman1 and Abul Hashem2,1Western Australia Herbicide Resistance Initiative, UWA; 2Department of Agriculture, 14. Timing of autumn tickle in important for non-wetting soils, Pippa Michael1, Peter Newman2 and Kathryn Steadman 2, 1Western Australia Herbicide Resistance Initiative, UWA, 2Department of Agriculture 15. Early investigation into weed seed burial by mouldboard plough, Sally Peltzer and Alex Douglas Department of Agriculture 16. Rolling post-emergent lupins to improve weed emergence and control on loamy sand, Paul Blackwell, Department of Agriculture and Dave Brindal, Strawberry via Mingenew IWM tools 17. Crop topping in 2001: How did we do? Peter Newman and Glenn Adam Department of Agriculture 18. Wickwipers work! Peter Newman and Glenn Adam Department of Agriculture 19. Wild radish and ryegrass seed collection at harvest: Chaff carts and other devices, Michael Walsh Western Australia Herbicide Resistance Initiative, UWA and Wayne Parker Department of Agriculture 20. Improving weed control in grazed pastures using legumes with low palatability, Clinton Revell, Giles Glasson Department of Agriculture, and Dean Thomas Faculty of Agriculture, University of Western Australia Adoption and modelling 21. Grower weed survey, Peter Newman and Glenn Adam Department of Agriculture 22. Agronomist survey, Peter Newman and Glenn Adam Department of Agriculture 23. Ryegrass RIM model stands the test of IWM field trial data, Alister Draper Western Australia Herbicide Resistance Initiative, UWA and Bill Roy, Western Australia Herbicide Resistance Initiative, UWA Agricultural Consulting and Research Services 24. Multi-species RIM: An update, Marta Monjardin1,2, David Pannell2 and Stephen Powles 1, 1Western Australia Herbicide Resistance Initiative, UWA, 2 ARE, University of Western Australia 25. RIM survey feedback, Robert Barrett-Lennard and Alister Draper Western Australia Herbicide Resistance Initiative, UWA 26. Effect of historic input and product prices on choice of ryegrass management strategies, Alister Draper1 and Martin Bent2, 1Western Australia Herbicide Resistance Initiative, UWA, 2Muresk Institute of Agriculture 27. Living with ryegrass – trading off weed control and economic performance, Martin Bent1 and Alister Draper2 , 1Muresk Institute of Agriculture, Curtin University, 2Western Australia Herbicide Resistance Initiative, UWA HERBICIDE RESISTANCE 28. Glyphosate resistance in WA and Australia: Where are we at? Paul Neve1, Art Diggle2, Patrick Smith3, Mechelle Owen1, Abul Hashem2, Christopher Preston4and Stephen Powles1,1Western Australian Herbicide Resistance Initiative, University of Western Australia, 2Department of Agriculture, 3CSIRO Sustainable Ecosystems, 4CRC for Australian Weed Management and Department of Applied and Molecular Ecology, Waite Campus, University of Adelaide 29. We need you weeds: A survey of knockdown resistance in the WA wheatbelt, Paul Neve1, Mechelle Owen1, Abul Hashem2 and Stephen Powles1 1Western Australian Herbicide Resistance Initiative, University of Western Australia, 2Department of Agriculture 30. A test for resistance testing, Mechelle Owen, Tracey Gillam, Rick Llewellyn and Steve Powles,Western Australia Herbicide Resistance Initiative, University of Western Australia 31. In field testing for herbicide resistance, a purpose built multi-treatment spray boom with results from 2001, Richard Quinlan, Elders Ltd 32. Advantages and limitations of a purpose built multi-treatment spray boom, Richard Quinlan, Elders Ltd 33. Group F resistant wild radish: What’s new? Aik Cheam, Siew Lee Department of Agriculture, and Mike Clarke Aventis Crop Science 34. Cross resistance of Brodal® resistant wild radish to Sniper®, Aik Cheam and Siew Lee, Department of Agriculture 35. Managing a biotype of wild radish with Group F and Group C resistance, Aik Cheam, Siew Lee, David Nicholson, Peter Newman Department of Agriculture and Mike Clarke, Aventis Crop Science HERBICIDE TOLERANCE 36. Herbicide tolerance of new wheat varieties, Harmohinder S. Dhammu, Terry Piper and David Nicholson, Agriculture Western Australia 37. Response of barley varieties to herbicides, Harmohinder S. Dhammu, Terry Piper, Department of Agriculture 38. Tolerance of barley to phenoxy herbicides, Harmohinder S. Dhammu, Terry Piper, Department of Agriculture and Chad Sayer, Nufarm Australia Limited 39. Response of Durum wheats to herbicides, Harmohinder S. Dhammu, Terry Piper, Department of Agriculture 40. Response of new field pea varieties to herbicides, Harmohinder S. Dhammu, Terry Piper and David Nicholson, Department of Agriculture 41. Herbicide tolerance of Desi chickpeas on marginal soil, Harmohinder S. Dhammu, Terry Piper and David Nicholson, Department of Agriculture 42. Herbicide tolerance of newer lupin varieties, Terry Piper, Harmohinder Dhammu and David Nicholson, Department of Agriculture 43. Herbicide tolerance of some annual pasture legumes, Clinton Revell and Ian Rose, Department of Agriculture 44. Herbicide tolerance of pasture legumes, Andrew Blake, Department of Agriculture HERBICIDES – NEW PRODUCTS/PRODUCT USES; USE 45. Knockdown herbicides do not reliably kill small grass weeds, Peter Newman and Glenn Adam, Department of Agriculture 46. ‘Hair Cutting’ wheat with Spray.Seed®: Does it work? Peter Newman and Glenn Adam, Department of Agriculture 47. ‘Haircutting’: Does the number one cut work? Robert Barrett-Lennard1 and Jerome Critch2,1WA Herbicide Resistance Initiative, University of WA, 2Student, University of WA 48. Hammer EC (Carfentrazone-ethyl): A mixing partner for glyphosate to enhance the control of difficult broadleaf weeds, Gordon R. Cumming, Crop Care Australasia 49. Marshmallow control in reduced tillage systems, Sam Taylor, Wesfarmers Landmark 50. Herbicide options for summer germinating marshmallow, Vanessa Stewart, Department of Agriculture 51. Dual Gold® safe in a dry year at Coorow, Peter Newman and Glenn Adam, Department of Agriculture 52. The effect of glyphosate, paraquat and diquat as a crop topping application on the germination of barley, John Moore and Roslyn Jettner, Department of Agriculture 53. Herbicide options for melon control, Vanessa Stewart, Department of Agriculture 54. Herbicide options for the control of Chloris truncate (windmill grass) Vanessa Stewart, Department of Agriculture 55. Allelopathic effects of crop, pasture and weed residues on subsequent crop and pasture establishment, Stuart Bee1, Lionel Martin1, Keith Devenish2 and Terry Piper2, 1Muresk Institute of Agriculture, Curtin University of Technology, Northam, Western Australia, 2Centre for Cropping Systems, Department of Agriculture WEED ISSUES 56. Role of Roundup ReadyÒ canola in the farming system, Art Diggle1, Patrick Smith2, Paul Neve3, Felicity Flugge4, Amir Abadi5 and Stephen Powles3, 1Department of Agriculture; 2CSIRO, Sustainable Ecosystems; 3Western Australian Herbicide Resistance Initiative; 4Centre for Legumes in Mediterranean Agriculture; 5Touchstone Consulting 57. ’Weeds for Feed’ and livestock enterprise structures: A feasibility study and farmer survey in the north-easern wheatbelt, Duncan Peter and Stuart McAlpine, Department of Agriculture and Liebe Group, Buntine 58. e-weed, Vanessa Stewart, Agriculture Western Australi

Influenza Virus A Infection of Human Monocyte and Macrophage Subpopulations Reveals Increased Susceptibility Associated with Cell Differentiation

Influenza virus infection accounts for significant morbidity and mortality world-wide. Interactions of the virus with host cells, particularly those of the macrophage lineage, are thought to contribute to various pathological changes associated with poor patient outcome. Development of new strategies to treat disease therefore requires a detailed understanding of the impact of virus infection upon cellular responses. Here we report that human blood-derived monocytes could be readily infected with the H3N2 influenza virus A/Udorn/72 (Udorn), irrespective of their phenotype (CD14++/CD16−, CD14++/CD16+ or CD14dimCD16++), as determined by multi-colour flow cytometry for viral haemagglutinin (HA) expression and cell surface markers 8–16 hours post infection. Monocytes are relatively resistant to influenza-induced cell death early in infection, as approximately 20% of cells showed influenza-induced caspase-dependent apoptosis. Infection of monocytes with Udorn also induced the release of IL-6, IL-8, TNFα and IP-10, suggesting that NS1 protein of Udorn does not (effectively) inhibit this host defence response in human monocytes. Comparative analysis of human monocyte-derived macrophages (Mph) demonstrated greater susceptibility to human influenza virus than monocytes, with the majority of both pro-inflammatory Mph1 and anti-inflammatory/regulatory Mph2 cells expressing viral HA after infection with Udorn. Influenza infection of macrophages also induced cytokine and chemokine production. However, both Mph1 and Mph2 phenotypes released comparable amounts of TNFα, IL-12p40 and IP-10 after infection with H3N2, in marked contrast to differential responses to LPS-stimulation. In addition, we found that influenza virus infection augmented the capacity of poorly phagocytic Mph1 cells to phagocytose apoptotic cells by a mechanism that was independent of either IL-10 or the Mer receptor tyrosine kinase/Protein S pathway. In summary, our data reveal that influenza virus infection of human macrophages causes functional alterations that may impact on the process of resolution of inflammation, with implications for viral clearance and lung pathology

Agents of May Fourth. Jing Yinyu, Xu Zhongnian, and the Early Introduction of Modern Chinese Literature in France

Jing Yinyu (1901-1931?) and Xu Zhongnian (1904-1981) played a pivotal role in the dissemination of modern Chinese literature in France at the turn of the 1930s. Best known as Lu Xun’s first translator into a Western language and a friend of Romain Rolland’s, Jing compiled the Anthologie des conteurs chinois modernes in 1929. In his Anthologie de la littérature chinoise. Des origines à nos jours, published in 1932, Xu also devoted a section to recent literary developments. By analyzing the nature of the two projects, the translated corpora, and their paratexts, I will describe the features of Jing’s and Xu’s dissemination of May Fourth literature in France and scrutinize their artistic and ideological stance vis-à-vis the new literary scene. Ultimately, I will attempt to pinpoint in what terms the two scholars-cum-translators’ agency contributed to foreign readers’ awareness of the cultural, social and political experience of the May Fourth Movement

Kynurenine–3–monooxygenase inhibition prevents multiple organ failure in rodent models of acute pancreatitis

Acute pancreatitis (AP) is a common and devastating inflammatory condition of the pancreas that is considered to be a paradigm of sterile inflammation leading to systemic multiple organ dysfunction syndrome (MODS) and death1,2 Acute mortality from AP-MODS exceeds 20%3 and for those who survive the initial episode, their lifespan is typically shorter than the general population4. There are no specific therapies available that protect individuals against AP-MODS. Here, we show that kynurenine-3-monooxygenase (KMO), a key enzyme of tryptophan metabolism5, is central to the pathogenesis of AP-MODS. We created a mouse strain deficient for Kmo with a robust biochemical phenotype that protected against extrapancreatic tissue injury to lung, kidney and liver in experimental AP-MODS. A medicinal chemistry strategy based on modifications of the kynurenine substrate led to the discovery of GSK180 as a potent and specific inhibitor of KMO. The binding mode of the inhibitor in the active site was confirmed by X-ray co-crystallography at 3.2 Å resolution. Treatment with GSK180 resulted in rapid changes in levels of kynurenine pathway metabolites in vivo and afforded therapeutic protection against AP-MODS in a rat model of AP. Our findings establish KMO inhibition as a novel therapeutic strategy in the treatment of AP-MODS and open up a new area for drug discovery in critical illness

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men