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BACKGROUND A standard-of-care has not been established for the management of DS patients who develop primary CNS GCTs – the most common CNS neoplasm in DS – despite being more susceptible to treatment-related adverse events. METHODS A review of the English-language medical literature between 1960 and 2020 was conducted. RESULTS Thirty-one cases of CNS GCTs in DS patients (median nine-years-old; 21 males) were reported; the majority (23/31) originated from East Asia. Twelve had germinomas (39%), 12 had non-germinomatous germ cell tumors (NGGCTs) (39%), and seven had teratomas (22%). Four patients (13%) died from tumor progression (one germinoma versus three teratoma). Seven patients (23%) died from treatment-related complications (four germinoma versus three NGGCT). Of the germinoma patients, two died from chemotherapy-related sepsis, one from post-surgery cardiopulmonary failure, and one from Moyamoya following radiation-therapy (RT) only. Of the NGGCT patients, one died from chemotherapy-related sepsis, one from post-surgical infection, and one from pneumonia following surgery/chemotherapy/RT. Three-year overall survival (OS) was 58.1% for all patients, 52.5% for germinoma, 64.8% for NGGCT, and 60% for teratoma. Three-year OS for patients who received RT or chemotherapy was 63.6% and 59.6% respectively. Twenty patients (65%) remain alive (seven germinoma versus nine NGCCT versus four teratoma). Ten patients (32%) experienced serious treatment-related complications (five germinoma versus five NGGCT). CONCLUSIONS Patients with DS and CNS GCTs are at an increased risk of treatment-related complications. Therefore, a different therapeutic approach may need to be considered for this patient population in order to mitigate the treatment-related complications and long-term neurocognitive sequelae.

References to "customers‟ have become commonplace in the policy discourses within UK government and other public sector bodies. It is a working assumption of UK public sector management that the concept of the "customer‟ can be applied to any public sector service agency or department; this paper analyses how the UK government‟s revenue department, formerly titled the Inland Revenue (IR), re-characterised firstly taxpayers and latterly tax claimants as "customers," rather than "users," of IR services. This paper identifies some problems, dilemmas and ambiguities associated with this reconceptualisation in the context of an organisation that is predominantly a regulating department. Far from being merely a reclassification of the taxpayer as customer, the emerging discourse and associated practices of the IR were in part embedded in organisational change including the merger with HM Customs and Excise to form the present-day HMRC. Thus, this case analysis illustrates the limits of consumerism as a strategic tool of a government revenue department and raises wider questions for public management.

Genetic modification of NK cells to enhance cancer immunotherapy has potential application to treat a wide range of cancers. Recently, we developed a new strategy in which CRISPR/Cas9 elements are introduced into NK cells as ribonucleoproteins (RNPs) via electroporation, followed by expansion on feeder cells expressing 4-1BBL and membrane-bound IL-21 to generate large numbers of genetically modified NK cells. This method was used to genetically modify several genes in primary and expanded NK cells including suppressor of cytokine signaling 3 (SOCS3). SOCS3 negatively regulates cytokine signaling through the JAK/STAT pathway. We hypothesized that disruption of SOCS3 in primary NK cells using Cas9/RNPs could potentially maintain STAT3 signaling levels and subsequently increase their proliferation and cytotoxic function. We designed gRNAs to target exon 2 of the SOCS3 gene and electroporated them along with Cas9 protein as Cas9/RNPs into primary NK cells using the Lonza 4D electroporator. We tested 6 different conditions of gRNAs alone or in combination. The NK cells in the control group were electroporated with no Cas9/RNPs. After electroporation, the cells were rested in culture media supplemented with 100 IU of human IL-2 for 48 hours and then expanded using irradiated feeder cells. At day 7, an equal number of cells were restimulated with irradiated feeder cells to test the effect of SOCS3 KO on proliferation. Western blot was used to assay the knock out efficacy at the protein level. Calcein assay and IncuCyte Zoom (Essen) were performed to measure cytotoxicity against two cancer cell lines, K562 and Daoy. Our results showed a significant reduction in SOCS3 protein levels in 3 conditions (gRNA1, gRNA3 and gRNA1+ gRNA3) in comparison to the control group. The calcein assay and IncuCyte zoom showed the modified SOCS3 KO NK cells could kill the tumors more efficiently in comparison to the control. Proliferation data showed the SOCS3 KO cells can grow faster than the control group. In conclusion, our data demonstrate the role of SOCS3 and JAK/STAT pathway in NK cell function and suggests that SOCS3 may be a good target for genetic modification to improve cancer immunotherapy using NK cells. Disclosures Lee: CytoSen Therapeutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck, Sharp, and Dohme: Consultancy; Courier Therapeutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees.

This review essay suggests considerations to be addressed in research design if research on a taxation subject is to succeed as rigorous accounting research, well grounded in relevant historical scholarship. Tax research must focus on substantive subjects that are recognizable as “accounting”; the methods, approach, and exposition must be “historical” to an acceptable standard; and the research must engage with relevant portions of the existing body of accounting historical scholarship. Further, scholarly engagement with the best researchers and liveliest debates that the disciplines of accounting and history have to offer will enrich the treatment of tax in accounting history

Seven British income tax disputes over depreciation (1875–1897) are analyzed in this contextual study. The legal cases reveal how uncertainty over meanings for “depreciation,” “profits,” and “capital” reflected social and political tensions which had commercial accounting implications. Case analysis yields evidence of how judicial support reinforced the Inland Revenue's technical authority over a competing tax administration institution and enabled its modern regulatory control over taxpayers to be constructed. The British example illustrates the ways in which technical and administrative practices may emerge from the contestation of meanings that takes place both in a wide political context and within particular institutional settings.

In 1855 Jane Carlyle, wife of historian Thomas Carlyle, appeared before the General Commissioners of Income Tax to appeal against her husband's assessment. Moulded around her memoire of the appeal, this paper explores the process of and social context for mid-nineteenth century English income taxation of profits, and the associated accountings and processes of accountability. It reveals how local tax authorities employed sovereign powers as the basis for regulatory control. The paper outlines conditions of possibility for the emergence of modern Inland Revenue powers based on disciplinary technologies.

Taxation practice represents a significant part of what may be classed as accounting practice. In contrast, taxation research represents a very small part of the accounting research field. This pap...

This paper constructs a method for assessing the degree of connection between tax rules and practices and financial reporting rules and practices in a country. Five types of connection and disconnection are suggested, and 15 arenas of accounting are proposed for assessment on this basis. The method is applied to four countries, partly in order to test the claim of a clear distinction between Anglo-Saxon and continental European countries.

The relationship between accounting and taxation in the United Kingdom is explored in this article. The first section considers historical reasons for the relative independence of contemporary calculations of accounting profits and taxable profits. Despite the formal independence of important aspects of the calculation regimes, effective interdependence of practice is a feature of the United Kingdom's tax and accounting histories. The second section outlines the current law and practice governing the recognition of taxable profits, and reviews the financial reporting standards and practices that have been developed to deal with tax/accounting differences. Finally, recent developments in financial report-ing and taxation are identified that are likely to have an impact on the character of the relationship between tax and accounting in the future.