Journal articles on the topic 'Erwin frink'

Nota biográfica sobre Erwin Heinrich Frank (1950-2008), antropólogo alemão que trabalhou no Peru, Equador e Brasil. Neste último país, Frank foi professor na Universidade Federal do Pará e na Universidade Federal de Roraima. Escrita pela esposa do cientista, a nota apresenta elementos da formação, do trabalho de campo e da obra do antropólogo, incluindo o projeto de pesquisa que deu origem ao texto inédito publicado neste mesmo número da revista, sobre a etnografia de Theodor Koch-Grünberg.

By 1909 the French actor, playwright, and director Max Linder was probably the most popular male film star of his time, and his success as an innovative writer-actor of variety and revue continued until the outbreak of the First World War. But this followed five years of frustration in stage-ornament roles on the professional, ‘legitimate’ stage, and only after success in the cinema did his playlets, integrating filmed and live action, further enhance his fame in variety venues across Europe. After the war, and Linder's stints in Hollywood, his long descent into bouts of manic depression tragically began. But his theatrical spirit survives in the cine-stage works of the Prague theatre, Laterna Magika, and Frank Bren also discusses here his possible influence on the work of Erwin Piscator, and more surely on the spectacular Paris music-hall production, Jour de fête à l'Olympia, created by and starring Jacques Tati in 1961. This was plainly modelled on Linder's cinema-theatre creations of 1910–1914, with Tati and Pierre Etaix the outstanding successors to Max in French film comedy. Australian actor-author Frank Bren is currently writing a biography of Pierre Etaix, whose classic film comedies of the sixties are now being restored for international re-release – two of them paying discreet homage to Max Linder. Bren has written or co-written histories of Polish and Chinese cinema and theatre as well as articles for diverse international periodicals.

Abstract Aging is the leading risk factor for cancer. While some have proposed that the age-related accumulation of somatic mutations drives this relationship, it is likely not the full story. Here, we show that both aging and cancer share a common epigenetic replication signature, which we modeled from DNA methylation data in extensively passaged immortalized human cells in vitro and tested on clinical tissues. This epigenetic signature of replication – termed CellDRIFT – increased with age across multiple tissues, distinguished tumor from normal tissue, and was escalated in normal breast tissue from cancer patients. Additionally, within-person tissue differences were correlated with both predicted lifetime tissue-specific stem cell divisions and tissue-specific cancer risk. Overall, our findings suggest that age-related replication drives epigenetic changes in cells, potentially pushing them towards a more tumorigenic state. Citation Format: Christopher J. Minteer, Kyra Thrush, Peter Niimi, Joel Rozowsky, Jason Liu, Mor Frank, Thomas McCabe, Erin Hofstatter, Mariya Rozenblit, Lajos Pusztai, Kenneth Beckman, Mark Gerstein, Morgan E. Levine. Revisiting the bad luck hypothesis: Cancer risk and aging are linked to replication-driven changes to the epigenome [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr PR009.

The relevance of research. In German literary criticism, there is no unambiguous definition of the phenomenon of literary realism, however, at the empirical level, it is understood as a literary system based on a mimetic-oriented depiction of reality, often critically comprehended and subjectively colored due to the norms and ideas that are taking shape in society. Research methodology. Complex and systematic methods of literature analysis are applied. In this article, the author comes to the conclusion that the realism of the turn of the XIX - early XX centuries. retains its main principles of artistic comprehension of the world, and at the same time the signs that do not allow talking about its dissolution in the eclectic picture of the emerging modernity. The main thing remains the disclosure of "the essence of life phenomena through their individualized generalization (typification)", analysis and specific historical logic of presentation Realism at the turn of the 19th - early 20th centuries. closely associated with such phenomena as regional literature, "new business-like", historical novel. On its basis, workers' and proletarian-revolutionary literature developed in many ways. In German literature of the twentieth century. realistic tendencies intensified in the times following the historical and political catastrophes, primarily after the two world wars lost by Germany. Realism played a significant role in the literature of the Weimar Republic (the works of E.M. Remarque, L. Feuchtwanger, L. Frank and others), while in contact with modernist and avant-garde trends (for example, with "new business-like"). Realism turned out to be no less significant after 1945, having equally influenced the formation of the literatures of West and East Germany (writers of the "group of 47", Erwin Strittmatter, "socialist realism", etc.). German realism, which emerged in the middle of the 19th century, was able to demonstrate its flexibility and ability to enter into alliances with other natural artistic directions, without losing its main specificity - the desire for materiality, the authenticity of personal and collective experience, as well as symbolizing the "obvious" with the goal of approaching the "true".

Abstract Abstract: Sarcopenia, a condition characterized by the loss of muscle mass, strength and function with age, is highly prevalent in cancer survivors. The relationship between sarcopenia and prognosis among cancer survivors is not well understood. Methods: From the Third National Health and Nutrition Examination Survey (NHANES III), we identified 946 participants who were diagnosed with cancer (mean age 60.6 years); the most common disease sites were breast, prostate, colon and melanoma. We assembled an age, sex and race-matched cohort of 1,857 participants without cancer (mean age, 60.2 years). Sarcopenia was defined by appendicular lean mass and body height (men <7.26 kg/m2, women <5.45 kg/m2). Proportional-hazard models were used to assess whether sarcopenia was associated with all cause and CVD-specific time to death after taking into account baseline age, sex, race/ethnicity, smoking status, and energy intake for each cohort. In the cancer survivor cohort, models were additionally adjusted for a history of having more than one cancer and time since diagnosis. Mortality was ascertained from the National Center for Health Statistics Linked Mortality Files. Results: There were 321 deaths among cancer survivors (33.9% of the cohort) during a median follow-up of 10.5 years versus 495 deaths among participants without cancer (26.7% of the cohort) during a median follow-up of 10.9 years. Deaths from cardiovascular disease (CVD) were observed in 58 (6.1%) cancer survivors versus 122 (6.6%) participants without cancer. Overall, sarcopenia was more prevalent among cancer survivors versus the matched cohort (22.2% versus 19.7% respectively). Rates of CVD death were more than twice higher among cancer survivors with versus without sarcopenia (adjusted hazard ratio, 2.17, 95% confidence interval [CI], 1.16 to 4.05). All-cause mortality was 79% higher (adjusted hazard ratio, 1.79; 95% CI, 1.36 to 2.36) among cancer survivors with versus without sarcopenia. No significant associations were seen between sarcopenia and rates of death from all causes and CVD specifically among participants without cancer. Conclusion: Cancer survivors with sarcopenia have an increased risk of all-cause and CVD-specific mortality. In contrast, sarcopenia was not a major predictor of these outcomes in the matched cohort without cancer. Citation Format: Dejana Braithwaite, Shama Karanth, Christiaan Leeuwenburgh, Todd M. Manini, Meghann Wheeler, Danting Yang, Livingstone Aduse-Poke, Stephen Anton, Frank Penedo, Erin M. Siegel, Jonathan D. Licht, Dongyu Zhang. Elevated all-cause and cardiovascular mortality in cancer survivors with sarcopenia [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr B001.

Abstract Glioblastoma (GBM) is the most common malignant brain tumor in adults with a dismal 15-month median survival. Standard therapy consisting of surgical resection, radiation, and temozolomide has been unsuccessful in meaningfully extending survival and preventing recurrence; thus, novel therapeutics are urgently needed. One proposed targeted treatment strategy for GBM involves using small molecule inhibitors against common genetic mutations. Epidermal growth factor receptor (EGFR) is the most commonly overexpressed oncogene in GBM (~56%). While EGFR tyrosine kinase inhibitors (TKI) have shown promise in other cancers, GBM clinical trials with EGFR TKI have failed. One reason for this failure is the development of adaptive therapeutic resistance. Understanding the mechanisms behind drug resistance is essential for the development of novel, effective therapeutics for GBM. To better understand adaptive resistance in GBM, we utilized two genetically engineered mouse astrocyte lines harboring common GBM mutations: Cdkn2a-/-, EGFRvIII (CEv3) and Cdkn2a-/-, Pten-/-, EGFRvIII (CEV3P). CDKN2A and PTEN are commonly deleted or otherwise inactivated tumor suppressor genes in GBM while the vIII variant of EGFR is the single most common oncogene mutation, making it an attractive therapeutic target. Cell lines CEv3 and CEv3P are both sensitive to neratinib, an irreversible second-generation EGFR TKI, at IC50 of 0.24μM and 0.13µM, respectively. To better understand adaptive response to neratinib treatment, we profiled the transcriptome with RNA sequencing at 0, 4, 24, and 48 hours. Our data shows that kinome rewiring is detectable after just 4 hours of treatment and sustained through 48 hours, with differential expression of 70% or more of the expressed kinome. We propose that differentially expressed kinases in response to neratinib can potentially activate alternative signaling pathways that bypass EGFR inhibition, which ultimately confers resistance to EGFR targeted therapy. Furthermore, we hypothesize that the epigenome is directly responsible for this adaptive kinome response through BRD4 dependent enhancer remodeling. Because dual therapy against EGFR and BRD4 has shown promising results in other cancers, targeting the epigenome through BRD4 represents a potential combination therapy with EGFR TKI in GBM. To profile BRD4-associated epigenomic changes, we used Cleavage Under Targets and Release Using Nuclease (CUT&RUN) to interrogate several regulatory marks (H3K4me1, K3K4me3, H3K27ac) in addition to BRD4. We seek to integrate RNA sequencing and CUT&RUN data to determine if kinases differentially expressed following neratinib treatment correlate with epigenetic marks for their respective enhancer(s). This work will provide insight into the adaptive resistance mechanism of EGFR driven GBM. Citation Format: Benjamin Lin, Julia Ziebro, Kasey R. Skinner, Abigail Shelton, Erin Smithberger, Ryan Bash, Frank B. Furnari, Ryan Miller. Elucidating the transcriptomic response to EGFR-targeted therapy in EGFR-driven glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1125.

List of abstract titles and authors:1. Antipsychotics across the spectrum: An overview of their mechanisms of actionAnissa Abi-Dargham2. Recent advances in the treatment of common anxiety disordersChrister Allgulander3. Psychiatry in Africa: The myths, the realities and the exoticO Gureje4. Mental Health policy developmet in Kenya and Tanznia - A DFID funded projectRachel Jenkins, David Kima, Joseph Mbatia, Frank Njenga5. Vascular factors in Alzheimer's diseaseR N Kalaria6. Depression as an immunologically based Neurodegenerative disorderBrian Leonard7. Eight years of progress in Arican PsychiatryF Njenga8. Treatment of Depression: Present and futureDr R.M. Pinder9. Imaging the Serotinergic system in impulsive aggressive personality disorder patientsLarry J Siever, Antonia S. New, Mari Goodman, Monte Buchsbaum, Erin Hazlett, Karen O'Flynn, Anissa Abi-argham, Marc Lauelle10. Mode of action of Atypical antipsychotic rugs: Focus on A2 AdrnoceptorsT.H. SvenssonNeuroscience: Selected Abstracts11. Chemical odulato of Fronto-execuitive functions: Neropsychiatric implicationsTrevor W Robbins12. Neural mechanisms of recognition memory and of social atacntProf. G Horn13. Estrogen signling after estrogen receptor ß (ERß)Jan-Ake Gustafsson14. Getting Lost: Hippocampal contributions to agerelated memory dysfunctionCarol BarnesMetals and the brain: Selected abstracts15. Modeling the contributin of iron mismanagement to Neurological disordersProf. J R C Connor16. Aluminium-triggered fibrillogenesis of B-AmyloidsProf. PZ Zatta, Dr D Drago, Mr G Tognon, Dr F RicchelliPsychiatry in Africa:17. Psychosocal aspects of Khat use among the youth of NairobiMs T M Khamis18. PTSD among motor vehicle accident survivors, KenyaDr F A Ongecha19. Psychiatric relities within African context - The Kenyan case StudyProf. D M N Ndetei20. Adolescent-parenta interactions from infancy, Nairobi KenyaDr L K Ksakhala, Prof. D M N Ndetei21. Alcohol use ong young persons: A focus group study in Southwest NigeriaO A Obeijide22. Personality disorders and personality traits among tyoe 2 Diabetic patientsProf. O El Rufaie, Dr M Sabosy, Dr M S Abuzeid23. Association of traumatic experiences with depression among Nigerian adolescentsDr O Omigbodun, Dr K BakareMs O B Yusuf, Dr O Esan24. Prevalence of depression among women attending outpatient clinics in MalawiDr M Tugumisirize, Prof. Agn, Dr Musisi25. Non-fatal suicidalbehaviour at the Johannesburg General HospitalDr M Y H Moosa, Prof. F Y Jeenah, Dr A Pillay, Pof. M Vorstere, Dr R Liebenberg26. Integrating mental health into general primary health care - Uganda's experienceDr N Kigozi27. Depression among Nigerian survivors of stroke:Prevalance and associated factorsDr F.O Fatoye Dr M A Komolafe, Dr A. O Adewuya, Dr B.A. Eegunranti Prof. M.A. Lawal28. NGO Involvement mental health care -The way forwardDr Basangwa29. Prevalen of Attenton Deficit Hyperactivity sorder among African school childrenDr E KashalaProf. T Tylleskar, Dr I Elgen, Dr K Sommerfelt30. Barriers to effective mental health care in NigeriaMs L. Kola31. Quay of life evaluation in patients with HIV-I infection with respect to the impact of Phyttherapy (Traditional Herb in Zimbabwe)M B Sebit, S K Chandiwaa, A S Latif, E Gomo, S W Acuda, F Makoni, J Vushe

Abstract Glioblastoma (GBM) is a devastating primary brain tumor with <5% 5-year survival. CDKN2A deletion (~60%) and EGFR amplification (~55%) mutations frequently co-occur in these tumors. EGFR is an attractive therapeutic target due to its mutational frequency and availability of brain-penetrant tyrosine kinase inhibitors (TKI). Several EGFR TKI have failed clinically, due in part to acquired resistance. To mechanistically examine this type of resistance, we used a panel of ten genetically engineered mouse astrocyte lines harboring Cdkn2a deletion and EGFRvIII, a common (~30%) activating mutation. Resistant cells were generated via long-term exposure to gefitinib or erlotinib, either in vitro or in vivo. Both transcriptomic (RNAseq) and proteomic (multiplexed inhibitor beads with mass spectrometry, MIB-MS) experiments showed that cell lines clustered primarily by resistance phenotype and secondarily by method of resistance development when analyzed using principal component analysis and unsupervised hierarchical clustering. Kinases involved in proliferation and differentiation signaling pathways (ex: Pdgfrb, Pdk2, Tnik, Mapk3, Fgfr2) were upregulated in both RNAseq and MIB-MS datasets and thus represent putative druggable targets for dual kinase inhibition. Analysis of commonly upregulated kinases and their commercially available inhibitors revealed dovitinib and dasatinib, two brain-penetrant drugs approved for other cancer indications, as candidates for dual inhibition with an EGFR TKI. Resistant cell lines were all more sensitive to dovitinib than their drug-naïve parents; however, sensitivity to dasatinib varied. BLISS analysis of dual treatment with EGFR TKI neratinib and dasatinib or dovitinib revealed synergistic drug interactions in most lines. Additionally, drug-naïve cells displayed a robust, acute proteomic response to EGFR TKI afatinib over 48h, while the response of resistant lines was significantly blunted. This model system can also be used to examine acute vs. long-term kinome response to EGFR TKI. Acute response was examined by treating drug-naïve cells with afatinib over 48h, and long-term kinome rewiring was observed by comparing untreated cells to gefitinib- and erlotinib-resistant cell lines. Combing both RNAseq datasets for kinases upregulated in both drug-naïve cells over a 48h EGFR TKI treatment course and in resistant cell lines compared to their sensitive parents reveals 21 and 13 common kinases, respectively, at p<0.001. Eight of these kinases (Cdk19, Ddr1, Kalrn, Khk, Mapk3, Pink1, Tnik, Ulk2) appear in both the in vitro and in vivo datasets, indicating a conserved kinome response regardless of method of resistance generation. Overall, integrated kinome profiling in GBM models with defined mutational profiles provides a powerful framework to identify novel therapeutic targets that could significantly alter current treatment paradigms. Citation Format: Abigail K. Shelton, Erin Smithberger, Madison Butler, Allie Stamper, Ryan E. Bash, Steve P. Angus, Michael P. East, Gary L. Johnson, Michael E. Berens, Frank B. Furnari, Ryan Miller. Acquired resistance to targeted inhibitors in EGFR-driven glioblastoma: Identification of dual kinase targets [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3248.

Abstract Glioblastoma (GBM) is a malignant brain tumor that has proven difficult to treat, despite expressing promising targets such as EGFRvIII. EGFRvIII, a mutant version of the epidermal growth factor receptor (EGFR), is constitutively active and not present in normal brain cells. The tumor specificity of EGFRvIII and the frequent EGFR amplification seen in GBM make EGFR a potentially attractive therapeutic target; however, clinical studies have shown little to no efficacy for EGFR tyrosine kinase inhibitors (TKI). One reason for this lack of efficacy may be adaptive resistance. We used RNA sequencing and multiplexed inhibitor beads with mass spectrometry (MIB-MS) to study the transcriptomes and kinomes of genetically engineered mouse astrocytes to investigate this resistance and identify potential targets for dual inhibition. Out of 329 kinases detected by MIB-MS, 76 were differentially expressed between cells with Cdkn2a deletion (“C”) and cells that also overexpressed EGFRvIII (“CEv3”). Thirty-four of these kinases were overexpressed in the CEv3 cells relative to the parental C cells (log2 fold change of 5.6, p<1x105). One of these kinases, Cdk6, is also significantly overexpressed in CEv3 cells versus cells that have a further loss of function mutation of Pten (“CEv3P”) (log2 fold change of 5.6, p<1x105). Despite this significant differential expression at the protein level, RNA expression of Cdk6 was similar between cell lines. When these cells were treated with the CDK6 inhibitor abemaciclib, CEv3 cells were found to be significantly more sensitive to inhibition than C and CEv3P cells (IC50 of 0.10 μM vs. 0.18 μM and 0.23 μM, respectively). Similarly, when cells were treated with abemaciclib in combination with the EGFR inhibitor neratinib, there was significantly higher synergy in CEv3 cells than C or CEv3P cells. Genotypically-matched patient-derived xenograft (PDX) cells were assayed for EGFR-CDK6 inhibitor synergy and showed a similar pattern of greater synergy in cells with EGFRvIII overexpression and functional PTEN than cells with EGFRvIII overexpression and PTEN loss. CEv3 and CEv3P cells were orthotopically implanted into mice and treated with neratinib, abemaciclib, or a combination. In CEv3-injected mice, combination treatment led to significantly longer survival than either single agent or control treatment. However, in CEv3P-injected mice, no survival difference was seen between any of the treatment arms. Taken together, these data provide strong evidence that CDK6 is a promising target for combination treatment with EGFR inhibitors in glioblastoma. Citation Format: Erin Smithberger, Abigail K. Shelton, Ryan E. Bash, Madison K. Butler, Alex R. Flores, Allie Stamper, Steven P. Angus, Michael P. East, Gary L. Johnson, Michael E. Berens, Frank B. Furnari, Ryan Miller. Glioblastoma growth is suppressed dual inhibition of EGFR and CDK6 kinases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1857.

Abstract Tumor Infiltrating Lymphocyte (TIL) therapy is an autologous adoptive cell therapy involving the isolation, ex vivo expansion and infusion of tumor infiltrating lymphocytes (TIL) into late-stage cancer patients for therapeutic benefit. While clinical responses to TIL therapy have been observed in metastatic melanoma, efficacy in other tumor types including non-small cell lung cancer (NSCLC), and head and neck squamous cell carcinoma (HNSCC) [SM1] is limited by the intrinsic functionality and persistence of transferred T cells and the immunosuppressive tumor microenvironment. To improve the clinical outcome of TIL therapy, we have developed KSQ-001EX, an engineered TIL therapy using CRISPR/Cas9 technology to knockout the SOCS1 gene, for the treatment of solid tumors. SOCS1 is a negative regulator of cytokine signaling in T cells that we previously identified as a top target restraining T cell anti-tumor function and persistence using genome-wide in vivo CRISPR screens. To streamline and shorten TIL manufacture, we established a next-generation manufacturing process with resected tumors or core biopsies as starting materials that eliminates the use of feeder cells and REP, shortening the length of manufacture to 22 days. We demonstrated robust manufacture of cryopreserved KSQ-001EX at clinical scale from NSCLC, HNSCC, checkpoint refractory melanoma, and heavily pre-treated colorectal carcinoma (CRC). KSQ-001EX manufactured from clinical-scale runs were highly viable (>90%) following cryopreservation and thaw, with > 90% SOCS1 on-target editing and complete knockdown of SOCS1 at the protein level. Importantly, KSQ-001EX across all indications assessed showed high frequency of CD8 (median ~80%), an attribute associated with TIL clinical responses. KSQ-001EX also retained high diversity of TCR repertoire. Consistent with the biology of SOCS1 editing, KSQ-001EX exhibited greater cytotoxicity and higher IFNγ production against tumor spheroids in comparison to TIL and enhanced induction of pSTAT4 upon IL-12 stimulation, demonstrating heightened sensitivity of KSQ-001EX to cytokines. In conclusion, KSQ-001EX, an engineered TIL therapy with CRISPR/Cas9 mediated inactivation of SOCS1, can be manufactured at clinical doses from surgical resections or core biopsies within 22 days using a simplified feeder-free manufacturing process from multiple indications. KSQ-001EX exhibits heightened anti-tumor activity in preclinical models, with therapeutic benefit to be evaluated in a planned clinical trial in patients with treatment-refractory melanoma, NSCLC, and HNSCC. [SM1]Spell out these at first instance? Citation Format: Sharon Lin, Gustavo Martinez, Marie-Andrée Forget, Katrina Adlerz, Mitali Ghose, Leila Williams, Paul Dunbar, Frank Thompson, Fiona Sharp, Hugh Gannon, Conor Calnan, Ashish Yeri, Dipen Sangurdekar, Donald Sakellariou-Thompson, Samantha Fix, Tamara Griffith, Ellie Jafari, Jane Zulovich, Priya Balasubramanian, Erin Willert, MIcah Benson, Chantale Bernatchez, Karrie Ka Wai Wong. KSQ-001EX: An engineered TIL therapy manufactured from a clinical-scale, feeder-free process for the treatment of solid tumor indications [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 20.

Abstract Introduction: It is well established that multidisciplinary tumor boards improve the decision-making process for cancer patients. Tumor boards have been shown to improve the accuracy of diagnosis and staging, optimize patient outcomes, increase adherence to guidelines, and educate our peers and trainees. However, over 80% of patients in the United States receive their cancer care in the community setting, where access to multi-disciplinary tumor boards may not be readily available. This may particularly impact underserved populations who often lack the resources to travel to an academic center for second opinions or treatment. The problem is worse in low-resource countries. Virtual expert tumor boards could provide an effective solution. Methods: Preeminent breast oncology faculty from around the Unites States were assembled into virtual tumor board panels via an online platform to discuss challenging cases submitted by community providers and trainees. These tumor boards consisted of a moderator, a breast radiologist, a breast medical oncologist, a breast surgeon, and a breast radiation oncologist. The purpose of this ongoing endeavor is to educate community oncologists on how to best manage challenging cases. Following tumor board discussions, written recommendations were shared with submitting providers within 48 hours and recordings of the discussions were also later provided. After submitting providers watched the recording of their case discussion, we conducted a survey to determine their perceived benefit of the expert panel discussion. Results: From Sept 2020 to June 2021, ten breast cancer panels were virtually convened with 17 expert faculty panelists. During that time, 21 providers submitted 94 cases from the U.S. and around the world to be discussed by the expert panel. Thirty-three percent of the providers who submitted a case to be discussed have subsequently submitted an additional case to a later panel. Surveys were sent to all submitting providers and responses were recorded from 16/21 submitters (76.2%). Conclusion: With more than three out of four submitters responding, we learned that not only is it feasible to convene virtual expert breast tumor boards to discuss challenging cases, but the vast majority of respondents learned new information, changed management of their patients, and wanted to submit additional cases. This effort could raise the level of breast cancer care around the world. Ongoing assessment of educational and patient care impacts will be necessary. QuestionNumber answered (n)Number who answered yes (%)Number who answered no (%)Did you learn something new from the PrecisCa discussion of your case scenario?1614 (87.5)2 (12.5)Will anything you learned from the PrecisCa discussion of your case scenario change the management of this or future patients?1615 (93.8)1 (6.2)Are you likely to submit a future challenging case scenario to PrecisCa?1616 (100)0 (0) Citation Format: Naomi Dempsey, Lauren Chiec, Mikala Lodder, Erin Shonkwiler, Kayla Haines, Reshma Mahtani, William Gradishar, Thomas Buchholz, Anne O'Dea, Norman Wolmark, Sara Hurvitz, Joyce O'Shaughnessy, Maxine Jochelson, Reni Butler, Eleftherios Mamounas, Frank Vicini, Mark Pegram, Chirag Shah, Tari King, Ruth O'Regan, Monica Morrow, Mohammad Jahanzeb. Raising the level of cancer care around the world: The feasibility and perceived benefit of a virtual breast tumor board [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-17-03.

BackgroundThe most recent update of the Global Burden of Disease figures (GBD 2013) estimated that 242 million people were living in the world with symptomatic and activity-limiting OA of the hip and/or knee. Many potential disease-modifying osteoarthritis drugs (DMOADs) have been investigated, but to date no DMOADs that slow or stop disease progression have been approved by the Food and Drug Administration (FDA) or the European Medicines Agency (EMA). A potential reason for the lack of demonstrated efficacy may be reliance on radiographs for defining structural inclusion and exclusion criteria for clinical trials, such as use of joint space width and Kellgren-Lawrence (KL) grade as surrogates for cartilage damage.ObjectivesTo estimate the distribution of cartilage damage seen on knee MRI in a sample of knees with radiographic KL 2 and 3 OA that would potentially qualify for a DMOAD trial.MethodsWe selected knees from the Osteoarthritis Initiative (OAI), a longitudinal cohort study of knees with or at risk of developing symptomatic radiographic OA, that met common structural inclusion criteria for DMOAD trial enrollment at OAI baseline: knees with radiographs centrally graded as KL 2 or 3 and medial minimum joint space width (mJSW) ≥ 1.5mm. A musculoskeletal radiologist with 10 years of experience in semi-quantitative MRI assessment scored knee cartilage damage in the medial and lateral tibiofemoral and patellofemoral compartments using WORMS (Whole-Organ Magnetic Resonance Imaging Score). Coronal intermediate weighted (IW) TSE and sagittal fat-suppressed IW TSE sequences on 3T MRI were used. The WORMS cartilage scores, which are based on both the extent and depth of cartilage damage, were collapsed into 4 categories: no cartilage damage (WORMS 0 and 1), focal partial or full-thickness (PT/FT) cartilage damage (WORMS 2 and 2.5), diffuse partial thickness (PT) cartilage damage (WORMS 3 and 4), and diffuse full-thickness (FT) cartilage damage (WORMS 5 and 6). We estimated the prevalence of each category of cartilage damage in KL2 and KL3 knees; 95% confidence intervals (CI) accounted for clustering at the participant-level since some participants contributed two knees to the analysis.ResultsWe identified 2,372 participants contributing 3,446 knees with radiographic OA (KL 2 and 3) and medial mJSW ≥ 1.5mm. There were 2,318 KL2 knees and 1,128 KL3 knees. The distribution of cartilage damage in each compartment by KL grade is presented in Table 1. We found no cartilage damage in any compartments in 9.8% (95%CI: 8.5, 11.1) of KL2 knees and 2.0% (95%CI: 1.1, 2.9) of KL3 knees. Cartilage damage was absent in the medial tibiofemoral compartment in 52.4% (95%CI: 50.1, 54.6) of KL2 knees, and 14.4% (95%CI: 12.2, 16.6) of KL3 knees, versus 61% (95%CI: 58.8, 63.2) of KL2 knees and 53.6% (95%CI: 50.4, 56.7) of KL3 knees in the lateral compartment. When medial and lateral compartments were combined, cartilage damage was absent in 34.8% (95%CI: 32.7, 36.9) of the KL2 knees, and 4.3% (95%CI: 3.0, 5.5) of the KL3 knees. Diffuse FT cartilage lesions in the medial compartment were found in 6.1% (95%CI: 5.0, 7.1) of KL2 knees and 42.5% (95%CI: 39.4, 45.6) of KL3 knees.ConclusionMRI screening prior to clinical trial enrollment may identify a substantial percentage of knees with normal cartilage, as well as knees with diffuse FT cartilage lesions that may not be responsive to DMOADs, depending on the mode of action of a given pharmacological compound.Disclosure of InterestsMohamed Jarraya: None declared, Frank Roemer Shareholder of: Boston Imaging Core Lab, Consultant of: California Institute of Biomedical Research, Erin Ashbeck: None declared, John Lynch: None declared, C. Kent Kwoh Consultant of: Novartis, Regeneron, LG Chem, Kolon Tissue Gene, Avalor, Grant/research support from: Pfizer, Lilly, Cumberland, Ali Guermazi Shareholder of: Stock options in BICL, Consultant of: Pfizer, TissueGene, MerckSerono, Regeneron, Novartis, AstraZeneca

BackgroundDue to its major public health impact, knee osteoarthritis (KOA) has been designated as a serious disease by the US Food and Drug Administration (FDA). Approval of a disease modifying osteoarthritis drug (DMOAD) to slow or prevent disease progression hinges on demonstrating both symptomatic (i.e., how a patient feels or functions) and structural improvement. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the questionnaire most commonly used to assess symptomatic improvement, may not adequately reflect pain reporting due to KOA. The lack of DMOAD approval to date has largely been attributed to the lack of clinical translation of structural benefits that also yield symptomatic improvements. Drugs targeting inflammation are an example of a therapeutic approach that has yielded evidence of structural benefit but not symptomatic improvement as assessed by the WOMAC.ObjectivesEvaluate potential heterogeneity of the effects of structural damage on knee pain reporting across activities assessed in the WOMAC pain subscale following recent development of radiographic knee osteoarthritis.MethodsThe Osteoarthritis Initiative is a longitudinal observational study of participants with or at risk of symptomatic knee OA. We identified incident cases of radiographic KOA, defined as Kellgren-Lawrence [KL] grade 2 or 3 based on centrally graded x-rays. Participants underwent bilateral posteroanterior fixed-flexion weight-bearing knee radiography at clinic visits annually or biannually through year 10. Non-contrast 3T MRI was also acquired at clinic visits up to year 8. Musculoskeletal radiologists graded structural damage, including effusion-synovitis (ES), Hoffa-synovitis (HS), bone marrow lesions (BMLs), cartilage and meniscal damage using the MRI Osteoarthritis Knee Score (MOAKS). The WOMAC knee pain subscale is calculated by adding reported pain scores from various activities, including walking on a flat surface, going up or down stairs, at night while in bed, sitting or lying down, and standing, during the last seven days, rated on a 5-point scale from none (0), mild (1), moderate (2), severe (3), or extreme [4]. Pain in each knee was reported separately. We fit a proportional odds logistic regression to model the ordinal pain scores reported for each activity on the WOMAC pain scale using penalized maximum likelihood estimation; predictors included each of the MRI structural damage scores, KL grade, age, and BMI at the same clinic visit, as well as sex and race. We estimated the predicted probability of pain rated moderate or worse (Pr[Y ≥ 2 | X]), and reported nonparametric bootstrap 95% confidence intervals (CI) with cluster sampling at the participant-level.ResultsWe identified 690 knees contributed by 623 participants that developed radiographic KOA. The mean participant age was 65 years (SD 9), mean BMI was 29.3 (SD 4.8), 66% reported female sex and 83% self-identified as white. The predicted probability of knee pain rated moderate or worse (≥2) increased with greater ES during walking and stair climbing, but there was no evidence that ES affected knee pain while in bed, sitting or lying down, or standing (Figure 1). We did not find evidence that HS, BMLs, cartilage or meniscal damage affected the WOMAC knee pain items cross-sectionally in our fully adjusted models.ConclusionOur study suggests that ES seen on MRI produces heterogeneous effects on pain reporting, depending on the type of activity. Treatments that are developed to target inflammation may reduce pain during some activities, such as walking and stair climbing, but may have little benefit during other activities, such as sitting or lying down. If a treatment effectively reduces or limits structural damage that differentially impacts pain across the activities included in the WOMAC pain subscale, analysis that focuses only on the WOMAC pain subscale score may mask the clinical benefit of the treatment.Figure 1.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsC. Kent Kwoh Consultant of: Avalor Therapeutics, Express Scripts, Kolon Tissue Gene, LG Chem Regeneron, Grant/research support from: AbbVie, Cumberland, Lilly, Pfizer, Frank Roemer Shareholder of: BICL, LLC, Consultant of: Calibr, Grünenthal, Ali Guermazi Shareholder of: BICL, LLC., Consultant of: Pfizer, Kolon TissueGene, Novartis, Regeneron, TrialSpark, Medipost, ICM, Erin Ashbeck: None declared.

Abstract PI3Kα is the most mutated kinase and the second most mutated oncogene in human cancer. Activation of PI3Ka can be achieved by receptor tyrosine kinases such as insulin receptor and insulin-like growth factor receptor 1 and/or by directly interacting with RAS family members. Previous elegant preclinical studies have established that RAS-driven PI3Ka activation is important in tumor cells but may not be involved in cell types controlling glucose metabolism. Alpelisib, a small molecule inhibitor of the kinase activity of PI3Ka, has been approved for the treatment of ER+ PIK3CA mutant breast cancer in combination with fulvestrant after endocrine therapy in advanced or metastatic breast cancer based on an improvement in PFS versus fulvestrant alone. Inhibition of PI3Ka activity by alpelisib in normal tissues resulted in a severe (G3/4) hyperglycemia rate of 37% with frequent dose interruptions and discontinuations. Additionally, preclinical studies have demonstrated that the dysregulation of glucose homeostasis resulting from PI3Ka kinase inhibition leads to hyperinsulinemia that increases pathway flux, rendering kinase inhibitors less effective. Here, we report on a novel covalent small molecule designed to inhibit RAS-mediated activation of the AKT pathway via PI3Ka without the resultant hyperglycemia associated with direct inhibition of PI3Ka kinase activity. BBO-10203 disrupts the physical interaction between RAS and PI3Ka in tumor cells resulting in potent signaling pathway inhibition. This agent selectively binds to PI3Ka and disrupts its interaction with K-,H-, and N-RAS with low single digit nanomolar potency (~5 nM). Breaking the interaction between these two oncogenes inhibits basal pAKT cellular levels (BT-474/KYSE-410 IC50: ~5 nM) in HER2 amplified (HER2amp) and wild-type or mutant PI3Ka cell lines. Even though BBO-10203 does not inhibit the kinase activity of PI3Ka, its effects on cancer cell signaling inhibition and transcriptional regulation highly resemble those of alpelisib. BBO-10203 displays excellent drug-like properties and oral bioavailability. Single dose treatment of KYSE-410 (HER2amp/KRASG12C) tumor bearing mice with increasing doses (1-100 mg/kg, PO) of BBO-10203 results in dose and time dependent inhibition of pAKT in vivo. Maximal inhibition (~80%) is achieved at 30 mg/kg and lasts for 24 hours. Repeated dose treatment of tumor bearing mice with BBO-10203 is well tolerated and results in significant efficacy in PIK3CA mutant as well as HER2amp human xenograft models. In the KYSE-410 xenograft model, BBO-10203 daily oral dosing of 30 mg/kg results in significant tumor regressions. Importantly, treatment with BBO-10203 does not affect insulin signaling in differentiated adipocytes in vitro, nor does it impact glucose metabolism in vivo at 3-times the maximal efficacious dose level in xenograft studies. In conclusion, we have identified a novel approach to inhibit the PI3Ka signaling pathway by blocking its interaction with, and activation by RAS. This approach can achieve strong pAKT inhibition in tumor cells without changes in glucose metabolism. Clinical investigation of BBO-10203 for the treatment of both ER+/PIK3CA mutant and HER2amp breast cancer is warranted. Citation Format: Pedro Beltran, Simanshu Dhirendra, Rui Xu, Ming Chen, Daniel Czyzyk, Sofia Donovan, Siyu Feng, Cindy Feng, Lijuan Fu, Felice Lightstone, Ken Lin, Anna Maciag, Dwight Nissley, Erin Riegler, Kerstin Sinkevicius, Andrew Stephen, James Stice, David Turner, Bin Wang, Keshi Wang, Yue Yang, Cathy Zhang, Frank McCormick, Eli Wallace. BBO-10203, a first-in-class, orally bioavailable, selective covalent small molecule that inhibits RAS-driven PI3Kalpha activity without affecting glucose metabolism [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr RF02-02.

Background:Methotrexate (MTX) is often used as first-line therapy for patients (pts) with psoriatic arthritis (PsA) despite limited efficacy and data on appropriate dosage. Minimal Disease Activity (MDA) is suggested as an optimal treat-to-target outcome. Biologic disease-modifying antirheumatic drugs (bDMARDs) have demonstrated improved outcomes (including MDA rates) over MTX. However, more data are needed to define the optimal timing of bDMARD initiation and characterize efficacy of MTX dose escalation, to achieve optimal outcomes.Objectives:To compare achievement of MDA between adding adalimumab (ADA) vs escalating MTX dose in PsA pts with inadequate disease control after initial MTX therapy.Methods:The open-label, 2-part CONTROL study enrolled bDMARD-naive adult pts with active PsA (not in MDA at screening and ≥3 tender and ≥3 swollen joints) despite MTX 15 mg every wk (ew) for ≥4 wks. Pts were randomized to ADA 40 mg every other wk + MTX 15 mg (ADA+MTX) or escalated MTX to 20–25 mg ew or highest tolerable dose during 16-wk part 1 (Fig 1). The primary endpoint was achievement of MDA, defined as fulfilling ≥5 of the 7 criteria: tender joint count 68 (TJC68) ≤1, swollen joint count 66 (SJC66) ≤1, Psoriasis Area Severity Index (PASI) ≤1 or body surface area (BSA) ≤3%, pt’s pain (visual analogue scale [VAS] 0–100) ≤15, Pt’s Global Assessment of disease activity (PtGA) VAS ≤20, Health Assessment Questionnaire Disability Index (HAQ-DI) ≤0.5 and tender entheseal points (0–8) ≤1. Key secondary efficacy endpoints were achievement of ACR20 and PASI75 and change from baseline in HAQ-DI and Leeds Enthesitis Index (LEI) at wk 16.Results:Overall, 246 pts were randomized; 245 received treatment (ADA+MTX, n=123; escalated MTX, n=122); 117 (95%) pts and 110 (90%) pts, respectively, completed part 1. Baseline characteristics were similar between groups (Table). During part 1, the average dose of MTX was 21.8 mg/wk (55% on oral MTX) in the escalated MTX group. Significantly higher proportion of pts in ADA+MTX (42%) vs escalated MTX (13%) group achieved MDA at wk 16 (non-responder imputation [NRI]; difference [95% CI] 28% [18%–39%];P<0.001;Fig 2). Observed case analysis confirmed the NRI analysis. Lower MDA rates at wk 16 were observed in the escalated MTX arm regardless of prior MTX duration (Fig 2). Significant improvements in key secondary endpoints were also observed with ADA+MTX vs escalated MTX (allP<0.05;Fig 2). In part 1, the proportion of patients with adverse events was similar between groups (ADA+MTX, 62% vs escalated MTX, 57%); no opportunistic infections, tuberculosis, malignancies, or deaths were reported during part 1.Conclusion:A significantly higher proportion of pts achieved MDA at wk 16 after introducing ADA compared with escalating MTX dose; higher rates were observed regardless of prior MTX duration. Significantly higher responses in musculoskeletal, skin, and quality of life measures were observed with ADA+MTX vs escalated MTX. No new safety signals with ADA were identified in this pt population.Table 1.Baseline DemographicsCharacteristics, mean (SD)ADA+MTXn=123Escalated MTXn=122Female, n (%)64 (52.0)59 (48.4)Age, y51.4 (12.2)48.8 (12.7)BSA >3%, n (%)74 (60.2)78 (63.9)Pt pain63.7 (19.5)62.3 (20.9)PtGA65.0 (19.9)62.9 (20.9)HAQ-DI1.2 (0.6)1.2 (0.7)LEI + plantar count3.5 (2.1)3.5 (2.1)Disclosure of Interests:Laura C Coates: None declared, William Tillett Grant/research support from: AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB, Consultant of: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, MSD, Pfizer Inc, UCB, Speakers bureau: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, Pfizer Inc, UCB, Maria Antonietta D’Agostino Consultant of: AbbVie, BMS, Novartis, and Roche, Speakers bureau: AbbVie, BMS, Novartis, and Roche, Proton Rahman Grant/research support from: Janssen and Novartis, Consultant of: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, and Pfizer., Speakers bureau: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, Frank Behrens Grant/research support from: Pfizer, Janssen, Chugai, Celgene, Lilly and Roche, Consultant of: Pfizer, AbbVie, Sanofi, Lilly, Novartis, Genzyme, Boehringer, Janssen, MSD, Celgene, Roche and Chugai, Philip G Conaghan Consultant of: AbbVie, BMS, Eli Lilly, EMD Serono, Flexion Therapeutics, Galapagos, GSK, Novartis, Pfizer, Speakers bureau: AbbVie, Eli Lilly, Novartis, Pfizer, Erin McDearmon-Blondell Shareholder of: AbbVie, Employee of: AbbVie, Xianwei Bu Shareholder of: AbbVie, Employee of: AbbVie, Liang Chen Shareholder of: AbbVie, Employee of: AbbVie, Mudra Kapoor Shareholder of: AbbVie, Employee of: AbbVie, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau

AbstractDocument Reviewers: Rudolf A. de Boer (CPG Review Co‐ordinator) (Netherlands), P. Christian Schulze (CPG Review Co‐ordinator) (Germany), Elena Arbelo (Spain), Jozef Bartunek (Belgium), Johann Bauersachs (Germany), Michael A. Borger (Germany), Sergio Buccheri (Sweden), Elisabetta Cerbai (Italy), Erwan Donal (France), Frank Edelmann (Germany), Gloria Färber (Germany), Bettina Heidecker (Germany), Borja Ibanez (Spain), Stefan James (Sweden), Lars Køber (Denmark), Konstantinos C. Koskinas (Switzerland), Josep Masip (Spain), John William McEvoy (Ireland), Robert Mentz (United States of America), Borislava Mihaylova (United Kingdom), Jacob Eifer Møller (Denmark), Wilfried Mullens (Belgium), Lis Neubeck (United Kingdom), Jens Cosedis Nielsen (Denmark), Agnes A. Pasquet (Belgium), Piotr Ponikowski (Poland), Eva Prescott (Denmark), Amina Rakisheva (Kazakhstan), Bianca Rocca (Italy), Xavier Rossello (Spain), Leyla Elif Sade (United States of America/Türkiye), Hannah Schaubroeck (Belgium), Elena Tessitore (Switzerland), Mariya Tokmakova (Bulgaria), Peter van der Meer (Netherlands), Isabelle C. Van Gelder (Netherlands), Mattias Van Heetvelde (Belgium), Christiaan Vrints (Belgium), Matthias Wilhelm (Switzerland), Adam Witkowski (Poland), and Katja Zeppenfeld (Netherlands)All experts involved in the development of this Focused Update have submitted declarations of interest. These have been compiled in a report and simultaneously published in a supplementary document to the Focused Update. The report is also available on the ESC website www.escardio.org/guidelinesSee the European Heart Journal online for supplementary documents that include evidence tables.

Abstract We investigate how discourse relations and their subtypes are signalled, extending the set of discourse signals from connectives and lexical cue phrases to the wide range of semantic, syntactic, and orthographic signals of the RST Signalling Corpus (Das, Debopam & Maite Taboada. 2018. RST signalling corpus. Language Resources and Evaluation 52. 149–184). This extension requires re-evaluating previous predictions on discourse signalling, in particular, those of Sanders, Ted. 2005. Coherence, causality and cognitive complexity in discourse. In M. Aurnague, M. Bras, A. Le Draoulec & L. Vieu (eds.), Proceedings/Actes SEM-05, first international symposium on the exploration and modelling of meaning, 105–114. Biarritz causality-by-default hypothesis, the hypothesis of uniform information density (Frank, Austin & Florian Jaeger. 2008. Speaking rationally: Uniform information density as an optimal strategy for language production. In Proceedings of the 30th annual meeting of the Cognitive Science Society, 933–938. https://escholarship.org/uc/item/7d08h6j4 (accessed 18 May 2022)), and the hypothesis that discourse is continuous by preference (Segal, Erwin, Judith Duchan & Paula Scott. 1991. The role of interclausal connectives in narrative structuring. Discourse Processes 14. 27–54; Murray, John. 1997. Connectives and narrative text. Memory and Cognition 25. 227–236). We evaluate the predictions of these theories on the conditional relations in the RST Discourse Treebank (Carlson, Lynn, Daniel Marcu & Mary Ellen Okurowski. 2002. RST Discourse Treebank. LDC2002T07. Philadelphia: Linguistic Data Consortium), using causal relations as a control group. Informativity and continuity are operationalized in terms of semantic complexity and Givón, Talmy. 1993. English grammar: A function-based introduction, vol. 2. Amsterdam: John Benjamins dimensions of deictic shift. Our results show that the hypotheses make accurate predictions only for the relation groups in their entirety but not for the observed in-group variation, in particular, the low amount of marking for the hypothetical subtype of conditional relations. We attribute this difference to the distribution of intra- and inter-sentential occurrences across the conditional subtypes: intra-sentential relations are consistently more marked than inter-sentential ones, and hypothetical relations are special in that they appear predominantly inter-sententially.

Alex Abou-Chebl, MD Michael Abraham, MD Joseph E. Acker, III, EMT-P, MPH Robert Adams, MD, MS, FAHA Eric Adelman, MD Opeolu Adeoye, MD DeAnna L. Adkins, PhD Maria Aguilar, MD Absar Ahmed, MD Naveed Akhtar, MD Rufus Akinyemi, MBBS, MSc, MWACP, FMCP(Nig) Karen C. Albright, DO, MPH Felipe Albuquerque, MD Andrei V. Alexandrov, MD Abdulnasser Alhajeri, MD Latisha Ali, MD Nabil J. Alkayed, MD, PhD, FAHA Amer Alshekhlee, MD, MSc Irfan Altafullah, MD Arun Paul Amar, MD Pierre Amarenco, MD, FAHA, FAAN Sepideh Amin-Hanjani, MD, FAANS, FACS, FAHA Catherine Amlie-Lefond, MD Aaron M. Anderson, MD David C. Anderson, MD, FAHA Sameer A. Ansari, MD, PhD Ken Arai, PhD Agnieszka Ardelt, MD, PhD Juan Arenillas, MD PhD William Armstead, PhD, FAHA Jennifer L. Armstrong-Wells, MD, MPH Negar Asdaghi, MD, MSc, FRCPC Nancy D. Ashley, APRN,BC, CEN,CCRN,CNRN Stephen Ashwal, MD Andrew Asimos, MD Rand Askalan, MD, PhD Kjell Asplund, MD Richard P. Atkinson, MD, FAHA Issam A. Awad, MD, MSc, FACS, MA (hon) Hakan Ay, MD, FAHA Michael Ayad, MD, PhD Cenk Ayata, MD Aamir Badruddin, MD Hee Joon Bae, MD, PhD Mark Bain, MD Tamilyn Bakas, PhD, RN, FAHA, FAAN Frank Barone, BA, DPhil Andrew Barreto, MD William G. Barsan, MD, FACEP, FAHA Nicolas G. Bazan, MD, PhD Kyra Becker, MD, FAHA Ludmila Belayev, MD Rodney Bell, MD Andrei B. Belousov, PhD Susan L. Benedict, MD Larry Benowitz, PhD Rohit Bhatia, MBBS, MD, DM, DNB Pratik Bhattacharya, MD MPh James A. Bibb, PhD Jose Biller, MD, FACP, FAAN, FAHA Randie Black Schaffer, MD, MA Kristine Blackham, MD Bernadette Boden-Albala, DrPH Cesar Borlongan, MA, PhD Susana M. Bowling, MD Monique M. B. Breteler, MD, PhD Jonathan Brisman, MD Allan L. Brook, MD, FSIR Robert D. Brown, MD, MPH Devin L. Brown, MD, MS Ketan R. Bulsara, MD James Burke, MD Cheryl Bushnell, MD, MHSc, FAHA Ken Butcher, MD, PhD, FRCPC Livia Candelise, MD S Thomas Carmichael, MD, PhD Bob S. Carter, MD, PhD Angel Chamorro, MD, PhD Pak H. Chan, PhD, FAHA Seemant Chaturvedi, MD, FAHA, FAAN Peng Roc Chen, MD Jun Chen, MD Eric Cheng, MD, MS Huimahn Alex Choi, MD Sherry Chou, MD, MMSc Michael Chow, MD, FRCS(C), MPH Marilyn Cipolla, PhD, MS, FAHA Kevin Cockroft, MD, MSc, FACS Domingos Coiteiro, MD Alexander Coon, MD Robert Cooney, MD Shelagh B. Coutts, BSc, MB.ChB., MD, FRCPC, FRCP(Glasg.) Elizabeth Crago, RN, MSN Steven C. Cramer, MD Carolyn Cronin, MD, PhD Dewitte T. Cross, MD Salvador Cruz-Flores, MD, FAHA Brett L. Cucchiara, MD, FAHA Guilherme Dabus, MD M Ziad Darkhabani, MD Stephen M. Davis, MD, FRCP, Edin FRACP, FAHA Deidre De Silva, MBBS, MRCP Amir R. Dehdashti, MD Gregory J. del Zoppo, MD, MS, FAHA Bart M. Demaerschalk, MD, MSc, FRCPC Andrew M. Demchuk, MD Andrew J. DeNardo, MD Laurent Derex, MD, PhD Gabrielle deVeber, MD Helen Dewey, MB, BS, PhD, FRACP, FAFRM(RACP) Mandip Dhamoon, MD, MPH Orlando Diaz, MD Martin Dichgans, MD Rick M. Dijkhuizen, PhD Michael Diringer, MD Jodi Dodds, MD Eamon Dolan, MD, MRCPI Amish Doshi, MD Dariush Dowlatshahi, MD, PhD, FRCPC Alexander Dressel, MD Carole Dufouil, MD Dylan Edwards, PhD Mitchell Elkind, MD, MS, FAAN Matthias Endres, MD Joey English, MD, PhD Conrado J. Estol, MD, PhD Mustapha Ezzeddine, MD, FAHA Susan C. Fagan, PharmD, FAHA Pierre B. Fayad, MD, FAHA Wende Fedder, RN, MBA, FAHA Valery Feigin, MD, PhD Johanna Fifi, MD Jessica Filosa, PhD David Fiorella, MD, PhD Urs Fischer, MD, MSc Matthew L. Flaherty, MD Christian Foerch, MD Gregg C. Fonarow, MD, FAHA Andria Ford, MD Christine Fox, MD, MAS Isabel Fragata, MD Justin Fraser, MD Don Frei, MD Gary H. Friday, MD, MPH, FAAN, FAHA Neil Friedman, MBChB Michael Froehler, MD, PhD Chirag D. Gandhi, MD Hannah Gardener, ScD Madeline Geraghty, MD Daniel P. Gibson, MD Glen Gillen, EdD, OTR James Kyle Goddard, III, MD Daniel A. Godoy, MD, FCCM Joshua Goldstein, MD, PhD, FAHA Nicole R. Gonzales, MD Hector Gonzalez, PhD Marlis Gonzalez-Fernandez, MD, PhD Philip B. Gorelick, MD, MPH, FAHA Matthew Gounis, PhD Prasanthi Govindarajan, MD Manu Goyal, MD, MSc Glenn D. Graham, MD, PhD Armin J. Grau, MD, PhD Joel Greenberg, PhD, FAHA Steven M. Greenberg, MD, PhD, FAHA David M. Greer, MD, MA, FCCM James C. Grotta, MD, FAHA Jaime Grutzendler, MD Rishi Gupta, MD Andrew Gyorke, MD Mary N. Haan, MPH, DrPH Roman Haberl, MD Maree Hackett, PhD Elliot Clark Haley, MD, FAHA Hen Hallevi, MD Edith Hamel, PhD Graeme J. Hankey, MBBS, MD, FRCP, FRCP, FRACP Amer Haque, MD Richard L. Harvey, MD Don Heck, MD Cathy M. Helgason, MD Thomas Hemmen, MD, PhD Dirk M. Hermann, MD Marta Hernandez, MD Paco Herson, PhD Michael D. Hill, MD, MSc, FRCPC Nancy K. Hills, PhD, MBA Robin C. Hilsabeck, PhD, ABPP-CN Judith A. Hinchey, MD, MS, FAHA Robert G. Holloway, MD, MPH William Holloway, MD Sherril K. Hopper, RN Jonathan Hosey, MD, FAAN George Howard, DPH, FAHA Virginia J. 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Staples of early United States Internet meme culture were sold via digital auctions for cryptocurrency (except one, which was sold for cash) throughout 2021. Through these transactions, Internet memes, or “the linguistic, image, audio, and video texts created, circulated, and transformed by countless cultural participants across vast networks and collectives” (Milner 1), were “minted” as non-fungible tokens—a marker within cryptocurrency economy that denotes the level of originality or irreplaceability of an (often digital) artifact (Wired). Early 2021 saw Internet memes (memes, hereafter) and non-fungible tokens (NFTs, hereafter) articulated to one another when a series of trades ignited a “buying frenzy”. In February 2021, the original animation file of the Nyan Cat meme (a rendering of a flying cat with a Pop-Tart body) was sold for 300 Ethereum, or US$600,000 (Griffith; Kay); in April 2021, the original photo file of the Disaster Girl meme (an image of a smiling child in front of a burning home) sold for 180 ETH, or nearly US$500,000 (BBC News); in May 2021, the original video file of the viral YouTube video “Charlie Bit My Finger” (wherein an infant bites the finger of their older sibling with glee) was sold for US$760,999, but no cryptocurrency was exchanged for this auction (Evans); in June 2021, the original image of the Shiba Inu who became Doge (image of a dog looking contemplative, often with text around the dog’s face) was sold for a record-breaking (for memes) 1,696.9 ETH, or US$4 million (Rosenblatt). Other notable memes were sold around this time, such as Bad Luck Brian (an unflattering school picture of a teenager who became synonymous with embarrassing social situations), Overly Attached Girlfriend (wide-eyed teenager who was portrayed as obsessive over their significant other), and Success Kid (an infant clenching their fist with a sense of achievement), but for lower prices (Wired; Dash; Gallagher). All the memes sold during this frenzy feature either animals or white individuals, and none of the creators or subjects of the original files are Black. That said, mainstream Internet culture, specifically within the United States, is predicated upon the Othering and exploitation of Black cultural production (Brock 97, 124; Benjamin). The fungible constitution of US Black culture is replete within digital cultures, from contemporary discussions of digital blackface in white use of memes featuring Black folks to express emotion (J.L. Green; Jackson, “Digital Blackface”, White Negroes) and/or using imagery featuring Black folks without permission (J.L. Green; Nakamura; Matamoros-Fernández). The advent of meme-based NFTs, however, offers new areas of inquiry into the triangulation of race, fungibility, and US digital cultures. I approach this cultural phenomenon with two general queries: What cultural and racial legacies of non/fungibility are present in the dynamics of memes becoming NFTs? What are the implications in digital media and US culture? Fungibility and Black Cultural Production As this issue explores, fungibility is a quality of interchangeable, performing persons or objects, but a turn to US Afro-pessimism illustrates how fungibility is a central quality to racialisation. (Continental African scholars coined Afro-pessimism, and its original formulation was markedly different from the US counterpart, which emerged with little to no engagement with the existing African canon. Afropessimism 1.0, as Greg Thomas names it, focusses on the postcolonial economic conditions across the continent. Importantly, there is an undergirding optimism, “the urge to positive social change”, to the inquiries into the poverty, colonial extractivism, and more; Amrah qtd. in Thomas 283; Rieff; de B’béri and Louw.) Fungibility, in US-borne Afro-pessimist literature, is used to describe (1) a major tenet of slavery wherein Black bodies are treated as interchangeable objects rather than human actors, and (2) how the afterlife of slavery continues to structure everyday experiences for Black folks (Bilge; Hartman; Wilderson, III et al.). US Afro-pessimism argues that slavery instantiated an ontological structure that articulates humanity as irreconcilable with Blackness and further articulates whiteness as for what (or whom) the Black body performs and labours (Bilge; Douglass et al.; Wilderson, III and Soong). Within the US, the fungibility of the Black body means it is always already vulnerable to and violable by “the whims of the [non-Black] world” (Wilderson, III 56; see also: Hartman; Lindsey). Indeed, Wilderson, building off Hartman, asserts, “the violence-induced fungibility of Blackness allows for its appropriation by White psyches as ‘property of enjoyment’” (89). The fungibility of Blackness aides in white “transpos[ition of Black] cultural gestures, the stuff of symbolic intervention onto another worldly good, a commodity of style” (Wilderson, III 56). This expropriation of Black digital “imaginative labour” by US white mainstream culture is part and parcel to Internet practices (Iloh; Lockett; Jackson). bell hooks argues white US mainstream culture treats Black cultural production as the “spice, [the] seasoning that can liven up the dull dish that is mainstream white culture” (21). By the same token, US white mainstream culture “desire[s] … sustained ‘labor’ … of a dark Other” that seeks to contiunously exploit fungible Black production (31). The constitutive fungibility of Blackness enriches, even if just affectively, the non-fungibility of whiteness; this parasitic relationship has extended to digital culture, with white actors extracting Black meme culture. Internet memes, until the advent of NFTs, did not necessarily provide monetary gain for the creators or original owners. For example, the creator of the iconic phrase “on fleek”, Kayla Newman (aka Peaches Monroee) is regularly discussed when considering the exploitation of Black digital culture (Parham; Maguire; Hazlehurst). The term came from a Vine of Newman hyping herself up in the front-facing camera of her smartphone—“We in this bitch! Finna get crunk. Eyebrows on fleek. Da fuq”—and quickly went viral. Maguire’s insightful analysis of Newman’s viral fame underscores the exploitation and appropriation of Black girl cultural production within the US. Maguire turns toward the legal intricacies of copyright and property as Newman sought ownership of her iconic phrase; however, Vats’s work on the legal rhetorics of intellectual property note its racial exclusivity in the US. (Moreton-Robinson traces similar white supremacist ownership within Australian contexts.) Meaning, only white actors benefit from such legal rhetorics. These forbearances point to the larger cultural legacies of fungibility that alienate Black bodies from their cultural production. US Black digital culture is alienated from the individuals who perform the imaginative labour that benefits and enriches whiteness (Wilderson, III; hooks). The legacies of mass enslavement fundamentally structured the capital and libidinal economies of US culture (Wilderson, III et al.; Spillers; Brock), therefore it stands to reason, like other forms of hegemonic ideologies, that such structuring logics of anti-Blackness are foundational to digital US culture (Benjamin; Brock; Towns; Matamoros-Fernández). Iloh, Williams, and Michele Jackson separately argue that the foundation of mainstream US Internet culture is indebted to the labour of Black users. However, as Brock argues, US Internet culture is a medium by which whiteness marks itself as the default even though Black labour, individuals, and culture are regularly exploited to perpetuate white engagement. Jackson specifically notes that the white performance of US Black culture “financially, artistically, socially, and intellectually” rewards white and other non-Black actors for demonstrating their understanding of Black cultural productions (Jackson, White Negroes 5; see also: hooks; Nakamura). Black individuals are not (fairly) compensated for this labour, even as white individuals gain clout. Newman’s term “on fleek” became a staple of US Vine and broader Internet culture, spawning a hashtag (#EyebrowsOnFleek) and being featured in multiple brand commercials (Maguire). Newman notes that she did not consider trademarking the term because she did not realise how quickly it would spread, allowing corporations and other actors to capitalise on her term free of charge (Hazlehurst; Maguire). Usage of the term became a signpost of the in-crowd within US millennial popular culture (Maguire). However, when Newman later launched a hair extensions company utilising her phrase (On Fleek Hair Extensions), she was resoundingly criticised. During a GoFundMe campaign to jumpstart the business, white digital actors accused Newman of milking her fame (Parham; Hazlehurst; Maguire). Mainstream digital actors forbade Newman’s ownership of her own labour after exploiting her creation throughout its popularity, marking her imaginative labour as fungible. These cultural dynamics exemplify of how anti-Blackness proliferates US digital culture, marking Black cultural labour as fungible and as the (shared) property of white actors. Whiteness regularly dichotomises itself against Blackness, needing the denigration and de-humanisation of Blackness to constitute whiteness’s perceived racial superiority (Wilderson, III et al.; Hartman; Thomas). Since Blackness has been constituted as fungible, alienating the labouring bodies from their production, whiteness (implicitly) constitutes itself as non-fungible. Thus, under this paradigm, white actors, their bodies, and their (property’s) cultural production are constituted as non-fungible, as the foil to fungible Blackness. Of course, anti-Blackness uses fungibility as a means of enriching whiteness, first evidenced by the logics of the Atlantic Slave Trade and extending throughout contemporary US culture. Newman’s iconic “on fleek” was easily detached from her (removing product from labourer) for the benefit of celebrities and companies. I argue that NFTs further these logics; as the next section explores, non-fungible tokens capacitate white monetisation of Black cultural labour. Non-Fungibility and Non-Black Cultural Agency The sale of meme-based NFTs offers a modern illustration of the fungibility of Black cultural production. Importantly, every seller of meme-based NFTs has been non-Black, with most being white or white-passing. NFTs, thus, seemingly give non-Black actors the agency to “reclaim” meme imagery via monetisation. Contemporary US meme culture is directly created by, influenced by, and appropriated from US Black (digital) culture (Jackson, White Negroes; Iloh; Brock; J.L. Green; Nakamura). Black cultural actors used memes largely as a space to share the joys and pains of Black US life (Brock); however, the connectivity of the Internet offered avenues for extraction and appropriation by non-Black actors (Iloh; Nakamura; J.L. Green; Matamoros-Fernández). Meme-based NFTs extend these anti-Black logics by monetising the cultural impact of certain memes. Specifically, memes are considered valuable only when minted as an NFT, which seeks to transform the fungible by a non-fungible agent. This section turns to the tensions between non-Black cultural agency over Black cultural influence within US Internet culture, using the Disaster Girl meme as an illustration. Memes, because of their participatory nature, require a certain level of fungibility to perpetuate circulation (Milner; Moreno-Almeida; Shifman). While certain digital actors proffer the original textual (e.g. #UKnowUrBlackWhen, a popular hashtag for Black users sharing experiences specific to US Black culture), graphic (e.g. Fail/Win, a popular meme genre for posting images of everyday chores tagged as Fail or Win), and/or contextual (e.g. Pepper Spray Cop, a meme genre where a police officer is pepper spraying protestors is photoshopped into different scenes) facets of a meme, these same characteristics must be manipulable for the meme to flourish (Parham; Jenkins; Huntington). Further, original creators must have an alienable relation to their cultural production, a “letting go” of the meme, so it may become part of broader cultural milieu, ever-evolving (Shifman; Jenkins). Minting memes into NFTs, however, reverses and obfuscates this cultural and imaginative labour by minting the original image. The sale of the Disaster Girl meme photograph as an NFT exhibits this erasure. The meme orginates from a photo Dave Roth took of his daughter, Zoë Roth, at a 2005 control-burn of a home in their neighbourhood (Fazio; Staff). D. Roth eventually submitted the image of his white, brown-haired daughter slyly smiling as the house burns in the background to a handful of photo contests, winning them (ibid.). The image was published online in 2008 and quickly circulated among social media platforms. Memes emerged as Internet users remixed the original image, either with text or by photoshopping Z. Roth into new disasters, thus dubbing her Disaster Girl (Green, Refinery). Since, Z. Roth’s four-year-old self has been “endlessly repurposed as a vital part of meme canon” (Fazio). Gesturing to the fungibility of meme culture, Z. Roth said she “love[s] seeing them because [she]’d never make any of them [her]self” (qtd in Fazio), meaning she (and her father) had willingly alienated themselves from the meme imagery. The agency to willingly turn over cultural production is solely attributable to non-Black bodies within the logics of fungible Blackness. Z. Roth’s non-participation did not prevent her from monetising the original meme, however. On 17 April 2021, Z. Roth sold the original photo file of the Disaster Girl meme (Fazio). Roth notes the creation and selling of an NFT is “the only thing memes can do to take control” (qtd. in Fazio). To exhibit agency of minting an NFT, Z. Roth collapses memes’ identities into the original image rather than the participation, remix, and becoming that meme culture involves. Memes, by nature, require the repeated and continual labour of digital public actors to continue circulating (Shifman; Milner; Jenkins). The stronger the meme’s circulatory impact, the more cultural heft it carries. However, the Roth family could only ever sell the original image. The minting of an NFT, for Z. Roth, “was a way for her to take control over a situation that she has felt powerless over since elementary school” (Fazio). Here, Z. Roth is further exerting non-Black agency to wilfully reclaim the previously fungible object. Ironically, the very thing Z. Roth is wanting to exert control over is what gives value to the meme in the first place. The virality and longevity of the Disaster Girl meme is its value, but given the fungibility of meme culture, this labour is easily obfuscated. As noted, memes must exhibit a certain level of fungibility to regenerate throughout digital cultures in various iterations; memes also require the fungible Black cultural production, especially within the US. Brock argues the capacity to laugh through pain or chaos is a characteristic of US Black humour and foundational to contemporary US meme humour. The Disaster Girl meme exemplifies the influences of US Black cultural humour both in the comedic frame—smiling in the face of disaster—and the composition of image—looking directly into the camera as if to break the fourth wall (Outley et al.; Brock). These facets influence the affectivity of the Disaster Girl image, or its capacity to move audiences to add their own remix to the meme. Remix is not only an inherently Black practice (Navas et al.), but it is also the lifeblood of meme culture and Internet culture more broadly. Iloh, Jackson, and Williams separately argue the proliferation of Black digital culture in the US means much of what enters mainstream US culture was shaped by Black users. Therefore, Black imaginative labour is an absent presence at the heart of Disaster Girl (or any) meme’s popularity—the popularity that made it valuable as an NFT. Minting the original image as a meme-based NFT consumes the labour of digital public actors to realise a value for the image owner. According to Cervenak, “NFTs can be seen as a tool for creators to be made whole for the work they put in” creating the original image (qtd. in Notopoulos). However, in memes the “work [being] put in”, the imaginative labour generating the memes, is that of various digital public actors. Neither the digital public actors, specifically Black public actors, nor the US Black cultural production and labour are recognised within the NFT economy. The reversion of memes back to the original image attempts to erase the Black cultural labour that generated the meme’s value. The work of digital public actors must be seen as both interchangeable and working in the service of the original “owner” of meme imagery to facilitate the trade of meme-based NFTs. Unlike Newman, Z. Roth was lauded for the monetisation of her meme-fame. Indeed, Newman’s imaginative labour needed to be obfuscated for the appropriation of “on fleek” by non-Black US culture. Z. Roth did very little labour in the invention and circulation of the Disaster Girl meme; however, her agency within anti-Black US culture created the conditions of possibility for her minting of the NFT. The dynamics of NFTs, Black US cultural labour, and anti-Blackness allow for the simultaneous obfuscation and appropriation of fungible meme-culture. Just as enslavement alienated Black bodies from the profits of their labour, NFTs similarly erase Black cultural production from the monetary benefit; NFTs (further) digitise these paradigms of anti-Blackness in US digital culture. Conclusion This essay has just barely chipped the surface on the articulations of race, fungibility, and NFTs. The arguments contained within demonstrate the legacies of fungible Blackness, which US Afro-pessimism links to the structuring logics of the Atlantic Slave Trade, and their manifestation in contemporary digital culture, specifically via meme-based NFTs. First, the essay traced the needed alienation and appropriation of Black cultural labour within US culture. Translating these practices to meme culture, the essay argues the minting of meme-based NFTs is a non-fungible agency only available to non-Black actors. There remains much to be explored, especially regarding equitable cultural practices. 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The Walking Dead is an American post-apocalyptic horror drama television series based on the comic book series of the same name. In the opening episode, Sheriff’s Deputy Rick Grimes awakens after months in a coma in an abandoned hospital to find a post-apocalyptic world dominated by flesh eating zombies. The cause of the apocalypse is unknown, and Grimes does not know what has happened to his family. The start of the programme is situated around his quest to find his family, and the encounters he has with the many other survivors along the way. The plot of The Walking Dead centres on the survivors of the apocalypse as they search for safe haven away from the “walkers”, or “biters”; the first series focuses on how they cope with the immediate realities of life in the post-apocalyptic world. From the outset, the programme finds its way through the upheaval and destruction of everyday American life. Decay is persistent and inevitable in the threat of death from the “walkers”; this familiar Gothic trope is ever-present throughout the series.This paper uses a Gothic focus to examine The Walking Dead and considers the disintegration of society and family after the zombie Apocalypse. It focuses primarily on the first series of The Walking Dead, and examines Gothic tropes through a discussion of the decay of the walkers, the decay of the family, and the decay of society.Zombie Gothic It is important to examine the zombie narrative within a Gothic framework. Kyle Bishop argues that “zombies and the narratives that surround them function as part of the larger Gothic literary tradition, even as they change that tradition as well” (31). In contrast to other Gothic traditions that began in literature, the zombie is unique as it began in folklore, cinema and drama. Similarities to other Gothic traditions exist, such as ghosts and vampires, and the zombie narrative serves as a vehicle to examine cultural anxieties and prevailing attitudes. In fact, Bishop suggests that the zombie narrative has now proven itself to be as interesting and complex as more established Gothic traditions (31). Just as earlier Gothic traditions allowed people to explore themselves in the mirror that Frankenstein (1818) or Dracula (1897) provided, the zombie allows for a more modern examination: a world that is increasingly complex with its technological and cybernetic advances yet a world where humanity has still not resolved the great differences that exist. Bishop argues that “during the latter half of the twentieth century, for example, zombie movies repeatedly reacted to social and political unrest, graphically representing the inescapable realities of an untimely death…” (11). The zombie narrative’s ability to adapt to cultural anxieties make it part of the Gothic tradition. Bishop also argues that, in a post–9/11 climate, the zombie film works as an important example of:the contemporary Gothic, readdressing “the central concerns of the classical Gothic,” such as “the dynamics of family, the limits of rationality and passion, the definition of statehood and citizenship, the cultural effects of technology.” In addition to exposing such repressed cultural anxieties, Fred Botting emphasizes how Gothic narratives “retain a double function in simultaneously assuaging and intensifying the anxieties with which they engage.” (26) The Gothic situates itself from the 18th century as writing of excess and this tendency permeates much of the genre’s narratives, characters and settings. The mutability in Gothic texts provides a platform for many social issues and anxieties to be addressed; its ability to shift and adapt in order to reflect contemporaneous social trends is partly what has enabled it to remain popular (Botting Gothic). The zombie forces a confrontation with the fears of life and death, freedom and enslavement, and the destruction of modern society. These include “the exploitation of the masses in capitalist society, the soullessness of modern-day life, our fear of global apocalypse, our revulsion at the reality of war, and the inevitability of death” (Graves 9). The rise of the zombie narrative plays on humanity’s fear for the future: that modern civilisation has many fundamental weaknesses that may ultimately collapse through one form of global disaster or another. The Gothic situates itself from the 18th century as writing of excess and this tendency permeates much of the genre’s narratives, characters and settings. The mutability in Gothic texts provides a platform for many social issues and anxieties to be addressed; its ability to shift and adapt in order to reflect contemporaneous social trends is partly what has enabled it to remain popular (Botting Gothic). The zombie forces a confrontation with the fears of life and death, freedom and enslavement, and the destruction of modern society. These include “the exploitation of the masses in capitalist society, the soullessness of modern-day life, our fear of global apocalypse, our revulsion at the reality of war, and the inevitability of death” (Graves 9). The rise of the zombie narrative plays on humanity’s fear for the future: that modern civilisation has many fundamental weaknesses that may ultimately collapse through one form of global disaster or another. I argue that the zombie is part of a new kind of Gothic with a new monster for a new age. This new monster facilitates the Gothic’s ability to remain relevant in a post-industrial, cyberspace era. Unnatural death is now more horrific, pervasive, and far-reaching than Walpole ever could have imagined when he wrote the now canonical Gothic novel The Castle of Otranto (1764), and the zombie works as a dramatic manifestation of this ever-present anxiety. The Gothic narratives of the zombie now represent a more modern reaction to the threats posed in the 21st-century, post-9/11 world which is potentially more traumatic than the threats posed in earlier Gothic novels of the 19th and 20th century. Global pandemics may manifest as a zombie apocalypse or disease that threaten complete annihilation of civilisation. Teresa Goddu emphasises how “the Gothic is not a trans-historical, static category but a dynamic mode that undergoes historical changes when specific agents adopt and transform its conventions” (32). Zombie narratives have updated Gothic conventions to then reflect modern day anxieties and fears. As Botting argues, “Gothic figures” represent anxieties associated with turning points in cultural historical progress (2002). Zombie narratives, then, serve to allow a confrontation with more modern terrors and threats that exist; the zombie narrative, it can be argued, confronts Gothic tropes and places them in a contemporary context. Cultural anxieties have been nurtured about the rise in terrorist activity around the world, witnessed with the collapse of the World Trade Centre towers, and the threats of pandemics that might eviscerate the human race in the form of SARS. The zombie narrative then represents a logical growth in Gothic monsters that have been used to explore modern day cultural anxieties. Post-Apocalyptic America and Gothic Zombies Apocalypse and zombie narratives represent the worst case scenario for both the people of USA and the world. Zombies, vampires and other apocalyptic monsters are used as faceless creatures to present either an unknown threat or pose them as social critique (Bo). The first signs of the Gothic are present from the start of The Walking Dead, where the familiar American suburban scene has altered into a mutilated disintegrating version of society. In the series, threat comes not just from the “walkers” but also from the fellow survivors who no longer obey the pre-apocalypse laws and way of life. Pre-apocalypse, Rick Grimes was a sheriff, and an upholder of the law. The series starts with Grimes in a police car having lunch with his best friend Shane Walsh while they discuss the differences between men and women. In a police shoot-out, Grimes is shot and awakens to find society as he knew it destroyed. After waking from his coma, he returns to his family home and meets two other survivors, Morgan Jones and his son Duane, who explain the implications of the zombie apocalypse to him. Grimes searches for his family and returns to the police station. He puts on his uniform which appears as a symbol of the normality he thinks he can return to. However, as he goes to get petrol, Grimes looks under a car and sees a young girl’s pink slippers. He calls to her saying “don’t worry little girl”, as the girl drags a pink rabbit. She turns around to face Grimes and runs at him: it is revealed she is a zombie. She is a grotesque parody of a little girl with her distorted and mutilated face; as Grimes draws out his gun and shoots her in the face, she is an uncanny reminder that humanity has permanently altered. The narrative of adults and police officers protecting innocent children is quickly subverted from the start of the series. From this moment, Rick Grimes is permanently fighting his own loss of morality and humanity in a society that has become a distortion of what it once was. The term “liminality” is employed by critics and theorists of the Gothic to refer to spaces or bodies situated:either on or at the recognized borders or boundaries of subjective existence. In eighteenth-century Gothic writing, these thresholds were mainly encountered through liminal spaces. These were often mountain ranges, secret rooms, and hidden passages. From the nineteenth century onward, the human body has increasingly become a liminal site where normative boundaries are challenged; the monster, vampire, and werewolf, are all liminal beings. (Hughes, Punter and Smith)The zombies continues the Gothic tradition of liminality and is perhaps more frightening as they represent the dissolution of death, yet are still in some form “alive”. In The Walking Dead, the survivors are also neither completely alive nor dead, as they are on the edge of losing life as they know it and becoming consumed by the undead. The “walkers” operate as terrifying prompts that what was once considered an incontrovertible fact—the difference between life and death—is not as final in the post-apocalyptic world of the series. The “walkers”, therefore, are walking manifestations of decay and liminality, a reminder that the fear of death has been transmuted into the fear if an even more dangerous entity, neither living nor dead. Gothic, Misha Kavka argues, is often about fear, localised in the shape of something monstrous that electrifies the collective mind (Kavka). In this case, the zombies are tangible displays of how a pandemic or global outbreak could alter humanity forever. Gothic is also about the paranoia around body manipulation, defined as a projection of the self on to the outside world where the boundaries blur between self and other (Kavka). In the zombie narrative of The Walking Dead, the boundaries between the living and dead collapse when decay reanimates into the liminal form of the “walkers”. Decay of the Family The death of the family unit as a recurring trope is raised early on in the series, and the initial problem for Rick Grimes is locating his missing family. Grimes teams up with Morgan Jones and his son Duane. Morgan has his own dilemma when faced with the thought of killing his wife who has turned into a “walker”. She returns to their family house, and seems caught between life and death as if she has some memory of the life she had before. Rick Grimes’s family dilemma is further exacerbated when he finds his wife and son with other survivors who have formed a group. Thinking that her husband Rick was dead, Lori Grimes has started a relationship with Grimes’ best friend, fellow police officer Shane Walsh; a growing tension grows between the two men as the series continues. Ultimately this leads to a fight between the two men as the jealousy grows and each have different ideas on how to best keep the survivors safe. Where the men were once allies and friends, the apocalypse has turned them into enemies. Though the zombies are the most manifest threat to the survivors, there are other threats that come to the fore in The Walking Dead. These threats are in the form of the changes that occur between the characters (Bo). What were once everyday events turns into dangerous events: getting water, petrol and food, for example, become life-threatening activities, and the survivors must trust people who they meet up with on their travels. Rick Grimes’ pre-apocalypse ethics and humanity are tested by the new society. For example, he allows his son Carl Grimes to carry a handgun which Carl later uses to save Rick’s life. In contrast to the Grimes family that is at the centre of the narrative, another group of survivors live at a farm and are led by Hershel Greene, a farmer and religious leader. Their treatment of the “walkers” represents a different approach to the zombie apocalypse. Hershel keeps zombies in a barn and sees them as sick people, while Rick sees them as monsters. Many in the barn are Hershel’s family members; it is only later in the series that Hershel comes to see the zombie family as monsters intent on killing all human survivors. With the connections to family and love, the zombies act as a mirror to the human survivors of what they may potentially become. Societal Decay From the start The Walking Dead Rick Grimes needs to grapple with a world profoundly altered by the zombie apocalypse. The hospital is abandoned except for stray zombie corpses, and it is clear that the once secure place of the hospital is no longer a haven for the sick. One of the most obvious signs of decay is the streets littered with abandoned vehicles, and there are outward markers of chaos and apocalypse. There is much that is Gothic and uncanny in The Walking Dead, where cognitive dissonance is opened up when the familiar becomes strange. The world ostensibly looks the same but will never be normal again for Rick Grimes and the survivors. Here the “true horror lies in that which is most immediately at hand that the most proximal bears the capacity to contain the utterly unfamiliar” (Chopra). The decay of society is made both manifest and melancholic as it evokes the anxiety of being simultaneously normal and abnormal. The once known, or normal, world has become strange and unfamiliar. For example, in the first series of The Walking Dead there is a reference to the classic zombie horror film Dawn of the Dead (1978), where the survivors find themselves trapped in a department store, a famous scene commented upon by Bishop:This instinctual “drive to shop,” as it were, is repeatedly emphasized by Romero, who shows the mindless creatures pressed up against glass doors and windows, clamouring to get inside the shops, in a gross parody of early-morning-sale shoppers, to resume their earthly activities of gluttonous consumption—indeed, as Kim Paffenroth points out, their addiction for the place exists beyond death. (Bishop 41) As the maniacal governor in The Walking Dead later observes about the zombies: “The thing you have to realize is that they’re just us—they’re no different. They want what they want, they take what they want and after they get what they want—they’re only content for the briefest span of time. Then they want more” (Bishop 140). The zombies then serve as a mirror for the worst of humanity. Zombies further mirror other aspects of humanity that are hidden and ignored. Barbara Creed suggests that the popular horror film brings about a confrontation with the abject (the corpse, bodily wastes, and the monstrous-feminine), and by doing so re-draws the boundaries between the human and non-human (Creed). She argues:Firstly, the horror film abounds in images of abjection, foremost of which is the corpse, whole and mutilated, followed by an array of bodily wastes such as blood, vomit, saliva, tears and putrefying flesh. (Creed 253)The zombies/”walkers” in The Walking Dead are abject, mutilated walking corpses. Creed argues that the blurred boundaries between life and death, and the antinomies that humans like to ignore or pretend do not exist, are seen in creatures like zombies. Abjection is usually represented by bodily fluids such as pus or blood or a kind of in-betweenness, such as the zombies’ state between life and death. Mark Bould and Sherryl Vint argue that apocalyptic fiction uses the scenario of the end of the world as a way to rebuild and reorganise society (23). The very question of possible futures and society in a post-apocalyptic world is raised and questioned in The Walking Dead when everyday survival is at stake. This alters, however, when Rick Grimes has to focus on the long-term survival of the group and his family when his wife becomes pregnant. Lori Grimes argues that the world they find themselves in is no place to raise a child and to establish new lives. Rick does not agree with Lori and her pessimistic view of society as it stands. In an uncanny twist, the survivors do not know what has caused the apocalypse, but they later learn that everyone is infected and will re-animate when dead: they are the “walking dead”.Conclusion The Walking Dead is a modern Gothic text that uses many of the tropes of the Gothic to explore cultural anxieties present today. One such area is that of decay, chaos and lawlessness in the post-apocalyptic world of the zombie. This is a key area of the Gothic tradition played out in the modern afflicted world. At the start of The Walking Dead, society is seen as “normal”, two police officers are eating lunch in their vehicle and talking about life. After Rick Grimes awakens after his coma what was once “normal” has transformed into a site of uncanny horror, suspense and terror. Much of the first series is spent with Grimes and his survivors trying to contain and combat the zombie threat. Botting argues that early Gothic fiction articulated a shift from a feudal economy to a capitalistic one (2008). In similar vein, in The Walking Dead the future is one where capitalist society has totally collapsed. This could be a critique of the 2008 financial crash, or a fear of what could happen if a pandemic were to occur that ended consumer life and society as it is known (Bishop 41). It also demonstrates that what is seen as established norms quickly disintegrate in the new post-apocalyptic society. Social structures in the post-apocalyptic world no longer function as they once did. The normality of a pregnancy which should, under “normal” circumstances, herald hope for the future, sets off ambivalence in the Grimes family about the life circumstances the survivors find themselves in, and the future that is available to them or their offspring. Core institutions and structures have fallen; the hospital at the start of the series no longer functions and the police are no longer upholders of the law. Chaos and anarchy are now the everyday life that confronts the survivors. The survivors are frequently left with questions about what is the point is of their lives. At the centre of the chaos is the change in family and society. The structures of modern society are seen as flimsy and easily disturbed in the post-apocalyptic zombie future. As Botting says, “uncertainties about the nature of power, law, society, family and sexuality dominate Gothic fiction” (Gothic 3). The modern day Gothic then questions these key areas of society. The death in the Gothic post-apocalyptic zombie future is that of society as well as individuals. References Bishop, Kyle William. American Zombie Gothic: The Rise and Fall (and Rise) of the Walking Dead in Popular Culture. Jefferson: McFarland Company, 2010. Bo, Kristian. Surviving the End. Thesis. University of Tromso, 2013. Botting, Fred. “Aftergothic: Consumption,Machines, and Black Holes.” In Hogle, The Cambridge Companion to Gothic Fiction. ———. The Gothic. London: Routledge. 1995. ———. Limits of Horror: Technology, Bodies, Gothic. New York: Manchester University Press, 2008. ———. “Science Fiction and Film in Gothic.” London: Routledge. 2005. Bould, Mark, and Sherryl Vint. The Routledge Concise History of Science Fiction. New York: Routledge, 2011. Creed, Barbara. “Horror and the Monstrous-Feminine: An Imaginary Abjection.” Feminist Film Theory: A Reader. Ed. Sue Thornham. New York: New York University Press, 1999. Chopra, Samir. “American Horror Story, The Walking Dead, and the American Gothic”. samirchopra.com, 2014. Goddu, Teresa A. Gothic America: Narrative, History, and Nation. New York: Columbia University Press, 1997. Hughes, William, David Punter and Andrew Smith. The Encyclopaedia of the Gothic. London: Wiley, 2014. Kavka, M. “The Gothic on Screen.” The Cambridge Companion to Gothic Fiction, ed. C. Jerold Hogle. Cambridge: Cambridge University Press, 2002. Overbey, Erin. “The Walking Dead Returns”. The New Yorker, 2012. The Walking Dead, Frank Darabont. AMC, 2010. DVD.

Introduction Music scholarship across genres is often concerned with music's metaphysical and ephemeral effects on individuals, communities, and society. These scholarly framings constitute a concept that we refer to here as “the magic of music”. Using this framing, this article addresses the ways that the magic is undermined by a range of worldly, non-magical realities, using the case study of the COVID-19 pandemic lockdowns and their devastating effects on the previously thriving live music industry in Naarm/Melbourne, Australia. The magic of music includes such aspects as the intangible sounds of music, the mysterious practice of creative music-making, and the transformative effects on audiences and others who participate in music culture. We begin with a broad discussion of the sonic properties of music as a form of magic—a common rhetoric that has been used across the world regardless of genre or cultural origin. Next, we turn to the social contexts surrounding music, such as live music settings. De Jong and Lebrun argue that “the power of music” can create “moments of rare, intense and direct interactions between individuals” that are often described as magical, and that “magic is, in this sense, understood as a perfectly natural and plausible, and not supernatural, experience, even if its intensity and rarity in one's life makes it extra-ordinary” (4). We use this framing of “music as magic” in our consideration of the specific context of Australia’s music industry from 2020 to the present. We posit that the devastating effects of the COVID-19 pandemic, alongside government-sanctioned lockdowns, cultural shifts such as an increased focus on poor working conditions and risk in music work, and detrimental arts funding policies worked together to effectively break the spell of “music as magic” for industry and patrons. Finally, we draw on key examples from popular music studies, industry reports and new government policies, to call attention to recent proposals to rehabilitate the magic through a re-enchantment of music and the music industry. Feels like Magic: The Social Context of Music Music is a form of organised sound and silence that people across cultures, history, and places, have articulated as possessing magical properties (Nettl). Music is not only sound waves but also a social category, thus the notion of magic extends beyond sound into everyday discourse in the social realm of music, which will be the focus of this article. Audiences/listeners may describe their own response to music as a magical feeling, stemming from the performer’s ability to convey emotion and provide a performance that “mirrors the performer’s [own] deep connection to the music” (Loeffler 19). Such ‘magical moments’ of deep connection among audience members and between audiences and performers may be elicited in various ways. Examples include the sense of emotional self-recognition found via personal lyrics, resonance with unique vocal timbres, or the shared sense of belonging that develops with fellow audience members, including strangers, during musical events (Anderson). For the latter, the magic (or “magick”, a spelling associated with stagecraft) of ritualised music performance is a common element of Paganism in music performance, with some popular music artists implicitly “appropriat[ing] the Pagan subculture's symbols for artistic inspiration and commercial gain”, presenting themselves as contemporary conduits that reconnect audiences to old magics (Sweeney Smith 91; see also Weston). When it comes to these sorts of ideas about magic and music, performers and audiences routinely make claims about magical musical powers such as “talent”, an idea deployed to describe the skills and charisma of certain musicians, and “creativity”, a “magic ingredient” (see McRobbie) that people who write or produce music are supposed to possess in order to perform their craft (Gadir 61–4; Gross and Musgrave 10, 22; see also Nairn). Music of all forms can provide profound affective experiences, regardless of how it is made and who plays it. There is also a magical discourse present in popular music that has reached millions of people in a globalised musical world dominated by recordings. For as long as music has had a mass market, its magic properties (as articulated in multiple ways across history) have been a selling point for musicians, records, and concerts. The recorded music industry’s very selection process is rooted in the idea that “creativity is based on ‘little bits of magic’ and that success is down to luck and timing” (Gross and Musgrave 140). Music writing (scholarly, criticism, journalism) tends to focus on these magical properties: from the sublime nature of a musical work and its form to the phenomenology of sound and affective experience of music, and even the inexplicable, elusive ‘talent’ of particular musicians. Jimi Hendrix labelled his music work “completely, utterly a magic science” (Clarke 195), while Joni Mitchell “consistently referred to Charles Mingus, Wayne Shorter, and Jaco Pastorius as ‘magicians’ and ‘shamans,’ thereby conferring a susceptibility to the miraculous upon the musicians she most respected” (Lloyd 124). As we show below, this conflation of magical and religious concepts is evident elsewhere in discourse on the intangibility of musical talent. Some genres of music have emphasised the idea of music as magic more than others. For example, scholarship on electronic dance music (EDM) has embraced the concept of “DJ as shaman” (Brewster and Broughton 19; Luckman 133; Rietveld “Introduction” 1; Rietveld This Is Our House) and the nightclub as a “pseudo-religious pilgrimage site” (Becker and Woebs 59), extending Benjamin’s argument for art’s origins in service of ritual (24). Miller has further alluded to a mystical DJ craft, both as a performer quoted in music media (Gallagher) and in his own academic writing: “gimme two records and I’ll make you a universe” (DJ Spooky That Subliminal Kid 127; Miller 497). Shamanism is also explored in rock music discourse (see Kennedy 81–90). Notions of musical magic extend beyond performances and personalities into the recording studio. Music mastering is commonly labelled a “dark art” (Hepworth-Sawyer and Golding 241; Hinksman 13; Nardi 211), and the music studio as a site where magic is made (Anthony 43, 194). Rolling Stone magazine has even deployed a recurrent editorial phrase—“the magic that can set you free”—to distinguish the authenticity of rock from pop music (Frith 164–5). We argue that two key ruptures of the last few years—namely, widespread lockdown policies during the COVID-19 pandemic, and emerging discussions on poor working conditions and harms in the music industries—have had the effect of breaking the magic spell of music. There has been a groundswell of musicians, commentators, and scholars pausing to query (and in some cases overturn entirely) some of the illusions that the music industry constructs around musicians. We use the city of Naarm/Melbourne in Australia to draw out some of these trends. When the Magic Dies: Breaking the Spell of the Music Industry The COVID-19 pandemic resulted in lengthy lockdowns in the city of Naarm/Melbourne. In total, over a two-year period, the city spent 262 days in home confinement under strict orders from the government, with limited travel and no access to the usual amenities of the city, including all public in-person entertainment (Jose). This had a profound effect on the state’s musicians and the music industries that service them. It completely closed the city’s music venues for an extended period, driving musicians into alternative, virtual modes of performance (Vincent) and driving other music workers into non-music-related employment. For a city often touted as “the live music capital of Australia” (see Homan et al.), the lockdowns effectively broke the spell of music as a key employer and as a driver of arts practice and social experience in Melbourne. Quite suddenly, the lockdown periods revealed the precarious lives of musicians away from the stage. Once stripped of the “magical” quality of live performance, musicians’ work and practice appeared both more complex and more routine. The COVID-19 pandemic broke the spell of music that takes place in social settings. At the start of 2020, live music was one of the first activities to be banned. Live music relies on people being near one another, often in enclosed spaces. It often involves people on stage and in the crowd singing, an activity identified early in the pandemic as an effective method of spreading the virus. These attributes, together with its status as “entertainment” rather than as an essential activity, meant that live music gatherings became entirely illegal (Strong and Cannizzo). Even as lockdowns were lifted, live music was one of the last activities to be reinstated, albeit with access restricted in various ways. People continued to engage with music via other means, for example, through virtual live-streamed performances and platform-based audio streaming. Globally, there was an increase in people listening to older, nostalgic music (Yeung)—an indicator that music was still being used for its magical self-soothing capacities, alleviating the worst pandemic anxieties. However, the closure of the Victorian live music sector drew attention to the material conditions of music making in new ways (“Losses Continue”). Many musicians and music workers could not take advantage of government schemes to support workers who had lost their income during the pandemic (Triscari). This highlighted what was already known to music industry workers: that their work was insecure. It also revealed the contradictions within government music policies: on the one hand, music’s utility for city branding, on the other, little regard for what support and resources are required for it to take place. As more and more musicians used the pandemic to draw attention to their already existing labour conditions, the precarious and mundane aspects of music-making became foregrounded in broader discussions (see Strong and Cannizzo). These included the overall degree to which musicians are exploited (see Nairn), whether musicians can earn a living wage, pay their rent, or receive other workplace benefits including safe working environments. These problems exist in stark contrast to the historically mythologised portrayals of musicians as concerned about their art and Dionysian social experience above all else, regardless of their physical or material conditions. In reality, live music work has always included mundane activities and routine labour. The historical mythology of the “star”, regardless of genre, tends to depict the lives of performers as exotic and removed from everyday life. In this sense, performers are perceived as magical as much as the music they make. The everyday world, within this mythology, is something akin to “a fearful, life-threatening condition that could ensnare you in its grasp … as relentless routine and the marker of social distinction” (Highmore 16). Audiences tend to view musicians as committed to alternative ways of being, and music performance as an escape from the everyday, wherein work becomes interchangeable with leisure and touring provides a nomadic lifestyle. However, in recent years, popular music studies research, together with musicians, fans, and media, have called these ideas into question. A career in live music performance appears to offer no escape from responsibility—something at the heart of fearful representations of everyday life. Inside of a music practice, new responsibilities emerge. Leisure becomes labour with all its attendance downsides. Close-knit familial-style relationships are formed, often based on financial and creative partnerships, including the risk of gender-based abuse that exists within such relationships (Fileborn et al.). The nomadic life of a performer involves its own cramped and confining aspects (a life of group transit and service entrances). This combines with an already in-progress push towards making the vicissitudes of this work more visible—afforded by social media, cultural formations such as #MeToo, and a significant upswing in research showing the harms of music work (Gross and Musgrave; Strong and Cannizzo)—to significantly undermine the myth of live music’s magical properties. In Naarm/Melbourne, prior to the pandemic, this myth was brittle. After years of lockdown, it arguably shattered. The emotional devastation wrought by an abrupt and almost complete cessation of live music activities also had flow-on effects on recorded music. For example, it prevented activities such as tours that support album releases, recording sessions, or rehearsing new musical material. Already existing mental health issues in the music industry were highlighted and amplified by these circumstances (Brunt and Nelligan). Together with the aforementioned financial disadvantage experienced by musicians, research had already shown for years before the pandemic that mental health was poor in this sector (Gross and Musgrave). Such mental health issues are due in part to the relationship between music work and conceptions of self and identity, where success or failure are felt as intensely personal (a by-product of the idea that music possesses magical qualities). Mental health problems are also associated with exclusion, bullying and harassment, which are not only widespread but have been normalised and even celebrated for decades. Pre-existing pressures such as these were exacerbated dramatically by the pandemic lockdowns, which spurred on further discussions about them (Strong and Cannizzo). During the pandemic, the magic of music had been disrupted in several ways: the ability of music to connect people to one another in live settings had been curtailed or removed, and the narratives of the creation of music being magical had been replaced with a vision of mundanity, hardship, and underappreciation. If the magic did not set musicians or music workers free, why should they return to long working hours for little pay in an industry that was frequently unsafe and that left them feeling bad—especially when they discovered that when the chips were down, they would be left out of the support offered to others? Re-Enchanting Music: Conjuring a Different Kind of Magic Weber used the term “enchantment” as a means of explaining the magic within worldly (empirical) phenomena. By contrast, he argued that disenchantment was the removal of magical experience from the real world and that this was the result of replacing the “supernatural” exclusively with rationality and calculation (Koshul 9). The easing of lockdown conditions heralded what we call here the “re-enchantment” of the music industry. An industry that is re-enchanted refers to a world which is “susceptible again to redemption” and is “reimbued not only with mystery and wonder but also with order [and] purpose” (Landy and Slalor 2). During the early post-lockdown period, the aim of government, patrons, and the entertainment industry was to rekindle the pre-COVID levels of audience engagement with live music. Audiences themselves were eager to return to live music and were prepared to spend money on concert tickets and music festivals, according to findings from the Australia Council’s Audience Outlook Monitor (Patternmakers). However, this report also showed that restrictions, fears of further outbreaks, and lockdowns were still looming in the minds of audiences and event organisers. This was compounded by a lack of investment in the creative industries broadly by the Australian Federal government during lockdowns and a staggered reopening, particularly in the state of Victoria, where lockdowns continued well into 2021. The road back to ‘normality’ would require putting audiences, industry, and, indeed, the government, back under the spell of music. Reaffirming the idea that music has a fundamental value in society and culture was the first step. The election of a federal Labor government in 2022 started this process, after a decade of conservative Liberal leadership that had actively worked to devalue and defund the arts. The new government quickly launched a consultation process around the arts in Australia, and launched the resulting policy, titled Revive: Australia's Cultural Policy for the Next Five Years, in mid-2023. This policy not only reaffirmed the central place of the arts, including music, in Australia's social life, but went further than any previous government in acknowledging some of the disenchantment in the industry. They committed to establishing Music Australia (Creative Australia) as a body dedicated to ensuring the prominence of music in arts activities, and the Centre for Arts and Entertainment Workplaces, a body that would, among other things, deal with complaints around workplace misconduct of various types. This later body was created partly in response to the Raising Their Voices report documenting widespread bullying and sexual harassment in music spaces. In addition to this, Australian state governments implemented various measures to encourage the re-normalisation of concert attendance. For example, the Victorian State Government’s Always Live funded programme was launched with a regional, one-off gig by the Foo Fighters. Initiatives such as these on the state and federal level served to bolster the struggling industry. An initially slow return to live shows, followed by a spate of visually spectacular, large-scale, sold-out shows by Harry Styles and Taylor Swift, indicate a return to a form of ‘business as usual’ for top-tier international touring artists. Although top-down policy can send a message that music work is valued, much of the ‘magic’ of music is created by communities and within grassroots spaces. In Naarm/Melbourne, the announcement that the iconic live music venue the Tote Hotel was being put up for sale has provided a flashpoint moment. The venue’s current owners have become emblematic of the problems in the industry, reportedly failing to provide proper benefits to their staff over a long period (Marozzi). The owners of the Last Chance Rock and Roll Bar have since announced a fundraiser for three million dollars to buy the Tote, which they have framed in terms of protecting the value of music to the Naarm/Melbourne community. The owners promised to not only protect music-making on the site but also to “leave the Tote to the bands and future generations for the rest of time” by “putting the building into a trust that will legally protect the Tote from being anything other than a Live Music Venue” (“Last Chance to Save the Tote”). References to the (dark) magic of this situation is visible in the designs for the t-shirts given out for contributors to the funding campaign: two zombies crawling from the grave of the Tote, beers in hand, ready to keep on rockin’. The zombies are indicative of a venue risen from the dead through the Naarm/Melbourne music community’s magical effort. The response of the public and commentators that have followed the achievement of this fundraising goal is akin to the wonderment of an audience seeing a magician perform an impressive trick. Notably, the community-led and community-focussed approach of the Tote draws on the magic of connection built around music scenes, not only corporate interests. This includes exploring how venues can be owned by the communities that use them (Wray), schemes that provide artists with a universal basic income (Caust), and “safer spaces” strategies that work to increase the accessibility of music for everyone (Hill et al.). 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