Oncolytic virus TG6002 safety and activity after intrahepatic artery administration in patients with liverdominant metastatic colorectal cancer

The TG6002.03 trial is a dose-escalation phase 1 clinical trial of TG6002 infusion via the hepatic artery in patients with liver-dominant colorectal cancer metastases. TG6002 is an engineered Copenhagen strain oncolytic Vaccinia virus, deleted of thymidine kinase and ribonucleotide reductase to enhance tumor selective viral replication and expressing FCU1, an enzyme converting the non-cytotoxic prodrug 5-fluorocytosine (5-FC) into the chemotherapeutic compound 5-fluorouracil (5-FU). In this trial, patients with advanced unresectable liver-dominant metastatic colorectal cancer who had failed previous oxaliplatin and irinotecan-based chemotherapy were treated with up to 2 cycles of TG6002 infusion 6 weeks apart via the hepatic artery on day 1 combined with oral 5-FC on days 5 to 14 (where day 1 = TG6002 infusion). TG6002 infusion was performed over 30 minutes via selective catheterization of the hepatic artery proper. 5-FC oral dosing was 50mg/kg x4 daily. Blood was sampled for TG6002 pharmacokinetics and 5-FC and 5-FU measurements. Sampling of liver metastases was performed at screening and on day 4 or day 8 for virus detection and 5-FC and 5-FU quantification. In total, 15 patients (median age 61 years, range 37-78) were treated in 1 UK centre and 2 centres in France and received a dose of TG6002 of 1 x 106 (n=3), 1 x 107 (n=3), 1 x 108 (n=3), or 1 x 109 pfu (n=6). Fourteen of the 15 patients received a single cycle of treatment, including one patient who did not received 5-FC, and one patient received two cycles. TG6002 was transiently detected in plasma following administration, suggesting a strong tissue selectivity for viral replication. In the highest dose cohort, a virus rebound was observed on day 8, concordant with replication time of the virus. In serum samples, 5-FU was present on day 8 in all patients with a high variability ranging from 0.8 to 1072 ng/mL and was measurable over several days after initiation of therapy. Seven of the 9 patients evaluable showed the biodistribution of the virus in liver lesions by PCR testing on day 4 or day 8. Translational blood samples showed evidence for T-cell activation and immune checkpoint receptor-ligand expression. At 1 x 109 pfu, there was evidence for T-cell proliferation and activation against tumour-associated antigens by ELISpot and for immunogenic cell death. In terms of safety, a total of 34 TG6002-related adverse events were reported, of which 32 were grade 1-2 and 2 were grade 3. The maximum tolerated dose was not reached, and a single dose-limiting toxicity was observed consisting of a myocardial infarction in a context of recent Covid-19 infection in a 78-year-old patient. These results indicate that TG6002 infused via the hepatic artery in combination with oral 5-FC was well tolerated, effectively localized and replicated in the tumor tissues, expressed its therapeutic payload and showed anti-tumoral immunological activity.

THE ROUTLEDGE COMPANION TO ADVERTISING AND PROMOTIONAL CULTURE: Second Edition

This comprehensive second edition provides an updated essential guide to the key issues, methodologies, concepts, debates, and policies that shape our everyday relationship with advertising. This updated edition takes a critical look at advertising and promotion during the explosion of digital and social media, as well as with significant social and cultural shifts, including the COVID-19 pandemic, the rise of the Black Lives Matter movement, the destabilization of democracies and rise of authoritarianism around the world, and intensification of the climate crisis. The book offers global perspectives on advertising and promotion with attention to issues of diversity and difference. It contains eight sections: Historical Perspectives on Advertising and Promotion;Promotional Industries;Advertising Audiences;Advertising Identities;Advertising and/in Crisis;Promotion and Politics;Promotionalism and Its Expansions;and Advertising, Promotion, and the Environment. With chapters written by leading international scholars working at the intersections of media and advertising studies, this book is a go-to source for scholars and students in communication, media studies, and advertising and marketing looking to understand the ways advertising has shaped consumer culture, in the past and present. © 2023 selection and editorial matter, Emily West and Matthew P. McAllister;individual chapters, the contributors.

Evaluation of a nutrition education and cooking programme (NEST) in vulnerable adults who are at high risk of food insecurity

Within Australia, the prevalence of food insecure individuals increased from 2.6 million in 2014-2016 (10.8%) to 3.1 million in 2018- 2020 (12.3%) due to the COVID-19 pandemic.(1) OzHarvest is a not-for-profit organisation that prioritises food salvaging, food waste prevention and nutrition education.(2) OzHarvest's education sector facilitates a programme known as Nutrition Education Skills Training (NEST). NEST is a 6-week programme providing weekly workshops of 2.5-hour duration offering skills training on cooking simple, healthy, and affordable meals to adults at risk of food insecurity. This study aimed to determine the immediate and longerterm impacts of participation in NEST. A quasi-experimental study with pre-post surveys (n = 258) and follow-up surveys (n = 20) was conducted from June 2019 to July 2022. Survey results were obtained from NEST program participants (18 years) from Adelaide Canberra, Melbourne, Newcastle, Queensland, and Sydney. Baseline (pre-) and post-surveys (at program completion) were administered to participants, with an option for a 6-month follow-up survey. Participants were required to complete both surveys to be eligible for this study. Questionnaires included 23 core questions adapted from previous studies,(3) allowing evaluation of nutrition knowledge confidence and self-efficacy, shopping, and food preparation behaviours, and eating behaviours. Food security was assessed using the standard 6-item indicator set for classifying households by food security status level. Using paired t-tests, Shapiro Wilks, and Wilcoxon sign-ranked tests for pre and post survey data, participants demonstrated overall improvement in nutrition knowledge (p < 0.001), confidence and self-efficacy (n = 222;p < 0.001) and food preparation behaviours (p < 0.001). The intake of discretionary foods overall decreased (p < 0.001) while fruit, vegetable and water intake increased (p < 0.001). Food security improved from 57% to 68% immediately within the population (p < 0.001). Using RMANOVA and Shapiro Wilks tests, the 6-month survey results were compared to the pre surveys suggested longer lasting improvements in nutrition knowledge (p < 0.001), cooking confidence (n = 8;p = 0.033), food preparation behaviours (p = 0.003), and increased vegetable intake (p = 0.032) and fruit intake (p = 0.012) Participation in OzHarvest's NEST programme results in short-term improvements in food security levels and dietary behaviours Over the longer term, these changes were sustained but to a lesser degree, indicating that systemic changes are required to address underlying socioeconomic disadvantage.

Learning Disability Awareness Week at Great Ormond Street Hospital

Background Learning Disability Week is an annual campaign from Mencap, dedicated to educating and raising awareness of learning disabilities. This year the theme of Learning Disability Week (20-26th June) was 'Living Life with a Learning Disability'. The campaign focuses on 'education and raising awareness about Learning Disabilities, ending discrimination and stigmas surrounding Learning Disabilities, and fighting and campaigning for equality and fair society' (Mencap). Aim The purpose of this presentation is to share examples and experiences of inclusive activities undertaken during LD Awareness week in a specialist children's hospital. Methods During the week the Learning Disability Team supported numerous guest visitors, activities and celebrations, and education sessions throughout the trust to promote awareness and engage positively with families and staff. Examples included music therapy, education, training on the use of specialist beds, and Dogs for Autism. The Learning Disability team collaborated with the Van Gogh Alive Exhibition on a spectacular display of sunflowers that brightened up the entrance of the hospital. We raised awareness by utilising Van Gogh's notable sunflower theme, as globally the sunflower is recognised as the symbol for hidden disabilities. During LD week the sunflower decals on the floor led the way to a stand in the main reception where the activities and information sharing took place. The Learning Disability team were supported during the week by Safeguarding, Play team, Neurodisability, Music Therapy, hospital school, Arts Team, communications team. Discussion Throughout the week the activities and education sessions were well attended and provided the team with a wonderful opportunity to engage with patients, families, and staff. The planning of the week took a considerate amount of time, including focus on health and safety, infection control and current COVID guidelines/social distancing measures. The support from members of multidisciplinary teams allowed for the planning and success of the week.

strange objects: surface reading popular art periodicals

Drawing on a private collection of popular British art periodicals from the 1920s to the 1950s, loaned to me during the COVID-19 pandemic, this article explores different ways of reading these magazines' visual and verbal contents. It takes the unique circumstances of the pandemic-inability to travel, or to access libraries and archives-and asks what we can learn from reading such magazines in isolation. Designed as an "experiment," it foregrounds acts of questioning and of description, placing an emphasis on curiosity and open-ended enquiry. Inspired by Sharon Marcus and Stephen Best's ideas around "surface reading," I use the collection to develop a taxonomy of image-text interactions in art periodicals such as The Studio, Colour, Drawing and Design, The Art Gallery, and Modern Masterpieces. To examine how these interactions worked in practice, I focus on The Artist (1931-present). Using creative-critical approaches, including my own practice as a watercolorist, I examine how didactic pairings of words and images helped to teach an amateur audience how to create their own art. Throughout, I seek not just to introduce readers to a new set of magazines, but to question what modes of enquiry and forms of expression constitute "proper knowledge" in periodical studies. © 2022 Penn State University Press. All rights reserved.

Trust in older black, Asian and minority ethics persons with dementia and caregivers: The effects of COVID-19

Introduction: Members of Black, Asian and minority ethnic (BAME) communities in the UK have faced significant burden due to COVID-19. This population has had higher incidence rates of COVID-19, and also higher death rates. The pandemic has also disproportionately affected older adults, including those with dementia and as a result their caregivers. This study aims to explore culturally specific experiences of trust surrounding government policies, guidelines and services in BAME populations in the UK. Methods: Semi-structured interviews with 11 caregivers and 7 older adults with dementia were performed as part of a wider study on BAME experiences under COVID-19. Participants were recruited from national registries, such as Join Dementia Research, social media and word-ofmouth. Data was then analysed using thematic analysis methods with a specific focus on experiences around trust in guidelines, services and policy. Results: The concept of trust featured heavily in respondent interviews. Trust was seen as both a personal and a wider community issue. When stratified by ethnicity (within BAME communities) and other demographic factors, differences in level of trust and perception of guidelines and policies were found between groups - such as how much trust was put into government messaging. Conclusions: This paper looks at groups highly vulnerable to COVID-19 and their experiences of health and social policy. It is clear that attention must be paid to differences between different groups' cultural norms and structures in formulating and providing health and social care interventions. A move away from 'one-size-fits-all' policies may improve both the experience of health and social care interventions and promote feelings of inclusion and trust towards providers.

Rapid review of decision-making for place of care and death in older people: Lessons for COVID-19

IntroductionThe coronavirus pandemic (COVID-19) has affected the functioning and capacity of healthcare systems worldwide. COVID-19 has also disproportionately affected older adults, including those living with dementia. In the context of COVID-19, decision-making surrounding place of care and place of death in this population involves significant new challenges.ObjectivesTo explore key factors that influence place of care and place of death decisions in older adults. A secondary aim was to investigate key factors that influence the process and outcome of these decisions in older adults. To apply findings from current evidence to the context of COVID-19.MethodsRapid review of reviews, undertaken using WHO guidance for rapid reviews. Ten papers were included for full data extraction. These papers were published between 2005-2020. Data extracted was synthesised using narrative synthesis, with thematic analysis and tabulation.ResultsPapers included discussed actual place of death, as well as preferred. Results were divided into papers that explored the process of decision-making, and those that explored decision-making outcomes. Factors such as caregiver capacity, the availability of multidisciplinary teams, cultural appropriateness of care packages and advanced care planning were found to be key.ConclusionsThe process and outcomes of decision-making for older people are affected by many factors – all of which have the potential to influence both patients and caregivers experience of illness and dying. Within the context of COVID-19, such decisions may have to be made rapidly and be reflexive to changing needs of systems and of families and patients.

Rapid development of a decision-aid for people with dementia and their families during COVID-19

IntroductionCOVID-19 as a pandemic has disproportionately affected older adults, including those with dementia. The effects on health and social care systems has necessitated a rapid-response approach to care planning and decision-making in this population, with reflexivity and responsiveness to changing individual and system needs at its core. In light of this, a decision-making tool to help families of persons with dementia was developed using a combination of qualitative data and evidence synthesis.ObjectivesTo develop a decision-aid using a combination of assessment and evidence-gathering methods for families of persons with dementia.MethodsSemi-structured interviews with helpline staff from national end-of-life and supportive care organisations formed the basis of the tool design. Co-design with people living with dementia, current and former carers and experts in general practice and social care shaped the next stage. Simultaneously, a rapid review of current evidence on making decisions with older people at the end of life was undertaken.ResultsOutput from interviews covered many topics, including trust, agency and confusion in making decisions in the context of COVID-19. The rapid review of existing evidence highlighted the need to consider both process and outcome elements of decision-making.ConclusionsCombining different sources and forms of evidence was efficient and valuable in creating a novel decision-making tool for persons with dementia and their families within the context of COVID-19. The decision-aid covered care planning, caregiver support systems, access to information and contingency considerations. Upon publication, the tool was adopted by NHS England and other leading healthcare organisations.DisclosureNo significant relationships.

Carer perspectives of trust and authority during COVID-19

The COVID-19 global pandemic has had a significant impact in the way services are accessed and perceived by patients and their carers. Trust in services has shifted, and relationships with healthcare professionals have been affected, with carers now seeking alternative and more accessible sources of support. The aim of this paper is to explore the challenges and concerns including issues around trust that carers of people living with dementia and terminal illness have brought to support helplines, the decisions they are having to make, and the impact that the pandemic has had on end of life care. Eight helpline support workers were recruited from the Dementia UK and Marie Curie organisations, and semi-structured qualitative interviews were conducted through video calls on Microsoft Teams. Interviews were recorded with participants' consent and transcribed and checked via the Microsoft Stream automated system. The data was analysed by means of thematic analysis on NVIVO 11. Interview data was coded according to the point of time in the pandemic;early, later, or general. It was found that issues of trust, perceived loss of agency and confusion regarding government guidelines were expressed from the beginning of the pandemic to the current day. These stemmed from situations including care within hospitals and care homes, particularly due to a lack of communication from the aforementioned about the welfare of their relatives, and choices being removed from carers about their relatives' discharge pathways. There were also concerns raised about the rapidly and constantly changing guidelines for vulnerable people during the pandemic, with carers seeking information and reassurance from charity helplines rather than authority figures and the government.

1 Carer perspectives of trust and authority during COVID-19

The COVID-19 global pandemic has had a significant impact in the way services are accessed and perceived by patients and their carers. Trust in services has shifted, and relationships with healthcare professionals have been affected, with carers now seeking alternative and more accessible sources of support. The aim of this paper is to explore the challenges and concerns including issues around trust that carers of people living with dementia and terminal illness have brought to support helplines, the decisions they are having to make, and the impact that the pandemic has had on end of life care. Eight helpline support workers were recruited from the Dementia UK and Marie Curie organisations, and semi-structured qualitative interviews were conducted through video calls on Microsoft Teams. Interviews were recorded with participants’ consent and transcribed and checked via the Microsoft Stream automated system. The data was analysed by means of thematic analysis on NVIVO 11. Interview data was coded according to the point of time in the pandemic;early, later, or general. It was found that issues of trust, perceived loss of agency and confusion regarding government guidelines were expressed from the beginning of the pandemic to the current day. These stemmed from situations including care within hospitals and care homes, particularly due to a lack of communication from the aforementioned about the welfare of their relatives, and choices being removed from carers about their relatives’ discharge pathways. There were also concerns raised about the rapidly and constantly changing guidelines for vulnerable people during the pandemic, with carers seeking information and reassurance from charity helplines rather than authority figures and the government.

Pathophysiology and Imaging Findings of COVID-19 Infection: An Organ-system Based Review.

BACKGROUND: COVID-19 commonly presents with upper respiratory symptoms; however, studies have shown that SARS-CoV-2 infection affects multiple organ systems. Here, we review the pathophysiology and imaging characteristics of SARS-CoV-2 infection in organ systems throughout the body and explore commonalities. OBJECTIVE: Familiarity with the underlying pathophysiology and imaging characteristics is essential for the radiologist to recognize these findings in patients with COVID-19 infection. Though pulmonary findings are the most prevalent presentation, COVID-19 may have multiple manifestations and recognition of the extrapulmonary manifestations is especially important because of the potential serious and long-term effects of COVID-19 on multiple organ systems.