Emma Crawford

A 40-year-old man developed acute brainstem dysfunction 3 days after hospital admission with symptoms of the novel SARS-CoV-2 infection (COVID-19). Magnetic resonance imaging showed changes in keeping with inflammation of the brainstem and the upper cervical cord, leading to a diagnosis of rhombencephalitis. No other cause explained the patient's abnormal neurological findings. He was managed conservatively with rapid spontaneous improvement in some of his neurological signs and was discharged home with continued neurology follow up.

BACKGROUND: Outcomes are poor for patients with large B-cell lymphoma who relapse after CD19-directed chimeric antigen receptor (CAR) T-cell therapy (CAR19). CD22 is a nearly universally expressed B-cell surface antigen and the efficacy of a CD22-directed CAR T-cell therapy (CAR22) in large B-cell lymphoma is unknown, which was what we aimed to examine in this study. METHODS: In this single centre, open-label, dose-escalation phase 1 trial, we intravenously administered CAR22 at two dose levels (1 million and 3 million CAR22-positive T cells per kg of bodyweight) to adult patients (aged ≥18 years) who relapsed after CAR19 or had CD19-negative large B-cell lymphoma. The primary endpoints were manufacturing feasibility, safety measured by the incidence and severity of adverse events and dose-limiting toxicities, and identification of the maximum tolerated dose (ie, the recommended phase 2 dose). This study is registered with ClinicalTrials.gov (NCT04088890) and is active, but closed for enrolment. FINDINGS: From Oct 17, 2019, to Oct 19, 2022, a total of 41 patients were assessed for eligibility; however, one patient withdrew. 40 patients underwent leukapheresis and 38 (95%) had CAR T-cell products manufactured successfully. The median age was 65 years (range 25-84), 17 (45%) were women, 32 (84%) had elevated pretreatment lactate dehydrogenase, 11 (29%) had refractory disease to all previous therapies, and patients had received a median of four lines of previous therapy (range 3-8). Of the 38 patients treated, 37 (97%) had relapsed after previous CAR19. The identified maximum tolerated dose was 1 million CAR T cells per kg. Of 29 patients who received the maximum tolerated dose, no patients developed a dose-limiting toxicity or grade 3 or higher cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or immune effector cell-associated haemophagocytic lymphohistiocytosis-like syndrome. INTERPRETATION: This trial identifies CD22 as an immunotherapeutic target in large B-cell lymphoma and demonstrates the durable clinical activity of CAR22 in patients with disease progression after CAR19 therapy. Although these findings are promising, it is essential to recognise that this is a phase 1 dose-finding study. Further investigations are warranted to establish the long-term efficacy and to delineate the patient subgroups that will derive the most benefit from this therapeutic approach. FUNDING: National Cancer Institute, National Institutes of Health, Stanford Cancer Institute, Leukemia & Lymphoma Society, Parker Institute for Cancer Immunotherapy, Lymph & Co, and the European Hematology Association.

Asylum seekers experience occupational deprivation in the context of restrictive social structures while awaiting refugee visa-status determination. How do social structures of citizenship status and policy shape asylum seekers’ experiences? Asylum seekers’ experiences in Australia are examined using constructivist grounded theory. Field notes from 10 months of weekly participant observation, 11 formal interviews, 34 survey responses and four policy documents are combined to identify a substantive theory - the Structural-Personal Interaction (SPI). The SPI explains how occupational deprivation arises from an interaction between social structures and personal characteristics. Social structures of citizenship status and policy interact with asylum seekers’ personal characteristics, resulting in experiences of “having nothing to do”, a fundamental component of occupational deprivation. From the SPI, new insights regarding occupational deprivation emerge. Occupational deprivation can stem from an interaction between social structures and personal characteristics. While the SPI is a substantive theory and further research across a range of settings would be beneficial for its generalization, occupational deprivation's structural roots and connections to human vulnerabilities and resilience are discernable when considered in light of the SPI. Strategies to address occupational deprivation might target changes to social structures as well as build on individual strengths and human diversity.

Abstract Testifying in court is a daunting experience for any witness and an understanding of legal terminology can be beneficial. Previous research has found that children under 11 years have significant gaps in their knowledge of court. However, while older children have been found to know more, their misunderstandings warrant further investigation. This study was designed to examine the understanding/misunderstanding of key legal words by older children (aged between 12 and 15 years). Also, it was predicted that within the current sample, participants from a selective school would know more than those from a non-selective school, females would know more than males, and older children would know more than younger children. A total of 111 participants were recruited from two secondary schools in Northern Ireland. This study was a 3×2×2 factorial design (12/13/15 years; female/male; school A/school B). Participants completed a knowledge-of-court questionnaire that asked them (i) if they recognized and (ii) to describe 16 legal terms. School type and age affected recognition and age affected description. Some notable mis-comprehensions were evident in all age groups, in particular for “cross-examination”, “jury” and “defendant”. The practical implications of these findings for witness preparation are discussed. Keywords: Childrencourtterminology