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A variety of magnetosphere‐ionosphere current systems and waves have been linked to geomagnetic disturbance (GMD) and geomagnetically induced currents (GIC). However, since many location‐specific factors control GMD and GIC intensity, it is often unclear what mechanisms generate the largest GMD and GIC in different locations. We address this challenge through analysis of multi‐satellite measurements and globally distributed magnetometer and GIC measurements. We find embedded within the magnetic cloud of the 23–24 April 2023 coronal mass ejection (CME) storm there was a global scale density pulse lasting for 10–20 min with compression ratio of ∼10 ${\sim} 10$. It caused substantial dayside displacements of the bow shock and magnetopause, changes of 6RE $6{R}_{E}$ and 1.3−2RE $1.3-2{R}_{E}$, respectively, which in turn caused large amplitude GMD in the magnetosphere and on the ground across a wide local time range. At the time this global GMD was observed, GIC measured in New Zealand, Finland, Canada, and the United States were observed. The GIC were comparable (within factors of 2–2.5) to the largest ever recorded during ≥ ${\ge} $14 year monitoring intervals in New Zealand and Finland and represented ∼ ${\sim} $2‐year maxima in the United States during a period with several Kp≥ ${\ge} $7 geomagnetic storms. Additionally, the GIC measurements in the USA and other mid‐latitude locations exhibited wave‐like fluctuations with 1–2 min period. This work suggests that large density pulses in CME should be considered an important driver of large amplitude, global GMD and among the largest GIC at mid‐latitude locations, and that sampling intervals ≤10s ${\le} 10s$ are required to capture these GMD/GIC. Plain Language Summary: We explore how disturbances in the Earth's magnetic field, known as geomagnetic disturbances (GMD), and the resulting geomagnetically induced currents (GIC) in power systems are influenced by different electrical currents and waves in near‐Earth space. One challenge is the lack of easily accessible data on GIC over long periods, which makes it hard to figure out what factors are most responsible for changes in GIC in different places. Also, there is limited research combining data from satellites with data collected on the ground to figure out exactly how GMD and GIC are generated. To tackle these issues, we looked at data collected by multiple satellites in different parts of near‐Earth space along with data from ground magnetometers and GIC measurements distributed around the world. Our results suggest that density pulses from coronal mass ejections, a particular type of structure in the solar wind, are important in causing significant disturbances in the Earth's magnetic field globally and contribute to some of the largest GIC seen in the mid‐latitude region of United States. We emphasize the importance of taking measurements with high sampling rates (≤10s) $(\le 10s)$ to accurately capture these disturbances and the resulting GIC. Key Points: A density pulse embedded in a coronal mass ejection drives global geomagnetic disturbances (GMD) and geomagnetically induced currents (GIC)Measured GIC's comparable to or exceed reference values in several regions, including 58.1 A in the mid‐latitude region of United StatesLarge‐amplitude density pulses are an important driver of GIC and GMD for mid‐latitude regions with large populations [ABSTRACT FROM AUTHOR]

During space weather events, geomagnetic disturbances (GMDs) induce geoelectric fields which drive geomagnetically induced currents (GICs) through electrically-grounded power transmission lines. Alberta, Canada--located near the auroral zone and thus prone to large GMDs--has a dense network of magnetometer stations and surface impedance measurements to better characterize the GMD and ground conductivity, respectively. GIC monitoring devices were recently installed at five substation transformer neutrals, providing a unique opportunity to compare data to modeled GICs. GICs are modeled across the >240 kV provincial power transmission network during a moderate GMD event on 24 April 2023. GIC monitoring devices measured larger neutral-to-ground currents than expected up to 117 Amps during peak storm time, providing unequivocal evidence linking network GICs with GMDs. The model performs reasonably well (correlation coefficients >0.5; performance parameter >0.15) at four of five substations, but generally underestimates peak GIC values (sometimes by a factor >2), suggesting that the present model underrepresents overall network risk. The model performs poorly at one of the five substations (correlation = 0.46; performance parameter = 0.10), the reasons for which may be due to simplifications and/or unknowns in network parameters. Despite these underestimates, during this GMD, the model predicts the largest GIC at substations located in the northeastern part of the province (240 kV) or around Edmonton (500 kV)--regions which have significant electrical and industrial infrastructure. Further refinement of the network model with transformer resistances, more line and earthing resistances, and/or including lower voltage levels is necessary to improve data fit. [ABSTRACT FROM AUTHOR]

This qualitative study aimed to explore the experiences of young men who have previously participated in a residential treatment programme based in North Wales for harmful sexual behaviours. In-depth interviews with 25 young men aged between 15 and 33 were conducted and thematically analysed. Findings highlight some key strengths of the treatment programme including building quality relationships with staff and the community and the learning of life skills that are also later employed to manage risk of sexual and non-sexual offending. The study supports recent research [Balfe, M., Hackett, D., Masson, H., & Phillips, J. (2019). Experiences of young people with harmful sexual behaviours in services: A qualitative study. Journal of Child Sexual Abuse, 28(6), 649–666. https://doi.org/10.1080/10538712.2019.1573390] that more social and psychological supports need to be available for young people post-treatment while in a period of transition and liminality. Finally, the study further supports other research [de Vries Robbe, M., Mann, R. E., Maruna, S., & Thornton, D. (2015). An exploration of protective factors supporting desistance from sexual offending. Sexual Abuse: A Journal of Research and Treatment, 27(1), 16–33. https://doi.org/10.1177/1079063214547582] in that emphasis should be placed on social, interpersonal, and environmental protective factors rather than psychological ones alone. [ABSTRACT FROM AUTHOR]

The clinical success of chimeric antigen receptor (CAR) T cell immunotherapy in the treatment of haematological cancers has encouraged the extensive development of CAR design to improve their function and increase their applicability. Advancements in protein engineering have seen modifications to both the ecto- and endo-domains of the CAR, with recent designs targeting multiple antigens and including inducible elements. These developments are likely to play an important role in inducing effective CAR T cell responses in a solid tumour context, where clinical responses have not been effective to date. This review highlights the spectrum of novel strategies being employed in CAR design, including for example variations in targeting tumour antigens by utilising different ectodomain designs such as dual chain CARs, natural receptor or ligand-based CARs, and T cell receptor fusion constructs, and also reviews some of the innovative approaches to a "universal" CAR and various multi-antigen targeting CAR strategies. We also explore how choices in the endodomain impact CAR function and how these need to be considered in the overall CAR design. [ABSTRACT FROM AUTHOR]

Objectives: In clinical chimeric antigen receptor (CAR) T cell therapy, one of the strongest correlates of favorable patient responses is lower levels of differentiation in T cells from the peripheral blood mononuclear cell (PBMC) starting material or the CAR T cell product. T cells from older patients are inherently more differentiated, but we hypothesised that specific activation protocols could be used to limit CAR T cell differentiation during manufacturing, particularly in older patients., Methods: We used PBMCs from young (20-30 years old) and older (60+ years old) healthy donors to generate CAR T cells using two activation protocols: soluble anti-(α) CD3 monoclonal antibody (mAb) vs immune complexes of αCD3 and αCD28 mAbs. Products were assessed for yield, function and differentiation, which was used as a measure of CAR T cell quality. T cells in PBMCs were assessed for CD28 expression and correlative analyses were performed., Results: Older samples generated fewer, more differentiated CAR T cells than young samples, and the αCD3/CD28 mAb protocol exacerbated this, further reducing yield and quality. CD28 expression by T cells correlated with CAR T cell differentiation, but T cell differentiation in PBMC starting material was a stronger correlate of CAR T cell differentiation., Conclusions: Choice of activation protocol can substantially impact on the yield and quality of CAR T cells during manufacturing. This is a key consideration for older patients whose samples already generate a poorer yield and lower quality of CAR T cells., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)