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Thwaites Glacier represents 15% of the ice discharge from the West Antarctic Ice Sheet and influences a wider catchment1-3. Because it is grounded below sea level4,5, Thwaites Glacier is thought to be susceptible to runaway retreat triggered at the grounding line (GL) at which the glacier reaches the ocean6,7. Recent ice-flow acceleration2,8 and retreat of the ice front8-10 and GL11,12 indicate that ice loss will continue. The relative impacts of mechanisms underlying recent retreat are however uncertain. Here we show sustained GL retreat from at least 2011 to 2020 and resolve mechanisms of ice-shelf melt at the submetre scale. Our conclusions are based on observations of the Thwaites Eastern Ice Shelf (TEIS) from an underwater vehicle, extending from the GL to 3 km oceanward and from the ice-ocean interface to the sea floor. These observations show a rough ice base above a sea floor sloping upward towards the GL and an ocean cavity in which the warmest water exceeds 2 °C above freezing. Data closest to the ice base show that enhanced melting occurs along sloped surfaces that initiate near the GL and evolve into steep-sided terraces. This pronounced melting along steep ice faces, including in crevasses, produces stratification that suppresses melt along flat interfaces. These data imply that slope-dependent melting sculpts the ice base and acts as an important response to ocean warming.

Bedforms of Thwaites Glacier, West Antarctica both record and affect ice flow, as shown by geophysical data and simple models. Thwaites Glacier flows across the tectonic fabric of the West Antarctic rift system with its bedrock highs and sedimentary basins. Swath radar and seismic surveys of the glacier bed have revealed soft‐sediment flutes 100 m or more high extending 15 km or more across basins downglacier from bedrock highs. Flutes end at prominent hard‐bedded moats on stoss sides of the next topographic highs. We use simple models to show that ice flow against topography increases pressure between ice and till upglacier along the bed over a distance that scales with the topography. In this basal zone of high pressure, ice‐contact water would be excluded, thus increasing basal drag by increasing ice‐till coupling and till flux, removing till to allow bedrock erosion that creates moats. Till carried across highlands would then be deposited in lee‐side positions forming bedforms that prograde downglacier over time, and that remain soft on top through feedbacks that match till‐deformational fluxes from well upglacier of the topography. The bedforms of the part of Thwaites surveyed here are prominent because ice flow has persisted over a long time on this geological setting, not because ice flow is anomalous. Bedform development likely has caused evolution of ice flow over time as till and lubricating water were redistributed, moats were eroded and bedforms grew. Plain Language Summary: Thwaites Glacier, West Antarctica, is of great interest because ongoing retreat could lead to faster future changes that could notably increase sea‐level rise. Wide‐ranging studies are thus focused on gaining broad understanding of the glacier. Geophysical surveys discussed here show that the bed of the glacier has been sculpted by the flowing ice, eroding large "moats" upglacier and to the sides of bedrock obstacles, and depositing long tails of soft sediment downglacier of those obstacles. We use simple models to show that these features formed over time because of the interactions among ice, bedrock, and subglacial water and sediment, and that the behavior of the glacier must have changed as these features developed. This knowledge does not directly affect estimates of the potential for future sea‐level rise, but does guide further studies to improve those estimates. This knowledge also may help understand the formation of glacially sculpted landscapes left in widespread regions by former ice sheets. Key Points: Extensive, well‐developed bedforms occur beneath upglacier regions of Thwaites Glacier, West Antarctica where ice flow is unremarkablePressure variations from ice flow over bedrock topography caused erosion and deposition, producing stoss‐side moats and lee‐side flutesBedforms both record and influence ice flow [ABSTRACT FROM AUTHOR]

Objectives: Clinical communication needs of teenagers and young adults with cancer (TYACs) are increasingly recognised to differ significantly from younger children and older adults. We sought to understand who is present with TYACs, TYACs' experiences of triadic communication and its impact. We generated three research questions to focus this review: (1) Who is present with TYACs in healthcare consultations/communication?, (2) What are TYACs' experiences of communication with the supporter present? and (3) What is the impact of a TYAC's supporter being present in the communication?, Design: Systematic review with narrative synthesis., Data Sources: The search was conducted across six databases: Medline, CINAHL, Embase, PsycINFO, Web of Science and AMED for all publications up to December 2023., Eligibility Criteria for Selecting Studies: Included papers were empirical research published after 2005; participants had malignant disease, diagnosed aged 13-24 years (for over 50% of participants); the research addressed any area of clinical communication., Data Extraction and Synthesis: Three independent reviewers undertook full-text screening. A review-specific data extraction form was used to record participant characteristics and methods from each included paper and results relevant to the three review questions., Results: A total of 8480 studies were identified in the search, of which 36 fulfilled the inclusion criteria. We found that mothers were the most common supporter present in clinical communication encounters. TYACs' experiences of triadic communication are paradoxical in nature-the supporter can help or hinder the involvement of the young person in care-related communication. Overall, young people are not included in clinical communication and decisions at their preferred level., Conclusion: Triadic communication in TYACs' care is common, complex and dynamic. Due to the degree of challenge and nuances raised, healthcare professionals need further training on effective triadic communication., Prospero Registration Number: CRD42022374528., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Thwaites Glacier is one of the fastest-changing ice-ocean systems in Antarctica 1-3 . Much of the ice sheet within the catchment of Thwaites Glacier is grounded below sea level on bedrock that deepens inland 4 , making it susceptible to rapid and irreversible ice loss that could raise the global sea level by more than half a metre 2,3,5 . The rate and extent of ice loss, and whether it proceeds irreversibly, are set by the ocean conditions and basal melting within the grounding-zone region where Thwaites Glacier first goes afloat 3,6 , both of which are largely unknown. Here we show-using observations from a hot-water-drilled access hole-that the grounding zone of Thwaites Eastern Ice Shelf (TEIS) is characterized by a warm and highly stable water column with temperatures substantially higher than the in situ freezing point. Despite these warm conditions, low current speeds and strong density stratification in the ice-ocean boundary layer actively restrict the vertical mixing of heat towards the ice base 7,8 , resulting in strongly suppressed basal melting. Our results demonstrate that the canonical model of ice-shelf basal melting used to generate sea-level projections cannot reproduce observed melt rates beneath this critically important glacier, and that rapid and possibly unstable grounding-line retreat may be associated with relatively modest basal melt rates., (© 2023. The Author(s).)

Measuring immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 19 (COVID-19), can rely on antibodies, reactive T cells and other factors, with T-cell-mediated responses appearing to have greater sensitivity and longevity. Because each T cell carries an essentially unique nucleic acid sequence for its T-cell receptor (TCR), we can interrogate sequence data derived from DNA or RNA to assess aspects of the immune response. This review deals with the utility of bulk, rather than single-cell, sequencing of TCR repertoires, considering the importance of study design, in terms of cohort selection, laboratory methods and analysis. The advances in understanding SARS-CoV-2 immunity that have resulted from bulk TCR repertoire sequencing are also be discussed. The complexity of sequencing data obtained by bulk repertoire sequencing makes analysis challenging, but simple descriptive analyses, clonal analysis, searches for specific sequences associated with immune responses to SARS-CoV-2, motif-based analyses, and machine learning approaches have all been applied. TCR repertoire sequencing has demonstrated early expansion followed by contraction of SARS-CoV-2-specific clonotypes, during active infection. Maintenance of TCR repertoire diversity, including the maintenance of diversity of anti-SARS-CoV-2 response, predicts a favourable outcome. TCR repertoire narrowing in severe COVID-19 is most likely a consequence of COVID-19-associated lymphopenia. It has been possible to follow clonotypic sequences longitudinally, which has been particularly valuable for clonotypes known to be associated with SARS-CoV-2 peptide/MHC tetramer binding or with SARS-CoV-2 peptide-induced cytokine responses. Closely related clonotypes to these previously identified sequences have been shown to respond with similar kinetics during infection. A possible superantigen-like effect of the SARS-CoV-2 spike protein has been identified, by means of observing V-segment skewing in patients with severe COVID-19, together with structural modelling. Such a superantigen-like activity, which is apparently absent from other coronaviruses, may be the basis of multisystem inflammatory syndrome and cytokine storms in COVID-19. Bulk TCR repertoire sequencing has proven to be a useful and cost-effective approach to understanding interactions between SARS-CoV-2 and the human host, with the potential to inform the design of therapeutics and vaccines, as well as to provide invaluable pathogenetic and epidemiological insights.

This article uses data from patients recruited using the 1994 case definition of chronic fatigue syndrome (CFS) to contrast those meeting criteria for the Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS) Canadian case definition with those that did not meet these criteria. The study also contrasts those meeting criteria for Myalgic Encephalomyelitis (ME) based on criteria from Ramsay and other theorists with those that did not meet the ME criteria. The ME/CFS case definition criteria identified a subset of patients with more functional impairments and physical, mental, and cognitive problems than the subset not meeting these criteria. The ME subset had more functional impairments, and more severe physical and cognitive symptoms than the subset not meeting ME criteria. When applied to a population meeting the 1994 CFS case definition, both ME/CFS and ME criteria appear to select a more severe subset of patients.

Diesel exhaust particles (DEP) have strong, selective Th2 adjuvant activity when inhaled with conventional Ags. We used a novel technique for measuring in vivo cytokine production to investigate possible mechanisms by which DEP might promote a Th2 response. Injection of DEP i.p. stimulated IL-6 secretion, but failed to increase IL-4, IL-10, or TNF-alpha secretion, and decreased basal levels of IFN-gamma. When injected with or before LPS, DEP had little effect on the LPS-induced TNF-alpha responses, but partially inhibited the LPS-induced IL-10 response and strongly inhibited the LPS-induced IFN-gamma response. DEP also inhibited the IFN-gamma responses to IL-12, IL-12 plus IL-18, IL-2, and poly(I.C). DEP treatment had little effect on the percentages of NK and NKT cells in the spleen, but inhibited LPS-induced IFN-gamma production by splenic NK and NKT cells. In contrast, DEP failed to inhibit the IFN-gamma response by anti-CD3 mAb-activated NKT cells. Taken together, these observations suggest that DEP inhibit Toll-like receptor ligand-induced IFN-gamma responses by interfering with cytokine signaling pathways that stimulate NK and NKT cells to produce IFN-gamma. Our observations also suggest that DEP may promote a Th2 response by stimulating production of inflammatory cytokines while simultaneously inhibiting production of IFN-gamma, and raise the possibility that the same mechanisms contribute to the association between DEP exposure and asthma.