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To understand the importance of methane on the levels of carbon emission reductions required to achieve temperature goals, a processed-based approach is necessary rather than reliance on the transient climate response to emissions. We show that plausible levels of methane (CH4) mitigation can make a substantial difference to the feasibility of achieving the Paris climate targets through increasing the allowable carbon emissions. This benefit is enhanced by the indirect effects of CH4 on ozone (O3). Here the differing effects of CH4 and CO2 on land carbon storage, including the effects of surface O3, lead to an additional increase in the allowable carbon emissions with CH4 mitigation. We find a simple robust relationship between the change in the 2100 CH4 concentration and the extra allowable cumulative carbon emissions between now and 2100 (0.27 ± 0.05 GtC per ppb CH4). This relationship is independent of modelled climate sensitivity and precise temperature target, although later mitigation of CH4 reduces its value and thus methane reduction effectiveness. Up to 12% of this increase in allowable emissions is due to the effect of surface ozone. We conclude early mitigation of CH4 emissions would significantly increase the feasibility of stabilising global warming below 1.5 °C, alongside having co-benefits for human and ecosystem health.

NASA has launched the decade-long Arctic-Boreal Vulnerability Experiment (ABoVE). While the initial phases focus on field and airborne data collection, early integration with modeling activities is important to benefit future modeling syntheses. We compiled feedback from ecosystem modeling teams on key data needs, which encompass carbon biogeochemistry, vegetation, permafrost, hydrology, and disturbance dynamics. A suite of variables was identified as part of this activity with a critical requirement that they are collected concurrently and representatively over space and time. Individual projects in ABoVE may not capture all these needs, and thus there is both demand and opportunity for the augmentation of field observations, and synthesis of the observations that are collected, to ensure that science questions and integrated modeling activities are successfully implemented.

Abstract Systemic anaplastic large cell lymphoma (ALCL) is a rare CD30-expressing T-cell non-Hodgkin lymphoma. Risk of systemic ALCL is highly increased among immunosuppressed individuals. Because risk of cancers associated with viruses is increased with immunosuppression, we conducted a metagenomic analysis of systemic ALCL to determine whether a known or novel pathogen is associated with this malignancy. Total RNA was extracted and sequenced from formalin-fixed paraffin-embedded tumor specimens from 19 systemic ALCL cases (including one case from an immunosuppressed individual with human immunodeficiency virus infection), 3 Epstein-Barr virus positive diffuse large B-cell lymphomas (DLBCLs) occurring in solid organ transplant recipients (positive controls), and 3 breast cancers (negative controls). We used a pipeline based on the Genome Analysis Toolkit (GATK)-PathSeq algorithm to subtract out human RNA reads and map the remaining RNA reads to microbes. No microbial association with ALCL was identified, but we found Epstein-Barr virus in the DLBCL positive controls and determined the breast cancers to be negative. In conclusion, we did not find a pathogen associated with systemic ALCL, but because we analyzed only one ALCL tumor from an immunosuppressed person, we cannot exclude the possibility that a pathogen is associated with some cases that arise in the setting of immunosuppression.

The extent to which temperature controls soil carbon storage remains highly uncertain. Here, the authors show that, globally, soil carbon stocks decline strongly with temperature, but the effect is much greater in coarse-textured soils with limited organic matter stabilisation capacities, than in fine-textured soils.

Enteropathy-associated T cell lymphoma (EATL) is a lethal, and the most common, neoplastic complication of celiac disease. Here, we defined the genetic landscape of EATL through whole-exome sequencing of 69 EATL tumors. SETD2 was the most frequently silenced gene in EATL (32% of cases). The JAK-STAT pathway was the most frequently mutated pathway, with frequent mutations in STAT5B as well as JAK1, JAK3, STAT3, and SOCS1 We also identified mutations in KRAS, TP53, and TERT Type I EATL and type II EATL (monomorphic epitheliotropic intestinal T cell lymphoma) had highly overlapping genetic alterations indicating shared mechanisms underlying their pathogenesis. We modeled the effects of SETD2 loss in vivo by developing a T cell-specific knockout mouse. These mice manifested an expansion of γδ T cells, indicating novel roles for SETD2 in T cell development and lymphomagenesis. Our data render the most comprehensive genetic portrait yet of this uncommon but lethal disease and may inform future classification schemes.

OBJECTIVES: The 2015 Workshop of the Society for Hematopathology/European Association for Haematopathology submitted small and large B-cell lymphomas (BCLs), including classical Hodgkin lymphoma (CHL), in the context of immunodeficiency. METHODS: Clinicopathologic and molecular features were studied to explore unifying concepts in malignant B-cell proliferations across immunodeficiency settings. RESULTS: Cases submitted to the workshop spanned small BCLs presenting as nodal or extranodal marginal zone lymphoma and lymphoplasmacytic lymphoma, Epstein-Barr virus (EBV) positive in 75% of cases. Submitted large BCLs formed a spectrum from diffuse large B-cell lymphoma (DLBCL) to CHL across immunodeficiency settings. Additional studies demonstrated overexpression of PD-L1 and molecular 9p24 alterations in the large BCL spectrum and across different immunodeficiency settings. CONCLUSIONS: Small BCLs occur in all immunodeficiency settings, and EBV positivity is essential for their recognition as immunodeficiency related. Large BCLs include a spectrum from DLBCL to CHL across all immunodeficiency settings; immunohistochemical and molecular features are suggestive of shared pathogenetic mechanisms involving PD-L1 immune checkpoints.

OBJECTIVES: The 2015 Workshop of the Society for Hematopathology/European Association for Haematopathology aimed to review immunodeficiency-related lymphoproliferative disorders with plasmablastic and plasma cell differentiation. METHODS: The workshop panel reviewed human herpes virus 8 (HHV8)/Kaposi sarcoma herpesvirus (KSHV)-associated lesions and other lesions exhibiting plasma cell differentiation, including plasmablastic proliferations with features of myeloma/plasmacytoma, plasmablastic neoplasms presenting in extranodal sites and effusion-based lymphomas, and rendered a consensus diagnosis. RESULTS: The spectrum of HHV8/KSHV-associated proliferations ranged from multicentric Castleman disease (MCD) to MCD with plasmablastic aggregates to HHV8+ diffuse large B-cell lymphoma and germinotrophic lymphoproliferative disorder. Comparisons across effusion-based lymphomas with and without HHV8/KSHV and plasmablastic lymphomas in immunodeficient and immunocompetent patients were discussed. CONCLUSIONS: The presence or absence of HHV8/KSHV is a defining feature in disorders associated with Castleman disease, although their differential diagnosis and recognition of progression may be challenging. Plasmablastic proliferations overlap with myeloma/plasmacytoma as well as extranodal and effusion-based lymphomas. The involvement of Epstein-Barr virus is typically variable.

OBJECTIVES: The 2015 Workshop of the Society for Hematopathology/European Association for Haematopathology aimed to review immunodeficiency-related T- and natural killer (NK)-cell lymphoproliferations. METHODS: The Workshop Panel reviewed 88 T- or NK-cell lymphoproliferations and rendered consensus diagnoses. RESULTS: Hyperplasias of T-cell subsets may be clonal; retained architecture and the clinical setting support a benign diagnosis. Specific associations include hepatosplenic T-cell lymphoma with iatrogenic immunosuppression and breast implants with an indolent variant of anaplastic large cell lymphoma. Epstein-Barr virus (EBV)-positive T-cell lymphomas rarely occur in the acquired immunodeficiency setting. Systemic T- and NK-cell lymphoma of childhood overlaps with chronic active EBV and reversible hemophagocytic lymphohistiocytosis-related T-cell lymphoproliferations. CONCLUSIONS: Immunodeficiencies predispose to T-cell hyperplasias, which must not be overdiagnosed as lymphoma. Many T-cell lymphomas in the immunodeficiency setting are likely coincidental, with specific exceptions. Systemic T- or NK-cell lymphomas are part of a spectrum of EBV+ T or NK lymphoproliferations and can present in the acquired immunodeficiency setting.

OBJECTIVES: The 2015 Workshop of the Society for Hematopathology/European Association for Haematopathology aimed to review primary immunodeficiency and related lymphoproliferations. METHODS: Primary immunodeficiencies were divided into immune dysregulation, DNA repair defects, low immunoglobulins, and combined immunodeficiencies. RESULTS: Autoimmune lymphoproliferative syndrome (ALPS) is a prototypical immune dysregulation-type immunodeficiency, with defects in T-cell signaling or apoptosis, expansion of T-cell subsets, and predisposition to hemophagocytic lymphohistiocytosis. DNA repair defects directly predispose to malignancy. Low immunoglobulin immunodeficiencies such as common variable immunodeficiency (CVID) have underlying T-cell repertoire abnormalities predisposing to autoimmunity and B-cell lymphoproliferations. The full spectrum of B-cell lymphoproliferative disorders occurs in primary immunodeficiency. CONCLUSIONS: Lymphoproliferations in primary immunodeficiency mirror those in other immunodeficiency settings, with monomorphic B- and sometimes T lymphoproliferative disorders enriched in DNA repair defects. Distinctive T-cell subset expansions in ALPS, CVID, and related entities can mimic lymphoma, and recognition of double-negative T-cell or cytotoxic T-cell expansions is key to avoid overdiagnosis.

OBJECTIVES: The 2015 Workshop of the Society for Hematopathology/European Association for Haematopathology aimed to review B-cell proliferations of varied malignant potential associated with immunodeficiency. METHODS: The Workshop Panel reviewed all cases of B-cell hyperplasias, polymorphic B-lymphoproliferative disorders, Epstein-Barr virus (EBV)-positive mucocutaneous ulcer, and large B-cell proliferations associated with chronic inflammation and rendered consensus diagnoses. Disease definitions, boundaries with more aggressive B-cell proliferations, and association with EBV were explored. RESULTS: B-cell proliferations of varied malignant potential occurred in all immunodeficiency backgrounds. Presentation early in the course of immunodeficiency and in younger age groups and regression with reduction of immunosuppression were characteristic features. EBV positivity was essential for diagnosis in some hyperplasias where other specific defining features were absent. CONCLUSIONS: This spectrum of B-cell proliferations show similarities across immunodeficiency backgrounds. Localized forms of immunodeficiency disorders arise in immunocompetent patients most likely due to chronic immune stimulation and, despite aggressive histologic features, often show indolent clinical behavior.

Scenarios avoiding global warming greater than 1.5 or 2 ∘C, as stipulated in the Paris Agreement, may require the combined mitigation of anthropogenic greenhouse gas emissions alongside enhancing negative emissions through approaches such as afforestation–reforestation (AR) and biomass energy with carbon capture and storage (BECCS). We use the JULES land surface model coupled to an inverted form of the IMOGEN climate emulator to investigate mitigation scenarios that achieve the 1.5 or 2 ∘C warming targets of the Paris Agreement. Specifically, within this IMOGEN-JULES framework, we focus on and characterise the global and regional effectiveness of land-based (BECCS and/or AR) and anthropogenic methane (CH4) emission mitigation, separately and in combination, on the anthropogenic fossil fuel carbon dioxide (CO2) emission budgets (AFFEBs) to 2100. We use consistent data and socio-economic assumptions from the IMAGE integrated assessment model for the second Shared Socioeconomic Pathway (SSP2). The analysis includes the effects of the methane and carbon–climate feedbacks from wetlands and permafrost thaw, which we have shown previously to be significant constraints on the AFFEBs. Globally, mitigation of anthropogenic CH4 emissions has large impacts on the anthropogenic fossil fuel emission budgets, potentially offsetting (i.e. allowing extra) carbon dioxide emissions of 188–212 Gt C. This is because of (a) the reduction in the direct and indirect radiative forcing of methane in response to the lower emissions and hence atmospheric concentration of methane and (b) carbon-cycle changes leading to increased uptake by the land and ocean by CO2-based fertilisation. Methane mitigation is beneficial everywhere, particularly for the major CH4-emitting regions of India, the USA, and China. Land-based mitigation has the potential to offset 51–100 Gt C globally, the large range reflecting assumptions and uncertainties associated with BECCS. The ranges for CH4 reduction and BECCS implementation are valid for both the 1.5 and 2 ∘C warming targets. That is the mitigation potential of the CH4 and of the land-based scenarios is similar for regardless of which of the final stabilised warming levels society aims for. Further, both the effectiveness and the preferred land management strategy (i.e. AR or BECCS) have strong regional dependencies. Additional analysis shows extensive BECCS could adversely affect water security for several regions. Although the primary requirement remains mitigation of fossil fuel emissions, our results highlight the potential for the mitigation of CH4 emissions to make the Paris climate targets more achievable.

Infrastructure built on perennially frozen ice-rich ground relies heavily on thermally stable subsurface conditions. Climate-warming-induced deepening of ground thaw puts such infrastructure at risk of failure. For better assessing the risk of large-scale future damage to Arctic infrastructure, improved strategies for model-based approaches are urgently needed. We used the laterally coupled 1D heat conduction model CryoGrid3 to simulate permafrost degradation affected by linear infrastructure. We present a case study of a gravel road built on continuous permafrost (Dalton highway, Alaska) and forced our model under historical and strong future warming conditions (following the RCP8.5 scenario). As expected, the presence of a gravel road in the model leads to higher net heat flux entering the ground compared to a reference run without infrastructure and thus a higher rate of thaw. Further, our results suggest that road failure is likely a consequence of lateral destabilisation due to talik formation in the ground beside the road rather than a direct consequence of a top-down thawing and deepening of the active layer below the road centre. In line with previous studies, we identify enhanced snow accumulation and ponding (both a consequence of infrastructure presence) as key factors for increased soil temperatures and road degradation. Using differing horizontal model resolutions we show that it is possible to capture these key factors and their impact on thawing dynamics with a low number of lateral model units, underlining the potential of our model approach for use in pan-Arctic risk assessments. Our results suggest a general two-phase behaviour of permafrost degradation: an initial phase of slow and gradual thaw, followed by a strong increase in thawing rates after the exceedance of a critical ground warming. The timing of this transition and the magnitude of thaw rate acceleration differ strongly between undisturbed tundra and infrastructure-affected permafrost ground. Our model results suggest that current model-based approaches which do not explicitly take into account infrastructure in their designs are likely to strongly underestimate the timing of future Arctic infrastructure failure. By using a laterally coupled 1D model to simulate linear infrastructure, we infer results in line with outcomes from more complex 2D and 3D models, but our model's computational efficiency allows us to account for long-term climate change impacts on infrastructure from permafrost degradation. Our model simulations underline that it is crucial to consider climate warming when planning and constructing infrastructure on permafrost as a transition from a stable to a highly unstable state can well occur within the service lifetime (about 30 years) of such a construction. Such a transition can even be triggered in the coming decade by climate change for infrastructure built on high northern latitude continuous permafrost that displays cold and relatively stable conditions today.

Understanding future changes in the terrestrial carbon cycle is important for reliable projections of climate change and impacts on ecosystems. It is well known that nitrogen (N) could limit plants' response to increased atmospheric carbon dioxide and it is therefore important to include a representation of the N cycle in Earth system models. Here we present the implementation of the terrestrial nitrogen cycle in the Joint UK Land Environment Simulator (JULES) – the land surface scheme of the UK Earth System Model (UKESM). Two configurations are discussed – the first one (JULES-CN) has a bulk soil biogeochemical model and the second one is a development configuration that resolves the soil biogeochemistry with depth (JULES-CNlayer). In JULES the nitrogen (N) cycle is based on the existing carbon (C) cycle and represents all the key terrestrial N processes in a parsimonious way. Biological N fixation is dependent on net primary productivity, and N deposition is specified as an external input. Nitrogen leaves the vegetation and soil system via leaching and a bulk gas loss term. Nutrient limitation reduces carbon-use efficiency (CUE – ratio of net to gross primary productivity) and can slow soil decomposition. We show that ecosystem level N limitation of net primary productivity (quantified in the model by the ratio of the potential amount of C that can be allocated to growth and spreading of the vegetation compared with the actual amount achieved in its natural state) falls at the lower end of the observational estimates in forests (approximately 1.0 in the model compared with 1.01 to 1.38 in the observations). The model shows more N limitation in the tropical savanna and tundra biomes, consistent with the available observations. Simulated C and N pools and fluxes are comparable to the limited available observations and model-derived estimates. The introduction of an N cycle improves the representation of interannual variability of global net ecosystem exchange, which was more pronounced in the C-cycle-only versions of JULES (JULES-C) than shown in estimates from the Global Carbon Project. It also reduces the present-day CUE from a global mean value of 0.45 for JULES-C to 0.41 for JULES-CN and 0.40 for JULES-CNlayer, all of which fall within the observational range. The N cycle also alters the response of the C fluxes over the 20th century and limits the CO2 fertilisation effect, such that the simulated current-day land C sink is reduced by about 0.5 Pg C yr−1 compared to the version with no N limitation. JULES-CNlayer additionally improves the representation of soil biogeochemistry, including turnover times in the northern high latitudes. The inclusion of a prognostic land N scheme marks a step forward in functionality and realism for the JULES and UKESM models.

The authors present two cases of conjunctival pediatric-type follicular lymphoma. A 14-year-old Black boy and 14-year-old Black girl were each referred for evaluation of a painless salmon-colored conjunctival lesion. Both patients underwent excisional biopsy. Histopathology demonstrated follicles with germinal centers composed of atypical B-cells with high Ki67 proliferation index, positive staining for CD20, CD10, and BCL6, and negative for BCL2. This series contributes two cases to the limited literature and presents the first case reported in a female. [J Pediatr Ophthalmol Strabismus. 2024;61(4):e33–e38.] [ABSTRACT FROM AUTHOR]

Achieving climate targets requires mitigation against climate change but also understanding of the response of land and ocean carbon systems. In this context, global soil carbon stocks and their response to environmental changes are key. This paper quantifies the global soil carbon feedbacks due to changes in atmospheric CO 2 , and the associated climate changes, for Earth system models (ESMs) in CMIP6. A standard approach is used to calculate carbon cycle feedbacks, defined here as soil carbon-concentration (βs) and carbon-climate (γs) feedback parameters, which are also broken down into processes which drive soil carbon change. The sensitivity to CO 2 is shown to dominate soil carbon changes at least up to a doubling of atmospheric CO 2. However, the sensitivity of soil carbon to climate change is found to become an increasingly important source of uncertainty under higher atmospheric CO 2 concentrations. [ABSTRACT FROM AUTHOR]

The fate of the carbon locked away in soil is uncertain, and there are vast differences between models. Here the authors apply observational, spatio-temporal constraints on carbon turnover projections and find that uncertainty in estimations of carbon dynamics are reduced by 50%.

Longitudinal studies are needed to evaluate the SARS-CoV-2 mRNA vaccine antibody response under real-world conditions. This longitudinal study investigated the quantity and quality of SARS-CoV-2 antibody response in 846 specimens from 350 patients, comparing BNT162b2-vaccinated individuals (19 previously diagnosed with COVID-19, termed RecoVax; and 49 never diagnosed, termed NaiveVax) with 122 hospitalized unvaccinated (HospNoVax) and 160 outpatient unvaccinated (OutPtNoVax) COVID-19 patients. NaiveVax experienced delay in generating SARS-CoV-2 total antibodies (TAb) and surrogate neutralizing antibodies (SNAb) after the first vaccine dose (D1) but rapid increase in antibody levels after the second dose (D2). However, these never reached RecoVax’s robust levels. In fact, NaiveVax TAb and SNAb levels decreased 4 weeks after D2. For the most part, RecoVax TAb persisted, after reaching maximal levels 2 weeks after D2, but SNAb decreased significantly about 6 months after D1. Although NaiveVax avidity lagged behind that of RecoVax for most of the follow-up periods, NaiveVax did reach similar avidity by about 6 months after D1. These data suggest that 1 vaccine dose elicits maximal antibody response in RecoVax and may be sufficient. Also, despite decreasing levels in TAb and SNAb over time, long-term avidity may be a measure worth evaluating and possibly correlating to vaccine efficacy.

BackgroundNPM1 mutation status can influence prognosis and management in AML. Accordingly, clinical testing (i.e., RT-PCR, NGS and IHC) for mutant NPM1 is increasing in order to detect residual disease in AML, alongside flow cytometry (FC). However, the relationship of the results from RT-PCR to traditional NGS, IHC and FC is not widely known among many practitioners. Herein, we aim to: i) describe the performance of RT-PCR compared to traditional NGS and IHC for the detection of mutant NPM1 in clinical practice, and also compare it to FC, and ii) provide our observations regarding the advantages and disadvantages of each approach in order to inform future clinical testing algorithms.MethodsPeripheral blood and bone marrow samples collected for clinical testing at variable time points during patient management were tested by quantitative, real-time, RT-PCR and results were compared to findings from a Myeloid NGS panel, mutant NPM1 IHC and FC.ResultsRT-PCR showed superior sensitivity compared to NGS, IHC and FC with the main challenge of NGS, IHC and FC being the ability to identify a low disease burden (