Radiation-induced DNA double-strand breaks in cortisol exposed fibroblasts as quantified with the novel foci-integrated damage complexity score (FIDCS).

Without the protective shielding of Earth's atmosphere, astronauts face higher doses of ionizing radiation in space, causing serious health concerns. Highly charged and high energy (HZE) particles are particularly effective in causing complex and difficult-to-repair DNA double-strand breaks compared to low linear energy transfer. Additionally, chronic cortisol exposure during spaceflight raises further concerns, although its specific impact on DNA damage and repair remains unknown. This study explorers the effect of different radiation qualities (photons, protons, carbon, and iron ions) on the DNA damage and repair of cortisol-conditioned primary human dermal fibroblasts. Besides, we introduce a new measure, the Foci-Integrated Damage Complexity Score (FIDCS), to assess DNA damage complexity by analyzing focus area and fluorescent intensity. Our results show that the FIDCS captured the DNA damage induced by different radiation qualities better than counting the number of foci, as traditionally done. Besides, using this measure, we were able to identify differences in DNA damage between cortisol-exposed cells and controls. This suggests that, besides measuring the total number of foci, considering the complexity of the DNA damage by means of the FIDCS can provide additional and, in our case, improved information when comparing different radiation qualities.

Influenza Virus Inactivated by Heavy Ion Beam Irradiation Stimulates Antigen-Specific Immune Responses.

The COVID-19 pandemic has made clear the need for effective and rapid vaccine development methods. Conventional inactivated virus vaccines, together with new technologies like vector and mRNA vaccines, were the first to be rolled out. However, the traditional methods used for virus inactivation can affect surface-exposed antigen, thereby reducing vaccine efficacy. Gamma rays have been used in the past to inactivate viruses. We recently proposed that high-energy heavy ions may be more suitable as an inactivation method because they increase the damage ratio between the viral nucleic acid and surface proteins. Here, we demonstrate that irradiation of the influenza virus using heavy ion beams constitutes a suitable method to develop effective vaccines, since immunization of mice by the intranasal route with the inactivated virus resulted in the stimulation of strong antigen-specific humoral and cellular immune responses.

Global patterns of tree wood density.

Wood density is a fundamental property related to tree biomechanics and hydraulic function while playing a crucial role in assessing vegetation carbon stocks by linking volumetric retrieval and a mass estimate. This study provides a high-resolution map of the global distribution of tree wood density at the 0.01° (~1 km) spatial resolution, derived from four decision trees machine learning models using a global database of 28,822 tree-level wood density measurements. An ensemble of four top-performing models combined with eight cross-validation strategies shows great consistency, providing wood density patterns with pronounced spatial heterogeneity. The global pattern shows lower wood density values in northern and northwestern Europe, Canadian forest regions and slightly higher values in Siberia forests, western United States, and southern China. In contrast, tropical regions, especially wet tropical areas, exhibit high wood density. Climatic predictors explain 49%-63% of spatial variations, followed by vegetation characteristics (25%-31%) and edaphic properties (11%-16%). Notably, leaf type (evergreen vs. deciduous) and leaf habit type (broadleaved vs. needleleaved) are the most dominant individual features among all selected predictive covariates. Wood density tends to be higher for angiosperm broadleaf trees compared to gymnosperm needleleaf trees, particularly for evergreen species. The distributions of wood density categorized by leaf types and leaf habit types have good agreement with the features observed in wood density measurements. This global map quantifying wood density distribution can help improve accurate predictions of forest carbon stocks, providing deeper insights into ecosystem functioning and carbon cycling such as forest vulnerability to hydraulic and thermal stresses in the context of future climate change.

In-situ experiment reveals CO2 enriched fluid migration in faulted caprock.

The sealing characteristics of the geological formation located above a CO2 storage reservoir, the so-called caprock, are essential to ensure efficient geological carbon storage. If CO2 were to leak through the caprock, temporal changes in fluid geochemistry can reveal fundamental information on migration mechanisms and induced fluid-rock interactions. Here, we present the results from a unique in-situ injection experiment, where CO2-enriched fluid was continuously injected in a faulted caprock analogue. Our results show that the CO2 migration follows complex pathways within the fault structure. The joint analysis of noble gases, ion concentrations and carbon isotopes allow us to quantify mixing between injected CO2-enriched fluid and resident formation water and to describe the temporal evolution of water-rock interaction processes. The results presented here are a crucial complement to the geophysical monitoring at the fracture scale highlighting a unique migration of CO2 in fault zones.

Widespread and complex drought effects on vegetation physiology inferred from space.

The response of vegetation physiology to drought at large spatial scales is poorly understood due to a lack of direct observations. Here, we study vegetation drought responses related to photosynthesis, evaporation, and vegetation water content using remotely sensed data, and we isolate physiological responses using a machine learning technique. We find that vegetation functional decreases are largely driven by the downregulation of vegetation physiology such as stomatal conductance and light use efficiency, with the strongest downregulation in water-limited regions. Vegetation physiological decreases in wet regions also result in a discrepancy between functional and structural changes under severe drought. We find similar patterns of physiological drought response using simulations from a soil-plant-atmosphere continuum model coupled with a radiative transfer model. Observation-derived vegetation physiological responses to drought across space are mainly controlled by aridity and additionally modulated by abnormal hydro-meteorological conditions and vegetation types. Hence, isolating and quantifying vegetation physiological responses to drought enables a better understanding of ecosystem biogeochemical and biophysical feedback in modulating climate change.

Comparative validation of the knee inflammation MRI scoring system and the MRI osteoarthritis knee score for semi-quantitative assessment of bone marrow lesions and synovitis-effusion in osteoarthritis: an international multi-reader exercise.

Background: Bone marrow lesions (BMLs) and synovitis on magnetic resonance imaging (MRI) are associated with symptoms and predict degeneration of articular cartilage in osteoarthritis (OA). Validated methods for their semiquantitative assessment on MRI are available, but they all have similar scoring designs and questionable sensitivity to change. New scoring methods with completely different designs need to be developed and compared to existing methods. Objectives: To compare the performance of new web-based versions of the Knee Inflammation MRI Scoring System (KIMRISS) with the MRI OA Knee Score (MOAKS) for quantification of BMLs and synovitis-effusion (S-E). Design: Retrospective follow-up cohort. Methods: We designed web-based overlays outlining regions in the knee that are scored for BML in MOAKS and KIMRISS. For KIMRISS, both BML and S-E are scored on consecutive sagittal slices. The performance of these methods was compared in an international reading exercise of 8 readers evaluating 60 pairs of scans conducted 1 year apart from cases recruited to the OA Initiative (OAI) cohort. Interobserver reliability for baseline status and baseline to 1 year change in BML and S-E was assessed by intra-class correlation coefficient (ICC) and smallest detectable change (SDC). Feasibility was assessed using the System Usability Scale (SUS). Results: Mean change in BML and S-E was minimal over 1 year. Pre-specified targets for acceptable reliability (ICC ⩾ 0.80 and ⩾ 0.70 for status and change scores, respectively) were achieved more frequently for KIMRISS for both BML and synovitis. Mean (95% CI) ICC for change in BML was 0.88 (0.83-0.92) and 0.69 (0.60-0.78) for KIMRISS and MOAKS, respectively. KIMRISS mean SUS usability score was 85.7 and at the 95th centile of ranking for usability versus a score of 55.4 and 20th centile for MOAKS. Conclusion: KIMRISS had superior performance metrics to MOAKS for quantification of BML and S-E. Both methods should be further compared in trials of new therapies for OA.

ASAS consensus definition of early axial spondyloarthritis.

OBJECTIVES: To develop a consensual definition for the term 'early axial spondyloarthritis-axSpA'-and 'early peripheral spondyloarthritis-pSpA'. METHODS: The ASAS (Assessment of SpondyloArthritis international Society-Spondyloarthritis EARly definition) steering committee convened an international working group (WG). Five consecutive steps were followed: (1) systematic literature review (SLR); (2) discussion of SLR results within the WG and ASAS community; (3) a three-round Delphi survey inviting all ASAS members to select the items that should be considered for the definition; (4) presentation of Delphi results to the WG and ASAS community and (5) ASAS voting and endorsement (2023 annual meeting). RESULTS: Following the SLR, consensus was to proceed with an expert-based definition for early axSpA (81% in favour) but not for pSpA (54% against). Importantly, early axSpA should be based on symptom duration taking solely axial symptoms into account. 151-164 ASAS members participated in the Delphi surveys. Consensus was achieved for considering the following items within early axSpA definition: duration of symptoms ≤2 years; axial symptoms defined as cervical/thoracic/back/buttock pain or morning stiffness; regardless of the presence/absence of radiographic damage. The WG agreed that in patients with a diagnosis of axSpA 'early axSpA' should be defined as a duration of ≤2 years of axial symptoms. Axial symptoms should include spinal/buttock pain or morning stiffness and should be considered by a rheumatologist as related to axSpA. The ASAS community endorsed this proposal (88% in favour). CONCLUSIONS: Early axSpA has newly been defined, based on expert consensus. This ASAS definition should be adopted in research studies addressing early axSpA.

Evolution of Magnetic Resonance Imaging Lesions at the Sacroiliac Joints During and After Pregnancy by Serial Magnetic Resonance Imaging From Gestational Week Twenty to Twelve Months Postpartum.

OBJECTIVE: Sacroiliac (SI) joint magnetic resonance imaging (MRI) findings simulating sacroiliitis related to axial spondyloarthritis (SpA) may occur in women before and after birth. This study was undertaken to explore the prevalence, evolution, and topography of SI joint MRI lesions in pregnant and postpartum women. METHODS: A prospective cohort study included 103 first-time mothers who underwent up to 5 serial SI joint MRI between gestational week 20 and 12 months postpartum. After calibration, 3 assessors independently evaluated bone marrow edema (BME), including sacroiliitis according to the Assessment of SpondyloArthritis international Society (ASAS), as well as structural lesions, using the Spondyloarthritis Research Consortium of Canada (SPARCC) and a novel 2-plane assessment method. RESULTS: BME was frequent both during pregnancy and the postpartum period, peaking at 3 months postpartum with a prevalence of 69% (SPARCC) and 80% (2-plane method), but still present in 54% (SPARCC) and 58% (2-plane method) of subjects at 12 months postpartum. At 12 months postpartum, sacroiliitis according to the current ASAS definition was met in 41%, while 21% and 14% of women fulfilled the newly proposed ASAS MRI thresholds for active and structural SI joint lesions, respectively. BME clustered in the anterior middle joint portions at all time points, and ligamentous BME was rare. At 12 months postpartum, SPARCC erosion scores ≥3 (ASAS threshold) were observed in only 2.8% of women. CONCLUSION: At 12 months postpartum, 41% of women met the current ASAS sacroiliitis definition, which may result in false-positive assignments of axial SpA diagnosis in postpartum women with back pain. The topographical BME distribution and virtually absent erosions (ASAS threshold) at 12 months postpartum may help discriminate postpartum strain-related conditions from axial SpA-related sacroiliitis.

Comparing MRI and conventional radiography for the detection of structural changes indicative of axial spondyloarthritis in the ASAS cohort.

OBJECTIVES: To compare MRI and conventional radiography of SI joints for detection of structural lesions typical for axial spondyloarthritis (axSpA). METHODS: Adult patients from the Assessment of SpondyloArthritis international Society (ASAS) cohort with symptoms suggestive of axSpA and both SI joint MRI and radiographs available for central reading were included. Radiographs were evaluated by three readers according to the modified New York (mNY) criteria grading system. The presence of structural damage on radiographs was defined as fulfilment of the radiographic mNY criterion and, additionally, a lower threshold for sacroiliitis of at least grade 2 unilaterally. MRI scans were assessed for the presence of structural changes indicative of axSpA by seven readers. Diagnostic performance [sensitivity, specificity, positive and negative predictive values (PPV and NPV) and positive and negative likelihood ratios (LR+ and LR-)] of MRI and radiographs (vs rheumatologist's diagnosis of axSpA) were calculated. RESULTS: Overall, 183 patients were included and 135 (73.7%) were diagnosed with axSpA. Structural lesions indicative of axSpA on MRI had sensitivity 38.5%, specificity 91.7%, PPV 92.9%, NPV 34.6%, LR+ 4.62 and LR- 0.67. Sacroiliitis according to the mNY criteria had sensitivity 54.8%, specificity 70.8%, PPV 84.1%, NPV 35.8%, LR+ 1.88 and LR- 0.64. Radiographic sacroiliitis of at least grade 2 unilaterally had sensitivity 65.2%, specificity 50.0%, PPV 78.6%, NPV 33.8%, LR+ 1.30 and LR- 0.69. CONCLUSION: Structural lesions of the SI joint detected by MRI demonstrated better diagnostic performance and better interreader reliability compared with conventional radiography.

Potential benefits of using radioactive ion beams for range margin reduction in carbon ion therapy.

Sharp dose gradients and high biological effectiveness make ions such as 12C an ideal tool to treat deep-seated tumors, however, at the same time, sensitive to errors in the range prediction. Tumor safety margins mitigate these uncertainties, but during the irradiation they lead to unavoidable damage to the surrounding healthy tissue. To fully exploit the Bragg peak benefits, a large effort is put into establishing precise range verification methods. Despite positron emission tomography being widely in use for this purpose in 12C therapy, the low count rates, biological washout, and broad activity distribution still limit its precision. Instead, radioactive beams used directly for treatment would yield an improved signal and a closer match with the dose fall-off, potentially enabling precise in vivo beam range monitoring. We have performed a treatment planning study to estimate the possible impact of the reduced range uncertainties, enabled by radioactive 11C ions treatments, on sparing critical organs in tumor proximity. Compared to 12C treatments, (i) annihilation maps for 11C ions can reflect sub- millimeter shifts in dose distributions in the patient, (ii) outcomes of treatment planning with 11C significantly improve and (iii) less severe toxicities for serial and parallel critical organs can be expected.

Levels of extracellular matrix metabolites are associated with changes in Ankylosing Spondylitis Disease Activity Score and MRI inflammation scores in patients with axial spondyloarthritis during TNF inhibitor therapy.

BACKGROUND/PURPOSE: In axial spondyloarthritis (axSpA) inflammation of the sacroiliac joints and spine is associated with local extracellular matrix (ECM) remodeling of affected tissues. We aimed to investigate the association of ECM metabolites with treatment response in axSpA patients treated with TNF-α inhibitory therapy for 46 weeks. METHODS: In a prospective clinical study of axSpA patients (n=55) initiating a TNF inhibitor (infliximab, etanercept, or adalimumab), serum concentrations of formation of type I (PRO-C1), type III (PRO-C3), and type VI (PRO-C6) collagen; turnover of type IV collagen (PRO-C4), and matrix-metalloproteinase (MMP)-degraded type III (C3M) collagen, MMP-degraded type IV (C4M), type VI (C6M), and type VII (C7M) collagen, and cathepsin-degraded type X collagen (C10C), MMP-mediated metabolite of C-reactive protein (CRPM), citrullinated vimentin (VICM), and neutrophil elastase-degraded elastin (EL-NE) were measured at baseline, week 2, week 22, and week 46. RESULTS: Patients were mostly males (82%), HLA-B27 positive (84%), with a median age of 40 years (IQR: 32-48), disease duration of 5.5 years (IQR: 2-10), and a baseline Ankylosing Spondylitis Disease Activity Score (ASDAS) of 3.9 (IQR: 3.0-4.5). Compared to baseline, PRO-C1 levels were significantly increased after two weeks of treatment, C6M levels were significantly decreased after two and 22 weeks (repeated measures ANOVA, p=0.0014 and p=0.0015, respectively), EL-NE levels were significantly decreased after 2 weeks (p=0.0008), VICM levels were significantly decreased after two and 22 weeks (p=0.0163 and p=0.0374, respectively), and CRP were significantly decreased after two and 22 weeks (both p=0.0001). Baseline levels of PRO-C1, PRO-C3, C6M, VICM, and CRP were all associated with ASDAS clinically important and major improvement after 22 weeks (ΔASDAS ≥1.1) (Mann-Whitney test, p=0.006, p=0.008, p<0.001, <0.001, <0.001, respectively), while C6M, VICM and CRP levels were associated with ASDAS clinically important and major improvement after 46 weeks (ΔASDAS ≥2.0) (p=0.002, p=0.044, and p<0.001, respectively). PRO-C1 and C6M levels were associated with a Bath AS Disease Activity Score (BASDAI) response to TNF-inhibitory therapy after 22 weeks (Mann-Whitney test, p=0.020 and p=0.049, respectively). Baseline levels of PRO-C4 and C6M were correlated with the total SPARCC MRI Spine and Sacroiliac Joint Inflammation score (Spearman's Rho ρ=0.279, p=0.043 and ρ=0.496, p=0.0002, respectively). CONCLUSIONS: Extracellular matrix metabolites were associated with ASDAS response, MRI inflammation, and clinical treatment response during TNF-inhibitory treatment in patients with axSpA.

High-resolution European daily soil moisture derived with machine learning (2003-2020).

Machine learning (ML) has emerged as a novel tool for generating large-scale land surface data in recent years. ML can learn the relationship between input and target, e.g. meteorological variables and in-situ soil moisture, and then estimate soil moisture across space and time, independently of prior physics-based knowledge. Here we develop a high-resolution (0.1°) daily soil moisture dataset in Europe (SoMo.ml-EU) using Long Short-Term Memory trained with in-situ measurements. The resulting dataset covers three vertical layers and the period 2003-2020. Compared to its previous version with a lower spatial resolution (0.25°), it shows a closer agreement with independent in-situ data in terms of temporal variation, demonstrating the enhanced usefulness of in-situ observations when processed jointly with high-resolution meteorological data. Regional comparison with other gridded datasets also demonstrates the ability of SoMo.ml-EU in describing the variability of soil moisture, including drought conditions. As a result, our new dataset will benefit regional studies requiring high-resolution observation-based soil moisture, such as hydrological and agricultural analyses.

Treatment with IL5-/IL-5 receptor antagonists in drug reaction with eosinophilia and systemic symptoms (DRESS).

Purpose: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe delayed drug hypersensitivity reaction with exanthema, eosinophilia, and organ manifestations. After culprit drug withdrawal, systemic corticosteroids (CS) are the most widely used treatment, often requiring high doses for months. Blocking the IL-5/IL­5 receptor axis with mepolizumab, reslizumab, and benralizumab is a promising targeted treatment with a good safety profile and no immunosuppressive effect. The aim of this study is to summarize current experience with the anti-IL5/IL-5-receptor therapy in DRESS. Methods: A retrospective analysis of all patients diagnosed with DRESS and treated with mepolizumab, reslizumab, or benralizumab in DRESS was performed. In addition, a PubMed-Medline search for publications on DRESS with anti-IL-5/IL­5 receptor treatment was performed. Results: Of the 14 cases identified, 6 patients were treated with mepolizumab, 6 with benralizumab, 1 patient with reslizumab, and 1 patient was switched from benralizumab to mepolizumab. The main indication for an IL­5 blockade was a therapy-refractory course (7/14 [50.0%]), recurrent relapses (3/14 [21.4%]), and severe organ dysfunction (2/14 [14.3%]). In 13/14 (93%) cases, a rapid clinical improvement with suppression of eosinophilia and reduction of CS could be achieved. In all but two cases under mepolizumab (dose 100-600 mg) or reslizumab (dose according to body weight), two or more doses were necessary until resolution of DRESS. In 4/7 cases under benralizumab, a single 30 mg dose was sufficient. Conclusion: Blockade of the IL-5/IL­5 receptor axis appears to be a promising treatment in DRESS with fast clinical improvement, which may allow more rapid reduction of CS, and a good safety profile. In addition, a summary of recommendations on when to use blockade of the IL-5/IL­5 receptor axis in DRESS treatment is provided.

Widespread increasing vegetation sensitivity to soil moisture.

Global vegetation and associated ecosystem services critically depend on soil moisture availability which has decreased in many regions during the last three decades. While spatial patterns of vegetation sensitivity to global soil water have been recently investigated, long-term changes in vegetation sensitivity to soil water availability are still unclear. Here we assess global vegetation sensitivity to soil moisture during 1982-2017 by applying explainable machine learning with observation-based leaf area index (LAI) and hydro-climate anomaly data. We show that LAI sensitivity to soil moisture significantly increases in many semi-arid and arid regions. LAI sensitivity trends are associated with multiple hydro-climate and ecological variables, and strongest increasing trends occur in the most water-sensitive regions which additionally experience declining precipitation. State-of-the-art land surface models do not reproduce this increasing sensitivity as they misrepresent water-sensitive regions and sensitivity strength. Our sensitivity results imply an increasing ecosystem vulnerability to water availability which can lead to exacerbated reductions in vegetation carbon uptake under future intensified drought, consequently amplifying climate change.

MRI lesions of the spine in patients with axial spondyloarthritis: an update of lesion definitions and validation by the ASAS MRI working group.

OBJECTIVES: Spinal MRI is used to visualise lesions associated with axial spondyloarthritis (axSpA). The ASAS MRI working group (WG) updated and validated the definitions for inflammatory and structural spinal lesions in the context of axSpA. METHODS: After review of the existing literature on all possible types of spinal MRI pathologies in axSpA, the group (12 rheumatologists and two radiologists) consented on the required revisions of lesion definitions compared with the existing nomenclature of 2012. In a second step, using 62 MRI scans from the ASAS classification cohort, the proposed definitions were validated in a multireader campaign by global (absent/present) and detailed (inflammation and structural) lesion assessment at the vertebral corner (VC), vertebral endplate, facet joints, transverse processes, lateral and posterior elements. Intraclass correlation coefficient (ICC) was used for analysis. RESULTS: Revisions were made for both inflammatory (bone marrow oedema, BMO) and structural (fat, erosion, bone spur and ankylosis) lesions, including localisation (central vs lateral), extension (VC vs vertebral endplate) and extent (minimum number of slices needed), while new definitions were suggested for the type of lesion based on lesion maturity (VC monomorphic vs dimorphic). The most reliably assessed lesions were VC fat lesion and VC monomorphic BMO (ICC (mean of all 36 reader pairs/overall 9 readers): 0.91/0.92; 0.70/0.67, respectively. CONCLUSIONS: The lesion definitions for spinal MRI lesions compatible with SpA were updated by consensus and validated by a group of experienced readers. The lesions with the highest frequency and best reliability were fat and monomorphic inflammatory lesions at the VC.

Roadmap: helium ion therapy.

Helium ion beam therapy for the treatment of cancer was one of several developed and studied particle treatments in the 1950s, leading to clinical trials beginning in 1975 at the Lawrence Berkeley National Laboratory. The trial shutdown was followed by decades of research and clinical silence on the topic while proton and carbon ion therapy made debuts at research facilities and academic hospitals worldwide. The lack of progression in understanding the principle facets of helium ion beam therapy in terms of physics, biological and clinical findings persists today, mainly attributable to its highly limited availability. Despite this major setback, there is an increasing focus on evaluating and establishing clinical and research programs using helium ion beams, with both therapy and imaging initiatives to supplement the clinical palette of radiotherapy in the treatment of aggressive disease and sensitive clinical cases. Moreover, due its intermediate physical and radio-biological properties between proton and carbon ion beams, helium ions may provide a streamlined economic steppingstone towards an era of widespread use of different particle species in light and heavy ion therapy. With respect to the clinical proton beams, helium ions exhibit superior physical properties such as reduced lateral scattering and range straggling with higher relative biological effectiveness (RBE) and dose-weighted linear energy transfer (LETd) ranging from ∼4 keVµm-1to ∼40 keVµm-1. In the frame of heavy ion therapy using carbon, oxygen or neon ions, where LETdincreases beyond 100 keVµm-1, helium ions exhibit similar physical attributes such as a sharp lateral penumbra, however, with reduced radio-biological uncertainties and without potentially spoiling dose distributions due to excess fragmentation of heavier ion beams, particularly for higher penetration depths. This roadmap presents an overview of the current state-of-the-art and future directions of helium ion therapy: understanding physics and improving modeling, understanding biology and improving modeling, imaging techniques using helium ions and refining and establishing clinical approaches and aims from learned experience with protons. These topics are organized and presented into three main sections, outlining current and future tasks in establishing clinical and research programs using helium ion beams-A. Physics B. Biological and C. Clinical Perspectives.

Development of an environmental contextual factor item set relevant to global functioning and health in patients with axial spondyloarthritis.

OBJECTIVE: To describe the development of an Environmental contextual factors (EF) Item Set (EFIS) accompanying the disease specific Assessment of SpondyloArthritis international Society Health Index (ASAS HI). METHOD: First, a candidate item pool was developed by linking items from existing questionnaires to 13 EF previously selected for the International Classification of Functioning, Disability and Health (ICF) /ASAS Core Set. Second, using data from two international surveys, which contained the EF item pool as well as the items from the ASAS HI, the number of EF items was reduced based on the correlation between the item and the ASAS HI sum score combined with expert opinion. Third, the final English EFIS was translated into 15 languages and cross-culturally validated. RESULTS: The initial item pool contained 53 EF addressing four ICF EF chapters: products and technology (e1), support and relationship (e3), attitudes (e4) and health services (e5). Based on 1754 responses of axial spondyloarthritis patients in an international survey, 44 of 53 initial items were removed based on low correlations to the ASAS HI or redundancy combined with expert opinion. Nine items of the initial item pool (range correlation 0.21-0.49) form the final EFIS. The EFIS was translated into 15 languages and field tested in 24 countries. CONCLUSIONS: An EFIS is available complementing the ASAS HI and helps to interpret the ASAS HI results by gaining an understanding of the interaction between a health condition and contextual factors. The EFIS emphasizes the importance of support and relationships, as well as attitudes of the patient and health services in relation to self-reported health.

Ultra-High Dose Rate (FLASH) Carbon Ion Irradiation: Dosimetry and First Cell Experiments.

PURPOSE: To establish a beam monitoring and dosimetry system to enable the FLASH dose rate carbon ion irradiation and investigate, at different oxygen concentrations, the in vitro biological response in comparison to the conventional dose rate. METHODS AND MATERIALS: CHO-K1 cell response to irradiation at different dose rates and at different levels of oxygenation was studied using clonogenic assay. The Heidelberg Ion-Beam Therapy Center (HIT) synchrotron, after technical improvements, was adjusted to extract ≥5 × 108 12C ions within approximately 150 milliseconds. The beam monitors were filled with helium. RESULTS: The FLASH irradiation with beam scanning yields a dose of 7.5 Gy (homogeneity of ±5%) for a 280 MeV/u beam in a volume of at least 8 mm in diameter and a corresponding dose rate of 70 Gy/s (±20%). The dose repetition accuracy is better than 2%, the systematic uncertainty is better than 2%. Clonogenic assay demonstrates a significant FLASH sparing effect which is strongly oxygenation-dependent and mostly pronounced at 0.5% O2 but absent at 0% and 21% O2. CONCLUSION: The FLASH dose rates >40 Gy/s were achieved with carbon beams. Cell survival analysis revealed FLASH dose rate sparing in hypoxia (0.5%-4% O2).

Global sensitivities of forest carbon changes to environmental conditions.

The responses of forest carbon dynamics to fluctuations in environmental conditions at a global scale remain elusive. Despite the understanding that favourable environmental conditions promote forest growth, these responses have been challenging to observe across different ecosystems and climate gradients. Based on a global annual time series of aboveground biomass (AGB) estimated from radar satellites between 1992 and 2018, we present forest carbon changes and provide insights on their sensitivities to environmental conditions across scales. Our findings indicate differences in forest carbon changes across AGB classes, with regions with carbon stocks of 50-125 MgC ha-1 depict the highest forest carbon gains and losses, while regions with 125-150 MgC ha-1  have the lowest forest carbon gains and losses in absolute terms. Net forest carbon change estimates show that the arc-of-deforestation and the Congo Basin were the main hotspots of forest carbon loss, while a substantial part of European forest gained carbon during the last three decades. Furthermore, we observe that changes in forest carbon stocks were systematically positively correlated with changes in forest cover fraction. At the same time, it was not necessarily the case with other environmental variables, such as air temperature and water availability at the bivariate level. We also used a model attribution method to demonstrate that atmospheric conditions were the dominant control of forest carbon changes (56% of the total study area) followed by water-related (29% of the total study area) and vegetation (15% of the total study area) conditions. Regionally, we find evidence that carbon gains from long-term forest growth covary with long-term carbon sinks inferred from atmospheric inversions. Our results describe the contributions from the atmosphere, water-related and vegetation conditions to forest carbon changes and provide new insights into the underlying mechanisms of the coupling between forest growth and the global carbon cycle.

Imaging in Axial Spondyloarthritis: What is Relevant for Diagnosis in Daily Practice?

PURPOSE OF REVIEW: To explore how imaging may assist diagnosing axial spondyloarthritis in rheumatology practice. RECENT FINDINGS: A diagnosis of axial spondyloarthritis is based on pattern recognition by synthesizing clinical, laboratory, and imaging findings. In health care settings providing low threshold access to advanced imaging, sacroiliac joint MRI is the preferred imaging modality in clinically suspected axial spondyloarthritis. In daily routine, the optimum protocol to assess suspected inflammatory back pain combines sacroiliac joint and spine MRI fitting a 30-min slot. Contextual assessment of concomitant structural and active MRI lesions is key to enhance diagnostic utility. In women with postpartum back pain suggestive of axial spondyloarthritis, recent reports advocate waiting 6-12 months after delivery before acquiring sacroiliac joint MRI. Major unmet needs are consistent MRI protocols, standardized training modules on how to evaluate axial MRI, and timely dissemination of imaging advances into mainstream practice both in rheumatology and in radiology. In rheumatology practice, MRI has become indispensable to help diagnose early axial spondyloarthritis. However, major gaps in training and knowledge transfer to daily care need to be closed.