Comparison and validation of FDG-PET/CT scores for polymyalgia rheumatica

OBJECTIVES: To compare and validate the diagnostic accuracy of fluorodeoxyglucose (FDG)-PET/CT scores for PMR; and to explore their association with clinical factors. METHODS: This retrospective study included 39 consecutive patients diagnosed with PMR and 19 PMR comparators. The final clinical diagnosis was established after 6 months follow-up. Patients underwent FDG-PET/CT prior to glucocorticoid treatment. Visual grading of FDG uptake was performed at 30 anatomic sites. Three FDG-PET/CT scores (the Leuven Score, two Besançon Scores) and two algorithms (the Saint-Etienne and Heidelberg Algorithms) were investigated. Receiver operating characteristic (ROC) analysis with area under the curve (AUC) was performed. Diagnostic accuracy was assessed at predefined cut-off points. RESULTS: All three FDG-PET/CT scores showed high diagnostic accuracy for a clinical diagnosis of PMR in the ROC analysis (AUC 0.889–0.914). The Leuven Score provided a sensitivity of 89.7% and specificity of 84.2% at its predefined cut-off point. A simplified Leuven Score showed similar diagnostic accuracy to that of the original score. The Besançon Scores showed limited specificity at their predefined cut-off points (i.e. 47.4% and 63.2%), while ROC analysis suggested that substantially higher cut-off points are needed for these scores. The Heidelberg and Saint-Etienne Algorithms demonstrated high sensitivity, but lower specificity (i.e. 78.9% and 42.1%, respectively) for PMR. Female sex and presence of large-vessel vasculitis were associated with lower FDG-PET/CT scores in patients with PMR. CONCLUSION: The Leuven Score showed the highest diagnostic utility for PMR. A modified, concise version of the Leuven Score provided similar diagnostic accuracy to that of the original score

Ontogenetic movements of cod in Arctic fjords and the Barents Sea as revealed by otolith microchemistry

The distribution of Atlantic cod (Gadus morhua) in northern Norwegian waters is expanding eastward and northward in the Barents Sea and along western Svalbard. In the Arctic fjords of Svalbard, cod has become abundant, but little is known about the biology, origin, or residence patterns of these populations. To address this issue, we used laser ablation inductively coupled plasma mass spectrometry to quantify the trace elemental composition of cod otoliths at age-0, age-3 and the year of spawning at five distinct locations in northern Norway and western Svalbard. Chemical composition data was used to identify natal sources of cod, their broad-scale migration patterns, and to determine if cod are currently resident in Arctic fjords. Our results suggest that cod collected at Kongsfjord, Isfjord, outside Svalbard, Lofoten, and Porsangerfjord were recruited mainly from the Barents Sea, conforming to the Northeast Arctic cod ecotype. The degree of chemical overlap between Porsangerfjord and Isfjord cod, however, varied with fish age, suggesting individual movements consistent with the Norwegian coastal cod ecotype. Finally, the chemical composition of mature fish at Isfjord, and to a lesser extent Kongsfjord, suggests that cod from the Barents Sea might have recently established residency in these two Arctic fjords.acceptedVersio

Angiopoietin-2/-1 ratios and MMP-3 levels as an early warning sign for the presence of giant cell arteritis in patients with polymyalgia rheumatica

BACKGROUND: Diagnosing patients with giant cell arteritis (GCA) remains difficult. Due to its non-specific symptoms, it is challenging to identify GCA in patients presenting with symptoms of polymyalgia rheumatica (PMR), which is a more common disease. Also, commonly used acute-phase markers CRP and ESR fail to discriminate GCA patients from PMR and (infectious) mimicry patients. Therefore, we investigated biomarkers reflecting vessel wall inflammation for their utility in the accurate diagnosis of GCA in two international cohorts. METHODS: Treatment-naïve GCA patients participated in the Aarhus AGP cohort (N = 52) and the Groningen GPS cohort (N = 48). The AGP and GPS biomarker levels and symptoms were compared to patients presenting phenotypically as isolated PMR, infectious mimicry controls and healthy controls (HCs). Serum/plasma levels of 12 biomarkers were measured by ELISA or Luminex. RESULTS: In both the AGP and the GPS cohort, we found that weight loss, elevated erythrocyte sedimentation rate (ESR) and higher angiopoietin-2/-1 ratios but lower matrix metalloproteinase (MMP)-3 levels identify concomitant GCA in PMR patients. In addition, we confirmed that elevated platelet counts are characteristic of GCA but not of GCA mimicry controls and that low MMP-3 and proteinase 3 (PR3) levels may help to discriminate GCA from infections. CONCLUSION: This study, performed in two independent international cohorts, consistently shows the potential of angiopoietin-2/-1 ratios and MMP-3 levels to identify GCA in patients presenting with PMR. These biomarkers may be used to select which PMR patients require further diagnostic workup. Platelet counts may be used to discriminate GCA from GCA look-alike patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13075-022-02754-5

Cytokine producing B-cells and their capability to polarize macrophages in giant cell arteritis

OBJECTIVE: The lack of disease-specific autoantibodies in giant cell arteritis (GCA) suggests an alternative role for B-cells readily detected in the inflamed arteries. Here we study the cytokine profile of tissue infiltrated and peripheral blood B-cells of patients with GCA. Moreover, we investigate the macrophage skewing capability of B-cell-derived cytokines.METHODS: The presence of various cytokines in B-cell areas in temporal artery (n = 11) and aorta (n = 10) was identified by immunohistochemistry. PBMCs of patients with GCA (n = 11) and polymyalgia rheumatica (n = 10), and 14 age- and sex-matched healthy controls (HC) were stimulated, followed by flow cytometry for cytokine expression in B-cells. The skewing potential of B-cell-derived cytokines (n = 6 for GCA and HC) on macrophages was studied in vitro.RESULTS: The presence of IL-6, GM-CSF, TNFα, IFNγ, LTβ and IL-10 was documented in B-cells and B-cell rich areas of GCA arteries. In vitro, B-cell-derived cytokines (from both GCA and HC) skewed macrophages towards a pro-inflammatory phenotype with enhanced expression of IL-6, IL-1β, TNFα, IL-23, YKL-40 and MMP-9. In vitro stimulated peripheral blood B-cells from treatment-naïve GCA patients showed an enhanced frequency of IL-6+ and TNFα+IL-6+ B-cells compared to HCs. This difference was no longer detected in treatment-induced remission. Erythrocyte sedimentation rate positively correlated with IL-6+TNFα+ B-cells.CONCLUSION: B-cells are capable of producing cytokines and steering macrophages towards a pro-inflammatory phenotype. Although the capacity of B-cells in skewing macrophages is not GCA specific, these data support a cytokine-mediated role for B-cells in GCA and provide grounds for B-cell targeted therapy in GCA.</p

Growth portfolios buffer climate-linked environmental change in marine systems

Large-scale, climate-induced synchrony in the productivity of fish populations is becoming more pronounced in the world's oceans. As synchrony increases, a population's “portfolio” of responses can be diminished, in turn reducing its resilience to strong perturbation. Here we argue that the costs and benefits of trait synchronization, such as the expression of growth rate, are context dependent. Contrary to prevailing views, synchrony among individuals could actually be beneficial for populations if growth synchrony increases during favorable conditions, and then declines under poor conditions when a broader portfolio of responses could be useful. Importantly, growth synchrony among individuals within populations has seldom been measured, despite well-documented evidence of synchrony across populations. Here, we used century-scale time series of annual otolith growth to test for changes in growth synchronization among individuals within multiple populations of a marine keystone species (Atlantic cod, Gadus morhua). On the basis of 74,662 annual growth increments recorded in 13,749 otoliths, we detected a rising conformity in long-term growth rates within five northeast Atlantic cod populations in response to both favorable growth conditions and a large-scale, multidecadal mode of climate variability similar to the East Atlantic Pattern. The within-population synchrony was distinct from the across-population synchrony commonly reported for large-scale environmental drivers. Climate-linked, among-individual growth synchrony was also identified in other Northeast Atlantic pelagic, deep-sea and bivalve species. We hypothesize that growth synchrony in good years and growth asynchrony in poorer years reflects adaptive trait optimization and bet hedging, respectively, that could confer an unexpected, but pervasive and stabilizing, impact on marine population productivity in response to large-scale environmental change.publishedVersio

One way or another? Criminal investigators' beliefs regarding the disclosure of evidence in interviews with suspects in England and Wales

The research base concerning interviews with suspects remains to be comprehensively developed. For example, the extant literature provides differing views regarding how best to undertake the important interview task of disclosing evidence. In the current study, using a self-report questionnaire, 224 investigators based in England and Wales were asked as to their own preferred methods. Most respondents advocated a gradual method of disclosing evidence, stating that this approach would better reveal inconsistencies and obtain a complete version of events (similar to the reasoning of those who preferred disclosing evidence later). Those who advocated revealing evidence early stated this approach would more likely elicit confessions. Several respondents would not commit to one single method, arguing that their chosen strategy was contextually dependent. The study’s findings suggest that it remains arguable as to whether there is one best approach to evidence disclosure and/or whether particular circumstances should influence interviewing strategies

The response of tropical rainforests to drought : lessons from recent research and future prospects

Key message: we review the recent findings on the influence of drought on tree mortality, growth or ecosystem functioning in tropical rainforests. Drought plays a major role in shaping tropical rainforests and the response mechanisms are highly diverse and complex. The numerous gaps identified here require the international scientific community to combine efforts in order to conduct comprehensive studies in tropical rainforests on the three continents. These results are essential to simulate the future of these ecosystems under diverse climate scenarios and to predict the future of the global earth carbon balance. - Context: tropical rainforest ecosystems are characterized by high annual rainfall. Nevertheless, rainfall regularly fluctuates during the year and seasonal soil droughts do occur. Over the past decades, a number of extreme droughts have hit tropical rainforests, not only in Amazonia but also in Asia and Africa. The influence of drought events on tree mortality and growth or on ecosystem functioning (carbon and water fluxes) in tropical rainforest ecosystems has been studied intensively, but the response mechanisms are complex.- Aims: herein, we review the recent findings related to the response of tropical forest ecosystems to seasonal and extreme droughts and the current knowledge about the future of these ecosystems. - Results: this review emphasizes the progress made over recent years and the importance of the studies conducted under extreme drought conditions or in through-fall exclusion experiments in understanding the response of these ecosystems. It also points to the great diversity and complexity of the response of tropical rainforest ecosystems to drought. - Conclusion: the numerous gaps identified here require the international scientific community to combine efforts in order to conduct comprehensive studies in tropical forest regions. These results are essential to simulate the future of these ecosystems under diverse climate scenarios and to predict the future of the global earth carbon balance