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Abstract Immune checkpoint inhibitor (ICI) treatment has proven successful for advanced melanoma, but is associated with potentially severe toxicity and high costs. Accurate biomarkers for response are lacking. The present work is the first to investigate the value of deep learning on CT imaging of metastatic lesions for predicting ICI treatment outcomes in advanced melanoma. Adult patients that were treated with ICI for advanced melanoma were retrospectively identified from ten participating centers. A deep learning model (DLM) was trained on volumes of lesions on baseline CT to predict clinical benefit. The DLM was compared to and combined with a model of known clinical predictors (presence of liver and brain metastasis, level of lactate dehydrogenase, performance status and number of affected organs). A total of 730 eligible patients with 2722 lesions were included. The DLM reached an area under the receiver operating characteristic (AUROC) of 0.607 [95%CI 0.565–0.648]. In comparison, a model of clinical predictors reached an AUROC of 0.635 [95%CI 0.59 –0.678]. The combination model reached an AUROC of 0.635 [95% CI 0.595–0.676]. Differences in AUROC were not statistically significant. The output of the DLM was significantly correlated with four of the five input variables of the clinical model. The DLM reached a statistically significant discriminative value, but was unable to improve over known clinical predictors. The present work shows that the assessment over known clinical predictors is an essential step for imaging-based prediction and brings important nuance to the almost exclusively positive findings in this field.

Vegetation optical depth (VOD) is a model-based indicator of the total water content stored in the vegetation canopy derived from microwave Earth observations. As such, it is related to vegetation density, abundance, and above-ground biomass (AGB). Moesinger et al. (2020) introduced the global microwave VOD Climate Archive (VODCA v1), which harmonises VOD retrievals from several individual sensors into three long-term, multi-sensor VOD products in the C, X, and Ku frequency bands, respectively. VODCA v1 was the first VOD dataset spanning over 30 years of observations, thus allowing the monitoring of long-term changes in vegetation. Several studies have used VODCA in applications such as phenology analysis; drought monitoring; gross primary productivity monitoring; and the modelling of land evapotranspiration, live fuel moisture, and ecosystem resilience. This paper presents VODCA v2, which incorporates several methodological improvements compared to the first version and adds two new VOD datasets to the VODCA product suite. The VODCA v2 products are computed with a novel weighted merging scheme based on first-order autocorrelation of the input datasets. The first new dataset merges observations from multiple sensors in the C-, X-, and Ku-band frequencies into a multi-frequency VODCA CXKu product indicative of upper canopy dynamics. VODCA CXKu provides daily observations in a 0.25° resolution for the period 1987–2021. The second addition is an L-band product (VODCA L), based on the Soil Moisture and Ocean Salinity (SMOS) and Soil Moisture Active Passive (SMAP) missions, which in theory is more sensitive to the entire canopy, including branches and trunks. VODCA L covers the period 2010–2021 and has a temporal resolution of 10 d and a spatial resolution of 0.25°. The sensitivity of VODCA CXKu to the upper vegetation layer and that of VODCA L to above-ground biomass (AGB) are analysed using independent vegetation datasets. VODCA CXKu exhibits lower random error levels and improved temporal sampling compared to VODCA v1 single-frequency products. It provides complementary spatio-temporal information to optical vegetation indicators containing additional information on the state of the canopy. As such, VODCA CXKu shows moderate positive agreement in short vegetation (Spearman's R: 0.57) and broadleaf forests (Spearman's R: 0.49) with the fraction of absorbed photosynthetically active radiation from MODIS. VODCA CXKu also shows moderate agreement with the slope of the backscatter incidence angle relation of MetOp ASCAT in grassland (Spearman's R: 0.48) and cropland (Spearman's R: 0.46). Additionally, VODCA CXKu shows temporal patterns similar to the Normalized Microwave Reflection Index (NMRI) from in situ L-band GNSS measurements of the Plate Boundary Observatory (PBO) and sap flow measurements from SAPFLUXNET. VODCA L shows strong spatial agreement (Spearman's R: 0.86) and plausible temporal patterns with respect to yearly AGB maps from the Xu et al. (2021) dataset. VODCA v2 enables monitoring of plant water dynamics, stress, and biomass change and can provide insights, even into areas that are scarcely covered by optical data (i.e. due to cloud cover). VODCA v2 is open-access and available at https://doi.org/10.48436/t74ty-tcx62 (Zotta et al., 2024).

Living labs have emerged as a long-term, collaborative approach to addressing complex societal challenges, such as sustainable land and water management and climate change adaption. While these transdisciplinary environments foster continuous knowledge exchange and interactions among actors from diverse disciplines and sectors, the role of learning in realizing the impacts of living labs on participating actors and broader society is often underexplored. This paper aims to identify and analyze learning that occurs within a sequence of co-creative activities and their resulting outcomes, using the concept of ‘learning pathways’. The ‘living lab learning framework’ provides a systematic approach to organizing and categorizing living lab activities, enabling to infer learning pathways. An ex-post analysis of an empirical case study on a climate adaptation project, KLIMAP, resulted in seven distinct learning pathways: 1) harnessing collective integrated knowledge, 2) building collaborative networks, 3) enhancing stakeholder capacity, 4) adapting and contextualizing knowledge, 5) diffusing knowledge, 6) facilitating co-creation, and 7) reflecting on learning. These pathways were developed by examining the types of learning activities, their processes, and the entities involved, linking them to the outcomes achieved. The findings highlight that learning pathways contribute to identifying outcomes and broader impacts of living labs.

Background: The predictive value of tumor-infiltrating lymphocytes (TILs) in immune-related adverse event (irAE) development remains unknown, although an association between tumor immunogenicity and irAEs has been suggested. We investigated the association between TIL abundance in pretreatment primary and metastasis specimens and the subsequent development of severe irAEs. Patients and methods: We retrospectively identified patients with advanced cutaneous melanoma who received first-line anti-programmed cell death protein 1 (PD-1) with or without anti-cytotoxic T-lymphocyte associated protein 4 (anti-CTLA-4) from 10 hospitals in the Netherlands. TILs were scored on representative hematoxylin and eosin (H&E) stains of the primary melanoma and pretreatment melanoma metastasis as ‘absent’, ‘nonbrisk’, or ‘brisk’. A univariable logistic regression analysis was carried out to assess the association between the TIL scores and the development of severe irAEs. Fine and Gray subdistribution hazard models were used to estimate the cumulative incidence of severe irAEs. Results: Of the 1346 eligible patients, 536 patients had primary melanoma specimens available, and 613 patients had metastasis specimens available. Severe irAEs occurred in 15% of anti-PD-1-treated patients and 49% of anti-PD-1 + anti-CTLA-4-treated patients. The presence of TILs was not associated with the occurrence of grade ≥3 irAEs in primary melanoma specimens (P = 0.70) nor pretreatment metastasis specimens (P = 0.91). In the univariable analysis, patients with brisk TILs did not have a higher chance of developing severe irAEs compared with patients with absent TILs, for both primary specimen (odds ratio 1.15, 95% confidence interval 0.60-2.18) and metastasis specimen (odds ratio 0.77, 95% confidence interval 0.37-1.59). There was also no significant difference in the lifetime risk or timing of the development of severe irAEs in patients with TILs present compared with patients with TILs absent. Conclusion: There was no association between the TIL scores on H&E-stained slides from the primary melanoma or pretreatment metastasis and the development of grade 3 or higher irAEs. Additionally, no correlation was found between the presence of TILs and the timing of irAEs.

A financing gap is seen as a crucial barrier, hampering the further uptake and upscaling of Nature-based Solutions (NbS). However, it is not always clear what is meant by this, nor is it clear why this barrier exists and persists. The aim of this paper is to generate an enhanced understanding of financial barriers to NbS. This is accomplished through first conceptually and theoretically clarifying the difference between funding and financing and then exploring these through an integrative literature review. We expose three different dimensions of financial barriers in NbS projects, namely the occurrence of multiple types of funding gaps, the occurrence of multiple types of financing gaps, and the particular and complex cost structures of NbS. NbS funding gaps can be broken down into public funding gaps, private funding gaps, and funding gaps specific for lifecycle phases, activities, and cost types. Bridging the funding gap is a necessary (although not sufficient) condition for bridging the finance gap and financing alone cannot solve a funding problem. We further find that these different dimensions of financial barriers can be explained by the misalignment between the characteristics of NbS and the characteristics of our existing institutions. These misalignments occur through different institutional mechanism, including (i) Funders’ preferences, (ii) Revenue generation enablers, (iii) Justification requirements, (iv) Funders’ regimes, (v) Financiers’ preferences and (vi) Finance application processes. All mechanisms influence the occurrence of public and private funding and financing gaps and they influence the cost structure of NbS, in particular transaction costs. The results of this analysis suggest that overcoming NbS funding and financing challenges requires a systemic, multi-level approach as the barriers to project implementation are not all located within a project's sphere of influence or control.

The C-band Synthetic Aperture Radar (SAR) on board of the Sentinel-1 satellites have a strong potential to retrieve Surface Soil Moisture (SSM). Using a change detection model to Sentinel-1 backscatter, an SSM product at a kilometre scale resolution over Europe could be established in the Copernicus Global Land Service (CGLS). Over areas with dense vegetation and high biomass. The geometry and water content influence the seasonality of the backscatter dynamics and hamper the SSM retrieval quality from Sentinel-1. This study demonstrates the effect of woody vegetation on SSM retrievals and proposes a masking method at the native resolution of Sentinel-1’s Interferometric Wide (IW) swath mode. At a continental 20 m grid, four dense vegetation masks are implemented over Europe in the resampling of the backscatter to a kilometre scale. The resulting backscatter is then used as input for the TUWien (TUW) change detection model and compared to both in-situ and modelled SSM. This paper highlights the potential of high-resolution vegetation datasets to mask for non-soil moisture-sensitive pixels at a sub-kilometre resolution. Results show that both correlation and seasonality of the retrieved SSM are improved by masking the dense vegetation at a 20 m resolution.

Abstract Objective: The aim of this study is to explore nutrition-related health needs, the perceptions and beliefs regarding the double burden of malnutrition, as well as barriers and facilitators in accessing nutritious food among the local population in rural Tanzania. Design: A qualitative study design using semi-structured individual interviews and focus-group discussions (FGD) was used. Basic socio-demographic information was obtained from all participants. Setting: The study was conducted in four villages within the catchment area of the Shirati KMT Hospital in Rorya district, in north-western Tanzania. Participants: Men and women in the reproductive age as well as Community Health Workers (CHW) were included. Results: In total, we performed fourteen interviews (N 41), consisting of four FGD, one dual and nine individual interviews. The three most significant topics that were identified are the large knowledge gap concerning overweight and obesity as a health problem, changing weather patterns and its implications on food supply and the socio-cultural drivers including gender roles and household dynamics. Conclusion: Environmental and socio-cultural factors play a crucial role in the determinants for DBM, which underlines the importance of understanding the local context and the nutrition practices and beliefs of the communities. Future nutritional interventions should aim towards more inclusion of men in project implementation as well as support of women empowerment. CHW could play a key role in facilitating some of the suggested interventions, including nutritional counselling and increasing awareness on the drivers of the double burden of malnutrition.

Introduction In the Netherlands, bariatric surgery in adolescents is currently only allowed in the context of scientific research. Besides this, there was no clinical pathway for bariatric surgery in adolescents. In this paper, the development of a comprehensive clinical pathway for bariatric surgery in adolescents with severe obesity in the is described. Methods The clinical pathway for bariatric surgery in adolescents consists of an eligibility assessment as well as comprehensive peri- and postoperative care. Regarding the eligibility assessment, the adolescents need to be identified by their attending pediatricians and afterwards be evaluated by specialized pediatric obesity units. If the provided treatment is considered to be insufficiently effective, the adolescent will anonymously be evaluated by a national board. This is an additional diligence procedure specifically established for bariatric surgery in adolescents. The national board consists of independent experts regarding adolescent bariatric surgery, and evaluates whether the adolescents meet the criteria defined by the national professional associations. The final step is an assessment by a multidisciplinary team for adolescent bariatric surgery. The various disciplines (pediatrician, bariatric surgeon, psychologist, dietician) evaluate whether an adolescent is eligible for bariatric surgery. In this decision-making process, it is crucial to assess whether the adolescent is expected to adhere to postoperative behavioral changes and follow-up. When an adolescent is deemed eligible for bariatric surgery, he or she will receive preoperative counselling by a bariatric surgeon to decide on the type of bariatric procedure (Roux-en-Y gastric bypass or sleeve gastrectomy). Postoperative care consists of intensive guidance by the multidisciplinary team for adolescent bariatric surgery. In this guidance, several regular appointments are included and additional care will be provided based on the needs of the adolescent and his or her family. Furthermore, the multidisciplinary lifestyle intervention, in which the adolescents participated before bariatric surgery, continues in coordination with the multidisciplinary team for adolescent bariatric surgery, and this ensures long-term counselling and follow-up. Conclusion The implementation of bariatric surgery as an integral part of a comprehensive treatment for adolescents with severe obesity requires the development of a clinical pathway with a variety of disciplines.