Shaping and enhancing resilient forests for a resilient society.

The world is currently facing uncertainty caused by environmental, social, and economic changes and by political shocks. Fostering social-ecological resilience by enhancing forests' ability to provide a range of ecosystem services, including carbon sequestration, habitat provision, and sustainable livelihoods, is key to addressing such uncertainty. However, policy makers and managers currently lack a clear understanding of how to operationalise the shaping of resilience through the combined challenges of climate change, the biodiversity crisis, and changes in societal demand. Based on a scientific literature review, we identified a set of actions related to ecosystem services, biodiversity conservation, and disturbance and pressure impacts that forest managers and policy makers should attend to enhance the resilience of European forest systems. We conclude that the resilience shaping of forests should (1) adopt an operational approach, which is currently lacking, (2) identify and address existing and future trade-offs while reinforcing win-wins and (3) attend to local particularities through an adaptive management approach.

A balancing act: Principles, criteria and indicator framework to operationalize social-ecological resilience of forests.

Against a background of intensifying climate-induced disturbances, the need to enhance the resilience of forests and forest management is gaining urgency. In forest management, multiple trade-offs exist between different demands as well as across and within temporal and spatial scales. However, methods to assess resilience that consider these trade-offs are presently lacking. Here we propose a hierarchical framework of principles, criteria, and indicators to assess the resilience of a social-ecological system by focusing on the mechanisms behind resilience. This hierarchical framework balances trade-offs between mechanisms, different parts of the social-ecological system, ecosystem services, and spatial as well as temporal scales. The framework was developed to be used in a participatory manner in forest management planning. It accounts for the major parts of the forest-related social-ecological system and considers the multiple trade-offs involved. We demonstrate the utility of the framework by applying it to a landscape dominated by Norway spruce (Picea abies (L.) Karst.) in Central Europe, managed for three different management goals. The framework highlights how forest resilience varies with the pursued management goals and related management strategies. The framework is flexible and can be applied to various forest management contexts as part of a participatory process with stakeholders. It thus is an important step towards operationalizing social-ecological resilience in forest management systems.

Significant increase in natural disturbance impacts on European forests since 1950.

Over the last decades, the natural disturbance is increasingly putting pressure on European forests. Shifts in disturbance regimes may compromise forest functioning and the continuous provisioning of ecosystem services to society, including their climate change mitigation potential. Although forests are central to many European policies, we lack the long-term empirical data needed for thoroughly understanding disturbance dynamics, modeling them, and developing adaptive management strategies. Here, we present a unique database of >170,000 records of ground-based natural disturbance observations in European forests from 1950 to 2019. Reported data confirm a significant increase in forest disturbance in 34 European countries, causing on an average of 43.8 million m3 of disturbed timber volume per year over the 70-year study period. This value is likely a conservative estimate due to under-reporting, especially of small-scale disturbances. We used machine learning techniques for assessing the magnitude of unreported disturbances, which are estimated to be between 8.6 and 18.3 million m3 /year. In the last 20 years, disturbances on average accounted for 16% of the mean annual harvest in Europe. Wind was the most important disturbance agent over the study period (46% of total damage), followed by fire (24%) and bark beetles (17%). Bark beetle disturbance doubled its share of the total damage in the last 20 years. Forest disturbances can profoundly impact ecosystem services (e.g., climate change mitigation), affect regional forest resource provisioning and consequently disrupt long-term management planning objectives and timber markets. We conclude that adaptation to changing disturbance regimes must be placed at the core of the European forest management and policy debate. Furthermore, a coherent and homogeneous monitoring system of natural disturbances is urgently needed in Europe, to better observe and respond to the ongoing changes in forest disturbance regimes.

In vitrovascularization of hydrogel-based tissue constructs via a combined approach of cell sheet engineering and dynamic perfusion cell culture.

The bioengineering of artificial tissue constructs requires special attention to their fast vascularization to provide cells with sufficient nutrients and oxygen. We addressed the challenge ofin vitrovascularization by employing a combined approach of cell sheet engineering, 3D printing, and cellular self-organization in dynamic maturation culture. A confluent cell sheet of human umbilical vein endothelial cells (HUVECs) was detached from a thermoresponsive cell culture substrate and transferred onto a 3D-printed, perfusable tubular scaffold using a custom-made cell sheet rolling device. Under indirect co-culture conditions with human dermal fibroblasts (HDFs), the cell sheet-covered vessel mimic embedded in a collagen gel together with additional singularized HUVECs started sprouting into the surrounding gel, while the suspended cells around the tube self-organized and formed a dense lumen-containing 3D vascular network throughout the gel. The HDFs cultured below the HUVEC-containing cell culture insert provided angiogenic support to the HUVECs via molecular crosstalk without competing for space with the HUVECs or inducing rapid collagen matrix remodeling. The resulting vascular network remained viable under these conditions throughout the 3 week cell culture period. This static indirect co-culture setup was further transferred to dynamic flow conditions, where the medium perfusion was enabled via two independently addressable perfusion circuits equipped with two different cell culture chambers, one hosting the HDFs and the other hosting the HUVEC-laden collagen gel. Using this system, we successfully connected the collagen-embedded HUVEC culture to a dynamic medium flow, and within 1 week of the dynamic cell culture, we detected angiogenic sprouting and dense microvascular network formation via HUVEC self-organization in the hydrogel. Our approach of combining a 3D-printed and cell sheet-covered vascular precursor that retained its sprouting capacity together with the self-assembling HUVECs in a dynamic perfusion culture resulted in a vascular-like 3D network, which is a critical step toward the long-term vascularization of bioengineeredin vitrotissue constructs.

Flow-induced glycocalyx formation and cell alignment of HUVECs compared to iPSC-derived ECs for tissue engineering applications.

The relevance of cellular in vitro models highly depends on their ability to mimic the physiological environment of the respective tissue or cell niche. Static culture conditions are often unsuitable, especially for endothelial models, since they completely neglect the physiological surface shear stress and corresponding reactions of endothelial cells (ECs) such as alignment in the direction of flow. Furthermore, formation and maturation of the glycocalyx, the essential polysaccharide layer covering all endothelial surfaces and regulating diverse processes, is highly dependent on applied fluid flow. This fragile but utterly important macromolecular layer is hard to analyze, its importance is often underestimated and accordingly neglected in many endothelial models. Therefore, we exposed human umbilical vein ECs (HUVECs) and human induced pluripotent stem cell-derived ECs (iPSC-ECs) as two relevant EC models in a side-by-side comparison to static and physiological dynamic (6.6 dyn cm-2) culture conditions. Both cell types demonstrated an elongation and alignment along the flow direction, some distinct changes in glycocalyx composition on the surface regarding the main glycosaminoglycan components heparan sulfate, chondroitin sulfate or hyaluronic acid as well as an increased and thereby improved glycocalyx thickness and functionality when cultured under homogeneous fluid flow. Thus, we were able to demonstrate the maturity of the employed iPSC-EC model regarding its ability to sense fluid flow along with the general importance of physiological shear stress for glycocalyx formation. Additionally, we investigated EC monolayer integrity with and without application of surface shear stress, revealing a comparable existence of tight junctions for all conditions and a reorganization of the cytoskeleton upon dynamic culture leading to an increased formation of focal adhesions. We then fabricated cell sheets of EC monolayers after static and dynamic culture via non-enzymatic detachment using thermoresponsive polymer coatings as culture substrates. In a first proof-of-concept we were able to transfer an aligned iPSC-EC sheet to a 3D-printed scaffold thereby making a step in the direction of vascular modelling. We envision these results to be a valuable contribution to improvements of in vitro endothelial models and vascular engineering in the future.

The 2018 European heatwave led to stem dehydration but not to consistent growth reductions in forests.

Heatwaves exert disproportionately strong and sometimes irreversible impacts on forest ecosystems. These impacts remain poorly understood at the tree and species level and across large spatial scales. Here, we investigate the effects of the record-breaking 2018 European heatwave on tree growth and tree water status using a collection of high-temporal resolution dendrometer data from 21 species across 53 sites. Relative to the two preceding years, annual stem growth was not consistently reduced by the 2018 heatwave but stems experienced twice the temporary shrinkage due to depletion of water reserves. Conifer species were less capable of rehydrating overnight than broadleaves across gradients of soil and atmospheric drought, suggesting less resilience toward transient stress. In particular, Norway spruce and Scots pine experienced extensive stem dehydration. Our high-resolution dendrometer network was suitable to disentangle the effects of a severe heatwave on tree growth and desiccation at large-spatial scales in situ, and provided insights on which species may be more vulnerable to climate extremes.

Physiological Shear Stress Enhances Differentiation, Mucus-Formation and Structural 3D Organization of Intestinal Epithelial Cells In Vitro.

Gastrointestinal (GI) mucus plays a pivotal role in the tissue homoeostasis and functionality of the gut. However, due to the shortage of affordable, realistic in vitro GI models with a physiologically relevant mucus layer, studies with deeper insights into structural and compositional changes upon chemical or physical manipulation of the system are rare. To obtain an improved mucus-containing cell model, we developed easy-to-use, reusable culture chambers that facilitated the application of GI shear stresses (0.002-0.08 dyn∙cm-2) to cells on solid surfaces or membranes of cell culture inserts in bioreactor systems, thus making them readily accessible for subsequent analyses, e.g., by confocal microscopy or transepithelial electrical resistance (TEER) measurement. The human mucus-producing epithelial HT29-MTX cell-line exhibited superior reorganization into 3-dimensional villi-like structures with highly proliferative tips under dynamic culture conditions when compared to static culture (up to 180 vs. 80 µm in height). Additionally, the median mucus layer thickness was significantly increased under flow (50 ± 24 vs. 29 ± 14 µm (static)), with a simultaneous accelerated maturation of the cells into a goblet-like phenotype. We demonstrated the strong impact of culture conditions on the differentiation and reorganization of HT29-MTX cells. The results comprise valuable advances towards the improvement of existing GI and mucus models or the development of novel systems using our newly designed culture chambers.

Quantifying the Relationship Between Increasing Life Expectancy and Nonprostate Cancer Mortality After Radical Prostatectomy.

OBJECTIVE: To investigate the relationship between increasing life expectancy and nonprostate cancer (competing) mortality after radical prostatectomy. PATIENTS AND METHODS: We studied a single-center sample of 6809 consecutive patients who underwent radical prostatectomy between 1992 and 2016 with a median age of 65 years and a median follow-up of 7.9 years. Multivariate competing risk analyses were performed with competing mortality as endpoint. Linear trends over the years of surgery for 5-year competing mortality rates and for mean ages were calculated using linear regression analyses. We estimated the number of live years gained over time using a heuristic model-based calculation: (hazard ratio year of surgery) 24 calendar years × (hazard ratio age at surgery) gained life years = 1. RESULTS: After controlling for age, nonprostate cancer mortality decreased significantly during the observation period. Accumulated over the 24 years, this decrease of mortality corresponded to the effect of 6.3 years of calendric age. Most of the decrease in nonprostate cancer mortality (predominantly attributable to noncancer causes of death) was seen in patients aged 65 years or older (8.1 years gained), whereas there was only a marginal decrease in patients younger than 65 years (only 1 year gained). The decrease in nonprostate cancer mortality was accompanied by a slight increase of mean age at surgery (2.7 years) that did not nearly compensate the decreasing risk. CONCLUSION: Clinicians should be aware of the decreasing competing mortality risk in elderly candidates for radical prostatectomy in order to avoid undertreatment.

Are forest disturbances amplifying or canceling out climate change-induced productivity changes in European forests?

Recent studies projecting future climate change impacts on forests mainly consider either the effects of climate change on productivity or on disturbances. However, productivity and disturbances are intrinsically linked because 1) disturbances directly affect forest productivity (e.g. via a reduction in leaf area, growing stock or resource-use efficiency), and 2) disturbance susceptibility is often coupled to a certain development phase of the forest with productivity determining the time a forest is in this specific phase of susceptibility. The objective of this paper is to provide an overview of forest productivity changes in different forest regions in Europe under climate change, and partition these changes into effects induced by climate change alone and by climate change and disturbances. We present projections of climate change impacts on forest productivity from state-of-the-art forest models that dynamically simulate forest productivity and the effects of the main European disturbance agents (fire, storm, insects), driven by the same climate scenario in seven forest case studies along a large climatic gradient throughout Europe. Our study shows that, in most cases, including disturbances in the simulations exaggerate ongoing productivity declines or cancel out productivity gains in response to climate change. In fewer cases, disturbances also increase productivity or buffer climate-change induced productivity losses, e.g. because low severity fires can alleviate resource competition and increase fertilization. Even though our results cannot simply be extrapolated to other types of forests and disturbances, we argue that it is necessary to interpret climate change-induced productivity and disturbance changes jointly to capture the full range of climate change impacts on forests and to plan adaptation measures.

Is enhanced biodiversity protection conflicting with ambitious bioenergy targets in eastern Finland?

The study describes how qualitative stakeholder feedback can be used in quantitative scenarios to simulate forest resource use under alternative management objectives. In earlier studies in the region of eastern Finland, stakeholders did not see a possible conflict between increased bioenergy use and nature conservation; this finding is contrary to the results of other studies. The aim of this study was to test with a quantitative modelling approach whether the stakeholder expectation holds and whether forest management in eastern Finland can simultaneously increase biomass utilization and biodiversity protection. Prior to this study, three alternative scenarios on forest resource use were created in a participatory stakeholder process, involving a broad range of stakeholders, with half of them being from research and education. In the current study, a large-scale forest resource planning model (MELA) and a sustainability impact assessment tool (ToSIA) were used to simulate the different alternative scenarios and present the results back to the stakeholders in order to evaluate them. The scenarios were evaluated by stakeholders using multi-criteria analysis. In a survey, the stakeholders indicated that biodiversity, employment, recreational value and greenhouse gas emissions were the most important indicators to them, whereas growing stock, amount of harvested roundwood, energy wood and protected forest area were considered less important. Of the created scenarios, the scenario combining bioenergy and biodiversity targets was the most preferred by the stakeholders as it performed well on those indicators that were identified by stakeholders as the most important. In this scenario, the area of protected forest and bioenergy production were increased simultaneously. With this study we offer a framework for evaluating different alternatives for future land use. The framework helps to identify key issues that are important to the stakeholders so that they can be taken into consideration in future land-use planning. In addition, the results confirm the stakeholder expectation that by protecting more forests while simultaneously increasing the mobilization of potentially available wood resources, both targets can be met without compromising too much other forest functions such as timber production and recreation.

A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents.

Systemic absorption and metabolism of drugs in the small intestine, metabolism by the liver as well as excretion by the kidney are key determinants of efficacy and safety for therapeutic candidates. However, these systemic responses of applied substances lack in most in vitro assays. In this study, a microphysiological system maintaining the functionality of four organs over 28 days in co-culture has been established at a minute but standardized microsystem scale. Preformed human intestine and skin models have been integrated into the four-organ-chip on standard cell culture inserts at a size 100,000-fold smaller than their human counterpart organs. A 3D-based spheroid, equivalent to ten liver lobules, mimics liver function. Finally, a barrier segregating the media flow through the organs from fluids excreted by the kidney has been generated by a polymeric membrane covered by a monolayer of human proximal tubule epithelial cells. A peristaltic on-chip micropump ensures pulsatile media flow interconnecting the four tissue culture compartments through microfluidic channels. A second microfluidic circuit ensures drainage of the fluid excreted through the kidney epithelial cell layer. This four-organ-chip system assures near to physiological fluid-to-tissue ratios. In-depth metabolic and gene analysis revealed the establishment of reproducible homeostasis among the co-cultures within two to four days, sustainable over at least 28 days independent of the individual human cell line or tissue donor background used for each organ equivalent. Lastly, 3D imaging two-photon microscopy visualised details of spatiotemporal segregation of the two microfluidic flows by proximal tubule epithelia. To our knowledge, this study is the first approach to establish a system for in vitro microfluidic ADME profiling and repeated dose systemic toxicity testing of drug candidates over 28 days.

Chip-based human liver-intestine and liver-skin co-cultures--A first step toward systemic repeated dose substance testing in vitro.

Systemic repeated dose safety assessment and systemic efficacy evaluation of substances are currently carried out on laboratory animals and in humans due to the lack of predictive alternatives. Relevant international regulations, such as OECD and ICH guidelines, demand long-term testing and oral, dermal, inhalation, and systemic exposure routes for such evaluations. So-called "human-on-a-chip" concepts are aiming to replace respective animals and humans in substance evaluation with miniaturized functional human organisms. The major technical hurdle toward success in this field is the life-like combination of human barrier organ models, such as intestine, lung or skin, with parenchymal organ equivalents, such as liver, at the smallest biologically acceptable scale. Here, we report on a reproducible homeostatic long-term co-culture of human liver equivalents with either a reconstructed human intestinal barrier model or a human skin biopsy applying a microphysiological system. We used a multi-organ chip (MOC) platform, which provides pulsatile fluid flow within physiological ranges at low media-to-tissue ratios. The MOC supports submerse cultivation of an intact intestinal barrier model and an air-liquid interface for the skin model during their co-culture with the liver equivalents respectively at (1)/100.000 the scale of their human counterparts in vivo. To increase the degree of organismal emulation, microfluidic channels of the liver-skin co-culture could be successfully covered with human endothelial cells, thus mimicking human vasculature, for the first time. Finally, exposure routes emulating oral and systemic administration in humans have been qualified by applying a repeated dose administration of a model substance - troglitazone - to the chip-based co-cultures.

Climate change and European forests: what do we know, what are the uncertainties, and what are the implications for forest management?

The knowledge about potential climate change impacts on forests is continuously expanding and some changes in growth, drought induced mortality and species distribution have been observed. However despite a significant body of research, a knowledge and communication gap exists between scientists and non-scientists as to how climate change impact scenarios can be interpreted and what they imply for European forests. It is still challenging to advise forest decision makers on how best to plan for climate change as many uncertainties and unknowns remain and it is difficult to communicate these to practitioners and other decision makers while retaining emphasis on the importance of planning for adaptation. In this paper, recent developments in climate change observations and projections, observed and projected impacts on European forests and the associated uncertainties are reviewed and synthesised with a view to understanding the implications for forest management. Current impact assessments with simulation models contain several simplifications, which explain the discrepancy between results of many simulation studies and the rapidly increasing body of evidence about already observed changes in forest productivity and species distribution. In simulation models uncertainties tend to cascade onto one another; from estimating what future societies will be like and general circulation models (GCMs) at the global level, down to forest models and forest management at the local level. Individual climate change impact studies should not be uncritically used for decision-making without reflection on possible shortcomings in system understanding, model accuracy and other assumptions made. It is important for decision makers in forest management to realise that they have to take long-lasting management decisions while uncertainty about climate change impacts are still large. We discuss how to communicate about uncertainty - which is imperative for decision making - without diluting the overall message. Considering the range of possible trends and uncertainties in adaptive forest management requires expert knowledge and enhanced efforts for providing science-based decision support.

Trade-offs between forest protection and wood supply in Europe.

Forest protection is one of the main measures to prevent loss of biological and landscape diversity. This study aimed to assess to what extent forests are currently protected and how felling restrictions affect the potential annual wood supply within 27 European Union member states, Norway, and Switzerland and to discuss trade-offs between intensified use of forest biomass and forest protection efforts. Protected forests covered 33 million ha (20% of total forest area) in 2005, of which 16 million ha was protected for biodiversity and the remaining area for landscape diversity. Within the protected areas, on average 48% of the volume cannot be harvested in forests protected for biodiversity and 40% in forests protected for landscapes. Consequently, 73 million m(3) (10% of the annual theoretical potential supply from the total forest area) of wood cannot be felled from the protected forests in Europe. Protected forests do not necessarily affect wood supply given the current demand for wood in Europe. However, if demand for wood from European forests for material and energy use significantly increases, the impact of existing protected forest networks may become significant after all. On the other hand, wood harvesting is allowed to a fair extent in many protected areas. Hence, the question could be raised whether biodiversity and landscape diversity within designated areas are sufficiently protected. Careful planning is required to accommodate both the protection of biological and landscape diversity and demand for wood, while not forgetting all other services that forests provide.

Stakeholder engagement in scenario development process - bioenergy production and biodiversity conservation in eastern Finland.

In this study participatory approaches were used to develop alternative forest resource management scenarios with particular respect to the effects on increased use of forest bioenergy and its effect on biodiversity in Eastern Finland. As technical planning tools, we utilized a forest management planning system (MELA) and the Tool for Sustainability Impact Assessment (ToSIA) to visualize the impacts of the scenarios. We organized a stakeholder workshop where group discussions were used as a participatory method to get the stakeholder preferences and insights concerning forest resource use in the year 2030. Feedback from the workshop was then complemented with a questionnaire. Based on the results of the workshop and a questionnaire we developed three alternative forest resource scenarios: (1) bioenergy 2030 - in which energy production is more centralized and efficient; (2) biodiversity 2030 - in which harvesting methods are more nature friendly and protected forests make up 10% of the total forest area; and (3) mixed bioenergy + biodiversity 2030 scenario - in which wood production, recreation and nature protection are assigned to the most suitable areas. The study showed that stakeholder engagement combined with the MELA and ToSIA tools can be a useful approach in scenario development.

A conceptual framework for analysing and measuring land-use intensity.

Large knowledge gaps currently exist that limit our ability to understand and characterise dynamics and patterns of land-use intensity: in particular, a comprehensive conceptual framework and a system of measurement are lacking. This situation hampers the development of a sound understanding of the mechanisms, determinants, and constraints underlying changes in land-use intensity. On the basis of a review of approaches for studying land-use intensity, we propose a conceptual framework to quantify and analyse land-use intensity. This framework integrates three dimensions: (a) input intensity, (b) output intensity, and (c) the associated system-level impacts of land-based production (e.g. changes in carbon storage or biodiversity). The systematic development of indicators across these dimensions would provide opportunities for the systematic analyses of the trade-offs, synergies and opportunity costs of land-use intensification strategies.

Challenges and opportunities in mapping land use intensity globally.

Future increases in land-based production will need to focus more on sustainably intensifying existing production systems. Unfortunately, our understanding of the global patterns of land use intensity is weak, partly because land use intensity is a complex, multidimensional term, and partly because we lack appropriate datasets to assess land use intensity across broad geographic extents. Here, we review the state of the art regarding approaches for mapping land use intensity and provide a comprehensive overview of available global-scale datasets on land use intensity. We also outline major challenges and opportunities for mapping land use intensity for cropland, grazing, and forestry systems, and identify key issues for future research.

Ecosystem service supply and vulnerability to global change in Europe.

Global change will alter the supply of ecosystem services that are vital for human well-being. To investigate ecosystem service supply during the 21st century, we used a range of ecosystem models and scenarios of climate and land-use change to conduct a Europe-wide assessment. Large changes in climate and land use typically resulted in large changes in ecosystem service supply. Some of these trends may be positive (for example, increases in forest area and productivity) or offer opportunities (for example, "surplus land" for agricultural extensification and bioenergy production). However, many changes increase vulnerability as a result of a decreasing supply of ecosystem services (for example, declining soil fertility, declining water availability, increasing risk of forest fires), especially in the Mediterranean and mountain regions.

Application of volume growth and survival graphs in the evaluation of four process-based forest growth models.

Volume growth and survival (VGS) graphs, which show volume growth rate and risk of mortality for individual trees (or tree size classes), have been proposed as a tool for assessing the validity of models that describe the development over time of tree size distributions within forest stands. We examined the utility of the VGS method in evaluating four process-based models. The performance of the models FORSKA, 4C, MORG, and PipeQual is analyzed against long-term data from a Scots pine stand in Evo, Finland, and the models FORSKA and 4C are also assessed with respect to data from a beech stand in Fabrikschleichach, Germany. Comparison of the measurement-based VGS graphs with those produced from the model-based data shows that although the models yield similar stand-level predictions, they can differ widely in their projections of individual tree growth and size distributions. Examination of the discrepancies between models and data in the context of the VGS graphs reveals several areas in which the models could be improved. We conclude that the method is useful in model evaluation, especially if used in combination with indicators of stand structure, such as the height/diameter ratio.