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The recently developed time of flight-aerosol chemical speciation monitor with the capture vaporizer and a PM2.5 aerodynamic lens (TOF-ACSM-CV-PM2.5) aims to improve the collection efficiency and chemical characterization of aerosol particles with a diameter smaller than 2.5 µm. In this study, comprehensive cross-comparisons were performed between real-time online measurements and offline filter analysis with 24-hour collection time. The goal was to evaluate the capabilities of the TOF-ACSM-CV-PM2.5 lens, as well as the accuracy of the TOF-ACSM-CV-PM2.5. The experiments were conducted at Cabauw Experimental Site for Atmospheric Research (CESAR) during the RITA-2021 campaign. The non-refractory fine particulate matter PM1.0 and PM2.5 were measured by two co-located TOF-ACSM-CV-PM2.5 by placing them behind a PM2.5 and PM1.0 inlet, respectively. A comparison between the ACSMs and PM2.5 and PM1.0 filter samples showed a much better accuracy than ±30 % less given in the previous reports, with average differences less than ± 10 % for all inorganic chemical species. In addition, the ACSMs were compared to a Monitoring Instrument for Aerosol and Gas (MARGA) (slope between 0.78–0.97 for inorganic compounds, R2 ≥ 0.93), and a Mobility Particle Size Spectrometer (MPSS) measuring the particle size distribution from around 10 to 800 nm (slope was around 1.00, R2 = 0.91). The intercomparison of the online measurements and the comparison between the online and offline measurements indicated a low bias (< 10 % for inorganic compounds) and demonstrated the high accuracy and stability of the TOF-ACSM-CV-PM2.5 lens for the atmospheric observations of particle matters. The two ACSMs exhibited an excellent agreement, with differences less than 7 %, which allowed a quantitative estimate of PM1.0 vs PM2.5 chemical composition. The result showed that the PM1.0 accounted for about 70–80 % of the PM2.5 on average. The NO3 mass fraction increased but the OC mass fraction decreased from PM1.0 to PM2.5, indicating the size-dependence on chemical composition.

Human prefrontal cortex (hPFC) is a complex brain region involved in cognitive and emotional processes and several psychiatric disorders. Here, we present an overview of the distribution of the peptidergic systems in 17 subregions of hPFC and three reference cortices obtained by microdissection and based on RNA sequencing and RNAscope methods integrated with published single-cell transcriptomics data. We detected expression of 60 neuropeptides and 60 neuropeptide receptors in at least one of the hPFC subregions. The results reveal that the peptidergic landscape in PFC consists of closely located and functionally different subregions with unique peptide/transmitter-related profiles. Neuropeptide-rich PFC subregions were identified, encompassing regions from anterior cingulate cortex/orbitofrontal gyrus. Furthermore, marked differences in gene expression exist between different PFC regions (>5-fold; cocaine and amphetamine-regulated transcript peptide) as well as between PFC regions and reference regions, for example, for somatostatin and several receptors. We suggest that the present approach allows definition of, still hypothetical, microcircuits exemplified by glutamatergic neurons expressing a peptide cotransmitter either as an agonist (hypocretin/orexin) or antagonist (galanin). Specific neuropeptide receptors have been identified as possible targets for neuronal afferents and, interestingly, peripheral blood-borne peptide hormones (leptin, adiponectin, gastric inhibitory peptide, glucagon-like peptides, and peptide YY). Together with other recent publications, our results support the view that neuropeptide systems may play an important role in hPFC and underpin the concept that neuropeptide signaling helps stabilize circuit connectivity and fine-tune/modulate PFC functions executed during health and disease. Funding agency: National Genomics Infrastructure in Stockholm - Science for Life Laboratory; Knut and Alice Wallenberg Foundation; Swedish Research Council [2018-02753, 2020-02956]; SciLifeLab; Wallenberg Data Driven Life Science Program [KAW 2020.0239]; Hungarian Brain Research Program [2017-1.2.1-NKP-201700002]

Additional file 1. Supplementary Figures S1 ��� S8

Shorelines bordering ebb deltas are often subject to deformation by the approach and attachment of ebb-tidal shoals. Although this is a common behaviour, little attention has been paid to the link between shoal migration and the multi-annual development of the adjacent beach-dune system. This study aims to understand beach-dune systems' behaviour during the approach phase of an ebb-tidal shoal attachment event. Topographic and bathymetric data of the barrier island of Texel (NL) was used to calculate shoreline position, beach and dune volume, dunefoot position, and shoal displacement rates. Two classical beach-dune interaction models were used to understand the observed behaviour: the surfzone-beach-dune model and the sediment budget model. The analysis revealed how a larger bank on the land-facing side of the ebb delta split into two smaller shoals with different morphological behaviours. One of the shoals (S1) moved consistently landwards, recently attaching the shore, whereas the second shoal (S2) is still evolving and presents a milder landward movement than S1. In parallel to the landward movement of S1, the adjacent coastline was subject to erosion, partially counterbalanced by nourishments. However, despite the erosion, dunes are growing in volume, suggesting a net positive transfer of sand from the beach to the dunes. In the surfzone-beach-dune model, regular nourishments positively affect beach state by maintaining sufficient beach size for aeolian sediment transport and reducing shoreline erosion. In the budget model, dune volume growth may occur despite a slightly negative beach budget. Framing Texel in the budget model implies that the beach budget before the start of the approach phase is crucial in defining the behaviour of the dune system during this phase. If the shoal approach significantly reduces the beach budget, the system may cross the budget threshold that dune building is possible. Thus, the dune system may evolve to an erosional state, including dune ridge dissection and blowout development. Hence, nourishments have been essential in keeping the current morphological state during the attachment of the shoal, as they restrict the system from crossing the negative morphological threshold. Thus, without the nourishments, beach erosion driven by the shoal might have led to morphological changes in the dune system that could lead to years of a weakened level of protection until foredune recovery after attachment.

The long-term physical existence of sandy shores critically depends on a balanced sediment budget. From the principles of Building with Nature it follows that a sustainable protection of sandy shores should employ some form of shore nourishment. In the spatial design process of urbanized sandy shores, where multiple functions must be integrated, the knowledge and the prediction of sediment dynamics and beach-dune morphology thus play an essential role. This expertise typically resides with coastal scientists who have condensed their knowledge in various types of morphological models that serve different purposes and rely on different assumptions, thus have their specific strengths and limitations. This paper identifies morphological information needs for the integrated spatial design of urbanized sandy shores using BwN principles, outlines capabilities of different types of morphological models to support this and identifies current gaps between the two. A clear mismatch arises from the absence of buildings and accompanying human activities in current numerical models simulating morphological developments in beach-dune environments.

Single-cell RNA analysis has been integrated with spatial protein profiling to create a single–cell type map of human tissues., Advances in molecular profiling have opened up the possibility to map the expression of genes in cells, tissues, and organs in the human body. Here, we combined single-cell transcriptomics analysis with spatial antibody-based protein profiling to create a high-resolution single–cell type map of human tissues. An open access atlas has been launched to allow researchers to explore the expression of human protein-coding genes in 192 individual cell type clusters. An expression specificity classification was performed to determine the number of genes elevated in each cell type, allowing comparisons with bulk transcriptomics data. The analysis highlights distinct expression clusters corresponding to cell types sharing similar functions, both within the same organs and between organs.

Sandy shores worldwide suffer from coastal erosion due to a lack of sediment input and sea-level rise. In response, coastal sand nourishments are executed using ‘Building with Nature’ techniques (BwN), in which the sand balance is amplified and natural dynamics are instrumental in the redistribution of sand, cross- and alongshore. These nourishments contribute to the growth of beaches and dunes, serving various design objectives (such as flood safety, nature, and recreation). Nevertheless, human interference (such as buildings and traffic) along urbanized sandy shores may have significant, yet poorly understood, effects on beach and dune development. Better insight is required into the interplay of morphological, ecological and urban processes to support Aeolian BwN processes for dune formation and contribute to the sustainable design of urbanized coastal zones. This paper aims to bridge the gap between coastal engineering and urban design by formulating design principles for BwN along urbanized sandy shores, combining nourishments, natural dune formation and urban development on a local scale to strengthen the coastal buffer. The first part of the paper analyses sedimentation processes in the (built) sea-land interface and identifies spatial mechanisms that relate coastal occupation to dune formation. Hence a preliminary set of design principles is derived by manipulating wind-driven sediment transport for BwN dune formation after nourishment. In the second part of the paper, these principles are applied and contextualized in two case-studies to compare their capability for BwN in different coastal profiles: the vast, rural, geomorphologically high dynamic profile of a mega-nourishment (Sand Motor); versus the compact, highly urbanized, profile(s) of a coastal resort (Noordwijk). Conclusions reflect on the applicability of BwN design principles within different coastal settings (dynamics, urbanity) and spatial arrangements facilitating BwN dune formation.

3D imaging reveals gradual degeneration of liver sympathetic nerves in human and experimental nonalcoholic fatty liver disease., Hepatic nerves have a complex role in synchronizing liver metabolism. Here, we used three-dimensional (3D) immunoimaging to explore the integrity of the hepatic nervous system in experimental and human nonalcoholic fatty liver disease (NAFLD). We demonstrate parallel signs of mild degeneration and axonal sprouting of sympathetic innervations in early stages of experimental NAFLD and a collapse of sympathetic arborization in steatohepatitis. Human fatty livers display a similar pattern of sympathetic nerve degeneration, correlating with the severity of NAFLD pathology. We show that chronic sympathetic hyperexcitation is a key factor in the axonal degeneration, here genetically phenocopied in mice deficient of the Rac-1 activator Vav3. In experimental steatohepatitis, 3D imaging reveals a severe portal vein contraction, spatially correlated with the extension of the remaining nerves around the portal vein, enlightening a potential intrahepatic neuronal mechanism of portal hypertension. These fundamental alterations in liver innervation and vasculature uncover previously unidentified neuronal components in NAFLD pathomechanisms.

Buildings at the beach-dune interface, such as restaurants and (holiday) houses, affect wind-driven sand transport in their surroundings. Hereby they shape the development of the beach-dune system. This can have implications for the flood protection offered by dunes. Therefore, this research aims to understand the effect of buildings at the beach-dune interface on beach-dune morphology. In this contribution we present the results of a field experiment which focused on the effect of building size and geometry on the size and location of the deposition patterns directly around buildings.Recorded Presentation from the vICCE (YouTube Link): https://youtu.be/hlcMP7Ev1m0

Chuang Lyu,1 Gong-Wei Lyu,2 Jan Mulder,3,4 Aurora Martinez,5 Tie-Jun Sten Shi5 1State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150069, People’s Republic of China; 2Department of Neurology, 1st Hospital of Harbin Medical University, Harbin 150001, People’s Republic of China; 3Department of Neuroscience, Karolinska Institutet, Stockholm SE-171 77, Sweden; 4Science for Life Laboratory, Karolinska Institutet, Stockholm SE-171 65, Sweden; 5Department of Biomedicine, University of Bergen, Bergen 5009, NorwayCorrespondence: Chuang Lyu Tel +86 13304503501Email htylv123@126.comTie-Jun Sten Shi Tel +47 45392855Email tiejun.shi@uib.noBackground: G protein-gated inwardly rectifying potassium (GIRK) channels are involved in the regulation of neuronal excitability. Four GIRK subunits (GIRK1-4) are expressed in rat dorsal root ganglia (DRGs). Recently, we have characterized the expression of GIRK1 and − 2, and both are downregulated in rat DRGs and spinal cord after a complete sciatic nerve transection (axotomy). Here, we aimed to study the neurochemical characteristics of GIRK3, and its regulation in rat DRGs and spinal cord induced by nerve injury.Methods: A sciatic nerve axotomy was performed to study the influences of injury on GIRK3 expression in DRGs and spinal cord. A dorsal root rhizotomy and a sciatic nerve crush were employed to study the axonal transport of GIRK3 protein, respectively. Immunohistochemistry analysis was employed for investigating the neurochemical characteristics of GIRK3.Results: In control DRGs, ∼ 18% of neuron profiles (NPs) were GIRK3-positive (+), and ∼ 41%, ∼ 48% and ∼ 45% of GIRK3+ NPs were CGRP+, IB4+ and NF200+, respectively. GIRK3-like immunoreactivity was observed in glabrous skin of hind paws and axons originating from DRG neurons. Fourteen days after axotomy, more than one-third of DRG NPs were GIRK3+, and among these ∼ 51% and ∼ 56% coexpressed galanin and neuropeptide Y, respectively. In control animals, a small group of interneurons found in the dorsal horn was GIRK3+. In addition, GIRK3+ processes could be observed in superficial laminae of spinal dorsal horn. After nerve injury, the intensity of GIRK3-like immunoreactivity in the superficial layers was increased. Evidence based on rhizotomy and sciatic nerve crush indicated both anterograde and retrograde transport of GIRK3.Conclusion: Our study demonstrates that GIRK3 is expressed in sensory neurons and spinal cord. GIRK3 has both anterograde and retrograde axonal transport. GIRK3 expression can be regulated by peripheral nerve injury.Keywords: GIRK channels, Kir3, axotomy, DRGs, spinal cord, chronic pain

Maternal drug abuse during pregnancy is a rapidly escalating societal problem. Psychostimulants, including amphetamine, cocaine, and methamphetamine, are amongst the illicit drugs most commonly consumed by pregnant women. Neuropharmacology concepts posit that psychostimulants affect monoamine signaling in the nervous system by their affinities to neurotransmitter reuptake and vesicular transporters to heighten neurotransmitter availability extracellularly. Exacerbated dopamine signaling is particularly considered as a key determinant of psychostimulant action. Much less is known about possible adverse effects of these drugs on peripheral organs, and if in utero exposure induces lifelong pathologies. Here, we addressed this question by combining human RNA-seq data with cellular and mouse models of neuroendocrine development. We show that episodic maternal exposure to psychostimulants during pregnancy coincident with the intrauterine specification of pancreatic beta cells permanently impairs their ability of insulin production, leading to glucose intolerance in adult female but not male offspring. We link psychostimulant action specifically to serotonin signaling and implicate the sex-specific epigenetic reprogramming of serotonin-related gene regulatory networks upstream from the transcription factor Pet1/Fev as determinants of reduced insulin production.

ObjectiveA survey was held to establish whether laypeople knew the location of their temporomandibular joint. MethodsA sample of 61 participants, visiting their dental office for a routine check-up, was given a three-question survey of whether they knew the location of their temporomandibular joint and could point to this location. ResultsThirty-eight participants answered the question affirmatively. Only 13 pointed to the correct location. Of these, six participants received consultation for TMD in the past, three participants were healthcare providers, and four participants actually had knowledge of the exact location. Out of 23 participants who did not know the location, one accidently designated the correct position. ConclusionThe location of the temporomandibular joint is not a well-known site for many patients. In the presence of orofacial pain, it seems advisable to let the patient designate and record the site of the pain on a drawing on the patient chart.

OBJECTIVES:: To investigate the incidence and risk factors of immune reconstitution inflammatory syndrome (IRIS) associated with toxoplasmic encephalitis (TE) in patients starting cART. DESIGN:: A historical multicenter cohort study. METHODS:: We included all HIV-infected patients diagnosed with TE in six Dutch hospitals between 1996 and 2016. Diagnosis of TE-IRIS was made using predefined IRIS criteria. We distinguished paradoxical TE-IRIS (worsening of underlying treated infection) from unmasking TE-IRIS (unmasking of subclinical infection after start of cART). We compared CD4 count, plasma viral load and timing of cART initiation between patients with and without paradoxical TE-IRIS. RESULTS:: 211 TE cases were included. Among 143 cases at risk for paradoxical TE-IRIS, we identified five cases of paradoxical TE-IRIS (3.5%). In six other cases we could not differentiate paradoxical TE-IRIS from recurrence of disease due to inadequate secondary Toxoplasma prophylaxis. There was no difference in time between start of TE treatment and cART initiation for patients who did or did not develop paradoxical TE-IRIS (p = 0.50). Within the group of 2228 patients who started cART while having a CD4 count below 200?×?10/L and receiving adequate primary prophylaxis, we identified eight cases of unmasking TE-IRIS (0.36%). Unmasking TE-IRIS could not be differentiated from a newly occurring TE in six other patients, as they were not receiving adequate primary prophylaxis against Toxoplasma. CONCLUSION:: Unmasking TE-IRIS was rare in this cohort, whereas paradoxical TE-IRIS did occur more often. We found no relationship between the timing of cART initiation and the occurrence of paradoxical TE-IRIS.

Chronically elevated nitrogen (N) deposition has led to severe nutrient imbalance in forest soils. Particularly in tropical and subtropical forest ecosystems, increasing N loading has aggravated phosphorus (P) limitation of biomass production, and has resulted in elevated emissions of nitrous oxide (N2O) and reduced uptake of methane (CH4), both of which are important greenhouse gases. Yet, the interactions of N and P and their effects on greenhouse gas emissions remain elusive. Here, we report N2O and CH4 emissions together with soil N and P data for a period of 18 months following a single P addition (79 kg P ha−1, as NaH2PO4 powder) to an N-saturated, Masson pine-dominated forest soil at TieShanPing (TSP), Chongqing, south-western (SW) China. We observed a significant decline in both nitrate (NO3−) concentrations in soil water (5 and 20 cm depths) and in soil N2O emissions, following P application. We hypothesise that enhanced N uptake by plants in response to P addition, resulted in less available NO3− for denitrification. By contrast to most other forest ecosystems, TSP is a net source of CH4. P addition significantly decreased CH4 emissions and turned the soil from a net source into a net sink. Based on our observation and previous studies in South America and China, we believe that P addition relieves N inhibition of CH4 oxidation. Within the 1.5 years after P addition, no significant increase of forest growth was observed and P stimulation of forest N uptake by understorey vegetation remains to be confirmed. Our study indicates that P fertilisation of N-saturated, subtropical forest soils may mitigate N2O and CH4 emissions, in addition to alleviating nutrient imbalances and reducing losses of N through NO3− leaching.

In the 'Building-with-Nature'(BwN) philosophy, the focus of erosion control no longer is predominantly on counteracting destructive forces, but just as much on stimulating constructive forces. It implies a shift towards a pro-active approach, implying that BwN interventions require a long-term perspective and understanding of the coastal system at a large scale. Furthermore, BwN solutions also require understanding of the social system of stakeholders involved in the coastal problem. It is the interaction between these two that creates a series of challenges for BwN, including the necessity to consider multiple scales in both coastal system and social system and the linkages between them. We argue that a way to meet those challenges may be found in a collaborative design approach (co- design), in which systems understanding is shared between all stakeholders involved in the BwN solution. This approach will be practiced and analyzed for its effectiveness in the CoCoChannel project.

Adequate estimation of neuroinflammatory processes following ischemic stroke is essential for better understanding of disease mechanisms, and for the development of treatment strategies. With the TSPO (18kDa translocator protein) positron emission tomography (PET) radioligand [11C]PBR28, we monitored longitudinally the inflammatory response post-transient cerebral ischemia in rats, using a recently developed rat stroke model that produces isolated focal cortical infarcts with clinical relevance in size and pathophysiology. Six Sprague-Dawley rats were subjected to 90min transient endovascular occlusion of the M2 segment of the middle cerebral artery (M2CAO). Animals were imaged with a nanoScan®PET/MRI system at 1, 4, 7 and 14days after M2CAO with a bolus injection of [11C]PBR28. In the infarct region, we found a significantly increased uptake of [11C]PBR28 on day 4, 7 and 14 compared to day 1 as well as compared to the contralateral cortex. No significant increase was detected in the contralateral cortex during the 14days of imaging. The activation in the infarct region gradually decreased between day 4 and day 14. In an additional group of animals (n=26), immunofluorescence studies were performed with antibodies for activated microglia/monocytes (Cd11b), phagocytes (Cd68), astrocytes (glial fibrillary acidic protein) and TSPO. The TSPO immunofluorescence signal indicated reactive microgliosis post injury, corresponding to PET findings. The present clinically relevant animal model and TSPO PET ligand appear to be well suited for studies on neuroinflammation after ischemic stroke.

Presented investigations focused on spatial variability of forest soil pH on an example of luvisols derived from loess with underlier of marlstones. Four study plots were located in different parts of the slope. Marlstones, present deeper than 1 m under loess layer, had most significant influence on spatial variability of topsoil pH. Despite relatively thick separation from the surface, the marlstone layer altered topsoil via upward water movement (influence distributed evenly) or throughout exposed deeper soil layers as an effect of uprooting (specific island−mosaic of pH). Analysis of spatial variability of soil pH emphasize such phenomena as zero distance variability that reached up to 20% of sill, and 2−4 meters of autocorrelation distances. Thus, there is a need of extended soil sampling to cover both: nugget effect and autocorrelation., Sylwan 157 (2): 149-157

International audience

Coastal policy in the Netherlands is characterised by three scale levels. The smallest scale is aimed at the preservation of safety agaisnt flooding by maintaining a minimum dune strength; the middle- and large scales at preservation of sustainable safety and of functions in the coastal zone by maintaining the coast line, respectively the sand volume in the coastal foundation. The definition of three scales basically implies a pro-active approach, based on the idea that the larger scale sets boundary conditions for the smaller scale. This pro-active approach appears to be succesful: nourishments since 1990 not only have resulted in maintaining the coast line, but also in an extension of the dunes, contributing to an increased safety against flooding. The succes has been achieved by a yearly nourishment volume of 12 Mm3. Recent studies have indicated the need to upscale the yearly averaged nourishment volume. A recent update of the sediment balance of the coastal foundation shows a negative total of ca. 20 Mm3 per year; so apparently 12 Mm3 nourishments per year is insufficient to maintain the total active sand volume of the system. Besides, in a study on future adaptation options to climate change in the Netherlands, the authoritive Deltacommissie (2008) even recommends a raise of nourishment budgets up to 85 Mm3/year until the year 2050, taking into account an ultimate worst case scenario of a sea level rise of 13 cm in 2100. To investigate innovative ways of nourishing larger volumes of sand, a Pilot project Sand Engine has been developed. The pilot implies a mega-nourishment of approximately 20 Mm3 (~ 10000 m3/m) on the coast of Holland, between Hook of Holland and The Hague. In the design phase of the pilot, a morphodynamic Delft3d model has been used to calculate morphological effects of several alternatives. The Environmental Impact Assessment EIA has decided on a shore attached cross shore bar with a length of ca. 1.5 km, as the preferent alternative. Implementation is planned for 2011, starting december 2010.

Position paper of the Netherlands Center for Coastal Research

Background, Aim and Scope: Coastal and river plains are the surfaces of depositional systems, to which sediment input is a parameter of key-importance. Their habitation and economic development usually requires protection with dikes, quays, etc., which are effective in retaining floods but have the side effect of retarding sedimentation in their hinterlands. The flood-protected Dutch lowlands (so-called dike-ring areas) have been sediment-starved for up to about a millennium. In addition to this, peat decomposition and soil compaction, brought about by land drainage, have caused significant land subsidence. Sediment deficiency, defined as the combined effect of sediment-starvation and drainage-induced volume losses, has already been substantial in this area, and it is expected to become urgent in view of the forecasted effects of climate change (sea-level rise, intensified precipitation and run-off). We therefore explore this deficiency, compare it with natural (Holocene) and current human sediment inputs, and discuss it in terms of long-term land-use options. Materials and Methods: We use available 3D geological models to define natural sediment inputs to our study area. Recent progress in large-scale modelling of peat oxidation and compaction enables us to address volume loss associated with these processes. Human sediment inputs are based on published minerals statistics. All results are given as first-order approximations. Results: The current sediment deficit in the diked lowlands of the Netherlands is estimated at 136 ± 67 million m3/a. About 85% of this volume is the hypothetical amount of sediment required to keep up with sea-level rise, and 15% is the effect of land drainage (peat decomposition and compaction). The average Holocene sediment input to our study area (based on a total of 145 km3) is ~14 million m3/a, and the maximum (millennium-averaged) input ~26 million m3/a. Historical sediment deficiency has resulted in an unused sediment accommodation space of about 13.3 km3. Net human input of sediment material currently amounts to ~23 million m3/a. Discussion: As sedimentary processes in the Dutch lowlands have been retarded, the depositional system's natural resilience to sea-level rise is low, and all that is left to cope is human countermeasure. Preserving some sort of status quo with water management solutions may reach its limits in the foreseeable future. The most viable long-term solutions therefore seem a combination of allowing for more water in open country (anything from flood-buffer zones to open water) and raising lands that are to be built up (enabling their lasting protection). As to the latter, doubling or tripling the use of filling sand in a planned and sustained effort may resolve up to one half of the Dutch sediment deficiency problems in about a century. Conclusions, Recommendations and Perspectives: We conclude that sediment deficiency – past, present and future – challenges the sustainable habitation of the Dutch lowlands. In order to explore possible solutions, we recommend the development of long-term scenarios for the changing lowland physiography, that include the effects of Global Change, compensation measures, costs and benefits, and the implications for long-term land-use options. Recommendations and Perspectives: We conclude that sediment deficiency – past, present and future – challenges the sustainable habitation of the Dutch lowlands. In order to explore possible solutions, we recommend the development of long-term scenarios for the changing lowland physiography, that include the effects of Global Change, compensation measures, costs and benefits, and the implications for long-term land-use options.