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Abstract Changes in upstream land-use have significantly transformed downstream coastal ecosystems around the globe. Restoration of coastal ecosystems often focuses on local-scale processes, thereby overlooking landscape-scale interactions that can ultimately determine restoration outcomes. Here we use an idealized bio-morphodynamic model, based on estuaries in New Zealand, to investigate the effects of both increased sediment inputs caused by upstream deforestation following European settlement and mangrove removal on estuarine morphology. Our results show that coastal mangrove removal initiatives, guided by knowledge on local-scale bio-morphodynamic feedbacks, cannot mitigate estuarine mud-infilling and restore antecedent sandy ecosystems. Unexpectedly, removal of mangroves enhances estuary-scale sediment trapping due to altered sedimentation patterns. Only reductions in upstream sediment supply can limit estuarine muddification. Our study demonstrates that bio-morphodynamic feedbacks can have contrasting effects at local and estuary scales. Consequently, human interventions like vegetation removal can lead to counterintuitive responses in estuarine landscape behavior that impede restoration efforts, highlighting that more holistic management approaches are needed.

Abstract Climate change adaptation is paramount, but increasing evidence suggests that adaptation action is subject to a range of constraints. For a realistic assessment of future adaptation prospects, it is crucial to understand the timescales needed to overcome these constraints. Here, we combine data on documented adaptation from the Global Adaptation Mapping Initiative with national macro indicators and assess future changes in adaptation constraints alongside the Shared Socioeconomic Pathways, spanning a wide range of future socio-economic development scenarios. We find that even in the most optimistic scenario, it will take until well after 2050 to overcome key constraints, which will limit adaptation for decades to come particularly in vulnerable countries. The persistence of adaptation constraints calls for stringent mitigation, improved adaptation along with dedicated finance and increasing efforts to address loss and damage. Our approach allows to ground truth indicators that can be further used in climate modelling efforts, improving the representation of adaptation and its risk reduction potential.

While causal reasoning is a core facet of our cognitive abilities, its time-course has not received proper attention. As the duration of reasoning might prove crucial in understanding the underlying cognitive processes, we asked participants in two experiments to make probabilistic causal inferences while manipulating time pressure. We found that participants are less accurate under time pressure, a speed-accuracy-tradeoff, and that they respond more conservatively. Surprisingly, two other persistent reasoning errors-Markov violations and failures to explain away-appeared insensitive to time pressure. These observations seem related to confidence: Conservative inferences were associated with low confidence, whereas Markov violations and failures to explain were not. These findings challenge existing theories that predict an association between time pressure and all causal reasoning errors including conservatism. Our findings suggest that these errors should not be attributed to a single cognitive mechanism and emphasize that causal judgements are the result of multiple processes.

A comparison of salt marsh and mangrove channel networks around the world exhibited different network extents. This could be linked to differences in vegetation colonization strategies, with major implications on coastal development.

AimsTo evaluate whether parameters of post-hypoglycemic hyperglycemia (PHH) correlated with glucose homeostasis during the first year after type 1 diabetes onset and helped to distinguish pediatric patients undergoing partial remission or not.MethodsIn the GLUREDIA (GLUcagon Response to hypoglycemia in children and adolescents with new-onset type 1 DIAbetes) study, longitudinal values of clinical parameters, continuous glucose monitoring metrics and residual β-cell secretion from children with new-onset type 1 diabetes were analyzed during the first year after disease onset. PHH parameters were calculated using an in-house algorithm. Correlations between PHH parameters (i.e., PHH frequency, PHH duration, PHH area under the curve [PHHAUC]) and glycemic homeostasis markers were studied using adjusted mixed-effects models.ResultsPHH parameters were strong markers to differentiate remitters from non-remitters with PHH/Hyperglycemia duration ratio being the most sensitive (ratioConclusionPHH parameters are new minimal-invasive markers to discriminate remitters from non-remitters and evaluate glycemic homeostasis during the first year of type 1 diabetes. PHH parameters may also allow patient-targeted therapeutic management of hypoglycemic episodes.

In a world that is uncertain and noisy, perception makes use of optimization procedures that rely on the statistical properties of previous experiences. A well-known example of this phenomenon is the central tendency effect observed in many psychophysical modalities. For example, in interval timing tasks, previous experiences influence the current percept, pulling behavioural responses towards the mean. In Bayesian observer models, these previous experiences are typically modelled by unimodal statistical distributions, referred to as the prior. Here, we critically assess the validity of the assumptions underlying these models and propose a model that allows for more flexible, yet conceptually more plausible, modelling of empirical distributions. By representing previous experiences as a mixture of lognormal distributions, this model can be parametrized to mimic different unimodal distributions and thus extends previous instantiations of Bayesian observer models. We fit the mixture lognormal model to published interval timing data of healthy young adults and a clinical population of aged mild cognitive impairment patients and age-matched controls, and demonstrate that this model better explains behavioural data and provides new insights into the mechanisms that underlie the behaviour of a memory-affected clinical population.

Classical value-based decision theories state that economic choices are solely based on the value of available options. Experimental evidence suggests, however, that individuals' choices are biased towards default options, prompted by the framing of decisions. Although the effects of default options created by exogenous framing-such as how choice options are displayed-are well-documented, little is known about the potential effects and properties of endogenous framing, that is, originating from an individual's internal state. In this study, we investigated the existence and properties of endogenous default options in a task involving choices between risky lotteries. By manipulating and examining the effects of three experimental features-time pressure, time spent on task and relative choice proportion towards a specific option-, we reveal and dissociate two features of endogenous default options which bias individuals' choices: a natural tendency to prefer certain types of options (natural default), and the tendency to implicitly learn a default option from past choices (learned default). Additional analyses suggest that while the natural default may bias the standard choice process towards an option category, the learned default effects may be attributable to a second independent choice process. Overall, these investigations provide a first experimental evidence of how individuals build and apply diverse endogenous default options in economic decision-making and how this biases their choices.

Sustainable irrigation expansion over water limited croplands is an important measure to enhance agricultural yields and increase the resilience of crop production to global warming. While existing global assessments of irrigation expansion mainly illustrate the biophysical potential for irrigation, socioeconomic factors such as weak governance or low income, that demonstrably impede the successful implementation of sustainable irrigation, remain largely underexplored. Here we provide five scenarios of sustainable irrigation deployment in the 21st century integrated into the framework of Shared Socioeconomic Pathways, which account for biophysical irrigation limits and socioeconomic constraints. We find that the potential for sustainable irrigation expansion implied by biophysical limits alone is considerably reduced when socioeconomic factors are considered. Even under an optimistic scenario of socio-economic development, we find that additional calories produced via sustainable irrigation by 2100 might reach only half of the maximum biophysical potential. Regions with currently modest socioeconomic development such as Sub-Saharan Africa are found to have the highest potential for improvements. In a scenario of sustainable development, Sub-Saharan Africa would be able to almost double irrigated food production and feed an additional 70 million people compared to 2020, whereas in a scenario where regional rivalry prevails, this potential would be halved. Increasing sustainable irrigation will be key for countries to meet the projected food demands, tackle malnutrition and rural poverty in the context of increasing impacts of anthropogenic climate change on food systems. Our results suggest that improving governance levels for example through enhancing the effectiveness of institutions will constitute an important leverage to increase adaptive capacity in the agricultural sector.

BackgroundKetorolac has been associated with a lower risk of recurrence in retrospective studies, especially in patients with positive inflammatory markers. It is still unknown whether a single dose of pre-incisional ketorolac can prolong recurrence-free survival.MethodsThe KBC trial is a multicenter, placebo-controlled, randomized phase III trial in high-risk breast cancer patients powered for 33% reduction in recurrence rate (from 60 to 40%). Patients received one dose of ketorolac tromethamine or a placebo before surgery. Eligible patients were breast cancer patients, planned for curative surgery, and with a Neutrophil-to-Lymphocyte Ratio≥4, node-positive disease or a triple-negative phenotype. The primary endpoint was Disease-Free Survival (DFS) at two years. Secondary endpoints included safety, pain assessment and overall survival.FindingsBetween February 2013 and July 2015, 203 patients were assigned to ketorolac (n = 96) or placebo (n = 107). Baseline characteristics were similar between arms. Patients had a mean age of 55.7 (SD14) years. At two years, 83.1% of the patients were alive and disease free in the ketorolac vs. 89.7% in the placebo arm (HR: 1.23; 95%CI: 0.65-2.31) and, respectively, 96.8% vs. 98.1% were alive (HR: 1.09; 95%CI: 0.34-3.51).ConclusionsA single administration of 30 mg of ketorolac tromethamine before surgery does not increase disease-free survival in high risk breast cancer patients. Overall survival difference between ketorolac tromethamine group and placebo group was not statistically significant. The study was however underpowered because of lower recurrence rates than initially anticipated. No safety concerns were observed.Trial registrationClinicalTrials.gov NCT01806259.

Mangrove forests are valuable ecosystems, but their extent and diversity are increasingly threatened by sea-level rise and anthropogenic pressures. Here we develop a bio-morphodynamic model that captures the interaction between multiple mangrove species and hydro-sedimentary processes across a dynamic coastal profile. Numerical experiments are conducted to elucidate the response of mangrove assemblages under a range of sea-level rise and sediment supply conditions, both in the absence and presence of anthropogenic barriers impeding inland migration. We find that mangrove coverage can increase despite sea-level rise if sediment supply is sufficient and landward accommodation space is available. Tidal barriers are mainly detrimental to mangrove coverage and result in species loss. Importantly, we show that bio-morphodynamic feedbacks can cause spatio-temporal variations in sediment delivery across the forest, leading to upper-forest sediment starvation and reduced deposition despite extended inundation. As such, bio-morphodynamic feedbacks can decouple accretion rates from inundation time, altering mangrove habitat conditions and causing mangrove diversity loss even when total forest coverage remains constant or is increasing. A further examination of bio-morphodynamic feedback strength reveals that vegetation-induced flow resistance linked to mangrove root density is a major factor steering the inundation-accretion decoupling and as such species distribution. Our findings have important implications for ecosystem vulnerability assessments, which should account for the interactions between bio-morphodynamics and mangrove diversity when evaluating the impacts of sea-level rise on species assemblages.

Whole-Body Magnetic Resonance Imaging (WB-MRI) is increasingly used for metastatic screening in oncology. This prospective single center study assesses the diagnostic value of WB-MRI including diffusion weighted imaging (DWI) and identifies the sufficient protocol for metastatic lymph node detection in patients with testicular germ cell cancer (TGCC). Forty-three patients underwent contrast enhanced thoraco-abdominopelvic CT (TAP-CT) and WB-MRI with DWI for metastatic lymph node screening. Two independent readers reviewed CTs and WB-MRIs. The diagnostic performance of different imaging protocols (CT, complete WB-MRI, T1W + DWI, T2W + DWI), the agreement between these protocols and the reference standard, the reproducibility of findings and the image quality (Signal and contrast to Noise Ratios, Likert scale) were studied. Reproducibility was very good regardless of both lesion locations (retroperitoneal vs distant lymph nodes, other lesions) and the reader. Diagnostic accuracy of MRI was ≥95% (regardless of the locations and imaging protocol); accuracy of CT was ≥93%. There was a strict overlap of 95% CIs associated with this accuracy between complete WB-MRI, T1W + DWI and T2W + DWI, regardless of the reader. Higher Likert score and SNR were observed for DWI, followed by T2W and T1W sequences. In conclusion, a fast WB-MRI protocol including T2W and DWI is a sufficient, accurate, non-irradiating alternative to TAP-CT for metastatic lymph node screening in TGCC.

Abstract Currently little is known about structure-function mappings in the human subcortex. Here we present a large-scale automated meta-analysis on the literature to understand the structure-function mapping in the human subcortex. The results provide converging evidence into unique large scale structure-function mappings of the human subcortex based on their functional and anatomical similarity.

The notion of "mixtures" has become pervasive in behavioral and cognitive sciences, due to the success of dual-process theories of cognition. However, providing support for such dual-process theories is not trivial, as it crucially requires properties in the data that are specific to mixture of cognitive processes. In theory, one such property could be the fixed-point property of binary mixture data, applied-for instance- to response times. In that case, the fixed-point property entails that response time distributions obtained in an experiment in which the mixture proportion is manipulated would have a common density point. In the current article, we discuss the application of the fixed-point property and identify three boundary conditions under which the fixed-point property will not be interpretable. In Boundary condition 1, a finding in support of the fixed-point will be mute because of a lack of difference between conditions. Boundary condition 2 refers to the case in which the extreme conditions are so different that a mixture may display bimodality. In this case, a mixture hypothesis is clearly supported, yet the fixed-point may not be found. In Boundary condition 3 the fixed-point may also not be present, yet a mixture might still exist but is occluded due to additional changes in behavior. Finding the fixed-property provides strong support for a dual-process account, yet the boundary conditions that we identify should be considered before making inferences about underlying psychological processes.

The environmental toxin bisphenol A (BPA) is a known mammalian hormone disrupter but its effects on plants have not been well established. The effect of BPA on gene expression in Arabidopsis thaliana was determined using microarray analysis and quantitative gene PCR. Many hormone responsive genes showed changes in expression after BPA treatment. BPA disrupted flowering by a mechanism that may involve disruption of auxin signaling. The results presented here indicate that BPA is a plant hormone disrupter.

An artificial neural network (ANN) was developed to predict the depth-integrated alongshore suspended sediment transport rate using 4 input variables (water depth, wave height and period, and alongshore velocity). The ANN was trained and validated using a dataset obtained on the intertidal beach of Egmond aan Zee, the Netherlands. Root-mean-square deviation between observations and predictions was calculated to show that, for this specific dataset, the ANN (εrms=0.43) outperforms the commonly used Bailard (1981) formula (εrms=1.63), even when this formula is calibrated (εrms=0.66). Because of correlations between input variables, the predictive quality of the ANN can be improved further by considering only 3 out of the 4 available input variables (εrms=0.39). Finally, we use the partial derivatives method to "open and lighten" the generated ANNs with the purpose of showing that, although specific to the dataset in question, they are not "black-box" type models and can be used to analyze the physical processes associated with alongshore sediment transport. In this case, the alongshore component of the velocity, by itself or in combination with other input variables, has the largest explanatory power. Moreover, the behaviour of the ANN indicates that predictions can be unphysical and therefore unreliable when the input lies outside the parameter space over which the ANN has been developed. Our approach of combining the strong predictive power of ANNs with "lightening" the black box and testing its sensitivity, demonstrates that the use of an ANN approach can result in the development of generalized models of suspended sediment transport.

To determine the prevalence, determinants, and potential clinical relevance of adherence with the Dutch dosing guideline in patients with impaired renal function at hospital discharge.Retrospective cohort study between January 2007 and July 2011.Academic teaching hospital in the Netherlands.Patients with an estimated glomerular filtration rate (eGFR) between 10-50 ml/min/1.73 m(2) at discharge and prescribed one or more medicines of which the dose is renal function dependent.The prevalence of adherence with the Dutch renal dosing guideline was investigated, and the influence of possible determinants, such as reporting the eGFR and severity of renal impairment (severe: eGFR

INTRODUCTION:The cholinergic anti-inflammatory pathway can downregulate inflammation via the release of acetylcholine (ACh) by the vagus nerve. This neurotransmitter binds to the α7 subunit of nicotinic acetylcholine receptors (α7nAChR), expressed on macrophages and other immune cells. We tested the pharmacological and functional profile of two novel compounds, PMP-311 and PMP-072 and investigated their role in modulating collagen-induced arthritis (CIA) in mice. METHODS:Both compounds were characterized with binding, electrophysiological, and pharmacokinetic studies. For in vivo efficacy studies in the CIA model the compounds were administered daily by oral gavage from day 20 till sacrifice at day 34. Disease progression was monitored by visual clinical scoring and measurement of paw swelling. Inflammation and joint destruction were examined by histology and radiology. RESULTS:Treatment with PMP-311 was effective in preventing disease onset, reducing clinical signs of arthritis, and reducing synovial inflammation and bone destruction. PMP-072 also showed a trend in arthritis reduction at all concentrations tested. The data showed that while both compounds bind to α7nAChR with high affinity, PMP-311 acts like a classical agonist of ion channel activity, and PMP-072 can actually act as an ion channel antagonist. Moreover, PMP-072 was clearly distinct from typical competitive antagonists, since it was able to act as a silent agonist. It synergizes with the allosteric modulator PNU-120596, and subsequently activates desensitized α7nAChR. However, PMP-072 was less efficacious than PMP-311 at both channel activation and desensitization, suggesting that both conducting and non-conducting states maybe of importance in driving an anti-inflammatory response. Finally, we found that the anti-arthritic effect can be observed despite limited penetration of the central nervous system. CONCLUSIONS:These data provide direct evidence that the α7nAChR in immune cells does not require typical ion channel activation to exert its antiinflammatory effects.

When multiple strategies can be used to solve a type of problem, the observed response time distributions are often mixtures of multiple underlying base distributions each representing one of these strategies. For the case of two possible strategies, the observed response time distributions obey the fixed-point property. That is, there exists one reaction time that has the same probability of being observed irrespective of the actual mixture proportion of each strategy. In this paper we discuss how to compute this fixed-point, and how to statistically assess the probability that indeed the observed response times are generated by two competing strategies. Accompanying this paper is a free R package that can be used to compute and test the presence or absence of the fixed-point property in response time data, allowing for easy to use tests of strategic behavior.

A recent study by van Ede et al. (2012) shows that the accuracy and reaction time in humans of tactile perceptual decisions are affected by an attentional cue via distinct cognitive and neural processes. These results are controversial as they undermine the notion that accuracy and reaction time are influenced by the same latent process that underlie the decision process. Typically, accumulation-to-bound models (like the drift diffusion model) can explain variability in both accuracy and reaction time by a change of a single parameter. To elaborate the findings of van Ede et al., we fitted the drift diffusion model to their behavioral data. Results show that both changes in accuracy and reaction time can be partly explained by an increase in the accumulation of sensory evidence (drift rate). In addition, a change in non-decision time is necessary to account for reaction time changes as well. These results provide a subtle explanation of how the underlying dynamics of the decision process might give rise to differences in both the speed and accuracy of perceptual tactile decisions. Furthermore, our analyses highlight the importance of applying a model-based approach, as the observed changes in the model parameters might be ecologically more valid, since they have an intuitive relationship with the neuronal processes underlying perceptual decision making.

BACKGROUND: Some studies suggest that the clinical parameter "amenorrhea" is insufficient to define the menopausal status of women treated with chemotherapy or tamoxifen. In this study, we investigated and compared the ovarian function defined either by clinical or biological parameters in pre-menopausal breast cancer patients treated with tamoxifen administered as adjuvant therapy. MATERIALS AND METHODS: Between 1999 and 2003, 138 premenopausal patients consecutively treated for early breast cancer were included. Sixty-eight received tamoxifen in monotherapy as the only adjuvant systemic treatment (Group I) and 70 were treated with tamoxifen after adjuvant chemotherapy (Group II). All patients had a confirmed premenopausal status based on clinical parameters and hormonal values at study entry. They were followed prospectively every 3 months for 3 years: menses data, physical examination and blood tests (LH, FSH, 17-beta-estradiol). Vaginal ultrasonography was carried out every 6 months. After 3 years, prospective evaluation was completed and monitoring of ovarian function was performed as usual in our institution (1x/year). All data were retrospectively evaluated in 2011. RESULTS: Three patients were excluded from the study in group I and 2 were excluded in group II. Patients were divided into 4 subgroups according to clinical data, i.e. menses patterns. These patterns were assessed by questionnaires. a: Regular menses (>10 cycles/year) b: Oligomenorrhea (5 to 9 cycles/year) c: Severe oligomenorrhea (1 to 4 cycles/year) d: Complete amenorrhea Estrogen levels did not appear to have any impact on disease-free survival rates after 3 or 8 years. FSH values were also documented and analyzed. They exhibited the same profile as estradiol values. CONCLUSIONS: Amenorrhea is an insufficient parameter to define menopausal status in patients receiving tamoxifen. Low estradiol levels must be coupled with other biological parameters to characterize endocrine status. These data are very important for the choice of endocrine therapy.