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The infrastructure for chemical synthesis typically lies at either end of a spectrum: small-scale studies in ad hoc assemblies of glassware or large-scale production in capital-intensive custom reactors. Kitson et al. report a hybrid protocol that customizes a blueprint for synthesis of a target compound in a series of interconnected plastic modules, which can be assembled en masse by 3D printing (see the Perspective by Hornung). The approach, demonstrated for the commercial muscle relaxant baclofen, establishes a systematic workflow that is potentially amenable to automation: All that is necessary for synthesis and purification is the introduction of stock solutions and variation of temperature or pressure. Science , this issue p. 314 ; see also p. 273 A blueprint for chemical synthesis in plasticware offers an alternative to capital-intensive reactors for low-volume targets. Chemical manufacturing is often done at large facilities that require a sizable capital investment and then produce key compounds for a finite period. We present an approach to the manufacturing of fine chemicals and pharmaceuticals in a self-contained plastic reactionware device. The device was designed and constructed by using a chemical to computer-automated design (ChemCAD) approach that enables the translation of traditional bench-scale synthesis into a platform-independent digital code. This in turn guides production of a three-dimensional printed device that encloses the entire synthetic route internally via simple operations. We demonstrate the approach for the γ-aminobutyric acid receptor agonist, (±)-baclofen, establishing a concept that paves the way for the local manufacture of drugs outside of specialist facilities.

1. Forest ecosystems contain several climate-sensitive drivers that respond differentially to changes in climate and climate variability. For example, growth and regeneration processes are \"stand-scale\" drivers, while natural disturbances operate at \"landscape scale\". The relative contributions of these different scale drivers of change in ecosystems create great uncertainty when simulating potential responses of a forest to changes in climate. 2. Here, we assess those contributions, along with harvesting effects, on biomass (both total and of individual species) in the southern boreal forest of Canada under three climate scenarios (RCP 2.6, RCP 4.5 and RCP 8.5). 3. Projections were performed for three future 30-year time periods, in four study regions located on an east-west transect, using a forest landscape model (LANDIS- II), parameterized using a forest patch model (PICUS). Projected future impacts were assessed for each driver of change, and found to vary greatly among regions, impacts, species, future period and forcing scenarios. Fire, and stand-scale climate-induced had the strongest effects on forest vegetation, as well as on total and speafter 2050, particularly with the RCP 8.5 scenario. 4. The relative importance and trends in species-specific impacts varied, both spatially and according to the different RCP scenarios. Western regions were generally more sensitive to stand-scale climate-induced changes, whereas eastern regions were more sensitive to changes in fire regime. Our study also highlights the imporing the sensitivity of forest landscapes to a given driver of change in the context of increasing anthropogenic climate forcing. 5. Synthesis. Increases in fire activity, and direct impacts of climate change on fores growth and regeneration, will be the most important drivers of future changes in southern boreal forest landscapes.

Kawasaki disease is an acute self-limited vasculitis of unknown aetiology. The prognosis depends mainly on coronary damage. There is no consensus regarding optimal adjunctive therapeutics for refractory forms to treatment by intravenous immunoglobulins and corticosteroids. We report the case of an 18-month-old infant with refractory Kawasaki disease complicated by diffuse aneurysms of coronary arteries and successfully treated by anakinra with partial regression of coronary aneurysms

Accurate detection and quantification of unruptured intracranial aneurysms (UIAs) is important for rupture risk assessment and to allow an informed treatment decision to be made. Currently, 2D manual measures used to assess UIAs on Time-of-Flight magnetic resonance angiographies (TOF-MRAs) lack 3D information and there is substantial inter-observer variability for both aneurysm detection and assessment of aneurysm size and growth. 3D measures could be helpful to improve aneurysm detection and quantification but are time-consuming and would therefore benefit from a reliable automatic UIA detection and segmentation method. The Aneurysm Detection and segMentation (ADAM) challenge was organised in which methods for automatic UIA detection and segmentation were developed and submitted to be evaluated on a diverse clinical TOF-MRA dataset. A training set (113 cases with a total of 129 UIAs) was released, each case including a TOF-MRA, a structural MR image (T1, T2 or FLAIR), annotation of any present UIA(s) and the centre voxel of the UIA(s). A test set of 141 cases (with 153 UIAs) was used for evaluation. Two tasks were proposed: (1) detection and (2) segmentation of UIAs on TOF-MRAs. Teams developed and submitted containerised methods to be evaluated on the test set. Task 1 was evaluated using metrics of sensitivity and false positive count. Task 2 was evaluated using dice similarity coefficient, modified hausdorff distance (95th percentile) and volumetric similarity. For each task, a ranking was made based on the average of the metrics. In total, eleven teams participated in task 1 and nine of those teams participated in task 2. Task 1 was won by a method specifically designed for the detection task (i.e. not participating in task 2). Based on segmentation metrics, the top two methods for task 2 performed statistically significantly better than all other methods. The detection performance of the top-ranking methods was comparable to visual inspection for larger aneurysms. Segmentation performance of the top ranking method, after selection of true UIAs, was similar to interobserver performance. The ADAM challenge remains open for future submissions and improved submissions, with a live leaderboard to provide benchmarking for method developments at https://adam.isi.uu.nl/.

We aimed to evaluate the importance of modulations of within-tree carbon (C) allocation by water and low-temperature stress for the prediction of annual forest growth with a process-based model. A new C allocation scheme was implemented in the CASTANEA model that accounts for lagged and direct environmental controls of C allocation. Different approaches (static vs dynamic) to modelling C allocation were then compared in a model–data fusion procedure, using satellite-derived leaf production estimates and biometric measurements at c. 104 sites. The modelling of the environmental control of C allocation significantly improved the ability of CASTANEA to predict the spatial and year-to-year variability of aboveground forest growth along regional gradients. A significant effect of the previous year’s water stress on the C allocation to leaves and wood was reported. Our results also are consistent with a prominent role of the environmental modulation of sink demand in the wood growth of the studied species. Data available at large scales can inform forest models about the processes driving annual and seasonal C allocation. Our results call for a greater consideration of C allocation drivers, especially sink–demand fluctuations, for the simulations of current and future forest productivity with process-based models.

The aim of this study was to evaluate the frequency of neurodevelopmental disorders (NDD) in children with significant congenital heart disease (CHD) and to determine associated factors to NDD and frequency of follow-up in developmental therapies. Two hundred and ten children with significant CHD aged from 6 to 66 months were enrolled over a period of six months. The Ages & Stages Questionnaire Third Edition in French (ASQ-3) was used to assess neurodevelopmental domains. NDD were defined if cut-off scores were ≤ − 1SD. – 1SD corresponded to “Monitor” range: children with minor or emerging disorders; − 2SD corresponded to “Refer” range: children exhibiting neurodevelopmental delays. Forty children were in “Monitor” range and 86 in “Refer” range. NDD rate was 60.0% (n = 126, 95% CI, 53.4 to 66.6%). There was no difference regarding CHD severity (p = 0.99). Only the presence of non-cardiac disease (OR = 2.14; 95% CI, 1.11 to 4.20) was associated with NDD. Forty-six children with NDD had no developmental follow-up (among them 21 were in “Refer” range (10%)) despite this being available.Conclusion: Children with significant CHD are at risk for NDD regardless of CHD severity. Systematic and early monitoring in a specific care program is required. Barriers that prevent access of care must be identified.Trial registration: Neurodevelopmental Disorders in Children With Congenital Heart Disease. NeuroDis-CHD. NCT03360370. https://clinicaltrials.gov/ct2/show/NCT03360370What is Known:• Children with CHD are at risk for neurodevelopmental disorders and behavioural problems impacting their social adaptation, academic achievements and quality of personal and family life even in adulthood.What is New:• Children with CHD are at risk for neurodevelopmental disorders regardless of the complexity of the CHD.• Even with the availability of appropriate developmental services, children with CHD are not correctly followed, highlighting the need of a specific program of care for a better outcome. Local barriers that prevent access of care of those children must be identified.

The current paper describes a novel passive aeration simultaneous nitrification and denitrification (PASND) zeolite amended biofilm reactor that removes organic carbon and nitrogen from wastewater with low-energy consumption. Next to the ammonium oxidizing bacteria (AOB), this reactor contained naturally enriched glycogen accumulating organisms (GAOs) and zeolite powder to initially adsorb BOD (acetate) and ammonium (NH4+-N) from synthetic wastewater under anaerobic conditions. Draining of the treated wastewater exposed the biofilm directly to air enabling low-energy oxygen supply by passive aeration. This allowed the adsorbed ammonium to be oxidized by the AOB and the produced nitrite and nitrate to be reduced simultaneously by the GAOs using the adsorbed BOD (stored as PHAs) as carbon source. Overall, with an operation mode of 1 h anaerobic and 4 h aerobic phase, the nutrient removal efficiency after single treatment was about 94.3% for BOD and 72.2% for nitrogen (NH4+-N). As high-energy aeration of the bulk solution for oxygen supply is completely avoided, the energy requirement of the proposed PASND biofilm reactor can be theoretically cut down to more than 50% compared to the traditional activated sludge process.

Sone Essoh, W.; Onguene, R.; Ndongo, B.; Nshagali, G.; Colmet-Daage, A.; Marie, G.; Iroume, J.; Stieglitz, T.; Besck, F.; Efole Ewoukem, T.; Tomedi Eyango, M.; Etame, J., and Braun, J.J., 2023. Using GIS and multicriteria analysis to map flood risk areas of the Tongo Bassa River Basin (Douala, Cameroon). Journal of Coastal Research, 39(3), 531–543. Charlotte (North Carolina), ISSN 0749-0208. The present study aimed to map the areas at risk of flooding in the Tongo Bassa watershed (42 km2) located in the heart of the Cameroonian economic capital (Douala) in the tropical zone of Central Africa, more precisely in the Wouri Estuary, at the bottom of the Gulf of Guinea. Like most of the world's major cities, Douala is subject to floods. The methodological approach was to identify the flooding risk determinants in the area from an extensive literature review and field surveys and then analyze these factors and map areas at risk of flooding using the analytical hierarchy process approach coupled with the GIS environment. The results revealed that four parameters of the natural environment (elevation, drainage density, distance to the river, and land cover) were the factors that mainly influenced the phenomenon of flooding in the region. Three major classes of flood risk were highlighted: low risk, medium risk, and high risk. To validate the effectiveness of the flood risk map obtained, the flood points collected in the field were cross-checked for ground truth after a flood occurred in the watershed. This cross-check between the resulting map and the flood points using GIS tools showed a good representation of the flooded area. This result is quite interesting because the areas where the risk of flooding is high are consistent with those where flooding is most frequent. The presented results constitute a basic decision support tool for the management of flood zones by the public authorities and the decentralized territorial communities of the city of Douala.

New (a)biotic conditions resulting from climate change are expected to change disturbance dynamics, such as windthrow, forest fires, droughts, and insect outbreaks, and their interactions. These unprecedented natural disturbance dynamics might alter the capability of forest ecosystems to buffer atmospheric CO2 increases, potentially leading forests to transform from sinks into sources of CO2. This study aims to enhance the ORCHIDEE land surface model to study the impacts of climate change on the dynamics of the bark beetle, Ips typographus, and subsequent effects on forest functioning. The Ips typographus outbreak model is inspired by previous work from Temperli et al. (2013) for the LandClim landscape model. The new implementation of this model in ORCHIDEE r8627 accounts for key differences between ORCHIDEE and LandClim: (1) the coarser spatial resolution of ORCHIDEE; (2) the higher temporal resolution of ORCHIDEE; and (3) the pre-existing process representation of windthrow, drought, and forest structure in ORCHIDEE. Simulation experiments demonstrated the capability of ORCHIDEE to simulate a variety of post-disturbance forest dynamics observed in empirical studies. Through an array of simulation experiments across various climatic conditions and windthrow intensities, the model was tested for its sensitivity to climate, initial disturbance, and selected parameter values. The results of these tests indicated that with a single set of parameters, ORCHIDEE outputs spanned the range of observed dynamics. Additional tests highlighted the substantial impact of incorporating Ips typographus outbreaks on carbon dynamics. Notably, the study revealed that modeling abrupt mortality events as opposed to a continuous mortality framework provides new insights into the short-term carbon sequestration potential of forests under disturbance regimes by showing that the continuous mortality framework tends to overestimate the carbon sink capacity of forests in the 20- to 50-year range in ecosystems under high disturbance pressure compared to scenarios with abrupt mortality events. This model enhancement underscores the critical need to include disturbance dynamics in land surface models to refine predictions of forest carbon dynamics in a changing climate.