Hysteresis of tropical forests in the 21st century

Tropical forests modify the conditions they depend on through feedbacks at different spatial scales. These feedbacks shape the hysteresis (history-dependence) of tropical forests, thus controlling their resilience to deforestation and response to climate change. Here, we determine the emergent hysteresis from local-scale tipping points and regional-scale forest-rainfall feedbacks across the tropics under the recent climate and a severe climate-change scenario. By integrating remote sensing, a global hydrological model, and detailed atmospheric moisture tracking simulations, we find that forest-rainfall feedback expands the geographic range of possible forest distributions, especially in the Amazon. The Amazon forest could partially recover from complete deforestation, but may lose that resilience later this century. The Congo forest currently lacks resilience, but is predicted to gain it under climate change, whereas forests in Australasia are resilient under both current and future climates. Our results show how tropical forests shape their own distributions and create the climatic conditions that enable them

Effects of land use change on water-related ecosystem services in the Amazon Basin

Land use changes can affect many dimensions of the hydrological cycle which in turn affect the provisioning of water and its related ecosystem services to society. Modification at different spatial and temporal extents due to seasonal changes in water supply and land use intensities may compound and challenge our ability to predict the cascade of processes that lead to the supply of ecosystem services, i.e., ecosystem service cascade (ecosystem property, supply and service). In the Amazon basin, land use changes may affect water supply through modification of moisture recycling periodicity, and a quantification of its effects on other water-related ecosystem services, namely crop production and biodiversity, is scarce. We investigated this process using a moisture-tracking model, to show that upstream land use changes will affect the persistence of cropland in the Amazon arch of deforestation. We also show that biodiversity trait distributions affect the provision of water that maintains the cascades of moisture recycling, and different trait combinations enable regulation of atmospheric water regulation and land surface temperature. As trait combinations are a result of land use changes, the future of moisture recycling in the Amazon and its dependence downstream may require a better land use planning that incorporates these processes more explicitly

Gut-directed hypnotherapy in children with irritable bowel syndrome or functional abdominal pain (syndrome): A randomized controlled trial on self exercises at home using CD versus individual therapy by qualified therapists

Background: Irritable bowel syndrome (IBS) and functional abdominal pain (syndrome) (FAP(S)) are common pediatric disorders, characterized by chronic or recurrent abdominal pain. Treatment is challenging, especially in children with persisting symptoms. Gut-directed hypnotherapy (HT) performed by a therapist has been shown to be effective in these children, but is still unavailable to many children due to costs, a lack of qualified child-hypnotherapists and because it requires a significant investment of time by child and parent(s). Home-based hypnotherapy by means of exercises on CD has been shown effective as well, and has potential benefits, such as lower costs and less time investment. The aim of this randomized controlled trial (RCT) is to compare cost-effectiveness of individual HT performed by a qualified therapist with HT by means of CD recorded self-exercises at home in children with IBS or FAP(S).Methods/Design: 260 children, aged 8-18 years with IBS or FAP(S) according to Rome III criteria are included in this currently conducted RCT with a follow-up period of one year. Children are randomized to either 6 sessions of individual HT given by a qualified therapist over a 3-month period or HT through self-exercises at home with CD for 3 months.The primary outcome is the proportion of patients in which treatment is successful at the end of treatment and after one year follow-up. Treatment success is defined as at least 50% reduction in both abdominal pain frequency and intensity scores. Secondary outcomes include adequate relief, cost-effectiveness an

Exome sequencing in patient-parent trios suggests new candidate genes for early-onset primary sclerosing cholangitis

BACKGROUND & AIMS Primary sclerosing cholangitis (PSC) is a rare bile duct disease strongly associated with inflammatory bowel disease (IBD). Whole-exome sequencing (WES) has contributed to understanding the molecular basis of very early-onset IBD, but rare protein-altering genetic variants have not been identified for early-onset PSC. We performed WES in patients diagnosed with PSC METHODS In this multicentre study, WES was performed on 87 DNA samples from 29 patient-parent trios with early-onset PSC. We selected rare (minor allele frequency <2%) coding and splice-site variants that matched recessive (homozygous and compound heterozygous variants) and dominant (de novo) inheritance in the index patients. Variant pathogenicity was predicted by an in-house developed algorithm (GAVIN), and PSC-relevant variants were selected using gene expression data and gene function. RESULTS In 22 of 29 trios we identified at least 1 possibly pathogenic variant. We prioritized 36 genes, harbouring a total of 54 variants with predicted pathogenic effects. In 18 genes, we identified 36 compound heterozygous variants, whereas in the other 18 genes we identified 18 de novo variants. Twelve of 36 candidate risk genes are known to play a role in transmembrane transport, adaptive and innate immunity, and epithelial barrier function. CONCLUSIONS The 36 candidate genes for early-onset PSC need further verification in other patient cohorts and evaluation of gene function before a causal role can be attributed to its variants.Peer reviewe

Evaluation of exclusive enteral nutrition and corticosteroid induction treatment in new-onset moderate-to-severe luminal paediatric Crohn's disease

To induce remission in luminal paediatric Crohn's disease (CD), the ESPGHAN/ECCO guideline recommends treatment with exclusive enteral nutrition (EEN) or oral corticosteroids. In newly diagnosed moderate-to-severe paediatric CD patients, we determined the proportion of patients in which EEN or corticosteroids induced remission and maintained remission on azathioprine monotherapy. We included patients from the "TISKids" study assigned to the conventional treatment arm. Patients were aged 3-17 years and had new-onset, untreated luminal CD with weighted paediatric CD activity index (wPCDAI)> 40. Induction treatment consisted of EEN or oral corticosteroids; all received azathioprine maintenance treatment from start of treatment. The primary outcome of this study was endoscopic remission defined as a SES-CD score Conclusion: In children with moderate-to-severe newly diagnosed CD, induction treatment with EEN or CS regularly is insufficient to achieve endoscopic remission without treatment escalation at week 10.Peer reviewe

Diagnostic test strategies in children at increased risk of inflammatory bowel disease in primary care

In children with symptoms suggestive of inflammatory bowel disease (IBD) who present in primary care, the optimal test strategy for identifying those who require specialist care is unclear. We evaluated the following three test strategies to determine which was optimal for referring children with suspected IBD to specialist care: 1) alarm symptoms alone, 2) alarm symptoms plus c-reactive protein, and 3) alarm symptoms plus fecal calprotectin.A prospective cohort study was conducted, including children with chronic gastrointestinal symptoms referred to pediatric gastroenterology. Outcome was defined as IBD confirmed by endoscopy, or IBD ruled out by either endoscopy or unremarkable clinical 12 month follow-up with no indication for endoscopy. Test strategy probabilities were generated by logistic regression analyses and compared by area under the receiver operating characteristic curves (AUC) and decision curves.We included 90 children, of whom 17 (19%) had IBD (n = 65 from primary care physicians, n = 25 from general pediatricians). Adding fecal calprotectin to alarm symptoms increased the AUC significantly from 0.80 (0.67-0.92) to 0.97 (0.93-1.00), but adding c-reactive protein to alarm symptoms did not increase the AUC significantly (p > 0.05). Decision curves confirmed these patterns, showing that alarm symptoms combined with fecal calprotectin produced the diagnostic test strategy with the highest net benefit at reasonable threshold probabilities.In primary care, when children are identified as being at high risk for IBD, adding fecal calprotectin testing to alarm symptoms was the optimal strategy for improving risk stratification

Randomised clinical trial: First-line infliximab biosimilar is cost-effective compared to conventional treatment in paediatric Crohn's disease

Background: Data on cost-effectiveness of first-line infliximab in paediatric patients with Crohn's disease are limited. Since biologics are increasingly prescribed and accompanied by high costs, this knowledge gap needs to be addressed. Aim: To investigate the cost-effectiveness of first-line infliximab compared to conventional treatment in children with moderate-to-severe Crohn's disease. Methods: We included patients from the Top-down Infliximab Study in Kids with Crohn's disease randomised controlled trial. Children with newly diagnosed moderate-to-severe Crohn's disease were treated with azathioprine maintenance and either five induction infliximab (biosimilar) infusions or conventional induction treatment (exclusive enteral nutrition or corticosteroids). Direct healthcare consumption and costs were obtained per patient until week 104. This included data on outpatient hospital visits, hospital admissions, drug costs, endoscopies and surgeries. The primary health outcome was the odds ratio of being in clinical remission (weighted paediatric Crohn's disease activity index<12.5) during 104 weeks. Results: We included 89 patients (44 in the first-line infliximab group and 45 in the conventional treatment group). Mean direct healthcare costs per patient were €36,784 for first-line infliximab treatment and €36,874 for conventional treatment over 2 years (p = 0.981). The odds ratio of first-line infliximab versus conventional treatment to be in clinical remission over 104 weeks was 1.56 (95%CI 1.03–2.35, p = 0.036). Conclusions: First-line infliximab treatment resulted in higher odds of being in clinical remission without being more expensive, making it the dominant strategy over conventional treatment in the first 2 years after diagnosis in children with moderate-to-severe Crohn's disease. Trial registration number: NCT02517684

First-line treatment with infliximab versus conventional treatment in children with newly diagnosed moderate-to-severe Crohn's disease: An open-label multicentre randomised controlled trial

Objective: In newly diagnosed paediatric patients with moderate-to-severe Crohn's disease (CD), infliximab (IFX) is initiated once exclusive enteral nutrition (EEN), corticosteroid and immunomodulator therapies have failed. We aimed to investigate whether starting first-line IFX (FL-IFX) is more effective to achieve and maintain remission than conventional treatment. Design: In this multicentre open-label randomised controlled trial, untreated patients with a new diagnosis of CD (3-17 years old, weighted Paediatric CD Activity Index score (wPCDAI) >40) were assigned to groups that received five infusions of 5 mg/kg IFX at weeks 0, 2, 6, 14 and 22 (FL-IFX), or EEN or oral prednisolone (1 mg/kg, maximum 40 mg) (conventional). The primary outcome was clinical remission on azathioprine, defined as a wPCDAI <12.5 at week 52, without need for treatment escalation, using intention-to-treat analysis. Results: 100 patients were included, 50 in the FL-IFX group and 50 in the conventional group. Four patients did not receive treatment as per protocol. At week 10, a higher proportion of patients in the FL-IFX group than in the conventional group achieved clinical (59% vs 34%, respectively, p=0.021) and endoscopic remission (59% vs 17%, respectively, p=0.001). At week 52, the proportion of patients in clinical remission was no

Double cropping in the Amazon: its relation with moisture recycling

Land use and land cover change in the Amazon results in the loss and degradation of ecosystem services vital to human wellbeing. The land-use transitions from forest to grasslands and to croplands modify the hydrological cycle as the non-forest cover has lower evapotranspiration and increased runoff. The high rates of evapotranspiration of the Amazon forest drive the atmospheric moisture recycling system, which not only supports the forest itself but provides atmospheric moisture for precipitation downwind, important for agriculture, human consumption and hydropower across central Brazil. While deforestation reduces overall precipitation, deforestation has also been correlated with a delay in the wet season onset leading to a longer dry season. Therefore agriculture presents itself as an interesting conundrum, as it is the main driver of deforestation, it also acts as both the degrader and one of the main beneficiaries of the system. Recent advances in soybean double-cropping have increased agricultural productivity. However, as sowing is tightly coupled to the wet season onset, this strategy is dependent on a stable wet season onset. Here, we analyse the contribution of terrestrial evapotranspiration to precipitation during the early wet season. We employed a Lagrangian moisture transport model which connects moisture source (evapotranspiration) locations with moisture sink (precipitation) locations in the agriculture state of Mato Grosso, Brazil. We calculated the fraction of precipitation derived from moisture recycling as well as estimate the delay in wet season precipitation under a scenario without moisture recycling. Finally, using this moisture transport model we identified and mapped source areas that contribute to two existing double-cropping locations, one in the Amazon biome (North) and one in the Cerrado biome (South). We found that during the wet season transition, roughly 35% of the precipitation across Mato Grosso originates from moisture recycling. The fraction of moisture recycled precipitation is spatially correlated with latitude and longitude with the lowest fraction in the Northeast ≈20% and highest in the Southwest ≈60%. Both cropping locations showed a highly dispersed source area of precipitation. With 30% of recycled rainfall generated within 250 km of the precipitation location. The two cropping locations we analyzed shared a number of forest source areas highlighting their importance for moisture recycling. We found a 10-day delay in accumulated precipitation in our scenario without moisture recycling. This implies that double-cropping systems would become more uncertain as the sowing of soybean would most likely be delayed further into the year

Local moisture recycling across the globe

Changes in evaporation over land affect terrestrial precipitation via atmospheric moisture recycling and, consequently, freshwater availability. Although global moisture recycling at regional and continental scales is relatively well understood, the patterns of local moisture recycling and the main variables that impact it remain unknown. We calculate the local moisture recycling ratio (LMR) as the fraction of evaporated moisture that precipitates within a distance of 0.5° (typically 50 km) of its source, identify variables that correlate with it over land globally, and study its model dependency. We derive the seasonal and annual LMR using a 10-year climatology (2008-2017) of monthly averaged atmospheric moisture connections at a scale of 0.5° obtained from a Lagrangian atmospheric moisture tracking model. We find that, annually, an average of 1.7% (SD of 1.1%) of evaporated moisture returns as precipitation locally, although with large temporal and spatial variability, and the LMR peaks in summer and over wet and mountainous regions. Our results show that wetness, orography, latitude, convective available potential energy, wind speed, and total cloud cover correlate clearly with the LMR, indicating that wet regions with little wind and strong ascending air are particularly favourable for a high LMR. Finally, we find that spatial patterns of local recycling are consistent between different models, yet the magnitude of recycling varies. Our results can be used to study the impacts of evaporation changes on local precipitation, with implications for, for example, regreening and water management