Climate-controlled root zone parameters show potential to improve water flux simulations by land surface models

The root zone storage capacity (Sr) is the maximum volume of water in the subsurface that can potentially be accessed by vegetation for transpiration. It influences the seasonality of transpiration as well as fast and slow runoff processes. Many studies have shown that Sr is heterogeneous as controlled by local climate conditions, which affect vegetation strategies in sizing their root system able to support plant growth and to prevent water shortages. Root zone parameterization in most land surface models does not account for this climate control on root development and is based on lookup tables that prescribe the same root zone parameters worldwide for each vegetation class. These lookup tables are obtained from measurements of rooting structure that are scarce and hardly representative of the ecosystem scale. The objective of this research is to quantify and evaluate the effects of a climate-controlled representation of Sr on the water fluxes modeled by the Hydrology Tiled ECMWF Scheme for Surface Exchanges over Land (HTESSEL) land surface model. Climate-controlled Sr is estimated here with the “memory method” (MM) in which Sr is derived from the vegetation's memory of past root zone water storage deficits. Sr,MM is estimated for 15 river catchments over Australia across three contrasting climate regions: tropical, temperate and Mediterranean. Suitable representations of Sr,MM are implemented in an improved version of HTESSEL (Moisture Depth – MD) by accordingly modifying the soil depths to obtain a model Sr,MD that matches Sr,MM in the 15 catchments. In the control version of HTESSEL (CTR), Sr,CTR is larger than Sr,MM in 14 out of 15 catchments. Furthermore, the variability among the individual catchments of Sr,MM (117–722 mm) is considerably larger than of Sr,CTR (491–725 mm). The climate-controlled representation of Sr in the MD version results in a significant and consistent improvement of the modeled monthly seasonal climatology (1975–2010) and interannual anomalies of river discharge compared with observations. However, the effects on biases in long-term annual mean river discharge are small and mixed. The modeled monthly seasonal climatology of the catchment discharge improved in MD compared to CTR: the correlation with observations increased significantly from 0.84 to 0.90 in tropical catchments, from 0.74 to 0.86 in temperate catchments and from 0.86 to 0.96 in Mediterranean catchments. Correspondingly, the correlations of the interannual discharge anomalies improve significantly in MD from 0.74 to 0.78 in tropical catchments, from 0.80 to 0.85 in temperate catchments and from 0.71 to 0.79 in Mediterranean catchments. The results indicate that the use of climate-controlled Sr,MM can significantly improve the timing of modeled discharge and, by extension, also evaporation fluxes in land surface models. On the other hand, the method has not been shown to significantly reduce long-term climatological model biases over the catchments considered for this study.</p

On the importance of cascading moisture recycling in South America

Continental moisture recycling is a crucial process of the South American climate system. In particular, evapotranspiration from the Amazon basin contributes substantially to precipitation regionally as well as over other remote regions such as the La Plata basin. Here we present an in-depth analysis of South American moisture recycling mechanisms. In particular, we quantify the importance of cascading moisture recycling (CMR), which describes moisture transport between two locations on the continent that involves re-evaporation cycles along the way. Using an Eulerian atmospheric moisture tracking model forced by a combination of several historical climate data sets, we were able to construct a complex network of moisture recycling for South America. Our results show that CMR contributes about 9–10% to the total precipitation over South America and 17–18% over the La Plata basin. CMR increases the fraction of total precipitation over the La Plata basin that originates from the Amazon basin from 18–23 to 24–29% during the wet season. We also show that the south-western part of the Amazon basin is not only a direct source of rainfall over the La Plata basin, but also a key intermediary region that distributes moisture originating from the entire Amazon basin towards the La Plata basin during the wet season. Our results suggest that land use change in this region might have a stronger impact on downwind rainfall than previously thought. Using complex network analysis techniques, we find the eastern side of the sub-tropical Andes to be a key region where CMR pathways are channeled. This study offers a better understanding of the interactions between the vegetation and the atmosphere on the water cycle, which is needed in a context of land use and climate change in South America

The 3^3He(e, e′'d)p Reaction in qω\omega-constant Kinematics

The cross section for the $^3$He(e, e$'$d)p reaction has been measured as a function of the missing momentum $p_m$ in q$\omega$ -constant kinematics at beam energies of 370 and 576 MeV for values of the three-momentum transfer $q$ of 412, 504 and 604 \mevc. The L(+TT), T and LT structure functions have been separated for $q$ = 412 and 504 \mevc. The data are compared to three-body Faddeev calculations, including meson-exchange currents (MEC), and to calculations based on a covariant diagrammatic expansion. The influence of final-state interactions and meson-exchange currents is discussed. The $p_m$-dependence of the data is reasonably well described by all calculations. However, the most advanced Faddeev calculations, which employ the AV18 nucleon-nucleon interaction and include MEC, overestimate the measured cross sections, especially the longitudinal part, and at the larger values of $q$. The diagrammatic approach gives a fair description of the cross section, but under(over)estimates the longitudinal (transverse) structure function.Comment: 17 pages, 7 figure

A prospective, randomized, open-label trial of 6-month versus 12-month dual antiplatelet therapy after drug-eluting stent implantation in ST-elevation myocardial infarction: Rationale and design of the \u201cDAPT-STEMI trial\u201d

Background The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention with second-generation drug eluting stents (DESs) is unclear. Because prolonged DAPT is associated with higher bleeding risk and health care costs, establishing optimal DAPT duration is of paramount importance. No other randomized controlled trials have evaluated the safety of shorter DAPT duration in ST-elevation myocardial infarction (STEMI) patients treated with second-generation DESs and latest P2Y12 platelet receptor inhibitors. Hypothesis Six months of DAPT after Resolute Integrity stent implantation in STEMI patients is not inferior to 12 months of DAPT in clinical outcomes. Study design The Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation In ST-elevation Myocardial Infarction (DAPT-STEMI) trial is a randomized, multicenter, international, open-label trial designed to examine the safety (noninferiority) of 6-month DAPT after Resolute Integrity stent implantation in STEMI patients compared with 12-month DAPT. Event-free patients on DAPT at 6month will be randomized (1:1 fashion) between single (aspirin only) versus DAPT for an additional 6 months and followed until 2 years after primary percutaneous coronary intervention. The primary end point is a patient-oriented composite endpoint of all-cause mortality, any myocardial infarction, any revascularization, stroke, and major bleeding (net adverse clinical events [NACE]) at 18 months after randomization. To achieve a power of 85% for a noninferiority limit of 1.66, a total of 1100 enrolled patients are required. Summary The DAPT-STEMI trial aims to assess in STEMI patients treated with second-generation DESs whether discontinuation of DAPT after 6 months of event-free survival is noninferior to routine 12-month DAPT

Introduction of a breast cancer care programme including ultra short hospital stay in 4 early adopter centres: framework for an implementation study

<p>Abstract</p> <p>Background</p> <p>Whereas ultra-short stay (day care or 24 hour hospitalisation) following breast cancer surgery was introduced in the US and Canada in the 1990s, it is not yet common practice in Europe. This paper describes the design of the MaDO study, which involves the implementation of ultra short stay admission for patients after breast cancer surgery, and evaluates whether the targets of the implementation strategy are reached. The ultra short stay programme and the applied implementation strategy will be evaluated from the economic perspective.</p> <p>Methods/design</p> <p>The MaDO study is a pre-post-controlled multi-centre study, that is performed in four hospitals in the Netherlands. It includes a pre and post measuring period of six months each with six months of implementation in between in at least 40 patients per hospital per measurement period.</p> <p>Primary outcome measure is the percentage of patients treated in ultra short stay. Secondary endpoints are the percentage of patients treated according to protocol, degree of involvement of home care nursing, quality of care from the patient's perspective, cost-effectiveness of the ultra short stay programme and cost-effectiveness of the implementation strategy. Quality of care will be measured by the QUOTE-breast cancer instrument, cost-effectiveness of the ultra short stay programme will be measured by means of the EuroQol (administered at four time-points) and a cost book for patients. Cost-effectiveness analysis will be performed from a societal perspective. Cost-effectiveness of the implementation strategy will be measured by determination of the costs of implementation activities.</p> <p>Discussion</p> <p>This study will reveal barriers and facilitators for implementation of the ultra short stay programme. Moreover, the results of the study will provide information about the cost-effectiveness of the ultra short stay programme and the implementation strategy.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN77253391.</p

Isotopic signatures reveal zinc cycling in the natural habitat of hyperaccumulator Dichapetalum gelonioides subspecies from Malaysian Borneo

Background: Some subspecies of Dichapetalum gelonioides are the only tropical woody zinc (Zn)-hyperaccumulator plants described so far and the first Zn hyperaccumulators identified to occur exclusively on non-Zn enriched 'normal' soils. The aim of this study was to investigate Zn cycling in the parent rock-soil-plant interface in the native habitats of hyperaccumulating Dichapetalum gelonioides subspecies (subsp. pilosum and subsp. sumatranum). We measured the Zn isotope ratios (δ66Zn) of Dichapetalum plant material, and associated soil and parent rock materials collected from Sabah (Malaysian Borneo). Results: We found enrichment in heavy Zn isotopes in the topsoil (δ66Zn 0.13 ‰) relative to deep soil (δ66Zn -0.15 ‰) and bedrock (δ66Zn -0.90 ‰). This finding suggests that both weathering and organic matter influenced the Zn isotope pattern in the soil-plant system, with leaf litter cycling contributing significantly to enriched heavier Zn in topsoil. Within the plant, the roots were enriched in heavy Zn isotopes (δ66Zn ~ 0.60 ‰) compared to mature leaves (δ66Zn ~ 0.30 ‰), which suggests highly expressed membrane transporters in these Dichapetalum subspecies preferentially transporting lighter Zn isotopes during root-to-shoot translocation. The shoots, mature leaves and phloem tissues were enriched in heavy Zn isotopes (δ66Zn 0.34–0.70 ‰) relative to young leaves (δ66Zn 0.25 ‰). Thisindicates that phloem sources are enriched in heavy Zn isotopes relative to phloem sinks, likely because of apoplastic retention and compartmentalization in the Dichapetalum subspecies. Conclusions: The findings of this study reveal Zn cycling in the rock-soil-plant continuum within the natural habitat of Zn hyperaccumulating subspecies of Dichapetalum gelonioides from Malaysian Borneo. This study broadens our understanding of the role of a tropical woody Zn hyperaccumulator plant in local Zn cycling, and highlights the important role of leaf litter recycling in the topsoil Zn budget. Within the plant, phloem plays key role in Zn accumulation and redistribution during growth and development. This study provides an improved understanding of the fate and behaviour of Zn in hyperaccumulator soil-plant systems, and these insights may be applied in the biofortification of crops with Zn.Antony van der Ent, Philip Nti Nkrumah, Mark G. M. Aarts, Alan J. M. Baker, Fien Degryse, Chris Wawryk, and Jason K. Kirb

Functional Restoration of CFTR Nonsense Mutations in Intestinal Organoids

Background: Pharmacotherapies for people with cystic fibrosis (pwCF) who have premature termination codons (PTCs) in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are under development. Thus far, clinical studies focused on compounds that induce translational readthrough (RT) at the mRNA PTC location. Recent studies using primary airway cells showed that PTC functional restoration can be achieved through combining compounds with multiple mode-of-actions. Here, we assessed induction of CFTR function in PTC-containing intestinal organoids using compounds targeting RT, nonsense mRNA mediated decay (NMD) and CFTR protein modulation. Methods: Rescue of PTC CFTR protein was assessed by forskolin-induced swelling of 12 intestinal organoid cultures carrying distinct PTC mutations. Effects of compounds on mRNA CFTR level was assessed by RT-qPCRs. Results: Whilst response varied between donors, significant rescue of CFTR function was achieved for most donors with the quintuple combination of a commercially available pharmacological equivalent of the RT compound (ELX-02-disulfate or ELX-02ds), NMD inhibitor SMG1i, correctors VX-445 and VX-661 and potentiator VX-770. The quintuple combination of pharmacotherapies reached swelling quantities higher than the mean swelling of three VX-809/VX-770-rescued F508del/F508del organoid cultures, indicating level of rescue is of clinical relevance as VX-770/VX-809-mediated F508del/F508del rescue in organoids correlate with substantial improvement of clinical outcome. Conclusions: Whilst variation in efficacy was observed between genotypes as well as within genotypes, the data suggests that strong pharmacological rescue of PTC requires a combination of drugs that target RT, NMD and protein function

CFTR Function Restoration upon Elexacaftor/Tezacaftor/Ivacaftor Treatment in Patient-Derived Intestinal Organoids with Rare CFTR Genotypes

Cystic fibrosis (CF) is caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. The combination of the CFTR modulators elexacaftor, tezacaftor, and ivacaftor (ETI) enables the effective rescue of CFTR function in people with the most prevalent F508del mutation. However, the functional restoration of rare CFTR variants remains unclear. Here, we use patient-derived intestinal organoids (PDIOs) to identify rare CFTR variants and potentially individuals with CF that might benefit from ETI. First, steady-state lumen area (SLA) measurements were taken to assess CFTR function and compare it to the level observed in healthy controls. Secondly, the forskolin-induced swelling (FIS) assay was performed to measure CFTR rescue within a lower function range, and to further compare it to ETI-mediated CFTR rescue in CFTR genotypes that have received market approval. ETI responses in 30 PDIOs harboring the F508del mutation served as reference for ETI responses of 22 PDIOs with genotypes that are not currently eligible for CFTR modulator treatment, following European Medicine Agency (EMA) and/or U.S. Food and Drug Administration (FDA) regulations. Our data expand previous datasets showing a correlation between in vitro CFTR rescue in organoids and corresponding in vivo ppFEV1 improvement upon a CFTR modulator treatment in published clinical trials, and suggests that the majority of individuals with rare CFTR variants could benefit from ETI. CFTR restoration was further confirmed on protein levels using Western blot. Our data support that CFTR function measurements in PDIOs with rare CFTR genotypes can help to select potential responders to ETI, and suggest that regulatory authorities need to consider providing access to treatment based on the principle of equality for people with CF who do not have access to treatment.</p

The effect of high dose inhaled corticosteroids on wheeze in infants after respiratory syncytial virus infection: randomised double blind placebo controlled trial

Objective To determine whether early initiated anti-inflammatory therapy with prolonged high dose inhaled glucocorticoids influences the occurrence and severity of recurrent wheeze after respiratory syncytial virus related lower respiratory tract infections