Infiltration from the pedon to global grid scales: an overview and outlook for land surface modelling

Infiltration in soils is a key process that partitions precipitation at the land surface in surface runoff and water that enters the soil profile. We reviewed the basic principles of water infiltration in soils and we analyzed approaches commonly used in Land Surface Models (LSMs) to quantify infiltration as well as its numerical implementation and sensitivity to model parameters. We reviewed methods to upscale infiltration from the point to the field, hill slope, and grid cell scale of LSMs. Despite the progress that has been made, upscaling of local scale infiltration processes to the grid scale used in LSMs is still far from being treated rigorously. We still lack a consistent theoretical framework to predict effective fluxes and parameters that control infiltration in LSMs. Our analysis shows, that there is a large variety in approaches used to estimate soil hydraulic properties. Novel, highly resolved soil information at higher resolutions than the grid scale of LSMs may help in better quantifying subgrid variability of key infiltration parameters. Currently, only a few land surface models consider the impact of soil structure on soil hydraulic properties. Finally, we identified several processes not yet considered in LSMs that are known to strongly influence infiltration. Especially, the impact of soil structure on infiltration requires further research. In order to tackle the above challenges and integrate current knowledge on soil processes affecting infiltration processes on land surface models, we advocate a stronger exchange and scientific interaction between the soil and the land surface modelling communities

Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue

Merkel Cell Carcinoma of the Skin: Deducing the Pattern of Spread from an International Aggregated Database of 949 Patients

(1) Background: It is controversial if Merkel cell carcinomas (MCCs) spread to lymph nodes or distant metastases (LNM/DM) first. (2) Methods: A total of 303 patients from six institutions (March 1982–February 2015) were combined with individual patient data from a PubMed search, totaling 949 patients. The primary outcome was recurrence patterns. (3) Results: (a) More patients presented with lymph node metastases (LNMs) than DMs at diagnosis: 17.9% (166 among the 929 patients with known staging) vs. 1.9% (18/929); (b) 310/929 (33.4%) developed lifetime DM, of whom 220/310 also developed LNM. The majority (133 patients) of patients were documented to have developed LNM before DM. (c) A shorter median time of 1.5 months (range: 0–47.0) from initial diagnosis to LNM, versus 8 months (range: 0–107.8) to DM, was also found. Another observation was that 2.4% (23/949) of patients with primary tumors ≤1 cm developed lifetime DM, with the smallest being 0.2 cm. (4) Conclusions: Three observations support the idea that prior LNM gives rise to subsequent DM as the main pathway of dissemination in MCC. This implies that patients with nodal metastases should be considered for adjuvant systemic therapy studies as an enriched population. Participation in clinical trials is strongly encouraged

Merkel-Cell Carcinoma: Local Recurrence Rate Versus Radiation Dose Study from a 949-Patient Database

(1) Background: Knowledge regarding the optimal radiotherapy dose for Merkel-cell carcinoma (MCC) remains limited. (2) Methods: Following a PubMed search, equivalent doses in 2 Gy fractions (Gy2) were compared. (3) Results: Of the 949 patients, 939 were evaluable, with 728 (77.5%) cases localized to the primary site and 171 irradiated without chemotherapy. The overall local recurrence rate (LRR) was 23% (40/171). After definitive radiotherapy with EQD2 < 50 Gy2 versus ≥50 Gy2, the LRRs were 23.1% (3/13) and 12.5% a(1/8), respectively (p = 0.0004). (4) Conclusions: For definitive radiotherapy, EQD2 < 50 Gy2 demonstrates a significantly higher LRR than ≥50 Gy2 (p = 0.0004). This study is clinically useful and unique with stratification by definitive/adjuvant settings and positive/negative resection margins. A future prospective multicenter study is needed to determine the optimal radiotherapy doses

Energy Gap of the Even-Denominator Fractional Quantum Hall State in Bilayer Graphene

Bernal bilayer graphene hosts even-denominator fractional quantum Hall states thought to be described by a Pfaffian wave function with non-Abelian quasiparticle excitations. Here, we report the quantitative determination of fractional quantum Hall energy gaps in bilayer graphene using both thermally activated transport and by direct measurement of the chemical potential. We find a transport activation gap of 5.1 K at B=12  T for a half filled N=1 Landau level, consistent with density matrix renormalization group calculations for the Pfaffian state. However, the measured thermodynamic gap of 11.6 K is smaller than theoretical expectations for the clean limit by approximately a factor of 2. We analyze the chemical potential data near fractional filling within a simplified model of a Wigner crystal of fractional quasiparticles with long-wavelength disorder, explaining this discrepancy. Our results quantitatively establish bilayer graphene as a robust platform for probing the non-Abelian anyons expected to arise as the elementary excitations of the even-denominator state

Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments.

International audienceSHANK genes code for scaffold proteins located at the post-synaptic density of glutamatergic synapses. In neurons, SHANK2 and SHANK3 have a positive effect on the induction and maturation of dendritic spines, whereas SHANK1 induces the enlargement of spine heads. Mutations in SHANK genes have been associated with autism spectrum disorders (ASD), but their prevalence and clinical relevance remain to be determined. Here, we performed a new screen and a meta-analysis of SHANK copy-number and coding-sequence variants in ASD. Copy-number variants were analyzed in 5,657 patients and 19,163 controls, coding-sequence variants were ascertained in 760 to 2,147 patients and 492 to 1,090 controls (depending on the gene), and, individuals carrying de novo or truncating SHANK mutations underwent an extensive clinical investigation. Copy-number variants and truncating mutations in SHANK genes were present in ∼1% of patients with ASD: mutations in SHANK1 were rare (0.04%) and present in males with normal IQ and autism; mutations in SHANK2 were present in 0.17% of patients with ASD and mild intellectual disability; mutations in SHANK3 were present in 0.69% of patients with ASD and up to 2.12% of the cases with moderate to profound intellectual disability. In summary, mutations of the SHANK genes were detected in the whole spectrum of autism with a gradient of severity in cognitive impairment. Given the rare frequency of SHANK1 and SHANK2 deleterious mutations, the clinical relevance of these genes remains to be ascertained. In contrast, the frequency and the penetrance of SHANK3 mutations in individuals with ASD and intellectual disability-more than 1 in 50-warrant its consideration for mutation screening in clinical practice

Scientific evidence on farming practices improving sustainable water management in agriculture

→ This brief reports the results of a systematic review on the effects of 34 farming practices on water management in agriculture (i.e. water use efficiency, water consumption, soil water retention, water quality and nutrients leaching and run-off). → The analysis identifies 10 farming practices that are potentially beneficial to reduce water use quantity and 13 for improving water quality, with a total of 15 farming practices that can enhance water management in agriculture. → The following farming practices have at least two positive effects: crop residue management, mulching, cover and catch crops, buffer strips and small wetlands, soil amendment with biochar, water-saving irrigation practices in flooded and non-flooded lands, grassland management, and no tillage and reduced tillage.JRC.D.5 - Food Securit

Quantifying the impact of sustainable farming practices on environment and climate

Agriculture plays a pivotal role in meeting global food demands and maintaining socio-economic stability. However, some agricultural practices may negatively contribute to environmental concerns such as greenhouse gas emissions, nutrient losses, and biodiversity decline, impacting climate change, water quality and quantity, and ecosystem functioning. In response, the European Commission (EC) fosters the integration of environmental sustainability within agricultural policy frameworks, including the Common Agricultural Policy (CAP). In this context, identifying sustainable farming practices is crucial for achieving the EU's sustainability objectives, in particular to assess the environmental and climate performance of the agricultural sector. To support this, we present in this report a comprehensive collection of coefficients quantifying the environmental impacts of farming practices. Focusing on greenhouse gas emissions, carbon sequestration, and nutrient losses, these coefficients are sourced from scientific articles, primarily meta-analyses, which have been reviewed through systematic literature analysis. They offer valuable insights into the effects of different agricultural management options, directly relevant to assess the likely impacts of CAP interventions on the environment and the climate. The report presents a collection of over 100 tables containing quantitative coefficients that assess the environmental impacts of 35 farming practices (ranging from single farming practices to cropping systems or conservation and restoration actions), offering clear links to specific scholar references, along with detailed contextual information. This work is part of the iMAP4agri project, commissioned by the EC's Directorate-General for Agriculture and Rural Development (DG AGRI) to the Joint Research Centre (JRC), drawing on experience from previous CAP periods and materials developed for the current policy cycle. By synthesizing existing meta-analyses and applying a systematic review framework, we ensure a robust and transparent approach that can be implemented within the time and data availability constraints of policymaking processes.JRC.D.5 - Food Securit

Budesonide Oral Suspension Improves Symptomatic, Endoscopic, and Histologic Parameters Compared With Placebo in Patients With Eosinophilic Esophagitis

BACKGROUND & AIMS: Pharmacologic treatment of eosinophilic esophagitis (EoE) is limited to off-label use of corticosteroids not optimized for esophageal delivery. We performed a randomized, controlled phase 2 trial to assess the ability of budesonide oral suspension (BOS), a novel muco-adherent topical steroid formulation, to reduce symptoms and esophageal eosinophilia in adolescents and adults with EoE. METHODS: In this multicenter, randomized, double-blind, placebo-controlled, parallel-group trial, 93 EoE patients between the ages of 11 and 40 years with dysphagia and active esophageal eosinophilia were randomized to receive either BOS 2 mg or placebo twice daily for 12 weeks. Co-primary outcomes were change in Dysphagia Symptom Questionnaire (DSQ) score from baseline, and proportion of patients with a histologic response (≤6 eosinophils/high-power field) after treatment. Endoscopic severity scores and safety parameters were assessed. RESULTS: At baseline, mean DSQ scores were 29.3 and 29.0, and mean peak eosinophil counts were 156 and 130 per hpf in the BOS and placebo groups, respectively. After treatment, DSQ scores were 15.0 and 21.5, and mean peak eosinophil counts were 39 and 113 per high-power field, respectively (P < .05 for all). For BOS vs placebo, change in DSQ score was -14.3 vs -7.5 (P = .0096), histologic response rates were 39% vs 3% (P < .0001), and change in endoscopic severity score was -3.8 vs 0.4 (P < .0001). Adverse events were similar between groups. CONCLUSIONS: Treatment with BOS was well tolerated in adolescent and young adult patients with EoE and resulted in improvement in symptomatic, endoscopic, and histologic parameters using validated outcome instruments. ClinicalTrials.gov ID NCT01642212