Production of a Natural Antibody to the Mouse Polyoma Virus Is a Multigenic Trait

MA/MyJ mice express a natural antibody to the highly oncogenic polyoma virus. C57BR/cdJ mice lack this antibody but mount an adaptive T-cell response to the virus. Analysis of F2 progeny of a cross between these strains reveals a pattern of inheritance of expression of the natural antibody involving two genes in an epistatic relationship

German pig farmers' perceived agency under different nitrogen policies

Agricultural nitrogen (N) emissions represent the most substantial N source in Germany. Even though multiple policies have been introduced at the EU and German national level to reduce agriculturally sourced reactive Nitrogen (N), Germany is exceeding the target of the government’s national sustainability strategy to limit N surpluses. To form a better view of the current N policy challenges, this paper seeks to identify what constrains family-managed pig farmers in Germany from adopting N-reduced farming practices. Our study applies a practice-based approach and reconstructs farmers’ practice and individual perception of the possible capability to change practices (perceived agency) through problem-centred interviews. The study identifies different ideal types of farmers based on their reported farming practices and perceived agency: The first type feeling overburdened and weary of the current requirements, the second type acting based on routine and incremental improvement efforts, and the third type adapting early and inventing. However, regarding the perceived agency to adopt N-reduced farming practices our results show that all three farmer types report only low to little agency. Based on the findings, the study identifies type-specific and type-spanning constraining factors. To resolve farmers’ perceived contradictions and inconsistencies which result in the unwillingness to accept further N reduction measures, we argue that policies need to address these factors. To enhance long-term paths for sustainable N-reduced farming practices, this study concludes that N policies need to shift towards outcome-oriented policies to create a collective and holistic understanding of the desired outcome while considering their embeddedness into regional and individual contexts.Wellcome Trust and The Rockefeller FoundationPeer Reviewe

The Noninvasive Urinary Polyomavirus Haufen Test Predicts BK Virus Nephropathy in Children After Hematopoietic Cell Transplantation: A Pilot Study

After hematopoietic cell transplantation (HCT), polyoma-BK virus is associated with hemorrhagic cystitis and also with polyomavirus nephropathy (PVN). However, the true burden of post-HCT PVN is unknown because kidney biopsies are avoided due to their bleeding risk. The novel, non-invasive urinary PV-Haufen test detects PVN in kidney transplant recipients with >95% positive/negative predictive values. We hypothesized that the detection of PV-Haufen in voided urine samples–a positive PV-Haufen test–was also clinically significant after HCT

Quantifying synergies and trade-offs in the global water-land-food-climate nexus using a multi-model scenario approach

The human-earth system is confronted with the challenge of providing a range of resources for a growing and more prosperous world population while simultaneously reducing environmental degradation. The sustainable development goals and the planetary boundaries define targets to manage this challenge. Many of these are linked to the land system, such as biodiversity, water, food, nutrients and climate, and are strongly interconnected. A key question is how measures can be designed in the context of multi-dimensional sustainability targets to exploit synergies. To address this, a nexus approach is adopted that acknowledges the interconnectedness between the important sub-systems water, land, food, and climate. This study quantifies synergies and trade-offs from ambitious interventions in different components of this water-land-fod-climate nexus at the global scale. For this purpose, a set of six harmonized scenarios is simulated with the model of agricultural production and its impact on the environment and Integrated model to assess the global environment models. The multi-model approach improves robustness of the results while shedding light on variations coming from different modelling approaches. Our results show that measures in the food component towards healthy diets with low meat consumption have synergies with all other nexus dimensions: Increased natural land improving terrestrial biodiversity (+4% to +8%), lower greenhouse gas emissions from land (−45% to −58%), reduced irrigation water withdrawals to protect or restore hydrological environmental flows (−3% to −24%), and reductions in nitrogen surpluses (−23% to −35%). Climate mitigation measures in line with the Paris Agreement have trade-offs with the water and food components of the nexus, as they adversely affect irrigation water withdrawals (+5% to +30% in 2050 compared to reference scenario) and food prices (+1% to +20%). The analysis of a scenario combining all measures reveals how certain measures are in conflict while others reinforce each other. This study provides an example of a nexus approach to scenario analysis providing input to the next generation of pathways aiming to achieve multiple dimensions of sustainable development.SHAPEHorizon 2020 Framework Programmehttp://dx.doi.org/10.13039/100010661Deutsche Bundesstiftung Umwelthttp://dx.doi.org/10.13039/100007636Peer Reviewe

German pig farmers’ perceived agency under different nitrogen policies

Agricultural nitrogen (N) emissions represent the most substantial N source in Germany. Even though multiple policies have been introduced at the EU and German national level to reduce agriculturally sourced reactive Nitrogen (N), Germany is exceeding the target of the government’s national sustainability strategy to limit N surpluses. To form a better view of the current N policy challenges, this paper seeks to identify what constrains family-managed pig farmers in Germany from adopting N-reduced farming practices. Our study applies a practice-based approach and reconstructs farmers’ practice and individual perception of the possible capability to change practices (perceived agency) through problem-centred interviews. The study identifies different ideal types of farmers based on their reported farming practices and perceived agency: The first type feeling overburdened and weary of the current requirements, the second type acting based on routine and incremental improvement efforts, and the third type adapting early and inventing. However, regarding the perceived agency to adopt N-reduced farming practices our results show that all three farmer types report only low to little agency. Based on the findings, the study identifies type-specific and type-spanning constraining factors. To resolve farmers’ perceived contradictions and inconsistencies which result in the unwillingness to accept further N reduction measures, we argue that policies need to address these factors. To enhance long-term paths for sustainable N-reduced farming practices, this study concludes that N policies need to shift towards outcome-oriented policies to create a collective and holistic understanding of the desired outcome while considering their embeddedness into regional and individual contexts

MAgPIE 4 – a modular open-source framework for modeling global land systems

The open-source modeling framework MAgPIE (Model of Agricultural Production and its Impact on the Environment) combines economic and biophysical approaches to simulate spatially explicit global scenarios of land use within the 21st century and the respective interactions with the environment. Besides various other projects, it was used to simulate marker scenarios of the Shared Socioeconomic Pathways (SSPs) and contributed substantially to multiple IPCC assessments. However, with growing scope and detail, the non-linear model has become increasingly complex, computationally intensive and non-transparent, requiring structured approaches to improve the development and evaluation of the model. Here, we provide an overview on version 4 of MAgPIE and how it addresses these issues of increasing complexity using new technical features: modular structure with exchangeable module implementations, flexible spatial resolution, in-code documentation, automatized code checking, model/output evaluation and open accessibility. Application examples provide insights into model evaluation, modular flexibility and region-specific analysis approaches. While this paper is focused on the general framework as such, the publication is accompanied by a detailed model documentation describing contents and equations, and by model evaluation documents giving insights into model performance for a broad range of variables. With the open-source release of the MAgPIE 4 framework, we hope to contribute to more transparent, reproducible and collaborative research in the field. Due to its modularity and spatial flexibility, it should provide a basis for a broad range of land-related research with economic or biophysical, global or regional focus

Efficacy and safety of indacaterol 150 μg once-daily in COPD: a double-blind, randomised, 12-week study

<p>Abstract</p> <p>Background</p> <p>Indacaterol is a novel, once-daily (o.d.) inhaled, long-acting <it>β</it>₂-agonist in development for chronic obstructive pulmonary disease (COPD). This 12-week, double-blind study compared the efficacy, safety, and tolerability of indacaterol to that of placebo in patients with moderate-to-severe COPD.</p> <p>Methods</p> <p>Efficacy variables included 24-h trough FEV₁(mean of 23 h 10 min and 23 h 45 min post-dose) at Week 12 (primary endpoint) and after Day 1, and the percentage of COPD days with poor control (i.e., worsening symptoms). Safety was assessed by adverse events (AEs), mean serum potassium and blood glucose, QTc (Fridericia), and vital signs.</p> <p>Results</p> <p>Patients were randomised (n = 416, mean age 63 years) to receive either indacaterol 150 <it>μ</it>g o.d. (n = 211) or placebo (n = 205) via a single-dose dry-powder inhaler; 87.5% completed the study. Trough FEV₁(LSM ± SEM) at Week 12 was 1.48 ± 0.018 L for indacaterol and 1.35 ± 0.019 L for placebo, a clinically relevant difference of 130 ± 24 mL (p < 0.001). Trough FEV₁after one dose was significantly higher with indacaterol than placebo (p < 0.001). Indacaterol demonstrated significantly higher peak FEV₁than placebo, both on Day 1 and at Week 12, with indacaterol-placebo differences (LSM ± SEM) of 190 ± 28 (p < 0.001) and 160 ± 28 mL (p < 0.001), respectively. Standardised AUC measurements for FEV₁(between 5 min and 4 h, 5 min and 1 h, and 1 and 4 h post-dose) at Week 12 were all significantly greater with indacaterol than placebo (p < 0.001), with LSM (± SEM) differences of 170 ± 24, 180 ± 24, and 170 ± 24 mL, respectively. Indacaterol significantly reduced the percentage of days of poor control versus placebo by 22.5% (p < 0.001) and was also associated with significantly reduced use of rescue medication (p < 0.001). The overall rates of AEs were comparable between the groups (indacaterol 49.3%, placebo 46.8%), with the most common AEs being COPD worsening (indacaterol 8.5%, placebo 12.2%) and cough (indacaterol 6.2%, placebo 7.3%). One patient died in the placebo group. Serum potassium and blood glucose levels did not differ significantly between the two groups, and no patient had QTc >500 ms.</p> <p>Conclusions</p> <p>Indacaterol 150 <it>μ</it>g o.d. provided clinically significant and sustained bronchodilation, reduced rescue medication use, and had a safety and tolerability profile similar to placebo.</p> <p>Trial registration</p> <p>NCT00624286</p

Bright emission from a random Raman laser

Random lasers are a developing class of light sources that utilize a highly disordered gain medium as opposed to a conventional optical cavity. Although traditional random lasers often have a relatively broad emission spectrum, a random laser that utilizes vibration transitions via Raman scattering allows for an extremely narrow bandwidth, on the order of 10 cm(−1). Here we demonstrate the first experimental evidence of lasing via a Raman interaction in a bulk three-dimensional random medium, with conversion efficiencies on the order of a few percent. Furthermore, Monte Carlo simulations are used to study the complex spatial and temporal dynamics of nonlinear processes in turbid media. In addition to providing a large signal, characteristic of the Raman medium, the random Raman laser offers us an entirely new tool for studying the dynamics of gain in a turbid medium