Life cycle modelling of environmental impacts of application of processed organic municipal solid waste on agricultural land (EASEWASTE)

A model capable of quantifying the potential environmental impacts of agricultural application of composted or anaerobically digested source-separated organic municipal solid waste (MSW) is presented. In addition to the direct impacts, the model accounts for savings by avoiding the production and use of commercial fertilizers. The model is part of a larger model, Environmental Assessment of Solid Waste Systems and Technology (EASEWASTE), developed as a decisionsupport model, focusing on assessment of alternative waste management options. The environmental impacts of the land application of processed organic waste are quantified by emission coefficients referring to the composition of the processed waste and related to specific crop rotation as well as soil type. The model contains several default parameters based on literature data, field experiments and modelling by the agro-ecosystem model, Daisy. All data can be modified by the user allowing application of the model to other situations. A case study including four scenarios was performed to illustrate the use of the model. One tonne of nitrogen in composted and anaerobically digested MSW was applied as fertilizer to loamy and sandy soil at a plant farm in western Denmark. Application of the processed organic waste mainly affected the environmental impact categories global warming (0.4–0.7 PE), acidification (–0.06 (saving)–1.6 PE), nutrient enrichment (–1.0 (saving)–3.1 PE), and toxicity. The main contributors to these categories were nitrous oxide formation (global warming), ammonia volatilization (acidification and nutrient enrichment), nitrate losses (nutrient enrichment and groundwater contamination), and heavy metal input to soil (toxicity potentials). The local agricultural conditions as well as the composition of the processed MSW showed large influence on the environmental impacts. A range of benefits, mainly related to improved soil quality from long-term application of the processed organic waste, could not be generally quantified with respect to the chosen life cycle assessment impact categories and were therefore not included in the model. These effects should be considered in conjunction with the results of the life cycle assessment

The evolution of multiple mating: Costs and benefits of polyandry to females and of polygyny to males

Polyandry is a paradox: why do females mate multiple times when a single ejaculate often provides enough sperm for lifetime egg production? Gowaty et al. addressed explanations for polyandry in Drosophila pseudoobscura from the perspective of hypotheses based on sex differences in costs of reproduction (CoR). Contrary to CoR, Gowaty et al. showed that (1) a single ejaculate was inadequate for lifetime egg production; (2) polyandry provided fitness benefits to females beyond provision of adequate sperm and (3) fitness benefits of polyandry were not offset by costs. Here, I discuss predictions of the ad hoc hypotheses of CoR and three alternative hypotheses to CoR to facilitate a discussion and further development of a strong inference approach to experiments on the adaptive significance of polyandry for females. Each of the hypotheses makes testable predictions; simultaneous tests of the predictions will provide a strong inference approach to understanding the adaptive significance of multiple mating. I describe a sex-symmetric experiment meant to evaluate variation in fitness among lifelong virgins (V); monogamous females and males with one copulation (MOC); monogamous females and males with multiple copulations (MMC); PAND, polyandrous females; and PGYN, polygynous males. Last, I recommend the study of many different species, while taking care in choice of study species and attention to the assumptions of specific hypotheses. I particularly urge the study of many more Drosophila species both in laboratory and the wild to understand the “nature of flies in nature,” where opportunities and constraints mold evolutionary responses

On the relative expressiveness of higher-order session processes

By integrating constructs from the λ-calculus and the π-calculus, in higher-order process calculi exchanged values may contain processes. This paper studies the relative expressiveness of HOπ, the higher-order π-calculus in which communications are governed by session types. Our main discovery is that HO, a subcalculus of HOπ which lacks name-passing and recursion, can serve as a new core calculus for session-typed higher-order concurrency. By exploring a new bisimulation for HO, we show that HO can encode HOπ fully abstractly (up to typed contextual equivalence) more precisely and efficiently than the first-order session π-calculus (π). Overall, under session types, HOπ, HO, and π are equally expressive; however, HOπ and HO are more tightly related than HOπ and π

New in vitro interaction-parasite reduction ratio assay for early derisk in clinical development of antimalarial combinations

The development and spread of drug-resistant phenotypes substantially threaten malaria control efforts. Combination therapies have the potential to minimize the risk of resistance development but require intensive preclinical studies to determine optimal combination and dosing regimens. To support the selection of new combinations, we developed a novel in vitro-in silico combination approach to help identify the pharmacodynamic interactions of the two antimalarial drugs in a combination which can be plugged into a pharmacokinetic/pharmacodynamic model built with human monotherapy parasitological data to predict the parasitological endpoints of the combination. This makes it possible to optimally select drug combinations and doses for the clinical development of antimalarials. With this assay, we successfully predicted the endpoints of two phase 2 clinical trials in patients with the artefenomel-piperaquine and artefenomel-ferroquine drug combinations. In addition, the predictive performance of our novel in vitro model was equivalent to that of the humanized mouse model outcome. Last, our more informative in vitro combination assay provided additional insights into the pharmacodynamic drug interactions compared to the in vivo systems, e.g., a concentration-dependent change in the maximum killing effect (Emax) and the concentration producing 50% of the killing maximum effect (EC50) of piperaquine or artefenomel or a directional reduction of the EC50 of ferroquine by artefenomel and a directional reduction of Emax of ferroquine by artefenomel. Overall, this novel in vitro-in silico-based technology will significantly improve and streamline the economic development of new drug combinations for malaria and potentially also in other therapeutic areas

Efficacy of FODMAP Elimination and Subsequent Blinded Placebo-Controlled Provocations in a Randomised Controlled Study in Patients with Ulcerative Colitis in Remission and Symptoms of Irritable Bowel Syndrome:A Feasibility Study

Background: Patients with inflammatory bowel disease (IBD) and symptoms of irritable bowel syndrome (IBS) may be intolerant to fermentable carbohydrates (FODMAPs). The aim of this study was to test the feasibility of eliminating and subsequently reintroducing FODMAPs in patients with IBS symptoms as part of the IBD manifestation and to compare the severity of IBS symptoms and pain, bloating and quality of life (QoL). Methods: An eight-week randomised open-label FODMAP elimination with double-blinded, crossover provocations of FODMAP and placebo. Diet patients were on a low-FODMAP diet for eight weeks with blinded two-week provocations after two and six weeks. Questionnaires, blood and stool samples were collected. Results: Patient enrolment was challenging. Nineteen participants were included in the study. Eliminating low FODMAP for two weeks resulted in significant decreases in pain and bloating scores (p 0.05). Conclusions: The results document the possibility of performing a randomised controlled study following the gold standard for testing food intolerance with blinding of the Low FODMAP diet. Recruitment of participants was challenging