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BACKGROUND/OBJECTIVES: Enteral feeding will induce remission in as many as 80–90% of compliant patients with active Crohn’s disease (CD), but its method of action remains uncertain. This study was designed to examine its effects on the colonic microbiome. METHODS/SUBJECTS: Healthy volunteers and patients with CD followed a regimen confined to enteral feeds alone for 1 or 2 weeks, respectively. Chemicals excreted on breath or in faeces were characterised at the start and at the end of the feeding period by gas chromatography/mass spectrometry. RESULTS: One week of feeding in healthy volunteers caused significant changes in stool colour and deterioration in breath odour, together with increased excretion of phenol and indoles on the breath. Feeding for 2 weeks in patients with CD produced significant improvements in symptoms and a decrease in the concentration of C-reactive protein. The faecal concentrations of microbial products, including short-chain fatty acids (SCFAs), and potentially toxic substances, including 1-propanol, 1-butanol and the methyl and ethyl esters of SCFAs, showed significant falls. CONCLUSIONS: A significant change occurs in the production of microbial metabolites after enteral feeding in both healthy volunteers and patients with CD. Many of those detected in CD are toxic and may feasibly lead to the immunological attack on the gut microbiota, which is characteristic of inflammatory bowel disease. The reduction in the production of such metabolites after enteral feeding may be the reason for its effectiveness in CD.

This article is oriented to the degradation of nickel in an ionic state at laboratory level from synthetic water made with nickel sulfate, using the electrocoagulation process with aluminum cathodes and modifying this process by the addition of the Fenton reagent, which results from the combination of hydrogen peroxide (H2O2) and ferrous sulfate (FeSO4) being this reagent a catalyst and oxo-coagulant agent, The efficiency of this reagent will be compared with the typical treatment with aluminum sulfate, which is a typical process based on ion exchange/coagulation at the same percentage concentrations as the Fenton reagent. For this purpose, the optimum conditions of the advanced electrocoagulation process were determined, which consisted of determining the concentrations of Fenton’s reagent at concentrations of 150 ppm, 300 ppm, and 450 ppm, in addition to the operating variables such as pH of 8 and 10, voltage of 17.5 V and 19 V and their reaction time, which were compared with aluminum sulfate at 300 ppm, 600 ppm, and 900 ppm. The results obtained with respect to the typical treatment were 0% nickel degradation. However, with the advanced oxidation treatment, an average reduction of 97.5% was found at the conditions of 19 V, pH 10, and Fenton 150 ppm in a time of 30 min.

The authors report interim results of the WHO Solidarity trial of four repurposed antiviral drugs — remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a — in patients hospitalized with Covid-19. Effects on overall mortality, initiation of ventilation, and duration of hospital stay are compared.

One hundred and ten Zika virus genomes from ten countries and territories involved in the Zika virus epidemic reveal rapid expansion of the epidemic within Brazil and multiple introductions to other regions. Zika epidemiology Three papers in this issue present a wealth of new Zika virus (ZIKV) genome sequences and further insights into the genetic epidemiology of ZIKV. Nathan Grubaugh et al . provide 39 new ZIKV genome sequences from infected patients and Aedes aegypti mosquitoes in Florida. Phylogenetic analysis suggests that the virus has been introduced on multiple separate occasions, probably linked to travel from the Caribbean. They find a low probability of long-term persistence of ZIKV transmission chains within Florida, suggesting that the potential for future ZIKV outbreaks there will depend on transmission dynamics in the Americas. Nuno Faria et al . and Hayden Metsky et al . reconstruct the spread of ZIKV in Brazil and the Americas. Faria et al . provide 54 new ZIKV genomes, several sequenced in real time in a mobile genomics laboratory. They trace the spatial origins and spread of ZIKV in Brazil and the Americas and date the timing of the international spread of ZIKV from Brazil. They find that northeast Brazil had a crucial role in the establishment of the epidemic and the spread of the virus within Brazil and the Americas. Metsky et al . generate 110 ZIKV genomes from clinical and mosquito samples from ten regions. They also see rapid expansion of the epidemic within Brazil and multiple introductions to other geographic areas. In agreement with Faria et al ., they find that ZIKV circulated unobserved for many months before transmission was detected. Metsky et al . additionally describe ZIKV evolution and discuss how the accumulation of mutations might affect the performance of diagnostic tests in the future. Although the recent Zika virus (ZIKV) epidemic in the Americas and its link to birth defects have attracted a great deal of attention 1 , 2 , much remains unknown about ZIKV disease epidemiology and ZIKV evolution, in part owing to a lack of genomic data. Here we address this gap in knowledge by using multiple sequencing approaches to generate 110 ZIKV genomes from clinical and mosquito samples from 10 countries and territories, greatly expanding the observed viral genetic diversity from this outbreak. We analysed the timing and patterns of introductions into distinct geographic regions; our phylogenetic evidence suggests rapid expansion of the outbreak in Brazil and multiple introductions of outbreak strains into Puerto Rico, Honduras, Colombia, other Caribbean islands, and the continental United States. We find that ZIKV circulated undetected in multiple regions for many months before the first locally transmitted cases were confirmed, highlighting the importance of surveillance of viral infections. We identify mutations with possible functional implications for ZIKV biology and pathogenesis, as well as those that might be relevant to the effectiveness of diagnostic tests.

Consideration of soil as a living ecosystem offers the potential for innovative and sustainable solutions to geotechnical problems. This is a new paradigm for many in geotechnical engineering. Realising the potential of this paradigm requires a multidisciplinary approach that embraces biology and geochemistry to develop techniques for beneficial ground modification. This paper assesses the progress, opportunities, and challenges in this emerging field. Biomediated geochemical processes, which consist of a geochemical reaction regulated by subsurface microbiology, currently being explored include mineral precipitation, gas generation, biofilm formation and biopolymer generation. For each of these processes, subsurface microbial processes are employed to create an environment conducive to the desired geochemical reactions among the minerals, organic matter, pore fluids, and gases that constitute soil. Geotechnical applications currently being explored include cementation of sands to enhance bearing capacity and liquefaction resistance, sequestration of carbon, soil erosion control, groundwater flow control, and remediation of soil and groundwater impacted by metals and radionuclides. Challenges in biomediated ground modification include upscaling processes from the laboratory to the field, in situ monitoring of reactions, reaction products and properties, developing integrated biogeochemical and geotechnical models, management of treatment by-products, establishing the durability and longevity/reversibility of the process, and education of engineers and researchers.

Despite newly approved treatments, metastatic melanoma remains a life-threatening condition. We aimed to evaluate the efficacy of the MAGE-A3 immunotherapeutic in patients with stage IIIB or IIIC melanoma in the adjuvant setting. DERMA was a phase 3, double-blind, randomised, placebo-controlled trial done in 31 countries and 263 centres. Eligible patients were 18 years or older and had histologically proven, completely resected, stage IIIB or IIIC, MAGE-A3-positive cutaneous melanoma with macroscopic lymph node involvement and an Eastern Cooperative Oncology Group performance score of 0 or 1. Randomisation and treatment allocation at the investigator sites were done centrally via the internet. We randomly assigned patients (2:1) to receive up to 13 intramuscular injections of recombinant MAGE-A3 with AS15 immunostimulant (MAGE-A3 immunotherapeutic; 300 μg MAGE-A3 antigen plus 420 μg CpG 7909 reconstituted in AS01B to a total volume of 0·5 mL), or placebo, over a 27-month period: five doses at 3-weekly intervals, followed by eight doses at 12-weekly intervals. The co-primary outcomes were disease-free survival in the overall population and in patients with a potentially predictive gene signature (GS-positive) identified previously and validated here via an adaptive signature design. The final analyses included all patients who had received at least one dose of study treatment; analyses for efficacy were in the as-randomised population and for safety were in the as-treated population. This trial is registered with ClinicalTrials.gov, number NCT00796445. Between Dec 1, 2008, and Sept 19, 2011, 3914 patients were screened, 1391 randomly assigned, and 1345 started treatment (n=895 for MAGE-A3 and n=450 for placebo). At final analysis (data cutoff May 23, 2013), median follow-up was 28·0 months [IQR 23·3–35·5] in the MAGE-A3 group and 28·1 months [23·7–36·9] in the placebo group. Median disease-free survival was 11·0 months (95% CI 10·0–11·9) in the MAGE-A3 group and 11·2 months (8·6–14·1) in the placebo group (hazard ratio [HR] 1·01, 0·88–1·17, p=0·86). In the GS-positive population, median disease-free survival was 9·9 months (95% CI 5·7–17·6) in the MAGE-A3 group and 11·6 months (5·6–22·3) in the placebo group (HR 1·11, 0·83–1·49, p=0·48). Within the first 31 days of treatment, adverse events of grade 3 or worse were reported by 126 (14%) of 894 patients in the MAGE-A3 group and 56 (12%) of 450 patients in the placebo group, treatment-related adverse events of grade 3 or worse by 36 (4%) patients given MAGE-A3 vs six (1%) patients given placebo, and at least one serious adverse event by 14% of patients in both groups (129 patients given MAGE-A3 and 64 patients given placebo). The most common adverse events of grade 3 or worse were neoplasms (33 [4%] patients in the MAGE-A3 group vs 17 [4%] patients in the placebo group), general disorders and administration site conditions (25 [3%] for MAGE-A3 vs four [<1%] for placebo) and infections and infestations (17 [2%] for MAGE-A3 vs seven [2%] for placebo). No deaths were related to treatment. An antigen-specific immunotherapeutic alone was not efficacious in this clinical setting. Based on these findings, development of the MAGE-A3 immunotherapeutic for use in melanoma has been stopped. GlaxoSmithKline Biologicals SA.

Given that few ecosystems on the Earth have been unaffected by humans, restoring them holds great promise for stemming the biodiversity crisis and ensuring ecosystem services are provided to humanity. Nonetheless, few studies have documented the recovery of ecosystems globally or the rates at which ecosystems recover. Even fewer have addressed the added benefit of actively restoring ecosystems versus allowing them to recover without human intervention following the cessation of a disturbance. Our meta-analysis of 400 studies worldwide that document recovery from large-scale disturbances, such as oil spills, agriculture and logging, suggests that though ecosystems are progressing towards recovery following disturbances, they rarely recover completely. This result reinforces conservation of intact ecosystems as a key strategy for protecting biodiversity. Recovery rates slowed down with time since the disturbance ended, suggesting that the final stages of recovery are the most challenging to achieve. Active restoration did not result in faster or more complete recovery than simply ending the disturbances ecosystems face. Our results on the added benefit of restoration must be interpreted cautiously, because few studies directly compared different restoration actions in the same location after the same disturbance. The lack of consistent value added of active restoration following disturbance suggests that passive recovery should be considered as a first option; if recovery is slow, then active restoration actions should be better tailored to overcome specific obstacles to recovery and achieve restoration goals. We call for a more strategic investment of limited restoration resources into innovative collaborative efforts between scientists, local communities and practitioners to develop restoration techniques that are ecologically, economically and socially viable.

The blowout of the Macondo oil well in the Gulf of Mexico in April 2010 injected up to 500,000 tonnes of natural gas, mainly methane, into the deep sea. Spatially extensive measurements of methane dynamics in the months following the spill reveal a rapid rise and fall in the microbial consumption of methane. The blowout of the Macondo oil well in the Gulf of Mexico in April 2010 injected up to 500,000 tonnes of natural gas, mainly methane, into the deep sea 1 . Most of the methane released was thought to have been consumed by marine microbes between July and August 2010 2 , 3 . Here, we report spatially extensive measurements of methane concentrations and oxidation rates in the nine months following the spill. We show that although gas-rich deepwater plumes were a short-lived feature, water column concentrations of methane remained above background levels throughout the rest of the year. Rates of microbial methane oxidation peaked in the deepwater plumes in May and early June, coincident with a rapid rise in the abundance of known and new methane-oxidizing microbes. At this time, rates of methane oxidation reached up to 5,900 nmol l −1 d −1 —the highest rates documented in the global pelagic ocean before the blowout 4 . Rates of methane oxidation fell to less than 50 nmol l −1 d −1 in late June, and continued to decline throughout the remainder of the year. We suggest the precipitous drop in methane consumption in late June, despite the persistence of methane in the water column, underscores the important role that physiological and environmental factors play in constraining the activity of methane-oxidizing bacteria in the Gulf of Mexico.

An improved understanding of present-day climate variability and change relies on high-quality data sets from the past 2 millennia. Global efforts to model regional climate modes are in the process of being validated against, and integrated with, records of past vegetation change. For South America, however, the full potential of vegetation records for evaluating and improving climate models has hitherto not been sufficiently acknowledged due to an absence of information on the spatial and temporal coverage of study sites. This paper therefore serves as a guide to high-quality pollen records that capture environmental variability during the last 2 millennia. We identify 60 vegetation (pollen) records from across South America which satisfy geochronological requirements set out for climate modelling, and we discuss their sensitivity to the spatial signature of climate modes throughout the continent. Diverse patterns of vegetation response to climate change are observed, with more similar patterns of change in the lowlands and varying intensity and direction of responses in the highlands. Pollen records display local-scale responses to climate modes; thus, it is necessary to understand how vegetation–climate interactions might diverge under variable settings. We provide a qualitative translation from pollen metrics to climate variables. Additionally, pollen is an excellent indicator of human impact through time. We discuss evidence for human land use in pollen records and provide an overview considered useful for archaeological hypothesis testing and important in distinguishing natural from anthropogenically driven vegetation change. We stress the need for the palynological community to be more familiar with climate variability patterns to correctly attribute the potential causes of observed vegetation dynamics. This manuscript forms part of the wider LOng-Term multi-proxy climate REconstructions and Dynamics in South America – 2k initiative that provides the ideal framework for the integration of the various palaeoclimatic subdisciplines and palaeo-science, thereby jump-starting and fostering multidisciplinary research into environmental change on centennial and millennial timescales.

Ecosystem recovery from anthropogenic disturbances, either without human intervention or assisted by ecological restoration, is increasingly occurring worldwide. As ecosystems progress through recovery, it is important to estimate any resulting deficit in biodiversity and functions. Here we use data from 3,035 sampling plots worldwide, to quantify the interim reduction of biodiversity and functions occurring during the recovery process (that is, the 'recovery debt'). Compared with reference levels, recovering ecosystems run annual deficits of 46-51% for organism abundance, 27-33% for species diversity, 32-42% for carbon cycling and 31-41% for nitrogen cycling. Our results are consistent across biomes but not across degrading factors. Our results suggest that recovering and restored ecosystems have less abundance, diversity and cycling of carbon and nitrogen than 'undisturbed' ecosystems, and that even if complete recovery is reached, an interim recovery debt will accumulate. Under such circumstances, increasing the quantity of less-functional ecosystems through ecological restoration and offsetting are inadequate alternatives to ecosystem protection.