Biorefinery potential of sustainable municipal wastewater treatment using fast-growing willow.

The use of willow plantations can be a sustainable approach for treating primary municipal wastewater, potentially reducing both the environmental and economic burdens associated with conventional treatment. However, the impact of wastewater irrigation upon the willow biorefinery potential has not yet been established. To investigate this effect, three-year-old field grown willows were harvested from plots kept as either controls or irrigated with primary municipal wastewater effluent at 29.5 million L ha-1 yr-1. Biomass compositional analysis, ionic liquid pretreatment and enzymatic saccharification were assessed and differential abundance of persistent extractable phytochemicals was evaluated using untargeted metabolite profiling. Glucan significantly increased by 8% in wastewater treated trees, arabinose and galactose were significantly decreased by 8 and 29%, respectively, while xylose, mannose and lignin content were unaltered. Ionic liquid pretreatment and enzymatic saccharification efficiencies did not vary significantly, releasing >95% of the cell wall glucose and recovering 35% of the lignin. From a total of 213 phytochemical features, 83 were significantly depleted and 14 were significantly enriched due to wastewater irrigation, including flavonoids and lignan derivatives. Considered alongside increased biomass yield from wastewater irrigation (+200%), lignocellulosic bioenergy yields increased to 8.87 t glucose ha-1 yr-1 and 1.89 t ha-1 yr-1 recovered lignin, while net extractives yields increased to 1.48 t ha-1 yr-1, including phytochemicals of interest. The maintenance of glucose accessibility after low-cost ionic liquid pretreatment is promising evidence that sustainable lignocellulose bioenergy production can complement wastewater treatment. Untargeted metabolite assessment revealed some of the phytochemical toolkit employed by wastewater irrigated willows, including accumulation of flooding and salinity tolerance associated flavonoids glabraoside A and glabrene. The extractable phytochemicals underpin a novel high biomass phenotype in willow and, alongside lignocellulosic yields, could help enhance the economic feasibility of this clean wastewater treatment biotechnology through integration with sustainable biorefinery.

Reanalysis of the Mars500 experiment reveals common gut microbiome alterations in astronauts induced by long-duration confinement.

Maintaining astronaut health throughout long-duration spaceflight is essential to the feasibility of a manned mission to Mars. The ground-based Mars500 experiment investigated long-duration health by isolating six astronauts for 520 days, the longest controlled human confinement study conducted to date. After 520 days, astronauts had uniform strength and lean body mass losses, and increased fasting plasma glucose, calprotectin, and neutrophil levels characteristic of intestinal inflammation but previous analyses revealed no common significant changes in gut microbiota. This study reanalysed data from early (days 7-45) and late (days 420-520) faecal samples and identified 408 exact sequence variants (ESVs), including 213 shared by all astronauts. Thirty-two ESVs were significantly differentially abundant over time, including depletion of keystone resistant starch degrading, anti-inflammatory and insulin sensitivity-associated species, such as Faecalibacterium prausnitzii, Ruminococcus bromii, Blautia luti, Anaerostipes hadrus, Roseburia faecis, and Lactobacillus rogosae, and enrichment of yet-to-be-cultured bacteria. Additionally, the extraordinary experimental confinement allowed observation of microbiota potentially shared between astronauts and their habitat. Forty-nine species were shared, representing 49% and 12% of the human and environmental microbiome diversity, respectively. These findings reveal the microbiota which significantly altered in relative abundance throughout confinement, including species known to influence inflammation and host glucose homeostasis consistent with astronaut symptoms. Identification of microbiome alterations after 520 days of isolation represents a missing piece connecting Mars500 astronaut physiological studies. Knowledge of the impact of long-term confinement upon the human microbiome helps to improve our understanding of how humans interact with their habitats and is a valuable step forward towards enabling long-duration spaceflight.

High biomass yield increases in a primary effluent wastewater phytofiltration are associated to altered leaf morphology and stomatal size in Salix miyabeana.

Municipal wastewater treatment using willow 'phyto'-filtration has the potential for reduced environmental impact compared to conventional treatment practices. However, the physiological adaptations underpinning tolerance to high wastewater irrigation in willow are unknown. A one-hectare phytofiltration plantation established using the Salix miyabeana cultivar 'SX67' in Saint-Roch-de-l'Achigan, Quebec, Canada, tested the impact of unirrigated, potable water or two loads of primary effluent wastewater 19 and 30 ML ha-1 yr-1. A nitrogen load of 817 kg N ha-1 from wastewater did not increase soil pore water nitrogen concentrations beyond Quebec drinking water standards. The willow phytofiltration phenotype had increased leaf area (+106-142%) and leaf nitrogen (+94%) which were accompanied by significant increases in chlorophyll a + b content. Wastewater irrigated trees had higher stomatal sizes and a higher stomatal pore index, despite lower stomatal density, resulting in increased stomatal conductance (+42-78%). These developmental responses led to substantial increases in biomass yields of 56-207% and potable water controls revealed the nitrogen load to be necessary for the high productivity of 28-40 t ha-1 yr-1 in wastewater irrigated trees. Collectively, this study suggests phytofiltration plantations could treat primary effluent municipal wastewater at volumes of at least 19 million litres per hectare and benefit from increased yields of sustainable biomass over a two-year coppice cycle. Added-value cultivation practices, such as phytofiltration, have the potential to mitigate negative local and global environmental impact of wastewater treatment while providing valuable services and sustainable bioproducts.

Co-cropping with three phytoremediation crops influences rhizosphere microbiome community in contaminated soil.

Human industrial activities have left millions of hectares of land polluted with trace element metals and persistent organic pollutants (POPs) around the world. Although contaminated sites are environmentally damaging, high economic costs often discourage soil remediation efforts. Phytoremediation is a potential green technology solution but can be challenging due to the diversity of anthropogenic contaminants. Co-cropping could provide improved tolerance to diverse soil challenges by taking advantage of distinct crop capabilities. Co-cropping of three species with potentially complementary functions, Festuca arundinacea, Salix miyabeana and Medicago sativa, perform well on diversely contaminated soils. Here, rhizosphere microbiomes of each crop in monoculture and in all co-cropping combinations were compared using 16S rRNA gene amplification, sequencing and differential abundance analysis. The hyperaccumulating F. arundinacea rhizosphere microbiome included putative plant growth promoting bacteria (PGPB) and metal tolerance species, such as Rhizorhapis suberifaciens, Cellvibrio fibrivorans and Pseudomonas lini. The rhizosphere microbiome of the fast-growing tree S. miyabeana included diverse taxa involved in POP degradation, including the species Phenylobacterium panacis. The well-characterised nitrogen-fixing M. sativa microbiome species, Sinorhizobium meliloti, was identified alongside others involved in nutrient acquisition and putative yet-to-be-cultured Candidatus saccharibacteria (TM7-1 group). The majority of differentially abundant rhizosphere-associated bacterial species were maintained in co-cropping pairs, with pairs having higher numbers of differentially abundant taxa than monocultures in all cases. This was not the case when all three crops were co-cropped, where most host-specific bacterial species were not detected as differentially abundant, indicating the potential for reduced rhizosphere functionality. The crops cultivated in pairs here retained rhizosphere microbiome bacteria involved in these monoculture ecosystem services of plant growth promotion, POP tolerance and degradation, and improved nutrient acquisition. These findings provide a promising outlook of the potential for complementary co-cropping strategies for phytoremediation of the multifaceted anthropogenic pollution which can disastrously affect soils around the world.

Trees, fungi and bacteria: tripartite metatranscriptomics of a root microbiome responding to soil contamination.

BACKGROUND: One method for rejuvenating land polluted with anthropogenic contaminants is through phytoremediation, the reclamation of land through the cultivation of specific crops. The capacity for phytoremediation crops, such as Salix spp., to tolerate and even flourish in contaminated soils relies on a highly complex and predominantly cryptic interacting community of microbial life. METHODS: Here, Illumina HiSeq 2500 sequencing and de novo transcriptome assembly were used to observe gene expression in washed Salix purpurea cv. 'Fish Creek' roots from trees pot grown in petroleum hydrocarbon-contaminated or non-contaminated soil. All 189,849 assembled contigs were annotated without a priori assumption as to sequence origin and differential expression was assessed. RESULTS: The 839 contigs differentially expressed (DE) and annotated from S. purpurea revealed substantial increases in transcripts encoding abiotic stress response equipment, such as glutathione S-transferases, in roots of contaminated trees as well as the hallmarks of fungal interaction, such as SWEET2 (Sugars Will Eventually Be Exported Transporter). A total of 8252 DE transcripts were fungal in origin, with contamination conditions resulting in a community shift from Ascomycota to Basidiomycota genera. In response to contamination, 1745 Basidiomycota transcripts increased in abundance (the majority uniquely expressed in contaminated soil) including major monosaccharide transporter MST1, primary cell wall and lamella CAZy enzymes, and an ectomycorrhiza-upregulated exo-ß-1,3-glucanase (GH5). Additionally, 639 DE polycistronic transcripts from an uncharacterised Enterobacteriaceae species were uniformly in higher abundance in contamination conditions and comprised a wide spectrum of genes cryptic under laboratory conditions but considered putatively involved in eukaryotic interaction, biofilm formation and dioxygenase hydrocarbon degradation. CONCLUSIONS: Fungal gene expression, representing the majority of contigs assembled, suggests out-competition of white rot Ascomycota genera (dominated by Pyronema), a sometimes ectomycorrhizal (ECM) Ascomycota (Tuber) and ECM Basidiomycota (Hebeloma) by a poorly characterised putative ECM Basidiomycota due to contamination. Root and fungal expression involved transcripts encoding carbohydrate/amino acid (C/N) dialogue whereas bacterial gene expression included the apparatus necessary for biofilm interaction and direct reduction of contamination stress, a potential bacterial currency for a role in tripartite mutualism. Unmistakable within the metatranscriptome is the degree to which the landscape of rhizospheric biology, particularly the important but predominantly uncharacterised fungal genetics, is yet to be discovered.

Cost-effectiveness in Canada of azacitidine for the treatment of higher-risk myelodysplastic syndromes.

OBJECTIVE: Our goal was to determine the economic value of azacitidine in Canada compared with conventional care regimens (ccrs), including best supportive care (bsc) and low- or standard-dose chemotherapy plus bsc in the treatment of higher-risk myelodysplastic syndromes (mdss) and acute myeloid leukemia (aml) with 20%-30% blasts. METHODS: The cost-utility model is a lifetime probabilistic Markov model with a 35-day cycle length consisting of 3 health states: mds; transformation to aml with more than 30% blasts; and death. A third-party public payer perspective was adopted. Overall survival was extrapolated beyond the time horizon of the aza-001 trial comparing azacitidine with ccr. Resource use was determined through a questionnaire completed by Canadian hematologists. Utility values were obtained from two studies in which EQ-5D health questionnaire values were mapped from the European Organization for Research and Treatment of Cancer qlq-C30 survey, and SF-6D scores were mapped from the Short Form 12, elicited from 191 and 43 patients in two different trials. RESULTS: In the base case, azacitidine had an incremental cost-effectiveness ratio (icer) of $86,182 (95% confidence limits: $69,920, $107,157) per quality-adjusted life year (qaly) gained relative to ccr. Comparing azacitidine with bsc, low-dose chemotherapy plus bsc, and standard-dose chemotherapy plus bsc, the icers were, respectively, $86,973, $84,829, and $2,152 per qaly gained. Results were most sensitive to the utility for azacitidine after 6 months of treatment and to overall survival. CONCLUSIONS: The prolonged 9-month median overall survival with azacitidine relative to ccr fills a gap w hen treating patients with higher-risk mds and aml with 20%-30% blasts. The economic value of azacitidine is within the threshold of willingness-to-pay for third-party public payers for oncology treatments in Canada.

Is it possible to agree on a value for inorganic arsenic in food? The outcome of IMEP-112.

Two of the core tasks of the European Union Reference Laboratory for Heavy Metals in Feed and Food (EU-RL-HM) are to provide advice to the Directorate General for Health and Consumers (DG SANCO) on scientific matters and to organise proficiency tests among appointed National Reference Laboratories. This article presents the results of the 12th proficiency test organised by the EU-RL-HM (IMEP-112) that focused on the determination of total and inorganic arsenic in wheat, vegetable food and algae. The test items used in this exercise were: wheat sampled in a field with a high concentration of arsenic in the soil, spinach (SRM 1570a from NIST) and an algae candidate reference material. Participation in this exercise was open to laboratories from all around the world to be able to judge the state of the art of the determination of total and, more in particular, inorganic arsenic in several food commodities. Seventy-four laboratories from 31 countries registered to the exercise; 30 of them were European National Reference Laboratories. The assigned values for IMEP-112 were provided by a group of seven laboratories expert in the field of arsenic speciation analysis in food. Laboratory results were rated with z and ζ scores (zeta scores) in accordance with ISO 13528. Around 85 % of the participants performed satisfactorily for inorganic arsenic in vegetable food and 60 % did for inorganic arsenic in wheat, but only 20 % of the laboratories taking part in the exercise were able to report satisfactory results in the algae test material.

The cost-effectiveness of celecoxib vs diclofenac in the treatment of osteoarthritis in the UK; an update to the NICE model using data from the CONDOR trial.

OBJECTIVES: The National Institute for Health and Clinical Excellence (NICE) health economic model for assessing the cost-effectiveness of celecoxib plus a proton pump inhibitor (PPI) compared to diclofenac plus PPI in the treatment of osteoarthritis has been updated using new adverse event (AE) risks from the CONDOR trial. In light of this new information, this study aimed to evaluate the incremental cost-effectiveness ratio (ICER) of celecoxib plus PPI compared to diclofenac plus PPI. METHODS: NICE developed a health economic model as part of their 2008 multiple technology assessment of treatments for osteoarthritis. The model was adapted for this study to update the relative risks of adverse events, using data from the CONDOR trial. RESULTS: Using the AE data from the CLASS trial alone, celecoxib plus PPI has an ICER of £9538 per QALY when compared to diclofenac plus PPI. When the AE data from CONDOR alone is used, this ICER decreases to £4773 per QALY. Using the pooled data from both trials, celecoxib plus PPI has an ICER of £9377 per QALY compared to diclofenac plus PPI. DISCUSSION: The results suggest that when new AE risks are used, celecoxib plus PPI remains a cost-effective treatment for OA when compared to diclofenac plus PPI. However, this analysis is limited by the short time horizon, and additional AEs that have not been considered.

The cost effectiveness of zoledronic acid 5 mg for the management of postmenopausal osteoporosis in women with prior fractures: evidence from Finland, Norway and the Netherlands.

OBJECTIVE: This study was conducted to assess the cost effectiveness of zoledronic acid 5 mg as a first-line treatment for the secondary prevention of fragility fractures in women with postmenopausal osteoporosis in Finland, Norway and the Netherlands. METHODS: A discrete-event, individual-patient computer-simulation model was used to compare the cost effectiveness of zoledronic acid with that of basic treatment (calcium and vitamin D) and commonly prescribed bisphosphonates in postmenopausal women aged 50-80 years who have experienced one previous fracture and have a bone mineral density T-score of -2.5. RESULTS: The cost per quality-adjusted life-year (QALY) gained with zoledronic acid compared with basic treatment ranged from being cost saving in all age groups in Norway, to costing approximately €19,000 in Finland and €22,300 in the Netherlands. Compared with the other branded bisphosphonates, zoledronic acid was cost saving in many scenarios, including all age groups in Finland. In Norway, zoledronic acid dominated branded risedronate and ibandronate in all age groups and dominated or had incremental cost-effectiveness ratios (ICERs) of up to NOK83,954 per QALY gained compared with branded alendronate. In the Netherlands, zoledronic acid dominated branded intravenous ibandronate in all age groups; compared with branded risedronate and oral ibandronate, zoledronic acid dominated or had ICERs of up to €4832 per QALY gained; compared with branded alendronate, it had ICERs of up to €48,383 per QALY gained. In all three countries, zoledronic acid may be cost effective compared with generic alendronate when patient compliance with drug therapy is taken into account. Sensitivity analyses showed that the model was robust to changes in key values. The main model limitations were the lack of real-life compliance and persistence data, and lack of country-specific data for some parameters. CONCLUSIONS: Using local or commonly used thresholds, this analysis suggests that zoledronic acid would be a cost-effective first-line option compared with other branded bisphosphonates and, in some scenarios, compared with generic alendronate, for the secondary prevention of fractures in women with postmenopausal osteoporosis in Finland, Norway and the Netherlands.

An initial study to assess the use of geological parent materials to predict the Se concentration in overlying soils and in five staple foodstuffs produced on them in Scotland.

Evidence suggests that dietary-intakes of the essential element selenium have fallen in Scotland in recent years, due to changing sources of bread-making wheat. The Scottish environment is thought to be Se-poor due to the geology and climate. This initial study assessed whether geological parent-materials could be used to predict relatively high and low soil-Se areas in Scotland and whether differences in soil-Se were reflected in foodstuff-Se produced on them. Samples (n=8 per farm) of wheat, calabrese (broccoli), potato, beef-steak, milk, cattle pasture (grass) and soil were collected from pairs of farms (one in each high/low predicted Se area (PSA)). Potatoes and soils were collected from a further 34 farms in high/low PSAs to assess a greater geographical zone. Total soil-Se ranged from 0.115 to 0.877mgkg(-1) but most samples (90%) could be classed as Se-deficient (<0.6mgkg(-1)), irrespective of PSA. Total soil-Se was significantly higher (p<0.05) in the high than in the low PSAs as expected; however, the difference between the two was small (mean 0.48 and 0.37mgkg(-1), respectively). Water-soluble soil-Se (6.69 to 26.78µgkg(-1)) concentrations were not significantly different between the two PSAs (p=0.71). Soil loss-on-ignition (indicating organic matter content) correlated significantly with total and water-soluble soil-Se (p<0.001) and exerted a greater control than parent-material on soil-Se. Significant differences between the PSAs for beef-Se (p<0.001), wheat-Se (p<0.001), calabrese-Se (p<0.01) and beef-farm grass-Se (p<0.05) indicated partial success of the parent-material soil-Se prediction. However, only wheat-Se (p<0.001) and potato-Se (p<0.001) correlated significantly with total soil-Se. The results suggest that soil-Se concentrations in the main agricultural areas of Scotland are generally low. Given the low Se concentrations also reported in the food commodities; further investigations may be warranted to fully characterise the Se-status of Scottish produce and dietary-Se intakes in Scotland.

Docosahexaenoic acid therapy in peroxisomal diseases: results of a double-blind, randomized trial.

OBJECTIVES: Peroxisome assembly disorders are genetic disorders characterized by biochemical abnormalities, including low docosahexaenoic acid (DHA). The objective was to assess whether treatment with DHA supplementation would improve biochemical abnormalities, visual function, and growth in affected individuals. METHODS: This was a randomized, double-blind, placebo-controlled trial conducted at a single center. Treatment groups received supplements of DHA (100 mg/kg per day). The primary outcome measures were the change from baseline in the visual function and physical growth during the 1 year follow-up period. RESULTS: Fifty individuals were enrolled and randomized. Two were subsequently excluded from study analysis when it was determined that they had a single enzyme disorder of peroxisomal beta oxidation. Thirty-four returned for follow-up. Nine patients died during the trial of their disorder, and 5 others were lost to follow-up. DHA supplementation was well tolerated. There was no difference in the outcomes between the treated and untreated groups in biochemical function, electroretinogram, or growth. Improvements were seen in both groups in certain individuals. CONCLUSIONS: DHA supplementation did not improve the visual function or growth of treated individuals with peroxisome assembly disorders. CLASSIFICATION OF EVIDENCE: This interventional study provides Class II evidence that DHA supplementation did not improve the visual function or growth of treated individuals with peroxisome assembly disorders during an average of 1 year of follow-up in patients aged 1 to 144 months.

Dietary exposure to metals and other elements in the 2006 UK Total Diet Study and some trends over the last 30 years.

Concentrations of 24 elements including metals in the 2006 UK Total Diet Study (TDS) were measured and dietary exposures estimated. Composite samples for the 20 TDS food groups (bread, fish, fruit, etc.) were collected from 24 UK towns and analysed for their levels of aluminium, antimony, arsenic, barium, bismuth, cadmium, chromium, copper, germanium, indium, lead, manganese, mercury, molybdenum, nickel, palladium, platinum, rhodium, ruthenium, selenium, strontium, thallium, tin, and zinc. Concentrations of each of the elements in the food groups were lower than or similar to those reported in the previous TDS survey, conducted in 2000, with the exception of aluminium, barium, and manganese. Dietary exposures to the 24 elements were estimated for UK consumers and compared with previous estimates made over the last 30 years in order to examine any trends in exposure to these elements in the typical UK diet. Population exposures to the elements have generally declined over time, and exposures to most of these elements remain at low levels. The independent UK Government scientific Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT) commented on the estimated dietary exposures, taking into account their previous evaluations (in 2003 and 2008), and identified no major concerns for the health of consumers, but did advise that there was a need for more information on aluminium and barium, and also commented that dietary exposure to inorganic arsenic and to lead should continue to be reduced.

"Lorenzo's oil" therapy for X-linked adrenoleukodystrophy: rationale and current assessment of efficacy.

X-linked adrenoleukodystrophy (X-ALD) is a genetic disorder that damages the nervous system and is associated with the accumulation of saturated very long chain fatty acids (SVLCFA). Oral administration of "Lorenzo's oil" (LO), a 4:1 mixture of glyceryl trioleate and glyceryl trierucate, normalizes the SVLCFA levels in plasma, but its clinical efficacy and the clinical indications for its use have been controversial for more than 15 years. We review the biochemical effects of LO administration and the rationale for its use and present a current appraisal of its capacity to reduce the risk for the childhood cerebral phenotype when administered to asymptomatic boys and to slow progression of adrenomyeloneuropathy in patients without cerebral involvement. We also present current efforts to provide definitive evaluation of its clinical efficacy and discuss its possible role in the new therapeutic opportunities that will arise if newborn screening for X-ALD is validated and implemented.

Follow-up of 89 asymptomatic patients with adrenoleukodystrophy treated with Lorenzo's oil.

OBJECTIVES: To identify asymptomatic boys with X-linked adrenoleukodystrophy who have a normal magnetic resonance image (MRI), and to assess the effect of 4:1 glyceryl trioleate-glyceryl trierucate (Lorenzo's oil) on disease progression. METHOD: Eighty-nine boys (mean +/- SD baseline age, 4.7 +/- 4.1 years; range, 0.2-15 years) were identified by a plasma very long-chain fatty acids assay used to screen at-risk boys. All were treated with Lorenzo's oil and moderate fat restriction. Plasma fatty acids and clinical status were followed for 6.9 +/- 2.7 years. Changes in plasma hexacosanoic acid levels were assessed by measuring the length-adjusted area under the curve, and a proportional hazards model was used to evaluate association with the development of abnormal MRI results and neurological abnormalities. RESULTS: Of the 89 boys, 24% developed MRI abnormalities and 11% developed both neurological and MRI abnormalities. Abnormalities occurred only in the 64 patients who were aged 7 years or younger at the time therapy was started. There was significant association between the development of MRI abnormalities and a plasma hexacosanoic acid increase. (For a 0.1-microg/mL increase in the length-adjusted area under the curve for the hexacosanoic acid level, the hazard ratio for incident MRI abnormalities in the whole group was 1.36; P = .01; 95% confidence interval, 1.07-1.72.) Results for patients aged 7 years or younger were similar (P = .04). CONCLUSIONS: In this single-arm study, hexacosanoic acid reduction by Lorenzo's oil was associated with reduced risk of developing MRI abnormalities. We recommend Lorenzo's oil therapy in asymptomatic boys with X-linked adrenoleukodystophy who have normal brain MRI results.