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Copper (Cu) is the main co‐factor in the functioning of the ammonia monooxygenase (AMO) enzyme, which is responsible for the first step of ammonia oxidation. We report a greenhouse‐based pot experiment that examines the response of ammonia‐oxidizing bacteria and archaea (AOB and AOA) to different bioavailable Cu concentrations in three pastoral soils (Recent, Pallic, and Pumice soils) planted with ryegrass (Lolium perenneL.). Five treatments were used: control (no urine and Cu), urine only at 300 mg N kg−1soil (Cu0), urine + 1 mg Cu kg−1soil (Cu1), urine + 10 mg Cu kg−1soil (Cu10), and urine + 100 mg Cu kg−1soil (Cu100). Pots were destructively sampled at Day 0, 1, 7, 15, and 25 after urine application. The AOB/AOA amoAgene abundance was analyzed by real‐time quantitative polymerase chain reaction at Days 1 and 15. The AOB amoAgene abundance increased 10.0‐ and 22.6‐fold in the Recent soil and 2.1‐ and 2.5‐fold in the Pallic soil for the Cu10 compared with Cu0 on Days 1 and 15, respectively. In contrast, the Cu100 was associated with a reduction in AOB amoAgene abundance in the Recent and Pallic soils but not in the Pumice soil. This may be due to the influence of soil cation exchange capacity differences on the bioavailable Cu. Bioavailable Cu in the Recent and Pallic soils influenced nitrification and AOB amoAgene abundance, as evidenced by the strong positive correlation between bioavailable Cu, nitrification, and AOB amoA. However, bioavailable Cu did not influence the nitrification and AOA amoAgene abundance increase. Copper concentration 0.24‐0.33 mg kg‐1increased nitrification rate for Recent and Pallic soils but inhibited above 6 mg kg‐1.Changes in nitrification rate in Recent and Pallic soils were positively correlated with AOB amoA gene abundance.AOA amoA gene was stimulated at higher Cu concentration in Recent and Pallic soils but not in Pumice soil.

BackgroundSeveral randomised clinical trials (RCTs) performing faecal microbiota transplantation (FMT) for the management of inflammatory bowel disease (IBD), particularly for ulcerative colitis, have recently been published, but with major variations in study design. These include differences in administered dose, route and frequency of delivery, type of placebo and evaluated endpoints. Although the overall outcomes appear to be promising, they are highly dependent on both donor and recipient factors.ObjectiveTo develop concensus-based statements and recommendations for the evaluation, management and potential treatment of IBD using FMT in order to move towards standardised practices.DesignAn international panel of experts convened several times to generate evidence-based guidelines by performing a deep evaluation of currently available and/or published data. Twenty-five experts in IBD, immunology and microbiology collaborated in different working groups to provide statements on the following key issues related to FMT in IBD: (A) pathogenesis and rationale, (B) donor selection and biobanking, (C) FMT practices and (D) consideration of future studies and perspectives. Statements were evaluated and voted on by all members using an electronic Delphi process, culminating in a plenary consensus conference and generation of proposed guidelines.Results and conclusionsOur group has provided specific statements and recommendations, based on best available evidence, with the end goal of providing guidance and general criteria required to promote FMT as a recognised strategy for the treatment of IBD.

ObjectiveFaecal microbiota transplantation (FMT) has variable efficacy in treating UC. Recently, oral lyophilised FMT was found to induce remission in patients with UC, with one donor having 100% efficacy compared with a second donor (36% efficacy). We characterised differences in the gut microbiota of these two donors with the aim of improving FMT donor selection.DesignFaecal samples from the two donors were collected over a period of 44 (donor 1) or 70 (donor 2) weeks. The microbiome and metabolome were profiled using shotgun metagenomics and untargeted metabolomicsResultsGut microbiome long-term stability was highly evident in the effective donor. Donor microbiota species evenness was a robust feature associated with clinical efficacy across two clinical trials of FMT in UC, leading to increased donor species engraftment in patients. Alpha diversity and beta diversity of donor gut microbiotas significantly differed. 90 bacterial species and one archaeon were differentially abundant between donors, 44 of which were >0.1% in relative abundance. 17/44 species were enriched in the effective donor, 11 of which (64.7%) were assembled into high-quality genomes that were prevalent (≥75% samples) in that donor, and six showed evidence of engraftment in patients. Taxonomic differences between donors translated to substantial microbial functional differences that were validated using metabolomics.ConclusionDonor microbiota stability and species evenness were identified as novel metrics that were associated with therapeutic efficacy in UC, beyond individual microbial species or metabolites. These metrics may represent community resilience that translates to better engraftment in the host.Trial registration numberACTRN12619000611123.

Youth with Duchenne and Becker muscular dystrophy (DBMD) experience challenges in attaining adult roles, which may impact quality of life. New interventions and treatments may facilitate adult role attainment through improved function. Historical data on adult role attainment is important to assess the impact of new interventions on teens and young adults with DBMD. This study assesses medical knowledge, independence and employment, and relationships among adolescents and young adults with DBMD. This study uses data from a 2013 Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) survey on adult transition. Males with DBMD aged 16–30 years were included. Sixty-five of 258 eligible males participated; we report results on 60 participants with an MD STARnetcase definition of DMD or BMD. Individuals with BMD reported higher rates than those with DMD of frequently staying home without supervision (50% BMD; 14% DMD), independently performing daily physical needs (93% BMD; 7% DMD) and being employed full or part time (33% BMD; 4% DMD). Most participants understood medication and physical therapy goals; less than half indicated being often or always responsible for scheduling DMBD-related management and refilling medications. Most had not been in a romantic relationship but reported desiring such relationships. Our data reinforce the impact of DMD (and to a lesser extent, BMD) on transition to adult roles. These results provide an important historical comparator for teen and adult patients who are trying new interventions and therapies. Such data are important for assessing the quality-of-life impact of new treatments and to inform support and training programs for people with DBMD as they transition to new adult roles and responsibilities.

Faecal microbiota transplantation (FMT) delivered via colonoscopic infusion or enemas have been shown to induce remission in a proportion of patients with active ulcerative colitis. Whether orally administered FMT is effective in ulcerative colitis is unknown. We aimed to assess the efficacy of oral lyophilised FMT for the treatment of active ulcerative colitis.

Context Cadmium (Cd) accumulation is a concern in permanent pasture soils, as it can lead to increased Cd uptake by plants. Aims This study aimed to quantify the effect of full inversion tillage (FIT or ploughing deeper than 30cm), used during pasture renewal, on the redistribution of Cd within the soil profile and on plant Cd concentration. Methods Two field trials (Trial 1, Alfisol; Trial 2, Andisol) were established in New Zealand using contrasting tillage practices (FIT; SIT, shallow tillage; and NT, no tillage) to sow turnips as summer forage crops, followed by autumn re-sowing of perennial ryegrass/white clover pasture. Key results In the Alfisol, no measurable differences (P >0.05) in soil and plant Cd were detected among the tillage treatments. In the Andisol, FIT decreased (P P =0.034) extractable soil Cd concentration than the ST treatment. In addition, the subsequent new pasture had lower (P =0.007) average Cd concentration following FIT compared to ST (0.03 vs 0.05mg/kg). Conclusions We demonstrated that the use of FIT during pasture renewal is a potential solution to reduce topsoil Cd concentration. Implications The FIT is more effective in soil where total soil Cd concentration or its degree of vertical stratification with depth is relatively high.

ABSTRACTIntroduction: The peak age of diagnosis of inflammatory bowel disease (IBD) occurs during childbearing years, therefore management of IBD during pregnancy is a frequent occurrence. Maintenance of disease remission is crucial to optimize pregnancy outcomes, and potential maternal or fetal toxicity from medications must be balanced against the risks of untreated IBD.Areas covered: This review summarizes the literature on safety and use of medications for IBD during pregnancy and lactation.Expert opinion: 5-aminosalicylates, corticosteroids and thiopurines are safe for use during pregnancy, while methotrexate and tofacitinib should only be used with extreme caution. Anti-TNF agents (except certolizumab), vedolizumab, ustekinumab and tofacitinib readily traverse the placenta via active transport, therefore theoretically may affect fetal development. Certolizumab only undergoes passive transfer across the placenta, thus has markedly lower cord blood levels making it likely the safest biologic agent for infants. There is reasonable evidence to support the safety of anti-TNF monotherapy and combination therapy during pregnancy and lactation. Vedolizumab and ustekinumab are also thought to be safe in pregnancy and lactation, while tofacitinib is generally avoided due to teratogenic effects in animal studies.

Mobility of teleoperated unmanned ground vehicles can be significantly compromised under large communication delays, if the delays are not compensated. This article considers a recently developed delay compensation theory and presents its first empirical evaluation in improving mobility and drivability of a high-speed teleoperated vehicle under large delays. The said delay compensation theory is a predictor-based framework. Two realizations of this framework are considered: a model-free realization that relies only on model-free predictors, and a blended realization, where the heading predictions from the model-free predictor are blended with those from a steering-model-based feedforward predictor for a more accurate prediction of the vehicle heading. A teleoperated track-following task is designed in a human-in-the-loop simulation platform. This platform is used to compare the teleoperation performance with and without the predictor-based framework under both constant and varying delays. Through repeated measurement analysis of variance, it is concluded that the predictor-based framework is effective in achieving a higher vehicle speed, more accurate lateral control, and better drivability as indicated by the three performance metrics of track completion time, track keeping error, and steering control effort, respectively. In addition, it is shown that the blended architecture can lead to further improvements in these metrics compared to using the model-free predictors alone. The analysis also shows that there is no statistically significant difference between constant and varying delay cases in the designed experiment, nor there is any direct relation between drivers' skill level and level of improvement in metrics.

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The intestinal microbiota is implicated in the pathogenesis of ulcerative colitis. Faecal microbiota transplantation is a novel form of therapeutic microbial manipulation, but its efficacy in ulcerative colitis is uncertain. We aimed to establish the efficacy of intensive-dosing, multidonor, faecal microbiota transplantation in active ulcerative colitis.

Autonomous systems are the future of the Army and Ground Vehicle Systems Center has aligned itself accordingly to support unmanned ground vehicle (UGV) development. Physically testing autonomous algorithms and vehicle systems can be expensive and time consuming, a problem addressed by the use of modelling and simulation (M&S) tools. A multitude of both Government owned and commercial off-the-shelf tools (COTS) are widely available, all claim to virtually evaluate autonomous ground vehicles operating on various environments and scenarios. Most of the COTS tools primarily focus on the commercial automotive industry where vehicles are driven in a structured environment. In this paper two M&S tools, viz., Autonomous Navigation Virtual Environment Laboratory (ANVEL) and rover analysis modelling and simulation (ROAMS) are evaluated for military applications, where the demands for navigation include both on-road and off-road, as well as both structured and unstructured environments as a preliminary benchmark.

Workload management is of critical concern in teleoperation of unmanned vehicles, because high workload can lead to sub-optimal task performance and can harm human operators’ long-term well-being. In the present study, we conducted a human-in-the-loop experiment, where the human operator teleoperated a simulated High Mobility Multipurpose Wheeled Vehicle (HMMWV) and performed a secondary visual search task. We measured participants’ gaze trajectory and pupil size, based on which their workload level was estimated. We proposed and tested a Bayesian inference (BI) model for assessing workload in real time. Results show that the BI model can achieve an encouraging 0.69 F1score, 0.70 precision, and 0.69 recall.

ABSTRACTIntroduction: Medications in treating Crohn’s disease (CD) have evolved over the last two decades, particularly with the use of biologic agents. There are, however, concerns about the safety and adverse events associated with these medications. The authors review the safety profile of immunosuppressive medications used in Crohn’s disease in adult patients.Areas covered: The authors performed a literature search until October 2018 to examine safety data on thiopurines, methotrexate, anti-TNFα agents, vedolizumab and ustekinumab. The authors focused on ‘trial’ and ‘real-world’ data for the biologic agents. Safety in pregnancy and the elderly are also presented.Expert opinion: Available data in CD suggest that immunosuppressive medications are relatively safe, although there are concerns about an elevated risk of serious infections, skin cancer and lymphoma particularly with thiopurines and anti-TNFα agents. Data on vedolizumab and ustekinumab suggest these newer biologic agents are well tolerated; however, longer term data in CD are required to identify risks with extended use. Apart from methotrexate, there appear to be no adverse congenital outcomes with exposure of drugs during pregnancy.

In the United States and some other NATO (North Atlantic Treaty Organization) countries, the NATO Reference Mobility Model is currently used to evaluate military ground vehicle mobility. The module of the NATO Reference Mobility Model for predicting the cross-country performance of military vehicles is empirically based and was developed using test data collected decades ago. The NATO Reference Mobility Model has inherent limitations, such as the uncertainty whether its empirical relations can be extrapolated beyond the test conditions upon which they were derived or whether it can be used for evaluating new-generation military vehicles. This suggests that there is a need for the development of a physics-based model that takes into account the advancements in terramechanics and modelling/simulation techniques. This paper describes the results of a detailed evaluation of a physics-based model – the Nepean Tracked Vehicle Performance Model – for assessing military tracked vehicle cross-country performance. The performance of a notional tracked vehicle (an armoured personnel carrier) predicted by the latest version of the Nepean Tracked Vehicle Performance Model is compared with test data obtained on sandy terrain, muskeg and snow-covered terrain. The correlations between the predicted and measured performance are evaluated using the coefficient of correlation, coefficient of determination, root mean square deviation and coefficient of variation. The applications of the Nepean Tracked Vehicle Performance Model to predicting the maximum possible vehicle speed (speed-made-good) on a given terrain, the sensitivity of vehicle performance to variations in the values of terrain parameters and the mean maximum pressure are demonstrated. The results of this study indicate that the Nepean Tracked Vehicle Performance Model has potential to form the basis for the development of the next-generation cross-country performance assessment methodology for military tracked vehicles.

This paper describes a model for deformable soil based on triangular meshes with vertical deformation. Such soil model can be used in a multi-body simulation environment to study the performance of wheeled or tracked vehicles. The formulation is inspired by the soil contact model (SCM), but unlike the original idea, our implementation uses triangular meshes with arbitrary topology. We leverage on this representation of the soil in order to provide a system that automatically refines the level of detail (LOD) of the mesh when tyres or track shoes sink into the soil; this allows the use of coarse meshes as initial approximations of large areas, for the sake of faster performance and lowoverhead on computer memory. A general-purpose collision detection algorithm is used to detect the shape of contacting objects, hence allowing the use of generic geometries to represent lugs, tyre threads, or even track shoes or robotic legs. The method has also been tested with deformable tyres.

Assessing the mobility of off-road vehicles is a complex task that most often falls back on semi-empirical approaches to quantify the tire-terrain interaction. We introduce a high-fidelity ground vehicle mobility simulation framework that uses physics-based models of the vehicle, tyres, and terrain to factor in both tyre flexibility and soil deformation. The tyres are modelled using a nonlinear finite element approach that involves layers of orthotropic shell elements. The soil is represented as a large collection of rigid elements that interact through contact, friction, and cohesive forces. The high-fidelity vehicle models incorporate suspension, steering, driveline, and powertrain models. To alleviate the prohibitive computational costs associated with a coupled simulation of the overall problem, we propose a decoupled approach implemented as an explicit, force-displacement co-simulation framework which is demonstrated on several full-vehicle on soft soil simulations. UNCLASSIFIED: Distribution Statement A. Approved for public release; distribution is unlimited. #28937.

Background: Earlier goals of care (GOC) discussions in patients with advanced cancer are associated with less aggressive end-of-life care including decreased use of medical technologies. Unfortunately, conversations often occur late in the disease trajectory when patients are acutely unwell. Here, we evaluate practitioner perspectives of patient, family, physician, and external barriers to early GOC discussions in the ambulatory oncology setting.Methods: A previously published survey to assess barriers to GOC discussions among clinicians on inpatient medical wards was modified for the ambulatory oncology setting and distributed to oncologists from 12 centers in Ontario, Canada. Physicians were asked to rank the importance of various barriers to having GOC discussions (1 = extremely unimportant to 7 = extremely important).Results: Questionnaires were completed by 30 (24%) of 127 physicians. Respondents perceived patient- and family-related factors as the most important barriers to GOC discussions. Of these, patient difficulty accepting prognosis or desire for aggressive treatment were perceived as most important. Patients’ inflated expectation of treatment benefit was also considered an important barrier to discontinuing active cancer-directed therapy. While physician barriers were ranked lower than patient-related factors, clinicians’ self-identified difficulty estimating prognosis and uncertainty regarding treatment benefits were also considered important. Patient’s refusal for referral was the most highly rated barrier to early palliative care referral. Most respondents were nonetheless very or extremely willing to initiate (90%) or lead (87%) GOC discussions.Conclusion: Oncologists ranked patient- and family-related factors as the most important barriers to GOC discussions, while clinicians’ self-identified difficulty estimating prognosis and uncertainty regarding treatment benefits were also considered important. Further work is required to assess patient preferences and perceptions and develop targeted interventions.