The effect of organic and conventional management on the yield and quality of wheat grown in a long-term field trial

The performance of winter wheat was evaluated under organic (ORG) and conventional (CON) management systems in the Nafferton Factorial Systems Comparison (NFSC) long-term field trial. The present study separates out the crop protection and fertility management components of organic and conventional production systems using two levels each of crop protection (CP) and fertility management (FM). The experimental design provided the four combinations of crop protection and fertility (CON-CP CONFM, CON-CP ORG-FM, ORG-CP CON-FM and ORG-CP ORG-FM) to evaluate their effects on yield, quality (protein content and hectolitre weight) and disease levels during the period 2004–2008. The conventional management system (CON-CP CON-FM) out-yielded the organic management system (ORG-CP ORG-FM) in all years by an average of 3.1 t ha−1, i.e. 7.9 t ha−1 vs. 4.8 t ha−1. Fertility management was the key factor identified limiting both yield and grain protein content in the ORG management system. The CON-FM produced on average a 3% higher protein content than ORG-FM in all years (12.5% vs. 9.7%). However the ORG-CP system produced higher protein levels than CON-CP although it was only in 2008 that this was statistically significant. In contrast to protein content it was ORG-FM which produced a higher hectolitre weight than the CON-FM system (71.6 kg hl−1 vs. 71.0 kg hl−1). The clear and significant differences in yield and protein content between the ORG-FM and CON-FM systems suggest a limited supply of available N in the organic fertility management system which is also supported by the significant interaction effect of the preceding crop on protein content. The pRDA showed that although fertilisation had the greatest effect on yield, quality and disease there was also a considerable effect of crop protection and the environment

The influence of organic and conventional fertilisation and crop protection practices, preceding crop, harvest year and weather conditions on yield and quality of potato (Solanum tuberosum) in a long-term management trial

The effects of organic versus conventional crop management practices (fertilisation, crop protection) and preceding crop on potato tuber yield (total, marketable, tuber size grade distribution) and quality (proportion of diseased, green and damaged tubers, tuber macro-nutrient concentrations) parameters were investigated over six years (2004–2009) as part of a long-term factorial field trial in North East England. Inter-year variability (the effects of weather and preceding crop) was observed to have a profound effect on yields and quality parameters, and this variability was greater in organic fertility systems. Total and marketable yields were significantly reduced by the use of both organic crop protection and fertility management. However, the yield gap between organic and conventional fertilisation regimes was greater and more variable than that between crop protection practices. This appears to be attributable mainly to lower and less predictable nitrogen supply in organically fertilised crops. Increased incidence of late blight in organic crop protection systems only occurred when conventional fertilisation was applied. In organically fertilised crops yield was significantly higher following grass/red clover leys than winter wheat, but there was no pre-crop effect in conventionally fertilised crops. The results highlight that nitrogen supply from organic fertilisers rather than inefficient pest and disease control may be the major limiting factor for yields in organic potato production systems

System-wide approaches to antimicrobial therapy and antimicrobial resistance in the UK: the AMR-X framework

Antimicrobial resistance (AMR) threatens human, animal, and environmental health. Acknowledging the urgency of addressing AMR, an opportunity exists to extend AMR action-focused research beyond the confines of an isolated biomedical paradigm. An AMR learning system, AMR-X, envisions a national network of health systems creating and applying optimal use of antimicrobials on the basis of their data collected from the delivery of routine clinical care. AMR-X integrates traditional AMR discovery, experimental research, and applied research with continuous analysis of pathogens, antimicrobial uses, and clinical outcomes that are routinely disseminated to practitioners, policy makers, patients, and the public to drive changes in practice and outcomes. AMR-X uses connected data-to-action systems to underpin an evaluation framework embedded in routine care, continuously driving implementation of improvements in patient and population health, targeting investment, and incentivising innovation. All stakeholders co-create AMR-X, protecting the public from AMR by adapting to continuously evolving AMR threats and generating the information needed for precision patient and population care

A facilitated home-based cardiac rehabilitation intervention for people with heart failure and their caregivers:a research programme including the REACH-HF RCT

Background: Rates of participation in centre (hospital)-cardiac rehabilitation by patients with heart failure are suboptimal. Heart failure has two main phenotypes differing in underlying pathophysiology: Heart failure with reduced ejection fraction is characterised by depressed left ventricular systolic function (‘reduced ejection fraction’), whereas heart failure with preserved ejection fraction is diagnosed after excluding other causes of dyspnoea with normal ejection fraction. This programme aimed to develop and evaluate a facilitated home-based cardiac rehabilitation intervention that could increase the uptake of cardiac rehabilitation while delivering the clinical benefits of centre-based cardiac rehabilitation. Objectives: To develop an evidence-informed, home-based, self-care cardiac rehabilitation programme for patients with heart failure and their caregivers [the REACH-HF (Rehabilitation Enablement in Chronic Heart Failure) intervention]. To conduct a pilot randomised controlled trial to assess the feasibility of a full trial of the clinical effectiveness and cost-effectiveness of the REACH-HF intervention in addition to usual care in patients with heart failure with preserved ejection fraction. To assess the short- and long-term clinical effectiveness and cost-effectiveness of the REACH-HF intervention in addition to usual care in patients with heart failure with reduced ejection fraction and their caregivers. Design: Intervention mapping to develop the REACH-HF intervention; uncontrolled feasibility study; pilot randomised controlled trial in those with heart failure with preserved ejection fraction; randomised controlled trial with a trial-based cost-effectiveness analysis in those with heart failure with reduced ejection fraction; qualitative studies including process evaluation; systematic review of cardiac rehabilitation in heart failure; and modelling to assess long-term cost-effectiveness (in those with heart failure with reduced ejection fraction). Setting: Four centres in England and Wales (Birmingham, Cornwall, Gwent and York); one centre in Scotland (Dundee) for a pilot randomised controlled trial. Participants: Adults aged ≥ 18 years with heart failure with reduced ejection fraction (left ventricular ejection fraction &lt; 45%) for the main randomised controlled trial (n = 216), and those with heart failure with preserved ejection fraction (left ventricular ejection fraction ≥ 45%) for the pilot randomised controlled trial (n = 50). Intervention: A self-care, facilitated cardiac rehabilitation manual was offered to patients (and participating caregivers) at home over 12 weeks by trained health-care professionals in addition to usual care or usual care alone. Main outcome measures: The primary outcome was disease-specific health-related quality of life measured using the Minnesota Living with Heart Failure Questionnaire at 12 months. Secondary outcomes included deaths and hospitalisations. Results: The main randomised controlled trial recruited 216 participants with heart failure with reduced ejection fraction and 97 caregivers. A significant and clinically meaningful between-group difference in the Minnesota Living with Heart Failure Questionnaire score (primary outcome) at 12 months (–5.7 points, 95% confidence interval –10.6 to –0.7 points) favoured the REACH-HF intervention (p = 0.025). Eight (4%) patients (four in each group) had died at 12 months. There was no significant difference in hospital admissions, at 12 months, with 19 participants in the REACH-HF intervention group having at least one hospital admission, compared with 24 participants in the control group (odds ratio 0.72, 95% confidence interval 0.35 to 1.51; p = 0.386). The mean cost of the intervention was £418 per participant with heart failure with reduced ejection fraction. The costs at 12 months were, on average, £401 higher in the intervention group than in the usual care alone group. Model-based economic evaluation, extrapolating from the main randomised controlled trial in those with heart failure with reduced ejection fraction over 4 years, found that adding the REACH-HF intervention to usual care had an estimated mean cost per participant of £15,452 (95% confidence interval £14,240 to £16,780) and a mean quality-adjusted lifeyear gain of 4.47 (95% confidence interval 3.83 to 4.91) years, compared with £15,051 (95% confidence interval £13,844 to £16,289) and 4.24 (95% confidence interval 4.05 to 4.43) years, respectively, for usual care alone. This gave an incremental cost per quality-adjusted life-year of £1721. The probabilistic sensitivity analysis indicated 78% probability that the intervention plus usual care versus usual care alone has a cost-effectiveness below the willingness-to-pay threshold of £20,000 per quality-adjusted life-year gained. The intervention was well received by participants with heart failure with reduced ejection fraction and those with heart failure with preserved ejection fraction, as well as their caregivers. Both randomised controlled trials recruited to target, with &gt; 85% retention at follow-up. Limitations: Key limitations included (1) lack of blinding – given the nature of the intervention and the control we could not mask participants to treatments, so our results may reflect participant expectation bias; (2) that we were not able to capture consistent participant-level data on level of intervention adherence; (3) that there may be an impact on the generalisability of findings due to the demographics of the trial patients, as most were male (78%) and we recruited only seven people from ethnic minorities. Conclusions: Evaluation of the comprehensive, facilitated, home-based REACH-HF intervention for participants with heart failure with reduced ejection fraction and caregivers indicated clinical effectiveness in terms of health-related quality of life and patient self-care but no other secondary outcomes. Although the economic analysis conducted alongside the full randomised controlled trial did not produce significant differences on the EuroQol-5 Dimensions or in quality-adjusted life-years, economic modelling suggested greater cost-effectiveness of the intervention than usual care. Our REACH-HF intervention offers a new evidence-based cardiac rehabilitation option that could increase uptake of cardiac rehabilitation in patients with heart failure not attracted to or able to access hospital-based programmes. Future work: Systematic collection of real-world data would track future changes in uptake of and adherence to alternative cardiac rehabilitation interventions in heart failure with reduced ejection fraction and increase understanding of how changes in service delivery might affect clinical and health economic outcomes. The findings of our pilot randomised controlled trial in patients with heart failure with preserved ejection fraction support progression to a full multicentre randomised controlled trial. </p

A facilitated home-based cardiac rehabilitation intervention for people with heart failure and their caregivers:a research programme including the REACH-HF RCT

Background: Rates of participation in centre (hospital)-cardiac rehabilitation by patients with heart failure are suboptimal. Heart failure has two main phenotypes differing in underlying pathophysiology: Heart failure with reduced ejection fraction is characterised by depressed left ventricular systolic function (‘reduced ejection fraction’), whereas heart failure with preserved ejection fraction is diagnosed after excluding other causes of dyspnoea with normal ejection fraction. This programme aimed to develop and evaluate a facilitated home-based cardiac rehabilitation intervention that could increase the uptake of cardiac rehabilitation while delivering the clinical benefits of centre-based cardiac rehabilitation. Objectives: To develop an evidence-informed, home-based, self-care cardiac rehabilitation programme for patients with heart failure and their caregivers [the REACH-HF (Rehabilitation Enablement in Chronic Heart Failure) intervention]. To conduct a pilot randomised controlled trial to assess the feasibility of a full trial of the clinical effectiveness and cost-effectiveness of the REACH-HF intervention in addition to usual care in patients with heart failure with preserved ejection fraction. To assess the short- and long-term clinical effectiveness and cost-effectiveness of the REACH-HF intervention in addition to usual care in patients with heart failure with reduced ejection fraction and their caregivers. Design: Intervention mapping to develop the REACH-HF intervention; uncontrolled feasibility study; pilot randomised controlled trial in those with heart failure with preserved ejection fraction; randomised controlled trial with a trial-based cost-effectiveness analysis in those with heart failure with reduced ejection fraction; qualitative studies including process evaluation; systematic review of cardiac rehabilitation in heart failure; and modelling to assess long-term cost-effectiveness (in those with heart failure with reduced ejection fraction). Setting: Four centres in England and Wales (Birmingham, Cornwall, Gwent and York); one centre in Scotland (Dundee) for a pilot randomised controlled trial. Participants: Adults aged ≥ 18 years with heart failure with reduced ejection fraction (left ventricular ejection fraction &lt; 45%) for the main randomised controlled trial (n = 216), and those with heart failure with preserved ejection fraction (left ventricular ejection fraction ≥ 45%) for the pilot randomised controlled trial (n = 50). Intervention: A self-care, facilitated cardiac rehabilitation manual was offered to patients (and participating caregivers) at home over 12 weeks by trained health-care professionals in addition to usual care or usual care alone. Main outcome measures: The primary outcome was disease-specific health-related quality of life measured using the Minnesota Living with Heart Failure Questionnaire at 12 months. Secondary outcomes included deaths and hospitalisations. Results: The main randomised controlled trial recruited 216 participants with heart failure with reduced ejection fraction and 97 caregivers. A significant and clinically meaningful between-group difference in the Minnesota Living with Heart Failure Questionnaire score (primary outcome) at 12 months (–5.7 points, 95% confidence interval –10.6 to –0.7 points) favoured the REACH-HF intervention (p = 0.025). Eight (4%) patients (four in each group) had died at 12 months. There was no significant difference in hospital admissions, at 12 months, with 19 participants in the REACH-HF intervention group having at least one hospital admission, compared with 24 participants in the control group (odds ratio 0.72, 95% confidence interval 0.35 to 1.51; p = 0.386). The mean cost of the intervention was £418 per participant with heart failure with reduced ejection fraction. The costs at 12 months were, on average, £401 higher in the intervention group than in the usual care alone group. Model-based economic evaluation, extrapolating from the main randomised controlled trial in those with heart failure with reduced ejection fraction over 4 years, found that adding the REACH-HF intervention to usual care had an estimated mean cost per participant of £15,452 (95% confidence interval £14,240 to £16,780) and a mean quality-adjusted lifeyear gain of 4.47 (95% confidence interval 3.83 to 4.91) years, compared with £15,051 (95% confidence interval £13,844 to £16,289) and 4.24 (95% confidence interval 4.05 to 4.43) years, respectively, for usual care alone. This gave an incremental cost per quality-adjusted life-year of £1721. The probabilistic sensitivity analysis indicated 78% probability that the intervention plus usual care versus usual care alone has a cost-effectiveness below the willingness-to-pay threshold of £20,000 per quality-adjusted life-year gained. The intervention was well received by participants with heart failure with reduced ejection fraction and those with heart failure with preserved ejection fraction, as well as their caregivers. Both randomised controlled trials recruited to target, with &gt; 85% retention at follow-up. Limitations: Key limitations included (1) lack of blinding – given the nature of the intervention and the control we could not mask participants to treatments, so our results may reflect participant expectation bias; (2) that we were not able to capture consistent participant-level data on level of intervention adherence; (3) that there may be an impact on the generalisability of findings due to the demographics of the trial patients, as most were male (78%) and we recruited only seven people from ethnic minorities. Conclusions: Evaluation of the comprehensive, facilitated, home-based REACH-HF intervention for participants with heart failure with reduced ejection fraction and caregivers indicated clinical effectiveness in terms of health-related quality of life and patient self-care but no other secondary outcomes. Although the economic analysis conducted alongside the full randomised controlled trial did not produce significant differences on the EuroQol-5 Dimensions or in quality-adjusted life-years, economic modelling suggested greater cost-effectiveness of the intervention than usual care. Our REACH-HF intervention offers a new evidence-based cardiac rehabilitation option that could increase uptake of cardiac rehabilitation in patients with heart failure not attracted to or able to access hospital-based programmes. Future work: Systematic collection of real-world data would track future changes in uptake of and adherence to alternative cardiac rehabilitation interventions in heart failure with reduced ejection fraction and increase understanding of how changes in service delivery might affect clinical and health economic outcomes. The findings of our pilot randomised controlled trial in patients with heart failure with preserved ejection fraction support progression to a full multicentre randomised controlled trial. </p

Infection-related morbidity and mortality among older patients with DLBCL treated with full- or attenuated-dose R-CHOP

Infection-related morbidity and mortality are increased in older patients with diffuse large B-cell lymphoma (DLBCL) compared with population-matched controls. Key predictive factors for infection-related hospitalization during treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and deaths as a result of infection in older patients during and after treatment with R-CHOP remain incompletely understood. For this study, 690 consecutively treated patients age 70 years or older who received full-dose or attenuated-dose R-CHOP treatment were analyzed for risk of infection-related hospitalization and infection-related death. Median age was 77 years, and 34.4% were 80 years old or older. Median follow-up was 2.8 years (range, 0.4-8.9 years). Patient and baseline disease characteristics were assessed in addition to intended dose intensity (IDI). Of all patients, 72% were not hospitalized with infection. In 331 patients receiving an IDI $80$1 infections compared with 23.3% of 355 patients receiving an IDI of,80% (odds ratio, 1.61; 95% confidence interval, 1.15-2.25; P 5 .006). An increased risk of infection-related admission was independently associated with IDI .80% across the whole cohort. Primary quinolone prophylaxis independently reduced infection-related admission. A total of 51 patients died as a result of infection. The 6-month, 12-month, 2-year, and 5-year cumulative incidences of infection-related death were 3.3%, 5.0%, 7.2%, and 11.1%, respectively. Key independent factors associated with infection-related death were an International Prognostic Index (IPI) score of 3 to 5, Cumulative Illness Rating Scale for Geriatrics (CIRS-G) score $6, and low albumin, which enabled us to generate a predictive risk score. We defined a smaller group (15%) of patients (IPI score of 0-2, albumin .36 g/L, CIRS-G score,6) in which no cases of infection-related deaths occurred at 5 years of follow-up. Whether patients at higher risk of infection-related death could be targeted with enhanced antimicrobial prophylaxis remains unknown and will require a randomized trial

SNOntology: Myriads of novel snornas or just a mirage?

<p>Abstract</p> <p>Background</p> <p>Small nucleolar RNAs (snoRNAs) are a large group of non-coding RNAs (ncRNAs) that mainly guide 2'-O-methylation (C/D RNAs) and pseudouridylation (H/ACA RNAs) of ribosomal RNAs. The pattern of rRNA modifications and the set of snoRNAs that guide these modifications are conserved in vertebrates. Nearly all snoRNA genes in vertebrates are localized in introns of other genes and are processed from pre-mRNAs. Thus, the same promoter is used for the transcription of snoRNAs and host genes.</p> <p>Results</p> <p>The series of studies by Dahai Zhu and coworkers on snoRNAs and their genes were critically considered. We present evidence that dozens of species-specific snoRNAs that they described in vertebrates are experimental artifacts resulting from the improper use of Northern hybridization. The snoRNA genes with putative intrinsic promoters that were supposed to be transcribed independently proved to contain numerous substitutions and are, most likely, pseudogenes. In some cases, they are localized within introns of overlooked host genes. Finally, an increased number of snoRNA genes in mammalian genomes described by Zhu and coworkers is also an artifact resulting from two mistakes. First, numerous mammalian snoRNA pseudogenes were considered as genes, whereas most of them are localized outside of host genes and contain substitutions that question their functionality. Second, Zhu and coworkers failed to identify many snoRNA genes in non-mammalian species. As an illustration, we present 1352 C/D snoRNA genes that we have identified and annotated in vertebrates.</p> <p>Conclusions</p> <p>Our results demonstrate that conclusions based only on databases with automatically annotated ncRNAs can be erroneous. Special investigations aimed to distinguish true RNA genes from their pseudogenes should be done. Zhu and coworkers, as well as most other groups studying vertebrate snoRNAs, give new names to newly described homologs of human snoRNAs, which significantly complicates comparison between different species. It seems necessary to develop a uniform nomenclature for homologs of human snoRNAs in other vertebrates, e.g., human gene names prefixed with several-letter code denoting the vertebrate species.</p

Analysis of mass spectrometry data from the secretome of an explant model of articular cartilage exposed to pro-inflammatory and anti-inflammatory stimuli using machine learning

Background: Osteoarthritis (OA) is an inflammatory disease of synovial joints involving the loss and degeneration of articular cartilage. The gold standard for evaluating cartilage loss in OA is the measurement of joint space width on standard radiographs. However, in most cases the diagnosis is made well after the onset of the disease, when the symptoms are well established. Identification of early biomarkers of OA can facilitate earlier diagnosis, improve disease monitoring and predict responses to therapeutic interventions. Methods: This study describes the bioinformatic analysis of data generated from high throughput proteomics for identification of potential biomarkers of OA. The mass spectrometry data was generated using a canine explant model of articular cartilage treated with the pro-inflammatory cytokine interleukin 1 β (IL-1β). The bioinformatics analysis involved the application of machine learning and network analysis to the proteomic mass spectrometry data. A rule based machine learning technique, BioHEL, was used to create a model that classified the samples into their relevant treatment groups by identifying those proteins that separated samples into their respective groups. The proteins identified were considered to be potential biomarkers. Protein networks were also generated; from these networks, proteins pivotal to the classification were identified. Results: BioHEL correctly classified eighteen out of twenty-three samples, giving a classification accuracy of 78.3% for the dataset. The dataset included the four classes of control, IL-1β, carprofen, and IL-1β and carprofen together. This exceeded the other machine learners that were used for a comparison, on the same dataset, with the exception of another rule-based method, JRip, which performed equally well. The proteins that were most frequently used in rules generated by BioHEL were found to include a number of relevant proteins including matrix metalloproteinase 3, interleukin 8 and matrix gla protein. Conclusions: Using this protocol, combining an in vitro model of OA with bioinformatics analysis, a number of relevant extracellular matrix proteins were identified, thereby supporting the application of these bioinformatics tools for analysis of proteomic data from in vitro models of cartilage degradation

A facilitated home-based cardiac rehabilitation intervention for people with heart failure and their caregivers: a research programme including the REACH-HF RCT

This programme found adding the intervention to usual care for people with heart failure with reduced ejection fraction improved quality of life at 12 months compared with usual care alone

The effects and costs of home-based rehabilitation for heart failure with reduced ejection fraction : The REACH-HF multicentre randomized controlled trial

Background Cardiac rehabilitation improves health-related quality of life (HRQoL) and reduces hospitalizations in patients with heart failure, but international uptake of cardiac rehabilitation for heart failure remains low. Design and methods The aim of this multicentre randomized trial was to compare the REACH-HF (Rehabilitation EnAblement in CHronicHeart Failure) intervention, a facilitated self-care and home-based cardiac rehabilitation programme to usual care for adults with heart failure with reduced ejection fraction (HFrEF). The study primary hypothesis was that the addition of the REACH-HF intervention to usual care would improve disease-specific HRQoL (Minnesota Living with Heart Failure questionnaire (MLHFQ)) at 12 months compared with usual care alone. Results The study recruited 216 participants, predominantly men (78%), with an average age of 70 years and mean left ventricular ejection fraction of 34%. Overall, 185 (86%) participants provided data for the primary outcome. At 12 months, there was a significant and clinically meaningful between-group difference in the MLHFQ score of –5.7 points (95% confidence interval –10.6 to –0.7) in favour of the REACH-HF intervention group (p = 0.025). With the exception of patient self-care (p  0.05) at follow-up compared with usual care. The mean cost of the REACH-HF intervention was £418 per participant. Conclusions The novel REACH-HF home-based facilitated intervention for HFrEF was clinically superior in disease-specific HRQoL at 12 months and offers an affordable alternative to traditional centre-based programmes to address current low cardiac rehabilitation uptake rates for heart failure