Assessment of the environmental impacts of ASR schemes.

This report describes the results of modelling studies undertaken to assess the impacts of ASR on the local environment. Understanding and quantifying these impacts, in relation to other existing or proposed schemes, will be vital in the development, and subsequent licensing of any ASR scheme. As each individual scheme has its own hydrogeological and environmental setting, as well as operational requirements, an all-encompassing model cannot be prescribed. Rather, a set of models, of increasing complexity, have been run for ‘typical’ scenarios to illustrate their use and limitations. They are designed to act as screening tools to assist practitioners, at all stages of an investigation, to decide on the suitability of a site and to identify what additional data are required in order to proceed to the next stage. The models are appended to the report so practitioners can apply them to their specific site, as appropriate

Arbuscular mycorrhizal fungal‐induced tolerance is determined by fungal identity and pathogen density

Societal Impact Statement Plant-parasitic nematodes are a major concern for global food security, and many existing control options are being phased out due to adverse impacts on the environment. Here, we show that although application of arbuscular mycorrhizal fungi (AMF) increases host tolerance to these parasites, these benefits decrease as the parasite burden increases, limiting long-term benefits. This effect was consistent between experiments in the glasshouse and in the field environment, demonstrating the relevance of research into usable technologies. Our findings have potential to aid decision making regarding application of AMF inocula for optimum results in agricultural systems. Summary Plant-parasitic nematodes are a leading global threat to crop production and food security aims. Control strategies based on nematicides and fertilisers are increasingly undesirable due to economic and environmental impacts. Arbuscular mycorrhizal fungi (AMF) may induce host tolerance against pests such as the potato cyst nematode (PCN). Here, we determined the impact of PCN density on the tolerance induced by AMF-host interactions. Additionally, we evaluated the effects of five AMF inocula on PCN fitness though glasshouse and field trials. Greater PCN densities reduce the increased tolerance that AMF may confer on their hosts. This may be due to reduced mycorrhizal colonisation of hosts under higher PCN infection and potentially a threshold at which the presence of PCN severely impacts fungal growth. When tested in the field, the outcomes of AMF inoculation on crop yields were still positive. Inoculation of soil in the field also increased PCN multiplication, suggesting that AMF-induced tolerance may become reduced in the near future when the threshold PCN density is reached. Addition of AMF to agricultural soils may provide a short-term benefit yet lead to a long-term detriment by increasing PCN populations. The effects observed were driven by only one out of the five introduced AMF species, indicating that the remaining species were redundant for this application. This raises important considerations for future application of AMF inocula in agricultural systems and aids our understanding of how widely used ‘beneficial’ soil amendments impact the agricultural ecosystem

Addressing the threat of climate change to agriculture requires improving crop resilience to short-term abiotic stress

Climate change represents a serious threat to global agriculture, necessitating the development of more environmentally resilient crops to safeguard the future of food production. The effects of climate change are appearing to include a higher frequency of extreme weather events and increased day-to-day weather variability. As such, crops which are able to cope with short-term environmental stress, in addition to those that are tolerant to longer term stress conditions are required . It is becoming apparent that the hitherto relatively little studied process of post-stress plant recovery could be key to optimizing growth and production under fluctuating conditions with intermittent transient stress events. Developing more durable crops requires the provision of genetic resources to identify useful traits through the development of screening protocols. Such traits can then become the objective of crop breeding programmes. In this study, we discuss these issues and outline example research in leafy vegetables that is investigating resilience to short-term abiotic stress

Comparison of two non-primitive methods for path integral simulations: Higher-order corrections vs. an effective propagator approach

Two methods are compared that are used in path integral simulations. Both methods aim to achieve faster convergence to the quantum limit than the so-called primitive algorithm (PA). One method, originally proposed by Takahashi and Imada, is based on a higher-order approximation (HOA) of the quantum mechanical density operator. The other method is based upon an effective propagator (EPr). This propagator is constructed such that it produces correctly one and two-particle imaginary time correlation functions in the limit of small densities even for finite Trotter numbers P. We discuss the conceptual differences between both methods and compare the convergence rate of both approaches. While the HOA method converges faster than the EPr approach, EPr gives surprisingly good estimates of thermal quantities already for P = 1. Despite a significant improvement with respect to PA, neither HOA nor EPr overcomes the need to increase P linearly with inverse temperature. We also derive the proper estimator for radial distribution functions for HOA based path integral simulations.Comment: 17 pages, latex, 6 postscript figure

A standardization approach to compare treatment safety and effectiveness outcomes between clinical trials and real-world populations in psoriasis.

BACKGROUND: Patients recruited in randomized controlled trials (RCTs) for biologic therapies in psoriasis are not fully representative of the real-world psoriasis population. OBJECTIVES: Firstly, to investigate whether patient characteristics are associated with being included in a psoriasis RCT. Secondly, to estimate the differences in the incidence of severe adverse events (SAEs) and the response rate between RCT and real-world populations of patients on biologic therapies for psoriasis using a standardization method. METHODS: Data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) were appended to individual participant-level data from two RCTs assessing ustekinumab in patients with psoriasis. Baseline variables were assessed for association of being in an RCT using a multivariable logistic regression model. Propensity score weights were derived to reweigh the registry population so that variables had the distribution of the trial population. We measured the C-statistic of the model with trial status as the dependent variable, and the risk differences in the incidence rate of SAEs in the first year and Psoriasis Area and Severity Index (PASI) after 6 months in the BADBIR cohort before and after weighting. RESULTS: In total 6790 registry and 2021 RCT participants were included. The multivariable logistic regression model had a C-statistic of 0.82 [95% confidence interval (CI) 0.81-0.83]. The risk differences for the incidence rate of SAEs and the proportion of patients with PASI < 1.5 were 9.27 (95% CI -3.91-22.5) per 1000 person-years and 0.95 (95% CI -1.98-4.15), respectively. CONCLUSIONS: Our results suggest that RCTs of biologic therapies in patients with psoriasis are not fully representative of the real-world population, but this lack of external validity does not account for the efficacy-effectiveness gap. What's already known about this topic? Patients with psoriasis who would not be eligible for randomized controlled trials (RCTs) investigating biologic therapies have a greater risk of serious adverse events and lower treatment effectiveness than patients who would have been eligible. What does this study add? Baseline patient characteristics were shown to be predictive of whether a patient would have been eligible for enrolment in an RCT for psoriasis biologic therapy. We did not find any efficacy-effectiveness gap between the sample representative of the real-world population of patients with psoriasis and the sample representative of the RCT population. Factors outside of baseline patient characteristics, such as observer effect and higher adherence in RCTs, may be more influential in any efficacy-effectiveness gap between trial and real-world populations of patients with psoriasis

Risk of major cardiovascular events in patients with psoriasis receiving biologic therapies: a prospective cohort study

Background: The cardiovascular safety profile of biologic therapies used for psoriasis is unclear. Objectives: To compare the risk of major cardiovascular events (CVEs; acute coronary syndrome, unstable angina, myocardial infarction and stroke) in patients with chronic plaque psoriasis treated with adalimumab, etanercept or ustekinumab in a large prospective cohort. Methods: Prospective cohort study examining the comparative risk of major CVEs was conducted using the British Association of Dermatologists Biologics and Immunomodulators Register. The main analysis compared adults with chronic plaque psoriasis receiving ustekinumab with tumour necrosis‐α inhibitors (TNFi: etanercept and adalimumab), whilst the secondary analyses compared ustekinumab, etanercept or methotrexate against adalimumab. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using overlap weights by propensity score to balance baseline covariates among comparison groups. Results: We included 5468 biologic‐naïve patients subsequently exposed (951 ustekinumab; 1313 etanercept; and 3204 adalimumab) in the main analysis. The secondary analyses also included 2189 patients receiving methotrexate. The median (p25–p75) follow‐up times for patients using ustekinumab, TNFi, adalimumab, etanercept and methotrexate were as follows: 2.01 (1.16–3.21), 1.93 (1.05–3.34), 1.94 (1.09–3.32), 1.92 (0.93–3.45) and 1.43 (0.84–2.53) years, respectively. Ustekinumab, TNFi, adalimumab, etanercept and methotrexate groups had 7, 29, 23, 6 and 9 patients experiencing major CVEs, respectively. No differences in the risk of major CVEs were observed between biologic therapies [adjusted HR for ustekinumab vs. TNFi: 0.96 (95% CI 0.41–2.22); ustekinumab vs. adalimumab: 0.81 (0.30–2.17); etanercept vs. adalimumab: 0.81 (0.28–2.30)] and methotrexate against adalimumab [1.05 (0.34–3.28)]. Conclusions: In this large prospective cohort study, we found no significant differences in the risk of major CVEs between three different biologic therapies and methotrexate. Additional studies, with longer term follow‐up, are needed to investigate the potential effects of biologic therapies on incidence of major CVEs

Diagnostic applications of molecular and serological assays for bluetongue and African horse sickness

The availability of rapid, highly sensitive and specific molecular and serologic diagnostic assays, such as competitive enzyme-linked immunosorbent assay (cELISA), has expedited the diagnosis of emerging transboundary animal diseases, including bluetongue (BT) and African horse sickness (AHS), and facilitated more thorough characterisation of their epidemiology. The development of assays based on real-time, reverse-transcription polymerase chain reaction (RT-PCR) to detect and identify the numerous serotypes of BT virus (BTV) and AHS virus (AHSV) has aided in-depth studies of the epidemiology of BTV infection in California and AHSV infection in South Africa. The subsequent evaluation of pan-serotype, real-time, RT-PCR-positive samples through the use of serotype-specific RT-PCR assays allows the rapid identification of virus serotypes, reducing the need for expensive and time-consuming conventional methods, such as virus isolation and serotype-specific virus neutralisation assays. These molecular assays and cELISA platforms provide tools that have enhanced epidemiologic surveillance strategies and improved our understanding of potentially altered Culicoides midge behaviour when infected with BTV. They have also supported the detection of subclinical AHSV infection of vaccinated horses in South Africa. Moreover, in conjunction with whole genome sequence analysis, these tests have clarified that the mechanism behind recent outbreaks of AHS in the AHS-controlled area of South Africa was the result of the reversion to virulence and/or genome reassortment of live attenuated vaccine viruses. This review focuses on the use of contemporary molecular diagnostic assays in the context of recent epidemiologic studies and explores their advantages over historic virus isolation and serologic techniques.https://www.woah.org/en/what-we-do/publications/scientific-and-technical-reviewVeterinary Tropical Disease

Development and validation of a multivariable risk prediction model for serious infection in patients with psoriasis receiving systemic therapy

BACKGROUND: Patients with psoriasis are often concerned about the risk of serious infection associated with systemic psoriasis treatments. OBJECTIVES: To develop and externally validate a prediction model for serious infection in patients with psoriasis within 1 year of starting systemic therapies. METHODS: The risk prediction model was developed using the British Association of Dermatologists Biologic Interventions Register (BADBIR), and the German Psoriasis Registry PsoBest was used as the validation dataset. Model discrimination and calibration were assessed internally and externally using the C-statistic, the calibration slope and the calibration in the large. RESULTS: Overall 175 (1·7%) out of 10 033 participants from BADBIR and 41 (1·7%) out of 2423 participants from PsoBest developed a serious infection within 1 year of therapy initiation. Selected predictors in a multiple logistic regression model included nine baseline covariates, and starting infliximab was the strongest predictor. Evaluation of model performance showed a bootstrap optimism-corrected C-statistic of 0·64 [95% confidence interval (CI) 0·60-0·69], calibration in the large of 0·02 (95% CI -0·14 to 0·17) and a calibration slope of 0·88 (95% CI 0·70-1·07), while external validation performance was poor, with C-statistic 0·52 (95% CI 0·42-0·62), calibration in the large 0·06 (95% CI -0·25 to 0·37) and calibration slope 0·36 (95% CI -0·24 to 0·97). CONCLUSIONS: We present the first results of the development of a multivariable prediction model. This model may help patients and dermatologists in the U.K. and the Republic of Ireland to identify modifiable risk factors and inform therapy choice in a shared decision-making process