Development of PSP1: A Biostimulant Based on the Elicitor AsES for Disease Management in Monocot and Dicot Crops

In this work we present a novel biostimulant for sustainable crop disease management named PSP1. PSP1 is based on the plant defense-elicitor AsES, an extracellular protease produced by the strawberry fungal pathogen Acremonium strictum. Fungal fermentation conditions and downstream processing were determined to maximize extracellular protein production, product stability and a high plant defense-eliciting activity, as monitored by anthracnose resistance in supernatant-treated strawberry plants subsequently infected with a viral strain of Colletotrichum acutatum. Fermentation batches were shown to reduce anthracnose development by 30 to 60% as compared to infected non-treated plants. Product formulation was shown to be stable for 6 months when stored at temperatures up to 45°C and toxicological tests showed that PSP1 was harmless to beneficial organisms and non-toxic to mammalian species at concentrations 50 times higher than those used in plant experiments. Furthermore, disease protection studies using dilutions of PSP1 indicated that there is a minimum threshold protease activity needed to induce pathogen defense in strawberry and that this induction effect is dose-independent. A significant characteristic of PSP1 is its broad-range protection against different diseases in various crop species. In soybean, PSP1 reduced the symptomatology by 70% of Corynespora cassiicola, etiological agent of the target spot. This protection effect was similar to the commercial inducer BION 500 WG based on BTH, and both products were shown to induce an oxidative burst and up-regulated PR1-gene expression in soybean. Furthermore, a double PSP1-treatment on greenhouse-grown sugarcane plants provided protection against bacterial red stripe disease caused by Acidovorax avenae and a double foliar application of PSP1 on field-grown wheat plants significantly increased resistance against Fusarium graminearum, causal agent of head blight disease, manifested mainly in an increased seed germination rate. In summary, these disease protection studies demonstrated an effective control against both bacterial and fungal pathogens in both monocot and dicot crop species, which together with its low production cost, effectiveness at low concentrations, long shelf-life, tolerance to high temperatures, harmlessness to non-target organisms and simple handling and application, make PSP1 a very promising candidate for effective and sustainable disease management in many crop species.Fil: Chalfoun, Nadia Regina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto de Tecnología Agroindustrial del Noroeste Argentino; Argentina. Estación Experimental Agroindustrial Obispo Colombres; ArgentinaFil: Sandra B. Durman. Bayer S.A., Argentina – Crop Science LATAM 2, Crop Science Research, Buenos Aires; ArgentinaFil: Budeguer, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto de Tecnología Agroindustrial del Noroeste Argentino; Argentina. Estación Experimental Agroindustrial Obispo Colombres; ArgentinaFil: Caro, María del Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Romina P. Bertani. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto de Tecnología Agroindustrial del Noroeste Argentino; Argentina. Estación Experimental Agroindustrial Obispo Colombres; ArgentinaFil: Pia d.l.A. di-Peto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto de Tecnología Agroindustrial del Noroeste Argentino;; Argentina. Estación Experimental Agroindustrial Obispo Colombres; ArgentinaFil: Sebastian A. Stenglein. Laboratorio de Biología Funcional y Biotecnología, Universidad Nacional del Centro de la Provincia de Buenos Aires-Comisión de Investigaciones Científicas de la Provincia de Buenos Aires and Instituto de Investigaciones en Biodiversidad y Biotecnología – Consejo Nacional de Investigaciones Científicas y Técnicas, Azul; ArgentinaFil: Filippone, María Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto de Tecnología Agroindustrial del Noroeste Argentino; Argentina. Estación Experimental Agroindustrial Obispo Colombres; ArgentinaFil: Enrique R. Moretti. Annuit S.a; ArgentinaFil: Juan C. Díaz Ricci. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Bjorn Welin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto de Tecnología Agroindustrial del Noroeste Argentino; Argentina. Estación Experimental Agroindustrial Obispo Colombres; ArgentinaFil: Castagnaro, Atilio Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto de Tecnología Agroindustrial del Noroeste Argentino; Argentina. Estación Experimental Agroindustrial Obispo Colombres; Argentin

Daily precipitation statistics in a EURO-CORDEX RCM ensemble: added value of raw and bias-corrected high-resolution simulations

Daily precipitation statistics as simulated by the ERA-Interim-driven EURO-CORDEX regional climate model (RCM) ensemble are evaluated over two distinct regions of the European continent, namely the European Alps and Spain. The potential added value of the high-resolution 12 km experiments with respect to their 50 km resolution counterparts is investigated. The statistics considered consist of wet-day intensity and precipitation frequency as a measure of mean precipitation, and three precipitation-derived indicators (90th percentile on wet days?90pWET, contribution of the very wet days to total precipitation?R95pTOT and number of consecutive dry days?CDD). As reference for model evaluation high resolution gridded observational data over continental Spain (Spain011/044) and the Alpine region (EURO4M-APGD) are used. The assessment and comparison of the two resolutions is accomplished not only on their original horizontal grids (approximately 12 and 50 km), but the high-resolution RCMs are additionally regridded onto the coarse 50 km grid by grid cell aggregation for the direct comparison with the low resolution simulations. The direct application of RCMs e.g. in many impact modelling studies is hampered by model biases. Therefore bias correction (BC) techniques are needed at both resolutions to ensure a better agreement between models and observations. In this work, the added value of the high resolution (before and after the bias correction) is assessed and the suitability of these BC methods is also discussed. Three basic BC methods are applied to isolate the effect of biases in mean precipitation, wet-day intensity and wet-day frequency on the derived indicators. Daily precipitation percentiles are strongly affected by biases in the wet-day intensity, whereas the dry spells are better represented when the simulated precipitation frequency is adjusted to the observed one. This confirms that there is no single optimal way to correct for RCM biases, since correcting some distributional features typically leads to an improvement of some aspects but to a deterioration of others. Regarding mean seasonal biases before the BC, we find only limited evidence for an added value of the higher resolution in the precipitation intensity and frequency or in the derived indicators. Thereby, evaluation results considerably depend on the RCM, season and indicator considered. High resolution simulations better reproduce the indicators? spatial patterns, especially in terms of spatial correlation. However, this improvement is not statistically significant after applying specific BC methods.The authors are grateful to Prof. C. Schär for his helpful comments and E. van Meijgaard for making available the RACMO model data. We acknowledge the observational data providers. Calculations for WRF311F were made using the TGCC super computers under the GENCI time allocation GEN6877. The WRF331A from CRP-GL (now LIST) was funded by the Luxembourg National Research Fund (FNR) through grant FNR C09/SR/16 (CLIMPACT). The KNMI-RACMO2 simulations were supported by the Dutch Ministry of Infrastructure and the Environment. The CCLM and REMO simulations were supported by the Federal Ministry of Education and Research (BMBF) and performed under the Konsortial share at the German Climate Computing Centre (DKRZ). The CCLM simulations were furthermore supported by the Swiss National Supercomputing Centre (CSCS) under project ID s78. Part of the SMHI contribution was carried out in the Swedish Mistra-SWECIA programme founded by Mistra (the Foundation for Strategic Environmental Research). This work is supported by CORWES (CGL2010-22158-C02) and EXTREMBLES (CGL2010-21869) projects funded by the Spanish R&D programme and the European COST ACTION VALUE (ES1102). A. C. thanks the Spanish Ministry of Economy and Competitiveness for the funding provided within the FPI programme (BES-2011-047612 and EEBB-I-13-06354). We also thank two anonymous referees for their useful comments that helped to improve the original manuscript

Prevalence of hallux valgus in the general population: a systematic review and meta-analysis

BACKGROUND: Hallux valgus (HV) is a foot deformity commonly seen in medical practice, often accompanied by significant functional disability and foot pain. Despite frequent mention in a diverse body of literature, a precise estimate of the prevalence of HV is difficult to ascertain. The purpose of this systematic review was to investigate prevalence of HV in the overall population and evaluate the influence of age and gender. METHODS: Electronic databases (Medline, Embase, and CINAHL) and reference lists of included papers were searched to June 2009 for papers on HV prevalence without language restriction. MeSH terms and keywords were used relating to HV or bunions, prevalence and various synonyms. Included studies were surveys reporting original data for prevalence of HV or bunions in healthy populations of any age group. Surveys reporting prevalence data grouped with other foot deformities and in specific disease groups (e.g. rheumatoid arthritis, diabetes) were excluded. Two independent investigators quality rated all included papers on the Epidemiological Appraisal Instrument. Data on raw prevalence, population studied and methodology were extracted. Prevalence proportions and the standard error were calculated, and meta-analysis was performed using a random effects model. RESULTS: A total of 78 papers reporting results of 76 surveys (total 496,957 participants) were included and grouped by study population for meta-analysis. Pooled prevalence estimates for HV were 23% in adults aged 18-65 years (CI: 16.3 to 29.6) and 35.7% in elderly people aged over 65 years (CI: 29.5 to 42.0). Prevalence increased with age and was higher in females [30% (CI: 22 to 38)] compared to males [13% (CI: 9 to 17)]. Potential sources of bias were sampling method, study quality and method of HV diagnosis. CONCLUSIONS: Notwithstanding the wide variation in estimates, it is evident that HV is prevalent; more so in females and with increasing age. Methodological quality issues need to be addressed in interpreting reports in the literature and in future research

Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial

Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects. Methods FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762. Findings Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months. Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function. Funding UK Stroke Association and NIHR Health Technology Assessment Programme

Section 50 agreements

Central Research Unit paperSIGLEAvailable from British Library Document Supply Centre- DSC:MFE 1169(CH--92.3233)(microfiche) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Quality assessment in development control

SIGLEAvailable from British Library Document Supply Centre-DSC:3579.0195(no 42) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Home-based exercise in patients with refractory fatigue associated with primary biliary cholangitis: a protocol for the EXerCise Intervention in cholesTatic LivEr Disease (EXCITED) feasibility trial.

INTRODUCTION Fatigue is the most commonly reported symptom of the liver disease primary biliary cholangitis (PBC). It affects 40%-80% of patients, has no effective treatment and is associated with heightened mortality risk. The pathogenesis is unknown, but muscle bioenergetic abnormalities have been proposed to contribute. Directly observed exercise has been shown to attenuate symptoms in small groups; however, due to the rare nature of the disease, home-based interventions need to be evaluated for feasibility, safety and efficacy. METHODS AND ANALYSIS This is a phase 1/pilot, single-arm, open-label clinical trial evaluating a novel home-based exercise programme in patients with PBC with severe fatigue. Forty patients with moderate-severe fatigue (PBC40 fatigue domain score >33; other causes of fatigue excluded) will be selected using a convenience sampling method. A 12-week home-based exercise programme, consisting of individualised resistance, aerobic exercises and telephone health calls (first 6 weeks only), will be delivered. Measures of fatigue (PBC40 fatigue domain; fatigue impact scale), quality of life, sleep (Epworth Sleep Score), physical activity, anxiety and depression, aerobic exercise capacity (incremental shuttle walk test; Duke Activity Status Index) and functional capacity (short physical performance battery) will be assessed at baseline and at 6 and 12 weeks following the intervention. ETHICS AND DISSEMINATION The protocol is approved by the National Research Ethics Service Committee London (IRAS 253115). Recruitment commenced in April 2019 and ended in March 2020. Participant follow-up is due to finish by December 2020. Findings will be disseminated through peer-reviewed publication, conference presentation and social media. TRIAL REGISTRATION NUMBER NCT04265235