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Phoma stem canker is an internationally important disease of oilseed rape (Brassica napus, canola, rapeseed), causing serious losses in Europe, Australia and North America. UK losses of Euro56M per season are estimated using national disease survey data and a yield loss formula. Phoma stem canker pathogen populations comprise two main species, Leptosphaeria maculans, associated with damaging stem base cankers, and Leptosphaeria biglobosa, often associated with less damaging upper stem lesions. Both major gene and quantitative trait loci mediated resistance to L. maculans have been identified in B. napus, but little is known about resistance to L. biglobosa. Leptosphaeria maculans, which has spread into areas in North America and eastern Europe where only L. biglobosa was previously identified, now poses a threat to large areas of oilseed rape production in Asia. Epidemics are initiated by air-borne ascospores; major gene resistance to initial infection by L. maculans operate! s in the leaf lamina of B. napus. It is not clear whether the quantitative trait loci involved in the resistance to the pathogen that can be assessed only at the end of the season operate in the leaf petioles or stems. In countries where serious phoma stem canker epidemics occur, a minimum standard for resistance to L. maculans is included in national systems for registration of cultivars. This review provides a background to a series of papers on improving strategies for managing B. napus resistance to L. maculans, which is a model system for studying genetic interactions between hemi-biotrophic pathogens and their hosts

Place cells in hippocampal area CA1 may receive positional information from the intrahippocampal associative network in area CA3 or directly from the entorhinal cortex. To determine whether direct entorhinal connections support spatial firing and spatial memory, we removed all input from areas CA3 to CA1, thus isolating the CA1 area. Pyramidal cells in the isolated CA1 area developed sharp and stable place fields. Rats with an isolated CA1 area showed normal acquisition of an associative hippocampal-dependent spatial recognition task. Spatial recall was impaired. These results suggest that the hippocampus contains two functionally separable memory circuits: The direct entorhinal-CA1 system is sufficient for recollection-based recognition memory, but recall depends on intact CA3-CA1 connectivity.

Background:Gout appears to be one of the most common form of inflammatory arthritis, but few informations are available in routine practice about current management and satisfaction of French patients.Objectives:Describe the experience of gouty patients through a real-life survey, including their disease experience and management.Methods:The survey, initiated by the Association de Patients AFLAR (Association Française de Lutte Anti Rhumatismale) was conducted under the aegis of a steering committee (expert rheumatologist, GP, pharmacist, patients and AFLAR representative). The design and content of the survey has been developed together with several patient representatives and experts. The questionnaire was tested in advance to ensure that patients understood it and that it was consistent with their expectations. The questionnaire, made of closed questions mainly with simple choice, non-blocking, is Google Form type, self-administered and anonymized. The recruitment process is focused on adult patients with gout who are either adhering or not adhering to the AFLAR. Their solicitation was initiated by this association (Questionnaire linked to the AFLAR newsletter and social networks (FB, Linkedin) before being relayed by patients between them. The survey took place from 04/01/2023 to 27/01/2023.Results:The population of 211 respondents is 60% male, 83% aged 60 and over, composed of retirees at 69%, and followed by a General Practitioner at over 73% or a GP/rheumatologist duo at 18%.The gouty disease is advanced and active with a diagnosis made for 5 years or 1 to 5 years for 75% of patients, with 2 or more attacks in the last 12 months for 45.7% of patients and at least 2 affected joints for 57% of patients. The most challenging symptoms are severe joint pain eight times out of 10, walking disability more than seven times out of 10, and decreased quality of life four times out of 10. Patients who receive treatment report feeling better or significantly better three out of four times and consider having a solid understanding of what to do in the event of a crisis, including taking medication prescribed beforehand or during an earlier crisis. Treatment during the last gout attack was based on colchicine (alone or combined with tiemonium and opium powder) or NSAIDs respectively in 68% and 24% of cases. In 64% of cases, additional analgesics are used, with one in two cases opting for a level 1 analgesic and three out of four cases opting for a prescription. More than 9 times out of 10 patients are satisfied with their treatment, with their satisfaction being highest for the 3 most troublesome symptoms in the same order. Information on the use of the drug in combination and on the potential effects of the drug are given respectively 6 times out of 10 and 1 time out of 2 mainly by the GP to 86% and 81%. During the last crisis, people preferred to follow proper diet and drinking plenty of water over resting and applying cold, with 38% and 33% respectively compared to 8% and 21%.Conclusion:French Gouty patients know their disease well, are satisfied with the treatment, follow the advice relatively well and could benefit more from information by health care professionals.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:Didier Poivret: None declared, Gilles Le Pape: None declared, Jean Michel Mrozovski: None declared, Francoise Alliot Launois: None declared, Marie Hélène Brun: None declared, Franck Henri Mayoli.

ObjectivesTo describe the application of the model described in part A and part B of this series of articles for risk assessment (RA) and risk control (RC) of non-sterility during aseptic handling. The model was applied in nine hospital pharmacies.MethodsThe starting point was an audit of each hospital pharmacy. The determined risk reduction and remaining risks were entered into a risk assessment model. The corresponding risk prioritisation numbers (RPNs) for each source of risk were calculated and these values were summed up to a cumulative RPN. Subsequently, all hospital pharmacies started an improvement programme, using the risk assessment as input. Results of aseptic process simulation (APS) and microbiological monitoring (MM) were also collected. The participants were informed about their progress of risk reduction and results of APS and MM during the study period. At the end of the study (about 4 years after the start), a final assessment was executed by using a checklist with risk reducing measures for each source of risk. Additional risk reduction and remaining risks were put in an RA and RC template and corresponding RPN values and a new cumulative RPN were determined.ResultsAt the start of the study differences in cumulative RPN values were relatively small (from 630 to 825). At the end they were relatively great (from 230 to 725), which illustrates a different sense of urgency for reducing the risk of non-sterility. Of all the risk reducing measures, a yearly audit of all operators had the greatest impact on reducing the risk of non-sterility. Except for glove prints, there was no correlation between process improvement (lower cumulative RPN) and results of microbiological controls.ConclusionA systematic and science-based reduction of the risks of non-sterility can be done by using a checklist with risk reducing measures and an RA & RC template. Prospectively, the relevance of each risk reducing measure can be demonstrated by RPN calculations. Microbiological controls are an important part of the overall assurance of product quality. However, the results are less useful for assessing the risk of non-sterility.

Resistance of Brassica napus (oilseed rape, canola) conferred by three different major resistance genes has been overcome by changes in virulence of Leptosphaeria maculans populations in France and Australia. In South Australia where B. napus cultivars with major gene resistance derived from Brassica rapa ssp. sylvestris were grown extensively, resistance was rendered ineffective within 3 years of commercial release of the cultivar. Disease severity was higher on cultivars with sylvestris-derived resistance than cultivars with polygenic resistance. This Australian situation is compared to that in France, where resistance conferred by the Rlm1 gene was overcome nation-wide in 5 years under commercial cropping practices, and also where a source of resistance introgressed into B. napus from B. juncea was rendered inefficient in 3 years in experimental field plots near Rennes.

ObjectivesTo improve the disinfection methods for materials with a non-sterile surface to be used in aseptic handling.MethodsThe surface bioburden on ampoules (A) and injection vials (IV) is determined by contact plates and total immersion. The occurrence of spore-forming bacteria is determined by strain colouring and matrix-assisted laser desorption ionisation-time of flight mass spectrometry. The disinfection procedures of non-sterile materials in 10 hospital pharmacies are judged by observing.ResultsAfter wiping according to local disinfection methods, the mean surface bioburden determined by contact plates in 10 hospital pharmacies is 0.36 (plastic A), 0.50 (glass A) and 0.29 colony-forming unit (cfu) (IV). The observers found great differences in accuracy of wiping and degree of wetting the sterile gauzes.After improved wiping with commercially available alcohol impregnated sterile wipes and a two-towel technique (one-step TT disinfection), the mean surface bioburden determined by contact plates is 0.03 (plastic A), 0.2 (glass A) and 0.13 cfu (IV). Further improvement can be reached by submerging A and IV in ethanol 70% followed by improved wiping (two-step TT disinfection), but still micro-organisms will remain (mean surface bioburden determined by total immersion is 0 (plastic A) and 0.3 cfu (IV); glass A not determined). Two-step TT disinfection is more labour intensive. Spilling of alcohol is another disadvantage. However, we presume one-step TT disinfection is effective enough in daily practice. Routine surface bioburden determinations have to prove this.The effectiveness of the combination of spray and wipe is not examined because we observed a quick disappearance of alcohols from vertical as well as horizontal surfaces, which shortens the contact time to far below the advised 2 min.Spore-forming bacteria disappear as quickly as other micro-organisms during disinfection by alcohols.ConclusionLocal disinfection procedures can be improved. Complete removal of micro-organisms from materials with a non-sterile surface, even after two-step TT disinfection, is impossible. Routine surface bioburden determinations have to prove if one-step TT disinfection is effective enough.

The most common and effective way to control phoma stem canker (blackleg) caused by Leptosphaeria maculans in oilseed rape (Brassica napus) is through the breeding of resistant cultivars. Race specific major genes that mediate resistance from the seedling stage have been identified in B. napus or have been introgressed from related species. Many race specific major genes have been described and some of them are probably identical in B. napus (allotetraploid AACC) and the parental species B. rapa (diploid AA). More work is needed using a set of well-characterised isolates to determine the number of different major resistance genes available. In some B. napus cultivars, there is resistance which is polygenic (mediated by Quantitative Trait Loci) and postulated to be race non-specific. Many of these major genes and Quantitative Trait Loci for resistance to L. maculans have been located on B. napus genetic maps. Genes involved in race specific and polygenic resistance are generally distinct.

[...]clinical problems can be solved with knowledge of the product. [...]there are factors that require a prominent role for preparations in hospital pharmacies: [...]delivery between pharmacies will be needed with regard to efficiency, quality and costs. [...]an alternative form of registration is desirable and possible, certainly when we work together in product development and sharing outcome data with regard to efficacy and safety.

It has frequently been hypothesized that quantitative resistance increases the durability of qualitative (R-gene mediated) resistance but supporting experimental evidence is rare. To test this hypothesis, near-isogenic lines with/without the R-gene Rlm6 introduced into two Brassica napus cultivars differing in quantitative resistance to Leptosphaeria maculans were used in a 5-yr field experiment. Recurrent selection of natural fungal populations was done annually on each of the four plant genotypes, using crop residues from each genotype to inoculate separately the four series of field trials for five consecutive cropping seasons. Severity of phoma stem canker was measured on each genotype and frequencies of avirulence alleles in L. maculans populations were estimated. Recurrent selection of virulent isolates by Rlm6 in a susceptible background rendered the resistance ineffective by the third cropping season. By contrast, the resistance was still effective after 5 yr of selection by the genotype combining this gene with quantitative resistance. No significant variation in the performance of quantitative resistance alone was noted over the course of the experiment. We conclude that quantitative resistance can increase the durability of Rlm6. We recommend combining quantitative resistance with R-gene mediated resistance to enhance disease control and crop production.

ObjectivesTo develop methods for surface bioburden determination of ampoules and vials to be used in the validation of the disinfection procedures and in routine monitoring of ampoules and vials.MethodsThe surface bioburdens of ampoules and vials are determined before and after disinfection by contact plates and total immersion.ResultsThe mean surface bioburdens of non-disinfected ampoules and vials taken straight from the original boxes are 2.4 and 5.01 cfu (total immersion; n = 20), and 0.97 and 0.94 cfu (contact plates; n = 60). The mean surface bioburdens of ampules and vials after disinfection by wiping are 1.15 and 7.50 cfu (total immersion; n = 20), and 0.12 and 0.10 cfu (contact plates; n = 60). The high number of cfu on vials (total immersion) indicate hidden cfu around the neck not removable by wiping and not detected by contact plates. Total immersion needs special laboratory facilities and is expensive (about €50 a sample). Therefore, it is less appropriate for use in routine monitoring. However, because of the high recovery, it is the method of choice for the validation of the disinfection procedure. Surface bioburden determination by contact plates is relatively simple. Non-flat surfaces cannot be reached, but the recovery from the touched flat part of the surface is high (around 50%). The recovery from swabs is low (around 10%). Another disadvantage of swabs is the laboratory work after sampling. We therefore advise contact plates for routine monitoring. To get a reliable value of the mean surface bioburden at least 30 samples need to be examined.ConclusionTotal immersion is the method of choice for the determination of the effectiveness of a disinfection procedure for ampoules and vials. Contact plate is the method of choice for routine monitoring of the surfaces of ampoules and vials.