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International audience; In the context of climate change, plant mortality is increasing worldwide in both natural and agroecosystems. However, our understanding of the underlying causes is limited by the complex interactions between abiotic and biotic factors and the technical challenges that limit investigations of these interactions. Here, we studied the interaction between two main drivers of mortality, drought and vascular disease (esca), in one of the world’s most economically valuable fruit crops, grapevine. We found that drought totally inhibited esca leaf symptom expression. We disentangled the plant physiological response to the two stresses by quantifying whole-plant water relations (i.e., water potential and stomatal conductance) and carbon balance (i.e., CO 2 assimilation, chlorophyll, and nonstructural carbohydrates). Our results highlight the distinct physiology behind these two stress responses, indicating that esca (and subsequent stomatal conductance decline) does not result from decreases in water potential and generates different gas exchange and nonstructural carbohydrate seasonal dynamics compared to drought.

Um den Einfluss verschiedener Erziehungssysteme bzw. Rebschnittmethoden auf die Entwicklung einer Rebstockkrankheit – in diesem Fall Esca - zu veranschaulichen, wurde eine Studie durchgefuhrt, die auf im Rahmen von zwei Projekten erzielen Ergebnisse basiert: CASDAR/ CNIV (2013-2017) und 'GTDfree', finanziert von der ANR und der Maison Hennessy (2016-2021). Eine bedeutende Schlussfolgerung ist, dass im Rahmen der Pravention und des Managements von Esca, insbesondere bei empfindlichen Rebsorten, extrem vereinfachte Erziehungssysteme und ubermasig strenge Rebschnitte vermieden werden sollten.

Hydraulic failure has been extensively studied during drought-induced plant dieback, but its role in plant-pathogen interactions is under debate. During esca, a grapevine (Vitis vinifera) disease, symptomatic leaves are prone to irreversible hydraulic dysfunctions but little is known about the hydraulic integrity of perennial organs over the short- and long-term. We investigated the effects of esca on stem hydraulic integrity in naturally infected plants within a single season and across season(s). We coupled direct (ks) and indirect (kth) hydraulic conductivity measurements, and tylose and vascular pathogen detection with in vivo X-ray microtomography visualizations. Xylem occlusions (tyloses) and subsequent loss of stem hydraulic conductivity (ks) occurred in all shoots with severe symptoms (apoplexy) and in more than 60% of shoots with moderate symptoms (tiger-stripe), with no tyloses in asymptomatic shoots. In vivo stem observations demonstrated that tyloses occurred only when leaf symptoms appeared, and resulted in more than 50% loss of hydraulic conductance in 40% of symptomatic stems, unrelated to symptom age. The impact of esca on xylem integrity was only seasonal, with no long-term impact of disease history. Our study demonstrated how and to what extent a vascular disease such as esca, affecting xylem integrity, could amplify plant mortality through hydraulic failure.

Hydraulic failure has been extensively studied during drought-induced plant dieback, but its role in plant-pathogen interactions is under debate. During esca, a grapevine (Vitis vinifera) disease, symptomatic leaves are prone to irreversible hydraulic dysfunctions but little is known about the hydraulic integrity of perennial organs over the short- and long-term. We investigated the effects of esca on stem hydraulic integrity in naturally infected plants within a single season and across season(s). We coupled direct (ks) and indirect (kth) hydraulic conductivity measurements, and tylose and vascular pathogen detection with in vivo X-ray microtomography visualizations. We found xylem occlusions (tyloses), and subsequent loss of stemks, in all of the shoots with severe symptoms (apoplexy) and in more than 60% of the shoots with moderate symptoms (tiger-stripe), and no tyloses in shoots that were currently asymptomatic. In vivo stem observations demonstrated that tyloses were observed only when leaf symptoms appeared, and resulted in more than 50% PLC in 40% of symptomatic stems, unrelated to symptom age. The impact of esca on xylem integrity was only seasonal and no long-term impact of disease history was recorded. Our study demonstrated how and to what extent a vascular disease such as esca, affecting xylem integrity, could amplify plant mortality by hydraulic failure.HighlightOur study reveals that esca can critically affect xylem water movement in grapevine perennial organs, by the presence of plant-derived tyloses.

International audience; Background. The assessment of value along the clinical development of new biopharmaceutical compounds is a challenging task. Complex and uncertain evidence has to be analyzed, considering a multitude of value preferences from different stakeholders. Objective. To investigate the use of multicriteria decision analysis (MCDA) to support decision making during drug development while considering payer and health technology assessment (HTA) value concerns, by applying the Advance Value Framework in nonalcoholic steatohepatitis (NASH) and testing for the consistency of the results. Design. A multiattribute value theory methodology was applied and 2 rounds of decision conferences (DCs) were organized in 3 countries (England, France, and Germany), with the participation of national key experts and stakeholders using the MACBETH questioning protocol and algorithm. A total of 51 health care professionals, patient advocates, and methodologists, including (ex-) committee members or assessors from national HTA bodies, participated in 6 DCs in the study countries. Target Population. NASH patients in fibrosis stages F2 to 3 were considered. Interventions. The value of a hypothetical product profile was assessed against 3 compounds under development using their phase 2 results. Outcome Measures. DC participants' value preferences were elicited involving criteria selection, options scoring, and criteria weighting. Results. Highly consistent valuation rankings were observed in all DCs, always favoring the same compound. Highly consistent rankings of criteria clusters were observed, favoring therapeutic benefit criteria, followed by safety profile and innovation level criteria. Limitations. There was a lack of comparative treatment effects, early evidence on surrogate endpoints was used, and stakeholder representativeness was limited in some DCs. Conclusions. The use of MCDA is promising in supporting early HTA, illustrating high consistency in results across countries and between study rounds.

Background Mendelian Randomization is a type of instrumental variable (IV) analysis that uses inherited genetic variants as instruments to estimate causal effects attributable to genetic factors. This study aims to estimate the impact of obesity on annual inpatient healthcare costs in the UK using linked data from the UK Biobank and Hospital Episode Statistics (HES). Methods UK Biobank data for 482,127 subjects was linked with HES inpatient admission records, and costs were assigned to episodes of care. A two-stage least squares (TSLS) IV model and a TSLS two-part cost model were compared to a naïve regression of inpatient healthcare costs on body mass index (BMI). Results The naïve analysis of annual cost on continuous BMI predicted an annual cost of £21.61 [95% CI £20.33 – £22.89] greater cost per unit increase in BMI. The TSLS IV model predicted an annual cost of £14.36 [95% CI £0.31 – £28.42] greater cost per unit increase in BMI. Modelled with a binary obesity variable, the naïve analysis predicted that obese subjects incurred £205.53 [95% CI £191.45 – £219.60] greater costs than non-obese subjects. The TSLS model predicted a cost £201.58 [95% CI £4.32 – £398.84] greater for obese subjects compared to non-obese subjects. Conclusions The IV models provide evidence for a causal relationship between obesity and higher inpatient healthcare costs. Compared to the naïve models, the binary IV model found a slightly smaller marginal effect of obesity, and the continuous IV model found a slightly smaller marginal effect of a single unit increase in BMI.

Grapevine trunk diseases (GTDs) are among the most destructive diseases of vineyards worldwide, including Algeria. In the fungal complex involved in GTD symptoms, referred as grapevine trunk-pathogens, Paeomoniella chlamydospora and Phaeoacremonium minimum have a determining infecting role as pioneer fungi. Due to the lack of efficiency of conventional disease management practices, a search for alternative strategies, such as biocontrol, is needed. Taking the approach of looking for biocontrol candidates in the environment surrounding the plant, the present study explored actinobacteria diversity within vineyard soils of six grape-producing regions in Algeria. Based on their 16S rRNA gene sequence, identification and phylogenic analysis were performed on the 40 isolates of actinobacteria obtained. Forty percent of strains were attached to Streptomyces, including two evidenced new species, and 32.5% were affiliated to Saccharothrix. The other less represented genera were Actinoplanes, Nocardia, Nocardiopsis, Lentzea, Nonomuraea, Promicromonospora, Saccharopolyspora and Streptosporangium. Screening based on antagonistic and plant growth promotion (PGP) abilities of the strains showed that 47.5% of the isolates exhibited appreciable antagonistic activities against both Pa. chlamydospora and Pm. minimum, with the two best strains being Streptomyces sp. Ms18 and Streptomyces sp. Sb11. Screening for plant growth promoting properties demonstrated that majority of the strains were able to produce indole acetic acid, siderophores, ammonia, ACC deaminase, cellulase and amylase, and fix N2. Through a PGP-traits-based cluster analysis, the most interesting strains were highlighted. Taking into account both antagonistic and PGP properties, Streptomyces sp Sb11 was selected as the most promising candidate for further evaluations of its efficiency in a GTDs context.

Achieving comprehensive patient centricity in cost-effectiveness analyses (CEAs) requires a statistical approach that accounts for patients' preferences and clinical and demographic characteristics. Increased availability and accessibility of patient-level health-related utility data from clinical trials or observational database provide enhanced opportunities to conduct more patient-centered CEA. Regression-based approaches that incorporate patient-level data hold great promise for enhancing CEAs to be more patient centered; this paper provides guidance regarding two CEA approaches that apply regression-based approaches utilizing patient-level health-related utility and costs data. The first approach utilizes patient-reported preferences to determine patient-specific utility. This approach evaluates how individuals' unique clinical and demographic factors affect their utility and cost levels over the course of treatment. The underlying motivation of this approach is to produce CEA estimates that reflect patient-level utilities and costs while adjusting for socio-demographic and clinical factors to aid patient-centered coverage and treatment decision-making. In the second approach, patient utilities are estimated based on the clinically defined health states through which a patient may transition throughout the course of treatment. While this approach is grounded on the widely used Markov transition model, we refine the model to facilitate an enhancement in conducting regression-based analysis to achieve transparent understanding of differences in utilities and costs across diverse patient populations. We discuss the unique statistical challenges of each approach and describe how these analytical strategies are related to non-regression-based models in health services research.

Auf Englisch Black measles, auf Franzosisch Esca, auf Italienisch Escha, auf Spanisch Yesca, auf Griechisch Iska… Uber diesen Schrecken der Winzer in aller Welt herrscht viel Verunsicherung bezuglich Eigenschaften und Entwicklung. Allerdings hat die Forschung hier Fortschritte gemacht und eine jungste wissenschaftliche Untersuchung uber die Auswirkungen von Veredelungsmethoden auf Blattsymptome hat dem komplexen Puzzle, den das Wissen uber diese Krankheit darstellt, ein weiteres Teil hinzugefugt. Pfropfveredelungen, die direkt in der Parzelle erfolgen, weisen wesentlich bessere Ergebnisse auf.

International audience; Esca is a Grapevine Trunk Disease (GTD) caused by a broad range of taxonomically unrelated fungal pathogens. These attack grapevine wood tissues inducing necroses even in the conductive vascular tissues, thus affecting the vine physiology and potentially leading to plant death. However, the influence of Esca on leaf and whole-plant water transport disruption remains poorly understood. In this paper, a detailed analysis of xylem-related physiological parameters in grapevines that expressed Esca-foliar symptoms was carried out. The experiments were conducted in a vineyard in the Bordeaux region (France) on cv. Cabernet-Sauvignon (Vitis vinifera L.) grapevines, which were monitored for Esca-foliar symptoms over a two-year period. Heat dissipation sap-flow sensors were installed during the summer on grapevines having expressed or not Esca-foliar symptoms. Leaf water potential, stomatal conductance and leaf transpiration were also measured. Physiological monitoring showed that sap flow density and whole-plant transpiration of Esca-infected grapevines decreased significantly a week before the first foliar symptoms appeared. When atmospheric water demand (Vapour Pressure Deficit, VPD) was the highest, both parameters tended to be about twice as low in symptomatic grapevines as in asymptomatic ones. Sap flow density data at the maximum transpiration-time, was systematically 29-30% lower in Esca-infected grapevines compared to control plants before or after the appearance of Esca-foliar symptoms. This trend was observed whatever the temperatures and VPD values measured. In Esca-diseased plants, larger amounts of necrotic wood, mainly white rot, were found in the trunk and cordon of symptomatic grapevines compared to healthy ones, suggesting necroses have an influence in reducing the whole-plant hydraulic capacity. This study reveals that the use of physiological monitoring methods, together with the visual monitoring of foliar symptoms, could prove useful in providing accurate measurements of Esca disease severity.

Vascular pathogens cause disease in a large spectrum of perennial plants, with leaf scorch being one of the most conspicuous symptoms. Esca in grapevine (Vitis vinifera) is a vascular disease with huge negative effects on grape yield and the wine industry. One prominent hypothesis suggests that vascular disease leaf scorch is caused by fungal pathogen-derived elicitors and toxins. Another hypothesis suggests that leaf scorch is caused by hydraulic failure due to air embolism, the pathogen itself, and/or plant-derived tyloses and gels. In this study, we transplanted mature, naturally infected esca symptomatic vines from the field into pots, allowing us to explore xylem integrity in leaves (i.e. leaf midveins and petioles) using synchrotron-based in vivo x-ray microcomputed tomography and light microscopy. Our results demonstrated that symptomatic leaves are not associated with air embolism. In contrast, symptomatic leaves presented significantly more nonfunctional vessels resulting from the presence of nongaseous embolisms (i.e. tyloses and gels) than control leaves, but there was no significant correlation with disease severity. Using quantitative PCR, we determined that two vascular pathogen species associated with esca necrosis in the trunk were not found in leaves where occlusions were observed. Together, these results demonstrate that symptom development is associated with the disruption of vessel integrity and suggest that symptoms are elicited at a distance from the trunk where fungal infections occur. These findings open new perspectives on esca symptom expression where the hydraulic failure and elicitor/toxin hypotheses are not necessarily mutually exclusive.

IntroductionDementia is the fastest growing major cause of disability globally with a mounting social and financial impact for patients and their families but also to health and social care systems. This review aims to systematically synthesise evidence on the utilisation of resources and costs incurred by patients and their caregivers and by health and social care services across the full spectrum of dementia, from its preceding preclinical stage to end of life. The main drivers of resources used and costs will also be identified.Methods and analysisA systematic literature review was conducted in MEDLINE, EMBASE, CDSR, CENTRAL, DARE, EconLit, CEA Registry, TRIP, NHS EED, SCI, RePEc and OpenGrey between January 2000 and beginning of May 2017. Two reviewers will independently assess each study for inclusion and disagreements will be resolved by a third reviewer. Data will be extracted using a predefined data extraction form following best practice. Study quality will be assessed with the Effective Public Health Practice Project quality assessment tool. The reporting of costing methodology will be assessed using the British Medical Journal checklist. A narrative synthesis of all studies will be presented for resources used and costs incurred, by level of disease severity when available. If feasible, the data will be synthesised using appropriate statistical techniques.Ethics and disseminationIncluded articles will be reviewed for an ethics statement. The findings of the review will be disseminated in a related peer-reviewed journal and presented at conferences. They will also contribute to the work developed in the Real World Outcomes across the Alzheimer’s disease spectrum for better care: multi-modal data access platform (ROADMAP).Trial registration numberCRD42017071413.

Aims: To detect and identify the cultivable microorganisms putatively associated with esca disease in representative Lebanese vineyards.Methods and results: Two field surveys were conducted in Lebanon in 2005 and 2007 to study the fungal community associated with grapevine wood lesions. A total of 68 vines showing typical esca symptoms were randomly sampled in 17 vineyards and cross sections were obtained of cordons and trunks. The shape and type of inner necrosis and discoloration were examined and isolations were made from the symptomatic wood. Isolation results showed that inner necrosis and isolated fungi were similar to those previously found elsewhere, namely in Central Europe or Mediterranean countries. Additionally, three methods for numerical evaluation of micro-organisms found were compared.Conclusion: Most fungal pathogens generally associated with grapevine trunk diseases were detected, of which the basidiomycete Fomitiporia mediterranea and species of the ascomycete family Botryosphaeriaceae were the most frequently encountered. Additionally, a large diversity of other wood colonizing micro-organisms was detected. The putative role of some of the obtained micro-organisms in the process of wood degradation related to esca disease is discussed.Significance and impact of the study: This isolation study is presently the most completed that was carried out with grapevine wood samples collected in Lebanon. Besides, it is the first to provide isolation results based on a classification of inner necrosis in five categories and to compare three criteria for numerical evaluation. This study also tends to further highlight that Botryosphaeriaceae species are common wood inhabiting fungi that should be associated with esca.

Aim: The aim of the survey was to investigate if the grafting type influences the foliar expression of Esca during summer.Methods and Results: Observations were conducted on plots distributed in two French winegrowing regions (two different climatic regions) with two varieties (Cabernet-Sauvignon in the Bordeaux region and Mourvèdre in Provence). Three grafting types were compared: Omega graft, Whip and Tongue graft, and full cleft graft. For both varieties, we found a significant effect of the type of grafting on the foliar development of Esca symptoms. Full cleft grafted plots showed a significantly lower percentage of Esca foliar symptoms than the other two modalities, which were not significantly different from one another. Concerning Omega grafted plots, a significant difference in the rate of Esca foliar symptoms was highlighted compared to full cleft grafted plots, with a higher rate on Omega grafted plots, but these plots were also younger.Conclusions: The study established, for the first time, the difference between full cleft field grafted plots and Omega and Whip and Tongue grafted plots, revealing a higher incidence of Esca on the latter types of grafting.Significance and impact of the study: The spread of mechanical graft could be one of the factors explaining the increasing incidence of Esca in vineyard.

International audience; Grapevine wood hosts diverse fungal species, including pathogens that cause grapevine trunk diseases and wood decomposers, with detrimental effects on yields. This study focuses on the effects of two pruning systems, minimal (min-) or spur-pruning, on the community of trunk pathogens and other wood-colonizing fungi in the trunks of two cultivars, Mourvèdre and Syrah. Culture and DNA-based methods were used to describe the fungal communities. In both cultivars, especially Syrah, spur-pruned vines had more wood necrosis than min-pruned vines, and the community of spur-pruned Syrah was distinguished by its single-stranded conformational polymorphism (SSCP) profile. Diversity profiles of all 88 cultivated taxa and canonical correspondence analyses of the 15 most frequently isolated taxa revealed differences in community structure due to pruning system, trunk location, and/or wood type. Greater levels of wood necrosis may be due to the composition of the fungal community rather than to a greater diversity of taxa.

The generalist ascomycete fungus Eutypa lata causes Eutypa dieback of grapevine (Vitis vinifera) worldwide. To decipher the cosmopolitan distribution of this fungus, the population genetic structure of 17 geographic samples was investigated from four continental regions (Australia, California, Europe and South Africa), based on analysis of 293 isolates genotyped with nine microsatellite markers. High levels of haplotypic richness (R = 0·91–1) and absence of multilocus linkage disequilibrium among loci supported the preponderance of sexual reproduction in all regions examined. Nonetheless, the identification of identical multilocus haplotypes with identical vegetative compatibility groups, in some vineyards in California and South Africa, suggests that asexual dispersal of the fungus among neighbouring plants could be a rare means of disease spread. The greatest levels of allelic richness (A = 4·89–4·97) and gene diversity (H = 0·66–0·69) were found in Europe among geographic samples from coastal areas surrounding the Mediterranean Sea, whereas the lowest genetic diversity was found in South Africa and Australia (A = 2·78–3·74; H = 0·49–0·57). Samples from California, Australia and South Africa, which had lower genetic diversity than those of Europe, were also characterized by demographic disequilibrium and, thus, may represent founding populations of the pathogen. Low but significant levels of genetic differentiation among all samples (DEST = 0·12, P = 0·001; FST = 0·03, P = 0·001) are consistent with historical gene flow preventing differentiation at continental scales. These findings suggest that global, human-mediated spread of the fungus may have resulted in its current global distribution.

Background: For reimbursement purposes of pimecrolimus cream 1%, the Belgian authorities asked to document its consumption, its topical corticosteroid-sparing effect and quality of life within the routine clinical practice. Objectives: We aimed to address the 3 queries of the Belgian authorities. Methods: An open-label, observational, multicentre, 1-year study under drug prescription was performed. Results: A total of 416 consecutive patients were enrolled in 49 centres. The mean annual amount of prescribed pimecrolimuscream 1% per patient was 120.8 g (SD = 117.0), with an estimated consumption of 104.4 g (SD = 117.6). The median annual amount prescribed was 90.0 g [interquartile range (IQR) = 45–150] and the estimated consumption 63.6 g (IQR = 32.4–132). Topical corticosteroids had been used before the study in 81.7% of the population. With pimecrolimus cream 1% during the study, 83.3% of the previous corticosteroid users stated less topical corticosteroid use than before and 36% of them did not apply topical corticosteroids at all during the study. The mean improvements compared to baseline in Parents’ Index Quality of Life-Atopic Dermatitis and Quality of Life Index-Atopic Dermatitis scores were 34.5% (SD = 84.3) and 31.2% (SD = 70.8), respectively. The median improvements were 50.0% (IQR = 12.5–85.7%) and 46.4% (IQR = 0.0–85.0%), respectively. Conclusions: In routine practice the consumption of pimecrolimus cream 1% is relatively low, with corticosteroid-sparing effect, improvement in quality of life and good tolerability.

International audience; La Yesca es hoy la enfermedad de la madera la más preocupante en Francia. Su progreso desde el final del siglo XX, incluso antes de la prohibición de arsenito de sodio, fue tal que algunos la han considerado como una “enfermedad emergente”. Después de recordar los principales datos del Observatorio Nacional para evaluar la situación de las principales “Enfermedades de la Madera de la Vid” durante la última década, este artículo sugiere varias hipótesis que pueden explicar la progresión de este síndrome. Se complementa con una sección sobre los síntomas y la dinámica de su aparición, que no había sido revisado durante casi un siglo. Los resultados de las observaciones finas y regulares en viñedo en Francia o en el extranjero, dan lugar a una redefinición de los síntomas de la yesca y conducen a nuevas preguntas. Este texto está inspirado en gran parte de un artículo publicado en 2012 y presentado en una conferencia del AFPP (Asociación Francesa para la Protección de las Plantas).

International audience; Grapevine dieback is an increasing problem in grape vineyards in Algeria. We conducted field surveys each spring between 2006 and 2012 to determine the fungal pathogens associated with grapevine decline in various grape-growing regions. We isolated and identified 3 species of Botryosphaeriaceae (Botryosphaeria dothidea, Diplodia seriata, and Neofusicoccum parvum) from infected wood using a combination of morphological and cultural characters, as well as phylogenetic analyses of ribosomal DNA internal transcribed spacer (ITS) regions and fruiting body. We identified 20 isolates of Diplodia seriata, 13 isolates of Botryosphaeria dothidea, and 7 isolates of Neofusicoccum parvum. Inoculation of grapevine plantlets with the 3 Botryosphaeriaceae species produced necrosis and vascular lesions in the wood after a 6-week incubation; Neofusicoccum parvum isolates were the most virulent, followed by D. seriata and B. dothidea. All 3 species were re-isolated from lesions on infected plantlets. Our results represent the first report of a canker disease of grapevine associated with species of the Botryosphaeriaceae in Algeria.

National audience; Travail Au cours de la dernière décennie, un suivi précis et régulier du développement des symptômes foliaires caractéristiques de l'esca (tigrés) a été réalisé, principalement en Bordelais mais aussi en Europe et sur le pourtour méditerranéen. Résultats Les résultats permettent de redéfinir les symptôme selon leur aspect, leur gravité et leur évolution. Les éléments nouveaux, par rapport aux descriptions précédentes, sont précisés. L'enquête a révélé que les dommages foliaires d'esca sont très fréquemment associés à un un dommage vasculaire singulier, peu décrit et peu étudié par le passé : une altération du bois externe, de couleur orangée, superficielle, longitudinale, plus ou moins large, située juste sous l'écorce et dans la continuité des symptômes foliaires. A suivre Ces observations soulèvent de nouvelles questions quant à l'étiologie de l'esca. Elles permettent d'envisager des pistes prometteuses de recherche et de lutte, notamment en introduisant le facteur plante dans la compréhension de ce pathosystème complexe, et en matière de gestion des trajets de sève par la taille.

National audience; La lutte contre l’esca, maladie de dépérissement de la vigne est devenue une priorité d’action pour la filière viticole. Mais pour pouvoir choisir une méthode appropriée de contrôle, il faut au préalable bien identifier l’étiologie de ce syndrome complexe et cela implique une connaissance précise des symptômes. De leur nature et de leur mode de développement en découlent des enseignements et des pistes prometteuses de recherche ou de lutte. Cet article résume plus de 10 ans d’expérience acquise par le centre INRA de Bordeaux en matière d’observations des symptômes d’esca

International audience; Esca, a Grapevine Trunk Disease (GTD), is of major concern for viticulture worldwide. Our study compares the fungal communities that inhabit the wood tissues of vines that expressed or not foliar esca-symptoms. The trunk and rootstock tissues were apparently healthy, whether the 10 year-old plants were symptomatic or not. The only difference was in the cordon, which contained white rot, a typical form of esca, in 79% of symptomatic plants. Observations over a period of one year using a fingerprint method, Single Strand Conformation Polymorphism (SSCP), and the ITS-DNA sequencing of cultivable fungi, showed that shifts occurred in the fungal communities colonizing the healthy wood tissues. However, whatever the sampling time, spring, summer, autumn or winter, the fungi colonizing the healthy tissues of asymptomatic or symptomatic plants were not significantly different. Forty-eight genera were isolated, with species of Hypocreaceae and Botryosphaeriaceae being the most abundant species. Diverse fungal assemblages, made up of potentially plant-pathogenic and -protective fungi, colonized these non-necrotic tissues. Some fungi, possibly involved in GTD, inhabited the non-necrotic wood of young plants, but no increase in necrosis areas was observed over the one-year period.

Objective A 1-year semi-Markov model was constructed to simulate the cost-effectiveness of atypical and typical antipsychotic treatments for schizophrenia. Methods The core model comprised nine 6-week cycles and includes events such as survival, response, adverse events, and compliance. The nature, duration, intensity, and timing of adverse events were incorporated. Compliance was modeled as a function of health state, time, and adverse events. Three first-line treatments were considered (risperidone, olanzapine, and haloperidol oral) and the transition probabilities of switching between five different therapies (haloperidol oral, haloperidol depot, risperidone, olanzapine and clozapine) were included. Effectiveness was modeled based on a modified method of TWiST (time without symptoms and toxicity). The direct costs of utilization of medical resources are taken into account, including five different patient care settings, consultations, neuroleptic medication, laboratory tests, and treatment of side-effects. Results This paper reports the methodology used to construct the model and the results obtained when it was applied to the treatment of patients with schizophrenia in the Belgian health care system. Conclusions Over the study period, risperidone and olanzapine were more cost-effective than haloperidol and of the two major atypical drugs, risperidone was the more cost-effective.

Lyme disease produces a diverse clinical picture that can include serious and potentially debilitating cardiac, neurologic, joint, and skin involvement. It is characterized in three stages--early localized (stage I), early disseminated (stage II), and late disseminated (stage III)--and medical management is highly dependent on the stage at which the patient presents and the physician's awareness of available treatment options. This study was conducted to establish the medical and economic burden of Lyme disease in the overall US population, which included determining its endemicity in high-risk states and counties, describing current treatment patterns, measuring direct and indirect costs, and defining the cost burden by age group (18 years andor =18 years of age). Medical, epidemiologic, and economic data were collected, and an algorithm was developed representing the natural course of Lyme disease and the progress of health states over time following medical intervention. Using an annual mean incidence of 4.73 cases of Lyme disease per 100,000 population in the decision analysis model yielded an expected national expenditure of $2.5 billion (1996 dollars) over 5 years for therapeutic interventions to prevent 55,626 cases of Lyme disease sequelae. This estimate included both direct medical and indirect costs. However, there is evidence of considerable variation in incidence within states. Our findings support development of vaccination strategies for specific target groups.

The value of BIS for blossom blight risk assessment was studied from data collected in an experimental orchard in south-west France. Trees observed included mature commercial pear and apple trees and some young trees in experimental plots. There was a weather station in the orchard and beehives were present. Field records included flowering times of the pear and apple cultivars studied (mostly Passe-Crassane and Beurre Hardy, Royal Gala and Golden Delicious) and dates when blossom blight was first seen on each cultivar. Between 1980 and 1991, records of blight were available for 25 cases. In most cases, one or more infection risk (IR) days, as defined for BIS, could be found during bloom. DD13 mean sums (sums of degree days above a mean temperature of 13 °C) gave good guidance on times when early signs of blossom blight were present in 14 cases. There was only a slight divergence from BIS guides in a further five cases. Possible reasons for divergence and for non-fit in the remaining six cases are discussed. It is concluded from this study that BIS should give useful guidance on optimal times for protective spray applications and for timing of searches for signs of early blossom blight in south-west of France. Graphical presentations of data provide additional information.

A collection of 127 strains of Erwinia amylovora, the causative agent of fire blight, was tested by PCR amplification of a fragment of the plasmid pEA29. A variability in the length of the DNA fragment obtained was observed after digestion by MspI and Sau3A restriction enzymes. Strains were distributed into three groups according to the length of the DNA product. Most of the strains analysed were placed into two groups. Thirteen strains were clustered into a third group which was linked with the geographical origin of strains: they were all isolates from recently reported outbreaks of fire blight in Austria and in southern Bavaria in Germany. The variation in the length of the amplified fragment is probably due to an insertion into this fragment.

International audience; The National Grapevine Trunk Disease Survey was conducted in France from 2003 to 2008 to monitor grapevine trunk diseases (GTDs), eutypa dieback and esca/black dead arm (BDA). Data collected from seven regions, 329 vineyards and 12 cultivars were analysed. There were great variations amongst regions in the incidence of GTDs. For esca/BDA, two groups were distinguished: vineyards in Jura and Charentes had greater incidence (93-95%) than those of Bordeaux, Alsace and Bourgogne (54-82%). Incidence increased in Charentes over the 6-year survey, with the highest values being recorded during the last 2 years. For eutypa dieback, all vineyards of Charentes were affected, with 17 to 25% of vines expressing symptoms; for the other regions, 52 to 80% of vineyards were affected, with incidences below 3%. Cultivars Savagnin and Trousseau in Jura were especially affected by esca/BDA. Instead, Ugni Blanc in Charentes was most affected by eutypa dieback. One cultivar could be significantly more affected in one region than in another. The global health status of the vineyards was also investigated. (i) For four regions, 82% (Jura) to 87% (Alsace) of the grapevines were healthy, but this percentage decreased steadily (67%) in Charentes. (ii) Plants infected by GTDs were 32 and 18% in Jura and Charentes respectively, and only 2.9% in the Bourgogne region. (iii) The unproductive plants, i. e. dead, missing, replanted or restored, represented a significant part of the losses (6.6% in Charentes to 9.9% in Jura). The extension of GTDs is discussed with regard to the abiotic and biotic factors that may favour the diseases.

National audience