The clinical effectiveness and cost effectiveness of clozapine for inpatients with severe borderline personality disorder (CALMED study): A randomised placebo-controlled trial.

Background: Data from case series suggest that clozapine may benefit inpatients with borderline personality disorder (BPD), but randomised trials have not been conducted. Methods: Multicentre, double-blind, placebo-controlled trial. We aimed to recruit 222 inpatients with severe BPD aged 18 or over, who had failed to respond to other antipsychotic medications. We randomly allocated participants on a 1:1 ratio to receive up to 400mg of clozapine per day or an inert placebo using a remote web-based randomisation service. The primary outcome was total score on the Zanarini Rating scale for Borderline Personality Disorder (ZAN-BPD) at six months. Secondary outcomes included self-harm, aggression, resource use and costs, side effects and adverse events. We used a modified intention to treat analysis (mITT) restricted to those who took one or more dose of trial medication, using a general linear model fitted at six months adjusted for baseline score, allocation group and site. Results: The study closed early due to poor recruitment and the impact of the COVID-19 pandemic. Of 29 study participants, 24 (83%) were followed up at six months, of whom 21 (72%) were included in the mITT analysis. At six months, 11 (73%) participants assigned to clozapine and 6 (43%) of those assigned to placebo were still taking trial medication. Adjusted difference in mean total ZAN-BPD score at six months was -3.86 (95% Confidence Intervals = -10.04 to 2.32, p=0.22). There were 14 serious adverse events; six in the clozapine arm and eight in the placebo arm of the trial. There was little difference in the cost of care between groups. Interpretation: We recruited insufficient participants to test the primary hypothesis. The study findings highlight problems in conducting placebo-controlled trials of clozapine and in using clozapine for people with BPD, outside specialist inpatient mental health units. Trial registration ISRCTN18352058. https://doi.org/10.1186/ISRCTN1835205

Biochar successfully replaces activated charcoal for in vitro culture of two white poplar clones reducing ethylene concentration

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On the Origin and Spread of the Scab Disease of Apple: Out of Central Asia

Background Venturia inaequalis is an ascomycete fungus responsible for apple scab, a disease that has invaded almost all apple growing regions worldwide, with the corresponding adverse effects on apple production. Monitoring and predicting the effectiveness of intervention strategies require knowledge of the origin, introduction pathways, and population biology of pathogen populations. Analysis of the variation of genetic markers using the inferential framework of population genetics offers the potential to retrieve this information. Methodology/Principal Findings Here, we present a population genetic analysis of microsatellite variation in 1,273 strains of V. inaequalis representing 28 orchard samples from seven regions in five continents. Analysis of molecular variance revealed that most of the variation (88%) was distributed within localities, which is consistent with extensive historical migrations of the fungus among and within regions. Despite this shallow population structure, clustering analyses partitioned the data set into separate groups corresponding roughly to geography, indicating that each region hosts a distinct population of the fungus. Comparison of the levels of variability among populations, along with coalescent analyses of migration models and estimates of genetic distances, was consistent with a scenario in which the fungus emerged in Central Asia, where apple was domesticated, before its introduction into Europe and, more recently, into other continents with the expansion of apple growing. Across the novel range, levels of variability pointed to multiple introductions and all populations displayed signatures of significant post-introduction increases in population size. Most populations exhibited high genotypic diversity and random association of alleles across loci, indicating recombination both in native and introduced areas. Conclusions/Significance Venturia inaequalis is a model of invasive phytopathogenic fungus that has now reached the ultimate stage of the invasion process with a broad geographic distribution and well-established populations displaying high genetic variability, regular sexual reproduction, and demographic expansion.Contexte Venturia inaequalis est un champignon ascomycete responsable de la tavelure du pommier, une maladie qui a envahi presque toutes les régions du monde où le pommier est cultivé posant ainsi de graves problèmes en production. Prévenir et enrayer efficacement la réussite d’un tel succès invasif nécessite des connaissances approfondies sur l’origine, les voies d’introduction, la biologie et la génétique de ces populations invasives. En utilisant le potentiel d’inférence de la génétique des populations, l’analyse de la variation de marqueurs génétiques offre la possibilité d’accéder à ces informations. Méthodologie et Principaux résultats Ici nous présentons l’analyse de données microsatellites obtenues pour 1273 souches de V. inaequalis provenant de 28 vergers prélevées dans 7 régions sur les 5 continents. L’analyse de la variance moléculaire révèle que 88% de la variation se retrouve dans les vergers échantillonnés, ce qui est compatible avec d’importantes migrations historiques du champignon entre et à l’intérieur même des régions. Malgré cette très faible structuration des populations, les différentes analyses de clustering mettent en évidence un partage des populations en groupes séparés correspondant à leur origine géographique, montrant ainsi que chaque région héberge une population distincte du champignon. Ensemble, les résultats obtenus sur la comparaison du niveau de variabilité entre populations, les analyses de coalescence et les modèles de migration testés plaident en faveur d’un scénario dans lequel le champignon aurait émergé d’Asie Centrale, où le pommier a été domestiqué, avant d’être introduit en Europe puis plus récemment dans les autres continents suite à l’expansion de la culture du pommier. Les niveaux de variabilité indiquent que ces territoires ont subi des introductions multiples et que les populations portent toutes des signatures révélant de fortes expansions démographiques après leur introduction. Enfin, la forte diversité génotypique des populations et l’association aléatoire des allèles entre loci suggèrent que le champignon présente une reproduction sexuée régulière à la fois dans les régions où il a été introduit et dans sa région native. Conclusion et Portée. Venturia inaequalis est un modèle de champignons phytopathogène invasif qui a maintenant atteint le stade ultime du processus invasif, c’est à dire une très large distribution géographique par des populations bien établies montrant une grande diversité génétique, une reproduction sexuée régulière et une histoire d’expansion démographique

Lessons Learned from a Decade of Sudden Oak Death in California: Evaluating Local Management

Sudden Oak Death has been impacting California’s coastal forests for more than a decade. In that time, and in the absence of a centrally organized and coordinated set of mandatory management actions for this disease in California’s wildlands and open spaces, many local communities have initiated their own management programs. We present five case studies to explore how local-level management has attempted to control this disease. From these case studies, we glean three lessons: connections count, scale matters, and building capacity is crucial. These lessons may help management, research, and education planning for future pest and disease outbreaks

Mycorrhization of fagaceae forests within mediterranean ecosystems

Mediterranean Fagaceae forests are valuable due to their ecological and socioeconomic aspects. Some profitable plant species, such as Castanea (timber and chestnut), Quercus (timber and cork), and Fagus (timber), encounter in this habitat the excellent edaphoclimatic conditions to develop. All Fagaceae plants are commonly associated to ECM fungal species, which are found in these forests in quite stable communities, mainly enriched in Russulaceae and Telephoraceae species. Currently, the Mediterranean Basin is considered as one of the global biodiversity hotspots, since many of their endemic plant species are not found elsewhere and are now under threat. Due to climate changing and introduction of disease agents, Fagaceae forests are facing an adaptation challenge to both biotic and abiotic threats. Although ECM communities are highly disturbed by climate factors and tree disease incidence, they could play an important role in increasing water availability to the plant and also improving plant tree defense against pathogens. Recent advances, namely, on genomics and transcriptomics, are providing tools for increasing the understanding of Fagaceae mycorrhization process and stress responses to biotic and abiotic stresses. Such studies can provide new information for the implementation of the most adequate management policies for protecting threaten Mediterranean forests.info:eu-repo/semantics/publishedVersio

Effects of an invasive forest pathogen on abundance of ticks and their vertebrate hosts in a California Lyme disease focus

Invasive species, including pathogens, can have important effects on local ecosystems, including indirect consequences on native species. This study focuses on the effects of an invasive plant pathogen on a vertebrate community and Ixodes pacificus, the vector of the Lyme disease pathogen (Borrelia burgdorferi) in California. Phytophthora ramorum, the causative agent of sudden oak death, is a non-native pathogen killing trees in California and Oregon. We conducted a multi-year study using a gradient of SOD-caused disturbance to assess the impact on the dusky-footed woodrat (Neotoma fuscipes) and the deer mouse (Peromyscus maniculatus), two reservoir hosts of B. burgdorferi, as well as the impact on the Columbian black-tailed deer (Odocoileus hemionus columbianus) and the western fence lizard (Sceloporus occidentalis), both of which are important hosts for I. pacificus but are not pathogen reservoirs. Abundances of P. maniculatus and S. occidentalis were positively correlated with greater SOD disturbance, whereas N. fuscipes abundance was negatively correlated. We did not find a change in space use by O. hemionus. Our data show that SOD has a positive impact on the density of nymphal ticks, which is expected to increase the risk of human exposure to Lyme disease all else being equal. A positive correlation between SOD disturbance and the density of nymphal ticks was expected given increased abundances of two important hosts: deer mice and western fence lizards. However, further research is needed to integrate the direct effects of SOD on ticks, for example via altered abiotic conditions with host-mediated indirect effects

Assessing the Potential Impacts to Riparian Ecosystems Resulting from Hemlock Mortality in Great Smoky Mountains National Park

Hemlock Woolly Adelgid (Adelges tsugae) is spreading across forests in eastern North America, causing mortality of eastern hemlock (Tsuga canadensis [L.] Carr.) and Carolina hemlock (Tsuga caroliniana Engelm.). The loss of hemlock from riparian forests in Great Smoky Mountains National Park (GSMNP) may result in significant physical, chemical, and biological alterations to stream environments. To assess the influence of riparian hemlock stands on stream conditions and estimate possible impacts from hemlock loss in GSMNP, we paired hardwood- and hemlock-dominated streams to examine differences in water temperature, nitrate concentrations, pH, discharge, and available photosynthetic light. We used a Geographic Information System (GIS) to identify stream pairs that were similar in topography, geology, land use, and disturbance history in order to isolate forest type as a variable. Differences between hemlock- and hardwood-dominated streams could not be explained by dominant forest type alone as forest type yields no consistent signal on measured conditions of headwater streams in GSMNP. The variability in the results indicate that other landscape variables, such as the influence of understory Rhododendron species, may exert more control on stream conditions than canopy composition. The results of this study suggest that the replacement of hemlock overstory with hardwood species will have minimal impact on long-term stream conditions, however disturbance during the transition is likely to have significant impacts. Management of riparian forests undergoing hemlock decline should, therefore, focus on facilitating a faster transition to hardwood-dominated stands to minimize long-term effects on water quality