Cerebral amyloid angiopathy (CAA) is an age-related small vessel disease, characterised pathologically by progressive deposition of amyloid β in the cerebrovascular wall. The Boston criteria are used ...worldwide for the in-vivo diagnosis of CAA but have not been updated since 2010, before the emergence of additional MRI markers. We report an international collaborative study aiming to update and externally validate the Boston diagnostic criteria across the full spectrum of clinical CAA presentations.
In this multicentre, hospital-based, retrospective, MRI and neuropathology diagnostic accuracy study, we did a retrospective analysis of clinical, radiological, and histopathological data available to sites participating in the International CAA Association to formulate updated Boston criteria and establish their diagnostic accuracy across different populations and clinical presentations. Ten North American and European academic medical centres identified patients aged 50 years and older with potential CAA-related clinical presentations (ie, spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes), available brain MRI, and histopathological assessment for CAA diagnosis. MRI scans were centrally rated at Massachusetts General Hospital (Boston, MA, USA) for haemorrhagic and non-haemorrhagic CAA markers, and brain tissue samples were rated by neuropathologists at the contributing sites. We derived the Boston criteria version 2.0 (v2.0) by selecting MRI features to optimise diagnostic specificity and sensitivity in a prespecified derivation cohort (Boston cases 1994–2012, n=159), then externally validated the criteria in a prespecified temporal validation cohort (Boston cases 2012–18, n=59) and a geographical validation cohort (non-Boston cases 2004–18; n=123), comparing accuracy of the new criteria to the currently used modified Boston criteria with histopathological assessment of CAA as the diagnostic standard. We also assessed performance of the v2.0 criteria in patients across all cohorts who had the diagnostic gold standard of brain autopsy.
The study protocol was finalised on Jan 15, 2017, patient identification was completed on Dec 31, 2018, and imaging analyses were completed on Sept 30, 2019. Of 401 potentially eligible patients presenting to Massachusetts General Hospital, 218 were eligible to be included in the analysis; of 160 patient datasets from other centres, 123 were included. Using the derivation cohort, we derived provisional criteria for probable CAA requiring the presence of at least two strictly lobar haemorrhagic lesions (ie, intracerebral haemorrhages, cerebral microbleeds, or foci of cortical superficial siderosis) or at least one strictly lobar haemorrhagic lesion and at least one white matter characteristic (ie, severe visible perivascular spaces in centrum semiovale or white matter hyperintensities in a multispot pattern). The sensitivity and specificity of these criteria were 74·8% (95% CI 65·4–82·7) and 84·6% (71·9–93·1) in the derivation cohort, 92·5% (79·6–98·4) and 89·5% (66·9–98·7) in the temporal validation cohort, 80·2% (70·8–87·6) and 81·5% (61·9–93·7) in the geographical validation cohort, and 74·5% (65·4–82·4) and 95·0% (83·1–99·4) in all patients who had autopsy as the diagnostic standard. The area under the receiver operating characteristic curve (AUC) was 0·797 (0·732–0·861) in the derivation cohort, 0·910 (0·828–0·992) in the temporal validation cohort, 0·808 (0·724–0·893) in the geographical validation cohort, and 0·848 (0·794–0·901) in patients who had autopsy as the diagnostic standard. The v2.0 Boston criteria for probable CAA had superior accuracy to the current Boston criteria (sensitivity 64·5% 54·9–73·4; specificity 95·0% 83·1–99·4; AUC 0·798 0·741–0854; p=0·0005 for comparison of AUC) across all individuals who had autopsy as the diagnostic standard.
The Boston criteria v2.0 incorporate emerging MRI markers of CAA to enhance sensitivity without compromising their specificity in our cohorts of patients aged 50 years and older presenting with spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes. Future studies will be needed to determine generalisability of the v.2.0 criteria across the full range of patients and clinical presentations.
US National Institutes of Health (R01 AG26484).
We report the discovery in Mesozoic continental “red beds” of Anoual Syncline, Morocco, of the new Guelb el Ahmar (GEA) fossiliferous sites in the Bathonian Anoual Formation. They produced one of the ...richest continental biotic assemblages from the Jurassic of Gondwana, including plants, invertebrates and vertebrates. Both the sedimentological facies and the biotic assemblage indicate a lacustrine depositional environment. The flora is represented by tree trunks (three families), pollen (13 species, five major clades) and charophytes. It suggests local forests and humid (non-arid) conditions. The vertebrate fauna is dominated by microvertebrates recovered by screening–washing. It is rich and diverse, with at least 29 species of all major groups (osteichthyans, lissamphibians, chelonians, diapsids, mammals), except chondrichthyans. It includes the first mammals discovered in the Middle Jurassic of Arabo-Africa. The GEA sites yielded some of the earliest known representatives of osteoglossiform fishes, albanerpetontid and caudate amphibians, squamates (scincomorphans, anguimorphan), cladotherian mammals, and likely choristoderes. The choristoderes, if confirmed, are the first found in Gondwana, the albanerpetontid and caudatan amphibians are among the very few known in Gondwana, and the anguimorph lizard is the first known from the Mesozoic of Gondwana. Mammals (Amphitheriida, cf. Dryolestida) remain poorly known, but are the earliest cladotherians known in Gondwana. The GEA biotic assemblage is characterized by the presence of Pangean and Laurasian (especially European) taxa, and quasi absence of Gondwanan taxa. The paleobiogeographical analysis suggests either a major fossil bias in Gondwana during the Middle Jurassic, and an overall vicariant Pangean context for the GEA assemblage, or alternatively, noticeable Laurasian (European) affinities and North-South dispersals. The close resemblance between the Bathonian faunas of GEA and Britain is remarkable, even in a Pangean context. The similarity between the local Anoual Syncline Guelb el Ahmar and Ksar Metlili faunas raises questions on the ?Berriasian age of the latter.
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•First discovered Middle Jurassic flora and fauna with microvertebrates from Africa•It yields the first Middle Jurassic mammals from Africa (stem Cladotheria).•The fauna has either Laurasian or Pangean affinities.
•The relationships between resources and defenses in dead trees are poorly understood.•We measured the changes in constitutive and induced defenses of uprooted spruces.•Constitutive and induced ...terpenes don’t influence bark beetles’ selection and success.•Defense levels decrease and are positively correlated to phloem’s energetic content.•Wind-felled trees are poorly defended but allow the reproduction of I. typographus.
The weakened or suppressed hosts targeted by tree-killing conifer bark beetles during endemic phases are considered to be poorly defended and available to several competing species. Hosts face trade-offs in the allocation of resources in growth and reproduction or in defense, and the defense/resources status varies with time after host’s death or weakening event. Tree-killing bark beetles at endemic levels must choose along a spectrum, compromising between encountering minimal defense and facing high competition, or benefiting from high nutritional quality but facing high host defense.
The relationships between resources and defenses in dead/dying trees have not been quantitatively assessed to date, because most studies focus on epidemic conditions. We measured the changes in constitutive and induced defenses in the phloem of spruce trees artificially uprooted at different times (up to 17months prior to experiment initiation) and treated with methyl-jasmonate (MeJ) in order to induce chemical defense. We measured the effect of these changes on different steps of the host selection process and brood success of a major forest pest in Eurasia, Ips typographus (Coleoptera, Curculionidae).
Our results show that uprooted trees maintain some level of constitutive defenses, in particular monoterpenes, that decrease with time after uprooting. Moreover, the trees maintain some inducibility and can produce monoterpenes in response to MeJ treatment up to 7months after uprooting. These defenses are correlated in part with the energy available in the phloem, but are likely too weak to exert pressure on the beetles’ success and selection, the latter being related to the amount of energy available.
Our results confirm that wind-felled trees are poorly defended, consistent with the hypothesis of the evolution of the tree-killing behavior from saprophagy in response to an overwhelming interspecific competition on undefended hosts. Wind-felled trees still represent a useful resource, exposing endemic populations of aggressive beetles to low defense levels while facilitating reproduction, growth and development. The constraint on the beetles’ populations then becomes the ability to locate these scattered and unpredictable resources.
Many bark and ambrosia beetle species (Coleoptera: Scolytinae and Platypodinae) are known to have spread worldwide in relation to international trade. Concerns have been expressed within the European ...and Mediterranean Plant Protection Organization (EPPO) about recent introductions of non-indigenous species of these groups. Regulation of the non-coniferous wood trade into many EPPO member countries is currently not sufficient to cover such risks. In 2018–2019, an EPPO study on the risk of bark and ambrosia beetles associated with imported non-coniferous wood was carried out, and the key characteristics contributing to the pest risk from introduced species were determined using expert consensus. This paper summarizes the key findings of the study, which are available in full detail on the EPPO website. The study identified biological and other risk factors and illustrated them with examples from 26 beetle species or groups of species known to be invasive or posing a threat to plant health. These representative species were classified into three categories based on known damage and level of uncertainty. In the present article, factorial discriminant analyses were used to identify features of bark and ambrosia beetle biology associated with damage caused and invasiveness. Based on the information assembled and consideration of the risk factors, it was recommended that in order to prevent the introduction of new bark and ambrosia beetles via non-coniferous wood commodities, horizontal phytosanitary measures should be adopted, irrespective of the host plant species and the origin (i.e., for all genera of non-coniferous woody plants and from all origins). Phytosanitary measures are presented here for various wood commodities.
Phytosanitary import inspections are important to avoid entry of harmful pests on live plants. In the European Union (EU), all consignments of live plants must be inspected at the first point of ...entry, and plants allowed entry can be moved without further inspection among the 28 Member States and Switzerland. It is important that inspections in EU countries adhere to the same standard to avoid introduction of harmful organisms through countries with weaker methods. We tested whether sampling intensity and confidence in the inspection results were the same across these countries. Questionnaires were sent to inspectors in all countries, asking about inspections of individual consignments of woody plants for planting. Data about 102 lots, inspected at 13 points of entry in six countries, were analyzed. We used hypergeometric and binomial statistics for small and large consignments, respectively, to calculate the probability that <1 % of the plants were infested. The duration of the inspection increased with lot size, but the probability that the infestation level was below 1 % of the plants was lower for small than for large lots. Moreover, large international differences in inspection intensity and the probability that the inspections could detect a level of infestation below 1 % were found: the probability was consistently above 0.95 in one country, while the average probability was below 0.6 in the other countries. We suggest that the EU Member States adopt common maximum acceptable infestation levels and harmonized, statistics-based sampling protocols for plants for planting.
Dalcetrapib did not improve clinical outcomes, despite increasing high-density lipoprotein cholesterol by 30%. These results differ from other evidence supporting high-density lipoprotein as a ...therapeutic target. Responses to dalcetrapib may vary according to patients' genetic profile.
We conducted a pharmacogenomic evaluation using a genome-wide approach in the dal-OUTCOMES study (discovery cohort, n=5749) and a targeted genotyping panel in the dal-PLAQUE-2 imaging trial (support cohort, n=386). The primary endpoint for the discovery cohort was a composite of cardiovascular events. The change from baseline in carotid intima-media thickness on ultrasonography at 6 and 12 months was evaluated as supporting evidence. A single-nucleotide polymorphism was found to be associated with cardiovascular events in the dalcetrapib arm, identifying the ADCY9 gene on chromosome 16 (rs1967309; P=2.41×10(-8)), with 8 polymorphisms providing P<10(-6) in this gene. Considering patients with genotype AA at rs1967309, there was a 39% reduction in the composite cardiovascular endpoint with dalcetrapib compared with placebo (hazard ratio, 0.61; 95% confidence interval, 0.41-0.92). In patients with genotype GG, there was a 27% increase in events with dalcetrapib versus placebo. Ten single-nucleotide polymorphism in the ADCY9 gene, the majority in linkage disequilibrium with rs1967309, were associated with the effect of dalcetrapib on intima-media thickness (P<0.05). Marker rs2238448 in ADCY9, in linkage disequilibrium with rs1967309 (r(2)=0.8), was associated with both the effects of dalcetrapib on intima-media thickness in dal-PLAQUE-2 (P=0.009) and events in dal-OUTCOMES (P=8.88×10(-8); hazard ratio, 0.67; 95% confidence interval, 0.58-0.78).
The effects of dalcetrapib on atherosclerotic outcomes are determined by correlated polymorphisms in the ADCY9 gene.
URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00658515 and NCT01059682.
The sentinel plantation concept consists of assessing the impact of exotic factors, such as pests and pathogens, on plants of interest by planting them out of their native range. This tool is a way ...to enhance knowledge for pest risk analysis (PRA) by guiding decisions on how quarantine organisms should be regulated and where to focus prevention and surveillance efforts for an early detection. In this study, the sentinel method was used in the case of research on
Xylella fastidiosa
, a plant pathogenic bacterium that has recently been found established in southern Europe, but whose potential impact and possible host range are still poorly documented in northern areas where the bacterium is not known to occur. To improve knowledge on the susceptibility of potential hosts of
X. fastidiosa
in northern Europe, a sentinel plantation of
Prunus domestica
cv. Opal,
Quercus petraea
and
Salix alba
was established in the
X. fastidiosa
-infected area of Majorca. In order to assess the circulation of the bacterium in the sentinel plot and around it, surveys of the local flora and insect vectors were carried out, as well as the planting of a network of rosemary “spy plants”. Symptomatic monitoring and molecular analyses were performed on the sentinel plants for four years. During these years,
X. fastidiosa
was never detected in our sentinel plants most likely because of the low infectivity pressure recorded in the surroundings. This study underlines the complexity of conducting sentinel plantation assays combined with
X. fastidiosa
research, highlighting the need for long-term investigation and questioning the efficiency of the sentinel tool. However, this study is placed in perspective with other valuable sentinel plantations. It also highlights the complementarity of the tool and proposes elements to improve or re-orientate the implementation of future sentinel projects.
Mixed species stands might contribute to important goals of sustainable forest management, such as higher biological diversity, more resistance and resilience to disturbances and higher carbon ...storage. Knowledge of stakeholders' perceptions of such ecosystem services in mixed species stands is required for effective policy development. We showed that practitioners' and scientists' perceptions of ecosystem services in mixed species stands in Belgium differed from formal scientific knowledge derived from a synthesis of published studies. The positive perception of supporting, regulating and cultural services in mixed species stands contrasted with less conclusive results from the literature, where positive, negative and neutral effects were reported. Many respondents also signified a lack of information about regulating services. Furthermore, provisioning services were perceived as equal in mixed species stands and monocultures, in contrast to higher productivity demonstrated in mixed species stands in the literature. The regional (Flanders and Wallonia) ecological and socio-economic context influenced both the perception of ecosystem services and of the importance of management objectives. Our results highlighted the need to address the lack of scientific data, to adapt communication to the ecological and socio-economic context, as well as to improve information flow on regulating services and productivity.
1 In the early 2000s, beech forests in Western Europe suffered from a so far unexplained burst of mortality. Necroses, ambrosia‐beetle and fungal attacks were observed on the trunks. The symptoms ...were similar to previous events reported throughout the 20th Century. 2 One current hypothesis is that these phenomena were related to early frost events for which the trees were physiologically unprepared and which made them vulnerable to biotic attacks. In the present study, we aimed to test this hypothesis further, by retrospective meteorological analyses and also by an experimental approach. 3 Our meteorological analyses highlighted the occurrence of cold waves a year before the beech declines were reported in 1929, 1942 and 1998. 4 In our experimental approach, frost injuries were inflicted to mature trees in a beech stand using dry ice. The treated trees were more attractive to insects than untreated controls. Insect attacks were observed in the treated zones on the trees but colonization was not very successful. The galleries had aborted most of the time with only a few larval chambers. Very few insects were caught in emergence traps. 5 The results of these two approaches support and strengthen the hypothesis that frost induced beech dieback. Frost injuries increased tree attraction to ambrosia beetles to the point of inducing attacks. However, the overall success of these attacks was much lower than that observed in the 2000s. These differences might reflect limitations in our experimental approach, where frost wounding was applied locally to the trees.
Since the discovery of America, many domesticated animals and plants have been traded between the Old and the new World. They were often accompanied by damaging pests. Phylloxera invaded Europe in ...1863, and the gypsy moth became established in the USA in 1869. The most active pathways for forest pests are currently the trade in planting stock and wood packaging material. Under comparable circumstances (commercial flows etc.), the biological traits that favour an invader’s success are to some extent predictive. Scolytine beetles provide an excellent example. Analysis of establishment successes by alien species uncovers at least three non-exclusive features of an « efficient invader »: sib-mating, polyphagia and association with a virulent pathogen. These features allow the successfully establishment and spread of small inoculums; they give a low «Allee threshold » to these species.
Ravageurs animaux et maladies des plantes parcourent le monde. Le phylloxéra, venu d’Amérique, envahit l’Europe dès 1863 ; le bombyx disparate, eurasiatique, se répand aux États-Unis d’Amérique dès 1869. Plus récemment, le nématode du pin est découvert au Portugal en 1999 et Xylella fastidiosa en Italie en 2013. Les filières d’introduction les plus actives actuellement sont le commerce des plantes vivantes et le bois d’emballage. À contexte (flux commerciaux, etc.) égal, les caractéristiques biologiques qui favorisent le succès d’un envahisseur permettent certaines prédictions. Les scolytes sont exemplaires à cet égard. L’analyse des succès d’installation d’espèces exotiques nous indique au moins trois caractéristiques non exclusives d’un « envahisseur efficace » : mode de reproduction endogame, polyphagie et association avec un pathogène. Ces caractéristiques favorisent l’installation et la propagation de petits inoculums ; elles confèrent aux espèces qui en jouissent un « seuil Allee » bas.
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