Florbetapir F 18 amyloid PET and 36-month cognitive decline:a prospective multicenter study

This study was designed to evaluate whether subjects with amyloid beta (Aβ) pathology, detected using florbetapir positron emission tomorgraphy (PET), demonstrated greater cognitive decline than subjects without Aβ pathology. Sixty-nine cognitively normal (CN) controls, 52 with recently diagnosed mild cognitive impairment (MCI) and 31 with probable Alzheimer's disease (AD) dementia were included in the study. PET images obtained in these subjects were visually rated as positive (Aβ+) or negative (Aβ−), blind to diagnosis. Fourteen percent (10/69) of CN, 37% (19/52) of MCI and 68% (21/31) of AD were Aβ+. The primary outcome was change in ADAS-Cog score in MCI subjects after 36 months; however, additional outcomes included change on measures of cognition, function and diagnostic status. Aβ+ MCI subjects demonstrated greater worsening compared with Aβ− subjects on the ADAS-Cog over 36 months (5.66±1.47 vs −0.71±1.09, P=0.0014) as well as on the mini-mental state exam (MMSE), digit symbol substitution (DSS) test, and a verbal fluency test (P<0.05). Similar to MCI subjects, Aβ+ CN subjects showed greater decline on the ADAS-Cog, digit-symbol-substitution test and verbal fluency (P<0.05), whereas Aβ+ AD patients showed greater declines in verbal fluency and the MMSE (P<0.05). Aβ+ subjects in all diagnostic groups also showed greater decline on the CDR-SB (P<0.04), a global clinical assessment. Aβ+ subjects did not show significantly greater declines on the ADCS-ADL or Wechsler Memory Scale. Overall, these findings suggest that in CN, MCI and AD subjects, florbetapir PET Aβ+ subjects show greater cognitive and global deterioration over a 3-year follow-up than Aβ− subjects do

Gene family expansions and contractions are associated with host range in plant pathogens of the genus Colletotrichum

Background: Many species belonging to the genus Colletotrichum cause anthracnose disease on a wide range of plant species. In addition to their economic impact, the genus Colletotrichum is a useful model for the study of the evolution of host specificity, speciation and reproductive behaviors. Genome projects of Colletotrichum species have already opened a new era for studying the evolution of pathogenesis in fungi. Results: We sequenced and annotated the genomes of four strains in the Colletotrichum acutatum species complex (CAsc), a clade of broad host range pathogens within the genus. The four CAsc proteomes and secretomes along with those representing an additional 13 species (six Colletotrichum spp. and seven other Sordariomycetes) were classified into protein families using a variety of tools. Hierarchical clustering of gene family and functional domain assignments, and phylogenetic analyses revealed lineage specific losses of carbohydrate-active enzymes (CAZymes) and proteases encoding genes in Colletotrichum species that have narrow host range as well as duplications of these families in the CAsc. We also found a lineage specific expansion of necrosis and ethylene-inducing peptide 1 (Nep1)-like protein (NLPs) families within the CAsc. Conclusions: This study illustrates the plasticity of Colletotrichum genomes, and shows that major changes in host range are associated with relatively recent changes in gene content

GA4GH: International policies and standards for data sharing across genomic research and healthcare.

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits

A taxonomic backbone for the global synthesis of species diversity in the angiosperm order Caryophyllales

The Caryophyllales constitute a major lineage of flowering plants with approximately 12500 species in 39 families. A taxonomic backbone at the genus level is provided that reflects the current state of knowledge and accepts 749 genera for the order. A detailed review of the literature of the past two decades shows that enormous progress has been made in understanding overall phylogenetic relationships in Caryophyllales. The process of re-circumscribing families in order to be monophyletic appears to be largely complete and has led to the recognition of eight new families (Anacampserotaceae, Kewaceae, Limeaceae, Lophiocarpaceae, Macarthuriaceae, Microteaceae, Montiaceae and Talinaceae), while the phylogenetic evaluation of generic concepts is still well underway. As a result of this, the number of genera has increased by more than ten percent in comparison to the last complete treatments in the Families and genera of vascular plants” series. A checklist with all currently accepted genus names in Caryophyllales, as well as nomenclatural references, type names and synonymy is presented. Notes indicate how extensively the respective genera have been studied in a phylogenetic context. The most diverse families at the generic level are Cactaceae and Aizoaceae, but 28 families comprise only one to six genera. This synopsis represents a first step towards the aim of creating a global synthesis of the species diversity in the angiosperm order Caryophyllales integrating the work of numerous specialists around the world

Carcinogenicity of saccharin in laboratory animals and humans: letter to Dr. Harry Conacher of Health Canada

We appreciate this opportunity to provide input to the Health Protection Branch's (HPB's) review of the artificial sweetener saccharin. Concerns with regard to the safety of saccharin are of great public health significance and of great interest to the public because saccharin is consumed by tens of millions of people, including children and fetuses. Any evidence of carcinogenesis--and there is ample such evidence--of such a widely used chemical should spur health officials to minimize human exposure to it. It is worth noting that on October 31, 1997, the Board of Scientific Counselors of the National Toxicology Program, a unit of the National Institute of Environmental Health Sciences (NIEHS), voted not to delist saccharin from its Report on Carcinogens

A dense GNSS meteorological network for observing deep convection in the Amazon

A dense Global Navigation Satellite System (GNSS) meteorological network (∼20 stations) in the central Amazon Basin in Brazil is being developed for long-term studies of deep convection/water vapor interactions and feedback. In this article, the network is described and preliminary results are presented: GNSS-derived precipitable water vapor is useful for tracking water vapor advection and in identifying convective events and water vapor convergence timescales. Upon network completion (early 2011), 3D water vapor field analyses and participation in the intensive field campaign GPM-CHUVA will provide unique data sets for initializing, constraining or validating high-resolution models or refining convective parameterizations. © 2011 Royal Meteorological Society

Amyloid-&amp;bgr; assessed by florbetapir F 18 PET and 18-month cognitive decline

ObjectivesFlorbetapir F 18 PET can image amyloid-β (Aβ) aggregates in the brains of living subjects. We prospectively evaluated the prognostic utility of detecting Aβ pathology using florbetapir PET in subjects at risk for progressive cognitive decline.MethodsA total of 151 subjects who previously participated in a multicenter florbetapir PET imaging study were recruited for longitudinal assessment. Subjects included 51 with recently diagnosed mild cognitive impairment (MCI), 69 cognitively normal controls (CN), and 31 with clinically diagnosed Alzheimer disease dementia (AD). PET images were visually scored as positive (Aβ+) or negative (Aβ-) for pathologic levels of β-amyloid aggregation, blind to diagnostic classification. Cerebral to cerebellar standardized uptake value ratios (SUVr) were determined from the baseline PET images. Subjects were followed for 18 months to evaluate changes in cognition and diagnostic status. Analysis of covariance and correlation analyses were conducted to evaluate the association between baseline PET amyloid status and subsequent cognitive decline.ResultsIn both MCI and CN, baseline Aβ+ scans were associated with greater clinical worsening on the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog (p &lt; 0.01) and Clinical Dementia Rating-sum of boxes (CDR-SB) (p &lt; 0.02). In MCI Aβ+ scans were also associated with greater decline in memory, Digit Symbol Substitution (DSS), and Mini-Mental State Examination (MMSE) (p &lt; 0.05). In MCI, higher baseline SUVr similarly correlated with greater subsequent decline on the ADAS-Cog (p &lt; 0.01), CDR-SB (p &lt; 0.03), a memory measure, DSS, and MMSE (p &lt; 0.05). Aβ+ MCI tended to convert to AD dementia at a higher rate than Aβ- subjects (p &lt; 0.10).ConclusionsFlorbetapir PET may help identify individuals at increased risk for progressive cognitive decline

Umbrella Data Management Plans to integrate FAIR data:Lessons from the ISIDORe and BY-COVID consortia for pandemic preparedness

The Horizon Europe project ISIDORe is dedicated to pandemic preparedness and responsiveness research. It brings together 17 Research Infrastructures (RIs) and networks to provide a broad range of services to infectious disease researchers. An efficient and structured treatment of data is central to ISIDORe’s aim to furnish seamless access to its multidisciplinary catalogue of services, and to ensure that users’ results are treated FAIRly. ISIDORe therefore requires a data management plan (DMP) covering both access management and research outputs, applicable over a broad range of disciplines, and compatible with the constraints and existing practices of its diverse partners.We undertook an iterative, step-by-step, process to build a community-approved living document, identifying good practices and processes, on the basis of use cases, presented as proof of concepts. International fora such as the RDA and EOSC, and primarily the BY-COVID project, furnished registries, tools and online data platforms, as well as standards, and the support of data scientists. Together, these elements provide a path for building an umbrella, FAIR-compliant DMP, aligned as fully as possible with FAIR principles, which could also be applied as a framework for data management harmonisation in other large-scale, challenge-driven projects. Finally, we discuss how data management and reuse can be further improved through the writing of realistic DMPs using 'DMP profiles' and, in the future, the contribution of an inter RIs data steward network, to produce a Community of Practice that could be integrated into planned trans-RI competence centres