The first European Vasculitis Society (EUVAS) meeting report was published in 2017. Herein, we report on developments in the past 5 years which were greatly influenced by the pandemic. The ...adaptability to engage virtually, at this critical time in society, embodies the importance of networks and underscores the role of global collaborations. We outline state-of-the-art webinar topics, updates on developments in the last 5 years, and proposals for agendas going forward. A host of newly reported clinical trials is shaping practice on steroid minimization, maintenance strategies, and the role of newer therapies. To guide longer-term strategies, a longitudinal 10-year study investigating relapse, comorbidity, malignancy, and survival rates is at an advanced stage. Disease assessment studies are refining classification criteria to differentiate forms of vasculitis more fully. A large international validation study on the histologic classification of anti-neutrophil cytoplasmic antibody (ANCA) glomerulonephritis, recruiting new multicenter sites and comparing results with the Kidney Risk Score, has been conducted. Eosinophilic granulomatosis with polyangiitis (EGPA) genomics offers potential pathogenic subset and therapeutic insights. Among biomarkers, ANCA testing is favoring immunoassay as the preferred method for diagnostic evaluation. Consolidated development of European registries is progressing with an integrated framework to analyze large clinical data sets on an unprecedented scale.
Thyroid surgery outcomes have evolved from mortality control strategies to morbidity control measures. Most vocal outcomes research in thyroid surgery are focused on recurrent nerve anatomic and ...functional preservation. However, there are likely multiple causes of vocal dysfunction in thyroid patients. We prospectively analyzed preoperative patients with thyroid disease to define preoperative vocal characteristics of this population.
Quantify vocal and laryngeal baseline conditions in thyroid surgical patients.
Prospective study of preoperative stroboscopy findings and vocal function assessing the correlation between thyroid disease, compressive symptoms, baseline vocal conditions and laryngoscopy results.
Vocal quantitative scores were positive for dysphonia in 36% of patients and the Vocal Handicap Index confirmed either slight or Moderate impairment in most patients. Stroboscopy results were abnormal in 60% of cases with no diagnoses of immobility. Correlation was established for diagnosis of cancer and the absence of symptoms.
These results point to a multifactorial cause for vocal impairment in thyroid surgery patients. Research on vocal impairment in thyroid surgery should not be centered exclusively on recurrent nerve neuromonitoring and functional preservation, but also on other variables that may contribute to vocal change in thyroid disease and surgery.
Indigenous societies are known to have occupied the Amazon basin for more than 12,000 years, but the scale of their influence on Amazonian forests remains uncertain. We report the discovery, using ...LIDAR (light detection and ranging) information from across the basin, of 24 previously undetected pre-Columbian earthworks beneath the forest canopy. Modeled distribution and abundance of large-scale archaeological sites across Amazonia suggest that between 10,272 and 23,648 sites remain to be discovered and that most will be found in the southwest. We also identified 53 domesticated tree species significantly associated with earthwork occurrence probability, likely suggesting past management practices. Closed-canopy forests across Amazonia are likely to contain thousands of undiscovered archaeological sites around which pre-Columbian societies actively modified forests, a discovery that opens opportunities for better understanding the magnitude of ancient human influence on Amazonia and its current state.
Editor’s summary
Indigenous societies have lived in the Amazon for at least 12,000 years. Finding evidence of these societies, however, has been greatly hampered by the density of the forest in Amazonia. Peripato
et al
. used LIDAR (light detection and ranging) surveys to identify more than 20 previously unidentified developments and then modeled the occurrence of others across the Amazon. The authors predict that between 10,000 and 24,000 ancient earthworks are waiting to be discovered. Sampling of some of the LIDAR transects revealed a consistent set of domesticated tree species associated with the developments, suggesting active forestry practices among these societies. —Sacha Vignieri
Amazon-wide LIDAR surveys and predictive models suggest thousands of undocumented archaeological sites across the basin.
The calibration and validation of scientific analysis in simulations is a fundamental tool to ensure unbiased and robust results in observational cosmology. In particular, mock galaxy catalogs are a ...crucial resource to achieve these goals in the measurement of baryon acoustic oscillation (BAO) in the clustering of galaxies. Here we present a set of 1952 galaxy mock catalogs designed to mimic the Dark Energy Survey Year 3 BAO sample over its full photometric redshift range 0.6 <
z
photo
< 1.1. The mocks are based upon 488 ICE-COLA fast
N
-body simulations of full-sky light cones and were created by populating halos with galaxies, using a hybrid halo occupation distribution – halo abundance matching model. This model has ten free parameters, which were determined, for the first time, using an automatic likelihood minimization procedure. We also introduced a novel technique to assign photometric redshift for simulated galaxies, following a two-dimensional probability distribution with VIMOS Public Extragalactic Redshift Survey data. The calibration was designed to match the observed abundance of galaxies as a function of photometric redshift, the distribution of photometric redshift errors, and the clustering amplitude on scales smaller than those used for BAO measurements. An exhaustive analysis was done to ensure that the mocks reproduce the input properties. Finally, mocks were tested by comparing the angular correlation function
w
(
θ
), angular power spectrum
C
ℓ
, and projected clustering
ξ
p
(
r
⊥
) to theoretical predictions and data. The impact of volume replication in the estimate of the covariance is also investigated. The success in accurately reproducing the photometric redshift uncertainties and the galaxy clustering as a function of redshift render this mock creation pipeline as a benchmark for future analyses of photometric galaxy surveys.
Tropical forests are known for their high diversity. Yet, forest patches do occur in the tropics where a single tree species is dominant. Such "monodominant" forests are known from all of the main ...tropical regions. For Amazonia, we sampled the occurrence of monodominance in a massive, basin-wide database of forest-inventory plots from the Amazon Tree Diversity Network (ATDN). Utilizing a simple defining metric of at least half of the trees ≥ 10 cm diameter belonging to one species, we found only a few occurrences of monodominance in Amazonia, and the phenomenon was not significantly linked to previously hypothesized life history traits such wood density, seed mass, ectomycorrhizal associations, or Rhizobium nodulation. In our analysis, coppicing (the formation of sprouts at the base of the tree or on roots) was the only trait significantly linked to monodominance. While at specific locales coppicing or ectomycorrhizal associations may confer a considerable advantage to a tree species and lead to its monodominance, very few species have these traits. Mining of the ATDN dataset suggests that monodominance is quite rare in Amazonia, and may be linked primarily to edaphic factors.
Aim
Amazonia hosts more tree species from numerous evolutionary lineages, both young and ancient, than any other biogeographic region. Previous studies have shown that tree lineages colonized ...multiple edaphic environments and dispersed widely across Amazonia, leading to a hypothesis, which we test, that lineages should not be strongly associated with either geographic regions or edaphic forest types.
Location
Amazonia.
Taxon
Angiosperms (Magnoliids; Monocots; Eudicots).
Methods
Data for the abundance of 5082 tree species in 1989 plots were combined with a mega‐phylogeny. We applied evolutionary ordination to assess how phylogenetic composition varies across Amazonia. We used variation partitioning and Moran's eigenvector maps (MEM) to test and quantify the separate and joint contributions of spatial and environmental variables to explain the phylogenetic composition of plots. We tested the indicator value of lineages for geographic regions and edaphic forest types and mapped associations onto the phylogeny.
Results
In the terra firme and várzea forest types, the phylogenetic composition varies by geographic region, but the igapó and white‐sand forest types retain a unique evolutionary signature regardless of region. Overall, we find that soil chemistry, climate and topography explain 24% of the variation in phylogenetic composition, with 79% of that variation being spatially structured (R2 = 19% overall for combined spatial/environmental effects). The phylogenetic composition also shows substantial spatial patterns not related to the environmental variables we quantified (R2 = 28%). A greater number of lineages were significant indicators of geographic regions than forest types.
Main Conclusion
Numerous tree lineages, including some ancient ones (>66 Ma), show strong associations with geographic regions and edaphic forest types of Amazonia. This shows that specialization in specific edaphic environments has played a long‐standing role in the evolutionary assembly of Amazonian forests. Furthermore, many lineages, even those that have dispersed across Amazonia, dominate within a specific region, likely because of phylogenetically conserved niches for environmental conditions that are prevalent within regions.
Mitochondria play prominent roles in the maintenance, performance, and adaptability of the cerebral circulation, but methodological limitations have prevented the detailed study of mitochondrial ...dynamics in the in vivo parenchymal circulation. Previous studies primarily have been done in isolated tissue and mitochondria or in cell cultures using transient fluorescent labeling. To remedy this situation, we have developed an entirely new imaging approach involving permanent labeling of mitochondria to study mitochondrial characteristics such as location, morphology, density, and size in endothelium of cerebral blood vessels. B6;129S‐Gt( ROSA)26Sortm1(CAG‐COX8A/Dendra2)Dcc/J and B6.Cg‐Tg(Tek‐cre)1Ywa/J mice strains (Jackson Laboratory) were bred and the offspring were used to visualize cerebrovascular endothelial mitochondria, in vivo, expressing MitoDendra2. The following primers and conditions were used for genotyping the mice in order to verify success of the breeding program: 1) GTA GGT GGA AAT TCT AGC ATC ATC C; 2) CTA GGC CAC AGA ATT GAA AGA TCT; 3) GTG AAA CAG CAT TGC TGT CAC TT; 4) GCG GTC TGG CAG TAA AAA CTA TC; 5) TCA ATG GGC GGG GGT CGT T; 6) TCC TGG CTT CTG AGG ACC GC; and 7) TTC CCC TGC AGG ACA ACG CC (PCR conditions temperature, time, cycle: Stage 1: 94°C, 2 m, 1x; Stage 2: 94°C, 0.5 m, 35x; 58°C, 0.5 m, 35x, and 72°C, 0.5 m, 35x; Stage 3: 72°C, 10 m, 1x, and 4°C. Examination of the cerebral vasculature in these mice using multiphoton microscopy demonstrated the localization of Dendra2 only in the endothelium of parenchymal blood vessels of different sizes and locations. This novel approach allows us to study the mitochondrial characteristics of the in vivo parenchymal circulation in real time, repeatedly, in the same mice over the course of minutes, hours, days, and weeks under normal conditions and following stresses such as experimental strokes or chronic cerebral hypoperfusion. We can combine this approach with the use of mitochondrial fluoroprobes in vivo, and with electron microscopy, western blot, and measurements of mitochondrial respiration ex vivo for the investigation of mitochondrial mechanism in the cerebral vasculature.
Support or Funding Information
This work was supported by National Institutes of Health grants HL‐077731; HL093554 (DWB), and NS094834 (PVK), Louisiana Board of Regents Endowed Chairs for Eminent Scholars program (DWB), American Heart Association grants 15POST23040005; 17SDG33410366 (IR), and 14SDG20490359 (PVK).
This is from the Experimental Biology 2018 Meeting. There is no full text article associated with this published in The FASEB Journal.
A new class of Janus kinase (JAK) inhibitors was discovered using a rationally designed pyrrolo1,2-bpyridazine-3-carboxamide scaffold. Preliminary studies identified ...(R)-(2,2-dimethylcyclopentyl)amine as a preferred C4 substituent on the pyrrolopyridazine core (3b). Incorporation of amino group to 3-position of the cyclopentane ring resulted in a series of JAK3 inhibitors (4g-4j) that potently inhibited IFNγ production in an IL2-induced whole blood assay and displayed high functional selectivity for JAK3-JAK1 pathway relative to JAK2. Further modifications led to the discovery of an orally bioavailable (2-fluoro-2-methylcyclopentyl)amino analogue 5g which is a nanomolar inhibitor of both JAK3 and TYK2, functionally selective for the JAK3-JAK1 pathway versus JAK2, and active in a human whole blood assay.
The 2016 European Vasculitis Society (EUVAS) meeting, held in Leiden, the Netherlands, was centered around phenotypic subtyping in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis ...(AAV). There were parallel meetings of the EUVAS petals, which here report on disease assessment; database; and long-term follow-up, registries, genetics, histology, biomarker studies, and clinical trials. Studies currently conducted will improve our ability to discriminate between different forms of vasculitis. In a project that involves the 10-year follow-up of AAV patients, we are working on retrieving data on patient and renal survival, relapse rate, the cumulative incidence of malignancies, and comorbidities. Across Europe, several vasculitis registries were developed covering over 10,000 registered patients. In the near future, these registries will facilitate clinical research in AAV on a scale hitherto unknown. Current studies on the genetic background of AAV will explore the potential prognostic significance of genetic markers and further refine genetic associations with distinct disease subsets. The histopathological classification of ANCA-associated glomerulonephritis is currently evaluated in light of data coming out of a large international validation study. In our continuous search for biomarkers to predict clinical outcome, promising new markers are important subjects of current research. Over the last 2 decades, a host of clinical trials have provided evidence for refinement of therapeutic regimens. We give an overview of clinical trials currently under development, and consider refractory vasculitis in detail. The goal of EUVAS is to stimulate ongoing research in clinical, serological, and histological management and techniques for patients with systemic vasculitis, with an outlook on the applicability for clinical trials.
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