A comprehensive understanding of variables associated with spatial differences in community composition is essential to explain and predict biodiversity over landscape scales. In this study, spatial ...patterns of bird diversity in Central Kalimantan, Indonesia, were examined and associated with local-scale (habitat structure and heterogeneity) and landscape-scale (logging, slope position and elevation) environmental variables. Within the study area (c. 196 km^sup 2^) local habitat structure and heterogeneity varied considerably, largely due to logging. In total 9747 individuals of 177 bird species were recorded. Akaike's information criterion (AIC) revealed that the best explanatory models of bird community similarity and species richness included both local- and landscape-scale environmental variables. Important local-scale variables included liana abundance, fern cover, sapling density, tree density, dead wood abundance and tree architecture, while important landscape-scale variables were elevation, logging and slope position. Geographic distance between sampling sites was not significantly associated with spatial variation in either species richness or similarity. These results indicate that deterministic environmental processes, as opposed to dispersal-driven stochastic processes, primarily structure bird assemblages within the spatial scale of this study and confirm that highly variable local habitat measures can be effective means of predicting landscape-scale community patterns.PUBLICATION ABSTRACT
We report the first observations of formaldehyde (HCHO) flux measured via eddy covariance, as well as HCHO concentrations and gradients, as observed by the Madison Fiber Laser-Induced Fluorescence ...Instrument during the BEACHON-ROCS 2010 campaign in a rural, Ponderosa Pine forest northwest of Colorado Springs, CO. A median noon upward flux of ~80 μg m−2 h−1 (~24 pptv m s−1) was observed with a noon range of 37 to 131 μg m−2 h−1. Enclosure experiments were performed to determine the HCHO branch (3.5 μg m-2 h−1) and soil (7.3 μg m−2 h−1) direct emission rates in the canopy. A zero-dimensional canopy box model, used to determine the apportionment of HCHO source and sink contributions to the flux, underpredicted the observed HCHO flux by a factor of 6. Simulated increases in concentrations of species similar to monoterpenes resulted in poor agreement with measurements, while simulated increases in direct HCHO emissions and/or concentrations of species similar to 2-methyl-3-buten-2-ol best improved model/measurement agreement. Given the typical diurnal variability of these BVOC emissions and direct HCHO emissions, this suggests that the source of the missing flux is a process with both a strong temperature and radiation dependence.
Randomized trials in the late window have demonstrated the efficacy and safety of endovascular thrombectomy in large-vessel occlusions. Patients with M2-segment MCA occlusions were excluded from ...these trials. We compared outcomes with endovascular thrombectomy in patients with M2-versus-M1 occlusions presenting 6-24 hours after symptom onset.
Analyses were on pooled data from studies enrolling patients with stroke treated with endovascular thrombectomy 6-24 hours after symptom onset. We compared 90-day functional independence (mRS ≤ 2), mortality, symptomatic intracranial hemorrhage, and successful reperfusion (expanded TICI = 2b-3) between patients with M2 and M1 occlusions. The benefit of successful reperfusion was then assessed among patients with M2 occlusion.
Of 461 patients, 367 (79.6%) had M1 occlusions and 94 (20.4%) had M2 occlusions. Patients with M2 occlusions were older and had lower median baseline NIHSS scores. Patients with M2 occlusion were more likely to achieve 90-day functional independence than those with M1 occlusion (adjusted OR = 2.13; 95% CI, 1.25-3.65). There were no significant differences in the proportion of successful reperfusion (82.9% versus 81.1%) or mortality (11.2% versus 17.2%). Symptomatic intracranial hemorrhage risk was lower in patients with M2-versus-M1 occlusions (4.3% versus 12.2%,
= .03). Successful reperfusion was independently associated with functional independence among patients with M2 occlusions (adjusted OR = 2.84; 95% CI, 1.11-7.29).
In the late time window, patients with M2 occlusions treated with endovascular thrombectomy achieved better clinical outcomes, similar reperfusion, and lower symptomatic intracranial hemorrhage rates compared with patients with M1 occlusion. These results support the safety and benefit of endovascular thrombectomy in patients with M2 occlusions in the late window.
Data from four recent reanalysis projects ECMWF, NCEP-NCAR, NCEP-Department of Energy (DOE), NASA have been diagnosed at the scale of synoptic weather systems using an objective feature tracking ...method. The tracking statistics indicate that, overall, the reanalyses correspond very well in the Northern Hemisphere (NH) lower troposphere, although differences for the spatial distribution of mean intensities show that the ECMWF reanalysis is systematically stronger in the main storm track regions but weaker around major orographic features. A direct comparison of the track ensembles indicates a number of systems with a broad range of intensities that compare well among the reanalyses. In addition, a number of small-scale weak systems are found that have no correspondence among the reanalyses or that only correspond upon relaxing the matching criteria, indicating possible differences in location and/or temporal coherence. These are distributed throughout the storm tracks, particularly in the regions known for small-scale activity, such as secondary development regions and the Mediterranean. For the Southern Hemisphere (SH), agreement is found to be generally less consistent in the lower troposphere with significant differences in both track density and mean intensity. The systems that correspond between the various reanalyses are considerably reduced and those that do not match span a broad range of storm intensities. Relaxing the matching criteria indicates that there is a larger degree of uncertainty in both the location of systems and their intensities compared with the NH. At upper-tropospheric levels, significant differences in the level of activity occur between the ECMWF reanalysis and the other reanalyses in both the NH and SH winters. This occurs due to a lack of coherence in the apparent propagation of the systems in ERA 15 and appears most acute above 500 hPa. This is probably due to the use of optimal interpolation data assimilation in ERA 15. Also shown are results based on using the same techniques to diagnose the tropical easterly wave activity. Results indicate that the wave activity is sensitive not only to the resolution and assimilation methods used but also to the model formulation. PUBLICATION ABSTRACT
Abstract
Background
Somatic hypermutation (SHM) status of the immunoglobulin heavy variable (IGHV) gene plays a crucial role in determining the prognosis and treatment of patients with chronic ...lymphocytic leukemia (CLL). A common approach for determining SHM status is multiplex polymerase chain reaction and Sanger sequencing of the immunoglobin heavy locus; however, this technique is low throughput, is vulnerable to failure, and does not allow multiplexing with other diagnostic assays.
Methods
Here we designed and validated a DNA targeted capture approach to detect immunoglobulin heavy variable somatic hypermutation (IGHV SHM) status as a submodule of a larger next-generation sequencing (NGS) panel that also includes probes for ATM, BIRC3, CHD2, KLHL6, MYD88, NOTCH1, NOTCH2, POT1, SF3B1, TP53, and XPO1. The assay takes as input FASTQ files and outputs a report containing IGHV SHM status and V allele usage following European Research Initiative on CLL guidelines.
Results
We validated the approach on 35 CLL patient samples, 34 of which were characterized using Sanger sequencing. The NGS panel identified the IGHV SHM status of 34 of 35 CLL patients. We showed 100% sensitivity and specificity among the 33 CLL samples with both NGS and Sanger sequencing calls. Furthermore, we demonstrated that this panel can be combined with additional targeted capture panels to detect prognostically important CLL single nucleotide variants, insertions/deletions, and copy number variants (TP53 copy number loss).
Conclusions
A targeted capture approach to IGHV SHM detection can be integrated into broader sequencing panels, allowing broad CLL prognostication in a single molecular assay.
Manufactured nanomaterials (NM) are already used in consumer products and exposure modelling predicts releases of ng to low µg l−1 levels of NMs into surface waters. The exposure of aquatic ...ecosystems, and therefore fishes, to manufactured NMs is inevitable. This review uses a physiological approach to describe the known effects of NMs on the body systems of fishes and to identify the internal target organs, as well as outline aspects of colloid chemistry relevant to fish biology. The acute toxicity data, suggest that the lethal concentration for many NMs is in the mg l−1 range, and a number of sublethal effects have been reported at concentrations from c. 100 µg to 1 mg l−1. Exposure to NMs in the water column can cause respiratory toxicity involving altered ventilation, mucus secretion and gill pathology. This may not lead, however, to overt haematological disturbances in the short term. The internal target organs include the liver, spleen and haematopoietic system, kidney, gut and brain; with toxic effects involving oxidative stress, ionoregulatory disturbances and organ pathologies. Some pathology appears to be novel for NMs, such as vascular injury in the brain of rainbow trout Oncorhynchus mykiss with carbon nanotubes. A lack of analytical methods, however, has prevented the reporting of NM concentrations in fish tissues, and the precise uptake mechanisms across the gill or gut are yet to be elucidated. The few dietary exposure studies conducted show no effects on growth or food intake at 10–100 mg kg−1 inclusions of NMs in the diet of O. mykiss, but there are biochemical disturbances. Early life stages are sensitive to NMs with reports of lethal toxicity and developmental defects. There are many data gaps, however, including how water quality alters physiological responses, effects on immunity and chronic exposure data at environmentally relevant concentrations. Overall, the data so far suggest that the manufactured NMs are not as toxic as some traditional chemicals (e.g. some dissolved metals) and the innovative, responsible, development of nanotechnology should continue, with potential benefits for aquaculture, fisheries and fish health diagnostics.
Ecosystem processes are driven by both environmental variables and the attributes of component species. The extent to which these effects are independent and/or dependent upon each other has remained ...unclear. We assess the extent to which climate affects net primary productivity (NPP) both directly and indirectly via its effect on plant size and leaf functional traits.
Using species occurrences and functional trait databases for North and South America, we describe the upper limit of woody plant height within 200 × 200 km grid‐cells. In addition to maximum tree height, we quantify grid‐cell means of three leaf traits (specific leaf area, and leaf nitrogen and phosphorus concentration) also hypothesized to influence productivity. Using structural equation modelling, we test the direct and indirect effects of environment and plant traits on remotely sensed MODIS‐derived estimates of NPP, using plant size (satellite‐measured canopy height and potential maximum tree height), leaf traits, growing season length, soil nutrients, climate and disturbances as explanatory variables.
Our results show that climate affects NPP directly as well as indirectly via plant size in both tropical and temperate forests. In tropical forests NPP further increases with leaf phosphorus concentration, whereas in temperate forests it increases with leaf nitrogen concentration. In boreal forests, NPP most strongly increases with increasing temperature and neither plant size nor leaf traits have a significant influence.
Synthesis. Our results suggest that at large spatial scales plant size and leaf nutrient traits can improve predictions of forest productivity over those based on climate alone. However, at higher latitudes their role is overridden by stressful climate. Our results provide independent empirical evidence for where and how global vegetation models predicting carbon fluxes could benefit from including effects of plant size and leaf stoichiometry.
Our results suggest that at large spatial scales plant size and leaf nutrient traits can improve predictions of forest productivity over those based on climate alone. However, at higher latitudes their role is overridden by stressful climate. Our results provide independent empirical evidence for where and how global vegetation models predicting carbon fluxes could benefit from including effects of plant size and leaf stoichiometry.
Despite advances in next generation DNA sequencing (NGS), NGS-based single gene tests for diagnostic purposes require improvements in terms of completeness, quality, speed, and cost. Single-molecule ...molecular inversion probes (smMIPs) are a technology with unrealized potential in the area of clinical genetic testing. In this proof-of-concept study, we selected 2 frequently requested gene tests, those for the breast cancer genes BRCA1 and BRCA2, and developed an automated work flow based on smMIPs.
The BRCA1 and BRCA2 smMIPs were validated using 166 human genomic DNA samples with known variant status. A generic automated work flow was built to perform smMIP-based enrichment and sequencing for BRCA1, BRCA2, and the checkpoint kinase 2 (CHEK2) c.1100del variant.
Pathogenic and benign variants were analyzed in a subset of 152 previously BRCA-genotyped samples, yielding an analytical sensitivity and specificity of 100%. Following automation, blind analysis of 65 in-house samples and 267 Norwegian samples correctly identified all true-positive variants (>3000), with no false positives. Consequent to process optimization, turnaround times were reduced by 60% to currently 10-15 days. Copy number variants were detected with an analytical sensitivity of 100% and an analytical specificity of 88%.
smMIP-based genetic testing enables automated and reliable analysis of the coding sequences of BRCA1 and BRCA2. The use of single-molecule tags, double-tiled targeted enrichment, and capturing and sequencing in duplo, in combination with automated library preparation and data analysis, results in a robust process and reduces routine turnaround times. Furthermore, smMIP-based copy number variation analysis could make independent copy number variation tools like multiplex ligation-dependent probes amplification dispensable.
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