A first-ever spinal cord imaging meeting was sponsored by the International Spinal Research Trust and the Wings for Life Foundation with the aim of identifying the current state-of-the-art of spinal ...cord imaging, the current greatest challenges, and greatest needs for future development. This meeting was attended by a small group of invited experts spanning all aspects of spinal cord imaging from basic research to clinical practice. The greatest current challenges for spinal cord imaging were identified as arising from the imaging environment itself; difficult imaging environment created by the bone surrounding the spinal canal, physiological motion of the cord and adjacent tissues, and small cross-sectional dimensions of the spinal cord, exacerbated by metallic implants often present in injured patients. Challenges were also identified as a result of a lack of “critical mass” of researchers taking on the development of spinal cord imaging, affecting both the rate of progress in the field, and the demand for equipment and software to manufacturers to produce the necessary tools. Here we define the current state-of-the-art of spinal cord imaging, discuss the underlying theory and challenges, and present the evidence for the current and potential power of these methods. In two review papers (part I and part II), we propose that the challenges can be overcome with advances in methods, improving availability and effectiveness of methods, and linking existing researchers to create the necessary scientific and clinical network to advance the rate of progress and impact of the research.
•Methodological challenges encountered in imaging of the spinal cord are presented.•Techniques to overcome these challenges for fMRI and DTI are presented.•Methods for spinal cord MRI (fMRI, DTI, MWF, MTR), MRS, and PET are presented.•Post-processing methods to improve spinal cord MRI are discussed.•We discuss the future directions, and current needs, for spinal cord imaging.
A first-ever spinal cord imaging meeting was sponsored by the International Spinal Research Trust and the Wings for Life Foundation with the aim of identifying the current state-of-the-art of spinal ...cord imaging, the current greatest challenges, and greatest needs for future development. This meeting was attended by a small group of invited experts spanning all aspects of spinal cord imaging from basic research to clinical practice. The greatest current challenges for spinal cord imaging were identified as arising from the imaging environment itself; difficult imaging environment created by the bone surrounding the spinal canal, physiological motion of the cord and adjacent tissues, and small crosssectional dimensions of the spinal cord, exacerbated by metallic implants often present in injured patients. Challenges were also identified as a result of a lack of “critical mass” of researchers taking on the development of spinal cord imaging, affecting both the rate of progress in the field, and the demand for equipment and software to manufacturers to produce the necessary tools. Here we define the current state-of-the-art of spinal cord imaging, discuss the underlying theory and challenges, and present the evidence for the current and potential power of these methods. In two review papers (part I and part II), we propose that the challenges can be overcome with advances in methods, improving availability and effectiveness of methods, and linking existing researchers to create the necessary scientific and clinical network to advance the rate of progress and impact of the research.
•Clinical challenges encountered in imaging of the spinal cord are presented.•Description of functional MRI of the spinal cord applications•Description of diffusion tensor imaging of the spinal cord applications•Specific findings in spinal cord pathologies
Chronic myelomonocytic leukemia (CMML) is a hematologic malignancy nearly confined to the elderly. Previous studies to determine incidence and prognostic significance of somatic mutations in CMML ...have relied on candidate gene sequencing, although an unbiased mutational search has not been conducted. As many of the genes commonly mutated in CMML were recently associated with age-related clonal hematopoiesis (ARCH) and aged hematopoiesis is characterized by a myelomonocytic differentiation bias, we hypothesized that CMML and aged hematopoiesis may be closely related. We initially established the somatic mutation landscape of CMML by whole exome sequencing followed by gene-targeted validation. Genes mutated in ⩾10% of patients were SRSF2, TET2, ASXL1, RUNX1, SETBP1, KRAS, EZH2, CBL and NRAS, as well as the novel CMML genes FAT4, ARIH1, DNAH2 and CSMD1. Most CMML patients (71%) had mutations in ⩾2 ARCH genes and 52% had ⩾7 mutations overall. Higher mutation burden was associated with shorter survival. Age-adjusted population incidence and reported ARCH mutation rates are consistent with a model in which clinical CMML ensues when a sufficient number of stochastically acquired age-related mutations has accumulated, suggesting that CMML represents the leukemic conversion of the myelomonocytic-lineage-biased aged hematopoietic system.
GammaLib and ctools Knodlseder, J; Mayer, M; Deil, C ...
Astronomy and astrophysics (Berlin),
09/2016, Volume:
593
Journal Article
Peer reviewed
Open access
The field of gamma-ray astronomy has seen important progress during the last decade, yet to date no common software framework has been developed for the scientific analysis of gamma-ray telescope ...data. We propose to fill this gap by means of the GammaLib software, a generic library that we have developed to support the analysis of gamma-ray event data. GammaLib was written in C++ and all functionality is available in Python through an extension module. Based on this framework we have developed the ctools software package, a suite of software tools that enables flexible workflows to be built for the analysis of Imaging Air Cherenkov Telescope event data. The ctools are inspired by science analysis software available for existing high-energy astronomy instruments, and they follow the modular ftools model developed by the High Energy Astrophysics Science Archive Research Center. The ctools were written in Python and C++, and can be either used from the command line via shell scripts or directly from Python. In this paper we present the GammaLib and ctools software versions 1.0 that were released at the end of 2015. GammaLib and ctools are ready for the science analysis of Imaging Air Cherenkov Telescope event data, and also support the analysis of Fermi-LAT data and the exploitation of the COMPTEL legacy data archive. We propose using ctools as the science tools software for the Cherenkov Telescope Array Observatory.
Drought and resprouting plants Zeppel, Melanie J. B; Harrison, Sandy P; Adams, Henry D ...
The New phytologist,
April 2015, Volume:
206, Issue:
2
Journal Article
Peer reviewed
Open access
Many species have the ability to resprout vegetatively after a substantial loss of biomass induced by environmental stress, including drought. Many of the regions characterised by ecosystems where ...resprouting is common are projected to experience more frequent and intense drought during the 21st Century. However, in assessments of ecosystem response to drought disturbance there has been scant consideration of the resilience and post‐drought recovery of resprouting species. Systematic differences in hydraulic and allocation traits suggest that resprouting species are more resilient to drought‐stress than nonresprouting species. Evidence suggests that ecosystems dominated by resprouters recover from disturbance more quickly than ecosystems dominated by nonresprouters. The ability of resprouters to avoid mortality and withstand drought, coupled with their ability to recover rapidly, suggests that the impact of increased drought stress in ecosystems dominated by these species may be small. The strategy of resprouting needs to be modelled explicitly to improve estimates of future climate‐change impacts on the carbon cycle, but this will require several important knowledge gaps to be filled before resprouting can be properly implemented.
Most HIV transmissions among men who have sex with men (MSM), the group that accounted for 67% of new US infections in 2014, occur via exposure to the rectal mucosa. However, it is unclear how the ...act of condomless receptive anal intercourse (CRAI) may alter the mucosal immune environment in HIV-negative MSM. Here, we performed a comprehensive characterization of the rectal mucosal immune environment for the phenotype and production of pro-inflammatory cytokines by CD4 and CD8 T cells, global transcriptomic analyses, and the composition of microbiota in HIV-negative MSM. Our results show that compared with men who had never engaged in anal intercourse, the rectal mucosa of MSM engaging in CRAI has a distinct phenotype characterized by higher levels of Th17 cells, greater CD8+ T cell proliferation and production of pro-inflammatory cytokines, molecular signatures associated with mucosal injury and repair likely mediated by innate immune cells, and a microbiota enriched for the Prevotellaceae family. These data provide a high-resolution model of the immunological, molecular, and microbiological perturbations induced by CRAI, will have direct utility in understanding rectal HIV transmission among MSM, and will enhance the design of future biomedical prevention interventions, including candidate HIV vaccines.
Cytokine-induced activation of indoleamine 2,3-dioxygenase (IDO) catabolizes L-tryptophan (TRP) into L-kynurenine (KYN), which is metabolized to quinolinic acid (QUIN) and kynurenic acid (KA). QUIN ...and KA are neuroactive and may contribute to the behavioral changes experienced by some patients during exposure to inflammatory stimuli such as interferon (IFN)-alpha. A relationship between depressive symptoms and peripheral blood TRP, KYN and KA during treatment with IFN-alpha has been described. However, whether peripheral blood changes in these IDO catabolites are manifest in the brain and whether they are related to central nervous system cytokine responses and/or behavior is unknown. Accordingly, TRP, KYN, QUIN and KA were measured in cerebrospinal fluid (CSF) and blood along with CSF concentrations of relevant cytokines, chemokines and soluble cytokine receptors in 27 patients with hepatitis C after approximately 12 weeks of either treatment with IFN-alpha (n=16) or no treatment (n=11). Depressive symptoms were assessed using the Montgomery-Asberg Depression Rating Scale. IFN-alpha significantly increased peripheral blood KYN, which was accompanied by marked increases in CSF KYN. Increased CSF KYN was in turn associated with significant increases in CSF QUIN and KA. Despite significant decreases in peripheral blood TRP, IFN-alpha had no effect on CSF TRP concentrations. Increases in CSF KYN and QUIN were correlated with increased CSF IFN-alpha, soluble tumor necrosis factor-alpha receptor 2 and monocyte chemoattractant protein-1 as well as increased depressive symptoms. In conclusion, peripheral administration of IFN-alpha activated IDO in concert with central cytokine responses, resulting in increased brain KYN and QUIN, which correlated with depressive symptoms.
Early reports suggested that resistin is associated with obesity and insulin resistance in rodents. However, subsequent studies have not supported these findings. To our knowledge, the present study ...is the first assessment in human subjects of serum resistin and insulin sensitivity by the insulin clamp technique. Thirty-eight nonobese subjects age, 23 ± 4 yr; body mass index (BMI), 25.4 ± 4.3 kg/m2, 12 obese subjects (age, 54 ± 8 yr; BMI, 33.0 ± 2.5 kg/m2), and 22 obese subjects with type 2 diabetes (age, 59 ± 7 yr; BMI, 34.0 ± 2.4 kg/m2) were studied. Serum resistin concentrations were not different among nonobese (4.1 ± 1.7 ng/ml), obese (4.2 ± 1.6 ng/ml), and obese diabetic subjects (3.7 ± 1.2 ng/ml), and were not significantly correlated to glucose disposal rate during a hyperinsulinemic glucose clamp across groups. Serum resistin was, however, inversely related to insulin sensitivity in nonobese subjects only (r = −0.35; P = 0.05), although this association was lost after adjusting for percent body fat. Serum resistin was not related to percent fat, BMI, or fat cell size. A strong correlation was observed between serum resistin and resistin mRNA expression from abdominal sc adipose tissue in a separate group of obese subjects (r = 0.62; P < 0.01; n = 56). Although the exact function of resistin is unknown, we demonstrated only a weak relationship between resistin and insulin sensitivity in nonobese subjects, indicating that resistin is unlikely to be a major link between obesity and insulin resistance in humans.
ABSTRACT
The International Pulsar Timing Array 2nd data release is the combination of data sets from worldwide collaborations. In this study, we search for continuous waves: gravitational wave ...signals produced by individual supermassive black hole binaries in the local universe. We consider binaries on circular orbits and neglect the evolution of orbital frequency over the observational span. We find no evidence for such signals and set sky averaged 95 per cent upper limits on their amplitude h95. The most sensitive frequency is 10 nHz with h95 = 9.1 × 10−15. We achieved the best upper limit to date at low and high frequencies of the PTA band thanks to improved effective cadence of observations. In our analysis, we have taken into account the recently discovered common red noise process, which has an impact at low frequencies. We also find that the peculiar noise features present in some pulsars data must be taken into account to reduce the false alarm. We show that using custom noise models is essential in searching for continuous gravitational wave signals and setting the upper limit.
We present a benchmark system for global vegetation models. This system provides a quantitative evaluation of multiple simulated vegetation properties, including primary production; seasonal net ...ecosystem production; vegetation cover; composition and height; fire regime; and runoff. The benchmarks are derived from remotely sensed gridded datasets and site-based observations. The datasets allow comparisons of annual average conditions and seasonal and inter-annual variability, and they allow the impact of spatial and temporal biases in means and variability to be assessed separately. Specifically designed metrics quantify model performance for each process, and are compared to scores based on the temporal or spatial mean value of the observations and a "random" model produced by bootstrap resampling of the observations. The benchmark system is applied to three models: a simple light-use efficiency and water-balance model (the Simple Diagnostic Biosphere Model: SDBM), the Lund-Potsdam-Jena (LPJ) and Land Processes and eXchanges (LPX) dynamic global vegetation models (DGVMs). In general, the SDBM performs better than either of the DGVMs. It reproduces independent measurements of net primary production (NPP) but underestimates the amplitude of the observed CO2 seasonal cycle. The two DGVMs show little difference for most benchmarks (including the inter-annual variability in the growth rate and seasonal cycle of atmospheric CO2), but LPX represents burnt fraction demonstrably more accurately. Benchmarking also identified several weaknesses common to both DGVMs. The benchmarking system provides a quantitative approach for evaluating how adequately processes are represented in a model, identifying errors and biases, tracking improvements in performance through model development, and discriminating among models. Adoption of such a system would do much to improve confidence in terrestrial model predictions of climate change impacts and feedbacks.
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