The Bio-hydro-atmosphere interactions of Energy, Aerosols, Carbon, H2O, Organics & Nitrogen (BEACHON) project seeks to understand the feedbacks and inter-relationships between hydrology, biogenic ...emissions, carbon assimilation, aerosol properties, clouds and associated feedbacks within water-limited ecosystems. The Manitou Experimental Forest Observatory (MEFO) was established in 2008 by the National Center for Atmospheric Research to address many of the BEACHON research objectives, and it now provides a fixed field site with significant infrastructure. MEFO is a mountainous, semi-arid ponderosa pine-dominated forest site that is normally dominated by clean continental air but is periodically influenced by anthropogenic sources from Colorado Front Range cities. This article summarizes the past and ongoing research activities at the site, and highlights some of the significant findings that have resulted from these measurements. These activities include - soil property measurements; - hydrological studies; - measurements of high-frequency turbulence parameters; - eddy covariance flux measurements of water, energy, aerosols and carbon dioxide through the canopy; - determination of biogenic and anthropogenic volatile organic compound emissions and their influence on regional atmospheric chemistry; - aerosol number and mass distributions; - chemical speciation of aerosol particles; - characterization of ice and cloud condensation nuclei; - trace gas measurements; and - model simulations using coupled chemistry and meteorology. In addition to various long-term continuous measurements, three focused measurement campaigns with state-of-the-art instrumentation have taken place since the site was established, and two of these studies are the subjects of this special issue: BEACHON-ROCS (Rocky Mountain Organic Carbon Study, 2010) and BEACHON-RoMBAS (Rocky Mountain Biogenic Aerosol Study, 2011).
The 2016 revision of the World Health Organization classification of tumors of hematopoietic and lymphoid tissues is characterized by a closer integration of morphology and molecular genetics. ...Notwithstanding, the myelodysplastic syndrome (MDS) with isolated del(5q) remains so far the only MDS subtype defined by a genetic abnormality. Approximately half of MDS patients carry somatic mutations in spliceosome genes, with SF3B1 being the most commonly mutated one. SF3B1 mutation identifies a condition characterized by ring sideroblasts (RS), ineffective erythropoiesis, and indolent clinical course. A large body of evidence supports recognition of SF3B1-mutant MDS as a distinct nosologic entity. To further validate this notion, we interrogated the data set of the International Working Group for the Prognosis of MDS (IWG-PM). Based on the findings of our analyses, we propose the following diagnostic criteria for SF3B1-mutant MDS: (1) cytopenia as defined by standard hematologic values, (2) somatic SF3B1 mutation, (3) morphologic dysplasia (with or without RS), and (4) bone marrow blasts <5% and peripheral blood blasts <1%. Selected concomitant genetic lesions represent exclusion criteria for the proposed entity. In patients with clonal cytopenia of undetermined significance, SF3B1 mutation is almost invariably associated with subsequent development of overt MDS with RS, suggesting that this genetic lesion might provide presumptive evidence of MDS in the setting of persistent unexplained cytopenia. Diagnosis of SF3B1-mutant MDS has considerable clinical implications in terms of risk stratification and therapeutic decision making. In fact, this condition has a relatively good prognosis and may respond to luspatercept with abolishment of the transfusion requirement.
Cerebral amyloid angiopathy, which is defined by cerebrovascular deposition of amyloid β, is a common age-related small vessel pathology associated with intracerebral haemorrhage and cognitive ...impairment. Based on complementary lines of evidence from in vivo studies of individuals with hereditary, sporadic, and iatrogenic forms of cerebral amyloid angiopathy, histopathological analyses of affected brains, and experimental studies in transgenic mouse models, we present a framework and timeline for the progression of cerebral amyloid angiopathy from subclinical pathology to the clinical manifestation of the disease. Key stages that appear to evolve sequentially over two to three decades are (stage one) initial vascular amyloid deposition, (stage two) alteration of cerebrovascular physiology, (stage three) non-haemorrhagic brain injury, and (stage four) appearance of haemorrhagic brain lesions. This timeline of stages and the mechanistic processes that link them have substantial implications for identifying disease-modifying interventions for cerebral amyloid angiopathy and potentially for other cerebral small vessel diseases.
In recent years, the role of CTA and CTP for vasospasm diagnosis in the setting of ASAH has been the subject of many research studies. The purpose of this study was to perform a meta-analysis of the ...diagnostic performance of CTA and CTP for vasospasm in patients with ASAH by using DSA as the criterion standard.
The search strategy for research studies was based on the Cochrane Handbook for Systematic Reviews, including literature data bases (PubMed, Embase, Cochrane Database of Systematic Reviews, and the Web of Science) and reference lists of manuscripts published from January 1996 to February 2009. The inclusion criteria were the following: 1) published manuscripts, 2) original research studies with prospective or retrospective data, 3) patients with ASAH, 4) CTA or CTP as the index test, and 5) DSA as the reference standard. Three reviewers independently assessed the quality of these research studies by using the QUADAS tool. Pooled estimates of sensitivity, specificity, LR+, LR-, DOR, and the SROC curve were determined.
CTA and CTP searches yielded 505 and 214 manuscripts, respectively. Ten research studies met inclusion criteria for each CTA and CTP search. Six CTA and 3 CTP studies had sufficient data for statistical analysis. CTA pooled estimates had 79.6% sensitivity (95%CI, 74.9%-83.8%), 93.1%specificity (95%CI, 91.7%-94.3%), 18.1 LR+ (95%CI, 7.3-45.0), and 0.2 LR- (95%CI, 0.1-0.4); and CTP pooled estimates had 74.1% sensitivity (95%CI, 58.7%- 86.2%), 93.0% specificity (95% CI, 79.6%-98.7%), 9.3 LR+ (95%CI, 3.4-25.9), and 0.2 LR- (95%CI, 0.04-1.2). Overall DORs were 124.5 (95%CI, 28.4-546.4) for CTA and 43.0 (95%CI, 6.5-287.1) for CTP. Area under the SROC curve was 98 ± 2.0%for CTA and 97 ± 3.0% for CTP.
The high diagnostic accuracy determined for both CTA and CTP in this meta-analysis suggests that they are potentially valuable techniques for vasospasm diagnosis in ASAH. Awareness of these results may impact patient care by providing supportive evidence for more effective use of CTA and CTP imaging in ASAH.
Biogenic volatile organic compound (BVOC) emissions come from a variety of sources, including living above-ground foliar biomass and microbial decomposition of dead organic matter at the soil surface ...(litter and soil organic matter). There are, however, few reports that quantify the contributions of each component. Measurements of emission fluxes are now made above the vegetation canopy, but these include contributions from all sources. BVOC emission models currently include detailed parameterization of the emissions from foliar biomass but do not have an equally descriptive treatment of emissions from litter or other sources. We present here results of laboratory and field experiments to characterize the major parameters that control emissions from litter.
Litter emissions are exponentially dependent on temperature. The moisture content of the litter plays a minor role, except during and immediately following rain events. The percentage of carbon readily available for microbial and other decomposition processes decreases with litter age. These 3 variables are combined in a model to explain over 50% of the variance of individual BVOC emission fluxes measured. The modeled results of litter emissions were compared with above-canopy fluxes. Litter emissions constituted less than 1% of above-canopy emissions for all BVOCs measured. A comparison of terpene oil pools in litter and live needles with above-canopy fluxes suggests that there may be another canopy terpene source in addition to needle storage or that some terpene emissions may be light-dependent.
Ground enclosure measurements indicated that compensation point concentrations of BVOCs (equilibrium between BVOC emission and deposition) were usually higher than ambient air concentrations at the temperature of the measurements.
► Litter BVOC fluxes were measured by gradient flux and enclosure techniques. ► Emissions were shown to have exponential dependence on temperature and moisture. ► A litter BVOC emissions model was developed which successfully reproduced the emission measurements. ► Litter BVOC emissions make only a small contribution to the whole ecosystem flux of the BVOCs measured.
Risk stratification is critical in the care of patients with myelodysplastic syndromes (MDS). Approximately 10% have a complex karyotype (CK), defined as more than two cytogenetic abnormalities, ...which is a highly adverse prognostic marker. However, CK-MDS can carry a wide range of chromosomal abnormalities and somatic mutations. To refine risk stratification of CK-MDS patients, we examined data from 359 CK-MDS patients shared by the International Working Group for MDS. Mutations were underrepresented with the exception of TP53 mutations, identified in 55% of patients. TP53 mutated patients had even fewer co-mutated genes but were enriched for the del(5q) chromosomal abnormality (p < 0.005), monosomal karyotype (p < 0.001), and high complexity, defined as more than 4 cytogenetic abnormalities (p < 0.001). Monosomal karyotype, high complexity, and TP53 mutation were individually associated with shorter overall survival, but monosomal status was not significant in a multivariable model. Multivariable survival modeling identified severe anemia (hemoglobin < 8.0 g/dL), NRAS mutation, SF3B1 mutation, TP53 mutation, elevated blast percentage (>10%), abnormal 3q, abnormal 9, and monosomy 7 as having the greatest survival risk. The poor risk associated with CK-MDS is driven by its association with prognostically adverse TP53 mutations and can be refined by considering clinical and karyotype features.
Bacteria in nature often exist as sessile communities called biofilms. These communities develop structures that are morphologically and physiologically differentiated from free-living bacteria. A ...cell-to-cell signal is involved in the development of Pseudomonas aeruginosa biofilms. A specific signaling mutant, a/as/ mutant, forms flat, undifferentiated biofilms that unlike wild-type biofilms are sensitive to the biocide sodium dodecyl sulfate. Mutant biofilms appeared normal when grown in the presence of a synthetic signal molecule. The involvement of an intercellular signal molecule in the development of P aeruginosa biofilms suggests possible targets to control biofilm growth on catheters, in cystic fibrosis, and in other environments where P. aeruginosa biofilms are a persistent problem.
The early diagnosis of spinal vascular malformations suffers from the nonspecificity of their clinical and radiologic presentations. Spinal angiography requires a methodical approach to offer a high ...diagnostic yield. The prospect of false-negative studies is particularly distressing when addressing conditions with a narrow therapeutic window. The purpose of this study was to identify factors leading to missed findings or inadequate studies in patients with spinal vascular malformations.
The clinical records, laboratory findings, and imaging features of 18 patients with spinal arteriovenous fistulas and at least 1 prior angiogram read as normal were reviewed. The clinical status was evaluated before and after treatment by using the Aminoff-Logue Disability Scale.
Eighteen patients with 19 lesions underwent a total of 30 negative spinal angiograms. The lesions included 9 epidural arteriovenous fistulas, 8 dural arteriovenous fistulas, and 2 perimedullary arteriovenous fistulas. Seventeen patients underwent endovascular (11) or surgical (6) treatment, with a delay ranging between 1 week and 32 months; the Aminoff-Logue score improved in 13 (76.5%). The following factors were identified as the causes of the inadequate results: 1) lesion angiographically documented but not identified (55.6%); 2) region of interest not documented (29.6%); or 3) level investigated but injection technically inadequate (14.8%).
All the angiograms falsely reported as normal were caused by correctible, operator-dependent factors. The nonrecognition of documented lesions was the most common cause of error. The potential for false-negative studies should be reduced by the adoption of rigorous technical and training standards and by second opinion reviews.
Background
Despite increasing awareness of the disease, rates of undiagnosed psoriatic arthritis (PsA) are high in patients with psoriasis (PsO). The validated Psoriasis Epidemiology Screening Tool ...(PEST) is a five‐item questionnaire developed to help identify PsA at an early stage.
Objectives
To assess the risk of possible undiagnosed PsA among patients with PsO and characterize patients based on PEST scores.
Methods
This study included all patients enrolled in the Corrona PsO Registry with data on all five PEST questions. Demographics, clinical characteristics and patient‐reported outcomes were compared in Corrona PsO Registry patients with PEST scores ≥3 and <3 using t‐tests for continuous variables and chi‐squared tests for categorical variables; scores ≥3 may indicate PsA.
Results
Of 1516 patients with PsO, 904 did not have dermatologist‐reported PsA; 112 of these 904 patients (12.4%) scored ≥3 and were significantly older, female, less likely to be working, and had higher BMI than patients with scores <3. They also had significantly longer PsO duration, were more likely to have nail PsO and had worse health status, pain, fatigue, Dermatology Life Quality Index and activity impairment.
Conclusions
Improved PsA screening is needed in patients with PsO because the validated PEST identified over one‐tenth of registry patients who were not noted to have PsA as having scores ≥3, who could have had undiagnosed PsA. Appropriate, earlier care is important because these patients were more likely to have nail PsO, worse health‐related quality of life and worse activity impairment.
The brain’s network of perivascular channels for clearance of excess fluids and waste plays a critical role in the pathogenesis of several neurodegenerative diseases including cerebral amyloid ...angiopathy (CAA). CAA is the main cause of hemorrhagic stroke in the elderly, the most common vascular comorbidity in Alzheimer’s disease and also implicated in adverse events related to anti-amyloid immunotherapy. Remarkably, the mechanisms governing perivascular clearance of soluble amyloid β—a key culprit in CAA—from the brain to draining lymphatics and systemic circulation remains poorly understood. This knowledge gap is critically important to bridge for understanding the pathophysiology of CAA and accelerate development of targeted therapeutics. The authors of this review recently converged their diverse expertise in the field of perivascular physiology to specifically address this problem within the framework of a Leducq Foundation Transatlantic Network of Excellence on Brain Clearance. This review discusses the overarching goal of the consortium and explores the evidence supporting or refuting the role of impaired perivascular clearance in the pathophysiology of CAA with a focus on translating observations from rodents to humans. We also discuss the anatomical features of perivascular channels as well as the biophysical characteristics of fluid and solute transport.
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