Constraining ozone-precursor responsiveness using ambient measurements

This study develops probabilistic estimates of ozone (O3) sensitivities to precursor emissions by incorporating uncertainties in photochemical modeling and evaluating model performance based on ground-level observations of O3 and oxides of nitrogen (NOx). Uncertainties in model formulations and input parameters are jointly considered to identify factors that strongly influence O3 concentrations and sensitivities in the Dallas-Fort Worth region in Texas. Weightings based on a Bayesian inference technique and screenings based on model performance and statistical tests of significance are used to generate probabilistic representation of O3 response to emissions and model input parameters. Adjusted (observation-constrained) results favor simulations using the sixth version of the carbon bond chemical mechanism (CB6) and scaled-up emissions of NOx, dampening the overall sensitivity of O3 to NOx and increasing the sensitivity of O3 to volatile organic compounds in the study region. This approach of using observations to adjust and constrain model simulations can provide probabilistic representations of pollutant responsiveness to emission controls that complement the results obtained from deterministic air-quality modeling

S100b in acute ischemic stroke clots is a biomarker for post-thrombectomy intracranial hemorrhages

Background and purposePost-thrombectomy intracranial hemorrhages (PTIH) are dangerous complications of acute ischemic stroke (AIS) following mechanical thrombectomy. We aimed to investigate if S100b levels in AIS clots removed by mechanical thrombectomy correlated to increased risk of PTIH.MethodsWe analyzed 122 thrombi from 80 AIS patients in the RESTORE Registry of AIS clots, selecting an equal number of patients having been pre-treated or not with rtPA (40 each group). Within each subgroup, 20 patients had developed PTIH and 20 patients showed no signs of hemorrhage. Gross photos of each clot were taken and extracted clot area (ECA) was measured using ImageJ. Immunohistochemistry for S100b was performed and Orbit Image Analysis was used for quantification. Immunofluorescence was performed to investigate co-localization between S100b and T-lymphocytes, neutrophils and macrophages. Chi-square or Kruskal-Wallis test were used for statistical analysis.ResultsPTIH was associated with higher S100b levels in clots (0.33 [0.08–0.85] vs. 0.07 [0.02–0.27] mm2, H1 = 6.021, P = 0.014*), but S100b levels were not significantly affected by acute thrombolytic treatment (P = 0.386). PTIH was also associated with patients having higher NIHSS at admission (20.0 [17.0–23.0] vs. 14.0 [10.5–19.0], H1 = 8.006, P = 0.005) and higher number of passes during thrombectomy (2 [1–4] vs. 1 [1–2.5], H1 = 5.995, P = 0.014*). S100b co-localized with neutrophils, macrophages and with T-lymphocytes in the clots.ConclusionsHigher S100b expression in AIS clots, higher NIHSS at admission and higher number of passes during thrombectomy are all associated with PTIH. Further investigation of S100b expression in AIS clots by neutrophils, macrophages and T-lymphocytes could provide insight into the role of S100b in thromboinflammation

Bone bruise, lipohemarthrosis, and joint effusion in CT of non-displaced hip fracture.

BackgroundA suspected occult hip fracture after normal radiography is not uncommon in an elderly person after a fall. Despite a lack of robust validation in the literature, computed tomography (CT) is often used as secondary imaging.PurposeTo assess the frequency and clinical utility of non-cortical skeletal and soft tissue lesions as ancillary fracture signs in CT diagnosis of occult hip fractures.Material and MethodsAll fracture signs (cortical and trabecular fractures, bone bruise, joint effusion, and lipohemarthrosis) were recorded in 231 hip low-energy trauma cases with CT performed after normal or equivocal radiography in two trauma centers.ResultsThere were no fracture signs in 110 patients. Twelve of these had a joint effusion. In 121 patients with 46 cervical hip fractures and 75 trochanteric fractures one or more fracture signs were present. Cortical fractures were found in 115 patients. Bone bruise was found in 119 patients, joint effusion in 35, and lipohemarthrosis in 20 patients.ConclusionAncillary signs such as bone bruise and lipohemarthrosis can strengthen and sometimes indicate the diagnosis in CT of occult hip fractures. Joint effusion is a non-specific sign

Observer variation for radiography, computed tomography, and magnetic resonance imaging of occult hip fractures

Background: Conventional radiography is insufficient for diagnosis in a small but not unimportant number of hip fractures, and secondary imaging with computed tomography (CT) or magnetic resonance imaging (MRI) is warranted. There are no convincing observer variation studies performed for conventional radiography or CT in occult fractures, and no large materials for MRI. Purpose: To assess observer variation in radiography, CT and MRI of suspected occult, non-displaced hip fractures, and to evaluate to what extent observer experience or patient age may influence observer performance. Material and Methods: A total of 375 patients after hip trauma where radiography was followed by CT or MRI to evaluate a suspected occult hip fracture were collected retrospectively from two imaging centers. After scoring by three observers with varying degrees of radiologic experience, observer variation was assessed by using linear weighted kappa statistics. Results: For radiography, agreements between the three observers were moderate to substantial for intracapsular fractures, with kappa values in the ranges of 0.56-0.66. Kappa values were substantial for extracapsular fractures, in the ranges of 0.69-0.72. With increasing professional experience, fewer fractures were classified as equivocal at radiography. For CT and MRI, observer agreements were similar and almost perfect, with kappa values in the ranges of 0.85-0.97 and 0.93-0.97. Conclusion: There were almost perfect observer agreements for CT and MRI in diagnosing non-displaced, occult hip fractures. Observer agreements for radiography were moderate to substantial, and observer experience influenced agreement only at radiography

Bone bruise, lipohemarthrosis, and joint effusion in CT of non-displaced hip fracture

BackgroundA suspected occult hip fracture after normal radiography is not uncommon in an elderly person after a fall. Despite a lack of robust validation in the literature, computed tomography (CT) is often used as secondary imaging.PurposeTo assess the frequency and clinical utility of non-cortical skeletal and soft tissue lesions as ancillary fracture signs in CT diagnosis of occult hip fractures.Material and MethodsAll fracture signs (cortical and trabecular fractures, bone bruise, joint effusion, and lipohemarthrosis) were recorded in 231 hip low-energy trauma cases with CT performed after normal or equivocal radiography in two trauma centers.ResultsThere were no fracture signs in 110 patients. Twelve of these had a joint effusion. In 121 patients with 46 cervical hip fractures and 75 trochanteric fractures one or more fracture signs were present. Cortical fractures were found in 115 patients. Bone bruise was found in 119 patients, joint effusion in 35, and lipohemarthrosis in 20 patients.ConclusionAncillary signs such as bone bruise and lipohemarthrosis can strengthen and sometimes indicate the diagnosis in CT of occult hip fractures. Joint effusion is a non-specific sign

The most important thing is the tail: Multitudinous functionalities of intrinsically disordered protein termini

AbstractMany functional proteins do not have well-folded structures in their substantial parts, representing hybrids that possess both ordered and disordered regions. Disorder is unevenly distributed within these hybrid proteins and is typically more common at protein termini. Disordered tails are engaged in a wide range of functions, some of which are unique for termini and cannot be found in other disordered parts of a protein. This review covers some of the key functions of disordered protein termini and emphasizes that these tails are not simple flexible protrusions but are evolved to serve

Characterization of the `White' Appearing Clots that Cause

Objectives: Most clots retrieved from patients with acute ischemic stroke are ‘red’ in color. ‘White’ clots represent a less common entity and their histological composition is less known. Our aim was to investigate the composition, imaging and procedural characteristics of ‘white’ clots retrieved by mechanical thrombectomy. Materials and methods: Seventy five ‘white’ thrombi were selected by visual inspection from a cohort of 760 clots collected as part of the RESTORE registry. Clots were evaluated histopathologically. Results: Quantification of Martius Scarlett Blue stain identified platelets/other as the major component in ‘white’ clots’ (mean of 55% of clot overall composition) followed by fibrin (31%), red blood cells (6%) and white blood cells (3%). ‘White’ clots contained significantly more platelets/other (p<0.001*) and collagen/calcification (p<0.001*) and less red blood cells (p<0.001*) and white blood cells (p=0.018*) than ‘red’ clots. The mean platelet and von Willebrand Factor expression was 43% and 24%, respectively. Adipocytes were found in four cases. ‘White’ clots were significantly smaller (p=0.016*), less hyperdense (p=0.005*) on computed tomography angiography/non-contrast CT and were associated with a smaller extracted clot area (p<0.001*) than ‘red’ clots. They primarily caused the occlusion of middle cerebral artery, were less likely to be removed by aspiration and more likely to require rescue-therapy for retrieval. Conclusions: ‘White’ clots represented 14% of our cohort and were platelet, von Willebrand Factor and collagen/calcification-rich. ‘White’ clots were smaller, less hyperdense, were associated with significantly more distal occlusions and were less successfully removed by aspiration alone than ‘red’ clots

Investigating the Role of Brain Natriuretic Peptide (BNP) and N-Terminal-proBNP in Thrombosis and Acute Ischemic Stroke Etiology

The need for biomarkers for acute ischemic stroke (AIS) to understand the mechanisms implicated in pathological clot formation is critical. The levels of the brain natriuretic peptides known as brain natriuretic peptide (BNP) and NT-proBNP have been shown to be increased in patients suffering from heart failure and other heart conditions. We measured their expression in AIS clots of cardioembolic (CE) and large artery atherosclerosis (LAA) etiology, evaluating their location inside the clots, aiming to uncover their possible role in thrombosis. We analyzed 80 thrombi from 80 AIS patients in the RESTORE registry of AIS clots, 40 of which were of CE and 40 of LAA etiology. The localization of BNP and NT-BNP, quantified using immunohistochemistry and immunofluorescence, in AIS-associated white blood cell subtypes was also investigated. We found a statistically significant positive correlation between BNP and NT-proBNP expression levels (Spearman’s rho = 0.668 p p = 0.923) or in NT-proBNP expression (0.29 [0.11–0.58]% vs. 0.18 [0.05–0.51]%, p = 0.119), although there was a trend of higher NT-proBNP expression in the LAA clots. It was noticeable that BNP was distributed throughout the thrombus and especially within platelet-rich regions. However, NT-proBNP colocalized with neutrophils, macrophages, and T-lymphocytes, suggesting its association with the thrombo-inflammatory process