Fourier synthesis optical diffraction tomography for kilohertz rate volumetric imaging

Many biological and soft matter processes occur at high speeds in complex 3D environments, and developing imaging techniques capable of elucidating their dynamics is an outstanding experimental challenge. Here, we introduce Fourier Synthesis Optical Diffraction Tomography (FS-ODT), a novel approach for high-speed quantitative phase imaging capable of recording the 3D refractive index at kilohertz rates. FS-ODT introduces new pattern generation and inverse computational strategies that multiplex tens of illumination angles in a single tomogram, dramatically increasing the volumetric imaging rate. We validate FS-ODT performance by imaging samples of known composition and accurately recovering the refractive index for increasing pattern complexity. We further demonstrate the capabilities of FS-ODT for probing complex systems by studying the hindered diffusion of colloids in solution and the motility of single-cellular bacterial swimmers. We believe that FS-ODT is a promising approach for unlocking challenging imaging regimes in biophysics and soft matter that have been little explored, including understanding the physical interactions of colloids and microswimmers with their viscous 3D environment and the interplay between these stimuli and the molecular response of biological systems

What do we Know About the Effects of Macroprudential Policy, De Nederlandsche Bank Working

Abstract The literature on the effectiveness of macroprudential policy tools is still in its infancy and has so far provided only limited guidance for policy decisions. In recent years, however, increasing efforts have been made to fill this gap. Progress has been made in embedding macroprudential policy in theoretical models. There is increasing empirical work on the effect of some macroprudential tools on a range of target variables, such as quantities and prices of credit, asset prices, and on the amplitude of the financial cycle and financial stability. In this paper we review recent progress in theoretical and empirical research on the effectiveness of macroprudential instruments. Keyword

Cholinergic Signaling Attenuates Pro-Inflammatory Interleukin-8 Response in Colonic Epithelial Cells.

Infants affected by Hirschsprung disease (HSCR), a neurodevelopmental congenital disorder, lack ganglia of the intrinsic enteric nervous system (aganglionosis) in a variable length of the colon, and are prone to developing severe Hirschsprung-associated enterocolitis (HAEC). HSCR patients typically show abnormal dense innervation of extrinsic cholinergic nerve fibers throughout the aganglionic rectosigmoid. Cholinergic signaling has been reported to reduce inflammatory response. Consequently, a sparse extrinsic cholinergic innervation in the mucosa of the rectosigmoid correlates with increased inflammatory immune cell frequencies and higher incidence of HAEC in HSCR patients. However, whether cholinergic signals influence the pro-inflammatory immune response of intestinal epithelial cells (IEC) is unknown. Here, we analyzed colonic IEC isolated from 43 HSCR patients with either a low or high mucosal cholinergic innervation density (fiber-low versus fiber-high) as well as from control tissue. Compared to fiber-high samples, IEC purified from fiber-low rectosigmoid expressed significantly higher levels of IL-8 but not TNF-α, IL-10, TGF-β1, Muc-2 or tight junction proteins. IEC from fiber-low rectosigmoid showed higher IL-8 protein concentrations in cell lysates as well as prominent IL-8 immunoreactivity compared to IEC from fiber-high tissue. Using the human colonic IEC cell line SW480 we demonstrated that cholinergic signals suppress lipopolysaccharide-induced IL-8 secretion via the alpha 7 nicotinic acetylcholine receptor (a7nAChR). In conclusion, we showed for the first time that the presence of a dense mucosal cholinergic innervation is associated with decreased secretion of IEC-derived pro-inflammatory IL-8 in the rectosigmoid of HSCR patients likely dependent on a7nAChR activation. Owing to the association between IL-8 and enterocolitis-prone, fiber-low HSCR patients, targeted therapies against IL-8 might be a promising immunotherapy candidate for HAEC treatment

Sex-related differences in risk factors, type of treatment received and outcomes in patients with atrial fibrillation and acute stroke: Results from the RAF-study (Early Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation)

Introduction: Atrial fibrillation is an independent risk factor of thromboembolism. Women with atrial fibrillation are at a higher overall risk for stroke compared to men with atrial fibrillation. The aim of this study was to evaluate for sex differences in patients with acute stroke and atrial fibrillation, regarding risk factors, treatments received and outcomes. Methods Data were analyzed from the “Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation” (RAF-study), a prospective, multicenter, international study including only patients with acute stroke and atrial fibrillation. Patients were followed up for 90 days. Disability was measured by the modified Rankin Scale (0–2 favorable outcome, 3–6 unfavorable outcome). Results: Of the 1029 patients enrolled, 561 were women (54.5%) (p < 0.001) and younger (p < 0.001) compared to men. In patients with known atrial fibrillation, women were less likely to receive oral anticoagulants before index stroke (p = 0.026) and were less likely to receive anticoagulants after stroke (71.3% versus 78.4%, p = 0.01). There was no observed sex difference regarding the time of starting anticoagulant therapy between the two groups (6.4 ± 11.7 days for men versus 6.5 ± 12.4 days for women, p = 0.902). Men presented with more severe strokes at onset (mean NIHSS 9.2 ± 6.9 versus 8.1 ± 7.5, p < 0.001). Within 90 days, 46 (8.2%) recurrent ischemic events (stroke/TIA/systemic embolism) and 19 (3.4%) symptomatic cerebral bleedings were found in women compared to 30 (6.4%) and 18 (3.8%) in men (p = 0.28 and p = 0.74). At 90 days, 57.7% of women were disabled or deceased, compared to 41.1% of the men (p < 0.001). Multivariate analysis did not confirm this significance. Conclusions: Women with atrial fibrillation were less likely to receive oral anticoagulants prior to and after stroke compared to men with atrial fibrillation, and when stroke occurred, regardless of the fact that in our study women were younger and with less severe stroke, outcomes did not differ between the sexes

Improving college students’ fact-checking strategies through lateral reading instruction in a general education civics course

College students lack fact-checking skills, which may lead them to accept information at face value. We report findings from an institution participating in the Digital Polarization Initiative (DPI), a national effort to teach students lateral reading strategies used by expert fact-checkers to verify online information. Lateral reading requires users to leave the information (website) to find out whether someone has already fact-checked the claim, identify the original source, or learn more about the individuals or organizations making the claim. Instructor-matched sections of a general education civics course implemented the DPI curriculum (N=136 students) or provided business-as-usual civics instruction (N=94 students). At posttest, students in DPI sections were more likely to use lateral reading to fact-check and correctly evaluate the trustworthiness of information than controls. Aligning with the DPI’s emphasis on usingWikipedia to investigate sources, students in DPI sections reported greater use of Wikipedia at posttest than controls, but did not differ significantly in their trust of Wikipedia. In DPI sections, students who failed to read laterally at posttest reported higher trust of Wikipedia at pretest than students who read at least one problem laterally. Responsiveness to the curriculum was also linked to numbers of online assignments attempted, but unrelated to pretest media literacy knowledge, use of lateral reading, or self-reported use of lateral reading. Further research is needed to determine whether improvements in lateral reading are maintained over time and to explore other factors that might distinguish students whose skills improved after instruction from non-responders

Timing of initiation of oral anticoagulants in patients with acute ischemic stroke and atrial fibrillation comparing posterior and anterior circulation strokes

Background: The aim of this study in patients with acute posterior ischemic stroke (PS) and atrial fibrillation (AF) were to evaluate the risks of recurrent ischemic event and severe bleeding and these risks in relation with oral anticoagulant therapy (OAT) and its timing. Methods: Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of: stroke recurrence, TIA, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke. Results: A total of 2,470 patients were available for the analysis: 473 (19.1%) with PS and 1,997 (80.9%) AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39-2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16-1.80). Conclusions: Patients with posterior or anterior stroke and AF appear to have similar risks of ischemic or hemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT

Hemorrhagic transformation in acute ischemic stroke patients and atrial fibrillation: time to initiation of anticoagulants and outcome

Background: In patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation (HT). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT, (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days. Methods and Results: HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores >2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT. Patients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3–8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0–6.0) of those without HT; 53.1% of patients with HT were deceased or disabled compared with 35.8% of those without HT. On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24–2.35). Conclusions: In patients with HT, anticoagulation was initiated about 12 days later than patients without HT. This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability

The Impact of Atherosclerotic Burden on Vascular Outcomes in Patients with Stroke and Atrial Fibrillation: The ATHENA study

: Introduction: Patients with ischemic stroke (IS) and atrial fibrillation (AF) face a higher risk of recurrent vascular events. This study evaluates the impact of atherosclerotic vascular disease burden across different vascular territories on the risk of vascular events in patients with recent ischemic stroke and AF within 90 days. Patients and Methods: We included patients with IS and AF from the International RAF network in a prospective 90-day follow-up. Atherosclerotic vascular disease was identified by at least one of the following: Symptomatic ischemic heart disease, symptomatic peripheral artery disease, internal carotid stenosis ≥50%, or the presence of plaques in the aorta. The primary outcome was a composite of stroke, transient ischemic attack, systemic embolism, cerebral bleeding, and major extracranial bleeding within 90 days postacute stroke. Patients were categorized into 5 groups based on the number of affected atherosclerotic vascular territories, with those with no atherosclerotic vascular disease as the reference. Kaplan-Meier curves were generated and compared using the log-rank test to determine the predictive value of the number of diseased territories for the risk of events. Data analysis was performed with SPSS/PC Win Package 25.0. Results: Of the 2148 patients (mean age 77.59; 53.86% female), 744 (34.60%) had atherosclerosis. Multivariable analysis revealed that involvement of 3 (hazard ratio [HR] 2.80, 95% confidence interval [CI]: 1.20-6.53) or 4 (HR 6.81, 95% CI: 1.02-36.24) vascular territories was significantly associated with the risk of combined events. Conclusions: In patients with recent ischemic stroke and AF, atherosclerosis across multiple territories correlates with a higher risk of future vascular events