Dispersion enhancement and damping by buoyancy driven flows in 2D networks of capillaries

The influence of a small relative density difference on the displacement of two miscible liquids is studied experimentally in transparent 2D networks of micro channels. Both stable displacements in which the denser fluid enters at the bottom of the cell and displaces the lighter one and unstable displacements in which the lighter fluid is injected at the bottom and displaces the denser one are realized. Except at the lowest mean flow velocity U, the average $C(x,t)$ of the relative concentration satisfies a convection-dispersion equation. The dispersion coefficient is studied as function of the relative magnitude of fluid velocity and of the velocity of buoyancy driven fluid motion. A model is suggested and its applicability to previous results obtained in 3D media is discussed

Long-term cardiovascular safety of fenfluramine in patients with Dravet syndrome treated for up to 3 years: findings from serial echocardiographic assessments

© 2022 The Authors. Published by Elsevier Ltd on behalf of European Paediatric Neurology Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Objective: To assess the cardiovascular safety of fenfluramine when used to treat children and young adults with Dravet syndrome. Methods: Patients with Dravet syndrome who completed one of three phase 3 clinical trials of fenfluramine could enroll in the open-label extension (OLE) study (NCT02823145). All patients started fenfluramine treatment at an oral dose of 0.2 mg/kg/day. The dose was titrated based on efficacy and tolerability to a maximum of 0.7 mg/kg/day (absolute maximum 26 mg/day) or 0.4 mg/kg/day (absolute maximum 17 mg/day) in patients concomitantly receiving stiripentol. Serial transthoracic echocardiography was performed using standardized methods and blinded readings at OLE entry, after 4-6 weeks, and every 3 months thereafter. Valvular heart disease (VHD) was defined as ≥ moderate mitral regurgitation or ≥ mild aortic regurgitation combined with physical signs or symptoms attributable to valve dysfunction. Pulmonary artery hypertension (PAH) was defined as systolic pulmonary artery pressure >35 mmHg. Results: A total of 327 patients (median age, 9.0 years; range, 2-19 years) have enrolled in the OLE and received ≥1 dose of fenfluramine. The median duration of treatment was 23.9 months (range, 0.2-42.6 months) and the median dose of fenfluramine was 0.44 mg/kg/day. No patient demonstrated VHD or PAH at any time during the OLE. Significance/interpretation: This study, which represents the largest, longest, and most rigorous examination of cardiovascular safety of fenfluramine yet reported, found no cases of VHD or PAH. These results, combined with fenfluramine's substantial antiseizure efficacy, support a strong positive benefit-risk profile for fenfluramine in the treatment of Dravet syndrome.info:eu-repo/semantics/publishedVersio

One-Year Risk of Stroke after Transient Ischemic Attack or Minor Stroke

BACKGROUND Previous studies conducted between 1997 and 2003 estimated that the risk of stroke or an acute coronary syndrome was 12 to 20% during the first 3 months after a transient ischemic attack (TIA) or minor stroke. The TIAregistry.org project was designed to describe the contemporary profile, etiologic factors, and outcomes in patients with a TIA or minor ischemic stroke who receive care in health systems that now offer urgent evaluation by stroke specialists. METHODS We recruited patients who had had a TIA or minor stroke within the previous 7 days. Sites were selected if they had systems dedicated to urgent evaluation of patients with TIA. We estimated the 1-year risk of stroke and of the composite outcome of stroke, an acute coronary syndrome, or death from cardiovascular causes. We also examined the association of the ABCD2 score for the risk of stroke (range, 0 [lowest risk] to 7 [highest risk]), findings on brain imaging, and cause of TIA or minor stroke with the risk of recurrent stroke over a period of 1 year. RESULTS From 2009 through 2011, we enrolled 4789 patients at 61 sites in 21 countries. A total of 78.4% of the patients were evaluated by stroke specialists within 24 hours after symptom onset. A total of 33.4% of the patients had an acute brain infarction, 23.2% had at least one extracranial or intracranial stenosis of 50% or more, and 10.4% had atrial fibrillation. The Kaplan–Meier estimate of the 1-year event rate of the composite cardiovascular outcome was 6.2% (95% confidence interval, 5.5 to 7.0). Kaplan–Meier estimates of the stroke rate at days 2, 7, 30, 90, and 365 were 1.5%, 2.1%, 2.8%, 3.7%, and 5.1%, respectively. In multivariable analyses, multiple infarctions on brain imaging, large-artery atherosclerosis, and an ABCD2 score of 6 or 7 were each associated with more than a doubling of the risk of stroke. CONCLUSIONS We observed a lower risk of cardiovascular events after TIA than previously reported. The ABCD2 score, findings on brain imaging, and status with respect to large-artery atherosclerosis helped stratify the risk of recurrent stroke within 1 year after a TIA or minor stroke. (Funded by Sanofi and Bristol-Myers Squibb.)Supported by an unrestricted grant from Sanofi and Bristol-Myers Squibb

Gastro-esophageal reflux disease symptoms and demographic factors as a pre-screening tool for Barrett's esophagus.

BACKGROUND: Barrett's esophagus (BE) occurs as consequence of reflux and is a risk factor for esophageal adenocarcinoma. The current "gold-standard" for diagnosing BE is endoscopy which remains prohibitively expensive and impractical as a population screening tool. We aimed to develop a pre-screening tool to aid decision making for diagnostic referrals. METHODOLOGY/PRINCIPAL FINDINGS: A prospective (training) cohort of 1603 patients attending for endoscopy was used for identification of risk factors to develop a risk prediction model. Factors associated with BE in the univariate analysis were selected to develop prediction models that were validated in an independent, external cohort of 477 non-BE patients referred for endoscopy with symptoms of reflux or dyspepsia. Two prediction models were developed separately for columnar lined epithelium (CLE) of any length and using a stricter definition of intestinal metaplasia (IM) with segments ≥ 2 cm with areas under the ROC curves (AUC) of 0.72 (95%CI: 0.67-0.77) and 0.81 (95%CI: 0.76-0.86), respectively. The two prediction models included demographics (age, sex), symptoms (heartburn, acid reflux, chest pain, abdominal pain) and medication for "stomach" symptoms. These two models were validated in the independent cohort with AUCs of 0.61 (95%CI: 0.54-0.68) and 0.64 (95%CI: 0.52-0.77) for CLE and IM ≥ 2 cm, respectively. CONCLUSIONS: We have identified and validated two prediction models for CLE and IM ≥ 2 cm. Both models have fair prediction accuracies and can select out around 20% of individuals unlikely to benefit from investigation for Barrett's esophagus. Such prediction models have the potential to generate useful cost-savings for BE screening among the symptomatic population

Monitoring computational clusters with OVIS.

Traditional cluster monitoring approaches consider nodes in singleton, using manufacturer-specified extreme limits as thresholds for failure ''prediction''. We have developed a tool, OVIS, for monitoring and analysis of large computational platforms which, instead, uses a statistical approach to characterize single device behaviors from those of a large number of statistically similar devices. Baseline capabilities of OVIS include the visual display of deterministic information about state variables (e.g., temperature, CPU utilization, fan speed) and their aggregate statistics. Visual consideration of the cluster as a comparative ensemble, rather than as singleton nodes, is an easy and useful method for tuning cluster configuration and determining effects of real-time changes

Magneto-electrodynamics at high frequencies in the antiferromagnetic and superconducting states of DyNi_2B_2C

We report the observation of novel behaviour in the radio frequency (rf) and microwave response of DyNi_2B_2C over a wide range of temperature (T) and magnetic field (H) in the antiferromagnetic (AFM) and superconducting (SC) states. At microwave frequencies of 10 GHz, the T dependence of the surface impedance Z_s=R_s+iX_s was measured which yields the T dependence of the complex conductivity \sigma_1-i\sigma_2 in the SC and AFM states. At radio frequencies (4 MHz), the H and T dependence of the penetration depth \lambda(T,H) were measured. The establishment of antiferromagnetic order at T_N=10.3 K results in a marked decrease in the scattering of charge carriers, leading to sharp decreases in R_s and X_s. However, R_s and X_s differ from each other in the AFM state. We show that the results are consistent with conductivity relaxation whence the scattering rate becomes comparable to the microwave frequency. The rf measurements yield a rich dependence of the scattering on the magnetic field near and below T_N. Anomalous decrease of scattering at moderate applied fields is observed at temperatures near and above T_N, and arises due to a crossover from a negative magnetoresistance state, possibly associated with a loss of spin disorder scattering at low fields, to a positive magnetoresistance state associated with the metallic nature. The normal state magnetoresistance is positive at all temperatures for \mu_0H>2T and at all fields for T>15K. Several characteristic field and temperature scales associated with metamagnetic transitions (H_M1(T), H_M2(T)) and onset of spin disorder H_D(T), in addition to T_c, T_N and H_c2(T) are observed in the rf measurements.Comment: 9 pages, Latex, Uses REVTeX, This and related publications also available at http://sagar.physics.neu.edu/ Submitted to Phys. Rev.

DNA methylation-based biological age, genome-wide average DNA methylation, and conventional breast cancer risk factors.

DNA methylation-based biological age (DNAm age), as well as genome-wide average DNA methylation, have been reported to predict breast cancer risk. We aimed to investigate the associations between these DNA methylation-based risk factors and 18 conventional breast cancer risk factors for disease-free women. A sample of 479 individuals from the Australian Mammographic Density Twins and Sisters was used for discovery, a sample of 3354 individuals from the Melbourne Collaborative Cohort Study was used for replication, and meta-analyses pooling results from the two studies were conducted. DNAm age based on three epigenetic clocks (Hannum, Horvath and Levine) and genome-wide average DNA methylation were calculated using the HumanMethylation 450 K BeadChip assay data. The DNAm age measures were positively associated with body mass index (BMI), smoking, alcohol drinking and age at menarche (all nominal P < 0.05). Genome-wide average DNA methylation was negatively associated with smoking and number of live births, and positively associated with age at first live birth (all nominal P < 0.05). The association of DNAm age with BMI was also evident in within-twin-pair analyses that control for familial factors. This study suggests that some lifestyle and hormonal risk factors are associated with these DNA methylation-based breast cancer risk factors, and the observed associations are unlikely to be due to familial confounding but are likely causal. DNA methylation-based risk factors could interplay with conventional risk factors in modifying breast cancer risk

Measurement of erythrocyte membrane mannoses to assess splenic function

ACKNOWLEDGEMENTS This work was funded by Aberdeen University Development Trust and Friends of Anchor. The University of Aberdeen is applying for a patent based on this work. Aberdeen University Development Trust (GrantNumber(s): DB10452-11) Friends of Anchor (GrantNumber(s): RS 2018 001)Peer reviewedPublisher PD

The dynamics of the ionized and molecular ISM in powerful obscured quasars at z>=3.5

We present an analysis of the kinematics and excitation of the warm ionized gas in two obscured, powerful quasars at z>=3.5 from the SWIRE survey, SWIRE J022513.90-043419.9 and SWIRE J022550.67-042142, based on imaging spectroscopy on the VLT. Line ratios in both targets are consistent with luminous narrow-line regions of AGN. SWIRE J022550.67-042142 has very broad (FWHM=2000 km/s), spatially compact [OIII] line emission. SWIRE J022513.90-043419.9 is spatially resolved, has complex line profiles of H-beta and [OIII], including broad wings with blueshifts of up to -1500 km/s relative to the narrow [OIII]5007 component, and widths of up to FWHM=5000 km/s. Estimating the systemic redshift from the narrow H-beta line, as is standard for AGN host galaxies, implies that a significant fraction of the molecular gas is blueshifted by up to ~ -1000 km/s relative to the systemic velocity. Thus the molecular gas could be participating in the outflow. Significant fractions of the ionized and molecular gas reach velocities greater than the escape velocity. We compare empirical and modeling constraints for different energy injection mechanisms, such as merging, star formation, and momentum-driven AGN winds. We argue that the radio source is the most likely culprit, in spite of the sources rather modest radio power of 10^25 W/Hz. Such a radio power is not uncommon for intense starburst galaxies at z~2. We discuss these results in light of the co-evolution of AGN and their host galaxy.Comment: Accepted by MNRA

Robustness of circadian clocks to daylight fluctuations: hints from the picoeucaryote Ostreococcus tauri

The development of systemic approaches in biology has put emphasis on identifying genetic modules whose behavior can be modeled accurately so as to gain insight into their structure and function. However most gene circuits in a cell are under control of external signals and thus quantitative agreement between experimental data and a mathematical model is difficult. Circadian biology has been one notable exception: quantitative models of the internal clock that orchestrates biological processes over the 24-hour diurnal cycle have been constructed for a few organisms, from cyanobacteria to plants and mammals. In most cases, a complex architecture with interlocked feedback loops has been evidenced. Here we present first modeling results for the circadian clock of the green unicellular alga Ostreococcus tauri. Two plant-like clock genes have been shown to play a central role in Ostreococcus clock. We find that their expression time profiles can be accurately reproduced by a minimal model of a two-gene transcriptional feedback loop. Remarkably, best adjustment of data recorded under light/dark alternation is obtained when assuming that the oscillator is not coupled to the diurnal cycle. This suggests that coupling to light is confined to specific time intervals and has no dynamical effect when the oscillator is entrained by the diurnal cycle. This intringuing property may reflect a strategy to minimize the impact of fluctuations in daylight intensity on the core circadian oscillator, a type of perturbation that has been rarely considered when assessing the robustness of circadian clocks