On the scaling of temperature fluctuations induced by frictional heating

The temperature fluctuations generated by viscous dissipation in an isotropic turbulent flow are studied using direct numerical simulation. It is shown that their scaling with Reynolds number is at odds with predictions from recent investigations. The origin of the discrepancy is traced back to the anomalous scaling of the dissipation rate fluctuations. Phenomenological arguments are presented which explain the observed results. The study shows that previously proposed models underpredict the variance of frictional temperature fluctuations by a factor proportional to the square of the Taylor-scale Reynolds number

Advanced lattice Boltzmann scheme for high-Reynolds-number magneto-hydrodynamic flows

International audienceIs the lattice Boltzmann method suitable to investigate numerically high-Reynolds-number magneto-hydrodynamic (MHD) ows? It is shown that a standard approach based on the Bhatnagar-Gross-Krook (BGK) collision operator rapidly yields unstable simulations as the Reynolds number increases. In order to circumvent this limitation, it is here suggested to address the collision procedure in the space of central moments for the uid dynamics. Therefore, an hybrid LB scheme is introduced, which couples a central-moment scheme for the velocity with a BGK scheme for the space-and-time evolution of the magnetic field. This method outperforms the standard approach in terms of stability, allowing us to simulate high-Reynolds-number MHD ows with non-unitary Prandtl number while maintaining accuracy and physical consistency

Randomized placebo-controlled trial of amlodipine in vasospastic angina

AbstractObjectives. This study was designed to assess the efficacy and safety of amlodipine, a long-acting calcium channel blocker, in patients with vasospastic angina.Background. Previous studies have established the value of short-acting calcium channel blockers in the treatment of coronary spasm.Methods. Fifty-two patients with well documented vasospastic angina were entered into the present study. After a single-blind placebo run-in period, patients were randomized (in a double-blind protocol) to receive either amlodipine (10 mg) or placebo every morning for 4 weeks. Twenty-four patients received amlodipine and 28 received placebo. All patients were given diaries in which to record both the frequency, severity, duration and circumstances of anginal episodes and their intake of sublingual nitroglycerin tablets.Results. The rate of anginal episodes decreased significantly (p = 0.009) with amlodipine treatment compared with placebo and the intake of nitroglycerin tablets showed a similar trend. Peripheral edema was the only adverse event seen more frequently in amlodipine-treated patients. No patient was withdrawn from the double-blind phase of the study because of an adverse event. Patients who completed the double-blind phase as responders to amlodipine or as nonresponders to placebo were offered the option of receiving amlodipine in a long-term, open label extension phase. During the extension, the daily dose of amlodipine was adjusted to 5 or 15 mg if needed and the rate of both anginal episodes and nitroglycerin tablet consumption showed statistically significant decreases between baseline and final assessment.Conclusion. This study suggests that amlodipine given once daily is efficacious and safe in the treatment of vasospastic angina

Temperature fluctuations induced by frictional heating in isotropic turbulence

La dynamique et l'évolution des fluctuations de température induites par la dissipation visqueuse dans une turbulence isotrope sont étudiées utilisant des Simulations Numériques Directes. Les résultats de ces simulations sont en désaccord avec les prédictions de deux études théoriques récentes. Les résultats sont expliqués par des arguments phénomenologiques

Correction to: Massive Gastrointestinal Bleeding Due to Splenic Artery Erosion by a PigTail Drain in a Post Sleeve Gastrectomy Leak: a Case Report

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Processing AIRS Scientific Data Through Level 2

The Atmospheric Infrared Spectrometer (AIRS) Science Processing System (SPS) is a collection of computer programs, denoted product generation executives (PGEs), for processing the readings of the AIRS suite of infrared and microwave instruments orbiting the Earth aboard NASA s Aqua spacecraft. AIRS SPS at an earlier stage of development was described in "Initial Processing of Infrared Spectral Data' (NPO-35243), NASA Tech Briefs, Vol. 28, No. 11 (November 2004), page 39. To recapitulate: Starting from level 0 (representing raw AIRS data), the PGEs and their data products are denoted by alphanumeric labels (1A, 1B, and 2) that signify the successive stages of processing. The cited prior article described processing through level 1B (the level-2 PGEs were not yet operational). The level-2 PGEs, which are now operational, receive packages of level-1B geolocated radiance data products and produce such geolocated geophysical atmospheric data products such as temperature and humidity profiles. The process of computing these geophysical data products is denoted "retrieval" and is quite complex. The main steps of the process are denoted microwave-only retrieval, cloud detection and cloud clearing, regression, full retrieval, and rapid transmittance algorithm

Particulate Air Pollution, Oxidative Stress Genes, and Heart Rate Variability in an Elderly Cohort

Background and Objectives: We have previously shown that reduced defenses against oxidative stress due to glutathione S-transferase M1 (GSTM1) deletion modify the effects of PM[2.5] (fine-particulate air pollution of < 2.5 μm in aerodynamic diameter) on heart rate variability (HRV) in a cross-sectional analysis of the Normative Aging Study, an elderly cohort. We have extended this to include a longitudinal analysis with more subjects and examination of the GT short tandem repeat polymorphism in the heme oxygenase-1 (HMOX-1) promoter. Methods: HRV measurements were taken on 539 subjects. Linear mixed effects models were fit for the logarithm of HRV metrics—including standard deviation of normal-to-normal intervals (SDNN), high frequency (HF), and low frequency (LF)—and PM2.5 concentrations in the 48 hr preceding HRV measurement, controlling for confounders and a random subject effect. Results: PM2.5 was significantly associated with SDNN (p = 0.04) and HF (p = 0.03) in all subjects. There was no association in subjects with GSTM1, whereas there was a significant association with SDNN, HF, and LF in subjects with the deletion. Similarly, there was no association with any HRV measure in subjects with the short repeat variant of HMOX-1, and significant associations in subjects with any long repeat. We found a significant three-way interaction of PM[2.5] with GSTM1 and HMOX-1 determining SDNN (p = 0.008), HF (p = 0.01) and LF (p = 0.04). In subjects with the GSTM1 deletion and the HMOX-1 long repeat, SDNN decreased by 13% [95% confidence interval (CI), −21% to −4%], HF decreased by 28% (95% CI, −43% to −9%), and LF decreased by 20% (95% CI, −35% to −3%) per 10 μg/m3 increase in PM. Conclusions: Oxidative stress is an important pathway for the autonomic effects of particles

Contribution of Somatic Ras/Raf/Mitogen-Activated Protein Kinase Variants in the Hippocampus in Drug-Resistant Mesial Temporal Lobe Epilepsy

Importance: Mesial temporal lobe epilepsy (MTLE) is the most common focal epilepsy subtype and is often refractory to antiseizure medications. While most patients with MTLE do not have pathogenic germline genetic variants, the contribution of postzygotic (ie, somatic) variants in the brain is unknown. Objective: To test the association between pathogenic somatic variants in the hippocampus and MTLE. Design, Setting, and Participants: This case-control genetic association study analyzed the DNA derived from hippocampal tissue of neurosurgically treated patients with MTLE and age-matched and sex-matched neurotypical controls. Participants treated at level 4 epilepsy centers were enrolled from 1988 through 2019, and clinical data were collected retrospectively. Whole-exome and gene-panel sequencing (each genomic region sequenced more than 500 times on average) were used to identify candidate pathogenic somatic variants. A subset of novel variants was functionally evaluated using cellular and molecular assays. Patients with nonlesional and lesional (mesial temporal sclerosis, focal cortical dysplasia, and low-grade epilepsy-associated tumors) drug-resistant MTLE who underwent anterior medial temporal lobectomy were eligible. All patients with available frozen tissue and appropriate consents were included. Control brain tissue was obtained from neurotypical donors at brain banks. Data were analyzed from June 2020 to August 2022. Exposures: Drug-resistant MTLE. Main Outcomes and Measures: Presence and abundance of pathogenic somatic variants in the hippocampus vs the unaffected temporal neocortex. Results: Of 105 included patients with MTLE, 53 (50.5%) were female, and the median (IQR) age was 32 (26-44) years; of 30 neurotypical controls, 11 (36.7%) were female, and the median (IQR) age was 37 (18-53) years. Eleven pathogenic somatic variants enriched in the hippocampus relative to the unaffected temporal neocortex (median [IQR] variant allele frequency, 1.92 [1.5-2.7] vs 0.3 [0-0.9]; P =.01) were detected in patients with MTLE but not in controls. Ten of these variants were in PTPN11, SOS1, KRAS, BRAF, and NF1, all predicted to constitutively activate Ras/Raf/mitogen-activated protein kinase (MAPK) signaling. Immunohistochemical studies of variant-positive hippocampal tissue demonstrated increased Erk1/2 phosphorylation, indicative of Ras/Raf/MAPK activation, predominantly in glial cells. Molecular assays showed abnormal liquid-liquid phase separation for the PTPN11 variants as a possible dominant gain-of-function mechanism. Conclusions and Relevance: Hippocampal somatic variants, particularly those activating Ras/Raf/MAPK signaling, may contribute to the pathogenesis of sporadic, drug-resistant MTLE. These findings may provide a novel genetic mechanism and highlight new therapeutic targets for this common indication for epilepsy surgery

Contribution of Somatic Ras/Raf/Mitogen-Activated Protein Kinase Variants in the Hippocampus in Drug-Resistant Mesial Temporal Lobe Epilepsy

Importance: Mesial temporal lobe epilepsy (MTLE) is the most common focal epilepsy subtype and is often refractory to antiseizure medications. While most patients with MTLE do not have pathogenic germline genetic variants, the contribution of postzygotic (ie, somatic) variants in the brain is unknown. Objective: To test the association between pathogenic somatic variants in the hippocampus and MTLE. Design, Setting, and Participants: This case-control genetic association study analyzed the DNA derived from hippocampal tissue of neurosurgically treated patients with MTLE and age-matched and sex-matched neurotypical controls. Participants treated at level 4 epilepsy centers were enrolled from 1988 through 2019, and clinical data were collected retrospectively. Whole-exome and gene-panel sequencing (each genomic region sequenced more than 500 times on average) were used to identify candidate pathogenic somatic variants. A subset of novel variants was functionally evaluated using cellular and molecular assays. Patients with nonlesional and lesional (mesial temporal sclerosis, focal cortical dysplasia, and low-grade epilepsy-associated tumors) drug-resistant MTLE who underwent anterior medial temporal lobectomy were eligible. All patients with available frozen tissue and appropriate consents were included. Control brain tissue was obtained from neurotypical donors at brain banks. Data were analyzed from June 2020 to August 2022. Exposures: Drug-resistant MTLE. Main Outcomes and Measures: Presence and abundance of pathogenic somatic variants in the hippocampus vs the unaffected temporal neocortex. Results: Of 105 included patients with MTLE, 53 (50.5%) were female, and the median (IQR) age was 32 (26-44) years; of 30 neurotypical controls, 11 (36.7%) were female, and the median (IQR) age was 37 (18-53) years. Eleven pathogenic somatic variants enriched in the hippocampus relative to the unaffected temporal neocortex (median [IQR] variant allele frequency, 1.92 [1.5-2.7] vs 0.3 [0-0.9]; P=.01) were detected in patients with MTLE but not in controls. Ten of these variants were in PTPN11, SOS1, KRAS, BRAF, and NF1, all predicted to constitutively activate Ras/Raf/mitogen-activated protein kinase (MAPK) signaling. Immunohistochemical studies of variant-positive hippocampal tissue demonstrated increased Erk1/2 phosphorylation, indicative of Ras/Raf/MAPK activation, predominantly in glial cells. Molecular assays showed abnormal liquid-liquid phase separation for the PTPN11 variants as a possible dominant gain-of-function mechanism. Conclusions and Relevance: Hippocampal somatic variants, particularly those activating Ras/Raf/MAPK signaling, may contribute to the pathogenesis of sporadic, drug-resistant MTLE. These findings may provide a novel genetic mechanism and highlight new therapeutic targets for this common indication for epilepsy surgery

Computational Modelling of Tissue-Engineered Cartilage Constructs

Cartilage is a fundamental tissue to ensure proper motion between bones and damping of mechanical loads. This tissue often suffers damage and has limited healing capacity due to its avascularity. In order to replace surgery and replacement of joints by metal implants, tissue engineered cartilage is seen as an attractive alternative. These tissues are obtained by seeding chondrocytes or mesenchymal stem cells in scaffolds and are given certain stimuli to improve establishment of mechanical properties similar to the native cartilage. However, tissues with ideal mechanical properties were not obtained yet. Computational models of tissue engineered cartilage growth and remodelling are invaluable to interpret and predict the effects of experimental designs. The current model contribution in the field will be presented in this chapter, with a focus on the response to mechanical stimulation, and the development of fully coupled modelling approaches incorporating simultaneously solute transport and uptake, cell growth, production of extracellular matrix and remodelling of mechanical properties.publishe