Description of the idealized bed roughness effects on tracer transport in water flumes by applying the strange attractor multifractal analysis

River hydrodynamicsTurbulent open channel flow and transport phenomen

Acoustic Holograms for Bilateral Blood-Brain Barrier Opening in a Mouse Model

[EN] Transcranial focused ultrasound (FUS) in conjunction with circulating microbubbles injection is the sole non-invasive technique that temporally and locally opens the blood-brain barrier (BBB), allowing targeted drug delivery into the central nervous system (CNS). However, single-element FUS technologies do not allow the simultaneous targeting of several brain structures with high-resolution, and multi-element devices are required to compensate the aberrations introduced by the skull. In this work, we present the first preclinical application of acoustic holograms to perform a bilateral BBB opening in two mirrored regions in mice. The system consisted of a single-element focused transducer working at 1.68 MHz, coupled to a 3D-printed acoustic hologram designed to produce two symmetric foci in anesthetized mice in vivo and, simultaneously, compensate the aberrations of the wavefront caused by the skull bones. T1-weighed MR images showed gadolinium extravasation at two symmetric quasi-spherical focal spots. By encoding time-reversed fields, holograms are capable of focusing acoustic energy with a resolution near the diffraction limit at multiple spots inside the skull of small preclinical animals. This work demonstrates the feasibility of hologram-assisted BBB opening for low-cost and highly-localized targeted drug delivery in the CNS in symmetric regions of separate hemispheres.This work was supported in part by the Spanish Ministry of Science, Innovation, and Universities (MICINN) through Grants "Juan de la Cierva -Incorporacion" IJC2018-037897-I, and PID2019-111436RB-C22, in part by the Agencia Valenciana de la Innovacio through Grants INNVAL10/19/016, INNCON/2021/8, and INNVA1/2020/92, in part by Generalitat Valenciana through Grants ACIF/2017/045, AICO/2020/268, and BEFPI/2019/075, and in part by the National Institutes of Health through Grants 5R01EB009041 and 5R01AG038961. Action co-financed by the European Union through the Programa Operativo del Fondo Europeo de Desarrollo Regional (FEDER) of the Comunitat Valenciana (IDIFEDER/2018/022 and IDIFEDER/2021/004)Jiménez-Gambín, S.; Jimenez, N.; Pouliopoulos, AN.; Benlloch Baviera, JM.; Konofagou, EE.; Camarena Femenia, F. (2022). Acoustic Holograms for Bilateral Blood-Brain Barrier Opening in a Mouse Model. IEEE Transactions on Biomedical Engineering. 69(4):1359-1368. https://doi.org/10.1109/TBME.2021.31155531359136869

First in-vivo Demonstration of Bilateral Blood-Brain Barrier Opening Using Acoustic Holograms in Mice

[EN] Focused ultrasound (FUS) with microbubbles allows for non-invasive targeted drug delivery into the central nervous system (CNS) by temporally and locally disrupting the bloodbrain barrier (BBB). However, current FUS technologies are not able to simultaneously target several brain structures. In this work, we open the BBB in two regions in a murine brain using a single-element transducer with a coupled 3D-printed holographic lens, which is designed to simultaneously create two symmetric foci in anesthetized mice in vivo. The proposed approach shows many advantages: (1) simple and low-cost; (2) correction of aberrations due to skull and water cone; and (3) multiple BBB opening (BBBO) locations with only one sonication, becoming a time- and cost-effective therapeutic system for neurological diseases. For the in-vivo experiment, contrast-enhanced, T1- weighted MRI scan was conducted following BBBO, showing gadolinium extravasation at two symmetric focal spots. The two BBBO regions were separated by 3.0 +- 0.7 mm (n=5 mice) compared to 5.3 mm in full-wave simulations. This work shows the capability of bifocal ultrasound generation in separate animals using a unique uCT scan. A bilateral BBBO was achieved with a single sonication using a holographic lens in mice, thus improving the efficiency and defining a new approach for several neurodegenerative diseases targeting symmetric brain structures, e.g. hippocampus, putamen or caudate. This study demonstrates the feasibility of hologram-assisted BBBO for targeted drug delivery in the CNS in symmetric regions in separate hemispheres.This research has been supported by the Spanish Ministry of Science, Innovation and Universities through grants Juan de la Cierva - Incorporacion (IJC2018-037897-I) and PID2019-111436RB-C22, by the Agencia Valenciana de la Innovación through grant INNVAL10/19/016, by Generalitat Valenciana through grants No. ACIF/2017/045 and BEFPI/2019/075, and by the National Institutes of Health through grants 5R01EB009041 and 5R01AG038961. Action co-financed by the European Union through the Programa Operativo del Fondo Europeo de Desarrollo Regional (FEDER) of the Comunitat Valenciana 2014-2020 (IDIFEDER/2018/022).Jiménez-Gambín, S.; Jimenez, N.; Benlloch Baviera, JM.; Camarena Femenia, F.; Pouliopoulos, AN.; Konofagou, EE. (2020). First in-vivo Demonstration of Bilateral Blood-Brain Barrier Opening Using Acoustic Holograms in Mice. IEEE. 1-4. https://doi.org/10.1109/IUS46767.2020.9251487S1

Transcranial propagation with an ultrasonic mono-element focused transducer

This article belongs to a special issue: 43rd Annual UIA Symposium 23—25 April 2014 CSIC Madrid, Spain. Edited By Margaret Lucas and Enrique Riera[EN] Focused Ultrasound is the only truly transient, local and non-invasive technique able to induce safe Blood-Brain Barrier Opening (BBBO), technique used in Parkinson or Alzheimer diseases research. However, the presence of the skull in the path usually affects the focus characteristics (gain, beam width, shape and maxima location). In this work, transcranial acoustic wave propagation generated by a mono-element focused transducer has been modeled using 2D and 3D FDTD methods. Skull structure of the non-human primate under test can be compared in terms of density and sound speed with polymethylmethacrylate (PMMA) films. Then, focus aberration and the phenomena that cause it are characterized, providing a better control of the beam focus using the BBBO technique. Results throw that focal axial displacements are constant with the angle of incidence for PMMA flat films. In normal incidence, a shift of 6 mm is given for axial displacement in the 2D transcranial propagation. Moreover, if the skull geometry under the action of the ultrasonic beam can be compared with the curvature radius of the transducer, displacements should be constant with angle independency, like those seeing in the homogenous flat films with the same thickness.This work was supported by: “Programa de Apoyo a la Investigación y Desarrollo de la Universidad Politécnica de Valencia” PAID-05-12 Ref: SP20120696, Spain.Iglesias, PC.; Jimenez, N.; Konofagou, E.; Camarena Femenia, F.; Redondo, J. (2015). Transcranial propagation with an ultrasonic mono-element focused transducer. Physics Procedia. 63:103-107. https://doi.org/10.1016/j.phpro.2015.03.017S1031076

Early estimates of seasonal influenza vaccine effectiveness in Europe among target groups for vaccination: results from the I-MOVE multicentre case-control study, 2011/12

To provide an early estimate of 2011/12 influenza vaccine effectiveness (VE), we conducted a multicentre case-control study based on seven sentinel surveillance networks. We included influenza-like illness cases up to week 7/2012 from the vaccination target groups, swabbed less than eight days after symptom onset. Laboratory-confirmed influenza A(H3) cases were compared to negative controls. Adjusted VE was 43% (95% confidence interval: -0.4 to 67.7), suggesting low to moderate VE against influenza A(H3) in the early 2011/12 season.The I-MOVE network has been funded by the European Centre for Disease Prevention and Control (ECDC) since 2007.S

Deep learning-derived cardiovascular age shares a genetic basis with other cardiac phenotypes

Artifcial intelligence (AI)-based approaches can now use electrocardiograms (ECGs) to provide expertlevel performance in detecting heart abnormalities and diagnosing disease. Additionally, patient age predicted from ECGs by AI models has shown great potential as a biomarker for cardiovascular age, where recent work has found its deviation from chronological age (“delta age”) to be associated with mortality and co-morbidities. However, despite being crucial for understanding underlying individual risk, the genetic underpinning of delta age is unknown. In this work we performed a genome-wide association study using UK Biobank data (n=34,432) and identifed eight loci associated with delta age (p ≤ 5 × 10−8), including genes linked to cardiovascular disease (CVD) (e.g. SCN5A) and (heart) muscle development (e.g. TTN). Our results indicate that the genetic basis of cardiovascular ageing is predominantly determined by genes directly involved with the cardiovascular system rather than those connected to more general mechanisms of ageing. Our insights inform the epidemiology of CVD, with implications for preventative and precision medicine

Early estimates of seasonal influenza vaccine effectiveness in Europe, 2010/11: I-MOVE, a multicentre case-control study

We present early estimates (up to week 4 of 2011) of the 2010/11 seasonal influenza vaccine effectiveness in preventing medically attended influenza-like illness(ILI) laboratory confirmed as influenza. Practitioners from seven European sentinel networks systematically swabbed ILI patients. We included patients meeting the European Union ILI case definition and swabbed less than eight days after symptom onset. Laboratory-confirmed influenza cases were compared with negative controls. The adjusted vaccine effectiveness was 42.3% (95% CI: -7.3 to 69.0%), suggesting moderate protection of the seasonal vaccine.The I-MOVE network has been funded by the European Centre for Disease Prevention and Control (ECDC) since 2007.S

Mid-Holocene Antarctic sea-ice increase driven by marine ice sheet retreat

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Ashley, K. E., McKay, R., Etourneau, J., Jimenez-Espejo, F. J., Condron, A., Albot, A., Crosta, X., Riesselman, C., Seki, O., Mass, G., Golledge, N. R., Gasson, E., Lowry, D. P., Barrand, N. E., Johnson, K., Bertler, N., Escutia, C., Dunbar, R., & Bendle, J. A. Mid-Holocene Antarctic sea-ice increase driven by marine ice sheet retreat. Climate of the Past, 17(1), (2021): 1-19, https://doi.org/10.5194/cp-17-1-2021.Over recent decades Antarctic sea-ice extent has increased, alongside widespread ice shelf thinning and freshening of waters along the Antarctic margin. In contrast, Earth system models generally simulate a decrease in sea ice. Circulation of water masses beneath large-cavity ice shelves is not included in current Earth System models and may be a driver of this phenomena. We examine a Holocene sediment core off East Antarctica that records the Neoglacial transition, the last major baseline shift of Antarctic sea ice, and part of a late-Holocene global cooling trend. We provide a multi-proxy record of Holocene glacial meltwater input, sediment transport, and sea-ice variability. Our record, supported by high-resolution ocean modelling, shows that a rapid Antarctic sea-ice increase during the mid-Holocene (∼ 4.5 ka) occurred against a backdrop of increasing glacial meltwater input and gradual climate warming. We suggest that mid-Holocene ice shelf cavity expansion led to cooling of surface waters and sea-ice growth that slowed basal ice shelf melting. Incorporating this feedback mechanism into global climate models will be important for future projections of Antarctic changes.This research has been supported by the Natural Environment Research Council (CENTA PhD; NE/L002493/1 and Standard Grant Ne/I00646X/1), Japanese Society for the Promotion of Science (JSPS/FF2/60 no. L-11523), NZ Marsden Fund (grant nos. 18-VUW-089 and 15-VUW-131), NSF (grant nos. PLR-1443347 and ACI-1548562), the U.S. Dept. of Energy (grant no. DE-SC0016105), ERC (StG ICEPROXY, 203441; ANR CLIMICE, FP7 Past4Future, 243908), L'Oréal-UNESCO New Zealand For Women in Science Fellowship, University of Otago Research Grant, the IODP U.S. Science Support Program, Spanish Ministry of Science and Innovation (grant no. CTM2017-89711-C2-1-P), and the European Union (FEDER)

External validation of a deep learning electrocardiogram algorithm to detect ventricular dysfunction

Objective - To validate a novel artificial-intelligence electrocardiogram algorithm (AI-ECG) to detect left ventricular systolic dysfunction (LVSD) in an external population. Background - LVSD, even when asymptomatic, confers increased morbidity and mortality. We recently derived AI-ECG to detect LVSD using ECGs based on a large sample of patients treated at the Mayo Clinic. Methods - We performed an external validation study with subjects from the Know Your Heart Study, a cross-sectional study of adults aged 35–69 years residing in two cities in Russia, who had undergone both ECG and transthoracic echocardiography. LVSD was defined as left ventricular ejection fraction ≤ 35%. We assessed the performance of the AI-ECG to identify LVSD in this distinct patient population. Results - Among 4277 subjects in this external population-based validation study, 0.6% had LVSD (compared to 7.8% of the original clinical derivation study). The overall performance of the AI-ECG to detect LVSD was robust with an area under the receiver operating curve of 0.82. When using the LVSD probability cut-off of 0.256 from the original derivation study, the sensitivity, specificity, and accuracy in this population were 26.9%, 97.4%, 97.0%, respectively. Other probability cut-offs were analysed for different sensitivity values. Conclusions - The AI-ECG detected LVSD with robust test performance in a population that was very different from that used to develop the algorithm. Population-specific cut-offs may be necessary for clinical implementation. Differences in population characteristics, ECG and echocardiographic data quality may affect test performance