Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 39
Filter
Add more filters

Country/Region as subject
Publication year range
1.
Nature ; 627(8005): 772-777, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38538941

ABSTRACT

The encoding of qubits in semiconductor spin carriers has been recognized as a promising approach to a commercial quantum computer that can be lithographically produced and integrated at scale1-10. However, the operation of the large number of qubits required for advantageous quantum applications11-13 will produce a thermal load exceeding the available cooling power of cryostats at millikelvin temperatures. As the scale-up accelerates, it becomes imperative to establish fault-tolerant operation above 1 K, at which the cooling power is orders of magnitude higher14-18. Here we tune up and operate spin qubits in silicon above 1 K, with fidelities in the range required for fault-tolerant operations at these temperatures19-21. We design an algorithmic initialization protocol to prepare a pure two-qubit state even when the thermal energy is substantially above the qubit energies and incorporate radiofrequency readout to achieve fidelities up to 99.34% for both readout and initialization. We also demonstrate single-qubit Clifford gate fidelities up to 99.85% and a two-qubit gate fidelity of 98.92%. These advances overcome the fundamental limitation that the thermal energy must be well below the qubit energies for the high-fidelity operation to be possible, surmounting a main obstacle in the pathway to scalable and fault-tolerant quantum computation.

2.
J Card Surg ; 32(10): 604-612, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28929526

ABSTRACT

BACKGROUND: We analyzed our early and midterm results with aortic valve reimplantation surgery to determine the influence of Marfan syndrome and bicuspid valves on outcomes with this technique. METHODS: Between March 2004 and December 2015, 267 patients underwent aortic valve reimplantation operations. The mean diameter of the sinuses of Valsalva was 50 ± 3 mm and moderate/severe aortic regurgitation was present in 34.4% of these patients. A bicuspid aortic valve was present in 21% and 40% had Marfan syndrome. RESULTS: Overall 30-day mortality was 0.37% (1/267). Mean follow-up was 59.7 ± 38.7 months. Overall survival at 1, 3, and 5 years was 98 ± 8%, 98 ± 1%, and 94 ± 2%, respectively. Freedom from reoperation and aortic regurgitation >II was 99 ± 5%, 98 ± 8%, 96.7 ± 8%, and 99 ± 6%, 98 ± 1%, 98 ± 1%, respectively at 1, 3, and 5 years follow-up, with no differences between Marfan and bicuspid aortic valve groups. (p = 0.94 and p = 0.96, respectively). No endocarditis or thromboembolic complications were documented, and 93.6% of the patients did not receive any anticoagulation therapy. CONCLUSIONS: The reimplantation technique for aortic root aneurysms is associated with excellent clinical and functional outcomes at short and mid-term follow-up.


Subject(s)
Aortic Aneurysm/etiology , Aortic Aneurysm/surgery , Aortic Valve/abnormalities , Aortic Valve/surgery , Heart Valve Diseases/complications , Heart Valve Prosthesis Implantation/methods , Marfan Syndrome/complications , Organ Sparing Treatments/methods , Adult , Aftercare , Aged , Aortic Aneurysm/mortality , Aortic Valve Insufficiency/etiology , Bicuspid Aortic Valve Disease , Female , Heart Valve Prosthesis Implantation/mortality , Humans , Male , Middle Aged , Retrospective Studies , Sinus of Valsalva/pathology , Time Factors , Treatment Outcome
3.
PLoS Genet ; 9(6): e1003531, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23785295

ABSTRACT

PARP inhibition can induce anti-neoplastic effects when used as monotherapy or in combination with chemo- or radiotherapy in various tumor settings; however, the basis for the anti-metastasic activities resulting from PARP inhibition remains unknown. PARP inhibitors may also act as modulators of tumor angiogenesis. Proteomic analysis of endothelial cells revealed that vimentin, an intermediary filament involved in angiogenesis and a specific hallmark of EndoMT (endothelial to mesenchymal transition) transformation, was down-regulated following loss of PARP-1 function in endothelial cells. VE-cadherin, an endothelial marker of vascular normalization, was up-regulated in HUVEC treated with PARP inhibitors or following PARP-1 silencing; vimentin over-expression was sufficient to drive to an EndoMT phenotype. In melanoma cells, PARP inhibition reduced pro-metastatic markers, including vasculogenic mimicry. We also demonstrated that vimentin expression was sufficient to induce increased mesenchymal/pro-metastasic phenotypic changes in melanoma cells, including ILK/GSK3-ß-dependent E-cadherin down-regulation, Snail1 activation and increased cell motility and migration. In a murine model of metastatic melanoma, PARP inhibition counteracted the ability of melanoma cells to metastasize to the lung. These results suggest that inhibition of PARP interferes with key metastasis-promoting processes, leading to suppression of invasion and colonization of distal organs by aggressive metastatic cells.


Subject(s)
Breast Neoplasms/genetics , Cell Transformation, Neoplastic/genetics , Melanoma, Experimental/genetics , Poly(ADP-ribose) Polymerases/genetics , Vimentin , Animals , Antigens, CD/genetics , Antigens, CD/metabolism , Breast Neoplasms/pathology , Cadherins/genetics , Cadherins/metabolism , Cell Line, Tumor , Dogs , Endothelial Cells/metabolism , Epithelial-Mesenchymal Transition/genetics , Female , Gene Expression Regulation, Neoplastic , Human Umbilical Vein Endothelial Cells , Humans , MCF-7 Cells , Melanoma, Experimental/pathology , Mice , Neoplasm Invasiveness/genetics , Neoplasm Metastasis , Poly (ADP-Ribose) Polymerase-1 , Poly(ADP-ribose) Polymerase Inhibitors , Vimentin/genetics , Vimentin/metabolism
4.
Telemed J E Health ; 21(7): 567-74, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25734829

ABSTRACT

BACKGROUND: Postpartum depression (PPD) is a disorder that often goes undiagnosed. The development of a screening program requires considerable and careful effort, where evidence-based decisions have to be taken in order to obtain an effective test with a high level of sensitivity and an acceptable specificity that is quick to perform, easy to interpret, culturally sensitive, and cost-effective. The purpose of this article is twofold: first, to develop classification models for detecting the risk of PPD during the first week after childbirth, thus enabling early intervention; and second, to develop a mobile health (m-health) application (app) for the Android(®) (Google, Mountain View, CA) platform based on the model with best performance for both mothers who have just given birth and clinicians who want to monitor their patient's test. MATERIALS AND METHODS: A set of predictive models for estimating the risk of PPD was trained using machine learning techniques and data about postpartum women collected from seven Spanish hospitals. An internal evaluation was carried out using a hold-out strategy. An easy flowchart and architecture for designing the graphical user interface of the m-health app was followed. RESULTS: Naive Bayes showed the best balance between sensitivity and specificity as a predictive model for PPD during the first week after delivery. It was integrated into the clinical decision support system for Android mobile apps. CONCLUSIONS: This approach can enable the early prediction and detection of PPD because it fulfills the conditions of an effective screening test with a high level of sensitivity and specificity that is quick to perform, easy to interpret, culturally sensitive, and cost-effective.


Subject(s)
Depression, Postpartum/etiology , Machine Learning , Telemedicine , Adult , Female , Forecasting , Humans , Prospective Studies , Risk Factors , Sensitivity and Specificity , Surveys and Questionnaires
5.
Nat Commun ; 15(1): 7656, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39227618

ABSTRACT

Semiconductor spin qubits represent a promising platform for future large-scale quantum computers owing to their excellent qubit performance, as well as the ability to leverage the mature semiconductor manufacturing industry for scaling up. Individual qubit control, however, commonly relies on spectral selectivity, where individual microwave signals of distinct frequencies are used to address each qubit. As quantum processors scale up, this approach will suffer from frequency crowding, control signal interference and unfeasible bandwidth requirements. Here, we propose a strategy based on arrays of degenerate spins coherently dressed by a global control field and individually addressed by local electrodes. We demonstrate simultaneous on-resonance driving of two degenerate qubits using a global field while retaining addressability for qubits with equal Larmor frequencies. Furthermore, we implement SWAP oscillations during on-resonance driving, constituting the demonstration of driven two-qubit gates. Significantly, our findings highlight how dressing can overcome the fragility of entangling gates between superposition states and increase their noise robustness. These results constitute a paradigm shift in qubit control in order to overcome frequency crowding in large-scale quantum computing.

6.
Nat Commun ; 15(1): 4299, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38769086

ABSTRACT

Spins of electrons in silicon MOS quantum dots combine exquisite quantum properties and scalable fabrication. In the age of quantum technology, however, the metrics that crowned Si/SiO2 as the microelectronics standard need to be reassessed with respect to their impact upon qubit performance. We chart spin qubit variability due to the unavoidable atomic-scale roughness of the Si/SiO2 interface, compiling experiments across 12 devices, and develop theoretical tools to analyse these results. Atomistic tight binding and path integral Monte Carlo methods are adapted to describe fluctuations in devices with millions of atoms by directly analysing their wavefunctions and electron paths instead of their energy spectra. We correlate the effect of roughness with the variability in qubit position, deformation, valley splitting, valley phase, spin-orbit coupling and exchange coupling. These variabilities are found to be bounded, and they lie within the tolerances for scalable architectures for quantum computing as long as robust control methods are incorporated.

7.
EJNMMI Phys ; 11(1): 73, 2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39174856

ABSTRACT

OBJECTIVE: Positron Emission Tomography (PET) is a well-known imaging technology for the diagnosis, treatment, and monitoring of several diseases. Most PET scanners use a Ring-Shaped Detector Configuration (RSDC), which helps obtain homogeneous image quality but are restricted to an invariable Field-of-View (FOV), scarce spatial resolution, and low sensitivity. Alternatively, few PET systems use Open Detector Configurations (ODC) to permit an accessible FOV adaptable to different target sizes, thus optimizing sensitivity. Yet, to compensate the lack of angular coverage in ODC-PET, developing a detector with high-timing performance is mandatory to enable Time-of-Flight (TOF) techniques during reconstruction. The main goal of this work is to provide a proof of concept PET scanner appropriate for constructing the new generation of ODC-PET suitable for biopsy guidance and clinical intervention during acquisition. The designed detector has to be compact and robust, and its requirements in terms of performance are spatial and time resolutions < 2 mm and < 200 ps, respectively. METHODS: The present work includes a simulation study of an ODC-PET based on 2-panels with variable distance. The image quality (IQ) and Derenzo phantoms have been simulated and evaluated. The phantom simulations have also been performed using a ring-shaped PET for comparison purposes of the ODC approach with conventional systems. Then, an experimental evaluation of a prototype detector that has been designed following the simulation results is presented. This study focused on tuning the ASIC parameters and evaluating the scintillator surface treatment (ESR and TiO2), and configuration that yields the best Coincidence Time Resolution (CTR). Moreover, the scalability of the prototype to a module of 64 × 64mm2 and its preliminary evaluation regarding pixel identification are provided. RESULTS: The simulation results reported sensitivity (%) values at the center of the FOV of 1.96, 1.63, and 1.18 for panel distances of 200, 250, and 300 mm, respectively. The IQ reconstructed image reported good uniformity (87%) and optimal CRC values, and the Derenzo phantom reconstruction suggests a system resolution of 1.6-2 mm. The experimental results demonstrate that using TiO2 coating yielded better detector performance than ESR. Acquired data was filtered by applying an energy window of ± 30% at the photopeak level. After filtering, best CTR of 230 ± 2 ps was achieved for an 8 × 8 LYSO pixel block with 2 × 2 × 12mm3 each. The detector performance remained constant after scaling-up the prototype to a module of 64 × 64mm2, and the flood map demonstrates the module's capabilities to distinguish the small pixels; thus, a spatial resolution < 2 mm (pixel size) is achieved. CONCLUSIONS: The simulated results of this biplanar scanner show high performance in terms of image quality and sensitivity. These results are comparable to state-of-the-art PET technology and, demonstrate that including TOF information minimizes the image artifacts due to the lack of angular projections. The experimental results concluded that using TiO2 coating provide the best performance. The results suggest that this scanner may be suitable for organ study, breast, prostate, or cardiac applications, with good uniformity and CRC.

8.
J Thorac Cardiovasc Surg ; 166(5): 1458-1467, 2023 11.
Article in English | MEDLINE | ID: mdl-35279289

ABSTRACT

OBJECTIVE: The study objective was to assess the benefits of del Nido cardioplegia compared with cold blood cardioplegia solution in terms of myocardial protection during adult cardiac surgery. METHODS: A total of 474 adult patients undergoing coronary artery bypass grafting, heart valve surgery, thoracic aortic surgery, or combined procedures were randomized to the del Nido cardioplegia group (n = 234) or the cold blood cardioplegia solution group (n = 240) after provided informed consent. The primary end points assessed inotropic support requirements, severe cardiovascular events, and troponin trend within the first 48 hours of intensive care unit stay. Reperfusion arrhythmias, aortic crossclamp and cardiopulmonary bypass times, and other clinical perioperative variables were considered as secondary end points. RESULTS: No statistically significant differences were found regarding postoperative inotropic support requirements or the incidence of severe cardiovascular events. The del Nido cardioplegia group showed a higher return to spontaneous sinus rhythm (P< .001), a lower number of defibrillation attempts (P< .001), and an earlier peak troponin value in the postoperative period. Peak blood glucose levels and intravenous insulin requirements were significantly lower in the del Nido cardioplegia group. We found no significant differences regarding aortic crossclamp or cardiopulmonary bypass time. We did observe a lower incidence of postoperative stroke in the del Nido cardioplegia group (2.6% vs 6.7%; P= .035). CONCLUSIONS: del Nido cardioplegia can be used safely and with comparable outcomes compared with traditional cardioplegia solutions. Additional advantages over glycemic control, reperfusion arrhythmias, and its comfortable redosing interval make del Nido an interesting alternative for myocardial protection in adult cardiac surgery. A significant decrease in postoperative stroke will require further research to shed light on the results of this study. VIDEO ABSTRACT.


Subject(s)
Cardiac Surgical Procedures , Cardiovascular Diseases , Stroke , Thoracic Surgery , Humans , Adult , Prospective Studies , Heart Arrest, Induced/adverse effects , Heart Arrest, Induced/methods , Cardiac Surgical Procedures/adverse effects , Cardioplegic Solutions/adverse effects , Troponin , Retrospective Studies
9.
Adv Mater ; 35(19): e2208557, 2023 May.
Article in English | MEDLINE | ID: mdl-36805699

ABSTRACT

The small size and excellent integrability of silicon metal-oxide-semiconductor (SiMOS) quantum dot spin qubits make them an attractive system for mass-manufacturable, scaled-up quantum processors. Furthermore, classical control electronics can be integrated on-chip, in-between the qubits, if an architecture with sparse arrays of qubits is chosen. In such an architecture qubits are either transported across the chip via shuttling or coupled via mediating quantum systems over short-to-intermediate distances. This paper investigates the charge and spin characteristics of an elongated quantum dot-a so-called jellybean quantum dot-for the prospects of acting as a qubit-qubit coupler. Charge transport, charge sensing, and magneto-spectroscopy measurements are performed on a SiMOS quantum dot device at mK temperature and compared to Hartree-Fock multi-electron simulations. At low electron occupancies where disorder effects and strong electron-electron interaction dominate over the electrostatic confinement potential, the data reveals the formation of three coupled dots, akin to a tunable, artificial molecule. One dot is formed centrally under the gate and two are formed at the edges. At high electron occupancies, these dots merge into one large dot with well-defined spin states, verifying that jellybean dots have the potential to be used as qubit couplers in future quantum computing architectures.

10.
Nat Nanotechnol ; 18(2): 131-136, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36635331

ABSTRACT

Once called a 'classically non-describable two-valuedness' by Pauli, the electron spin forms a qubit that is naturally robust to electric fluctuations. Paradoxically, a common control strategy is the integration of micromagnets to enhance the coupling between spins and electric fields, which, in turn, hampers noise immunity and adds architectural complexity. Here we exploit a switchable interaction between spins and orbital motion of electrons in silicon quantum dots, without a micromagnet. The weak effects of relativistic spin-orbit interaction in silicon are enhanced, leading to a speed up in Rabi frequency by a factor of up to 650 by controlling the energy quantization of electrons in the nanostructure. Fast electrical control is demonstrated in multiple devices and electronic configurations. Using the electrical drive, we achieve a coherence time T2,Hahn ≈ 50 µs, fast single-qubit gates with Tπ/2 = 3 ns and gate fidelities of 99.93%, probed by randomized benchmarking. High-performance all-electrical control improves the prospects for scalable silicon quantum computing.

11.
Lancet Glob Health ; 11(6): e933-e941, 2023 06.
Article in English | MEDLINE | ID: mdl-37202028

ABSTRACT

BACKGROUND: From the start of the SARS-CoV-2 outbreak, global sequencing efforts have generated an unprecedented amount of genomic data. Nonetheless, unequal sampling between high-income and low-income countries hinders the implementation of genomic surveillance systems at the global and local level. Filling the knowledge gaps of genomic information and understanding pandemic dynamics in low-income countries is essential for public health decision making and to prepare for future pandemics. In this context, we aimed to discover the timing and origin of SARS-CoV-2 variant introductions in Mozambique, taking advantage of pandemic-scale phylogenies. METHODS: We did a retrospective, observational study in southern Mozambique. Patients from Manhiça presenting with respiratory symptoms were recruited, and those enrolled in clinical trials were excluded. Data were included from three sources: (1) a prospective hospital-based surveillance study (MozCOVID), recruiting patients living in Manhiça, attending the Manhiça district hospital, and fulfilling the criteria of suspected COVID-19 case according to WHO; (2) symptomatic and asymptomatic individuals with SARS-CoV-2 infection recruited by the National Surveillance system; and (3) sequences from SARS-CoV-2-infected Mozambican cases deposited on the Global Initiative on Sharing Avian Influenza Data database. Positive samples amenable for sequencing were analysed. We used Ultrafast Sample placement on Existing tRees to understand the dynamics of beta and delta waves, using available genomic data. This tool can reconstruct a phylogeny with millions of sequences by efficient sample placement in a tree. We reconstructed a phylogeny (~7·6 million sequences) adding new and publicly available beta and delta sequences. FINDINGS: A total of 5793 patients were recruited between Nov 1, 2020, and Aug 31, 2021. During this time, 133 328 COVID-19 cases were reported in Mozambique. 280 good quality new SARS-CoV-2 sequences were obtained after the inclusion criteria were applied and an additional 652 beta (B.1.351) and delta (B.1.617.2) public sequences were included from Mozambique. We evaluated 373 beta and 559 delta sequences. We identified 187 beta introductions (including 295 sequences), divided in 42 transmission groups and 145 unique introductions, mostly from South Africa, between August, 2020 and July, 2021. For delta, we identified 220 introductions (including 494 sequences), with 49 transmission groups and 171 unique introductions, mostly from the UK, India, and South Africa, between April and November, 2021. INTERPRETATION: The timing and origin of introductions suggests that movement restrictions effectively avoided introductions from non-African countries, but not from surrounding countries. Our results raise questions about the imbalance between the consequences of restrictions and health benefits. This new understanding of pandemic dynamics in Mozambique can be used to inform public health interventions to control the spread of new variants. FUNDING: European and Developing Countries Clinical Trials, European Research Council, Bill & Melinda Gates Foundation, and Agència de Gestió d'Ajuts Universitaris i de Recerca.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , COVID-19/epidemiology , COVID-19/prevention & control , Pandemics/prevention & control , Phylogeny , Mozambique/epidemiology , Retrospective Studies , Prospective Studies
12.
Cureus ; 14(4): e24593, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35602797

ABSTRACT

We present a case of a 56-year-old female patient who presented to the emergency department with a one-day history of fever and confusion. She was found to have splenomegaly, multiple swan neck deformities, and pancytopenia. Chart review revealed that she had a three-year history of pancytopenia with two prior non-diagnostic bone marrow biopsies. Rheumatoid factor and cyclic citrullinated peptide antibody levels were elevated. The patient was ultimately diagnosed with Felty's syndrome (FS). Felty's syndrome is characterized by neutropenia, splenomegaly, and rheumatoid arthritis. This disease usually presents years after a diagnosis of rheumatoid arthritis is made. The neutropenia associated with Felty's syndrome can lead to life-threatening infections and therefore must be recognized so that the underlying cause of immunosuppression can be addressed.

13.
Physiol Meas ; 43(6)2022 06 28.
Article in English | MEDLINE | ID: mdl-35609610

ABSTRACT

Objective. Detecting different cardiac diseases using a single or reduced number of leads is still challenging. This work aims to provide and validate an automated method able to classify ECG recordings. Performance using complete 12-lead systems, reduced lead sets, and single-lead ECGs is evaluated and compared.Approach. Seven different databases with 12-lead ECGs were provided during thePhysioNet/Computing in Cardiology Challenge2021, where 88 253 annotated samples associated with none, one, or several cardiac conditions among 26 different classes were released for training, whereas 42 896 hidden samples were used for testing. After signal preprocessing, 81 features per ECG-lead were extracted, mainly based on heart rate variability, QRST patterns and spectral domain. Next, a One-versus-Rest classification approach made of independent binary classifiers for each cardiac condition was trained. This strategy allowed each ECG to be classified as belonging to none, one or several classes. For each class, a classification model among two binary supervised classifiers and one hybrid unsupervised-supervised classification system was selected. Finally, we performed a 3-fold cross-validation to assess the system's performance.Main results. Our classifiers received scores of 0.39, 0.38, 0.39, 0.38, and 0.37 for the 12, 6, 4, 3 and 2-lead versions of the hidden test set with the Challenge evaluation metric (CM). Also, we obtained a meanG-score of 0.80, 0.78, 0.79, 0.79, 0.77 and 0.74 for the 12, 6, 4, 3, 2 and 1-lead subsets with the public training set during our 3-fold cross-validation.Significance. We proposed and tested a machine learning approach focused on flexibility for identifying multiple cardiac conditions using one or more ECG leads. Our minimal-lead approach may be beneficial for novel portable or wearable ECG devices used as screening tools, as it can also detect multiple and concurrent cardiac conditions.


Subject(s)
Atrial Fibrillation , Heart Diseases , Atrial Fibrillation/diagnosis , Electrocardiography/methods , Humans , Machine Learning , Signal Processing, Computer-Assisted
14.
Front Microbiol ; 12: 803827, 2021.
Article in English | MEDLINE | ID: mdl-35095814

ABSTRACT

Objective: To analyze the SARS-CoV-2 genomic epidemiology in the Balearic Islands, a unique setting in which the course of the pandemic has been influenced by a complex interplay between insularity, severe social restrictions and tourism travels. Methods: Since the onset of the pandemic, more than 2,700 SARS-CoV-2 positive respiratory samples have been randomly selected and sequenced in the Balearic Islands. Genetic diversity of circulating variants was assessed by lineage assignment of consensus whole genome sequences with PANGOLIN and investigation of additional spike mutations. Results: Consensus sequences were assigned to 46 different PANGO lineages and 75% of genomes were classified within a VOC, VUI, or VUM variant according to the WHO definitions. Highest genetic diversity was documented in the island of Majorca (42 different lineages detected). Globally, lineages B.1.1.7 and B.1.617.2/AY.X were identified as the 2 major lineages circulating in the Balearic Islands during the pandemic, distantly followed by lineages B.1.177/B.1.177.X. However, in Ibiza/Formentera lineage distribution was slightly different and lineage B.1.221 was the third most prevalent. Temporal distribution analysis showed that B.1 and B.1.5 lineages dominated the first epidemic wave, lineage B.1.177 dominated the second and third, and lineage B.1.617.2 the fourth. Of note, lineage B.1.1.7 became the most prevalent circulating lineage during first half of 2021; however, it was not associated with an increased in COVID-19 cases likely due to severe social restrictions and limited travels. Additional spike mutations were rarely documented with the exception of mutation S:Q613H which has been detected in several genomes (n = 25) since July 2021. Conclusion: Virus evolution, mainly driven by the acquisition and selection of spike substitutions conferring biological advantages, social restrictions, and size population are apparently key factors for explaining the epidemic patterns registered in the Balearic Islands.

15.
mSphere ; 6(5): e0059621, 2021 10 27.
Article in English | MEDLINE | ID: mdl-34494886

ABSTRACT

The first descriptions of reinfection by SARS-CoV-2 have been recently reported. However, these studies focus exclusively on the reinfected case, without considering the epidemiological context of the event. Our objectives were to perform a complete analysis of the sequential infections and community transmission events around a SARS-CoV-2 reinfection, including the infection events preceding it, the exposure, and subsequent transmissions. Our analysis was supported by host genetics, viral whole-genome sequencing, phylogenomic viral population analysis, and refined epidemiological data obtained from interviews with the involved subjects. The reinfection involved a 53-year-old woman with asthma (Case A), with a first COVID-19 episode in April 2020 and a much more severe second episode 4-1/2 months later, with SARS-CoV-2 seroconversion in August, that required hospital admission. An extended genomic analysis allowed us to demonstrate that the strain involved in Case A's reinfection was circulating in the epidemiological context of Case A and was also transmitted subsequently from Case A to her family context. The reinfection was also supported by a phylogenetic analysis, including 348 strains from Madrid, which revealed that the strain involved in the reinfection was circulating by the time Case A suffered the second episode, August-September 2020, but absent at the time range corresponding to Case A's first episode. IMPORTANCE We present the first complete analysis of the epidemiological scenario around a reinfection by SARS-CoV-2, more severe than the first episode, including three cases preceding the reinfection, the reinfected case per se, and the subsequent transmission to another seven cases.


Subject(s)
COVID-19/epidemiology , Reinfection/epidemiology , COVID-19/genetics , COVID-19/transmission , COVID-19/virology , Contact Tracing , Family , Female , Genomics , Humans , Male , Middle Aged , Phylogeny , Reinfection/genetics , Reinfection/transmission , Reinfection/virology , SARS-CoV-2/genetics , Severity of Illness Index , Spain/epidemiology , Whole Genome Sequencing
16.
mBio ; 12(6): e0231521, 2021 12 21.
Article in English | MEDLINE | ID: mdl-34781748

ABSTRACT

We have detected two mutations in the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at amino acid positions 1163 and 1167 that appeared independently in multiple transmission clusters and different genetic backgrounds. Furthermore, both mutations appeared together in a cluster of 1,627 sequences belonging to clade 20E. This cluster is characterized by 12 additional single nucleotide polymorphisms but no deletions. The available structural information on the S protein in the pre- and postfusion conformations predicts that both mutations confer rigidity, which could potentially decrease viral fitness. Accordingly, we observed reduced infectivity of this spike genotype relative to the ancestral 20E sequence in vitro, and the levels of viral RNA in nasopharyngeal swabs were not significantly higher. Furthermore, the mutations did not impact thermal stability or antibody neutralization by sera from vaccinated individuals but moderately reduce neutralization by convalescent-phase sera from the early stages of the pandemic. Despite multiple successful appearances of the two spike mutations during the first year of SARS-CoV-2 evolution, the genotype with both mutations was displaced upon the expansion of the 20I (Alpha) variant. The midterm fate of the genotype investigated was consistent with the lack of advantage observed in the clinical and experimental data. IMPORTANCE We observed repeated, independent emergence of mutations in the SARS-CoV-2 spike involving amino acids 1163 and 1167, within the HR2 functional motif. Conclusions derived from evolutionary and genomic diversity analysis suggest that the co-occurrence of both mutations might pose an advantage for the virus and therefore a threat to effective control of the epidemic. However, biological characterization, including in vitro experiments and analysis of clinical data, indicated no clear benefit in terms of stability or infectivity. In agreement with this, continuous epidemiological surveillance conducted months after the first observations revealed that both mutations did not successfully outcompete other variants and stopped circulating 9 months after their initial detection. Additionally, we evaluated the potential of both mutations to escape neutralizing antibodies, finding that the presence of these two mutations on their own is not likely to confer antibody escape. Our results provide an example of how newly emerged spike mutations can be assessed to better understand the risk posed by new variants and indicate that some spike mutations confer no clear advantage to the virus despite independently emerging multiple times and are eventually displaced by fitter variants.


Subject(s)
Evolution, Molecular , Mutation , Phenotype , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Antibodies, Neutralizing/immunology , COVID-19/virology , Europe , Genetic Variation , Genome, Viral , Humans , Neutralization Tests , SARS-CoV-2/immunology
17.
Nat Genet ; 53(10): 1405-1414, 2021 10.
Article in English | MEDLINE | ID: mdl-34594042

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has affected the world radically since 2020. Spain was one of the European countries with the highest incidence during the first wave. As a part of a consortium to monitor and study the evolution of the epidemic, we sequenced 2,170 samples, diagnosed mostly before lockdown measures. Here, we identified at least 500 introductions from multiple international sources and documented the early rise of two dominant Spanish epidemic clades (SECs), probably amplified by superspreading events. Both SECs were related closely to the initial Asian variants of SARS-CoV-2 and spread widely across Spain. We inferred a substantial reduction in the effective reproductive number of both SECs due to public-health interventions (Re < 1), also reflected in the replacement of SECs by a new variant over the summer of 2020. In summary, we reveal a notable difference in the initial genetic makeup of SARS-CoV-2 in Spain compared with other European countries and show evidence to support the effectiveness of lockdown measures in controlling virus spread, even for the most successful genetic variants.


Subject(s)
COVID-19/epidemiology , COVID-19/transmission , Communicable Disease Control/organization & administration , Models, Statistical , SARS-CoV-2/genetics , COVID-19/virology , Communicable Disease Control/methods , Humans , Incidence , Phylogeny , Physical Distancing , Quarantine/methods , Quarantine/organization & administration , SARS-CoV-2/classification , SARS-CoV-2/pathogenicity , Severity of Illness Index , Spain/epidemiology
18.
Comput Biol Med ; 127: 104031, 2020 12.
Article in English | MEDLINE | ID: mdl-33096296

ABSTRACT

BACKGROUND: The Electrocardiographic Imaging (ECGI) technique, used to non-invasively reconstruct the epicardial electrical activity, requires an accurate model of the atria and torso anatomy. Here we evaluate a new automatic methodology able to locate the atrial anatomy within the torso based on an intrinsic electrical parameter of the ECGI solution. METHODS: In 28 realistic simulations of the atrial electrical activity, we randomly displaced the atrial anatomy for ±2.5 cm and ±30° on each axis. An automatic optimization method based on the L-curve curvature was used to estimate the original position using exclusively non-invasive data. RESULTS: The automatic optimization algorithm located the atrial anatomy with a deviation of 0.5 ± 0.5 cm in position and 16.0 ± 10.7° in orientation. With these approximate locations, the obtained electrophysiological maps reduced the average error in atrial rate measures from 1.1 ± 1.1 Hz to 0.5 ± 1.0 Hz and in the phase singularity position from 7.2 ± 4.0 cm to 1.6 ± 1.7 cm (p < 0.01). CONCLUSIONS: This proposed automatic optimization may help to solve spatial inaccuracies provoked by cardiac motion or respiration, as well as to use ECGI on torso and atrial anatomies from different medical image systems.


Subject(s)
Body Surface Potential Mapping , Electrocardiography , Algorithms , Diagnostic Imaging , Heart Atria/diagnostic imaging
19.
Gac Sanit ; 23(3): 222.e34-43, 2009.
Article in Catalan | MEDLINE | ID: mdl-19464767

ABSTRACT

OBJECTIVE: The aim of this study was to analyze patterns of scientific collaboration and the visibility generated by coauthorship of articles on smoking among different countries on a world-wide basis through the Science Citation Index-Expanded (SCI-expanded) from 1999 to 2003. MATERIAL AND METHODS: We selected articles on smoking resulting from collaboration among different countries in the SCI-Expanded (1999-2003). The underlying networks of collaboration among countries were analyzed by comparing production (number of articles published), visibility (number of citations received) and centrality (node degree, intermediation and proximity). RESULTS: A total of 3,484 articles were obtained, in which 5,008 institutions from 79 countries participated. The most productive country was the United Kingdom, with Germany and France in the second and third places. The United Kingdom also published the largest number of articles with inter-institutional collaboration (570 articles), with the USA and Germany in second and third places. The USA published the largest number of articles with international collaboration with the United Kingdom and France in the second and third places. All countries received a greater number of citations for articles resulting from international and inter-institutional collaboration than for those performed without collaboration. Networks of collaboration were completely connected through a single component and the annual increase in size of these inter-country networks was due to new countries joining the periphery of the network. CONCLUSIONS: We found a positive correlation between international and inter-institutional collaboration and the number of citations received by articles on smoking research. The number of citations per year remained constant throughout the 5-year study period.


Subject(s)
Authorship , Databases, Bibliographic , International Cooperation , Smoking
SELECTION OF CITATIONS
SEARCH DETAIL