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1.
Phys Rev Lett ; 129(11): 113201, 2022 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-36154428

RESUMEN

Spontaneous symmetry breaking is a property of Hamiltonian equilibrium states which, in the thermodynamic limit, retain a finite average value of an order parameter even after a field coupled to it is adiabatically turned off. In the case of quantum spin models with continuous symmetry, we show that this adiabatic process is also accompanied by the suppression of the fluctuations of the symmetry generator-namely, the collective spin component along an axis of symmetry. In systems of S=1/2 spins or qubits, the combination of the suppression of fluctuations along one direction and of the persistence of transverse magnetization leads to spin squeezing-a much sought-after property of quantum states, both for the purpose of entanglement detection as well as for metrological uses. Focusing on the case of XXZ models spontaneously breaking a U(1) [or even SU(2)] symmetry, we show that the adiabatically prepared states have nearly minimal spin uncertainty; that the minimum phase uncertainty that one can achieve with these states scales as N^{-3/4} with the number of spins N; and that this scaling is attained after an adiabatic preparation time scaling linearly with N. Our findings open the door to the adiabatic preparation of strongly spin-squeezed states in a large variety of quantum many-body devices including, e.g., optical-lattice clocks.

2.
Phys Rev Lett ; 118(21): 210401, 2017 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-28598671

RESUMEN

Using two-photon Bragg spectroscopy, we study the energy of particlelike excitations in a strongly interacting homogeneous Bose-Einstein condensate, and observe dramatic deviations from Bogoliubov theory. In particular, at large scattering length a the shift of the excitation resonance from the free-particle energy changes sign from positive to negative. For an excitation with wave number q, this sign change occurs at a≈4/(πq), in agreement with the Feynman energy relation and the static structure factor expressed in terms of the two-body contact. For a≳3/q we also see a breakdown of this theory, and better agreement with calculations based on the Wilson operator product expansion. Neither theory explains our observations across all interaction regimes, inviting further theoretical efforts.

3.
Bioinformatics ; 30(10): 1417-23, 2014 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-24463184

RESUMEN

MOTIVATION: Contamination of a cancer tissue by the surrounding benign (non-cancerous) tissue is a concern for molecular cancer diagnostics. This is because an observed molecular signature will be distorted by the surrounding benign tissue, possibly leading to an incorrect diagnosis. One example is molecular identification of the primary tumor site of metastases because biopsies of metastases typically contain a significant amount of benign tissue. RESULTS: A model of tissue contamination is presented. This contamination model works independently of the training of a molecular predictor, and it can be combined with any predictor model. The usability of the model is illustrated on primary tumor site identification of liver biopsies, specifically, on a human dataset consisting of microRNA expression measurements of primary tumor samples, benign liver samples and liver metastases. For a predictor trained on primary tumor and benign liver samples, the contamination model decreased the test error on biopsies from liver metastases from 77 to 45%. A further reduction to 34% was obtained by including biopsies in the training data. AVAILABILITY AND IMPLEMENTATION: http://www.math.ku.dk/∼richard/msgl/. CONTACT: vincent@math.ku.dk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Asunto(s)
Neoplasias Hepáticas/genética , Biopsia , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/secundario , MicroARNs/genética , Modelos Genéticos
4.
Phys Rev Lett ; 114(25): 255302, 2015 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-26197133

RESUMEN

We study the critical point for the emergence of coherence in a harmonically trapped two-dimensional Bose gas with tunable interactions. Over a wide range of interaction strengths we find excellent agreement with the classical-field predictions for the critical point of the Berezinskii-Kosterlitz-Thouless (BKT) superfluid transition. This allows us to quantitatively show, without any free parameters, that the interaction-driven BKT transition smoothly converges onto the purely quantum-statistical Bose-Einstein condensation transition in the limit of vanishing interactions.

5.
Appl Opt ; 49(16): 3092-5, 2010 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-20517380

RESUMEN

We demonstrate a compact laser source suitable for trapping and cooling potassium. By frequency doubling a fiber laser diode at 1534 nm in a waveguide, we produce 767 nm laser light. A current modulation of the diode allows us to generate the two required frequencies for cooling in a simple and robust apparatus. We successfully used this laser source to trap K39.

6.
N Engl J Med ; 354(21): 2235-49, 2006 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-16723615

RESUMEN

BACKGROUND: In December 2003 and April 2005, signs and symptoms suggestive of infection developed in two groups of recipients of solid-organ transplants. Each cluster was investigated because diagnostic evaluations were unrevealing, and in each a common donor was recognized. METHODS: We examined clinical specimens from the two donors and eight recipients, using viral culture, electron microscopy, serologic testing, molecular analysis, and histopathological examination with immunohistochemical staining to identify a cause. Epidemiologic investigations, including interviews, environmental assessments, and medical-record reviews, were performed to characterize clinical courses and to determine the cause of the illnesses. RESULTS: Laboratory testing revealed lymphocytic choriomeningitis virus (LCMV) in all the recipients, with a single, unique strain of LCMV identified in each cluster. In both investigations, LCMV could not be detected in the organ donor. In the 2005 cluster, the donor had had contact in her home with a pet hamster infected with an LCMV strain identical to that detected in the organ recipients; no source of LCMV infection was found in the 2003 cluster. The transplant recipients had abdominal pain, altered mental status, thrombocytopenia, elevated aminotransferase levels, coagulopathy, graft dysfunction, and either fever or leukocytosis within three weeks after transplantation. Diarrhea, peri-incisional rash, renal failure, and seizures were variably present. Seven of the eight recipients died, 9 to 76 days after transplantation. One recipient, who received ribavirin and reduced levels of immunosuppressive therapy, survived. CONCLUSIONS: We document two clusters of LCMV infection transmitted through organ transplantation.


Asunto(s)
Transmisión de Enfermedad Infecciosa , Coriomeningitis Linfocítica/transmisión , Virus de la Coriomeningitis Linfocítica/aislamiento & purificación , Trasplante de Órganos/efectos adversos , Adulto , Animales , Infecciones por Arenaviridae/veterinaria , Cricetinae , Resultado Fatal , Femenino , Humanos , Riñón/patología , Riñón/virología , Hígado/patología , Hígado/virología , Pulmón/patología , Pulmón/virología , Virus de la Coriomeningitis Linfocítica/clasificación , Virus de la Coriomeningitis Linfocítica/ultraestructura , Masculino , Microscopía Electrónica , Persona de Mediana Edad , Zoonosis/transmisión
7.
J Virol ; 81(23): 13271-6, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17898072

RESUMEN

Crimean-Congo hemorrhagic fever virus (CCHFV) causes severe human disease. The CCHFV medium RNA encodes a polyprotein which is proteolytically processed to yield the glycoprotein precursors PreGn and PreGc, followed by structural glycoproteins Gn and Gc. Subtilisin kexin isozyme-1/site-1 protease (SKI-1/S1P) plays a central role in Gn processing. Here we show that CCHFV-infected cells deficient in SKI-1/S1P produce no infectious virus, although PreGn and PreGc accumulated normally in the Golgi apparatus, the site of virus assembly. Only nucleoprotein-containing particles which lacked virus glycoproteins (Gn/Gc or PreGn/PreGc) were secreted. Complementation of SKI-1/S1P-deficient cells with a SKI-1/S1P expression vector restored release of infectious virus (>10(6) PFU/ml), confirming that SKI-1/S1P processing is required for incorporation of viral glycoproteins. SKI-1/S1P may represent a promising antiviral target.


Asunto(s)
Glicoproteínas/metabolismo , Virus de la Fiebre Hemorrágica de Crimea-Congo/fisiología , Proproteína Convertasas/metabolismo , Serina Endopeptidasas/metabolismo , Proteínas Estructurales Virales/metabolismo , Animales , Células CHO , Cricetinae , Cricetulus , Prueba de Complementación Genética , Aparato de Golgi/química , Humanos , Proproteína Convertasas/deficiencia , Procesamiento Proteico-Postraduccional/fisiología , Serina Endopeptidasas/deficiencia , Virión/química
8.
Catheter Cardiovasc Interv ; 71(5): 607-12, 2008 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-18360851

RESUMEN

OBJECTIVES: The goal of the present study was to test the impact of ST segment resolution (STR) after rescue percutaneous coronary intervention (PCI) on the short-term prognosis. BACKGROUND: The prognostic value of STR after rescue PCI for acute ST elevation myocardial infarction (STEMI) remains undetermined. METHODS: From the French regional database, we analyzed 168 consecutive patients with STEMI and failed lysis, defined by <50 percent STR, who underwent rescue PCI. Patients were classified into two groups according to the degree of STR from the maximal ST-elevation measured on the single worst ECG lead before lysis and after rescue PCI: the without STR group (<50% STR) vs. the with STR group (> or =50%). RESULTS: After rescue PCI, 26 (15%) patients did not have STR and 142 (85%) patients did. No difference was observed between the two groups regarding baseline characteristics, risk factors, and median time delay either from symptom onset to thrombolysis or from failed lysis to rescue PCI. We observed a lower proportion of patients with TIMI 2/3 flow post PCI in the without STR group (respectively 61% vs. 97%, P < 0.001) but an increased use of intra-aortic balloon counterpulsation (34% vs. 8%, P < 0.001) in this group. Thirty-day mortality was markedly higher in the without STR group than in the with STR group (27% vs. 9% respectively, P = 0.025). Moreover, multivariate analysis showed that absence of STR (OR: 5.65; 95% CI: 1.24-25.67), was an independent prognostic factor for mortality. CONCLUSIONS: We showed for the first time that analysis of ST-segment resolution may be a simple reliable tool to identify patients at high risk after rescue PCI, and may provide useful information for the elaboration of therapeutic strategies.


Asunto(s)
Angioplastia Coronaria con Balón/efectos adversos , Enfermedades Cardiovasculares/etiología , Circulación Coronaria , Infarto del Miocardio/terapia , Terapia Trombolítica , Anciano , Angioplastia Coronaria con Balón/instrumentación , Enfermedades Cardiovasculares/mortalidad , Electrocardiografía , Femenino , Francia , Encuestas de Atención de la Salud , Humanos , Contrapulsador Intraaórtico , Masculino , Persona de Mediana Edad , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/mortalidad , Infarto del Miocardio/fisiopatología , Oportunidad Relativa , Pronóstico , Estudios Prospectivos , Sistema de Registros , Medición de Riesgo , Stents , Factores de Tiempo , Insuficiencia del Tratamiento , Resultado del Tratamiento
9.
Am Heart J ; 154(2): 330-5, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17643584

RESUMEN

BACKGROUND: We aimed to investigate the determinants and outcomes of multiple complex lesions (MCLs) on coronary angiography in patients with an acute myocardial infarction. METHODS: One thousand one hundred fifty-two consecutive nonselected myocardial infarction patients who underwent coronary angiography within 24 hours after admission were analyzed. A complex lesion was defined by the presence of thrombus, ulceration, irregular plaque, and flow impairment. Patients with < or = 1 complex lesion were considered with single complex lesion (SCL), and patients with > 1 complex lesions with MCLs. RESULTS: Multiple complex lesions were identified in 360 patients (31%). Patients from the MCL group were older and had a higher rate of cardiovascular risk factors but were less likely to be smokers when compared with the SCL group. Patients with MCLs were more likely to have altered left ventricular ejection fraction and multivessel disease and showed a trend toward an increased median time delay to revascularization (360 vs 285 minutes; P = .070). Moreover, the C-reactive protein (CRP) plasma levels increased with the number of CLs. By multivariate analysis, multivessel disease and CRP level were associated with the presence of MCLs. When compared with the SCL group, patients with MCLs had a higher risk of inhospital cardiogenic shock (18% vs 11%; P = .005) and 30-day mortality (11% vs 6%; P = .002). At 1-year follow-up, the presence of MCLs was an independent predictive factor of death. CONCLUSIONS: This study shows that the presence of MCLs is associated with worse outcomes and that risk factors such as CRP are able to identify patients at a high risk for MCLs.


Asunto(s)
Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Infarto del Miocardio/diagnóstico por imagen , Anciano , Angiografía Coronaria , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Factores de Riesgo
10.
QJM ; 100(4): 211-6, 2007 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-17434911

RESUMEN

BACKGROUND: B-type natriuretic peptide and the N-terminal fragment of its prohormone, N-terminal pro-brain natriuretic peptide (Nt-proBNP), provide valuable prognostic information on short- and long-term mortality in patients with acute coronary syndrome AIM: To investigate the association between plasma NT-proBNP levels and ST-segment resolution (STR) after reperfusion in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: Consecutive patients from the French regional RICO survey with STEMI who were treated by primary PCI or lysis <12 h were included. Blood sample was taken on admission to measure plasma NT-proBNP. Maximal ST segment elevation was measured on the single worst ECG lead before and 90 min after reperfusion. Patients were categorized as STR(-) (<50% STR) or STR(+) (>or=50% STR). RESULTS: Of the 486 patients included, 133 (27%) were STR(-). STR(-) patients had similar cardiovascular risk factors but higher in-hospital mortality (5% vs. 1%, p=0.03) than STR(+) patients. The STR(-) group had higher median (IQR) levels of Nt-proBNP: 938 (211-3272) vs. 533 (169-1471) pg/ml, p=0.003. On multivariate analysis, the highest quartile of Nt-ProBNP, Q waves and lysis were independent risk factors for incomplete STR. DISCUSSION: Our data show a strong association between high levels of Nt-proBNP at admission and incomplete STR, suggesting that Nt-proBNP may be useful for early risk stratification in reperfusion therapy after acute myocardial infarction.


Asunto(s)
Infarto del Miocardio/sangre , Péptido Natriurético Encefálico/metabolismo , Fragmentos de Péptidos/metabolismo , Anciano , Biomarcadores/metabolismo , Diagnóstico Precoz , Electrocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/terapia , Reperfusión Miocárdica/métodos
11.
Virol J ; 4: 80, 2007 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-17711577

RESUMEN

Thottapalayam (TPM) virus belongs to the genus Hantavirus, family Bunyaviridae. The genomes of hantaviruses consist of three negative-stranded RNA segments (S, M and L) encoding the virus nucleocapsid (N), glycoprotein (Gn, Gc), and polymerase (L) proteins, respectively. The genus Hantavirus contains predominantly rodent-borne viruses, with the prominent exception of TPM virus which was isolated in India in 1964 from an insectivore, Suncus murinus, commonly referred to as the Asian house shrew or brown musk shrew. Analysis of the available TPM virus S (1530 nt) RNA genome segment sequence and the newly derived M (3621 nt) and L (6581 nt) segment sequences demonstrate that the entire TPM virus genome is very unique. Remarkably high sequence differences are seen at the nucleotide (up to S - 47%, M - 49%, L - 38%) and protein (up to N - 54%, Gn/Gc - 57% and L - 39%) levels relative to the rodent-borne hantaviruses, consistent with TPM virus having a unique host association.


Asunto(s)
Orthohantavirus/clasificación , Orthohantavirus/genética , Roedores/virología , Musarañas/virología , Animales , Variación Genética , Orthohantavirus/aislamiento & purificación , Filogenia
12.
Trans R Soc Trop Med Hyg ; 101(12): 1253-64, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17905372

RESUMEN

This study describes an RT-PCR assay targeting the L RNA segment of arenaviruses. Conserved regions were identified in the polymerase domain of the L gene on the basis of published sequences for Lassa virus, lymphocytic choriomeningitis virus (LCMV), Pichinde virus and Tacaribe virus, as well as 15 novel sequences for Lassa virus, LCMV, Ippy virus, Mobala virus and Mopeia virus determined in this study. Using these regions as target sites, a PCR assay for detection of all known Old World arenaviruses was developed and optimized. The concentration that yields 95% positive results in a set of replicate tests (95% detection limit) was determined to be 4290 copies of Lassa virus L RNA per ml of serum, corresponding to 30 copies per reaction. The ability of the assay to detect various Old World arenaviruses was demonstrated with in vitro transcribed RNA, material from infected cell cultures and samples from patients with Lassa fever and monkeys with LCMV-associated callitrichid hepatitis. The L gene PCR assay may be applicable: (i) as a complementary diagnostic test for Lassa virus and LCMV; (ii) to identify unknown Old World arenaviruses suspected as aetiological agents of disease; and (iii) for screening of potential reservoir hosts for unknown Old World arenaviruses.


Asunto(s)
Infecciones por Arenaviridae/diagnóstico , Fiebre de Lassa/diagnóstico , Virus Lassa/aislamiento & purificación , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Secuencia de Aminoácidos , Animales , Infecciones por Arenaviridae/genética , Arenavirus del Viejo Mundo/clasificación , Arenavirus del Viejo Mundo/genética , Secuencia de Bases , ADN Viral/análisis , Haplorrinos , Humanos , Fiebre de Lassa/genética , Virus Lassa/genética , Datos de Secuencia Molecular , Sensibilidad y Especificidad
13.
Genome Biol ; 18(1): 38, 2017 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-28222791

RESUMEN

The study of epigenetic heterogeneity at the level of individual cells and in whole populations is the key to understanding cellular differentiation, organismal development, and the evolution of cancer. We develop a statistical method, epiG, to infer and differentiate between different epi-allelic haplotypes, annotated with CpG methylation status and DNA polymorphisms, from whole-genome bisulfite sequencing data, and nucleosome occupancy from NOMe-seq data. We demonstrate the capabilities of the method by inferring allele-specific methylation and nucleosome occupancy in cell lines, and colon and tumor samples, and by benchmarking the method against independent experimental data.


Asunto(s)
Metilación de ADN , Epigenómica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento , Análisis de Secuencia de ADN , Programas Informáticos , Alelos , Islas de CpG , Perfilación de la Expresión Génica , Genotipo , Nucleosomas/metabolismo , Polimorfismo de Nucleótido Simple , Unión Proteica , Reproducibilidad de los Resultados
14.
Am J Cardiol ; 98(2): 167-71, 2006 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-16828586

RESUMEN

Hyperglycemia has been shown to be a powerful predictor of worse outcome after ST-segment-elevation myocardial infarction (STEMI), which could be related to impaired myocardial reperfusion. This study investigated the association between hyperglycemia and ST-segment resolution (STR) after thrombolysis. From the French regional Observatoire des Infarctus de Côte-d'Or survey, admission glucose in 371 patients with STEMIs who were treated by lysis<12 hours was analyzed. The single worst lead electrocardiogram before and 90 minutes after lysis was analyzed, and patients were divided into 3 groups according to the degree of STR: none (<30%), partial (30% to 70%), or complete (>or=70%). Of the 371 patients, 101 (27.2%) had no STR, 124 (33.4%) had partial STR, and 146 (39.4%) had complete STR. STR decreased with increasing glycemia (p=0.029), and patients with hyperglycemia (glycemia>or=11 mmol/L) were more likely to have no STR. Moreover, hyperglycemia was an independent predictor of incomplete STR even after adjustment for potential confounders (odds ratio 2.348, 95% confidence interval 1.212 to 4.547). In conclusion, the present study suggests a strong association between hyperglycemia and electrocardiographic signs of reperfusion in patients with STEMIs after lysis and suggests the usefulness of evaluating early glycemic control in the setting of reperfusion for acute myocardial infarction.


Asunto(s)
Electrocardiografía , Hiperglucemia/etiología , Infarto del Miocardio/terapia , Reperfusión Miocárdica/efectos adversos , Anciano , Glucemia/metabolismo , Angiografía Coronaria , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Hiperglucemia/sangre , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/fisiopatología , Pronóstico , Estudios Retrospectivos
15.
Virol J ; 2: 69, 2005 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-16115318

RESUMEN

BACKGROUND: Severe acute respiratory syndrome (SARS) is caused by a newly discovered coronavirus (SARS-CoV). No effective prophylactic or post-exposure therapy is currently available. RESULTS: We report, however, that chloroquine has strong antiviral effects on SARS-CoV infection of primate cells. These inhibitory effects are observed when the cells are treated with the drug either before or after exposure to the virus, suggesting both prophylactic and therapeutic advantage. In addition to the well-known functions of chloroquine such as elevations of endosomal pH, the drug appears to interfere with terminal glycosylation of the cellular receptor, angiotensin-converting enzyme 2. This may negatively influence the virus-receptor binding and abrogate the infection, with further ramifications by the elevation of vesicular pH, resulting in the inhibition of infection and spread of SARS CoV at clinically admissible concentrations. CONCLUSION: Chloroquine is effective in preventing the spread of SARS CoV in cell culture. Favorable inhibition of virus spread was observed when the cells were either treated with chloroquine prior to or after SARS CoV infection. In addition, the indirect immunofluorescence assay described herein represents a simple and rapid method for screening SARS-CoV antiviral compounds.


Asunto(s)
Antivirales/farmacología , Cloroquina/farmacología , Síndrome Respiratorio Agudo Grave/tratamiento farmacológico , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/efectos de los fármacos , Cloruro de Amonio/farmacología , Enzima Convertidora de Angiotensina 2 , Animales , Chlorocebus aethiops , Técnica del Anticuerpo Fluorescente Indirecta , Glicosilación , Glicoproteínas de Membrana/metabolismo , Peptidil-Dipeptidasa A/metabolismo , Síndrome Respiratorio Agudo Grave/metabolismo , Síndrome Respiratorio Agudo Grave/prevención & control , Síndrome Respiratorio Agudo Grave/virología , Glicoproteína de la Espiga del Coronavirus , Células Vero , Proteínas del Envoltorio Viral/metabolismo
16.
Arch Mal Coeur Vaiss ; 98(6): 608-14, 2005 Jun.
Artículo en Francés | MEDLINE | ID: mdl-16007813

RESUMEN

INTRODUCTION: The occurrence of atrial fibrillation (AF) in the acute phase of myocardial infarction with ST segment elevation is common and responsible for an excess hospital mortality. The aim of this work was to define the incidence, predictive factors, and the prognostic impact of AF during MI with and without raised ST segment in the RICO study. PATIENTS AND METHODS: Between January 2001 and July 2003, 1701 patients were included in this study: 130 (7.6%) had AF in the first 24 hours of management (AF+ group); 1571 (92.4%) remained in sinus rhythm (AF- group). RESULTS: Among the 1701 patients included in this study, 1197 (70.4%) had MI with raised ST and 504 (29.6%) had MI without raised ST. The incidence of AF was identical whatever the type of MI (7.6% with raised ST versus 7.7% without, p=0.334). The presence of Killip class >2 on admission and chronic obstructive pulmonary disease were independent predictive factors for the occurrence of AF (OR=3.84, p=0.007, and OR=2.47, p=0.014 respectively). The presence of AF was significantly associated with the occurrence of ventricular arrhythmia and/or cardiovascular mortality during admission in the non-selected MI population whatever the type of MI (raised ST ; AF+; 34% and AF-; 18%, p<0.01 versus without raised ST; AF+; 36% and AF-; 16%, p = 0.01). CONCLUSION: This study provides evidence that the incidence of AF during the first 24 hours of MI, as well as its poor prognosis, are identical whether or not there is ST segment elevation.


Asunto(s)
Fibrilación Atrial/etiología , Infarto del Miocardio/complicaciones , Anciano , Fibrilación Atrial/epidemiología , Fibrilación Atrial/patología , Electrocardiografía , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Factores de Riesgo
17.
Mol Oncol ; 9(1): 68-77, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25131495

RESUMEN

Identification of the primary tumor site in patients with metastatic cancer is clinically important, but remains a challenge. Hence, efforts have been made towards establishing new diagnostic tools. Molecular profiling is a promising diagnostic approach, but tissue heterogeneity and inadequacy may negatively affect the accuracy and usability of molecular classifiers. We have developed and validated a microRNA-based classifier, which predicts the primary tumor site of liver biopsies, containing a limited number of tumor cells. Concurrently we explored the influence of surrounding normal tissue on classification. MicroRNA profiling was performed using quantitative Real-Time PCR on formalin-fixed paraffin-embedded samples. 278 primary tumors and liver metastases, representing nine primary tumor classes, as well as normal liver samples were used as a training set. A statistical model was applied to adjust for normal liver tissue contamination. Performance was estimated by cross-validation, followed by independent validation on 55 liver core biopsies with a tumor content as low as 10%. A microRNA classifier developed, using the statistical contamination model, showed an overall classification accuracy of 74.5% upon independent validation. Two-thirds of the samples were classified with high-confidence, with an accuracy of 92% on high-confidence predictions. A classifier trained without adjusting for liver tissue contamination, showed a classification accuracy of 38.2%. Our results indicate that surrounding normal tissue from the biopsy site may critically influence molecular classification. A significant improvement in classification accuracy was obtained when the influence of normal tissue was limited by application of a statistical contamination model.


Asunto(s)
Neoplasias Hepáticas , Hígado/metabolismo , MicroARNs/biosíntesis , ARN Neoplásico/biosíntesis , Biopsia , Hígado/patología , Neoplasias Hepáticas/clasificación , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundario , Sensibilidad y Especificidad
18.
J Mol Diagn ; 16(1): 106-15, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24211363

RESUMEN

Carcinomas of unknown primary origin constitute 3% to 5% of all newly diagnosed metastatic cancers, with the primary source difficult to classify with current histological methods. Effective cancer treatment depends on early and accurate identification of the tumor; patients with metastases of unknown origin have poor prognosis and short survival. Because miRNA expression is highly tissue specific, the miRNA profile of a metastasis may be used to identify its origin. We therefore evaluated the potential of miRNA profiling to identify the primary tumor of known metastases. Two hundred eight formalin-fixed, paraffin-embedded samples, representing 15 different histologies, were profiled on a locked nucleic acid-enhanced microarray platform, which allows for highly sensitive and specific detection of miRNA. On the basis of these data, we developed and cross-validated a novel classification algorithm, least absolute shrinkage and selection operator, which had an overall accuracy of 85% (CI, 79%-89%). When the classifier was applied on an independent test set of 48 metastases, the primary site was correctly identified in 42 cases (88% accuracy; CI, 75%-94%). Our findings suggest that miRNA expression profiling on paraffin tissue can efficiently predict the primary origin of a tumor and may provide pathologists with a molecular diagnostic tool that can improve their capability to correctly identify the origin of hitherto unidentifiable metastatic tumors and, eventually, enable tailored therapy.


Asunto(s)
MicroARNs/genética , Técnicas de Diagnóstico Molecular/métodos , Neoplasias Primarias Desconocidas/clasificación , Neoplasias Primarias Desconocidas/genética , Análisis de Secuencia de ARN/métodos , Algoritmos , Secuencia de Bases , Biomarcadores de Tumor/genética , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Primarias Desconocidas/diagnóstico , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Especificidad de Órganos/genética , Adhesión en Parafina
19.
PLoS One ; 8(12): e80012, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24324589

RESUMEN

Terrestrial inputs (natural and anthropogenic) from rivers, the atmosphere and physical processes strongly impact the functioning of coastal pelagic ecosystems. The objective of this study was to develop a tool for the examination of these impacts on the Marseille coastal area, which experiences inputs from the Rhone River and high rates of atmospheric deposition. Therefore, a new 3D coupled physical/biogeochemical model was developed. Two versions of the biogeochemical model were tested, one model considering only the carbon (C) and nitrogen (N) cycles and a second model that also considers the phosphorus (P) cycle. Realistic simulations were performed for a period of 5 years (2007-2011). The model accuracy assessment showed that both versions of the model were able of capturing the seasonal changes and spatial characteristics of the ecosystem. The model also reproduced upwelling events and the intrusion of Rhone River water into the Bay of Marseille well. Those processes appeared to greatly impact this coastal oligotrophic area because they induced strong increases in chlorophyll-a concentrations in the surface layer. The model with the C, N and P cycles better reproduced the chlorophyll-a concentrations at the surface than did the model without the P cycle, especially for the Rhone River water. Nevertheless, the chlorophyll-a concentrations at depth were better represented by the model without the P cycle. Therefore, the complexity of the biogeochemical model introduced errors into the model results, but it also improved model results during specific events. Finally, this study suggested that in coastal oligotrophic areas, improvements in the description and quantification of the hydrodynamics and the terrestrial inputs should be preferred over increasing the complexity of the biogeochemical model.


Asunto(s)
Ecosistema , Monitoreo del Ambiente , Sedimentos Geológicos/análisis , Modelos Estadísticos , Atmósfera , Carbono/química , Clorofila/química , Clorofila A , Francia , Italia , Mar Mediterráneo , Nitrógeno/química , Fósforo/química , Ríos/química , Estaciones del Año , Agua de Mar/química
20.
Infect Genet Evol ; 11(5): 1111-20, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21511058

RESUMEN

Nairobi sheep disease (NSD) virus, the prototype tick-borne virus of the genus Nairovirus, family Bunyaviridae is associated with acute hemorrhagic gastroenteritis in sheep and goats in East and Central Africa. The closely related Ganjam virus found in India is associated with febrile illness in humans and disease in livestock. The complete S, M and L segment sequences of Ganjam and NSD virus and partial sequence analysis of Ganjam viral RNA genome S, M and L segments encoding regions (396 bp, 701 bp and 425 bp) of the viral nucleocapsid (N), glycoprotein precursor (GPC) and L polymerase (L) proteins, respectively, was carried out for multiple Ganjam virus isolates obtained from 1954 to 2002 and from various regions of India. M segments of NSD and Ganjam virus encode a large ORF for the glycoprotein precursor (GPC), (1627 and 1624 amino acids in length, respectively) and their L segments encode a very large L polymerase (3991 amino acids). The complete S, M and L segments of NSD and Ganjam viruses were more closely related to one another than to other characterized nairoviruses, and no evidence of reassortment was found. However, the NSD and Ganjam virus complete M segment differed by 22.90% and 14.70%, for nucleotide and amino acid respectively, and the complete L segment nucleotide and protein differing by 9.90% and 2.70%, respectively among themselves. Ganjam and NSD virus, complete S segment differed by 9.40-10.40% and 3.2-4.10 for nucleotide and proteins while among Ganjam viruses 0.0-6.20% and 0.0-1.4%, variation was found for nucleotide and amino acids. Ganjam virus isolates differed by up to 17% and 11% at the nucleotide level for the partial S and L gene fragments, respectively, with less variation observed at the deduced amino acid level (10.5 and 2%, S and L, respectively). However, the virus partial M gene fragment (which encodes the hypervariable mucin-like domain) of these viruses differed by as much as 56% at the nucleotide level. Phylogenetic analysis of partial sequence differences suggests considerable mixing and movement of Ganjam virus strains within India, with no clear relationship between genetic lineages and virus geographic origin or year of isolation. Surprisingly, NSD virus does not represent a distinct lineage, but appears as a variant with other Ganjam virus among NSD virus group.


Asunto(s)
Virus de la Enfermedad de los Ovinos de Nairobi/genética , África/epidemiología , Demografía , Variación Genética , Genoma Viral , India/epidemiología , Filogenia , ARN Viral/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Factores de Tiempo
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