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BACKGROUND: The severity of non-tuberculous mycobacterial pulmonary disease (NTM-PD) can be classified based on an assessment of the patient´s body mass index, age, presence of cavity, erythrocyte sediment rate and sex (BACES). In this study, changes in lung function according to disease severity were analysed.METHODS: Patients with NTM-PD who underwent at least two lung function tests between 1 January 2011 and 31 December 2021, were classified according to their BACES score into mild (0-1), moderate (2-3) and severe (4-5) groups, and changes in lung function were assessed using BACES scores.RESULTS: A total of 354 patients were divided into three groups: mild (n = 108), moderate (n = 216) and severe (n = 30). As disease severity increased, the decrease in forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) was greater: respectively 26.4 mL/year, 31.3 mL/year and 35.7 mL/year in case of FEV1 (P for trend = 0.002); 18.9 mL/year, 25.5 mL/year and 48.9 mL/year in case of FVC (P for trend = 0.002); and 0.7%/year, 1.3%/year and 2.5%/year for DLCO (P for trend = 0.023) in the mild, moderate and severe groups.CONCLUSION: The decrease in lung function in NTM-PD was correlated with disease severity.
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Enfermedades Pulmonares , Pulmón , Humanos , Micobacterias no Tuberculosas , Volumen Espiratorio Forzado , Capacidad Vital , Gravedad del Paciente , Capacidad de Difusión PulmonarRESUMEN
BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) poses a threat to public health as a result of high treatment costs and unsatisfactory outcomes.OBJECTIVE: To elucidate trend, demographic and clinical characteristics and treatment outcomes of patients with MDR-TB between 2011 and 2015 in South Korea.METHOD: Data of patients with MDR-TB diagnosed between 1 January 2011 and 31 December 2015 were retrieved from the nationwide Internet-based TB notification system and analysed retrospectively.RESULTS: During the study period, 5192 MDR-TB patients were notified. We identified an increasing number of MDR-TB patients among foreign populations (from 1.3% to 7.7%), decreasing resistance rates to other anti-TB drugs (e.g., resistance to pyrazinamide, from 40.9% to 28.2%), a decreasing interval from treatment initiation to negative conversion of sputum culture (from 165.7 to 103.7 days) and shortening of treatment duration (719.7 to 613.2 days). However, treatment success rates did not change, and had an average of 65.7%.CONCLUSION: Despite decreasing resistance rates to other drugs and faster treatment responses, treatment outcomes did not improve during the study period. Strict management of MDR-TB patients on treatment should be adopted to improve treatment outcomes.
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Antituberculosos/uso terapéutico , Notificación de Enfermedades , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Pulmonar/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antituberculosos/farmacología , Niño , Preescolar , Demografía , Femenino , Humanos , Lactante , Recién Nacido , Internet , Masculino , Tamizaje Masivo , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/aislamiento & purificación , República de Corea/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/prevención & control , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/microbiología , Tuberculosis Pulmonar/prevención & control , Adulto JovenRESUMEN
SETTING: A referral centre in South Korea. OBJECTIVE: To investigate trends in drug resistance, treatment modalities and outcomes, and adverse events of multidrug-resistant tuberculosis (MDR-TB) over two decades. DESIGN: MDR-TB patients treated at Seoul National Hospital University between 1996 and 2015 were divided into four 5-year cohorts according to the date of initial diagnosis. Changes in demographic characteristics, drug resistance, drugs used, treatment outcomes and adverse events over time were elucidated. RESULTS: Between 1996 and 2015, 418 patients were treated for MDR-TB: 86 patients between 1996 and 2000, 125 between 2001 and 2005, 123 between 2006 and 2010, and 84 between 2011 and 2015. The proportion of patients with positive acid-fast bacilli sputum (60.5-29.7%, P < 0.001) or cavities on chest radiographs (86.0-40.5%, P < 0.001) decreased over time. Resistance to pyrazinamide, fluoroquinolones, cycloserine and p-aminosalicylic acid decreased. Later-generation fluoroquinolones (77.9-90.5%) and linezolid (0-26.2%) became more frequently prescribed. The treatment success rate increased (45.3-88.1%, P < 0.001); neurological adverse events, including peripheral neuropathy also increased (4.7-13.1%, P = 0.027). CONCLUSION: MDR-TB patients presented with less severe disease and better resistance profiles over time in South Korea, with treatment outcomes improving continuously.
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Antituberculosos/administración & dosificación , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Adulto , Antituberculosos/farmacología , Estudios de Cohortes , Farmacorresistencia Bacteriana Múltiple , Femenino , Hospitales Universitarios , Humanos , Masculino , Persona de Mediana Edad , República de Corea/epidemiología , Estudios Retrospectivos , Esputo/microbiología , Resultado del Tratamiento , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/microbiologíaRESUMEN
SETTING: After several changes in treatment modalities, it is time to re-evaluate treatment outcomes of multidrug-resistant tuberculosis (MDR-TB). OBJECTIVE: To evaluate treatment outcomes, elucidate changes in outcomes over time and identify predictors of treatment success for MDR-TB. DESIGN: Patients diagnosed with MDR-TB at a tertiary referral centre in South Korea between January 2006 and December 2010 were included. Treatment modalities and outcomes were assessed. Predictors of treatment success were analysed using multiple logistic regression. The treatment modalities and outcomes of these patients were compared with those of MDR-TB patients between January 1996 and December 2005. RESULTS: Of the 123 MDR-TB patients diagnosed during the later study period, treatment was successful in 103 (83.7%). Extensive drug resistance (OR 0.31, P = 0.044) and additional resistance to fluoroquinolones (OR 0.23, P = 0.039) were inversely associated with treatment success. The treatment success rate improved from 53.5% in 1996-2000 to 68.8% in 2001-2005 and 83.7% in 2006-2010 (P < 0.001). Improved outcomes were accompanied with more frequent use of later-generation fluoroquinolones and linezolid and less frequent surgical resection. CONCLUSION: Treatment outcomes for MDR-TB improved at a tertiary referral centre in South Korea. The improvement was associated with more frequent use of later-generation fluoroquinolones and linezolid.
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Antituberculosos/uso terapéutico , Mycobacterium tuberculosis/efectos de los fármacos , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adulto , Antituberculosos/farmacología , Estudios de Cohortes , Tuberculosis Extensivamente Resistente a Drogas/diagnóstico , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Hospitales Universitarios , Humanos , Modelos Logísticos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Análisis Multivariante , Recurrencia , República de Corea , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Factores de Tiempo , Resultado del TratamientoRESUMEN
SETTING: The Xpert(®) MTB/RIF assay has been endorsed by the World Health Organization for the detection of pulmonary and extra-pulmonary tuberculosis (EPTB). OBJECTIVE: To determine the accuracy of the Xpert assay in diagnosing EPTB in South Korea, a country with an intermediate TB burden. DESIGN: We retrospectively reviewed the medical records of 1429 patients in whom the Xpert assay using EPTB specimens was requested between 1 January 2011 and 31 October 2013 in a tertiary referral hospital in South Korea. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the diagnosis of EPTB and detection of rifampicin (RMP) resistance were calculated. RESULTS: Using culture as gold standard, the sensitivity, specificity, PPV and NPV of the assay were respectively 67.7%, 98.1%, 60% and 98.6%. Using a composite reference standard, the sensitivity, specificity, PPV and NPV were respectively 49.3%, 100%, 100% and 95.1%. The sensitivity, specificity, PPV and NPV for the detection of RMP resistance among specimens with positive results for Mycobacterium tuberculosis were respectively 80%, 100%, 100% and 97.7%. CONCLUSION: The Xpert assay showed acceptable sensitivity in certain groups and excellent specificity in diagnosing EPTB and detecting RMP resistance in an intermediate TB burden country.
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Antibióticos Antituberculosos/farmacología , Farmacorresistencia Bacteriana Múltiple , Rifampin/farmacología , Tuberculosis Pulmonar/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/aislamiento & purificación , Valor Predictivo de las Pruebas , República de Corea , Estudios Retrospectivos , Sensibilidad y Especificidad , Manejo de Especímenes , Adulto JovenRESUMEN
This paper deals with strategic enterprise resource planning (ERP) in a health-care system using a multicriteria decision-making (MCDM) model. The model is developed and analyzed on the basis of the data obtained from a leading patient-oriented provider of health-care services in Korea. Goal criteria and priorities are identified and established via the analytic hierarchy process (AHP). Goal programming (GP) is utilized to derive satisfying solutions for designing, evaluating, and implementing an ERP. The model results are evaluated and sensitivity analyses are conducted in an effort to enhance the model applicability. The case study provides management with valuable insights for planning and controlling health-care activities and services.
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Toma de Decisiones Asistida por Computador , Toma de Decisiones en la Organización , Atención a la Salud/métodos , Atención a la Salud/organización & administración , Asignación de Recursos para la Atención de Salud , Planificación en Salud , Humanos , Corea (Geográfico) , Modelos OrganizacionalesRESUMEN
To treat cutting oil wastewater produced in metal surface treatment industry, Ultrasonication (US)-Fenton process, which is one of the advanced oxidation processes, was used. The optimum conditions to treat non-biodegradable pollutants using the US-Fenton process were that the application rates of H2O2 and FeSO4 were 10% and 3 g/L, respectively, the value of pH was 3, and the ultrasonication time was 30 min. It identified non-degradable pollutants such as ethylene diamine tetraacetic acid (EDTA) and Triethanolamine (TEA) in the cutting oil wastewater. TLC analysis of two compounds of treated water by the coagulation process was similar to that of raw water. However, TLC analysis of two compounds of US-Fenton process was different from that of raw water, meaning that US-Fenton process decomposed the EDTA and TEA. To study the possibility of application with the US-Fenton process to pilot plant, the pollutants treatment efficiency of three different methods, such as US-Fenton process, activated sludge process and coagulation process, in continuous experiments were compared. The removal rate of pollutants by the US-Fenton process according to the effluent time was higher than any other processes. The removal rates of COD, SS, T-N and T-P by US-Fenton process were 98, 93, 75 and 95%, respectively.
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Peróxido de Hidrógeno/química , Residuos Industriales , Hierro/química , Ultrasonido , Eliminación de Residuos Líquidos , Contaminantes Químicos del Agua/química , Purificación del Agua/métodos , Biodegradación Ambiental , Restauración y Remediación Ambiental , Compuestos Ferrosos/química , Compuestos Ferrosos/metabolismo , Peróxido de Hidrógeno/metabolismo , Concentración de Iones de Hidrógeno , Hierro/metabolismo , Metales/química , Aceites , Oxidación-Reducción , Factores de Tiempo , Contaminantes Químicos del Agua/metabolismoRESUMEN
The present study was carried out to observe the cytotoxicity of yellow sand in comparison with silica and titanium dioxide in a rat alveolar type II cell line (RLE-6TN). Yellow sand (China Loess) was obtained from the loess layer in the Gunsu Province of China. The mean particle diameter of yellow sand was about 0.003 +/- 0.001 mm. Major elements of yellow sand were Si(27.7 +/- 0.6%), Al(6.01 +/- 0.17%), and Ca(5.83 +/- 0.23%) in that order. Silica and yellow sand significantly decreased cell viability and increased [Ca2+]i. All three particles increased the generation of H2O2. TiO2 did not change Fenton activity, while silica induced a slight increase of Fenton activity. In contrast, yellow sand induced a significant increase of Fenton activity. Silica, yellow sand and TiO2 induced significant nitrite formations in RLE-6TN cells. Silica showed the highest increase in nitrite formation, while yellow sand induced the least formation of nitrite. Silica and yellow sand increased the release of TNF-a. Based on these results, we suggest that yellow sand can induce cytotoxicity in RLE-6TN cells and reactive oxygen species, Fenton activity and reactive nitrogen species might be involved in this toxicity.
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Células Epiteliales/metabolismo , Pulmón/citología , Pulmón/metabolismo , Macrófagos Alveolares/metabolismo , Dióxido de Silicio/toxicidad , Aluminio/química , Animales , Calcio/análisis , Calcio/química , Línea Celular , Supervivencia Celular/efectos de los fármacos , Medios de Cultivo Condicionados/química , Células Epiteliales/efectos de los fármacos , Peróxido de Hidrógeno/análisis , Peróxido de Hidrógeno/síntesis química , Macrófagos Alveolares/efectos de los fármacos , Nitritos/análisis , Tamaño de la Partícula , Ratas , Silicio/química , Dióxido de Silicio/química , Titanio/efectos adversos , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
This study presents an application of linear programming discriminant analysis (LPDA) to classify and to predict the symptomatic status of HIV/AIDS patients. We applied LPDA as well as several traditional discriminant analysis methods to the AIDS Cost and Services Utilization Survey data set in order to demonstrate the use of LPDA to classify the symptomatic status of HIV/AIDS patients. The potential benefit of LPDA in terms of the classification accuracy was also analyzed.
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Análisis Discriminante , Infecciones por VIH/fisiopatología , Programación Lineal , Diagnóstico por Computador , Femenino , Infecciones por VIH/clasificación , Humanos , Masculino , Índice de Severidad de la EnfermedadRESUMEN
Feature selection plays an important role in classifying systems such as neural networks (NNs). We use a set of attributes which are relevant, irrelevant or redundant and from the viewpoint of managing a dataset which can be huge, reducing the number of attributes by selecting only the relevant ones is desirable. In doing so, higher performances with lower computational effort is expected. In this paper, we propose two feature selection algorithms. The limitation of mutual information feature selector (MIFS) is analyzed and a method to overcome this limitation is studied. One of the proposed algorithms makes more considered use of mutual information between input attributes and output classes than the MIFS. What is demonstrated is that the proposed method can provide the performance of the ideal greedy selection algorithm when information is distributed uniformly. The computational load for this algorithm is nearly the same as that of MIFS. In addition, another feature selection algorithm using the Taguchi method is proposed. This is advanced as a solution to the question as to how to identify good features with as few experiments as possible. The proposed algorithms are applied to several classification problems and compared with MIFS. These two algorithms can be combined to complement each other's limitations. The combined algorithm performed well in several experiments and should prove to be a useful method in selecting features for classification problems.
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Attempts are being made at the international level within the framework of the Codex Alimentarius to establish guidelines for health claims. An important issue that has to be addressed is the process of substantiating any health claim. Previous papers have addressed aspects relating to the development and regulatory control of functional foods and certain issues relating to claims. This paper addresses several issues concerning the substantiation of health claims through the examination of the regulations and guidelines in several countries. They include (1) importance of human- and product-based studies; (2) concept of scientific consensus; (3) authorization of claim wording; (4) availability of scientific evidence to public (confidentiality). The paper finally proposes a system based on generic and innovative health claims.
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Alimentos Orgánicos/normas , Legislación Alimentaria/normas , Animales , Medicina Basada en la Evidencia , Salud Global , Humanos , Cooperación Internacional , Política NutricionalAsunto(s)
Personas con Discapacidad/estadística & datos numéricos , Hospitales Provinciales/tendencias , Personas con Discapacidades Mentales/estadística & datos numéricos , Instituciones Residenciales/tendencias , Adolescente , Adulto , Anciano , Niño , Preescolar , Desinstitucionalización/tendencias , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estados UnidosRESUMEN
In 1994 and 1995, the National Health Interview Survey included a Disability Supplement (NHIS-D) to collect extensive information about disabilities among individuals sampled as part of annual census-based household interview surveys. Here we describe the development and application of operational definitions of mental retardation and developmental disabilities to items in the NHIS-D to estimate prevalence. In our analyses, we estimate the prevalence of mental retardation in the noninstitutionalized population of the United States to be 7.8 people per thousand (.78%); of developmental disabilities, 11.3 people per thousand (1.13%); and the combined prevalence of mental retardation and/or developmental disabilities to be 14.9 per thousand (1.49%). Differences in prevalence estimates for mental retardation and developmental disabilities and among people of various ages are explored.
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Discapacidades del Desarrollo/epidemiología , Evaluación de la Discapacidad , Discapacidad Intelectual/epidemiología , Encuestas y Cuestionarios , Adolescente , Niño , Preescolar , Estudios de Cohortes , Discapacidades del Desarrollo/diagnóstico , Humanos , Discapacidad Intelectual/diagnóstico , Prevalencia , Estudios ProspectivosRESUMEN
We report results of a search for B-->tau(nu) in a sample of 9.7 x 10(6) charged B meson decays. We exclusively reconstruct the companion B decay to suppress background. We set an upper limit on the branching fraction B(B-->tau(nu))<8.4 x 10(-4) at 90% confidence level. We also establish B(B+/--->K+/-nu(nu))<2.4 x 10(-4) at 90% confidence level.
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Using data recorded with the CLEO II and CLEO II.V detector configurations at the Cornell Electron Storage Rings, we report the first observation and mass measurement of the Sigma(*+)(c) charmed baryon, and an updated measurement of the mass of the Sigma(+)(c) baryon. We find M(Sigma(*+)(c))-M(Lambda(+)(c)) = (231.0+/-1.1+/-2.0) MeV, and M(Sigma(+)(c))-M(Lambda(+)(c)) = (166.4+/-0.2+/-0.3) MeV, where the errors are statistical and systematic, respectively.
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In a sample of 9.66x10(6)B&Bmacr; pairs collected with the CLEO detector we make the first observation of B decays to an eta(c) and a kaon. We measure branching fractions B(B+-->eta(c)K+) = (0.69(+0.26)(-0.21)+/-0.08+/-0.20)x10(-3) and B(B degrees -->eta(c)K degrees ) = (1.09(+0.55)(-0.42)+/-0.12+/-0.31)x10(-3), where the first error is statistical, the second is systematic, and the third is from the eta(c) branching fraction uncertainty. From these we extract the eta(c) decay constant in the factorization approximation, f(eta(c)) = 335+/-75 MeV. We also search for B decays to a chi(c0) and a kaon. No evidence for a signal is found and we set 90% C.L. upper limits: B(B+-->chi(c0)K+)<4.8x10(-4) and B(B degrees -->chi(c0)K degrees )<5.0x10(-4).
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Using 13.4 fb(-1) of data collected with the CLEO detector at the Cornell Electron Storage Ring, we have observed 300 events for the two-photon production of ground-state pseudoscalar charmonium in the decay eta(c)-->K(0)(S)K-/+pi(+/-). We have measured the eta(c) mass to be [2980.4+/-2.3 (stat)+/-0.6 (syst)] MeV and its full width as [27.0+/-5.8 (stat)+/-1.4 (syst)] MeV. We have determined the two-photon partial width of the eta(c) meson to be [7.6+/-0.8 (stat)+/-0.4 (syst)+/-2.3 (br)] keV, with the last uncertainty associated with the decay branching fraction.
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PURPOSE: Vascular endothelial growth factor (VEGF) is upregulated by hypoxia and is a major stimulatory factor for retinal neovascularization in ischemic retinopathies such as diabetic retinopathy. This study sought to determine if VEGF is a stimulatory factor in a murine model of choroidal neovascularization (CNV). METHODS: Mice with laser-induced ruptures in Bruch's membrane were treated with vehicle alone; a drug that inhibits both VEGF and platelet-derived growth factor (PDGF) receptor kinases; a drug that inhibits PDGF, but not VEGF receptor kinase; or genistein, a nonspecific kinase inhibitor. After two weeks, CNV was quantified and compared. RESULTS: Blockade of phosphorylation by VEGF and PDGF receptors caused dramatic, almost complete inhibition of CNV. Genistein also had an inhibitory effect, but less so than the VEGF/PDGF receptor blocker. Blockade of phosphorylation by PDGF receptors, but not VEGF receptors, had no significant effect on CNV. CONCLUSIONS: These data and our previous study, which demonstrated that a kinase inhibitor that blocks VEGF and PDGF receptors and several isoforms of protein kinase C causing dramatic inhibition of CNV, suggest that VEGF signaling plays a critical role in the development of CNV in this model. If safety is established, the effect of inhibiting VEGF receptor kinase activity should be investigated in patients with CNV.
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Neovascularización Coroidal/metabolismo , Factores de Crecimiento Endotelial/fisiología , Linfocinas/fisiología , Animales , Neovascularización Coroidal/patología , Neovascularización Coroidal/prevención & control , Inhibidores Enzimáticos/farmacología , Genisteína/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Fosforilación , Ftalazinas/farmacología , Factor de Crecimiento Derivado de Plaquetas/fisiología , Proteína Quinasa C/antagonistas & inhibidores , Piridinas/farmacología , Pirimidinas/farmacología , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Receptores de Factores de Crecimiento/antagonistas & inhibidores , Receptores del Factor de Crecimiento Derivado de Plaquetas/antagonistas & inhibidores , Receptores de Factores de Crecimiento Endotelial Vascular , Transducción de Señal/fisiología , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
We report results of a search for the rare radiative decay &Bmacr;(0)-->D(*0)gamma. Using 9.66x10(6) B&Bmacr; meson pairs collected with the CLEO detector at the Cornell Electron Storage Ring, we set an upper limit on the branching ratio for this decay of 5.0x10(-5) at 90% C.L. This provides evidence that the anomalous enhancement is absent in W-exchange processes and that weak radiative B decays are dominated by the short-distance b-->sgamma mechanism in the standard model.
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Fibroblast growth factor-2 (FGF2) is a potent mitogen for vascular endothelial cells and exogenous administration of FGF2 stimulates angiogenesis. However, increased expression of FGF2 in the retina does not cause angiogenesis. One possible explanation is that FGF2 may not be capable of initiating angiogenesis unless it is administered in pharmacologic levels or there is coexpression of another angiogenic factor. Alternatively, there may be control mechanisms that sequester FGF2 in vivo, preventing it from manifesting its in vitro angiogenic activity. We tested the first hypothesis by crossing mice that express FGF2 in the retina with mice that express vascular endothelial growth factor (VEGF) in the retina. Surprisingly, despite comparable levels of VEGF expression, mice that expressed both FGF2 and VEGF had significantly less neovascularization than mice that expressed VEGF alone. The second hypothesis was tested by treating Rho/FGF2 transgenic mice with low-intensity laser photocoagulation that disrupts photoreceptors, but does not rupture Bruch's membrane, or intense laser that ruptures Bruch's membrane. In Rho/FGF2 transgenics, but not wild type mice, choroidal neovascularization developed in areas of low-intensity laser. Both wild type and transgenic mice developed choroidal neovascularization in areas of intense laser that ruptured Bruch's membrane, but the area of neovascularization was significantly greater in transgenics. These data suggest that increased retinal expression of FGF2 is angiogenic only when it is accompanied by cell injury that overcomes sequestration control mechanisms.