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1.
Phys Med Biol ; 68(17)2023 08 29.
Artículo en Inglés | MEDLINE | ID: mdl-37567226

RESUMEN

Objective. In this contribution we present a special Fano test for charged particles in presence of magnetic fields in the MC code TOol for PArticle Simulation (TOPAS), as well as the determination of magnetic field correction factorskBfor Farmer-type ionization chambers using proton beams.Approach. Customized C++ extensions for TOPAS were implemented to model the special Fano tests in presence of magnetic fields for electrons and protons. The Geant4-specific transport parameters,DRoverRandfinalRange,were investigated to optimize passing rate and computation time. ThekBwas determined for the Farmer-type PTW 30013 ionization chamber, and 5 custom built ionization chambers with same geometry but varying inner radius, testing magnetic flux density ranging from 0 to 1.0 T and two proton beam energies of 157.43 and 221.05 MeV.Main results. Using the investigated parameters, TOPAS passed the Fano test within 0.39 ± 0.15% and 0.82 ± 0.42%, respectively for electrons and protons. The chamber response (kB,M,Q) gives a maximum at different magnetic flux densities depending of the chamber size, 1.0043 at 1.0 T for the smallest chamber and 1.0051 at 0.2 T for the largest chamber. The local dose differencecBremained ≤ 0.1% for both tested energies. The magnetic field correction factorkB, for the chamber PTW 30013, varied from 0.9946 to 1.0036 for both tested energies.Significance. The developed extension for the special Fano test in TOPAS MC code with the adjusted transport parameters, can accurately transport electron and proton particles in magnetic field. This makes TOPAS a valuable tool for the determination ofkB. The ionization chambers we tested showed thatkBremains small (≤0.72%). To the best of our knowledge, this is the first calculations ofkBfor proton beams. This work represents a significant step forward in the development of MRgPT and protocols for proton dosimetry in presence of magnetic field.


Asunto(s)
Agricultores , Protones , Humanos , Método de Montecarlo , Radiometría/métodos , Campos Magnéticos
2.
Ophthalmologe ; 118(4): 337-344, 2021 Apr.
Artículo en Alemán | MEDLINE | ID: mdl-32638094

RESUMEN

The Sicca-Förderpreis (Dry Eye Award) supports the development of scientific research on the pathogenesis, diagnostics, and treatment of dry eye and ocular surface diseases. It is awarded after a limited call for proposals in German-speaking countries, written application and selection of the award winner after evaluation by a jury of ophthalmologists working in basic and clinical science. In this article examples of the results of funded projects of the Sicca-Förderpreis 2016 are cursorily described, which were presented at the Ophthalmological Academy of Germany 2019 (Augenärztliche Akademie Deutschland 2019) and therefore provide an insight into current scientific developments. The role of muscarinic receptors and those of urea in the pathogenesis of dry eye as well as the (missing) correlation of tear film stability, viscosity and surface tension are highlighted. A project on the early detection of ocular involvement in graft versus host disease and the idea of treating meibomian gland dysfunction with eyelid surgery techniques are also groundbreaking. The outlined projects represent the potential for further substantial developments in the understanding, diagnostics and treatment of dry eye; however, their long-term clinical relevance still needs to be established.


Asunto(s)
Distinciones y Premios , Síndromes de Ojo Seco , Enfermedades de los Párpados , Síndromes de Ojo Seco/diagnóstico , Síndromes de Ojo Seco/terapia , Alemania , Humanos , Glándulas Tarsales , Lágrimas
3.
J Orofac Orthop ; 76(2): 164-74, 2015 Mar.
Artículo en Inglés, Alemán | MEDLINE | ID: mdl-25744094

RESUMEN

OBJECTIVES: Permanent retention is currently the method of choice to stabilize orthodontic treatment results. Frequently, permanent retention schemes are adopted to prevent posttreatment changes in the esthetic zone of the anterior teeth. With increasingly prolonged times of intraoral device use, and retention to be provided in the maxilla despite limited space, the demands placed on well-planned and precise retainer positioning are becoming more exacting. The aim of the present study was to analyze the intraoral precision of lingual retainers made using computer-aided design and machining (CAD/CAM). MATERIALS AND METHODS: A custom manufacturer (Retaintechnology; Cologne, Germany) employing innovative CAD/CAM technology was commissioned to fabricate 16 lingual retainers. Following intraoral insertion using the manufacturer's recommended transfer system, impressions of the intraoral situations were taken and scanned for digitization. On this basis, the intraoral retainer positions were compared to the preceding virtual setups by superimposition with the manufacturer's datasets. Three-dimensional processing software (Geomagic Qualify 2012; Geomagic) was used to analyze the retainers, based on a total of 80 interproximal sites, for deviations from their planned positions along the horizontal (x-), sagittal (y-), and vertical (z-) axes. These deviations of the achieved from the intended positions were considered clinically relevant if ≥ 0.5 mm and, based on this premise, were subjected to a t-test with statistical software (Prism; GraphPad). RESULTS: The intraoral retainer positions were found to correlate closely with the preceding virtual setups (i.e., the positions as they had been planned by the custom manufacturer). Positional deviations were significantly less than 0.5 mm. They were very small in the horizontal and sagittal planes and moderately larger in the vertical plane. CONCLUSION: Highly precise intraoral results may be achieved by transferring three-dimensional virtual setups for lingual retainers to the actual patients. This CAD/CAM strategy of making retainers can offer high predictability even in anatomically demanding regions and in the presence of limited space.


Asunto(s)
Diseño Asistido por Computadora , Retención de Prótesis Dentales/instrumentación , Diseño de Aparato Ortodóncico/métodos , Retenedores Ortodóncicos , Ajuste de Prótesis/métodos , Simulación por Computador , Análisis de Falla de Equipo/métodos , Imagenología Tridimensional/métodos , Modelos Teóricos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Lengua
4.
Physiol Meas ; 36(2): 341-55, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25612737

RESUMEN

The analysis of uterine EMG (electrohysterogram-EHG) records may help solve the problem of predicting pre-term labor. We investigated the adaptive autoregressive (AAR) method to estimate the EHG signal spectrograms and sample entropy, to separate and classify sets of term and pre-term delivery records, using the Term-Preterm EHG Database. The database contains four sets of records divided according to the time of delivery (term or pre-term: â©¾37 or < 37 weeks of gestation, respectively) and according to the time of recording (early or later: before or after the 26th week of gestation, respectively). Using the AAR method the term and pre-term delivery records recorded early can be separated (p = 0.002), as well as all term and pre-term delivery records (p < 0.001). Using the sample entropy, the results showed that all term and pre-term delivery records can be separated (p = 0.022). The spectra of the signals for term delivery records have the tendency of moving to lower frequencies as the time of pregnancy increases. We investigated a few classifiers to classify records between term and pre-term delivery sets. Using median frequency measurements and additional clinical information with the synthetic minority over-sampling technique, the quadratic discriminant analysis classifier achieved a 97% classification accuracy for the records recorded early, and 86% for all records regardless of the time of recording; while for the sample entropy measurements, for the same sets of records, using the support vector machine classifier, the classification accuracies were 80% and 87%, respectively.


Asunto(s)
Electromiografía/métodos , Nacimiento Prematuro/fisiopatología , Nacimiento a Término/fisiología , Útero/fisiología , Algoritmos , Parto Obstétrico , Entropía , Femenino , Humanos , Embarazo , Procesamiento de Señales Asistido por Computador
6.
Physiol Meas ; 31(3): 323-37, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20130344

RESUMEN

In ambulatory ECG records, besides transient ischaemic ST segment deviation episodes, there are also transient non-ischaemic heart-rate related ST segment deviation episodes present, which appear only due to a change in heart rate and thus complicate automatic detection of true ischaemic episodes. The goal of this work was to automatically classify these two types of episodes. The tested features to classify the ST segment deviation episodes were changes of heart rate, changes of the Mahalanobis distance of the first five Karhunen-Loève transform (KLT) coefficients of the QRS complex, changes of time-domain morphologic parameters of the ST segment and changes of the Legendre orthonormal polynomial coefficients of the ST segment. We chose Legendre basis functions because they best fit typical shapes of the ST segment morphology, thus allowing direct insight into the ST segment morphology changes through the feature space. The classification was performed with the help of decision trees. We tested the classification method using all records of the Long-Term ST Database on all ischaemic and all non-ischaemic heart-rate related deviation episodes according to annotation protocol B. In order to predict the real-world performance of the classification we used second-order aggregate statistics, gross and average statistics, and the bootstrap method. We obtained the best performance when we combined the heart-rate features, the Mahalanobis distance and the Legendre orthonormal polynomial coefficient features, with average sensitivity of 98.1% and average specificity of 85.2%.


Asunto(s)
Algoritmos , Automatización , Electrocardiografía Ambulatoria/métodos , Frecuencia Cardíaca , Isquemia Miocárdica/fisiopatología , Procesamiento de Señales Asistido por Computador , Análisis de Varianza , Área Bajo la Curva , Bases de Datos como Asunto , Humanos , Isquemia Miocárdica/diagnóstico , Curva ROC , Sensibilidad y Especificidad
7.
Med Biol Eng Comput ; 46(9): 911-22, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18437439

RESUMEN

Various linear and non-linear signal-processing techniques were applied to three-channel uterine EMG records to separate term and pre-term deliveries. The linear techniques were root mean square value, peak and median frequency of the signal power spectrum and autocorrelation zero crossing; while the selected non-linear techniques were estimation of the maximal Lyapunov exponent, correlation dimension and calculating sample entropy. In total, 300 records were grouped into four groups according to the time of recording (before or after the 26th week of gestation) and according to the total length of gestation (term delivery records--pregnancy duration >or=37 weeks and pre-term delivery records--pregnancy duration <37 weeks). The following preprocessing band-pass Butterworth filters were tested: 0.08-4, 0.3-4, and 0.3-3 Hz. With the 0.3-3 Hz filter, the median frequency indicated a statistical difference between those term and pre-term delivery records recorded before the 26th week (p = 0.03), and between all term and all pre-term delivery records (p = 0.012). With the same filter, the sample entropy indicated statistical differences between those term and pre-term delivery records recorded before the 26th week (p = 0.035), and between all term and all pre-term delivery records (p = 0.011). Both techniques also showed noticeable differences between term delivery records recorded before and after the 26th week (p

Asunto(s)
Electromiografía/métodos , Trabajo de Parto Prematuro/diagnóstico , Procesamiento de Señales Asistido por Computador , Monitoreo Uterino/métodos , Femenino , Humanos , Miometrio/fisiopatología , Trabajo de Parto Prematuro/fisiopatología , Embarazo , Contracción Uterina
8.
Chirurg ; 78(9): 840-2, 2007 Sep.
Artículo en Alemán | MEDLINE | ID: mdl-17342350

RESUMEN

Perforation of the appendix through the anterior abdominal wall is a rare complication of a frequent disorder. We report on a 37-year old patient presenting with purulent secretion from the right lower abdomen. The CT scan of the abdomen revealed a perityphlitic abscess with perforation of the anterior abdominal wall. The patient underwent laparotomy with appendectomy and subsequent revision of the abdominal wall. Appendicocutaneous fistula due to perforation through the abdominal wall is a rarity. In analogy to empyema necessitatis, which would require the pleural empyema to penetrate the thoracic wall, the entity was denoted appendicitis necessitatis.


Asunto(s)
Absceso Abdominal/cirugía , Pared Abdominal/cirugía , Apendicitis/complicaciones , Apendicitis/cirugía , Absceso Abdominal/diagnóstico por imagen , Absceso Abdominal/etiología , Adulto , Apendicectomía , Fístula Cutánea/etiología , Fístula Cutánea/cirugía , Femenino , Estudios de Seguimiento , Humanos , Fístula Intestinal/etiología , Fístula Intestinal/cirugía , Laparotomía , Radiografía Abdominal , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Cicatrización de Heridas
9.
J Med Eng Technol ; 29(6): 288-96, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16287678

RESUMEN

The combined treatment of tumours in which delivery of a chemotherapeutic agent is followed by high voltage electroporation pulses has been termed electrochemotherapy. The electrochemotherapy of tumours located relatively close to the heart muscle can lead to fibrillation of the heart, especially if electroporation pulses are delivered in the vulnerable period of the heart or in coincidence with heart arrhythmias. We built an electroporation pulse delivery algorithm that enables safer use of electrochemotherapy. The algorithm is designed to deliver pulses outside the vulnerable period and to prevent pulses from being generated in the presence of heart arrhythmias. We evaluated the algorithm's performance using records of the Long-Term ST Database, thus simulating real-world conditions. The results of the evaluation, a sensitivity of 91.751%, a positive predictivity of 100.000% and a delivery error rate of 8.268% for electroporation pulse delivery (medians), suggest that the algorithm is accurate and appropriate for application in electrochemotherapy of tumours regardless of tumour location.


Asunto(s)
Antineoplásicos/administración & dosificación , Diagnóstico por Computador/métodos , Quimioterapia Asistida por Computador/métodos , Electrocardiografía/métodos , Electroporación/métodos , Síndrome de QT Prolongado/diagnóstico , Neoplasias/tratamiento farmacológico , Algoritmos , Antineoplásicos/efectos adversos , Sistemas de Liberación de Medicamentos/efectos adversos , Sistemas de Liberación de Medicamentos/métodos , Humanos , Neoplasias/complicaciones , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Fibrilación Ventricular/prevención & control
10.
Eur J Med Res ; 9(8): 383-90, 2004 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-15337628

RESUMEN

BACKGROUND AND OBJECTIVES: Topical glucocorticoids (GCs) are potent inhibitors of cellular inflammatory mediator production. Differences in receptor binding activities are believed to correlate with inhibition of mediator release and anti-inflammatory efficacy in vivo. To further assess this hypothesis we compared in cultured human monocytes the inhibitory activity of classic synthetic GCs on leukotriene B4 (LTB4), prostaglandin E2 (PGE2), interleukin 1 beta (IL-1beta) and c-phospholipase A 2 activity (cPLA2). METHODS: Normal human monocytes (10(5) /ml) were tested for 20 hrs with increasing concentrations (range 10(-12) -10(-5) M) of triamcinolone acetonide (TAA) compared to beclomethasone dipropionate (BDP), budesonide (BUD), dexamethasone (DEX), or the ethanol diluent together with 10 microg/ml of lipopolysaccharide (LPS). Mediator production and spontaneous cPLA subset 2-activity was determined by direct enzyme immunoassay methods. RESULTS: TAA at therapeutically relevant concentration (10(-8) M) inhibited significantly (p<0.01, n = 9) mediator production of TNF-alpha > IL-1beta > TxB2 > LTB subset 4 in a dose dependent manner by 75%, 65%, 41%, and 33%. IL-1beta inhibition at 10(-8) M by TAA (65%)> BDP (52%)> BUD (47%) was not different (ANOVA, p>0.2). Also spontaneous cPLA2-activity at 10(-8) M was inhibited to a similar degree (ANOVA, p> 0.6) by BUD (17.3%) > TAA (11.4%) > BDP (8.6%). In the same culture conditions spontaneous PGE2-secretion was inhibited by BDP (28.8%) > BUD (24.2%) > TAA (11.4%) with no significant effect for TAA. CONCLUSION: Clinically well established GCs have a similar inhibitory capacity on monocyte cytokine production and surprisingly only weak effects on AA-metabolism. Small receptor binding activity may account for the lack of cytokine inhibition by subtherapeutic (<10(-8) M) airway concentrations of TAA and BDP. Partial mediator inhibition by GCs at therapeutically known airway concentrations may be relevant to control bursts of airway inflammation during acute exacerbation but unfavourable to effectively delay progression of chronic airway inflammation.


Asunto(s)
Citocinas/antagonistas & inhibidores , Glucocorticoides/administración & dosificación , Glucocorticoides/farmacología , Fosfolipasas/antagonistas & inhibidores , Administración Cutánea , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacología , Ácido Araquidónico/metabolismo , Células Cultivadas , Citocinas/metabolismo , Relación Dosis-Respuesta a Droga , Humanos , Interleucina-1/antagonistas & inhibidores , Leucotrieno B4/metabolismo , Fosfolipasas/metabolismo , Prostaglandina-Endoperóxido Sintasas/metabolismo , Tromboxano B2/metabolismo , Triamcinolona Acetonida/farmacología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores
11.
Med Biol Eng Comput ; 42(3): 303-11, 2004 May.
Artículo en Inglés | MEDLINE | ID: mdl-15191074

RESUMEN

A novel automated system is presented for improved detection of transient ischaemic and heart rate-related ST-segment episodes in 'real-world' 24 h ambulatory ECG data. Using a combination of traditional time-domain and Karhunen-Loève transform-based approaches, the detector derives QRS complex and ST-segment morphology feature vectors and, by mimicking human examination of feature-vector time series and their trends, tracks the time-varying ST-segment reference level owing to clinically unimportant, non-ischaemic causes, such as slow drifts, axis shifts and conduction changes. The detector estimates the slowly varying ST-segment level trend, identifies step changes in the time series and subtracts the ST-segment reference level thus obtained from the ST-segment level to obtain the ST-segment deviation time series, which are suitable for detection of ST-segment episodes. The detector was developed using the Long-term ST database containing 24 h ambulatory ECG records with human-expert annotated transient ischaemic and heart rate-related ST-segment episodes. The average ST episode detection sensitivity/positive predictivity obtained when using the annotations of the annotation protocol B of the database were 78.9%/80.7%. Evaluation of the detector using the European Society of Cardiology ST-T database as a test database showed average ST episode detection sensitivity/positive predictivity of 81.3%/89.2%, which are better performances, comparable with those of the systems being developed using the European database.


Asunto(s)
Electrocardiografía Ambulatoria/métodos , Isquemia Miocárdica/diagnóstico , Procesamiento de Señales Asistido por Computador , Humanos , Sensibilidad y Especificidad , Procesamiento de Señales Asistido por Computador/instrumentación
12.
Surg Endosc ; 18(2): 314-8, 2004 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-14691713

RESUMEN

BACKGROUND: Patients who undergo unilateral adrenalectomy are known to benefit from the endoscopic procedure. Only a few reports on bilateral endoscopic adrenalectomy exist. The optimal approach and the value of this operation were assessed in this study. METHODS: For 18 patients, synchronous bilateral lateral adrenalectomy with intraoperative repositioning was performed for different indications. The transperitoneal and retroperitoneal approaches were varied on both sides. RESULTS: With the reported procedure, the operative time diminished considerably. Blood loss was low, and no blood transfusions were required. No conversion to an open procedure was necessary. There were no intraoperative or postoperative complications, except for one death from pulmonary embolism. The mean postoperative hospital stay was 7 days, and the follow-up evaluation showed overall improvement. CONCLUSION: The risk associated with endoscopic bilateral adrenalectomy is low. Transperitoneal and retroperitoneal lateral adrenalectomy are recommended as approaches of choice. The authors advocate early bilateral adrenalectomy for Cushing's disease after unsuccessful transsphenoidal operation and ectopic adrenocorticotropic hormone production from an inaccessible tumour.


Asunto(s)
Adrenalectomía/métodos , Endoscopía/métodos , Síndrome de ACTH Ectópico/complicaciones , Adenoma/complicaciones , Adenoma/patología , Adenoma/cirugía , Neoplasias de las Glándulas Suprarrenales/complicaciones , Neoplasias de las Glándulas Suprarrenales/patología , Neoplasias de las Glándulas Suprarrenales/cirugía , Adulto , Síndrome de Cushing/etiología , Síndrome de Cushing/patología , Síndrome de Cushing/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasia Endocrina Múltiple Tipo 2a/cirugía , Feocromocitoma/patología , Feocromocitoma/cirugía , Neoplasias Hipofisarias/complicaciones , Complicaciones Posoperatorias , Embolia Pulmonar/etiología , Resultado del Tratamiento
13.
Med Biol Eng Comput ; 41(2): 172-82, 2003 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-12691437

RESUMEN

The long-term ST database is the result of a multinational research effort. The goal was to develop a challenging and realistic research resource for development and evaluation of automated systems to detect transient ST segment changes in electrocardiograms and for supporting basic research into the mechanisms and dynamics of transient myocardial ischaemia. Twenty-four hour ambulatory ECG records were selected from routine clinical practice settings in the USA and Europe, between 1994 and 2000, on the basis of occurrence of ischaemic and non-ischaemic ST segment changes. Human expert annotators used newly developed annotation protocols and a specially developed interactive graphic editor tool (SEMIA) that supported paperless editing of annotations and facilitated international co-operation via the Internet. The database contains 86 two- and three-channel 24 h annotated ambulatory records from 80 patients and is stored on DVD-ROMs. The database annotation files contain ST segment annotations of transient ischaemic (1155) and heart-rate related ST episodes and annotations of non-ischaemic ST segment events related to postural changes and conduction abnormalities. The database is intended to complement the European Society of Cardiology ST-T database and the MIT-BIH and AHA arrhythmia databases. It provides a comprehensive representation of 'real-world' data, with numerous examples of transient ischaemic and non-ischaemic ST segment changes, arrhythmias, conduction abnormalities, axis shifts, noise and artifacts.


Asunto(s)
Bases de Datos Factuales , Electrocardiografía Ambulatoria , Isquemia Miocárdica/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Europa (Continente) , Femenino , Humanos , Cooperación Internacional , Masculino , Persona de Mediana Edad , Estados Unidos
14.
Am J Med Genet ; 85(3): 216-20, 1999 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-10398231

RESUMEN

A family is described in which X-linked mild to borderline mental retardation (MR) is associated with cleft lip/palate. Linkage analysis showed a maximum LOD score of Z=2.78 at straight theta=0.0 for the DXS441 locus with flanking markers DXS337 and DXS990, defining the region Xp11.3-q21.3 with a linkage interval of 25 cM.


Asunto(s)
Labio Leporino/complicaciones , Fisura del Paladar/complicaciones , Discapacidad Intelectual/genética , Cromosoma X/genética , Mapeo Cromosómico , ADN/genética , Salud de la Familia , Femenino , Ligamiento Genético , Humanos , Discapacidad Intelectual/complicaciones , Escala de Lod , Masculino , Repeticiones de Microsatélite , Linaje
15.
Comput Biomed Res ; 31(5): 305-22, 1998 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-9790738

RESUMEN

Using the European Society of Cardiology ST-T Database, we have developed a Karhunen-Loève transform-based algorithm for robust automated detection of transient ST segment episodes during ambulatory ECG monitoring. We review current approaches and systems to detect transient ST segment changes and describe the architecture of our algorithm and its development. The algorithm incorporates a single-scan trajectory-recognition technique in feature space using the Mahalanobis distance function between the feature vectors. The main characteristics of the algorithm are detection of noisy beats, correction of the reference ST segment level to correct for slow ST level drift, detection of sudden significant shifts of ST deviation due to shifts of the mean electrical axis of the heart, detection of transient ST episodes, and, by tracking the QRS complex morphology, differentiation between ischemic and nonischemic ST episodes as a result of axis shifts. We compared the algorithm's performance to other recently developed algorithms and estimated its real-world performance.


Asunto(s)
Algoritmos , Enfermedad Coronaria/diagnóstico , Diagnóstico por Computador , Electrocardiografía Ambulatoria/métodos , Enfermedad Coronaria/fisiopatología , Electrocardiografía Ambulatoria/estadística & datos numéricos , Humanos , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/fisiopatología , Diseño de Software
17.
J Med Eng Technol ; 22(1): 25-30, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-9491355

RESUMEN

This paper proposes principles and methods for assessing performance of ST analysers and algorithms. We describe an evaluation protocol and performance measures suitable for assessing the accuracy of: (1) detecting episodes of ischaemic ST changes, (2) distinguishing between ischaemic and non-ischaemic ST change episodes, and (3) measuring ST deviation and ischaemia duration. There is generally not a one-to-one correspondence between reference and analyser-annotated ST episodes, nor can non-events be counted. Sensitivity and positive predictivity measures which assess the accuracy of detecting ischaemic ST episodes and total ischaemic time are based on the concepts of matching and overlap, respectively. To address the question of predicting performance in a clinical environment, we have utilized the bootstrap statistical procedure, which estimates the mean as well as the standard deviation of the analyser's expected performance. We illustrate the use of the evaluation protocol and performance measures by a case study in which we present an evaluation of our 2-channel Karhunen-Loève transform based ST change detection algorithm using the European Society of Cardiology ST-T database.


Asunto(s)
Electrocardiografía , Isquemia Miocárdica/diagnóstico , Procesamiento de Señales Asistido por Computador , Algoritmos , Bases de Datos como Asunto , Electrocardiografía/estadística & datos numéricos , Estudios de Evaluación como Asunto , Predicción , Humanos , Isquemia Miocárdica/fisiopatología , Reconocimiento de Normas Patrones Automatizadas , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Factores de Tiempo
18.
Biophys J ; 74(3): 1492-501, 1998 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-9512045

RESUMEN

The vibrational spectrum (650-1750 cm(-1)) of the lumi-rhodopsin (lumi) intermediate formed in the microsecond time regime of the room-temperature rhodopsin (RhRT) photoreaction is measured for the first time using picosecond time-resolved coherent anti-Stokes Raman spectroscopy (PTR/CARS). The vibrational spectrum of lumi is recorded 2.5 micros after the 3-ps, 500-nm excitation of RhRT. Complementary to Fourier transform infrared spectra recorded at Rh sample temperatures low enough to freeze lumi, these PTR/CARS results provide the first detailed view of the vibrational degrees of freedom of room-temperature lumi (lumiRT) through the identification of 21 bands. The exceptionally low intensity (compared to those observed in bathoRT) of the hydrogen out-of-plane (HOOP) bands, the moderate intensity and absolute positions of C-C stretching bands, and the presence of high-intensity C==C stretching bands suggest that lumiRT contains an almost planar (nontwisting), all-trans retinal geometry. Independently, the 944-cm(-1) position of the most intense HOOP band implies that a resonance coupling exists between the out-of-plane retinal vibrations and at least one group among the amino acids comprising the retinal binding pocket. The formation of lumiRT, monitored via PTR/CARS spectra recorded on the nanosecond time scale, can be associated with the decay of the blue-shifted intermediate (BSI(RT)) formed in equilibrium with the bathoRT intermediate. PTR/CARS spectra measured at a 210-ns delay contain distinct vibrational features attributable to BSI(RT), which suggest that the all-trans retinal in both BSI(RT) and lumiRT is strongly coupled to part of the retinal binding pocket. With regard to the energy storage/transduction mechanism in RhRT, these results support the hypothesis that during the formation of lumiRT, the majority of the photon energy absorbed by RhRT transfers to the apoprotein opsin.


Asunto(s)
Rodopsina/química , Rodopsina/metabolismo , Animales , Bovinos , Diseño de Equipo , Rodopsina/análogos & derivados , Rodopsina/efectos de la radiación , Segmento Externo de la Célula en Bastón/metabolismo , Espectrometría Raman/instrumentación , Espectrometría Raman/métodos , Termodinámica , Vibración
19.
Biophys J ; 72(5): 2329-41, 1997 May.
Artículo en Inglés | MEDLINE | ID: mdl-9129836

RESUMEN

Time-resolved vibrational spectra are used to elucidate the structural changes in the retinal chromophore within the K-590 intermediate that precedes the formation of the L-550 intermediate in the room-temperature (RT) bacteriorhodopsin (BR) photocycle. Measured by picosecond time-resolved coherent anti-Stokes Raman scattering (PTR/CARS), these vibrational data are recorded within the 750 cm-1 to 1720 cm-1 spectral region and with time delays of 50-260 ns after the RT/BR photocycle is optically initiated by pulsed (< 3 ps, 1.75 nJ) excitation. Although K-590 remains structurally unchanged throughout the 50-ps to 1-ns time interval, distinct structural changes do appear over the 1-ns to 260-ns period. Specifically, comparisons of the 50-ps PTR/CARS spectra with those recorded with time delays of 1 ns to 260 ns reveal 1) three types of changes in the hydrogen-out-of-plane (HOOP) region: the appearance of a strong, new feature at 984 cm-1; intensity decreases for the bands at 957 cm-1, 952 cm-1, and 939 cm-1; and small changes intensity and/or frequency of bands at 855 cm-1 and 805 cm-1; and 2) two types of changes in the C-C stretching region: the intensity increase in the band at 1196 cm-1 and small intensity changes and/or frequency shifts for bands at 1300 cm-1 and 1362 cm-1. No changes are observed in the C = C stretching region, and no bands assignable to the Schiff base stretching mode (C = NH+) mode are found in any of the PTR/CARS spectra assignable to K-590. These PTR/CARS data are used, together with vibrational mode assignments derived from previous work, to characterize the retinal structural changes in K-590 as it evolves from its 3.5-ps formation (ps/K-590) through the nanosecond time regime (ns/K-590) that precedes the formation of L-550. The PTR/CARS data suggest that changes in the torsional modes near the C14-C15 = N bonds are directly associated with the appearance of ns/K-590, and perhaps with the KL intermediate proposed in earlier studies. These vibrational data can be primarily interpreted in terms of the degree of twisting of the C14-C15 retinal bond. Such twisting may be accompanied by changes in the adjacent protein. Other smaller, but nonetheless clear, spectral changes indicate that alterations along the retinal polyene chain also occur. The changes in the retinal structure are preliminary to the deprotonation of the Schiff base nitrogen during the formation of M-412. The time constant for the ps/ns K-590 transformation is estimated from the amplitude change of four vibrational bands in the HOOP region to be 40-70 ns.


Asunto(s)
Bacteriorodopsinas/química , Pigmentos Retinianos/química , Halobacterium , Modelos Teóricos , Bases de Schiff , Espectrometría Raman , Temperatura
20.
Biochemistry ; 33(36): 10878-82, 1994 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-7916209

RESUMEN

In order to investigate the molecular mechanism of rhodopsin photoactivation, site-directed mutants of bovine rhodopsin were studied by Fourier-transform infrared (FTIR) difference spectroscopy. Rhodopsin mutants E113D and E113A were prepared in which the retinylidene Schiff base counterion, Glu113, was replaced by Asp and Ala, respectively. FTIR difference spectra were recorded and compared with spectra of recombinant native rhodopsin. Both mutant pigments formed photoproducts at 0 degrees C with vibrational absorption bands typical of the metarhodopsin II (MII) state of rhodopsin. The FTIR difference spectrum of E113D was nearly identical to that of rhodopsin. A positive band at 1712 cm-1 caused by the protonation of an internal carboxylic acid in rhodopsin was shifted slightly to 1709 cm-1 in mutant E113D. E113A was studied at acidic pH in the presence of chloride as an inorganic counterion to the protonated Schiff base. The 1712-cm-1 (1709-cm-1) band was absent in the FTIR difference spectrum of mutant E113A. Therefore, we have assigned the 1712-cm-1 absorbance band to the C = O stretching vibration of protonated Glu113 in MII of rhodopsin. These results show that the Schiff base counterion of rhodopsin, the carboxylate side chain of Glu113, becomes protonated during MII formation.


Asunto(s)
Glutamatos/química , Rodopsina/análogos & derivados , Rodopsina/química , Bases de Schiff/química , Animales , Bovinos , Ácido Glutámico , Mutagénesis Sitio-Dirigida , Fotoquímica , Protones , Espectroscopía Infrarroja por Transformada de Fourier
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