Performance of gene-expression profiling test score variability to predict future clinical events in heart transplant recipients.

BACKGROUND A single non-invasive gene expression profiling (GEP) test (AlloMap®) is often used to discriminate if a heart transplant recipient is at a low risk of acute cellular rejection at time of testing. In a randomized trial, use of the test (a GEP score from 0-40) has been shown to be non-inferior to a routine endomyocardial biopsy for surveillance after heart transplantation in selected low-risk patients with respect to clinical outcomes. Recently, it was suggested that the within-patient variability of consecutive GEP scores may be used to independently predict future clinical events; however, future studies were recommended. Here we performed an analysis of an independent patient population to determine the prognostic utility of within-patient variability of GEP scores in predicting future clinical events. METHODS We defined the GEP score variability as the standard deviation of four GEP scores collected ≥315 days post-transplantation. Of the 737 patients from the Cardiac Allograft Rejection Gene Expression Observational (CARGO) II trial, 36 were assigned to the composite event group (death, re-transplantation or graft failure ≥315 days post-transplantation and within 3 years of the final GEP test) and 55 were assigned to the control group (non-event patients). In this case-controlled study, the performance of GEP score variability to predict future events was evaluated by the area under the receiver operator characteristics curve (AUC ROC). The negative predictive values (NPV) and positive predictive values (PPV) including 95 % confidence intervals (CI) of GEP score variability were calculated. RESULTS The estimated prevalence of events was 17 %. Events occurred at a median of 391 (inter-quartile range 376) days after the final GEP test. The GEP variability AUC ROC for the prediction of a composite event was 0.72 (95 % CI 0.6-0.8). The NPV for GEP score variability of 0.6 was 97 % (95 % CI 91.4-100.0); the PPV for GEP score variability of 1.5 was 35.4 % (95 % CI 13.5-75.8). CONCLUSION In heart transplant recipients, a GEP score variability may be used to predict the probability that a composite event will occur within 3 years after the last GEP score. TRIAL REGISTRATION Clinicaltrials.gov identifier NCT00761787.

El Test de Ramsey y las lógicas condicionales

Frank Ramsey (1931) estableció ciertas condiciones que deberían cumplirse a fin de evaluar las proposiciones condicionales, conocidas hoy como Test de Ramsey (TR) En este trabajo se muestra que las teorías sobre condicionales contrafácticos de Chisholmj, Stalnaker y D. Lewis, satisfacen el TR y la incompatibilidad de TR con la Teoría de la revisión de creencias (AGM). En la última sección se analiza el comportamiento del TR en la propuesta de G. Grocco y L. Fariñas del Cerro, basada en una generalización del cálculo de Secuentes pero introduciendo la novedad de secuencias auxiliares cuya noción de consecuencia es no-monótona.

El Test de Ramsey y las lógicas condicionales

Frank Ramsey (1931) estableció ciertas condiciones que deberían cumplirse a fin de evaluar las proposiciones condicionales, conocidas hoy como Test de Ramsey (TR) En este trabajo se muestra que las teorías sobre condicionales contrafácticos de Chisholmj, Stalnaker y D. Lewis, satisfacen el TR y la incompatibilidad de TR con la Teoría de la revisión de creencias (AGM). En la última sección se analiza el comportamiento del TR en la propuesta de G. Grocco y L. Fariñas del Cerro, basada en una generalización del cálculo de Secuentes pero introduciendo la novedad de secuencias auxiliares cuya noción de consecuencia es no-monótona.

El Test de Ramsey y las lógicas condicionales

Frank Ramsey (1931) estableció ciertas condiciones que deberían cumplirse a fin de evaluar las proposiciones condicionales, conocidas hoy como Test de Ramsey (TR) En este trabajo se muestra que las teorías sobre condicionales contrafácticos de Chisholmj, Stalnaker y D. Lewis, satisfacen el TR y la incompatibilidad de TR con la Teoría de la revisión de creencias (AGM). En la última sección se analiza el comportamiento del TR en la propuesta de G. Grocco y L. Fariñas del Cerro, basada en una generalización del cálculo de Secuentes pero introduciendo la novedad de secuencias auxiliares cuya noción de consecuencia es no-monótona.

Stable oxygen and carbon isotope ratios of foraminifera and test results after different sample cleaning procedures from ODP Leg 207 sediments

We report oxygen and carbon stable isotope analyses of foraminifers, primarily planktonic, sampled at low resolution in the Cretaceous and Paleogene sections from Sites 1257, 1258, and 1260. Data from two samples from Site 1259 are also reported. The very low resolution of the data only allows us to detect climate-driven isotopic events on the timescale of more than 500 k.y. A several million-year-long interval of overall increase in planktonic 18O is seen in the Cenomanian at Site 1260. Before and after this interval, foraminifers from Cenomanian and Turonian black shales have d18O values in the range -4.2 per mil to -5.0 per mil, suggestive of upper ocean temperatures higher than modern tropical values. The d18O values of upper ocean dwelling Paleogene planktonics exhibit a long-term increase from the early Eocene to the middle Eocene. During shipboard and postcruise processing, it proved difficult to extract well-preserved foraminifer tests from black shales by conventional techniques. Here, we report results of a test of procedures for cleaning foraminifers in Cretaceous organic-rich mudstone sediments using various combinations of soaking in bleach, Calgon/hydrogen peroxide, or Cascade, accompanied by drying, repeat soaking, or sonication. A procedure that used 100% bleach, no detergent, and no sonication yielded the largest number of clean, whole individual foraminifers with the shortest preparation time. We found no significant difference in d18O or d13C values among sets of multiple samples of the planktonic foraminifer Whiteinella baltica extracted following each cleaning procedure.

Planktic foraminiferal sieve size specific d13C and d18O values and maximum test diameter from ODP sites 171-1051 and 120-748

Many genera of modern planktic foraminifera are adapted to nutrient-poor (oligotrophic) surface waters by hosting photosynthetic symbionts, but it is unknown how they will respond to future changes in ocean temperature and acidity. Here we show that ca. 40 Ma, some fossil photosymbiont-bearing planktic foraminifera were temporarily 'bleached' of their symbionts coincident with transient global warming during the Middle Eocene Climatic Optimum (MECO). At Ocean Drilling Program (ODP) Sites 748 and 1051 (Southern Ocean and mid-latitude North Atlantic, respectively), the typically positive relationship between the size of photosymbiont-bearing planktic foraminifer tests and their carbon isotope ratios (d13C) was temporarily reduced for ~100 k.y. during the peak of the MECO. At the same time, the typically photosymbiont-bearing planktic foraminifera Acarinina suffered transient reductions in test size and relative abundance, indicating ecological stress. The coincidence of minimum d18O values and reduction in test size-d13C gradients suggests a link between increased sea-surface temperatures and bleaching during the MECO, although changes in pH and nutrient availability may also have played a role. Our findings show that host-photosymbiont interactions are not constant through geological time, with implications for both the evolution of trophic strategies in marine plankton and the reliability of geochemical proxy records generated from symbiont-bearing planktic foraminifera.

Stable carbon and oxygen isotope ratios for different test sizes of live benthic foraminifera from the Arabian Sea

We determined the stable oxygen and carbon isotopic composition of live (Rose Bengal stained) tests belonging to different size classes of two benthic foraminiferal species from the Pakistan continental margin. Samples were taken at 2 sites, with water depth of about 135 and 275 m, corresponding to the upper boundary and upper part of the core region of the oxygen minimum zone (OMZ). For Uvigerina ex gr. U. semiornata and Bolivina aff. B. dilatata, delta13C and delta18O values increased significantly with increasing test size. In the case of U. ex gr. U. semiornata, delta13C increased linearly by about 0.105 per mil for each 100-µm increment in test size, whereas delta18O increased by 0.02 to 0.06 per mil per 100 µm increment. For B. aff. B. dilatata the relationship between test size and stable isotopic composition is better described by logarithmic equations. A strong positive linear correlation is observed between delta18O and delta13C values of both taxa, with a constant ratio of delta18O and delta13C values close to 2:1. This suggests that the strong ontogenetic effect is mainly caused by kinetic isotope fractionation during CO2 uptake. Our data underline the necessity to base longer delta18O and delta13C isotope records derived from benthic foraminifera on size windows of 100 µm or less. This is already common practice in down-core isotopic studies of planktonic foraminifera.

Planktic foraminiferal populations and test flux in the eastern North Atlantic Ocean

Planktic foraminiferal assemblages vary in response to seasonal fluctuations of hydrographic properties, between water masses, and after periodical changes and episodic events (e.g. reproduction, storms). Distinct annual variability of the planktic foraminiferal flux is also known from sediment trap data. In this paper we discuss the short-term impacts on interannual flux rates based on data from opening-closing net hauls obtained between the ocean surface and 500 m water depth. Data were recorded during April, May, June, and August at around 47°N, 20°W (BIOTRANS) in 1988, 1989, 1990, 1992, 1993, and during May 1989 and 1992 at 57°N, 20-22°W. Species assemblages closely resemble each other when comparing the mixed layer fauna with the fauna of the upper 100 m and the upper 500 m of the water column. In addition, species assemblages >100 µm are almost indistinguishable from assemblages that are >125 µm in test size. The standing stock of planktic foraminifers at BIOTRANS can vary by more than one order of magnitude over different years; however, species assemblages may be similar when comparing corresponding seasons. Early summer assemblages (June) are distinctly different from late summer assemblages (August). Significant variations in the species composition during spring (April/May) are independent of the mixed layer depth. Spring assemblages are characterized by high numbers of Globigerinita glutinata. In particular, day-to-day variations of the number of specimens and in species composition may have the same order of magnitude as interannual variations. This appears to be independent of the reproduction cycle. Species assemblages at 47°N and 57°N are similar during spring, although surface water temperatures and salinities differ by up to 10°C and 0.7 (PSU). We suggest that the main factors controlling the planktic foraminiferal fauna are the trophic properties in the upper ocean productive layer. Planktic foraminiferal carbonate flux as calculated from assemblages reveals large seasonal variations, a quasi-annual periodicity in flux levels, and substantial differences in timing and magnitude of peak fluxes. At the BIOTRANS station, the average annual planktic foraminiferal CaCO3 fluxes at 100 and 500 m depth are estimated to be 22.4 and 10.0 g/m**2/yr, respectively.

A new device for 100 per cent humidification of inspired air

A new humidifier for use during mechanical ventilation in endotracheally intubated patients is described and tested. The humidifier is based on a heat-moisture exchanger, which absorbs the expired heat and moisture and releases it into the inspired air. External heat and water are then added at the patient side of the heat-moisture exchanger, so that the inspired gas should reach 100% humidity (44 mg/l) at 37°C. In bench tests using constant and decelerating inspiratory flow and minute volumes of 3–25 l the device gave an absolute humidity of 41–44 mg/l, and it reduced the amount of water consumed in eight mechanically ventilated patients compared with a conventional active humidifier. During a 24-h test period there was no water condensation in the ventilator tubing with the new device.

Valutazione del Beta Carba test per il rapido rilevamento di enterobatteri produttori di carbapenemasi (CPE)

L’antibiotico resistenza negli enterobatteri produttori di carbapenemasi (CPE) rappresenta una problematica emergente in sanità pubblica, dato che le opzioni alternative per il trattamento di pazienti infetti sono limitate. L’andamento epidemiologico di CPE a livello globale appare ad oggi molto variegato con differenze significative tra paesi. In Italia la diffusione di K. pneumoniae produttrice di KPC è endemica ed è stimata essere un terzo (32,9%) delle infezioni invasive (sangue e liquor) da K. pneumoniae. Pertanto, diventa indispensabile implementare gli studi di farmaco-resistenza per valutare e ridurre il potenziale di crescita di tali microrganismi. Questo studio presenta come fine la valutazione del Beta Carba test, metodo cromogeno, per il rapido rilevamento di CPE in confronto con il metodo standard di riferimento. Lo studio è stato svolto presso l’U.O. Microbiologia AUSL della Romagna ed è di natura retrospettiva, di tipo esclusivamente qualitativo. Sono stati analizzati 412 campioni completamente anonimizzati: 50 emocolture, 250 urine e 112 tamponi rettali di sorveglianza. La valutazione del test è stata condotta sia direttamente a partire dalle matrici biologiche (emocolture e urinocolture positive) che dalle colonie isolate di CPE da tamponi rettali di sorveglianza, urine o emocolture. I risultati sperimentali ottenuti in vitro con il β Carba, mostrano una totale concordanza con i metodi sia fenotipici che genotipici utilizzati come riferimento: sono state ottenute sensibilità e specificità del 100%. Inoltre, a favore del test si inserisce il parametro fondamentale della rapidità, consentendo quindi una celere rilevazione di CPE direttamente su campioni clinici con un tempo di risposta piuttosto veloce e affidabile pari a 15-30 minuti. In definitiva, grazie alla performance dimostrata in vitro, il test può rappresentare un valido strumento per arginare e limitare lo spreading di CPE, svolgendo un buon ruolo nella gestione dei pazienti infetti.

Do nations' mental health policies, programs and legislation influence their suicide rates? An ecological study of 100 countries

Objective: To test the hypothesis that the presence of national mental health policies, programs and legislation would be associated with lower national suicide rates. Method: Suicide rates from 100 countries were regressed on mental health policy, program and legislation indicators. Results: Contrary to the hypothesized relationship, the study found that after introducing mental health initiatives (with the exception of substance abuse policies), countries' suicide rates rose. Conclusion: It is of concern that most mental health initiatives are associated with an increase in suicide rates. However, there may be acceptable reasons for the observed findings, for example initiatives may have been introduced in areas of increasing need, or a case-finding effect may be operating. Data limitations must also be considered.

The macular mapping test:a reliability study

Background: Age-related macular degeneration (ARMD) is the leading cause of visual disability in people over 60 years of age in the developed world. The success of treatment deteriorates with increased latency of diagnosis. The purpose of this study was to determine the reliability of the macular mapping test (MMT), and to investigate its potential as a screening tool. Methods: The study population comprised of 31 healthy eyes of 31 participants. To assess reliability, four macular mapping test (MMT) measurements were taken in two sessions separated by one hour by two practitioners, with reversal of order in the second session. MMT readings were also taken from 17 age-related maculopathy (ARM), and 12 AMD affected eyes. Results: For the normal cohort, average MMT scores ranged from 85.5 to 100.0 MMT points. Scores ranged from 79.0 to 99.0 for the ARM group and from 9.0 to 92.0 for the AMD group. MMT scores were reliable to within ± 7.0 points. The difference between AMD affected eyes and controls (z = 3.761, p = < 0.001) was significant. The difference between ARM affected eyes and controls was not significant (z = -0.216, p = 0.829). Conclusion: The reliability data shows that a change of 14 points or more is required to indicate a clinically significant change. This value is required for use of the MMT as an outcome measure in clinical trials. Although there was no difference between MMT scores from ARM affected eyes and controls, the MMT has the advantage over the Amsler grid in that it uses a letter target, has a peripheral fixation aid, and it provides a numerical score. This score could be beneficial in office and home monitoring of AMD progression, as well as an outcome measure in clinical research. © 2005 Bartlett et al; licensee BioMed Central Ltd.

Clinical evaluation of a novel test strip technology for blood glucose monitoring:accuracy at hypoglycaemic glucose levels

Aim: To evaluate OneTouch® Verio™ test strip performance at hypoglycaemic blood glucose (BG) levels (<3.9mmol/L [<70mg/dL]) at seven clinical studies. Methods: Trained clinical staff performed duplicate capillary BG monitoring system tests on 700 individuals with type 1 and type 2 diabetes using blood from a single fingerstick lancing. BG reference values were obtained using a YSI 2300 STAT™ Glucose Analyzer. The number and percentage of BG values within ±0.83. mmol/L (±15. mg/dL) and ±0.56. mmol/L (±10. mg/dL) were calculated at BG concentrations of <3.9. mmol/L (<70. mg/dL), <3.3. mmol/L (<60. mg/dL), and <2.8. mmol/L (<50. mg/dL). Results: At BG concentrations <3.9. mmol/L (<70. mg/dL), 674/674 (100%) of meter results were within ±0.83. mmol/L (±15. mg/dL) and 666/674 (98.8%) were within ±0.56. mmol/L (±10. mg/dL) of reference values. At BG concentrations <3.3. mmol/L (<60. mg/dL), and <2.8. mmol/L (<50. mg/dL), 358/358 (100%) and 270/270 (100%) were within ±0.56. mmol/L (±10. mg/dL) of reference values, respectively. Conclusion: In this analysis of data from seven independent studies, OneTouch Verio test strips provide highly accurate results at hypoglycaemic BG levels. © 2012 Elsevier Ireland Ltd.

Valoración del Test de Alvarado en el diagnóstico dudoso de la apendicitis aguda. Hospital Vicente Corral Moscoso y José Carrasco Arteaga. Cuenca, octubre del 2002 a abril 2003

Se aplica el test de Alvarado a 100 pacientes mayores de 10 años que acuden a la emergencia de los hospitales José Carraasco Arteaga (IESS)Y VICENTE CORRAL MOSCOSO (HVCM) de esta ciudad, con síntomas sugerentes de apendicitis y con una evolución menor de 24 horas, sin haber ingerido un analgésico por lo menos 8 horas antes. La mayor incidencia de intervenciones quirúrgicas por apendicitis aguda (A.A.) estuvo entre los 16 y 15 años de edad, en el sexo femenino. Según el estudio en el test de AAlvardo el síntoma más significativo es el dolor en fosa iliíaca derecha (99), seguido del dolor al descomprimir 89, recuernto leucocitario mayor de 10mil/mm3 (82). El test tiene una alta sensibilidad (85.71, pero especificidad baja 44.4, con un valor predictivo positivo 93.9. Al tomar en cuenta los resultados de los exámenes anatomopatológicos, se encuentra un mayor porcentaje en la A.A. precoz 64, A.A supurativa 15, A.A perforada 8y apéndice normal 9lo que permite considerar: El test de Alvarado en el diagnóstico de apendicitis aguda tiene capacidad de decidir si el paciente se mantiene en observación o se raliza una intervención quirúrgica por lo que dbería ser usado en forma sistemática; la posibilidad de encontrar un apéndice sano es mayor mientras menor es el puntaje del test de Alvarado; la apendicitis aguda debe ser tratada por medios quirúrgicos, los esfuerzos diagnósticos dberán dirigirse particularmente a las mujeres, en las cuales el diagnóstico diferencial es más amplio, sobre todo las enfermedades ginecológicas; se sugiere cambiar el valor de la escala a 13 puntos, porque los signos más significativos son: dolor a la palpación en fosa ilíaca derecha y dolor al descomprimir, para mejorar la calidad del test en el diagnóstico oportuno de la apendicitis aguda