JWST detection of a supernova associated with GRB 221009A without an r-process signature.

Identifying the sites of r-process nucleosynthesis, a primary mechanism of heavy element production, is a key goal of astrophysics. The discovery of the brightest gamma-ray burst (GRB) to date, GRB 221009A, presented an opportunity to spectroscopically test the idea that r-process elements are produced following the collapse of rapidly rotating massive stars. Here we present James Webb Space Telescope observations of GRB 221009A obtained +168 and +170 rest-frame days after the gamma-ray trigger, and demonstrate that they are well described by a SN 1998bw-like supernova (SN) and power-law afterglow, with no evidence for a component from r-process emission. The SN, with a nickel mass of approximately 0.09 M ⊙, is only slightly fainter than the brightness of SN 1998bw at this phase, which indicates that the SN is not an unusual GRB-SN. This demonstrates that the GRB and SN mechanisms are decoupled and that highly energetic GRBs are not likely to produce significant quantities of r-process material, which leaves open the question of whether explosions of massive stars are key sources of r-process elements. Moreover, the host galaxy of GRB 221009A has a very low metallicity of approximately 0.12 Z ⊙ and strong H2 emission at the explosion site, which is consistent with recent star formation, hinting that environmental factors are responsible for its extreme energetics.

Dopamine D1 and D5 receptors differentially regulate oxidative stress through paraoxonase 2 in kidney cells.

BACKGROUND: The renal dopaminergic system plays an important role in the pathogenesis of hypertension. Dopamine D1-like receptors (D1R and D5R) decrease reactive oxygen species (ROS) production via inhibition of pro-oxidant enzymes such as NADPH oxidase. Paraoxonase 2 (PON2) is also involved in the inhibition of NADPH oxidase activity. Therefore, we tested the hypothesis that D1R and D5R inhibit ROS production by increasing the expression of PON2, including those in membrane microdomains. METHODS AND RESULTS: PON2 colocalized with D1R and D5R in mouse renal proximal tubules (RPTs), human RPT (hRPT) cells, and HEK293 cells heterologously expressing human D1R (HEK-hD1R) or D5R (HEK-hD5R). Fenoldopam, an agonist for both D1R and D5R, increased PON2 co-immunoprecipitation with D1R and D5R in HEK-hD1R and HEK-hD5R cells, respectively. Silencing PON2 increased ROS production and NADPH oxidase activity, and impaired the inhibitory effect of fenoldopam. Fenoldopam increased PON2 protein in both lipid rafts (LRs) and non-LRs in HEK-hD1R cells, but only in non-LRs in HEK-hD5R and hRPT cells. Long-term (hrs) fenoldopam stimulation increased PON2 protein in a time-dependent manner in HEK-hD5R, but not in HEK-hD1R cells. Because the effects of fenoldopam on non-LR and total PON2 expressions were similar in HEK-hD5R and hRPT cells, additional studies were performed to determine the relationship between D5R and PON2. Renal PON2 protein was decreased in D5(-/-) mice. In hRPT cells, silencing D5R decreased PON2 expression and increased ROS production. CONCLUSIONS: We conclude that D1-like receptors inhibit ROS production by altering PON2 distribution in membrane microdomains in the short-term, and by increasing PON2 expression in the long-term.

Role of health-related quality of life measurements in the design of drug clinical trials.

OBJECTIVE: Health-related quality of life (HRQL) measurements enable us to take patient perception into account when evaluating treatment outcomes from clinical trials (CTs). The purpose of this study was to evaluate the use of HRQL questionnaires as a measurement of efficacy in CT design. METHODS: A duplicate systematic review of the CTs examined by a Clinical Research Ethics Committee between 1995 and 2006 was performed to check for use of HRQL. We gathered data concerning general aspects including medical specialty, drugs evaluated, methodological quality and inclusion of economic variables. For CTs including HRQL measurements, we analysed the type of questionnaire in use. Where there were no HRQL measurements, we analysed the methodological possibilities for including them, and the relevance of their absence. RESULTS: A total of 242 CTs were analysed; 69 (28.5%) included HRQL measurements, and 10 CTs (4.1%) used them as a primary endpoint. Only 22 CTs used more than one questionnaire. Data analysis by therapeutic area showed that HRQL was most commonly studied in the fields of rheumatology, urology, psychiatry and oncology. Only 33 CTs included economic variables. CONCLUSIONS: Measurements based on clinical parameters are the most commonly used means of measuring efficacy. Only a small percentage of CTs take the patient's perception of his/her health into account, despite the increasing importance given to this parameter. Including HRQL questionnaires in CTs design is still far from common.

Role of “health-related quality of life” measurements in the design of drug clinical trials

Objective Health-related quality of life (HRQL) measurements enable us to take patient perception into account when evaluating treatment outcomes from clinical trials (CTs). The purpose of this study was to evaluate the use of HRQL questionnaires as a measurement of efficacy in CT design. Methods A duplicate systematic review of the CTs examined by a Clinical Research Ethics Committee between 1995 and 2006 was performed to check for use of HRQL. We gathered data concerning general aspects including medical specialty, drugs evaluated, methodological quality and inclusion of economic variables. For CTs including HRQL measurements, we analysed the type of questionnaire in use. Where there were no HRQL measurements, we analysed the methodological possibilities for including them, and the relevance of their absence. Results A total of 242 CTs were analysed; 69 (28.5%) included HRQL measurements, and 10 CTs (4.1%) used them as a primary endpoint. Only 22 CTs used more than one questionnaire. Data analysis by therapeutic area showed that HRQL was most commonly studied in the fields of rheumatology, urology, psychiatry and oncology. Only 33 CTs included economic variables. Conclusions Measurements based on clinical parameters are the most commonly used means of measuring efficacy. Only a small percentage of CTs take the patient's perception of his/her health into account, despite the increasing importance given to this parameter. Including HRQL questionnaires in CTs design is still far from common (AU)

Objetivo Las medidas de “calidad de vida relacionada con la salud” (CVRS) permiten incorporar la percepción del paciente en la evaluación de los resultados obtenidos en los ensayos clínicos (EC). El objetivo de este estudio fue evaluar el uso de cuestionarios de CVRS como medida de eficacia en el diseño de ECs. Métodos Se lleva a cabo una revisión sistemática por duplicado de los ECs analizados por un Comité Ético de Investigación Clínica, entre los años 1995 y 2006. Se recogieron datos relativos a aspectos generales como la especialidad médica, fármacos evaluados, calidad metodológica o inclusión de variables económicas. Para aquellos ECs que incluían medidas de CVRS, se analizó el tipo de cuestionario utilizado. Para aquellos que no analizaban CVRS, se analizó la posibilidad metodológica de su análisis, así como la relevancia de su ausencia. Resultados Se analizaron un total de 242 ECs, 69 (28,5%) de los cuales incluyeron medidas de CVRS, 10 (4,1%) como variable primaria. Únicamente 22 ECs emplearon más de un cuestionario. El análisis de datos por áreas terapéuticas puso de manifiesto que reumatología, urología, psiquiatría y oncología, fueron las áreas donde la CVRS fue analizada en una mayor proporción. Únicamente 33 ECs incluyeron variables económicas. Conclusiones Las medidas basadas en parámetros clínicos son las más usadas como medidas de eficacia. Una pequeña proporción de ECs considera la percepción del estado de salud del paciente, en contraste a la creciente importancia asignada a estos aspectos. La inclusión de cuestionarios de CVRS en el diseño de ECs, está lejos de ser una medida habitual (AU)

Chemical-wave dynamics in a vertically oscillating fluid layer.

Classical Faraday experiments were conducted on the oscillatory chemical Belousov-Zhabotinsky (BZ) reaction. The vertical periodic modulation of the acceleration induces flows in the system that change the BZ dynamics, and thus the patterns exhibited. The resulting reaction-diffusion-advection system exhibits four different types of pattern for increasing stirring amplitude: deformed targets and spiral waves, filamentary patterns arranged in large-scale vortices, advection phase waves, and finally front annihilation where the medium becomes homogeneous. A wave period analysis of the forced system has been carried out. Contrary to what is expected, i.e., a continuous increase of the wave period with increasing forcing, the period changes dramatically at the boundaries between pattern domains.

A complex intersex condition in a Holstein calf.

A case of disrupted embryonic development of the genital tract in a newborn Holstein calf is described. The physical examination of the calf evidenced several abnormalities, like atresia ani, rudimentary external genitalia and caudal vertebral agenesis. On necropsy, the excised genitalia consisted of bilateral streak gonads, apparently normal uterine tubes, a fluid-filled uterus, a long vagina and a very narrow clitoris-like structure covered with a discrete skin-fold. The urinary tract seemed normal and the urethra's opening was at the vestibule-vaginal junction. A cytogenetic analysis was requested. Karyotype revealed the existence of Y chromosome material in the two X chromosomes. However, the search for the sex-determining region Y (SRY) showed that this was an apparently absent gene. The histological examination of the gonads revealed the existence of ovarian dysplasia. Uterine sections evidenced the absence of the uterine epithelium, with only sporadic caruncles. Under microscopic examination, the uterine tubes and vagina structure was normal. The external genitalia sections revealed the existence of a skin-fold covering an erectile structure surrounding the urethra, a structure more similar to a penis than to a clitoris. This is an unusual situation of gonadal dysplasia combined with genital tract anomalies in cattle, probably associated to a genetic defect.

Noise correlation length effects on a Morris-Lecar neural network.

The role of spatially correlated stochastic perturbations on a Morris-Lecar neural network subject to an aperiodic subthreshold signal is analyzed in detail. Our results suggest that optimum signal-to-noise ratios can be obtained for two critical noise intensities due to the interplay of the subthreshold Poisson process and the correlated Gaussian forcing. For the second peak, most of the cells are periodically excited, the information transfer is enhanced, and a collective behavior develops measured in terms of the averaged activity of the network. The maximum signal-to-noise ratio increases with the correlation length, although it saturates for global coupling. It was found that there is a range of mean frequencies of the subthreshold signal that increases the signal-to-noise ratio output.

Consensus perspectives on surgery in haemophilia patients with inhibitors: summary statement.

Summary. Participants in an international workshop on surgery in haemophilia patients with inhibitors developed a consensus summary of the findings and conclusions of the meeting. In the consensus, participants agreed upon revised definitions for minor and major surgery, including an intermediate degree of surgery. An evaluation system of intraoperative and postoperative bleeding was developed. Recommended doses of FEIBA((R)) and rFVIIa (both in bolus injections and in continuous infusion) for surgery were agreed. Participants also agreed on the main blood tests to be performed peri-operatively. They also suggested the need of a prospective evaluation in the future. Finally, the approximate number of surgical procedures and costs performed on haemophilia patients with inhibitors were analysed.

[Modifications of the leukocytes in professional cyclists throughout the competition]. / Modificaciones de los leucocitos en ciclistas profesionales a lo largo de la competición.

In this work we plan to analyze and establish the leukocyte variations due to the effort of the competition, throughout 4 short-term turns (5 days and an average of 750 km each one), in 16 professional cyclists (24.8 2.3 year-old, 71.0 4.5 kg and 179.3 5.0 cm). The hematological parameters analyzed were leukocytes (WBC), neurtrophils (NEUT), lymphocytes (LYM), monocytes (MON), eosinophils (EOS) and basophils (BAS), and the results are presented as the percentage on the total number of leukocytes. The serum level of cortisol was also measured along study time (before and after each one of the 4 turns). The results show that the total number of leukocytes increase significantly in the turns, both in basal conditions (B) and after finishing the turn (F). The NEUT show an ongoing increase in their basal values from the first to the fourth round, but its values at the conclusion of this are significantly lower with respect to the situation of reference of the beginning of the cyclist turn. The LYM in rest upon beginning the turns are kept in similar values during the study period, increasing significantly after the 5 days of competition of each turn. The cortisol, as they are happening the turns, they decline its rates both in rest and after the competition (5 days turns). In conclusion the physical exercise throughout several cyclists turns give rise an increases in the leukocytes that is associated to a progressive decline of the cortisol levels probably because of the conditioning that the cyclist shows throughout the competition.

Modificaciones de los leucocitos en ciclistasprofesionales a lo largo de la competición / Modifications of the leukocytes in professional cyclists throughout the competition

En este trabajo nos planteamos analizar y objetivar las variaciones leucocitarias producidas por el esfuerzo de la competición, a lo largo de 4 vueltas de corta duración (5 días y una media de 750 km cada una), en 16 ciclistas profesionales (24,8 ñ 2,3 años, 71,0 ñ 4,5 kg y 179,3 ñ 5,0 cm).Los parámetros hematológicos analizados fueron leucocitos (WBC), neutrófilos (NEUT), linfocitos (LINF), monocitos (MON), eosinófilos (EOS) y basófilos (BAS) y sus resultados son presentados como porcentaje sobre el número total de leucocitos. También se midió el nivel sérico de cortisol en todos los momentos de estudio (antes y después de cada una de las 4 vueltas).Los resultados muestran que el número total de leucocitos aumenta significativamente en las vueltas, tanto en condiciones basales (A) como después de acabar la vuelta (D). Los neutrófilos van incrementando sus valores basales desde la primera a la cuarta vuelta, pero sus valores al finalizar ésta son significativamente menores con respecto a la situación de referencia del comienzo de la vuelta ciclista. Los linfocitos en reposo al comenzar las vueltas se mantienen en valores similares a lo largo del período de estudio, aumentando significativamente tras los 5 días de competición de cada vuelta. El cortisol, a medida que van pasando las vueltas, desciende sus tasas tanto en reposo como después de la competición (5 días de vuelta). En conclusión, el ejercicio físico a lo largo de varias vueltas ciclistas produce incrementos de los leucocitos que se acompañan de un progresivo descenso de las tasas de cortisol debido probablemente al acondicionamiento que el ciclista tiene a lo largo de la competición (AU)

Síndrome de overlap (lupus eritematoso sistémico asociado a síndrome de Sjögren) en una anciana de 76 años de edad / Overlap syndrome (systemic lupus erythematous associated with Sjögren's syndrome) in a 76-yearsold woman

Se realiza un seguimiento durante 6 años a una mujer de 76 años en la que clínicamente se sospecha la presencia de síndrome de Sjögren. De forma repentina desarrolla características clínicas y serológicas de lupus eritematoso sistémico. El lupus del anciano es un subtipo de lupus de características clínicas diferentes, y su curso es más benigno que en pacientes jóvenes (AU)

Spiral wave meandering induced by fluid convection in an excitable medium.

An isothermal reaction-diffusion system is considered in a two-dimensional fluid medium within a gravitational field. Inhomogeneities in the concentration field of the species give rise to a fluid flow due to buoyancy forces. A two-dimensional reaction-diffusion-convection model of an excitable medium is presented. The influence of hydrodynamics on spiral wave dynamics is systematically studied. A kinematic model is also introduced to better understand the mechanisms involved here.

Early introduction of cereals into children's diets as a risk-factor for grass pollen asthma.

BACKGROUND: The prevalence of asthma has increased from the 1950s to the 1990s. The relationship between diet and asthma is an area of controversy that has never been fully evaluated. Attempts at dietary prevention of asthma have produced conflicting results. We have recently identified allergens from cereals that show cross-reactivity with proteins in grass pollen. An early intake of cereals in the diet during early life might cause IgE sensitization to cereals. It is not known whether such sensitization predisposes the development of allergy to pollen. METHODS: To test this hypothesis, a cross-sectional study and an observational case-control analysis of reviewed data were carried out on 16381 patients who had been admitted to our Allergy Unit between 1989 and 1999. All the patients underwent allergy tests to identify asthma risk-factors. All information in our data base was analysed using the SPSS computer system. RESULTS: There has been an increase of 7.8% in incidences of allergic asthma and a 7.3% increase in asthma due to grass pollen in the last decade. Grass-pollen asthma was associated with sensitization to cereals. The early introduction of cereals in the diet of children was found to be a risk factor for grass-pollen asthma (OR = 5.95; 95% CI 3.89-9.10). CONCLUSIONS: These findings document the progression of allergic asthma during a decade in a large sample of people who were influenced by similar environmental conditions and studied with the same diagnostic methods. This study represents the largest database of patients in which a common food is shown to be a risk factor for asthma.

Acute cardio-respiratory effects in rats of PS4alpha, an antineoplastic peptidoglycan from Mycobacterium vaccae.

PS4alpha is a high molecular weight peptidoglycan extracted from Mycobacterium vaccae, which has demonstrated considerable antineoplastic activity in-vivo without apparent toxicity. Available fortesting in only small quantities, a sensitive in-vivo method for measuring pulse and breathing rates in cannulated rats was applied to this compound at doses of 5, 50 and 500 microg kg(-1). Various parameters (mean arterial pressure, maximum transpulmonary pressure, compliance, heart rate, minute volume, respiratory rate and tidal volume) were followed for up to 1 h and demonstrated no significant deviation in the baseline values obtained before injection. This compound at doses up to 500 microg kg(-1) had no apparent acute toxicity in rats, but chronic effects at this and higher doses have to be determined by more conventional toxicological methods before proceeding to evaluate PS4alpha as an antineoplastic agent.

Convective structures in a two-layer gel-liquid excitable medium

The onset of convection due to wave propagation is investigated in the framework of the Belousov-Zhabotinsky reaction. Numerical calculations are based on a three variable Oregonator model coupled with the Navier-Stokes hydrodynamic equations under the Boussineq approximation for a system consisting of two layers, a liquid and a gel, both in close contact through an interface where chemical concentration exchange is allowed. The influence on the formation of convective rolls associated to wave front propagation is studied in terms of the exchange rate through the interface, the liquid layer width, and the coupling strength between the fluid flow and chemical dynamics. Waves are initiated on the surface of the gel and this perturbation is allowed to propagate into the liquid initiating either two counterrotating convective cells (at both sides of the front) or a disordered pattern.

Effects of nuclear spins on the quantum relaxation of the magnetization for the molecular nanomagnet Fe8

The strong influence of nuclear spins on resonant quantum tunneling in the molecular cluster Fe8 is demonstrated for the first time by comparing the relaxation rate of the standard Fe8 sample with two isotopic modified samples: (i) 56Fe is replaced by 57Fe, and (ii) a fraction of 1H is replaced by 2H. By using a recently developed "hole digging" method, we measured an intrinsic broadening which is driven by the hyperfine fields. Our measurements are in good agreement with numerical hyperfine calculations. For T>1.5 K, the influence of nuclear spins on the relaxation rate is less important, suggesting that spin-phonon coupling dominates the relaxation rate.

Brownian motion of spiral waves driven by spatiotemporal structured noise

Spiral chemical waves subjected to a spatiotemporal random excitability are experimentally and numerically investigated in relation to the light-sensitive Belousov-Zhabotinsky reaction. Brownian motion is identified and characterized by an effective diffusion coefficient which shows a rather complex dependence on the time and length scales of the noise relative to those of the spiral. A kinematically based model is proposed whose results are in good qualitative agreement with experiments and numerics.