The effect of continuous positive airway pressure on total cerebral blood flow in healthy awake volunteers.

PURPOSE: Continuous positive airway pressure (CPAP) is the gold standard treatment for obstructive sleep apnea. However, the physiologic impact of CPAP on cerebral blood flow (CBF) is not well established. Ultrasound can be used to estimate CBF, but there is no widespread accepted protocol. We studied the physiologic influence of CPAP on CBF using a method integrating arterial diameter and flow velocity (FV) measurements obtained for each vessel supplying blood to the brain. METHODS: FV and lumen diameter of the left and right internal carotid, vertebral, and middle cerebral arteries were measured using duplex Doppler ultrasound with and without CPAP at 15 cm H(2)O, applied in a random order. Transcutaneous carbon dioxide (PtcCO(2)), heart rate (HR), blood pressure (BP), and oxygen saturation were monitored. Results were compared with a theoretical prediction of CBF change based on the effect of partial pressure of carbon dioxide on CBF. RESULTS: Data were obtained from 23 healthy volunteers (mean ± SD; 12 male, age 25.1 ± 2.6 years, body mass index 21.8 ± 2.0 kg/m(2)). The mean experimental and theoretical CBF decrease under CPAP was 12.5 % (p < 0.001) and 11.9 % (p < 0.001), respectively. The difference between experimental and theoretical CBF reduction was not statistically significant (3.84 ± 79 ml/min, p = 0.40). There was a significant reduction in PtcCO(2) with CPAP (p = <0.001) and a significant increase in mean BP (p = 0.0017). No significant change was observed in SaO(2) (p = 0.21) and HR (p = 0.62). CONCLUSION: Duplex Doppler ultrasound measurements of arterial diameter and FV allow for a noninvasive bedside estimation of CBF. CPAP at 15 cm H(2)O significantly decreased CBF in healthy awake volunteers. This effect appeared to be mediated predominately through the hypocapnic vasoconstriction coinciding with PCO(2) level reduction. The results suggest that CPAP should be used cautiously in patients with unstable cerebral hemodynamics.

Prognostic value of continuous EEG monitoring during therapeutic hypothermia after cardiac arrest.

Introduction: Continuous EEG (cEEG) is increasingly used to monitor brain function in neuro-ICU patients. However, its value in patients with coma after cardiac arrest (CA), particularly in the setting of therapeutic hypothermia (TH), is only beginning to be elucidated. The aim of this study was to examine whether cEEG performed during TH may predict outcome. Methods: From April 2009 to April 2010, we prospectively studied 34 consecutive comatose patients treated with TH after CA who were monitored with cEEG, initiated during hypothermia and maintained after rewarming. EEG background reactivity to painful stimulation was tested. We analyzed the association between cEEG findings and neurologic outcome, assessed at 2 months with the Glasgow-Pittsburgh Cerebral Performance Categories (CPC). Results: Continuous EEG recording was started 12 ± 6 hours after CA and lasted 30 ± 11 hours. Nonreactive cEEG background (12 of 15 (75%) among nonsurvivors versus none of 19 (0) survivors; P < 0.001) and prolonged discontinuous "burst-suppression" activity (11 of 15 (73%) versus none of 19; P < 0.001) were significantly associated with mortality. EEG seizures with absent background reactivity also differed significantly (seven of 15 (47%) versus none of 12 (0); P = 0.001). In patients with nonreactive background or seizures/epileptiform discharges on cEEG, no improvement was seen after TH. Nonreactive cEEG background during TH had a positive predictive value of 100% (95% confidence interval (CI), 74 to 100%) and a false-positive rate of 0 (95% CI, 0 to 18%) for mortality. All survivors had cEEG background reactivity, and the majority of them (14 (74%) of 19) had a favorable outcome (CPC 1 or 2). Conclusions: Continuous EEG monitoring showing a nonreactive or discontinuous background during TH is strongly associated with unfavorable outcome in patients with coma after CA. These data warrant larger studies to confirm the value of continuous EEG monitoring in predicting prognosis after CA and TH.

Buy-and-Hold Strategies and Comonotonic Approximations

[cat] En aquest article estudiem estratègies “comprar i mantenir” per a problemes d’optimitzar la riquesa final en un context multi-període. Com que la riquesa final és una suma de variables aleatòries dependents, on cadascuna d’aquestes correspon a una quantitat de capital que s’ha invertit en un actiu particular en una data determinada, en primer lloc considerem aproximacions que redueixen l’aleatorietat multivariant al cas univariant. A continuació, aquestes aproximacions es fan servir per determinar les estratègies “comprar i mantenir” que optimitzen, per a un nivell de probabilitat donat, el VaR i el CLTE de la funció de distribució de la riquesa final. Aquest article complementa el treball de Dhaene et al. (2005), on es van considerar estratègies de reequilibri constant.

Continuous recording intrarectal pressures during the second phase of labor.

Parameters of intrarectal pressure (surface area under pressure curve and peak pressure) recorded with a microsystem device during the second phase of labor showed no significant correlations with baby's weight or mode of delivery. AIM OF THE STUDY: Was to assess the biomechanical pressures delivered against pelvic floor structures during the second phase of labor in nulliparae women, and to correlate them with obstetrics parameters, i.e. baby'sweight and mode of delivery. MATERIAL: Using a microsystem device placed into the rectum at the beginning of the second phase of labor, two parameters were assessed during the bearing efforts in 59 nulliparae women: the surface area under the pressure curve and the peak pressure. RESULTS: During 11.5±9 bearing efforts of 99.1±16s duration, the mean value of surface area under the pressure curve was 32677±26058cm/s and the mean value of the peak pressure was 60.7±24cmH(2)O, exceeding 100cmH(2)O in 10% of women. These two parameters were not correlated with baby's weight (R: 0.19, P: 0.15 and R: 0.05, P: 0.71). In the same way, these two parameters were not correlated with the mode of delivery (spontaneous or forceps/vacuum-assisted). Furthermore, the individual values of these two parameters showed great variation from one woman to another. CONCLUSION: This study has showed that parameters of biomechanical pressures recorded into the rectum during second phase of labor had no significant correlations with obstetricals parameters, explaining why these latter have poor predicitive value of further pelvic floor problems.

Optimization of analytical methods for the assessment of the quality of fats and oils used in continuous deep fat frying

La aplicabilidad, repetibilidad y capacidad de diferentes métodos de análisis para discriminar muestras de aceites con diferentes grados de oxidación fueron evaluadas mediante aceites recogidos en procesos de fritura en continuo en varias empresas españolas. El objetivo de este trabajo fue encontrar métodos complementarios a la determinación del índice de acidez para el control de calidad rutinario de los aceites de fritura empleados en estas empresas. La optimización de la determinación de la constante dieléctrica conllevó una clara mejora de la variabilidad. No obstante, excepto en el caso del índice del ATB, el resto de métodos ensayados mostraron una menor variabilidad. La determinación del índice del ATB fue descartada ya que su sensibilidad fue insuficiente para discriminar entre aceites con diferente grado de oxidación. Los diferentes parámetros de alteración determinados en los aceites de fritura mostraron correlaciones significativas entre el índice de acidez y varios parámetros de oxidación diferentes, como la constante dieléctrica, el índice de p-anisidina, la absorción al ultravioleta y el contenido en polímeros de los triacilgliceroles. El índice de acidez solo evalúa la alteración hidrolítica, por lo que estos parámetros aportan información complementaria al evaluar la alteración termooxidativa.

Mean first-passage time of continuous non-Markovian processes driven by colored noise

An equation for mean first-passage times of non-Markovian processes driven by colored noise is derived through an appropriate backward integro-differential equation. The equation is solved in a Bourret-like approximation. In a weak-noise bistable situation, non-Markovian effects are taken into account by an effective diffusion coefficient. In this situation, our results compare satisfactorily with other approaches and experimental data.

Continuous sunitinib treatment in patients with unresectable hepatocellular carcinoma (HCC): A multicenter phase II trial (SAKK 77/06 and SASL 23)

Background: Sunitinib (SU) is a multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenetic activity. Evidence for clinical activity in HCC was reported in 2 phase II trials [Zhu et al and Faivre et al, ASCO 2007] using either a 37.5 or a 50 mg daily dose in a 4 weeks on, 2 weeks off regimen. The objective of this trial was to demonstrate antitumor activity of continuous SU treatment in patients (pts) with HCC. Methods: Key eligibility criteria included unresectable or metastatic HCC, no prior systemic anticancer treatment, measurable disease and Child- Pugh A or B liver dysfunction. Pts received 37.5 mg SU daily until progression or unacceptable toxicity. The primary endpoint was progression free survival at 12 weeks (PFS12) defined as 'success' if the patient was alive and without tumor progression assessed by 12 weeks (±7 days) after registration. A PFS12 of _20% was considered uninteresting and promising if _40%. Using the Simon-two minimax stage design with 90% power and 5% significance the sample size was 45 pts. Secondary endpoints included safety assessments, measurement of serum cobalamin levels and tumor density. Results: From September 2007 to August 2008 45 pts, mostly male (87%), were enrolled in 10 centers. Median age was 63 years, 89% had Child-Pugh A and 47% had distant metastases. Median largest lesion diameter was 84mm (range: 18-280) and 18% had prior TACE. Reasons for stopping therapy were: PD 60%, symptomatic deterioration 16%, toxicity 11%, death 2% (due to tumor), and other reasons 4%; 7% remain on therapy. PFS12 was rated as success in 15 pts (33%) (95% CI: 20%, 49%) and failure in 27 (60%); 3 were not evaluable (due to refusal). Over the whole trial period 1 CR and 40% SD as best response were achieved. Median PFS, duration of disease stabilization, TTP and OS were 2.8, 3.2, 2.8 and 9.3 months, respectively. Grade 3 and 4 adverse events were infrequent and all deaths due to the tumor. Conclusions: Continuous SU treatment with 37.5 mg/d daily is feasible and demonstrates moderate activity in pts with advanced HCC and mild to moderately impaired liver dysfunction. Under this trial design the therapy is considered promising (>13 PFS12 successes).

Induction of experimental endocarditis by continuous low-grade bacteremia mimicking spontaneous bacteremia in humans.

Transient high-grade bacteremia following invasive procedures carries a risk of infective endocarditis (IE). This is supported by experimental endocarditis. On the other hand, case-control studies showed that IE could be caused by cumulative exposure to low-grade bacteremia occurring during daily activities. However, no experimental demonstration of this latter possibility exists. This study investigated the infectivity in animals of continuous low-grade bacteremia compared to that of brief high-grade bacteremia. Rats with aortic vegetations were inoculated with Streptococcus intermedius, Streptococcus gordonii or Staphylococcus aureus (strains Newman and P8). Animals were challenged with 10(3) to 10(6) CFU. Identical bacterial numbers were given by bolus (1 ml in 1 min) or continuous infusion (0.0017 ml/min over 10 h). Bacteremia was 50 to 1,000 times greater after bolus than during continuous inoculation. Streptococcal bolus inoculation of 10(5) CFU infected 63 to 100% vegetations compared to 30 to 71% infection after continuous infusion (P > 0.05). When increasing the inoculum to 10(6) CFU, bolus inoculation infected 100% vegetations and continuous infusion 70 to 100% (P > 0.05). S. aureus bolus injection of 10(3) CFU infected 46 to 57% valves. This was similar to the 53 to 57% infection rates produced by continuous infusion (P > 0.05). Inoculation of 10(4) CFU of S. aureus infected 80 to 100% vegetations after bolus and 60 to 75% after continuous infusion (P > 0.05). These results show that high-level bacteremia is not required to induce experimental endocarditis and support the hypothesis that cumulative exposure to low-grade bacteremia represents a genuine risk of IE in humans.

Optimal and continuous anaemia control in a cohort of dialysis patients in Switzerland.

BACKGROUND: Guidelines for the management of anaemia in patients with chronic kidney disease (CKD) recommend a minimal haemoglobin (Hb) target of 11 g/dL. Recent surveys indicate that this requirement is not met in many patients in Europe. In most studies, Hb is only assessed over a short-term period. The aim of this study was to examine the control of anaemia over a continuous long-term period in Switzerland. METHODS: A prospective multi-centre observational study was conducted in dialysed patients treated with recombinant human epoetin (EPO) beta, over a one-year follow-up period, with monthly assessments of anaemia parameters. RESULTS: Three hundred and fifty patients from 27 centres, representing 14% of the dialysis population in Switzerland, were included. Mean Hb was 11.9 +/- 1.0 g/dL, and remained stable over time. Eighty-five % of the patients achieved mean Hb &gt;or= 11 g/dL. Mean EPO dose was 155 +/- 118 IU/kg/week, being delivered mostly by subcutaneous route (64-71%). Mean serum ferritin and transferrin saturation were 435 +/- 253 microg/L and 30 +/- 11%, respectively. At month 12, adequate iron stores were found in 72.5% of patients, whereas absolute and functional iron deficiencies were observed in only 5.1% and 17.8%, respectively. Multivariate analysis showed that diabetes unexpectedly influenced Hb towards higher levels (12.1 +/- 0.9 g/dL; p = 0.02). One year survival was significantly higher in patients with Hb &gt;or= 11 g/dL than in those with Hb &lt;11 g/dL (19.7% vs 7.3%, p = 0.006). CONCLUSION: In comparison to European studies of reference, this survey shows a remarkable and continuous control of anaemia in Swiss dialysis centres. These results were reached through moderately high EPO doses, mostly given subcutaneously, and careful iron therapy management.

Stability and robustness of blood variables in an antidoping context.

Introduction:  With the setting up of the newly Athlete's Biological Passport antidoping programme, novel guidelines have been introduced to guarantee results beyond reproach. We investigated in this context, the effect of storage time on the variables commonly measured for the haematological passport. We also wanted to assess for these variables, the within and between analyzer variations. Methods:  Blood samples were obtained from top level male professional cyclists (27 samples for the first part of the study and 102 for the second part) taking part to major stage races. After collection, they were transported under refrigerated conditions (2 °C < T < 12 °C), delivered to the antidoping laboratory, analysed and then stored at approximately 4 °C to conduct analysis at different time points up to 72 h after delivery. A mixed-model procedure was used to determine the stability of the different variables. Results:  As expected haemoglobin concentration was not affected by storage and showed stability for at least 72 h. Under the conditions of our investigation, the reticulocytes percentage showed a much better stability than previous published data (> 48 h) and the technical comparison of the haematology analyzer demonstrated excellent results. Conclusion:  In conclusion, our data clearly demonstrate that as long as the World Anti-Doping Agency's guidelines are followed rigorously, all blood results reach the quality level required in the antidoping context.

Effect of a 1-hour single bout of moderate-intensity exercise on fat oxidation kinetics.

The present study aimed to examine the effects of a prior 1-hour continuous exercise bout (CONT) at an intensity (Fat(max)) that elicits the maximal fat oxidation (MFO) on the fat oxidation kinetics during a subsequent submaximal incremental test (IncrC). Twenty moderately trained subjects (9 men and 11 women) performed a graded test on a treadmill (Incr), with 3-minute stages and 1-km.h(-1) increments. Fat oxidation was measured using indirect calorimetry and plotted as a function of exercise intensity. A mathematical model (SIN) including 3 independent variables (dilatation, symmetry, and translation) was used to characterize the shape of fat oxidation kinetics and to determine Fat(max) and MFO. On a second visit, the subjects performed CONT at Fat(max) followed by IncrC. After CONT performed at 57% +/- 3% (means +/- SE) maximal oxygen uptake (Vo(2max)), the respiratory exchange ratio during IncrC was lower at every stage compared with Incr (P < .05). Fat(max) (56.4% +/- 2.3% vs 51.5% +/- 2.4% Vo(2max), P = .013), MFO (0.50 +/- 0.03 vs 0.40 +/- 0.03 g.min(-1), P < .001), and fat oxidation rates from 35% to 70% Vo(2max) (P < .05) were significantly greater during IncrC compared with Incr. However, dilatation and translation were not significantly different (P > .05), whereas symmetry tended to be greater in IncrC (P = .096). This study showed that the prior 1-hour continuous moderate-intensity exercise bout increased Fat(max), MFO, and fat oxidation rates over a wide range of intensities during the postexercise incremental test. Moreover, the shape of the postexercise fat oxidation kinetics tended to have a rightward asymmetry.

The european higher education area at work: Lights and shadows defining continuous assessment

The aim of this paper is to analyse how learning assessment, particularly the Continuous Assessment system, has been defined in the Public Administration and Management Diploma Course of the University of Barcelona (Spain). This course was a pioneering experiment at this university in implementing the guidelines of the European Higher Education Area (EHEA), and thus represents a good case study for verifying whether one of the cornerstones of the EHEA has been accomplished with success. Using data obtained from the Teaching Plans elaborated by the lecturers of each subject, we are able to establish that the CA system has been progressively accepted to such an extent that it is now the assessment formula used by practically all of the lecturers, conforming in this way to the protocols laid down by the Faculty of Law in which this diploma course is taught. Nevertheless, we find that high dispersion exists in how Continuous Assessment is actually defined. Indeed, it seems that there is no unified view of how Continuous Assessment should be performed. This dispersion, however, seems to diminish over time and raises some questions about the advisability of agreement on criteria, considering the potential which CA has as a pedagogical tool. Moreover, we find that the Unique Assessment system, which students may also apply for, is an option chosen only by a minority, with lecturers usually defining it as merely a theoretical and/or practical test, of little innovation in relation to traditional tests.

The adaptive function of melanin-based coloration in the tawny owl (Strix aluco) ; the proximate role of the melanocortin system

Colour polymorphism is common in wild population. One of the main questioning of evolutionary biologists is to understand how different colour variants could have evolved and be maintained in fluctuating environments, a selective process that forces individuals to constantly adapt their strategies in order to survive. This issue is particularly true for traits that are genetically inherited. Natural selection erodes genotypes with lowest fitness (less adapted), reducing in turn global genetic variation within population. In this context, the study of the evolution and maintenance of melanin- based coloration is relevant since inter-individual variation in the deposition of these pigments is common in animal and plant kingdoms and is under strong genetic control. In this thesis, I focus on the specific case of the tawny owl (Strix aluco), a species displaying continuous variation in reddish pheomelanin-based coloration. Interestingly, empirical studies highlighted covariations between melanin-based coloration and important behavioural, physiological and life history traits. Recently, a genetic model pointed out the melanocortin system and their pleiotropic effects as a potential regulator of these covariations. Accordingly, this PhD thesis further investigates colour-specific behavioural, physiological, or life history strategies, while examining the proximate mechanisms underlying these reaction norms. We found that differently coloured tawny owls differently resolve fundamental trade-off between offspring number and quality (Chapter 1), light melanic individuals producing many low- quality offspring and dark, melanic ones producing few high-quality offspring. These reproductive strategies are likely to induce alternative physiological constraints. Indeed, we demonstrated that light melanic individuals produced higher levels of reactive oxygen species (ROS, Chapter 2), but also expressed higher levels of antioxidant (GSH, Chapters 2 & 3). Interestingly, we showed that light melanic breeding females could modulate their POMC prohormone levels according to the environmental conditions, while dark reddish ones produced constant levels of this prohormone {Chapter 4). Finally, we highlighted colour-specific patterns of prohormone convertase 1 (PCI) gene expression (Chapter 5), an enzyme responsible for POMC prohormone processing to ACTH and a- MSH, for instance. Altogether, these results provide strong evidence of colour-specific strategies, light and melanic tawny owls better coping with stressful and relaxed environments, respectively. Variation in melanin-based coloration is likely to be maintained by the heterogeneity of our study area and strong environmental stochasticity within and between years, these process favouring differently coloured tawny owls at different periods of time. From a proximate point of view, this PhD thesis supports the hypothesis that covariations between phenotypic traits and melanin-based coloration stems from the melanocortin system, especially the fundamental role of POMC gene expression and its processing to melanocortin peptides. - Le polymorphisme de couleur est une variation phénotypique très fréquente dans la nature. En biologie évolutive, une des problématiques clés est donc de comprendre comment différent morphes de couleur peuvent être apparus et maintenus au cours du temps dans des environnements aussi variables que les nôtres, surtout que ces fluctuations forcent ces morphes à s'adapter constamment pour assurer leur survie. Cette thématique est particulièrement réelle lorsque les variations phénotypiques sont héréditaires et donc sous forte influence génétique. La sélection naturelle a en effet le pouvoir d'éroder rapidement la variation génétique en éliminant les génotypes mal adaptés. Dans ce sens, l'étude de l'évolution, et de la maintenance de la coloration mélanique est donc tout à fait pertinente car la variation de coloration entre individus est très répandue à travers les règnes animal et végétal et sous forte influence génétique. Dans cette thèse, je me suis concentré sur le cas spécifique de la chouette hulotte (Strix aluco), une espèce présentant une variation continue dans la déposition de pigments pheomélaniques roux. De précédentes études ont déjà montré que cette variation de coloration était associée avec des variations de traits comportementaux, physiologiques ou d'histoire de vie. Récemment, une étude a souligné l'importance du système des mélanocortines et de leurs effets pléiotropes dans la régulation de ces covariations. En conséquence, cette thèse de doctoral a pour but d'étudier un peu plus les stratégies comportementales, physiologiques ou d'histoire de vie spécifiques à chaque morphe de couleur, tout en examinant un peu plus les mécanismes proximaux potentiellement à la base de ces normes de réactions. Nous constatons tout d'abord que les morphes de couleurs étaient associés à différentes stratégies dans la résolution de compromis telle que la production de beaucoup de jeunes ou des jeunes de qualité (Chapitre 1). Les morphes gris (dit peu mélaniques) ont tendance à produire beaucoup de jeunes mains de moindre qualité, alors que les morphes roux (dit fortement mélaniques) produisent moins de jeunes mais de meilleure qualité. Ces stratégies sont susceptibles alors d'induire certaines contraintes physiologiques. Par exemple, nous montrons que les morphes gris produisent plus de dérivés réactifs de l'oxygène (ROS, Chapitre 2), mais aussi plus d'antioxydants (GSH, Chapitres 2 & 3). Nous montrons ensuite que les femelles grises ont une plus grande capacité à moduler leur niveau de POMC prohormone dans le sang en fonction des conditions environnementales, alors que les femelles rousses gardent un niveau constant (Chapitre 4). Finalement, nous démontrons que les patterns d'expression du gène codant pour la prohormone convertase 1 varient chez des jeunes issus de parents gris ou roux (Chapitre 5). Ceci est particulièrement intéressant car cette enzyme permet de scinder la POMC prohormone en plusieurs peptides importants tels que l'ACTH ou l'a-MSH. En conclusion, ces résultats démontrent qu'il y a bel et bien des stratégies évolutives différentes entre les morphes de couleurs, les chouettes hulottes grises et rousses étant respectivement plus adaptés à des environnements stressants ou favorables. L'hétérogénéité de notre zone d'étude et la stochasticité environnementale qui caractérise ses habitats pourraient donc agir comme une source de sélection temporelle, laquelle favoriserait les différents morphes de couleurs à diverses périodes. D'un point de vue plus proximale maintenant, cette thèse de doctorat soutient l'hypothèse que les covariations observées entre la coloration mélanique et des traits phénotypiques importants sont modulées par les effets pléiotropes du système des mélanocortines, et met en avant le rôle prépondérant que pourrait jouer l'expression du gène POMC et sa post traduction en mélanocortines.