Nasal trauma due to continuous positive airway pressure in neonates.

PATIENTS: All neonates admitted between January 2002 and December 2007 treated by nCPAP were eligible. METHODS: Patients' noses were monitored during nCPAP. Nasal trauma was reported into three stages: (I) persistent erythema; (II) superficial ulceration; and (III) necrosis. RESULTS: 989 neonates were enrolled. Mean gestational age was 34 weeks (SD 4), mean birth weight 2142 g (SD 840). Nasal trauma was reported in 420 (42.5%) patients and it was of stage I, II and III in 371 (88.3%), 46 (11%) and 3 (0.7%) patients, respectively. Incidence and severity of trauma were inversely correlated with gestational age and birth weight. The risk of nasal trauma was greater in neonates <32 weeks of gestational age (OR 2.48, 95% CI 1.59 to 3.86), weighing <1500 g at birth (OR 2.28, 95% CI 1.43 to 3.64), treated >5 days by nCPAP (OR 5.36, 95% CI 3.82 to 7.52), or staying >14 days in the NICU (OR 1.67, 95% CI 1.22 to 2.28). Most cases of nasal trauma (90%) appeared during the first 6 days of nCPAP. Persistent visible scars were present in two cases. CONCLUSIONS: Nasal trauma is a frequent complication of nCPAP, especially in preterm neonates, but long-term cosmetic sequelae are very rare. This study provides a description of nasal trauma and proposes a simple staging system. This could serve as a basis to develop strategies of prevention and treatment of this iatrogenic event.

Towards a system analysis of the early steps of infectious endocarditis pathogenesis

L'endocardite infectieuse (EI) est une maladie potentiellement mortelle qui doit être prévenue dans toute la mesure du possible. Au cours de ces dernières 50 années, les recommandations Américaines et Européennes pour la prophylaxie de PEI proposaient aux patients à risques de prendre un antibiotique, préventif avant de subir une intervention médico-chirurgicale susceptible d'induire une bactériémie transitoire. Cependant, des études épidémiologiques récentes ont montré que la plupart des EI survenaient en dehors de tous actes médico-chirurgicaux, et indépendamment de la prise ou non de prophylaxie antibiotique . L'EI pourrait donc survenir suite à la cumulation de bactériémies spontanées de faibles intensités, associées à des activités de la vie courante telle que le brossage dentaire pour le streptocoques, ou à partir de tissus colonisés ou de cathéters infectés pour les staphylocoques. En conséquence, les recommandations internationales pour la prophylaxie de PEI ont été revues et proposent une diminution drastique de l'utilisation d'antibiotiques. Cependant, le risque d'EI représenté par le cumul de bactériémies de faibles intensités n'a pas été démontré expérimentalement. Nous avons développé un nouveau modèle d'EI expérimentale induite par une inoculation en continu d'une faible quantité de bactéries, simulant le cumul de bactériémies de faibles intensités chez l'homme, et comparé l'infection de Streptococcus gordonii et de Staphylococcus aureus dans ce modèle avec celle du modèle d'IE induite par une bactériémie brève, mais de forte intensité. Nous avons démontré, après injection d'une quantité égale de bactéries, que le nombre de végétations infectées était similaire dans les deux types d'inoculations. Ces résultats expérimentaux ont confirmé l'hypothèse qu'une exposition cumulée à des bactériémies de faibles intensités, en dehors d'une procédure médico-chirurgicale, représentait un risque pour le développement d'une El, comme le suggéraient les études épidémiologiques. En plus, ces résultats ont validé les nouvelles recommandations pour la prophylaxie de l'El, limitant drastiquement l'utilisation d'antibiotiques. Cependant, ces nouvelles recommandations laissent une grande partie (> 90%) de cas potentiels d'EI sans alternatives de préventions, et des nouvelles stratégies prophylactiques doivent être investiguées. Le nouveau modèle d'EI expérimentale représente un modèle réaliste pour étudier des nouvelles mesures prophylactiques potentielles appliquées à des expositions cumulées de bactériémies de faible nombre. Dans un contexte de bactériémies spontanées répétitives, les antibiotiques ne peuvent pas résoudre le problème de la prévention de l'EI. Nous avons donc étudié la une alternative de prévention par l'utilisation d'agents antiplaquettaires. La logique derrière cette approche était basée sur le fait que les plaquettes sont des composants clés dans la formation des végétations cardiaques, et le fait que les bactéries capables d'interagir avec les plaquettes sont plus enclines à induire une El. Les agents antiplaquettaires utilisés ont été l'aspirine (inhibiteur du COX1), la ticlopidine (inhibiteur du P2Y12, le récepteur de l'ADP), et l'eptifibatide et Pabciximab, deux inhibiteurs du GPIIb/IIIa, le récepteur plaquettaire pour le fibrinogène. Les anticoagulants étaient le dabigatran etexilate, inhibant lathrombine et l'acenocumarol, un antagoniste de la vitamine K. L'aspirine, la ticlopidine ou l'eptifibatide seuls n'ont pas permis de prévenir l'infection valvulaire (> 75% animaux infectés). En revanche, la combinaison d'aspirine et de ticlopidine, aussi bien que l'abciximab, ont protégé 45% - 88% des animaux de l'EI par S. gordonii et par S. aureus. L'antithrombotique dabigatran etexilate à protégé 75% des rats contre l'EI par S. aureus, mais pas (< 30% de protection) par S. gordonii. L'acenocoumarol n'a pas eu d'effet sur aucun des deux organismes. En général, ces résultats suggèrent un possible rôle pour les antiplaquettaires et du dabigatran etexilate dans la prophylaxie de l'EI dans un contexte de bactériémies récurrentes de faibles intensités. Cependant, l'effet bénéfique des antiplaquettaires doit être soupesé avec le risque d'hémorragie inhérent à ces molécules, et le fait que les plaquettes jouent un important rôle dans les défenses de l'hôte contre les infections endovasculaires. En plus, le double effet bénéfique du dabigatran etexilate devrait être revu chez les patients porteurs de valves prothétiques, qui ont besoin d'une anticoagulation à vie, et chez lesquels l'EI à S. aureus est associée avec une mortalité de près de 50%. Comme l'approche avec des antiplaquettaires et des antithrombotiques pourrait avoir des limites, une autre stratégie prophylactique pourrait être la vaccination contre des adhésines de surfaces des pathogènes. Chez S. aureus, la protéine de liaison au fibrinogène, ou dumping factor A (ClfA), et la protéine de liaison à la fibronectine (FnbpA) sont des facteurs de virulence nécessaires à l'initiation et l'évolution de PEI. Elles représentent donc des cibles potentielles pour le développement de vaccins contre cette infection. Récemment, des nombreuses publications ont décrit que la bactérie Lactococcus lactis pouvait être utilisée comme vecteur pour la diffusion d'antigènes bactériens in vivo, et que cette approche pourrait être une stratégie de vaccination contre les infections bactériennes. Nous avons exploré l'effet de l'immunisation par des recombinant de L. lactis exprimant le ClfA, la FnbpA, ou le ClfA ensemble avec et une forme tronquée de la FnbpA (Fnbp, comprenant seulement le domaine de liaison à la fibronectine mais sans le domaine A de liaison au fibrinogène [L. lactis ClfA/Fnbp]), dans la prophylaxie de PIE expérimentale à S. aureus. L. lactis ClfA a été utilisés comme agent d'immunisation contre la souche S. aureus Newman (qui a particularité de n'exprimer que le ClfA, mais pas la FnbpA). L. lactis ClfA, L. lactis FnbpA, et L. lactis ClfA/Fnbp, ont été utilisé comme agents d'immunisation contre une souche isolée d'une IE, S. aureus P8 (exprimant ClfA et FnbpA). L'immunisation avec L. lactis ClfA a généré des anticorps anti-ClfA fonctionnels, capables de bloquer la liaison de S. aureus Newman au fibrinogène in vitro et protéger 13/19 (69%) animaux d'une El due à S. aureus Newman (P < 0.05 comparée aux contrôles). L'immunisation avec L. lactis ClfA, L. lactis FnbpA, ou L. lactis ClfA/Fnbp, a généré des anticorps contre chacun de ces antigènes. Cependant, ils n'ont pas permis de bloquer l'adhésion de S. aureus P8 au fibrinogène et à la fibronectine in vitro. De plus, l'immunisation avec L. lactis ClfA ou L. lactis FnbpA s'est avérée inefficace in vivo (< 10% d'animaux protégés d'une El) et l'immunisation avec L. lactis ClfA/Fnbp a fourni une protection limitée de l'EI (8/23 animaux protégés; P < 0.05 comparée aux contrôles) après inoculation avec S. aureus P8. Dans l'ensemble, ces résultats indiquent que L. lactis est un système efficace pour la présentation d'antigènes in vivo et potentiellement utile pour la prévention de PEI à S. aureus. Cependant, le répertoire de protéines de surface de S. aureus capable d'évoquer une panoplie d'anticorps efficace reste à déterminer.. En résumé, notre étude a démontré expérimentalement, pour la première fois, qu'une bactériémie répétée de faible intensité, simulant la bactériémie ayant lieu, par exemple, lors des activités de la vie quotidienne, est induire un taux d'EI expérimentale similaire à celle induite par une bactériémie de haute intensité suite à une intervention médicale. Dans ce contexte, où l'utilisation d'antibiotiques est pas raisonnable, nous avons aussi montré que d'autres mesures prophylactiques, comme l'utilisation d'agents antiplaquettaires ou antithrombotiques, ou la vaccination utilisant L. lactis comme vecteur d'antigènes bactériens, sont des alternatives prometteuses qui méritent d'être étudiées plus avant. Thesis Summary Infective endocarditis (IE) is a life-threatening disease that should be prevented whenever possible. Over the last 50 years, guidelines for IE prophylaxis proposed the use of antibiotics in patients undergoing dental or medico-surgical procedures that might induce high, but transient bacteremia. However, recent epidemiological studies indicate that IE occurs independently of medico-surgical procedures and the fact that patients had taken antibiotic prophylaxis or not, i.e., by cumulative exposure to random low-grade bacteremia, associated with daily activities (e.g. tooth brushing) in the case of oral streptococci, or with a colonized site or infected device in the case of staphylococci. Accordingly, the most recent American and European guidelines for IE prophylaxis were revisited and updated to drastically restrain antibiotic use. Nevertheless, the relative risk of IE represented by such cumulative low-grade bacteremia had never been demonstrated experimentally. We developed a new model of experimental IE due to continuous inoculation of low-grade bacteremia, mimicking repeated low-grade bacteremia in humans, and compared the infectivity of Streptococcus gordonii and Staphylococcus aureus in this model to that in the model producing brief, high-level bacteremia. We demonstrated that, after injection of identical bacterial numbers, the rate of infected vegetations was similar in both types of challenge. These experimental results support the hypothesis that cumulative exposure to low-grade bacteremia, outside the context of procedure-related bacteremia, represents a genuine risk of IE, as suggested by human epidemiological studies. In addition, they validate the newer guidelines for IE prophylaxis, which drastic limit the procedures in which antibiotic prophylaxis is indicated. Nevertheless, these refreshed guidelines leave the vast majority (> 90%) of potential IE cases without alternative propositions of prevention, and novel strategies must be considered to propose effective alternative and "global" measures to prevent IE initiation. The more realistic experimental model of IE induced by low-grade bacteremia provides an accurate experimental setting to study new preventive measures applying to cumulative exposure to low bacterial numbers. Since in a context of spontaneous low-grade bacteremia antibiotics are unlikely to solve the problem of IE prevention, we addressed the role of antiplatelet and anticoagulant agents for the prophylaxis of experimental IE induced by S. gordonii and S. aureus. The logic of this approach was based on the fact that platelets are key players in vegetation formation and vegetation enlargement, and on the fact that bacteria capable of interacting with platelets are more prone to induce IE. Antiplatelet agents included the COX1 inhibitor aspirin, the inhibitor of the ADP receptor P2Y12 ticlopidine, and two inhibitors of the platelet fibrinogen receptor GPIIb/IIIa, eptifibatide and abciximab. Anticoagulants included the thrombin inhibitor dabigatran etexilate and the vitamin K antagonist acenocoumarol. Aspirin, ticlopidine or eptifibatide alone failed to prevent aortic infection (> 75% infected animals). In contrast, the combination of aspirin with ticlopidine, as well as abciximab, protected 45% to 88% of animals against IE due to S. gordonii and S. aureus. The antithrombin dabigatran etexilate protected 75% of rats against IE due to S. aureus, but failed (< 30% protection) against S. gordonii. Acenocoumarol had no effect against any bacteria. Overall, these results suggest a possible role for antiplatelet agents and dabigatran etexilate in the prophylaxis of IE in humans in a context of recurrent low- grade bacteremia. However, the potential beneficial effect of antiplatelet agents should be balanced against the risk of bleeding and the fact that platelets play an important role in the host defenses against intravascular infections. In addition, the potential dual benefit of dabigatran etexilate might be revisited in patients with prosthetic valves, who require life-long anticoagulation and in whom S. aureus IE is associated with high mortality rate. Because the antiplatelet and anticoagulant approach might be limited in the context of S. aureus bacteremia, other prophylactic strategies for the prevention of S. aureus IE, like vaccination with anti-adhesion proteins was tested. The S. aureus surface proteins fibrinogen-binding protein clumping-factor A (ClfA) and the fibronectin-binding protein A (FnbpA) are critical virulence factors for the initiation and development of IE. Thus, they represent key targets for vaccine development against this disease. Recently, numerous reports have described that the harmless bacteria Lactococcus lactis can be used as a bacterial vector for the efficient delivery of antigens in vivo, and that this approach is a promising vaccination strategy against bacterial infections. We therefore explored the immunization capacity of non- living recombinant L. lactis ClfA, L. lactis FnbpA, or L. lactis expressing ClfA together with Fnbp (a truncated form of FnbpA with only the fibronectin-binding domain but lacking the fibrinogen-binding domain A [L. lactis ClfA/Fnbp]), to protect against S. aureus experimental IE. L. lactis ClfA was used as immunization agent against the laboratory strain S. aureus Newman (expressing ClfA, but lacking FnbpA). L. lactis ClfA, L. lactis FnbpA, as well as L. lactis ClfA/Fnbp, were used as immunization agents against the endocarditis isolate S. aureus P8 (expressing both ClfA and FnbpA). Immunization with L. lactis ClfA produced anti-ClfA functional antibodies, which were able to block the binding of S. aureus Newman to fibrinogen in vitro and protect 13/19 (69%) animals from IE due to S. aureus Newman (P < 0.05 compared to controls). Immunization with L. lactis ClfA, L. lactis FnbpA or L. lactis ClfA/Fnbp, produced antibodies against each antigen. However, they were not sufficient to block S. aureus P8 binding to fibrinogen and fibronectin in vitro. Moreover, immunization with L. lactis ClfA or L. lactis FnbpA was ineffective (< 10% protected animals) and immunization with L. lactis ClfA/Fnbp conferred limited protection from IE (8/23 protected animals; P < 0.05 compared to controls) after challenge with S. aureus P8. Together, these results indicate that L. lactis is an efficient delivering antigen system potentially useful for preventing S. aureus IE. They also demonstrate that expressing multiple antigens in L. lactis, yet to be elucidated, will be necessary to prevent IE due to clinical S. aureus strains fully equipped with virulence determinants. In summary, our study has demonstrated experimentally, for the first time, the hypothesis that low-grade bacteremia, mimicking bacteremia occurring outside of a clinical intervention, is equally prone to induce experimental IE as high-grade bacteremia following medico-surgical procedures. In this context, where the use of antibiotics for the prophylaxis of IE is limited, we showed that other prophylactic measures, like the use of antiplatelets, anticoagulants, or vaccination employing L. lactis as delivery vector of bacterial antigens, are reasonable alternatives that warrant to be further investigated.

Optimum pilot overhead in wireless communication: a unified treatment of continuous and block-fading channels

The optimization of the pilot overhead in wireless fading channels is investigated, and the dependence of this overhead on various system parameters of interest (e.g., fading rate, signal-to-noise ratio) is quantified. The achievable pilot-based spectral efficiency is expanded with respect to the fading rate about the no-fading point, which leads to an accurate order expansion for the pilot overhead. This expansion identifies that the pilot overhead, as well as the spectral efficiency penalty with respect to a reference system with genie-aided CSI (channel state information) at the receiver, depend on the square root of the normalized Doppler frequency. It is also shown that the widely-usedblock fading model is a special case of more accurate continuous fading models in terms of the achievable pilot-based spectral efficiency. Furthermore, it is established that the overhead optimization for multiantenna systems is effectively the same as for single-antenna systems with thenormalized Doppler frequency multiplied by the number of transmit antennas.

Managers' perspective on continuous health education in a region of São Paulo State

OBJECTIVEAnalysing the concepts of Continuous Health Education - CHE (EPS - in Portuguese), operated by municipal managers and translated into official documents.METHODQualitative research with the use of official documents and semi-structured interviews with the Municipal Health Secretaries or Coordinators of Primary Health Care in the Northeast Region of São Paulo State, and thematic analysis of empirical material.RESULTSResults indicate difficulties in the municipalities problematizing their management practices, services and health care; EPS tools presented are insufficient and unsatisfactory for amending the array of problems raised and are still far from the routine of Primary Care services.CONCLUSIONDespite efforts to implement EPS actions for the strengthening of primary care, the process appears to be incipient.

Colonic movements in healthy subjects as monitored by a Magnet Tracking System.

The Magnet Tracking System (MTS) is a minimally-invasive technique of continuous evaluation of gastrointestinal motility. In this study, MTS was used to analyse colonic propulsive dynamics and compare the transit of a magnetic pill with that of standard radio-opaque markers. MTS monitors the progress in real time of a magnetic pill through the gut. Ten men and 10 women with regular daily bowel movements swallowed this pill and 10 radio-opaque markers at 8 pm. Five hours of recordings were conducted during 2 following mornings. Origin, direction, amplitude and velocity of movements were analysed relative to space-time plots of the pill trajectory. Abdominal radiographs were taken to compare the progress of both pill and markers. The magnetic pill lay idle for 90% of its sojourn in the colon; its total retrograde displacement accounted for only 20% of its overall movement. Analysis of these movements showed a bimodal distribution of velocities: around 1.5 and 50 cm min(-1), the latter being responsible for 2/3 of distance traversed. There were more movements overall and more mass movements in males. Net hourly forward progress was greater in the left than right colon, and greater in males. The position of the magnetic pill correlated well with the advancement of markers. MTS showed patterns and propulsion dynamics of colonic segments with as yet unmet precision. Detailed analysis of slow and fast patterns of colonic progress makes it possible to specify the motility of colonic segments, and any variability in gender. Such analysis opens up promising avenues in studies of motility disorders.

Variability of resting energy expenditure in healthy volunteers during fasting and continuous enteral feeding.

The magnitude of variability in resting energy expenditure (REE) during the day was assessed in nine healthy young subjects under two nutritional conditions: 1) mixed nutrient (53% carbohydrate, 30% fat, 17% protein) enteral feeding at an energy level corresponding to 1.44 REE; and 2) enteral fasting, with only water allowed. In each subject, six 30-min measurements of REE were performed using indirect calorimetry (hood system) at 90-min intervals from 9 AM to 5 PM. The mean REE and respiratory quotient were significantly (p less than .01) greater during feeding than during fasting (1.08 +/- 0.07 [SEM] vs. 1.00 +/- 0.06 kcal/min and 0.874 +/- 0.007 vs. 0.829 +/- 0.008 kcal/min, respectively). Mean postprandial thermogenesis was 4.9 +/- 0.4% of metabolizable energy administered. The intraindividual variability of REE throughout the day, expressed as the coefficient of variation, ranged from 0.7% to 2.0% in the fasting condition and from 1.2% to 4.1% in the feeding condition. There was no significant difference between the REE measured in the morning and that determined in the afternoon.

Physical quality of a yellow latossol under integrated crop-livestock system

Soil physical quality is essential to global sustainability of agroecosystems, once it is related to processes that are essential to agricultural crop development. This study aimed to evaluate physical attributes of a Yellow Latossol under different management systems in the savanna area in the state of Piaui. This study was developed in Uruçuí southwest of the state of Piauí. Three systems of soil management were studied: an area under conventional tillage (CT) with disk plowi and heavy harrow and soybean crop; an area under no-tillage with soybean-maize rotation and millet as cover crop (NT + M); two areas under Integrated Crop-Livestock System, with five-month pasture grazing and soybean cultivation and then continuous pasture grazing (ICL + S and ICL + P, respectively). Also, an area under Native Forest (NF) was studied. The soil depths studied were 0.00-0.05, 0.05-0.10 and 0.10-0.20 m. Soil bulk density, as well as porosity and stability of soil aggregates were analyzed as physical attributes. Anthropic action has changed the soil physical attributes, in depth, in most systems studied, in comparison to NF. In the 0.00 to 0.05 m depth, ICL + P showed higher soil bulk density value. As to macroporosity, there was no difference between the management systems studied and NF. The management systems studied changed the soil structure, having, as a result, a small proportion of soil in great aggregate classes (MWD). Converting native forest into agricultural production systems changes the soil physical quality. The Integrated Crop-Livestock System did not promote the improvement in soil physical quality.

Evaluation of Bridge Replacement Alternatives for the County Bridge System, HR-365 August 1994

Recent reports have indicated that 23.5 percent of the nation's highway bridges are structurally deficient and 17.7 percent are functionally obsolete. A significant number of these bridges are on the Iowa county road system. The objective of the investigation described in this report was to identify, review and evaluate replacement bridges currently being used by various counties in Iowa and surrounding states. Iowa county engineers, county engineers in neighboring states as well as private manufacturers of bridge components, and regional precad prestressed concrete manufacturers were contacted to determine the most common replacement bridge types being used. Depending upon the findings of the review, possible improvements and/or new replacement bridge systems were to be proposed. A questionnaire was developed and sent to county engineers in Iowa and several counties in surrounding states. The results of the questionnaire showed that the most common replacement bridges in Iowa are the continuous concrete slab and prestressed concrete bridges. The primary reason these types are used is because of the availability of standard designs and because of their ease of maintenance. Counties seldom construct these types of bridges using their own labor forces, but instead contract the work. However, county forces are used to construct steel stringer, precast reinforced concrete and timber bridges. In general, 69 percent of the counties indicate an ability and willingness to use their own forces to design and construct relatively short span bridges (i.e., 40 A or less) provided the construction procedures are relatively simple. Several unique replacement bridge types used in Iowa that are constructed by county forces are documented and presented in this report. Sufficient details are provided to allow county engineers to determine if some of these bridges could be used to resolve some of their own replacement bridge problems. Where possible, cost information has also been provided. Each of these bridge types were evaluated for various criteria (e.g., cost effectiveness, conformance to AASI-ITO standards, range of sizes, etc.) by a panel of four Iowa county engineers; a summary of this critique is included. After evaluating the questionnaire responses from the counties and evaluating the various bridge replacement concepts currently in use, one new bridge replacement concept and one modification of a current Iowa county bridge replacement concept were developed. Both of these concepts would utilize county labor forces.

Comparative assessment of intimal hyperplasia development after 14 days in two different experimental settings: tissue culture versus ex vivo continuous perfusion of human saphenous vein.

BACKGROUND: Intimal hyperplasia (IH) is a vascular remodeling process which often leads to failure of arterial bypass or hemodialysis access. Experimental and clinical work have provided insight in IH development; however, further studies under precise controlled conditions are required to improve therapeutic strategies to inhibit IH development. Ex vivo perfusion of human vessel segments under standardized hemodynamic conditions may provide an adequate experimental approach for this purpose. Therefore, chronically perfused venous segments were studied and compared to traditional static culture procedures with regard to functional and histomorphologic characteristics as well as gene expression. MATERIALS AND METHODS: Static vein culture allowing high tissue viability was performed as previously described. Ex vivo vein support system (EVVSS) was performed using a vein support system consisting of an incubator with a perfusion chamber and a pump. EVVSS allows vessel perfusion under continuous flow while maintaining controlled hemodynamic conditions. Each human saphenous vein was divided in two parts, one cultured in a Pyrex dish and the other part perfused in EVVSS for 14days. Testing of vasomotion, histomorphometry, expression of CD 31, Factor VIII, MIB 1, alpha-actin, and PAI-l were determined before and after 14days of either experimental conditions. RESULTS: Human venous segments cultured under traditional or perfused conditions exhibited similar IH after 14 days as shown by histomorphometry. Smooth-muscle cell (SMC) was preserved after chronic perfusion. Although integrity of both endothelial and smooth-muscle cells appears to be maintained in both culture conditions as confirmed by CD31, factor VIII, and alpha-actin expression, a few smooth-muscle cells in the media stained positive for factor VIII. Cell-proliferation marker MIB-1 was also detected in the two settings and PAI-1 mRNA expression and activity increased significantly after 14 days of culture and perfusion. CONCLUSION: This study demonstrates the feasibility to chronically perfuse human vessels under sterile conditions with preservation of cellular integrity and vascular contractility. To gain insights into the mechanisms leading to IH, it will now be possible to study vascular remodeling not only under static conditions but also in hemodynamic environment mimicking as closely as possible the flow conditions encountered in reconstructive vascular surgery.

Long-tailed trapping times and Lévy flights in a self-organized critical granular system

We present a continuous time random walk model for the scale-invariant transport found in a self-organized critical rice pile [K. Christensen et al., Phys. Rev. Lett. 77, 107 (1996)]. From our analytical results it is shown that the dynamics of the experiment can be explained in terms of Lvy flights for the grains and a long-tailed distribution of trapping times. Scaling relations for the exponents of these distributions are obtained. The predicted microscopic behavior is confirmed by means of a cellular automaton model.

Postmortem pump-driven reperfusion of the vascular system of porcine lungs: towards a new model for surgical training.

PURPOSE: The objective of this experiment is to establish a continuous postmortem circulation in the vascular system of porcine lungs and to evaluate the pulmonary distribution of the perfusate. This research is performed in the bigger scope of a revascularization project of Thiel embalmed specimens. This technique enables teaching anatomy, practicing surgical procedures and doing research under lifelike circumstances. METHODS: After cannulation of the pulmonary trunk and the left atrium, the vascular system was flushed with paraffinum perliquidum (PP) through a heart-lung machine. A continuous circulation was then established using red PP, during which perfusion parameters were measured. The distribution of contrast-containing PP in the pulmonary circulation was visualized on computed tomography. Finally, the amount of leak from the vascular system was calculated. RESULTS: A reperfusion of the vascular system was initiated for 37 min. The flow rate ranged between 80 and 130 ml/min throughout the experiment with acceptable perfusion pressures (range: 37-78 mm Hg). Computed tomography imaging and 3D reconstruction revealed a diffuse vascular distribution of PP and a decreasing vascularization ratio in cranial direction. A self-limiting leak (i.e. 66.8% of the circulating volume) towards the tracheobronchial tree due to vessel rupture was also measured. CONCLUSIONS: PP enables circulation in an isolated porcine lung model with an acceptable pressure-flow relationship resulting in an excellent recruitment of the vascular system. Despite these promising results, rupture of vessel walls may cause leaks. Further exploration of the perfusion capacities of PP in other organs is necessary. Eventually, this could lead to the development of reperfused Thiel embalmed human bodies, which have several applications.

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.

Adherence to oral anticancer treatment: focus on quality of execution during continuous schema of treatment

Background and objective: Oral anti-cancer treatments have expanded rapidly over the last years. While taking oral tablets at home ensures a better quality of life, it also exposes patients to the risk of sub-optimal adherence. The objective of this study is to assess how well ambulatory cancer patients execute their prescribed dosing regimen while they are engaged with continuous anti-cancer treatments. Design: This is an on-going longitudinal study. Consecutive patients starting an oral treatment are proposed to enter the study by the oncologist. Then they are referred to the pharmacy, where their oral anticancer treatment is dispensed in a Medication Event Monitoring System (MEMSTM), which records date and time of each opening of the drug container. Electronically compiled dosing history data from the MEMS are summarized and used as feedback during semistructured interviews with the pharmacist, which are dedicated to prevention and management of side effects. Interviews are scheduled before each medical visit. Report of the interview is available to the oncologist via an on-line secured portal. Setting: Seamless care approach between a Multidisciplinary Oncology Center and the Pharmacy of an Ambulatory Care and Community Medicine Department. Main outcome measures: For each patient, the comparison between the electronically compiled dosing history and the prescribed regimen was summarized using a daily binary indicator indicating whether yes or no the patient has taken the medication as prescribed. Results: Study started in March 2008. Among 22 eligible patients, 19 were included (11 men, median age 63 years old) and 3 (14%) refused to participate. 15 patients were prescribed a QD regimen, 3 patients a BID and 1 patient switched from QD to BID during follow-up. Median follow up was 182 days (IQR 72-252). Early discontinuation happened in four patients: side effects (n = 1), psychiatric reasons (n = 1), cancer progression (n = 1) and death (n = 1). On average, the daily number of medications was taken as prescribed in 99% of the follow-up days. Conclusions: Execution of the prescribed dosing regimens was almost perfect during the first 6 months. Maintaining this high degree of regimen execution and persistence over time might however be challenging in this population and need therefore to be confirmed in larger and longer follow-up cohort studies.

Strengthening of an Existing Continuous-Span, Steel-Beam, Concrete-Deck Bridge by Post-Tensioning, HR-308, 1990

The need to upgrade a large number of understrength and obsolete bridges in the U.S. has been well documented in the literature. Through several Iowa DOT projects, the concept of strengthening simple-span bridges by post-tensioning has been developed. The purpose of the project described in this report was to investigate the use of post-tensioning for strengthening continuous composite bridges. In a previous, successfully completed investigation, the feasibility of strengthening continuous, composite bridges by post-tensioning was demonstrated on a laboratory 1/3-scale-model bridge (3 spans: 41 ft 11 in. x 8 ft 8 in.). This project can thus be considered the implementation phase. The bridge selected for strengthening was in Pocahontas County near Fonda, Iowa, on County Road N28. With finite element analysis, a post-tensioning system was developed that required post-tensioning of the positive moment regions of both the interior and exterior beams. During the summer of 1988, the strengthening system was installed along with instrumentation to determine the bridge's response and behavior. Before and after post-tensioning, the bridge was subjected to truck loading (1 or 2 trucks at various predetermined critical locations) to determine the effectiveness of the strengthening system. The bridge, with the strengthening system in place, was inspected approximately every three months to determine any changes in its appearance or behavior. In 1989, approximately one year after the initial strengthening, the bridge was retested to identify any changes in its behavior. Post-tensioning forces were removed to reveal any losses over the one-year period. Post-tensioning was reapplied to the bridge, and the bridge was tested using the same loading program used in 1988. Except for at a few locations, stresses were reduced in the bridge the desired amount. At a few locations flexural stresses in the steel beams are still above 18 ksi, the allowable inventory stress for A7 steel. Although maximum stresses are above the inventory stress by about 2 ksi, they are about 5 ksi below the allowable operating stress; therefore, the bridge no longer needs to be load-posted.