Children's health care assistance according to their families: a comparison between models of Primary Care

OBJECTIVE To compare the health assistance models of Basic Traditional Units (UBS) with the Family Health Strategy (ESF) units for presence and extent of attributes of Primary Health Care (APS), specifically in the care of children. METHOD A cross-sectional study of a quantitative approach with families of children attended by the Public Health Service of Colombo, Paraná. The Primary Care Assessment Tool (PCA-Tool) was applied to parents of 482 children, 235 ESF units and 247 UBS units covering all primary care units of the municipality, between June and July 2012. The results were analyzed according to the PCA-Tool manual. RESULTS ESF units reached a borderline overall score for primary health care standards. However, they fared better in their attributes of Affiliation, Integration of care coordination, Comprehensiveness, Family Centeredness and Accessibility of use, while the attributes of Community Guidance/Orientation, Coordination of Information Systems, Longitudinality and Access attributes were rated as insufficient for APS. UBS units had low scores on all attributes. CONCLUSION The ESF units are closer to the principles of APS (Primary Health Care), but there is need to review actions of child care aimed at the attributes of APS in both care models, corroborating similar studies from other regions of Brazil.

Burnout and associated factors in employees of a Swiss teaching hospital

Background Working in a teaching hospital is a highly stressful occupation, which can lead to burnout. The consequences of burnout in health professionals can be very serious, both for themselves and patients. The aim of this cross-sectional study was to assess the extent of burnout and associated factors in hospital employees. Methods In the Fall of 2007, all employees of a Swiss teaching hospital were invited to complete a job satisfaction survey. It included the work-related burnout scale (scored 0-100) of the Copenhagen Burnout Inventory (CBI-French version), measuring the degree of physical and psychological fatigue and exhaustion perceived as related to the person's work; a high degree of burnout was defined as a score _50. Logistic regression analyses were used to determine factors associated with a high degree of burnout. Results A total of 4575 individuals returned the questionnaire (response rate 54%). Of them, 1503 (33%) had a high degree of burnout. The rate of burnout was higher among women (34.3% versus 30.5%, P = 0.012) and respondents younger than 40 years (37.7% versus 28.6%, P < 0.001). Executives were less prone to burnout than employees (27.1% versus 33.9%, P < 0.0019). Rates of burnout differed by profession: nurses and physicians had higher rates than administrative and logistic staff (42.8% and 37.4% versus 25.6% and 20.9%, respectively P < 0.001). Burnout was inversely associated with job satisfaction. In multivariate analysis, factors associated with burnout were overall dissatisfaction (OR 3.23; 95% CI 2.66-3.91), dissatisfaction with workload (OR 2.09; 95% CI 1.74-2.51) and work-life balance (OR 2.25; 95% CI 1.83-2.77), being a woman (OR 1.56; 95% CI 1.28-1.90), working fulltime (OR 1.41; 95% CI 1.08-1.85) and working as a nurse, a physician or in the psychosocial sector. Conclusions One-third of respondents, mostly nurses and physicians, experienced burnout and had lower levels of job satisfaction. The factors associated with burnout may help to tailor programmes aiming at reducing burnout at both the individual and organizational level within the hospital.

Internalization and homologous desensitization of the GLP-1 receptor depend on phosphorylation of the receptor carboxyl tail at the same three sites.

Homologous desensitization and internalization of the GLP-1 receptor correlate with phosphorylation of the receptor in a 33-amino acid segment of the cytoplasmic tail. Here, we identify the sites of phosphorylation as being three serine doublets located at positions 441/442, 444/445, and 451/452. The role of phosphorylation on homologous desensitization was assessed after stable expression in fibroblasts of the wild type or of mutant receptors in which phosphorylation sites were changed in various combinations to alanines. We showed that desensitization, as measured by a decrease in the maximal production of cAMP after a first exposure of the cells to GLP-1, was strictly dependent on phosphorylation. Furthermore, the number of phosphorylation sites correlated with the extent of desensitization with no, intermediate, or maximal desensitization observed in the presence of one, two, or three phosphorylation sites, respectively. Internalization of the receptor-ligand complex was assessed by measuring the rate of internalization of bound [125I]GLP-1 or the redistribution of the receptor to an endosomal compartment after agonist binding. Our data demonstrate that internalization was prevented in the absence of receptor phosphorylation and that intermediate rates of endocytosis were obtained with receptors containing one or two phosphorylation sites. Thus, homologous desensitization and internalization require phosphorylation of the receptor at the same three sites. However, the differential quantitative impairment of these two processes in the single and double mutants suggests different molecular mechanisms controlling desensitization and internalization.

Comparison of neoadjuvant cisplatin-based chemotherapy versus radiochemotherapy followed by resection for stage III (N2) NSCLC.

OBJECTIVE: Comparison of prospectively treated patients with neoadjuvant cisplatin-based chemotherapy vs radiochemotherapy followed by resection for mediastinoscopically proven stage III N2 non-small cell lung cancer with respect to postoperative morbidity, pathological nodal downstaging, overall and disease-free survival, and site of recurrence. METHODS: Eighty-two patients were enrolled between January 1994 to June 2003, 36 had cisplatin and doxetacel-based chemotherapy (group I) and 46 cisplatin-based radiochemotherapy up to 44 Gy (group II), either as sequential (25 patients) or concomitant (21 patients) treatment. All patients had evaluation of absence of distant metastases by bone scintigraphy, thoracoabdominal CT scan or PET scan, and brain MRI, and all underwent pre-induction mediastinoscopy, resection and mediastinal lymph node dissection by the same surgeon. RESULTS: Group I and II comprised T1/2 tumors in 47 and 28%, T3 tumors in 45 and 41%, and T4 tumors in 8 and 31% of the patients, respectively (P=0.03). There was a similar distribution of the extent of resection (lobectomy, sleeve lobectomy, left and right pneumonectomy) in both groups (P=0.9). Group I and II revealed a postoperative 90-d mortality of 3 and 4% (P=0.6), a R0-resection rate of 92 and 94% (P=0.9), and a pathological mediastinal downstaging in 61 and 78% of the patients (P<0.01), respectively. 5y-overall survival and disease-free survival of all patients were 40 and 36%, respectively, without significant difference between T1-3 and T4 tumors. There was no significant difference in overall survival rate in either induction regimens, however, radiochemotherapy was associated with a longer disease-free survival than chemotherapy (P=0.04). There was no significant difference between concurrent vs sequential radiochemotherapy with respect to postoperative morbidity, resectability, pathological nodal downstaging, survival and disease-free survival. CONCLUSIONS: Neoadjuvant cisplatin-based radiochemotherapy was associated with a similar postoperative mortality, an increased pathological nodal downstaging and a better disease-free survival as compared to cisplatin doxetacel-based chemotherapy in patients with stage III (N2) NSCLC although a higher number of T4 tumors were admitted to radiochemotherapy.

Safety Impacts of Pavement Edge Drop-offs, 2006

A vehicle may leave its travel lane for a number of reasons, such as driver error, poor surface conditions, or avoidance of a collision with another vehicle in the travel lane. When a vehicle leaves the travel lane, pavement edge drop-off poses a potential safety hazard because significant vertical differences between surfaces can affect vehicle stability and reduce a driver’s ability to handle the vehicle. Numerous controlled studies have tested driver response to encountering drop-offs under various conditions, including different speeds, vehicle types, drop-off height and shape, and tire scrubbing versus non-scrubbing conditions. The studies evaluated the drivers’ ability to return to and recover within their own travel lane after leaving the roadway and encountering a drop-off. Many of these studies, however, have used professional drivers as test subjects, so results may not always apply to the population of average drivers. Furthermore, test subjects are always briefed on what generally is to be expected and how to respond; thus, the sense of surprise that a truly naïve driver may experience upon realizing that one or two of his or her tires have just dropped off the edge of the pavement, is very likely diminished. Additionally, the studies were carried out under controlled conditions. The actual impact of pavement edge drop-off on drivers’ ability to recover safely once they leave the roadway, however, is not well understood under actual driving conditions. Additionally, little information is available that quantifies the number or severity of crashes that occur where pavement edge drop-off may have been a contributing factor. Without sufficient information about the frequency of edge drop-off-related crashes, agencies are not fully able to measure the economic benefits of investment decisions, evaluate the effectiveness of different treatments to mitigate edge drop-off, or focus maintenance resources. To address these issues, this report details research to quantify the contribution of pavement edge drop-off to crash frequency and severity. Additionally, the study evaluated federal and state guidance in sampling and addressing pavement edge drop-off and quantified the extent of pavement edge drop-off in two states. This study focused on rural two-lane paved roadways with unpaved shoulders, since they are often high speed facilities (55+ mph), have varying levels of maintenance, and are likely to be characterized by adverse roadway conditions such as narrow lanes or no shoulders.

Aortobronchial and aortoesophageal fistulae as risk factors in surgery of descending thoracic aortic aneurysms.

OBJECTIVE: Assess outcome of patients with descending thoracic aortic aneurysms complicated by aortobronchial and aortoesophageal fistulae in comparison to patients undergoing repair of aortic aneurysms without fistulae. METHODS: In a consecutive series of 145 patients (age 60 +/- 12 years) with repair of descending thoracic and thoracoabdominal aortic aneurysms, 11 patients (8%; age 63 +/- 9; NS) primarily presented for hematemesis and/or hemoptysis. In 8/11 patients (73%) an aortobronchial fistula was identified, and 3/11 patients (27%) suffered from an aortoesophageal fistula. Five of 11 patients (45%) had undergone previous aortic surgery in the same region. RESULTS: Extent of aortic segments (range 1-8) replaced was 3.1 +/- 1.4 for all versus 2.6 +/- 0.9 for fistulae (NS). Aortic cross clamp time was 38 +/- 22 min for all versus 45 +/- 15 min for fistulae (NS). Mortality at 30 days was 18/145 (12%) for all versus 16/134 (12%) without fistulae versus 2/11 (18%) with fistulae (NS). Paraparesis and or paraplegia was observed in 11/145 (8%) for all versus 10/134 (7%) without fistulae versus 1/11 (9%) for cases with fistulae (NS). Nine additional patients died after hospital discharge, seven without fistulae and two with fistulae (days 80, and 120) bringing the 1-year mortality up to 23/134 (17%) without fistulae versus 4/11 (36%) with fistulae (NS). Further analysis shows that the 1-year mortality accounts for 1/8 patients (13%) with aorto-bronchial fistulae versus to 3/3 patients (100%) with aorto-esophageal fistulae (esophageal versus bronchial fistula: P = 0.018; esophageal versus no fistula: P = 0.006). CONCLUSIONS: Outcome of patients suffering from descending thoracic aortic aneurysms complicated by aorto-bronchial fistulae can be similar to that without fistulae, whereas for cases complicated by aorto-esophageal fistulae the prognosis seems to remain poor even after successful hospital discharge.

A portrait of the Spanish accounting community

This study presents a portrait of the Spanish academic accountingcommunity in 1995, based upon a questionnaire circulated to Spanishaccounting academics in 1995 and upon an analysis of authorship andcitations in the main Spanish accounting journals. The approach tothese analyses is grounded in similar studies which have been carriedout in the United States, Spain and elsewhere. but the combination oftechniques used in this study is particularly broad in range.The results of the study are used to describe a range ofcharacteristics of Spanish accounting academics, for example,publications records and length of academic experience. The analysisof publications produces a ranking by institutional affiliation ofthe most significant contributors to current debates on accounting.Citation analysis is used to identify the range and extent ofinternational influences upon the Spanish academic accountingcommunity, and to provide an additional ranking by institutionalaffiliation of the most frequently cited sources A significantfinding was that the nature and extent of international influence hadchanged very little over the ten year period since Spain entered theEuropean Union and started to implement European Directives.Perceptions of journal quality were elicited by questionnaire. Fortyfive journals, Spanish and international are included in a listranked for perceived importance as outlets for publication. and assources of support for teaching and research. The results of thisexercise show that Spanish journals were ranked low relative tojournals published in the United Kingdom and United States.Finally the study examines the extent of purpose upon Spanishaccounting academies to publish, by presenting results of a questionabout criteria for promotion, and also by examining and increasingtendency to publish co-authored work.

Causes of subcontracting: Evidence from panel data on construction firms

This paper examines factors explaining subcontracting decisions in the construction industry. Rather than the more common cross-sectional analyses, we use panel data to evaluate the influence of all relevant variables. We design and use a new index of the closeness to small numbers situations to estimate the extent of hold-up problems. Results show that as specificity grows, firms tend to subcontract less. The opposite happens when output heterogeneity and the use of intangible assets and capabilities increase. Neither temporary shortage of capacity nor geographical dispersion of activities seem to affect the extent of subcontracting. Finally, proxies for uncertainty do not show any clear effect.

Entrepreneurial structure of the mercantile company in pre-industrial Catalonia

The mercantile company was the basic form of enterprise in pre-industrial Catalonia. The aim of this paper is to study the formation and development of the mercantile companies in Barcelona whose end was the wholesale and retail sale of textiles in the botigues de teles (textile retail shops) throughout the eighteenth century. These firms were officially registered before a notary and their deeds reveal how these establishments were administered and managed.The study covers a sample of 121 mercantile companies, and the articles and documentation that were put into effect by 32 notaries who were active in Barcelona in the 18th century have been consulted in their entirety. From an initial selection of documentation, a total of 228 deeds registering companies have been found, 107 of which (47%) relate to the creation of companies whose various activities were centred in taverns, textile manufacturing, braiding.... While the 121 companies, which make up our sample and which account for 53% of the deeds registered with the notaries mentioned above, focused exclusively on the management of textile retail shops located in the commercial heart of the city. Thus one point of interest that the documentation reveals is that the majority of the mercantile companies registered by Barcelona notaries throughout the 18th century were establishments which traded in textiles. The first part of the article focuses on the structural characteristics of these enterprises, the number and socio-professional status of the partners and the extent of each partner s involvement in the administration and management. The second part of the article examines the capital investment made by each partner, their rights and obligations agreed on, the sharing out of profits and possible losses and the duration of the companies. The final aim of the paper is to highlight the evolution of these companies through one specific case.

Partial melting of basic dykes in the contact aureoles of two shallow-level, gabbro-pyroxenite intrusions, Fuerteventura

THESIS ABSTRACT Low-pressure anatexis of basic dykes gave rise to unusual, zebra-like migmatites, in the contact metamorphic aureoles of two layered gabbro-pyroxenite intrusions, PXl and PX2, in the root zone of an ocean island, Fuerteventura Basal Complex (Canary Islands). This thesis focuses on the understanding of processes attributing to the partial melting and formation of these migmatites, characterised by a dense network of closely spaced, millimetre-wide leucocratic segregations with perfectly preserved igneous textures. The presence of fluids are required to decrease the solidus of basic igneous lithologies, to allow partial melting in such aloes-pressure (1-2 kb) environment. An oxygen isotope study was thus carried out on dykes inside and beyond the PX2 aureole, in order to decipher the nature and origin of such fluids. Low or negative δ18O values were obtained for whole rocks and mineral-separates, decreasing towards the contact, with the intrusion itself retaining fairly high values. This trend has been attributed to the advection of meteoric water during magma emplacement, with increasing fluid/rock ratios (higher dyke intensities towards the intrusion acting as fluid-pathways) and higher temperatures promoting increasing exchange during recrystallisation. A comparison of whole rock and mineral major- and trace- element data allowed the redistribution of elements .between different mineral phases and generations, during contact metamorphism and partial melting to be assessed. Certain trace-elements, e.g. Zr, Hf, Y, and REEs, were internally redistributed during contact metamorphic recrystallisation, causing- the enrichment of neocrystallised diopsides compared to relict phenocrysts. This has been assigned to the liberation of trace elements on the breakdown of primary minerals, kaersutite and sphene, on entering the thermal aureole. Major and trace element compositions of minerals in migmatite melanosomes and leucosomes are almost identical, pointing to a syn- or post- solidus reequilibration on cooling of the migmatite terrain. The mineralogical, textural and geochemical evolution of dykes in a contact metamorphic aureole, is recorded around an apophysis of the PX1 intrusion, where there is evidence of incipient partial melting. Hydrothermal mineral pseudomorphs in the outer parts of the aureole are progressively replaced by dry mineral assemblages, with increasingly recrystallised diopside and evidence of partial melting -the extent of which varies from one lithology to another. The appearance of more mafic lithologies towards the intrusion, with lower whole rock SiO2 and mobile element abundances, e.g. Rb, Cs, K, has been explained by the migration and accumulation of feldspathic material into leucosomes outside the samples. A micro-structural study of leucosomes and leucocratic pods, with the aid of high-resolution X-ray computed micro-tomography (HRXµCT), allowing the visualization and quantification of shapes and orientations, was carried out in order to better understand the processes of melt segregation in the PX1 aureole. Leucocratic pods, representing former amygdales, are considered as natural strain ellipsoids. Their short axes are oriented perpendicular to leucosome planes, which sub-parallel the intrusive contact. Leucosomes thus effectively represent foliation planes. This implies that the direction of maximum shortening, during migmatisation, was perpendicular to the orientation of leucosomes, contradicting earlier models that suggest leucosomes represent tension veins. RESUME DE LA THESE Un phénomène rare de fusion partielle de filons basiques à basse pression a été étudié dans les auréoles de contact de deux intrusions litées de gabbro-pyroxénite, PX1 et PX2, localisées dans le soubassement de l'île volcanique de Fuerteventura aux Canaries. Cette anatexie a engendré des migmatites finement zébrées d'aspect très inhabituel, dont les processus de formation ont été étudiés dans le présent travail. Ces roches sont caractérisées par un réseau dense de veinules leucocrates d'épaisseur millimétrique, dont les textures ignées sont parfaitement préservées. La fusion partielle de roches basiques à basse pression (1-2 kbar) requiert la présence d'eau afin d'abaisser le solidus du système à des températures géologiquement réalistes. Une étude comparative des isotopes de l'oxygène a ainsi été menée sur des filons respectivement affectés et non affectés par le métamorphisme de contact, afin de confirmer la présence de ces fluides, de déterminer l'importance de leur interaction avec les roches et leur origine. Des valeurs de δ180 basses ou négatives ont été mesurées sur roche totale et minéraux séparés, décroissantes en direction du contact, alors que l'intrusion elle-même a conservé des valeurs élevées. Ce gradient a été attribué à l'advection d'eau météorique durant la mise en place du magma, les températures les plus élevées favorisant d'autant plus la circulation des fluides et les échanges isotopiques durant la recristallisation des roches. Cette recristallisation engendré une redistribution chimique complète des éléments entre les différentes générations de minéraux résultant du métamorphisme de contact et de l'anatexie, mise en évidence par microanalyse. Certains éléments traces comme Zr, Hf, Y et les REE ont été concentrés dans le diopside néoformé consécutivement à la déstabilisation de minéraux primaires riches en ces éléments comme la kaersutite ou le sphène. Les compositions en éléments majeurs et traces des minéraux des mélanosomes et leucosomes des migmatites sont pratiquement identiques, indiquant une rééquilibration syn- à postsolidus lors du refroidissement de l'auréole de contact. La transformation progressive des filons basiques au niveau de leur minéralogie, textures et composition chimique a pu être observée en détail à l'approche du contact d'une apophyse de l'intrusion PX1. La paragenèse magmatique initiale n'est jamais préservée, les faciès les plus distants du contact étant constitués d'un assemblage pseudomorphique hydrothermal. Ce dernier est progressivement remplacé par des assemblages anhydres incluant du diopside néoformé, puis apparaissent les premiers signes de fusion partielle, dont l'importance varie fortement d'une lithologie à l'autre. L'apparition de faciès plus basiques en direction du contact, avec des teneurs réduites en SiO2 et en éléments incompatibles tels Rb, Cs, K, a été attribuée à l'échappement de leucosomes feldspathiques hors du système. Une étude microstructurale de la distribution spatiale du matériel leucocrate au sein des migmatites par microtomographie X de haute résolution (HRXµCT) a été menée pour mieux comprendre les processus de ségrégation des liquides dans l'auréole de PX1. De petites entités ovoïdes, représentant d'anciennes structures amygdalaires au sein des filons, ont été considérées comme des ellipsoïdes marqueurs de la déformation finie. Leur petit axe est orienté perpendiculairement aux plans définis par les leucosomes, eux-mêmes subparallèles au contact intrusif. Les leucosomes matérialisent donc des plans de clivage. Ainsi, la direction de raccourcissement maximum durant la fusion partielle était perpendiculaire à l'orientation des leucosomes, contrairement à ce qui a été dit dans de précédentes publications, qui suggéraient que les leucosomes représentaient des veines de tension. RESUME DE LA THESE (POUR LE GRAND PUBLIC) L'observation directe du soubassement d'une île volcanique est une occasion rare, accessible dans le «complexe de base » de l'île canarienne de Fuerteventura. Ce dernier a enregistré divers phénomènes magmatiques, métamorphiques et de fusion partielle induits par l'intrusion répétée de magmas alimentant des appareils volcaniques sus jacents, sous forme de petits plutons, essaims de filons et complexes annulaires de gabbros alcalins, pyroxénites, syénites et carbonatites. Dans ce contexte de flux de chaleur élevé, des filons basiques ont subi une fusion partielle au contact de deux intrusions de gabbro-pyroxénite, un phénomène extrêmement rare à une profondeur aussi réduite, estimée à quelque 3-6 km. Les produits de cette fusion partielle sont des liquides très riches en feldspath, concentrés en un réseau dense de veinules blanches (leucosomes) au sein du matériau résiduel sombre non fondu (mélanosome) pour former ce qu'on appelle des migmatites. Outre les aspects pétrologiques liés à la formation de ces migmatites, l'intérêt majeur du phénomène réside dans le fait qu'il puisse représenter la source des magmas évolués parfois observés sur les îles océaniques. A des pressions aussi faibles que dans le soubassement de Fuerteventura (1-2 Kbar), la présence de fluides abondants est nécessaire pour abaisser la température de début de fusion des roches (solidus) à des valeurs géologiquement réalistes. Des expériences ont montré que même en présence de plusieurs %-poids d'eau, une température de 1000°C était encore nécessaire pour obtenir une proportion de liquide équivalente à celle observée sur le terrain, soit 25%. Or les magmas alcalins des îles océaniques, bien qu'hydratés, n'en contiennent de loin pas autant, ce qui implique une source d'eau externe. Une étude isotopique de l'oxygène a été entreprise afin de tester cette hypothèse. Les valeurs obtenues en 5180 sont basses ou négatives et indiquent l'influence d'eau d'origine météorique. Cette eau de pluie se serait infiltrée le long des filons depuis la surface du volcan et les aurait complètement hydrothermalisés en profondeur (situation encore visible à l'extérieur de l'auréole de contact), leur permettant ainsi de stocker l'eau nécessaire à leur fusion partielle ultérieure. L'interaction entre eau de pluie et filons a été d'autant plus importante que ces derniers étaient proches du contact avec l'intrusion, ce qui suggère que la circulation de ces eaux et leur interaction avec les roches a été favorisée par la chaleur fournie par l'intrusion elle-même. Un autre aspect de ce travail s'est focalisé sur la redistribution des éléments traces au sein des minéraux des filons basiques durant le métamorphisme de contact et la fusion partielle. Ainsi, le pyroxène de seconde génération est-il sensiblement enrichi en traces telles Zr, Hf, Y et les terres rares, par rapport au pyroxène magmatique originel, en relation avec la déstabilisation de minéraux primaires riches en ces éléments tels le sphène et la kaersutite. Cependant, les compositions en éléments majeurs et traces des minéraux recristallisés des migmatites sont pratiquement les mêmes dans les leucosomes et les mélanosomes, suggérant une rééquilibration chimique complète durant le refroidissement de ces lithologies. Si certaines migmatites se sont comportées en système chimiquement fermé (hormis l'eau météorique), d'autres filons ont manifestement perdu une partie de leurs leucosomes, ainsi qu'en témoigne leur composition progressivement appauvrie en silice et autres éléments incompatibles mobiles, tels K et Rb à l'approche du contact de l'intrusion. Parallèlement à cette évolution chimique, les paragenèses hydrothermales distantes du contact sont progressivement remplacées par des paragenèses anhydres, puis par l'apparition des premiers leucosomes, tandis que les textures magmatiques initiales sont complètement effacées au profit d'une combinaison de textures magmatique dans les leucosomes et en mosaïque dans les mélanosomes. Enfin, la distribution spatiale des liquides de fusion partielle a été étudiée par microtomographie X de haute résolution, dans des filons contenant des entités ovoïdes leucocrates, sans doute d'anciennes amygdales à zéolites. Ces dernières ont été considérées comme des ellipsoïdes de la déformation finie. L'orientation de leur petit axe, perpendiculaire au plan défini par les veinules de leucosomes, indique que ces derniers représentent des plans de clivage perpendiculaires à la direction de raccourcissement maximum. Ainsi, la ségrégation des liquides de fusion partielle se serait faite dans les plans de compression et non dans des plans de dilatation, contrairement à ce que laisserait penser le sens commun.

Evaluation of a topical cyclosporine A prodrug on corneal graft rejection in rats.

PURPOSE: To assess the efficacy of a topical cyclosporine A (CsA), water-soluble prodrug, for promoting the survival of allogenic rat corneal grafts after penetrating keratoplasty (PKP). METHODS: Corneas of Brown-Norway rats (donors) were transplanted to Lewis rats (recipients). Transplanted rats were divided in three treatment groups: group I (PBS) and group II (0.26% Debio088) received drops five times per day. Group III received a daily intramuscular CsA injection (10 mg/kg/day). Blood CsA concentrations were measured on days 2 and 14. On day 4, 10, 13 after PKP, grafts were scored for corneal transparency, edema and extent of neovascularization. An opacity score of greater than or equal to 3 was considered as a nonreversible graft rejection process. On day 14, the experimental eyes were processed for histology. RESULTS: On day 13, 12 of the 18 corneal transplants (67%) in group I showed irreversible graft rejection. Three of 18 transplants (19%) in group II and 5 of 16 transplants (28%) in group III showed irreversible graft rejection (p=0.013/p=0.019, OR=0.14/0.06 versus vehicle). Each mean clinical score for edema, opacity, and neovessels in group II were significantly lower than those of the grafts in group I (respectively p=0.010, p=0.013, p=0.024) and III except for neovessels (respectively p=0.002, p=0.001, p=0.057). Histology confirmed the clinical results. The mean CsA blood levels for groups II and III were, respectively 54+/-141 mug/l and 755+/-319 mug/l on day 2 and 14+/-34 mug/l and 1318+/-463 mug/l on day 14. CONCLUSIONS: Debio088 CsA prodrug drops given five times daily are as effective as intramuscular injection of 10 mg/kg/day for the prevention of acute corneal graft rejection in rats.

Expression of the proto-oncogene c-fos in three-dimensional fetal brain cell cultures and the lack of correlation with maturation-inducing stimuli.

Previous work has shown that aggregating fetal brain cell cultures are able to attain a highly differentiated state, and that their development is greatly enhanced by growth and/or differentiation factors such as epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and the protein kinase C-activating tumor promoter mezerein. The present study shows that in these 3-dimensional cultures the peptide growth factors EGF and bFGF as well as mezerein are able to induce the expression of the proto-oncogene c-fos. This induction was rapid and transient, in good agreement with observations reported from a wide variety of cell types in vitro. The maximal levels of c-fos mRNA found after stimulation were low in immature cultures and increased greatly as maturation progressed. Of the three factors tested, mezerein was the most potent inducer of c-fos. In contrast to the peptide growth factors EGF and bFGF which were found to induce c-fos only in glial cells, mezerein was stimulatory in glial cells as well as in neurons. A similar cell type specificity has been observed previously for the maturation-enhancing response in immature aggregate cultures. However, in the present study no correlation was found between the degree of c-fos induction and the extent of the maturation-enhancing stimulation. Immature cultures known to be most sensitive and responsive to these maturation-enhancing agents required relatively high doses of peptide growth factors for the induction of c-fos, and the maximal levels of c-fos mRNA elicited were much lower than those in differentiated cultures which did not show any long-term response to these stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

A burst of segmental duplications in the genome of the African great ape ancestor

It is generally accepted that the extent of phenotypic change between human and great apes is dissonant with the rate of molecular change. Between these two groups, proteins are virtually identical, cytogenetically there are few rearrangements that distinguish ape-human chromosomes, and rates of single-base-pair change and retrotransposon activity have slowed particularly within hominid lineages when compared to rodents or monkeys. Studies of gene family evolution indicate that gene loss and gain are enriched within the primate lineage. Here, we perform a systematic analysis of duplication content of four primate genomes (macaque, orang-utan, chimpanzee and human) in an effort to understand the pattern and rates of genomic duplication during hominid evolution. We find that the ancestral branch leading to human and African great apes shows the most significant increase in duplication activity both in terms of base pairs and in terms of events. This duplication acceleration within the ancestral species is significant when compared to lineage-specific rate estimates even after accounting for copy-number polymorphism and homoplasy. We discover striking examples of recurrent and independent gene-containing duplications within the gorilla and chimpanzee that are absent in the human lineage. Our results suggest that the evolutionary properties of copy-number mutation differ significantly from other forms of genetic mutation and, in contrast to the hominid slowdown of single-base-pair mutations, there has been a genomic burst of duplication activity at this period during human evolution.

Long term global evaluation of a national AIDS prevention strategy: the case of Switzerland.

OBJECTIVES: The Swiss Aids prevention strategy has been subject to a continuous process of evaluation for the past 12 years. This paper describes the conceptual approach, methodology, results obtained and contribution to policy-making of that evaluation.¦DESIGN: The evaluation is on-going, global with respect to all components of the strategy, and utilization-focused. Each successive phase of the evaluation has included 10-20 studies centred either on aspects of process, of outcome or of environmental context. Findings are synthesized at the end of each phase. METHODS: Both quantitative and qualitative methods are used. Studies generally have one of three functions within the overall evaluation: assessment of trends through surveys or other types of repeated studies; evaluation of specific areas through a series of studies from different viewpoints; in-depth investigation or rapid assessment through one-off studies. Various methods of triangulation are used to validate findings. RESULTS: The evaluation has allowed for: the observation of behavioural change in different populations; the availability of scientific data in controversial fields such as drug-use policy; an understanding of the diversity of public appropriation of prevention messages. Recommendations are regularly formulated and have been used by policy-makers and field workers for strategy development. CONCLUSIONS: The global approach adopted corresponds well to the evaluation requirements of an integrated long-term prevention strategy. Cost is low relative to the extent of information provided. Such an evaluation cannot however address the question of causal relationship between the strategy and observed changes. The evaluation has contributed to the development of a culture of evaluation in Swiss AIDS prevention more generally.

Preclinical comparison of mTHPC and verteporfin for intracavitary photodynamic therapy of malignant pleural mesothelioma.

Efficacy and tumour selectivity of photodynamic therapy with two clinically approved sensitizers (mTHPC, verteporfin) were assessed for focal intracavitary photodynamic therapy (PDT) in rodents with malignant pleural mesothelioma (MPM) at recommended drug-light conditions and at escalating sensitizer dosages. MPM tumours were generated in 15 Fischer rats by subpleural mediastinal tumour cell injection followed after 5 days by intracavitary PDT with light delivery monitored by in situ dosimetry. Animals were intravenously sensitized either with mTHPC (0.1 mg/kg, n = 3; 0.2 mg/kg, n = 3) followed after 4 days by illumination with 20 J/cm(2) at 652 nm, or with verteporfin (0.6 mg/kg, n = 3; 1.2 mg/kg, n = 3) followed after 20 min by illumination with 100 J/cm(2) at 689 nm. Three untreated tumour-bearing animals served as controls. Histological evaluation of the treated tumour and of adjacent normal organs was performed 10 days after tumour implantation. The extent of PDT-induced tumour necrosis was compared to the non-necrosed area and expressed in percentage. A locally invasive growing MPM tumour (3.1 +/- 1 mm diameter) without spontaneous necrosis diameter was found in all animals. For both sensitizers, focal intracavitary PDT was well tolerated at drug-light conditions recommended for clinical applications. Mediastinal organs were spared for both sensitizers but verteporfin resulted in a higher extent of tumour necrosis (80%) than mTHPC (50%). Drug dose escalation revealed a higher extent of PDT-related tumour necrosis for both sensitizers (mTHPC 55%, verteporfin 88%), however, verteporfin-PDT was associated with a higher toxicity than mTHPC-PDT.