'Doctor, what would you do in my position?' Health professionals and the decision-making process in pregnancy monitoring.

OBJECTIVE: Routine prenatal screening for Down syndrome challenges professional non-directiveness and patient autonomy in daily clinical practices. This paper aims to describe how professionals negotiate their role when a pregnant woman asks them to become involved in the decision-making process implied by screening. METHODS: Forty-one semi-structured interviews were conducted with gynaecologists-obstetricians (n=26) and midwives (n=15) in a large Swiss city. RESULTS: Three professional profiles were constructed along a continuum that defines the relative distance or proximity towards patients' demands for professional involvement in the decision-making process. The first profile insists on enforcing patient responsibility, wherein the healthcare provider avoids any form of professional participation. A second profile defends the idea of a shared decision making between patients and professionals. The third highlights the intervening factors that justify professionals' involvement in decisions. CONCLUSIONS: These results illustrate various applications of the principle of autonomy and highlight the complexity of the doctor-patient relationship amidst medical decisions today.

Relationship between imatinib population pharmacokinetics and alpha-1-acid glycoprotein

Objectives: Considering the large inter-individual differences in the function of the systems involved in imatinib disposition, exposure to this drug can be expected to vary widely among patients. Among those known systems is alpha-1-acid glycoprotein (AGP), a circulating protein that strongly binds imatinib. This observational study aimed to explore the influence of plasma AGP on imatinib pharmacokinetics. Methods: A population pharmacokinetic analysis was performed using NONMEM based on 278 plasma samples from 51 oncologic patients, for whom both total imatinib and AGP plasma concentrations were measured. The influence of this biological covariate on oral clearance and volume of distribution was examined. Results: A one-compartment model with first-order absorption appropriately described the data. A hyperbolic relationship between plasma AGP levels and oral clearance, as well as volume of distribution was observed. A mechanistic approach was built up, postulating that only the unbound imatinib concentration was able to undergo first-order elimination through an unbound clearance process, and integrating the dissociation constant as a parameter in the model. This approach allowed determining an average (± SEM) free clearance of 1310 (± 172) L/h and a volume of distribution of 301 (± 23) L. By comparison, the total clearance previously determined was 14 (± 1) L/h. Free clearance was affected by body weight and pathology diagnosis. Moreover, this model provided consistent estimates of the association constant between imatinib and AGP (5.5?106 L/mol) and of the average in vivo free fraction of imatinib (1.1%). The variability observed (17% for free clearance and 66% for volume of distribution) was less than the one previously reported without considering AGP impact. AGP explained indeed about one half of the variability observed in total imatinib disposition. Conclusion: Such findings clarify in part the in vivo impact of protein binding on imatinib disposition and might raise again the question whether high levels of AGP could represent a resistance factor to imatinib. This remains however questionable, as it is not expected to affect free drug concentrations. On the other hand, would imatinib be demonstrated as a drug requiring therapeutic drug monitoring, either the measurement of free concentration or the correction of the total concentration by the actual AGP plasma levels should be considered for accurate interpretation of the results.

Is human lactation a particularly efficient process?

The recommended dietary allowances of many expert committees (UK DHSS 1979, FAO/WHO/UNU 1985, USA NRC 1989) have set out the extra energy requirements necessary to support lactation on the basis of an efficiency of 80 per cent for human milk production. The metabolic efficiency of milk synthesis can be derived from the measurements of resting energy expenditure in lactating women and in a matched control group of non-pregnant non-lactating women. The results of the present study in Gambian women, as well as a review of human studies on energy expenditure during lactation performed in different countries, suggest an efficiency of human milk synthesis greater than the value currently used by expert committees. We propose that an average figure of 95 per cent would be more appropriate to calculate the energy cost of human lactation.

Prise en charge des jeunes patients avec endocrinopathies pediatriques chroniques: les défis d'une transition souvent difficile [Caring for patients with pediatric endocrinopathies and diabetes into adulthood: challenges of an often difficult transition].

The success of therapies for a number of pediatric disorders has posed new challenges for the long-term follow-up of adolescents with chronic endocrinopathies. Unfortunately, too many patients are lost during the transfer from pediatric to adult clinics. The transition process should be well-organized and include the young person and family. Recognizing the special needs of these adolescents is an important step in developing patient-centered approaches to care that enable patients to develop autonomy and self care skills. Key elements in this process include structured policies and guidelines, communication and close collaboration between pediatric and adult clinics, and integrating nurse clinicians in the transition process to help close the gaps in care.

The Na+-dependent chloride-bicarbonate exchanger SLC4A8 mediates an electroneutral Na+ reabsorption process in the renal cortical collecting ducts of mice.

Regulation of sodium balance is a critical factor in the maintenance of euvolemia, and dysregulation of renal sodium excretion results in disorders of altered intravascular volume, such as hypertension. The amiloride-sensitive epithelial sodium channel (ENaC) is thought to be the only mechanism for sodium transport in the cortical collecting duct (CCD) of the kidney. However, it has been found that much of the sodium absorption in the CCD is actually amiloride insensitive and sensitive to thiazide diuretics, which also block the Na-Cl cotransporter (NCC) located in the distal convoluted tubule. In this study, we have demonstrated the presence of electroneutral, amiloride-resistant, thiazide-sensitive, transepithelial NaCl absorption in mouse CCDs, which persists even with genetic disruption of ENaC. Furthermore, hydrochlorothiazide (HCTZ) increased excretion of Na+ and Cl- in mice devoid of the thiazide target NCC, suggesting that an additional mechanism might account for this effect. Studies on isolated CCDs suggested that the parallel action of the Na+-driven Cl-/HCO3- exchanger (NDCBE/SLC4A8) and the Na+-independent Cl-/HCO3- exchanger (pendrin/SLC26A4) accounted for the electroneutral thiazide-sensitive sodium transport. Furthermore, genetic ablation of SLC4A8 abolished thiazide-sensitive NaCl transport in the CCD. These studies establish what we believe to be a novel role for NDCBE in mediating substantial Na+ reabsorption in the CCD and suggest a role for this transporter in the regulation of fluid homeostasis in mice.

Well-being and the frailty process in later life: an evaluation of the effectiveness of downward social comparison

This article, which is based on a longitudinal study conducted with a cohort ofoctogenarians, examines downward social comparison and its effectiveness as an adjustment mechanism during the frailty process. First of all, a paradoxical stability of subjective well-being is to be observed: it remains stable over five years notwithstanding the general decline in health. Next, an analysis based on individual health trajectories reveals that downward social comparison is associated with the maintenance of a stable level of well-being, whereas, when it is not associated with well-being, the latter tends to vary.

Tuberculosis comorbidity with communicable and non-communicable diseases: integrating health services and control efforts.

Recent data for the global burden of disease reflect major demographic and lifestyle changes, leading to a rise in non-communicable diseases. Most countries with high levels of tuberculosis face a large comorbidity burden from both non-communicable and communicable diseases. Traditional disease-specific approaches typically fail to recognise common features and potential synergies in integration of care, management, and control of non-communicable and communicable diseases. In resource-limited countries, the need to tackle a broader range of overlapping comorbid diseases is growing. Tuberculosis and HIV/AIDS persist as global emergencies. The lethal interaction between tuberculosis and HIV coinfection in adults, children, and pregnant women in sub-Saharan Africa exemplifies the need for well integrated approaches to disease management and control. Furthermore, links between diabetes mellitus, smoking, alcoholism, chronic lung diseases, cancer, immunosuppressive treatment, malnutrition, and tuberculosis are well recognised. Here, we focus on interactions, synergies, and challenges of integration of tuberculosis care with management strategies for non-communicable and communicable diseases without eroding the functionality of existing national programmes for tuberculosis. The need for sustained and increased funding for these initiatives is greater than ever and requires increased political and funder commitment.

SESAM - a new framework integrating macroecological and species distribution models for predicting spatio-temporal patterns of species assemblages

Two different approaches currently prevail for predicting spatial patterns of species assemblages. The first approach (macroecological modelling, MEM) focuses directly on realised properties of species assemblages, whereas the second approach (stacked species distribution modelling, S-SDM) starts with constituent species to approximate assemblage properties. Here, we propose to unify the two approaches in a single 'spatially-explicit species assemblage modelling' (SESAM) framework. This framework uses relevant species source pool designations, macroecological factors, and ecological assembly rules to constrain predictions of the richness and composition of species assemblages obtained by stacking predictions of individual species distributions. We believe that such a framework could prove useful in many theoretical and applied disciplines of ecology and evolution, both for improving our basic understanding of species assembly across spatio-temporal scales and for anticipating expected consequences of local, regional or global environmental changes. In this paper, we propose such a framework and call for further developments and testing across a broad range of community types in a variety of environments.

Assimilation process in a psychotherapy with a client presenting schizoid personality disorder

The assimilation of problematic experiences has been studied as change processes in psychotherapies of different client populations. Several theory-building case studies using the assimilation model have shown how important a meaning bridge is in such change processes. In a client presenting schizoid personality disorder the creation of meaning as an affect-evoking process may be a particularly important stage in the change process. The present case study aims to apply the assimilation model to a psychotherapy process with a highly disturbed client and focuses on the creation of a meaning bridge in the process. Moreover, the assimilation analysis focuses on the effect of an external person, i.e. the partner or the therapist, when responding to the client's unassimilated problematic experiences. Their effects on the client's assimilation processes are discussed.

TECTONICS OF THE HELVETIC NAPPE SYSTEM (W SWITZERLAND): CONTROL OF STRAIN LOCALIZATION AND BASEMENT-COVER DEFORMATION. Insights from models based on continuum mechanics

The Helvetic nappe system in Western Switzerland is a stack of fold nappes and thrust sheets em-placed at low grade metamorphism. Fold nappes and thrust sheets are also some of the most common features in orogens. Fold nappes are kilometer scaled recumbent folds which feature a weakly deformed normal limb and an intensely deformed overturned limb. Thrust sheets on the other hand are characterized by the absence of overturned limb and can be defined as almost rigid blocks of crust that are displaced sub-horizontally over up to several tens of kilometers. The Morcles and Doldenhom nappe are classic examples of fold nappes and constitute the so-called infra-Helvetic complex in Western and Central Switzerland, respectively. This complex is overridden by thrust sheets such as the Diablerets and Wildhörn nappes in Western Switzerland. One of the most famous example of thrust sheets worldwide is the Glariis thrust sheet in Central Switzerland which features over 35 kilometers of thrusting which are accommodated by a ~1 m thick shear zone. Since the works of the early Alpine geologist such as Heim and Lugeon, the knowledge of these nappes has been steadily refined and today the geometry and kinematics of the Helvetic nappe system is generally agreed upon. However, despite the extensive knowledge we have today of the kinematics of fold nappes and thrust sheets, the mechanical process leading to the emplacement of these nappe is still poorly understood. For a long time geologist were facing the so-called 'mechanical paradox' which arises from the fact that a block of rock several kilometers high and tens of kilometers long (i.e. nappe) would break internally rather than start moving on a low angle plane. Several solutions were proposed to solve this apparent paradox. Certainly the most successful is the theory of critical wedges (e.g. Chappie 1978; Dahlen, 1984). In this theory the orogen is considered as a whole and this change of scale allows thrust sheet like structures to form while being consistent with mechanics. However this theoiy is intricately linked to brittle rheology and fold nappes, which are inherently ductile structures, cannot be created in these models. When considering the problem of nappe emplacement from the perspective of ductile rheology the problem of strain localization arises. The aim of this thesis was to develop and apply models based on continuum mechanics and integrating heat transfer to understand the emplacement of nappes. Models were solved either analytically or numerically. In the first two papers of this thesis we derived a simple model which describes channel flow in a homogeneous material with temperature dependent viscosity. We applied this model to the Morcles fold nappe and to several kilometer-scale shear zones worldwide. In the last paper we zoomed out and studied the tectonics of (i) ductile and (ii) visco-elasto-plastic and temperature dependent wedges. In this last paper we focused on the relationship between basement and cover deformation. We demonstrated that during the compression of a ductile passive margin both fold nappes and thrust sheets can develop and that these apparently different structures constitute two end-members of a single structure (i.e. nappe). The transition from fold nappe to thrust sheet is to first order controlled by the deformation of the basement. -- Le système des nappes helvétiques en Suisse occidentale est un empilement de nappes de plis et de nappes de charriage qui se sont mis en place à faible grade métamorphique. Les nappes de plis et les nappes de charriage sont parmi les objets géologiques les plus communs dans les orogènes. Les nappes de plis sont des plis couchés d'échelle kilométrique caractérisés par un flanc normal faiblement défor-mé, au contraire de leur flanc inverse, intensément déformé. Les nappes de charriage, à l'inverse se caractérisent par l'absence d'un flanc inverse bien défini. Elles peuvent être définies comme des blocs de croûte terrestre qui se déplacent de manière presque rigide qui sont déplacés sub-horizontalement jusqu'à plusieurs dizaines de kilomètres. La nappe de Mordes et la nappe du Doldenhorn sont des exemples classiques de nappes de plis et constitue le complexe infra-helvétique en Suisse occidentale et centrale, respectivement. Ce complexe repose sous des nappes de charriages telles les nappes des Diablerets et du Widlhörn en Suisse occidentale. La nappe du Glariis en Suisse centrale se distingue par un déplacement de plus de 35 kilomètres qui s'est effectué à la faveur d'une zone de cisaillement basale épaisse de seulement 1 mètre. Aujourd'hui la géométrie et la cinématique des nappes alpines fait l'objet d'un consensus général. Malgré cela, les processus mécaniques par lesquels ces nappes se sont mises en place restent mal compris. Pendant toute la première moitié du vingtième siècle les géologues les géologues ont été confrontés au «paradoxe mécanique». Celui-ci survient du fait qu'un bloc de roche haut de plusieurs kilomètres et long de plusieurs dizaines de kilomètres (i.e., une nappe) se fracturera de l'intérieur plutôt que de se déplacer sur une surface frictionnelle. Plusieurs solutions ont été proposées pour contourner cet apparent paradoxe. La solution la plus populaire est la théorie des prismes d'accrétion critiques (par exemple Chappie, 1978 ; Dahlen, 1984). Dans le cadre de cette théorie l'orogène est considéré dans son ensemble et ce simple changement d'échelle solutionne le paradoxe mécanique (la fracturation interne de l'orogène correspond aux nappes). Cette théorie est étroitement lié à la rhéologie cassante et par conséquent des nappes de plis ne peuvent pas créer au sein d'un prisme critique. Le but de cette thèse était de développer et d'appliquer des modèles basés sur la théorie de la méca-nique des milieux continus et sur les transferts de chaleur pour comprendre l'emplacement des nappes. Ces modèles ont été solutionnés de manière analytique ou numérique. Dans les deux premiers articles présentés dans ce mémoire nous avons dérivé un modèle d'écoulement dans un chenal d'un matériel homogène dont la viscosité dépend de la température. Nous avons appliqué ce modèle à la nappe de Mordes et à plusieurs zone de cisaillement d'échelle kilométrique provenant de différents orogènes a travers le monde. Dans le dernier article nous avons considéré le problème à l'échelle de l'orogène et avons étudié la tectonique de prismes (i) ductiles, et (ii) visco-élasto-plastiques en considérant les transferts de chaleur. Nous avons démontré que durant la compression d'une marge passive ductile, a la fois des nappes de plis et des nappes de charriages peuvent se développer. Nous avons aussi démontré que nappes de plis et de charriages sont deux cas extrêmes d'une même structure (i.e. nappe) La transition entre le développement d'une nappe de pli ou d'une nappe de charriage est contrôlé au premier ordre par la déformation du socle. -- Le système des nappes helvétiques en Suisse occidentale est un emblement de nappes de plis et de nappes de chaînage qui se sont mis en place à faible grade métamoiphique. Les nappes de plis et les nappes de charriage sont parmi les objets géologiques les plus communs dans les orogènes. Les nappes de plis sont des plis couchés d'échelle kilométrique caractérisés par un flanc normal faiblement déformé, au contraire de leur flanc inverse, intensément déformé. Les nappes de charriage, à l'inverse se caractérisent par l'absence d'un flanc inverse bien défini. Elles peuvent être définies comme des blocs de croûte terrestre qui se déplacent de manière presque rigide qui sont déplacés sub-horizontalement jusqu'à plusieurs dizaines de kilomètres. La nappe de Morcles and la nappe du Doldenhorn sont des exemples classiques de nappes de plis et constitue le complexe infra-helvétique en Suisse occidentale et centrale, respectivement. Ce complexe repose sous des nappes de charriages telles les nappes des Diablerets et du Widlhörn en Suisse occidentale. La nappe du Glarüs en Suisse centrale est certainement l'exemple de nappe de charriage le plus célèbre au monde. Elle se distingue par un déplacement de plus de 35 kilomètres qui s'est effectué à la faveur d'une zone de cisaillement basale épaisse de seulement 1 mètre. La géométrie et la cinématique des nappes alpines fait l'objet d'un consensus général parmi les géologues. Au contraire les processus physiques par lesquels ces nappes sont mises en place reste mal compris. Les sédiments qui forment les nappes alpines se sont déposés à l'ère secondaire et à l'ère tertiaire sur le socle de la marge européenne qui a été étiré durant l'ouverture de l'océan Téthys. Lors de la fermeture de la Téthys, qui donnera naissance aux Alpes, le socle et les sédiments de la marge européenne ont été déformés pour former les nappes alpines. Le but de cette thèse était de développer et d'appliquer des modèles basés sur la théorie de la mécanique des milieux continus et sur les transferts de chaleur pour comprendre l'emplacement des nappes. Ces modèles ont été solutionnés de manière analytique ou numérique. Dans les deux premiers articles présentés dans ce mémoire nous nous sommes intéressés à la localisation de la déformation à l'échelle d'une nappe. Nous avons appliqué le modèle développé à la nappe de Morcles et à plusieurs zones de cisaillement provenant de différents orogènes à travers le monde. Dans le dernier article nous avons étudié la relation entre la déformation du socle et la défonnation des sédiments. Nous avons démontré que nappe de plis et nappes de charriages constituent les cas extrêmes d'un continuum. La transition entre nappe de pli et nappe de charriage est intrinsèquement lié à la déformation du socle sur lequel les sédiments reposent.