Quelle place pour la psychologie positive dans le champ de la psychothérapie ? Perspectives théoriques et empiriques

Ce travail vise à exposer le courant de la psychologie positive et à présenter une tentative d'articulation entre ce courant et le champ de la pratique psychothérapeutique. Nous présenterons, dans un premier temps, les fondements de la psychologie positive et les axes principaux qui la constituent. Dans cette perspective, la théorie des émotions positives de Fredrickson et la classification des vertus et des forces de caractères de Peterson et Seligman sont exposées plus en détails. Dans un second temps et à partir des travaux récents, deux facçons d'établir un pont entre psychologie positive et la psychothérapie sont discutées : (i) le développement de nouvelles stratégies thérapeutiques issues de la psychologie positive et (ii) une relecture des principaux modèles psychothérapeutiques au regard de la psychologie positive. / This article aims to present the field of positive psychology and the way it could be integrated in the area of psychotherapy. First, the historical grounding and the main contributions of positive psychology are presented. In this perspective, the Fredrickson's theory of positive emotions and the Peterson's classification of character strengths and virtues are particularly detailed. Secondly, based on recent research, two ways to link positive psychology to clinical practice emerged: (i) the development of new therapeutic strategies anchored in the positive psychology, and (ii) a critical look at different psychotherapeutic modalities based on positive psychology.

The positive effects of a protean career attitude for self-initiated expatriates: Cultural adjustment as a mediator

Purpose - The authors sought to explain why and how protean career attitude might influence self-initiated expatriates' (SIEs) experiences positively. A mediation model of cultural adjustment was proposed and empirically evaluated. Design/methodology/approach - Data from 132 SIEs in Germany containing measures of protean career attitude, cultural adjustment, career satisfaction, life satisfaction, and intention to stay in the host country were analysed using path analysis with a bootstrap method. Findings - Empirical results provide support for the authors' proposed model: the positive relations between protean career attitude and the three expatriation outcomes (career satisfaction, life satisfaction and intention to stay in the host country) were mediated by positive cross-cultural adjustment of SIEs. Research limitations/implications - All data were cross-sectional from a single source. The sample size was small and included a large portion of Chinese participants. The study should be replicated with samples in other destination countries, and longitudinal research is suggested. Practical implications - By fostering both a protean career attitude in skilled SIE employees and their cultural adjustment, corporations and receiving countries could be able to retain this international workforce better in times of talent shortage. Originality/value - This study contributes to the scarce research on the conceptual relatedness of protean career attitude and SIEs, as well as to acknowledging the cultural diversity of the SIE population.

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.

NADPH-diaphorase-positive ganglion cells of the rat adrenal gland: age- and sex-related changes in their number, size, and distribution.

The rat adrenal gland contains ganglion cells able to synthesize nitric oxide (NO). This messenger molecule controls and modulates adrenal secretory activity and blood flow. The present study analyzed the number, size, and distribution of NO-producing adrenal neurons in adulthood and during postnatal development by means of beta-nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry. This method reliably visualizes the enzyme responsible for NO generation. The reactive neurons per adrenal gland were 350-400 in both male and female adult rats. The positive nerve cell bodies were mostly located in the medulla, few being detected within the cortex and the subcapsular region. Dual labeling with anti-microtubule-associated protein 2 antibody, specific for neuronal elements, confirmed this distribution. Anti-microtubule-associated protein 1b antibody identified a subset of NADPH-d-positive neurons, displaying different degrees of maturation according to their position within the adrenal gland. At birth, there were about 220 NADPH-d-labeled neurons per adrenal gland in both sexes. As confirmed by dual immunocytochemical labeling, their great majority was evenly distributed between the cortex and the subcapsular region, the medulla being practically devoid of stained neurons. After birth, the number of adrenal NADPH-d-positive ganglion cells displayed a strong postnatal increase and reached the adult-like distribution after 1-2 months. During the period of increase, there was a transient difference in the numbers of these cells in the two sexes. Thus we present here evidence of plasticity in the number, size, and distribution of NADPH-d-positive adrenal neurons between birth and adulthood; in addition, we describe transient sex-related differences in their number and distribution during the 2nd postnatal week, which are possibly related to the epigenetic action of gonadal hormones during this period.

A positive FGFR3/FOXN1 feedback loop underlies benign skin keratosis versus squamous cell carcinoma formation in humans.

Seborrheic keratoses (SKs) are common, benign epithelial tumors of the skin that do not, or very rarely, progress into malignancy, for reasons that are not understood. We investigated this by gene expression profiling of human SKs and cutaneous squamous cell carcinomas (SCCs) and found that several genes previously connected with keratinocyte tumor development were similarly modulated in SKs and SCCs, whereas the expression of others differed by only a few fold. In contrast, the tyrosine kinase receptor FGF receptor-3 (FGFR3) and the transcription factor forkhead box N1 (FOXN1) were highly expressed in SKs, and close to undetectable in SCCs. We also showed that increased FGFR3 activity was sufficient to induce FOXN1 expression, counteract the inhibitory effect of EGFR signaling on FOXN1 expression and differentiation, and induce differentiation in a FOXN1-dependent manner. Knockdown of FOXN1 expression in primary human keratinocytes cooperated with oncogenic RAS in the induction of SCC-like tumors, whereas increased FOXN1 expression triggered the SCC cells to shift to a benign SK-like tumor phenotype, which included increased FGFR3 expression. Thus,we have uncovered a positive regulatory loop between FGFR3 and FOXN1 that underlies a benign versus malignant skin tumor phenotype.

CD30-positive peripheral T-cell lymphomas share molecular and phenotypic features.

Peripheral T-cell lymphoma, not otherwise specified is a heterogeneous group of aggressive neoplasms with indistinct borders. By gene expression profiling we previously reported unsupervised clusters of peripheral T-cell lymphomas, not otherwise specified correlating with CD30 expression. In this work we extended the analysis of peripheral T-cell lymphoma molecular profiles to prototypical CD30(+) peripheral T-cell lymphomas (anaplastic large cell lymphomas), and validated mRNA expression profiles at the protein level. Existing transcriptomic datasets from peripheral T-cell lymphomas, not otherwise specified and anaplastic large cell lymphomas were reanalyzed. Twenty-one markers were selected for immunohistochemical validation on 80 peripheral T-cell lymphoma samples (not otherwise specified, CD30(+) and CD30(-); anaplastic large cell lymphomas, ALK(+) and ALK(-)), and differences between subgroups were assessed. Clinical follow-up was recorded. Compared to CD30(-) tumors, CD30(+) peripheral T-cell lymphomas, not otherwise specified were significantly enriched in ALK(-) anaplastic large cell lymphoma-related genes. By immunohistochemistry, CD30(+) peripheral T-cell lymphomas, not otherwise specified differed significantly from CD30(-) samples [down-regulated expression of T-cell receptor-associated proximal tyrosine kinases (Lck, Fyn, Itk) and of proteins involved in T-cell differentiation/activation (CD69, ICOS, CD52, NFATc2); upregulation of JunB and MUM1], while overlapping with anaplastic large cell lymphomas. CD30(-) peripheral T-cell lymphomas, not otherwise specified tended to have an inferior clinical outcome compared to the CD30(+) subgroups. In conclusion, we show molecular and phenotypic features common to CD30(+) peripheral T-cell lymphomas, and significant differences between CD30(-) and CD30(+) peripheral T-cell lymphomas, not otherwise specified, suggesting that CD30 expression might delineate two biologically distinct subgroups.

Extracapsular tumor spread and the risk of local, axillary and supraclavicular recurrence in node-positive, premenopausal patients with breast cancer.

BACKGROUND: Extracapsular tumor spread (ECS) has been identified as a possible risk factor for breast cancer recurrence, but controversy exists regarding its role in decision making for regional radiotherapy. This study evaluates ECS as a predictor of local, axillary, and supraclavicular recurrence. PATIENTS AND METHODS: International Breast Cancer Study Group Trial VI accrued 1475 eligible pre- and perimenopausal women with node-positive breast cancer who were randomly assigned to receive three to nine courses of classical combination chemotherapy with cyclophosphamide, methotrexate, and fluorouracil. ECS status was determined retrospectively in 933 patients based on review of pathology reports. Cumulative incidence and hazard ratios (HRs) were estimated using methods for competing risks analysis. Adjustment factors included treatment group and baseline patient and tumor characteristics. The median follow-up was 14 years. RESULTS: In univariable analysis, ECS was significantly associated with supraclavicular recurrence (HR = 1.96; 95% confidence interval 1.23-3.13; P = 0.005). HRs for local and axillary recurrence were 1.38 (P = 0.06) and 1.81 (P = 0.11), respectively. Following adjustment for number of lymph node metastases and other baseline prognostic factors, ECS was not significantly associated with any of the three recurrence types studied. CONCLUSIONS: Our results indicate that the decision for additional regional radiotherapy should not be based solely on the presence of ECS.

Cardio-pulmonary interaction in premature newborn with nasal continuous positive airways pressure (n-CPAP) respiratory assistance evaluated with echocardiography

Introduction: Nasal continuous positive airways pressure (n-CPAP) is an effective treatment in premature infants with respiratory distress. The cardio-pulmonary interactions secondary to n-CPAP are well studied in adults, but less well described in premature infants. We postulated that there could be important interactions with regard to the patent ductus arteriosus (PDA). Methods: Prospective study, approved by the local ethic committee. Premature infants less than 32 weeks gestation, _7 days-old, needing n-CPAP for respiratory distress, but without the need of additional oxygen were included in the study. Every patient had a first echocardiography with n-CPAP and then n-CPAP was retrieved. 3 hours later the echocardiography was repeated by the same investigator and then the patient replaced on n-CPAP. Results: 14 premature newborn were included, mean gestational age of 28 _ 2 weeks, mean weight 1.1 _ 0.3 Kg and height 39 _ 3 cm. Echocardiographic measurements are depicted in Table 1. Significant finding were observed between measurement on n- CPAP or without n-CPAP: on end diastolic left ventricular diameter (12.8 _ 1.6 mm vs. 13.5 _ 2 mm), on end systolic left ventricular diameter (8.4 _ 1.3 mm vs. 9.1 _ 1.5 mm), left atrium diameter (8.9 _ 2.2 mm vs. 10.4 _ 2.5 mm), maximal velocity on tricuspid valve (46 _ 10 cm/s vs. 51 _ 9 cm/s), calculated Qp (3.7 _ 0.8 L/min/m2 vs. 4.3 _ 0.8 L/min/m2). Only three patients have demonstrated a PDA during the study. Conclusion: Positive end expiratory pressure (Peep) has hemodynamic effects which are: reduction of systemic and pulmonary venous return as shown by the changes on tricuspid valve inflow,on the calculated Qp and finally on the diameter of the left atrium and left ventricle.We found in premature infants the same hemodynamic effects than those described in adults but with lower Peep values. This could be due to the particular elasticity and weakness of the thoracic wall of premature infants. Interestingly the flow through a PDA seems also to be diminished with Peep, but the number of patients is insufficient to conclude. Further investigation will be needed to better understand these interactions. Table 1. Echocardiographic measurement (mean (SD)). With n-CPAP Without n-CPAP p value RV ED diameter (mm) 6.3 (1.7) 6.04 (1.1) NS LV ED diameter (mm) 12.8 (1.6) 13.5 (2.0) _0.05 LV ES diameter (mm) 8.4 (1.3) 9.1 (1.5) _0.05 SF (%) 34 (5) 33 (6) NS Ao valve diameter (mm) 7.4 (1.3) 7.4 (1.2) NS LA diameter (mm) 8.9 (2.2) 10.4 (2.5) _0.05 Vmax Ao (cm/s) 70 (16) 71 (18) NS Vmax PV (cm/s) 69 (15) 72 (16) NS Vmax TV (cm/s) 46 (10) 51 (9) _0.05 Vmax MV (cm/s) 53 (17) 54 (18) NS Qp (L/min/m2) 3.7 (0.8) 4.3 (0.8) _0.05 Qs (L/min/m2) 4.0 (0.8) 4.0 (0.7) NS Qp/Qs 0.92 (0.14) 1.09 (0.23) _0.05 RV: right ventricle, LV: left ventricle, ED: end diastolic, ES: end systolic, SF: shortening fraction,Ao: aortic valve, LA: left atrium,Vmax: maximum Doppler Velocity, Qp: pulmonary output, Qs: systemic output, NS: non significant.

Excision of the Staphylococcal Cassette Chromosome mec (SCCmec) and its crucial role in the horizontal transfer of methicillin resistance in staphylococci.

Staphylococcus aureus est un pathogène humain majeur ayant développé des résistances contre la quasi totalité des antibiotiques disponibles, incluant la très importante famille des β- lactamines. La résistance à cette classe d'antibiotiques est conférée par la « Staphylococcal Cassette Chromosome mec » (SCCmec), qui est un élément génétique mobile capable de s'insérer dans le chromosome bactérien et capable d'être transféré horizontalement chez d'autres staphylocoques. Le mécanisme moléculaire impliqué dans ce transfert horizontal demeure largement inconnu. L'une des premières étapes du transfert est l'excision du SCC mec du chromosome bactérien. Cette excision est promue par des enzymes codées par l'élément SCCmec lui- même et appelées de ce fait « Cassette Chromosome Recombinases » (Ccr). L'un des buts de ce travail de thèse a été de comprendre la régulation de l'expression des gènes codant pour les Ccr recombinases. En utilisant des outils moléculaires originaux, nous avons été en mesure de démontrer en premier lieu que les Ccr recombinases étaient exprimées de façon « bistable », c'est à dire qu'uniquement quelques pourcents de cellules dans une population exprimaient ces gènes à un temps donné. Dans un deuxième temps, nous avons également démontré que l'expression de ces gènes était régulée par des facteurs étrangers au SCC mec. L'expression bistable des recombinases est un concept important. Effectivement, cela permet à la majorité des cellules d'une population de conserver l'élément SCC mec, alors que seulement une petite fraction le perd afin de le rendre disponible pour un transfert. Ainsi, alors que l'élément SCC mec continue de se propager avec la multiplication des bactéries Staphylococcus aureus résistant à la méticilline (SARM), il peut être simultanément transmis à des souches susceptibles (Staphylococcus aureus susceptible à la méticilline, SASM), entraînant l'apparition de nouveaux SARM. De façon très intéressante, le fait que cette bistabilité est contrôlée par les bactéries, et non le SCCmec lui-même, montre que la décision de transférer ou non la cassette SCC mec appartient à la bactérie. En conséquence, il doit exister dans la nature des souches qui sont plus ou moins aptes à effectuer ce transfert. En nous appuyant sur ces observations, nous avons montré que l'excision du SCC mec était effectivement régulée de façon très étroite au cours de la division cellulaire, et ne se passait que pendant un temps limité au début de la croissance. Ce résultat est compatible avec une régulation génétique commandée par la densité cellulaire, qui pourrait être dépendante de la production de signaux extracellulaires, du type que l'on rencontre dans le quorum sensing. Les signaux hypothétiques entraînant l'excision du SCC mec restent inconnus à l'heure actuelle. La connaissance de ces signaux pourrait se révéler très importante afin de développer des stratégies pour interférer avec la dissémination de la résistance au β-lactamines. Deux sujets additionnels ont été logiquement investigués au vu de ces premiers résultats. Premièrement, si certaines souches de SARM sont plus ou moins aptes à déclencher l'excision du SCC mec, de même certaines souches de SASM devraient être plus ou moins aptes à acquérir cet élément. Deuxièmement, afin d'étudier ces mécanismes de transfert au niveau épidémiologique, il nous a été nécessaire de développer des outils nous permettant d'explorer le phénomène à une plus large échelle. Concernant le premier point, il a été postulé que certains SASM seraient réfractaires à l'intégration génomique d'un SCC mec en raison de polymorphismes particuliers à proximité du site d'insertion chromosomique (attB). En étudiant plus de 40 isolais de S. aureus, provenant de porteurs sains, nous avons confirmé ce polymorphisme dans l'environnement à'attB. De plus, nous avons pu montrer que ces régions polymorphiques ont évolué parallèlement à des groupes phylogénétiques bien connus. Ainsi, si des telles régions réfractaires à l'intégration de SCC mec existent, celles-ci devraient ségréger dans des complexes clonaux bien définis qui devraient être facilement identifiables au niveau épidémiologique. Concernant le second point, nous avons été capables de construire un système rapporteur de l'excision du SCCmec, en utilisant un plasmide à faible copie. Ce système consistait en un promoteur fort et un gène codant pour une protéine verte fluorescente (GFP) sous le contrôle d'un promoteur fort séparés à l'aide d'un élément SCC artificiel portant trois terminateurs de transcription. Ainsi, la fluorescence ne s'exprime que si l'élément SCC est excisé du plasmide. Ce système a été testé avec succès dans plusieurs types de staphylocoques, et est actuellement évalué dans d'autres souches et conditions stimulant ou inhibant l'excision. De manière générale, cette dissertation représente parcours scientifique à travers plusieurs aspects d'un problème de santé publique majeur en rapport avec la résistance bactérienne aux antibiotiques. Ce travail s'attaque à des problèmes fondamentaux concernant le transfert horizontal de l'élément SCC mec. De plus, il s'intéresse à des aspects plus généraux de cet élément génétique mobile qui pourraient se révéler très importants en terme de mouvement de gènes au sein des staphylocoques, voir d'autres bactéries gram-positives. Finalement ce travail de thèse met en place le fondamentaux requis pour des recherches futures visant à interférer avec le transfert horizontal de la résistance aux β-lactamines. - Staphylococcus aureus is a major human pathogen. Moreover, S. aureus have developed resistance to almost all available antibiotics, including the important family of β-lactam molecules. Intrinsic resistance to β-lactams is conferred by the Staphylococcal Cassette Chromosome mec (SCCmec), which is a mobile genomic island that inserts into the staphylococcal chromosome and can be horizontally transferred into other staphylococci. However, little is known about the molecular mechanisms involved in this horizontal transfer into naïve strains. One of the first steps in SCC mec horizontal transfer is its excision from the chromosome. Excision is mediated by recombinase enzymes that are encoded by SCC mec itself, and named accordingly Ccr recombinases - for Cassette Chromosome recombinases. One goal of this thesis was to understand the regulation these recombinase genes. By using original molecular tools we could demonstrate first that the Ccr recombinases were expressed in a "bistable" manner, i.e. in only few percentages of the bacterial cells at a given time, and second that they were regulated by determinants that were not encoded on the SCC mec element, but elsewhere on the staphylococcal genome. "Bistable" expression Ccr recombinases is an important concept. It allows SCC mec to be excised and thus available for horizontal transfer, while ensuring that only some cells, but not the whole population, loose their valuable SCC mec genes. Thus, while the SCC mec element expands with the multiplication of the MRSA colony, it can simultaneously be transmitted into methicillin-susceptible S. aureus (MSSA), which convert into new MRSA. Most interestingly, the fact that bistability was regulated by the cells, rather than by SCC mec, indicates that it was the choice of the bacteria to trigger or not SCC mec transfer. As a consequence, there must be, in nature, staphylococcal strains that are more or less prone to sustain SCC mec transfer. Following these seminal observations we found that excision was indeed tightly regulated during bacterial division, and occurred only during a limited period of time at the beginning of bacterial growth. This is compatible with cell-density mediated gene regulation, and may depend on the production of extracellular signal molecules that transmit appropriate orders to neighboring cells, such as in quorum sensing. The potential signal triggering SCCmec excision is as yet unknown. However, it could be critical in promoting the horizontal transfer of methicillin resistance, or for the possible development of means to interfere with it. Two additional hypothesis were logically investigated in the view of these first results. First, if some strains of MRSA might be more prone than others to promote SCC mec excision, then some strains of MS SA might be more or less prone to acquire the element as well. Second, to investigate these multiple mechanisms at an epidemiological level, one would need to develop tools amenable to explore S. aureus strains at a larger scale. Regarding the first issue, it was postulated by others that some MSSA might be refractory to SCC mec integration because they had peculiar DNA polymorphisms in the vicinity of the site-specific chromosomal entry point {attB) of SCC mec. By studying >40 S. aureus isolates from healthy carriers, we confirmed the polymorphism of the attB environment. Moreover, we could show that these polymorphic regions co-evolved with well-known phylogenic clonal clusters. Therefore, if SCCwec-refractory attB environments exist, then they would segregate in well- defined S. aureus clonal clusters that would be easy to identify at the epidemiological level. Regarding the second issue, we were able to construct a new excision reporter system in a low copy number S. aureus plasmid. The reporter system consists in a strong promoter driving a green fluorescent protein {gfp) gene, separated by an artificial SCC-like element carrying three transcriptional terminators. Thus, fluorescence is not expressed unless the SCC-like element is excised. The system has been successfully tested in several aureus and non- aureus staphylococci, and is now being applied to more strains and various excision- triggering or inhibiting conditions. Altogether the dissertation is a scientific journey through various aspects of a salient medical problem with regard to antibiotic resistance and public health threat. The research work tackles fundamental issues about the mechanisms of horizontal transfer of the SCC mec element. Moreover, it also addresses more general features of this mobile element, which could be of larger importance with regard to gene trafficking in staphylococci, and maybe other gram-positive bacteria. Finally, the dissertation sets the fundamentals for future work and possible new ways to interfere with the horizontal transfer of methicillin resistance.

Positive and negative regulation of cellular immune responses in physiologic conditions and diseases.

The immune system has evolved to allow robust responses against pathogens while avoiding autoimmunity. This is notably enabled by stimulatory and inhibitory signals which contribute to the regulation of immune responses. In the presence of a pathogen, a specific and effective immune response must be induced and this leads to antigen-specific T-cell proliferation, cytokines production, and induction of T-cell differentiation toward an effector phenotype. After clearance or control of the pathogen, the effector immune response must be terminated in order to avoid tissue damage and chronic inflammation and this process involves coinhibitory molecules. When the immune system fails to eliminate or control the pathogen, continuous stimulation of T cells prevents the full contraction and leads to the functional exhaustion of effector T cells. Several evidences both in vitro and in vivo suggest that this anergic state can be reverted by blocking the interactions between coinhibitory molecules and their ligands. The potential to revert exhausted or inactivated T-cell responses following selective blocking of their function made these markers interesting targets for therapeutic interventions in patients with persistent viral infections or cancer.

Missed opportunities among HIV-positive women to control viral replication during pregnancy and to have a vaginal delivery.

INTRODUCTION: Most national guidelines for the prevention of mother-to-child transmission of HIV in Europe updated between 2001 and 2010 recommend vaginal deliveries for women with undetectable or very low viral load (VL). Our aim was to explore the impact of these new guidelines on the rates of vaginal deliveries among HIV-positive women in Europe. METHODS: In a pooled analysis of data on HIV-positive pregnant women enrolled in the Swiss Mother & Child HIV Cohort Study and the European Collaborative Study 2000 to 2010, deliveries were classified as occurring pre- or postpublication of national guidelines recommending vaginal delivery. RESULTS: Overall, 2663 women with 3013 deliveries were included from 10 countries; 28% women were diagnosed with HIV during pregnancy. Combination antiretroviral therapy was used in most pregnancies (2020, 73%), starting during the first or second trimester in 78% and during the third trimester in 22%; in 25% pregnancies, the woman conceived on combination antiretroviral therapy. Overall, in 86% pregnancies, a VL < 400 copies per milliliter was achieved before delivery. The proportion of vaginal deliveries increased from 17% (414/2377) before the change in guidelines to 52% (313/600) after; elective Caesarean section rates decreased from 65% to 27%. The proportion of women with undetectable VL having a Caesarean section was 55% after implementation of new guidelines. We observed a decrease of late preterm deliveries from 16% (377/2354) before to 7% (42/599) after the change in guidelines (P < 0.001). CONCLUSION: There are still missed opportunities for women with HIV to fully suppress their VL and to deliver vaginally in Europe.

gcodeml: A Grid-enabled Tool for Detecting Positive Selection in Biological Evolution

One of the important questions in biological evolution is to know if certain changes along protein coding genes have contributed to the adaptation of species. This problem is known to be biologically complex and computationally very expensive. It, therefore, requires efficient Grid or cluster solutions to overcome the computational challenge. We have developed a Grid-enabled tool (gcodeml) that relies on the PAML (codeml) package to help analyse large phylogenetic datasets on both Grids and computational clusters. Although we report on results for gcodeml, our approach is applicable and customisable to related problems in biology or other scientific domains.