Vertical Syndication-Proof Competitive Prices in Multilateral Markets

[eng] A multi-sided Böhm-Bawerk assignment game (Tejada, to appear) is a model for a multilateral market with a finite number of perfectly complementary indivisible commodities owned by different sellers, and inflexible demand and support functions. We show that for each such market game there is a unique vector of competitive prices for the commodities that is vertical syndication-proof, in the sense that, at those prices, syndication of sellers each owning a different commodity is neither beneficial nor detrimental for the buyers. Since, moreover, the benefits obtained by the agents at those prices correspond to the nucleolus of the market game, we provide a syndication-based foundation for the nucleolus as an appropriate solution concept for market games. For different solution concepts a syndicate can be disadvantageous and there is no escape to Aumman’s paradox (Aumann, 1973). We further show that vertical syndicationproofness and horizontal syndication-proofness – in which sellers of the same commodity collude – are incompatible requirements under some mild assumptions. Our results build on a self-interesting link between multi-sided Böhm-Bawerk assignment games and bankruptcy games (O’Neill, 1982). We identify a particular subset of Böhm-Bawerk assignment games and we show that it is isomorphic to the whole class of bankruptcy games. This isomorphism enables us to show the uniqueness of the vector of vertical syndication-proof prices for the whole class of Böhm-Bawerk assignment market using well-known results of bankruptcy problems.

Qualitative analysis of barriers and facilitators encountered by HIV patients in an ART adherence programme.

Background Medication adherence is a complex, dynamic and changing behaviour that is affected by a variety of factors, including the patient's beliefs and life circumstances. Studies have highlighted barriers to medication adherence (e.g., unmanaged side effects or a lack of social support), as well as facilitators of medication adherence (e.g., technical simplicity of treatment and psychological acceptance of the disease). Since August 2004, in Lausanne (Switzerland), physicians have referred patients who are either experiencing or are at risk of experiencing problems with their HIV antiretroviral treatment (ART) to a routine interdisciplinary ART adherence programme. This programme consists of multifactorial intervention including electronic drug monitoring (MEMS(TM)). Objective This study's objective was to identify the barriers and facilitators encountered by HIV patients with suboptimal medication adherence (≤90 % adherence over the study period). Setting The community pharmacy of the Department of Ambulatory Care and Community Medicine in Lausanne (Switzerland). Method The study consisted of a retrospective, qualitative, thematic content analysis of pharmacists' notes that were taken during semi-structured interviews with patients and conducted as part of the ART adherence programme between August 2004 and May 2008. Main outcome measure Barriers and facilitators encountered by HIV patients. Results Barriers to and facilitators of adherence were identified for the 17 included patients. These factors fell into three main categories: (1) cognitive, emotional and motivational; (2) environmental, organisational and social; and (3) treatment and disease. Conclusion The pharmacists' notes revealed that diverse barriers and facilitators were discussed during medication adherence interviews. Indeed, the results showed that the 17 non-adherent patients encountered barriers and benefited from facilitators. Therefore, pharmacists should inquire about all factors, regardless of whether they have a negative or a positive impact on medication adherence, and should consider all dimensions of patient adherence. The simultaneous strengthening of facilitators and better management of barriers may allow healthcare providers to tailor care to a patient's specific needs and support each individual patient in improving his medication-related behaviour.

Analysis of an iterative deconvolution approach for estimating the source wavelet during waveform inversion of crosshole ground-penetrating radar data

A major issue in the application of waveform inversion methods to crosshole georadar data is the accurate estimation of the source wavelet. Here, we explore the viability and robustness of incorporating this step into a time-domain waveform inversion procedure through an iterative deconvolution approach. Our results indicate that, at least in non-dispersive electrical environments, such an approach provides remarkably accurate and robust estimates of the source wavelet even in the presence of strong heterogeneity in both the dielectric permittivity and electrical conductivity. Our results also indicate that the proposed source wavelet estimation approach is relatively insensitive to ambient noise and to the phase characteristics of the starting wavelet. Finally, there appears to be little-to-no trade-off between the wavelet estimation and the tomographic imaging procedures.

Dendritic cells exposed to MVA-based HIV-1 vaccine induce highly functional HIV-1-specific CD8+ T cell responses in HIV-1-infected individuals

Currently, MVA virus vectors carrying HIV-1 genes are being developed as HIV-1/AIDS prophylactic/therapeutic vaccines. Nevertheless, little is known about the impact of these vectors on human dendritic cells (DC) and their capacity to present HIV-1 antigens to human HIV-specific T cells. This study aimed to characterize the interaction of MVA and MVA expressing the HIV-1 genes Env-Gag-Pol-Nef of clade B (referred to as MVA-B) in human monocyte-derived dendritic cells (MDDC) and the subsequent processes of HIV-1 antigen presentation and activation of memory HIV-1-specific T lymphocytes. For these purposes, we performed ex vivo assays with MDDC and autologous lymphocytes from asymptomatic HIV-infected patients. Infection of MDDC with MVA-B or MVA, at the optimal dose of 0.3 PFU/MDDC, induced by itself a moderate degree of maturation of MDDC, involving secretion of cytokines and chemokines (IL1-ra, IL-7, TNF-α, IL-6, IL-12, IL-15, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, IP-10, MIG, and IFN-α). MDDC infected with MVA or MVA-B and following a period of 48 h or 72 h of maturation were able to migrate toward CCL19 or CCL21 chemokine gradients. MVA-B infection induced apoptosis of the infected cells and the resulting apoptotic bodies were engulfed by the uninfected MDDC, which cross-presented HIV-1 antigens to autologous CD8+ T lymphocytes. MVA-B-infected MDDC co-cultured with autologous T lymphocytes induced a highly functional HIV-specific CD8+ T cell response including proliferation, secretion of IFN-γ, IL-2, TNF-α, MIP-1β, MIP-1α, RANTES and IL-6, and strong cytotoxic activity against autologous HIV-1-infected CD4+ T lymphocytes. These results evidence the adjuvant role of the vector itself (MVA) and support the clinical development of prophylactic and therapeutic anti-HIV vaccines based on MVA-B.

Collaboration entre médecin de famille et psychiatre pour les problèmes de santé mentale [Family physicians and psychiatrists' collaborative care for mental health problems].

The burden of disease linked to mental disorders represents more than one-fifth of years lived with disability in the world. Less than half of people suffering from mental disorders are adequately treated. Three quarter of those who receive treatment are followed by primary care. Collaborative care aims to increase the efficiency of direct general practitioner's treatment. Main components are sustainable and individualized consultation-liaison relationship (1/2 day of psychiatrist by 15 days for 10-15 general practitioners), and support of a clinical case manager for complex situations. Collaboration is bidirectional: early or crisis access to specialist care and long-term followup by general practitioner. This model is a challenge for the doctor-patient dual relationship and requires incentives in a public health perspective.

Dendritic cells exposed to MVA-based HIV-1 vaccine induce highly functional HIV-1-specific CD8+ T cell responses in HIV-1-infected individuals

Currently, MVA virus vectors carrying HIV-1 genes are being developed as HIV-1/AIDS prophylactic/therapeutic vaccines. Nevertheless, little is known about the impact of these vectors on human dendritic cells (DC) and their capacity to present HIV-1 antigens to human HIV-specific T cells. This study aimed to characterize the interaction of MVA and MVA expressing the HIV-1 genes Env-Gag-Pol-Nef of clade B (referred to as MVA-B) in human monocyte-derived dendritic cells (MDDC) and the subsequent processes of HIV-1 antigen presentation and activation of memory HIV-1-specific T lymphocytes. For these purposes, we performed ex vivo assays with MDDC and autologous lymphocytes from asymptomatic HIV-infected patients. Infection of MDDC with MVA-B or MVA, at the optimal dose of 0.3 PFU/MDDC, induced by itself a moderate degree of maturation of MDDC, involving secretion of cytokines and chemokines (IL1-ra, IL-7, TNF-α, IL-6, IL-12, IL-15, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, IP-10, MIG, and IFN-α). MDDC infected with MVA or MVA-B and following a period of 48 h or 72 h of maturation were able to migrate toward CCL19 or CCL21 chemokine gradients. MVA-B infection induced apoptosis of the infected cells and the resulting apoptotic bodies were engulfed by the uninfected MDDC, which cross-presented HIV-1 antigens to autologous CD8+ T lymphocytes. MVA-B-infected MDDC co-cultured with autologous T lymphocytes induced a highly functional HIV-specific CD8+ T cell response including proliferation, secretion of IFN-γ, IL-2, TNF-α, MIP-1β, MIP-1α, RANTES and IL-6, and strong cytotoxic activity against autologous HIV-1-infected CD4+ T lymphocytes. These results evidence the adjuvant role of the vector itself (MVA) and support the clinical development of prophylactic and therapeutic anti-HIV vaccines based on MVA-B.

Cancer du sein et obésité, une liaison dangereuse [Breast cancer and obesity, a dangerous relation].

Obesity is associated with different cancers including breast cancer, whose incidence is increased in postmenopausal women. It has an adverse impact on the prognosis of the patients, regardless of their menopausal status. The fact of receiving a systemic adjuvant therapy does not neutralize the prognostic role of obesity. Moderate weight loss after cancer diagnosis could improve the outcome of the patients, while a weight gain during treatment seems without significant effect. Currently available data are still too incomplete to justify systematic programs to lose weight with an oncologic therapeutic aim. However, it is worth to encourage and support our patients to have an optimal diet, physical activity, and to lose weight as promotion of general health.

Learning wind fields with multiple kernels

This paper presents multiple kernel learning (MKL) regression as an exploratory spatial data analysis and modelling tool. The MKL approach is introduced as an extension of support vector regression, where MKL uses dedicated kernels to divide a given task into sub-problems and to treat them separately in an effective way. It provides better interpretability to non-linear robust kernel regression at the cost of a more complex numerical optimization. In particular, we investigate the use of MKL as a tool that allows us to avoid using ad-hoc topographic indices as covariables in statistical models in complex terrains. Instead, MKL learns these relationships from the data in a non-parametric fashion. A study on data simulated from real terrain features confirms the ability of MKL to enhance the interpretability of data-driven models and to aid feature selection without degrading predictive performances. Here we examine the stability of the MKL algorithm with respect to the number of training data samples and to the presence of noise. The results of a real case study are also presented, where MKL is able to exploit a large set of terrain features computed at multiple spatial scales, when predicting mean wind speed in an Alpine region.

CD99 is upregulated in placenta and astrocytomas with a differential subcellular distribution according to the malignancy stage.

In the present study, we searched for genes highly expressed in placenta and that could contribute to the establishment and maintenance of a malignant phenotype in different types of tumours, and in astrocytomas in particular. We employed a strategy based on the integration of in silico data from previously generated massively parallel signature sequencing and public serial analysis of gene expression databases. Among 12 selected genes, CD99 exhibited the highest relative mRNA expression in GBM compared to non-neoplastic brain tissues. In a larger cohort of astrocytic tumours, we further demonstrated increased CD99 expression in all malignant grades, with GBMs showing the highest values. These findings were confirmed at the protein level by Western blotting and immunohistochemistry. Additionally, we demonstrated the CD99 localisation profile in astrocytic tumours. Interestingly, CD99 expression was confined to the cytoplasm or membrane in more malignant astrocytomas, in contrast to non-neoplastic brain tissue or non-infiltrative pilocytic astrocytoma, which showed no obvious staining in these structures. Comparison of three GBM cell lines revealed higher CD99 expression at the membrane and higher migratory capacity in the A172 and U87MG lines, but lower CD99 expression and no migratory ability in the T98 line. Knocking down CD99 expression by siRNA decreased significantly the migration of both cell lines. These integrated CD99 gene and protein expression results suggest that CD99 expression in astrocytomas of different malignant grades might contribute to the infiltrative ability and support the importance of CD99 as a potential target to reduce infiltrative astrocytoma capacity in migration and invasion.

Source-wavelet estimation during full-waveform inversion of ground-penetrating radar data

A major issue in the application of waveform inversion methods to crosshole ground-penetrating radar (GPR) data is the accurate estimation of the source wavelet. Here, we explore the viability and robustness of incorporating this step into a recently published time-domain inversion procedure through an iterative deconvolution approach. Our results indicate that, at least in non-dispersive electrical environments, such an approach provides remarkably accurate and robust estimates of the source wavelet even in the presence of strong heterogeneity of both the dielectric permittivity and electrical conductivity. Our results also indicate that the proposed source wavelet estimation approach is relatively insensitive to ambient noise and to the phase characteristics of the starting wavelet. Finally, there appears to be little to no trade-off between the wavelet estimation and the tomographic imaging procedures.

Accuracy of out-of-field dose calculation of tomotherapy and cyberknife treatment planning systems: A dosimetric study.

PURPOSE: Late toxicities such as second cancer induction become more important as treatment outcome improves. Often the dose distribution calculated with a commercial treatment planning system (TPS) is used to estimate radiation carcinogenesis for the radiotherapy patient. However, for locations beyond the treatment field borders, the accuracy is not well known. The aim of this study was to perform detailed out-of-field-measurements for a typical radiotherapy treatment plan administered with a Cyberknife and a Tomotherapy machine and to compare the measurements to the predictions of the TPS. MATERIALS AND METHODS: Individually calibrated thermoluminescent dosimeters were used to measure absorbed dose in an anthropomorphic phantom at 184 locations. The measured dose distributions from 6 MV intensity-modulated treatment beams for CyberKnife and TomoTherapy machines were compared to the dose calculations from the TPS. RESULTS: The TPS are underestimating the dose far away from the target volume. Quantitatively the Cyberknife underestimates the dose at 40cm from the PTV border by a factor of 60, the Tomotherapy TPS by a factor of two. If a 50% dose uncertainty is accepted, the Cyberknife TPS can predict doses down to approximately 10 mGy/treatment Gy, the Tomotherapy-TPS down to 0.75 mGy/treatment Gy. The Cyberknife TPS can then be used up to 10cm from the PTV border the Tomotherapy up to 35cm. CONCLUSIONS: We determined that the Cyberknife and Tomotherapy TPS underestimate substantially the doses far away from the treated volume. It is recommended not to use out-of-field doses from the Cyberknife TPS for applications like modeling of second cancer induction. The Tomotherapy TPS can be used up to 35cm from the PTV border (for a 390 cm(3) large PTV).

Kernel-based Mapping of Meteorological Fields in Complex Orography

Due to the advances in sensor networks and remote sensing technologies, the acquisition and storage rates of meteorological and climatological data increases every day and ask for novel and efficient processing algorithms. A fundamental problem of data analysis and modeling is the spatial prediction of meteorological variables in complex orography, which serves among others to extended climatological analyses, for the assimilation of data into numerical weather prediction models, for preparing inputs to hydrological models and for real time monitoring and short-term forecasting of weather.In this thesis, a new framework for spatial estimation is proposed by taking advantage of a class of algorithms emerging from the statistical learning theory. Nonparametric kernel-based methods for nonlinear data classification, regression and target detection, known as support vector machines (SVM), are adapted for mapping of meteorological variables in complex orography.With the advent of high resolution digital elevation models, the field of spatial prediction met new horizons. In fact, by exploiting image processing tools along with physical heuristics, an incredible number of terrain features which account for the topographic conditions at multiple spatial scales can be extracted. Such features are highly relevant for the mapping of meteorological variables because they control a considerable part of the spatial variability of meteorological fields in the complex Alpine orography. For instance, patterns of orographic rainfall, wind speed and cold air pools are known to be correlated with particular terrain forms, e.g. convex/concave surfaces and upwind sides of mountain slopes.Kernel-based methods are employed to learn the nonlinear statistical dependence which links the multidimensional space of geographical and topographic explanatory variables to the variable of interest, that is the wind speed as measured at the weather stations or the occurrence of orographic rainfall patterns as extracted from sequences of radar images. Compared to low dimensional models integrating only the geographical coordinates, the proposed framework opens a way to regionalize meteorological variables which are multidimensional in nature and rarely show spatial auto-correlation in the original space making the use of classical geostatistics tangled.The challenges which are explored during the thesis are manifolds. First, the complexity of models is optimized to impose appropriate smoothness properties and reduce the impact of noisy measurements. Secondly, a multiple kernel extension of SVM is considered to select the multiscale features which explain most of the spatial variability of wind speed. Then, SVM target detection methods are implemented to describe the orographic conditions which cause persistent and stationary rainfall patterns. Finally, the optimal splitting of the data is studied to estimate realistic performances and confidence intervals characterizing the uncertainty of predictions.The resulting maps of average wind speeds find applications within renewable resources assessment and opens a route to decrease the temporal scale of analysis to meet hydrological requirements. Furthermore, the maps depicting the susceptibility to orographic rainfall enhancement can be used to improve current radar-based quantitative precipitation estimation and forecasting systems and to generate stochastic ensembles of precipitation fields conditioned upon the orography.

Integrating species distribution models (SDMs) and phylogeography for two species of Alpine Primula.

The major intention of the present study was to investigate whether an approach combining the use of niche-based palaeodistribution modeling and phylo-geography would support or modify hypotheses about the Quaternary distributional history derived from phylogeographic methods alone. Our study system comprised two closely related species of Alpine Primula. We used species distribution models based on the extant distribution of the species and last glacial maximum (LGM) climate models to predict the distribution of the two species during the LGM. Phylogeographic data were generated using amplified fragment length polymorphisms (AFLPs). In Primula hirsuta, models of past distribution and phylogeographic data are partly congruent and support the hypothesis of widespread nunatak survival in the Central Alps. Species distribution models (SDMs) allowed us to differentiate between alpine regions that harbor potential nunatak areas and regions that have been colonized from other areas. SDMs revealed that diversity is a good indicator for nunataks, while rarity is a good indicator for peripheral relict populations that were not source for the recolonization of the inner Alps. In P. daonensis, palaeo-distribution models and phylogeographic data are incongruent. Besides the uncertainty inherent to this type of modeling approach (e.g., relatively coarse 1-km grain size), disagreement of models and data may partly be caused by shifts of ecological niche in both species. Nevertheless, we demonstrate that the combination of palaeo-distribution modeling with phylogeographical approaches provides a more differentiated picture of the distributional history of species and partly supports (P. hirsuta) and partly modifies (P. daonensis and P. hirsuta) hypotheses of Quaternary distributional history. Some of the refugial area indicated by palaeodistribution models could not have been identified with phylogeographic data.

Telomere fluorescence measurements in granulocytes and T lymphocyte subsets point to a high turnover of hematopoietic stem cells and memory T cells in early childhood.

To study telomere length dynamics in hematopoietic cells with age, we analyzed the average length of telomere repeat sequences in diverse populations of nucleated blood cells. More than 500 individuals ranging in age from 0 to 90 yr, including 36 pairs of monozygous and dizygotic twins, were analyzed using quantitative fluorescence in situ hybridization and flow cytometry. Granulocytes and naive T cells showed a parallel biphasic decline in telomere length with age that most likely reflected accumulated cell divisions in the common precursors of both cell types: hematopoietic stem cells. Telomere loss was very rapid in the first year, and continued for more than eight decades at a 30-fold lower rate. Memory T cells also showed an initial rapid decline in telomere length with age. However, in contrast to naive T cells, this decline continued for several years, and in older individuals lymphocytes typically had shorter telomeres than did granulocytes. Our findings point to a dramatic decline in stem cell turnover in early childhood and support the notion that cell divisions in hematopoietic stem cells and T cells result in loss of telomeric DNA.