Rituximab treatment in non-malignant inflammatory sensory polyganglionopathy

Non-malignant inflammatory sensory polyganglionopathy (NISP) is the most common form of acquired ganglionopathies, a rare and distinct subgroup of peripheral nerve diseases characterized by a primary degeneration of sensory neurons in dorsal root ganglia. There is a rational for the use of immune modifying agents (IMA) in NISP since an underlying auto-immune process is demonstrated or suspected. However, commonly used IMA such as corticosteroids, azathioprine, methotrexate or IVIG do not prevent disease's progression in the majority of patients. The use of newer IMA, especially those directed against B-cells, may be a therapeutic alternative. An interesting candidate is rituximab, a mouse-human chimeric anti CD20 antibody that specifically eliminates B-cells and B-cells precursors.Objectives: This is a prospective open label pilot study to determine the efficacy of rituximab treatment in NISP patients, who did not respond to commonly used IMA.Methods: Five patients (40% male) with a mean age of 55 years (range 49-67), diagnosed with NISP after extensive work-up, were treated (schema used for one cure: 2 9 1gr within 15 days interval). Neurological scores (NIS, ISSS, ODSS) and B cell counts were assessed at baseline and during clinical follow-up at 2 and 6 monthsto assess treatment efficacy.Results: The treatment was generally well tolerated. Minor adverse events reported were transient arterial hypotension during the infusions in two patients and intermittent mild leucopenia in one patient. Clinical evolution during the follow-up period was characterized by a stability of the functional scores in four patients (80%) and the continuation of disability progression of one patient (20%). CD4 cells disappeared in all patients after the second infusion, an effect that lasted until the follow up at 6 months.Conclusion: The preliminary results of this pilot study indicate that rituximab is generally well tolerated and prevents progression of disability during the 6-month observation period in NISP patients. Inclusion of additional patients and extending of the follow-up period are intended to further investigate the efficacy of rituximab in NISP.

Essays in equilibrium asset pricing

Introduction This dissertation consists of three essays in equilibrium asset pricing. The first chapter studies the asset pricing implications of a general equilibrium model in which real investment is reversible at a cost. Firms face higher costs in contracting than in expanding their capital stock and decide to invest when their productive capital is scarce relative to the overall capital of the economy. Positive shocks to the capital of the firm increase the size of the firm and reduce the value of growth options. As a result, the firm is burdened with more unproductive capital and its value lowers with respect to the accumulated capital. The optimal consumption policy alters the optimal allocation of resources and affects firm's value, generating mean-reverting dynamics for the M/B ratios. The model (1) captures convergence of price-to-book ratios -negative for growth stocks and positive for value stocks - (firm migration), (2) generates deviations from the classic CAPM in line with the cross-sectional variation in expected stock returns and (3) generates a non-monotone relationship between Tobin's q and conditional volatility consistent with the empirical evidence. The second chapter proposes a standard portfolio-choice problem with transaction costs and mean reversion in expected returns. In the presence of transactions costs, no matter how small, arbitrage activity does not necessarily render equal all riskless rates of return. When two such rates follow stochastic processes, it is not optimal immediately to arbitrage out any discrepancy that arises between them. The reason is that immediate arbitrage would induce a definite expenditure of transactions costs whereas, without arbitrage intervention, there exists some, perhaps sufficient, probability that these two interest rates will come back together without any costs having been incurred. Hence, one can surmise that at equilibrium the financial market will permit the coexistence of two riskless rates that are not equal to each other. For analogous reasons, randomly fluctuating expected rates of return on risky assets will be allowed to differ even after correction for risk, leading to important violations of the Capital Asset Pricing Model. The combination of randomness in expected rates of return and proportional transactions costs is a serious blow to existing frictionless pricing models. Finally, in the last chapter I propose a two-countries two-goods general equilibrium economy with uncertainty about the fundamentals' growth rates to study the joint behavior of equity volatilities and correlation at the business cycle frequency. I assume that dividend growth rates jump from one state to other, while countries' switches are possibly correlated. The model is solved in closed-form and the analytical expressions for stock prices are reported. When calibrated to the empirical data of United States and United Kingdom, the results show that, given the existing degree of synchronization across these business cycles, the model captures quite well the historical patterns of stock return volatilities. Moreover, I can explain the time behavior of the correlation, but exclusively under the assumption of a global business cycle.

The effect of workplace smoking bans on heart rate variability and pulse wave velocity of non-smoking hospitality workers

OBJECTIVES: To investigate the effect of a change in second-hand smoke (SHS) exposure on heart rate variability (HRV) and pulse wave velocity (PWV), this study utilized a quasi-experimental setting when a smoking ban was introduced. METHODS: HRV, a quantitative marker of autonomic activity of the nervous system, and PWV, a marker of arterial stiffness, were measured in 55 non-smoking hospitality workers before and 3-12 months after a smoking ban and compared to a control group that did not experience an exposure change. SHS exposure was determined with a nicotine-specific badge and expressed as inhaled cigarette equivalents per day (CE/d). RESULTS: PWV and HRV parameters significantly changed in a dose-dependent manner in the intervention group as compared to the control group. A one CE/d decrease was associated with a 2.3 % (95 % CI 0.2-4.4; p = 0.031) higher root mean square of successive differences (RMSSD), a 5.7 % (95 % CI 0.9-10.2; p = 0.02) higher high-frequency component and a 0.72 % (95 % CI 0.40-1.05; p < 0.001) lower PWV. CONCLUSIONS: PWV and HRV significantly improved after introducing smoke-free workplaces indicating a decreased cardiovascular risk.

Physical interaction between bacterial heat shock protein (Hsp) 90 and Hsp70 chaperones mediates their cooperative action to refold denatured proteins.

In eukaryotes, heat shock protein 90 (Hsp90) is an essential ATP-dependent molecular chaperone that associates with numerous client proteins. HtpG, a prokaryotic homolog of Hsp90, is essential for thermotolerance in cyanobacteria, and in vitro it suppresses the aggregation of denatured proteins efficiently. Understanding how the non-native client proteins bound to HtpG refold is of central importance to comprehend the essential role of HtpG under stress. Here, we demonstrate by yeast two-hybrid method, immunoprecipitation assays, and surface plasmon resonance techniques that HtpG physically interacts with DnaJ2 and DnaK2. DnaJ2, which belongs to the type II J-protein family, bound DnaK2 or HtpG with submicromolar affinity, and HtpG bound DnaK2 with micromolar affinity. Not only DnaJ2 but also HtpG enhanced the ATP hydrolysis by DnaK2. Although assisted by the DnaK2 chaperone system, HtpG enhanced native refolding of urea-denatured lactate dehydrogenase and heat-denatured glucose-6-phosphate dehydrogenase. HtpG did not substitute for DnaJ2 or GrpE in the DnaK2-assisted refolding of the denatured substrates. The heat-denatured malate dehydrogenase that did not refold by the assistance of the DnaK2 chaperone system alone was trapped by HtpG first and then transferred to DnaK2 where it refolded. Dissociation of substrates from HtpG was either ATP-dependent or -independent depending on the substrate, indicating the presence of two mechanisms of cooperative action between the HtpG and the DnaK2 chaperone system.

Stability of cognitive performance in children with mild intellectual disability.

AIM: Longitudinal studies that have examined cognitive performance in children with intellectual disability more than twice over the course of their development are scarce. We assessed population and individual stability of cognitive performance in a clinical sample of children with borderline to mild non-syndromic intellectual disability. METHOD: Thirty-six children (28 males, eight females; age range 3-19y) with borderline to mild intellectual disability (Full-scale IQ [FSIQ] 50-85) of unknown origin were examined in a retrospective clinical case series using linear mixed models including at least three assessments with standardized intelligence tests. RESULTS: Average cognitive performance remained remarkably stable over time (high population stability, drop of only 0.38 IQ points per year, standard error=0.39, p=0.325) whereas individual stability was at best moderate (intraclass correlation of 0.58), indicating that about 60% of the residual variation in FSIQ scores can be attributed to between-child variability. Neither sex nor socio-economic status had a statistically significant impact on FSIQ. INTERPRETATION: Although intellectual disability during childhood is a relatively stable phenomenon, individual stability of IQ is only moderate, likely to be caused by test-to-test reliability (e.g. level of child's cooperation, motivation, and attention). Therefore, clinical decisions and predictions should not rely on single IQ assessments, but should also consider adaptive functioning and previous developmental history.

Better-quasi-order : ideals and spaces

This thesis deals with combinatorics, order theory and descriptive set theory. The first contribution is to the theory of well-quasi-orders (wqo) and better-quasi-orders (bqo). The main result is the proof of a conjecture made by Maurice Pouzet in 1978 his thèse d'état which states that any wqo whose ideal completion remainder is bqo is actually bqo. Our proof relies on new results with both a combinatorial and a topological flavour concerning maps from a front into a compact metric space. The second contribution is of a more applied nature and deals with topological spaces. We define a quasi-order on the subsets of every second countable To topological space in a way that generalises the Wadge quasi-order on the Baire space, while extending its nice properties to virtually all these topological spaces. The Wadge quasi-order of reducibility by continuous functions is wqo on Borei subsets of the Baire space, this quasi-order is however far less satisfactory for other important topological spaces such as the real line, as Hertling, Ikegami and Schlicht notably observed. Some authors have therefore studied reducibility with respect to some classes of discontinuous functions to remedy this situation. We propose instead to keep continuity but to weaken the notion of function to that of relation. Using the notion of admissible representation studied in Type-2 theory of effectivity, we define the quasi-order of reducibility by relatively continuous relations. We show that this quasi-order both refines the classical hierarchies of complexity and is wqo on the Borei subsets of virtually every second countable To space - including every (quasi-)Polish space. -- Cette thèse se situe dans les domaines de la combinatoire, de la théorie des ordres et de la théorie descriptive. La première contribution concerne la théorie des bons quasi-ordres (wqo) et des meilleurs quasi-ordres (bqo). Le résultat principal est la preuve d'une conjecture, énoncée par Pouzet en 1978 dans sa thèse d'état, qui établit que tout wqo dont l'ensemble des idéaux non principaux ordonnés par inclusion forme un bqo est alors lui-même un bqo. La preuve repose sur de nouveaux résultats, qui allient la combinatoire et la topologie, au sujet des fonctions d'un front vers un espace métrique compact. La seconde contribution de cette thèse traite de la complexité topologique dans le cadre des espaces To à base dénombrable. Dans le cas de l'espace de Baire, le quasi-ordre de Wadge est un wqo sur les sous-ensembles Boréliens qui a suscité énormément d'intérêt. Cependant cette relation de réduction par fonctions continues s'avère bien moins satisfaisante pour d'autres espaces d'importance tels que la droite réelle, comme l'ont fait notamment remarquer Hertling, Schlicht et Ikegami. Nous proposons de conserver la continuité et d'affaiblir la notion de fonction pour celle de relation. Pour ce faire, nous utilisons la notion de représentation admissible étudiée en « Type-2 theory of effectivity » initiée par Weihrauch. Nous introduisons alors le quasi-ordre de réduction par relations relativement continues et montrons que celui-ci à la fois raffine les hiérarchies classiques de complexité topologique et forme un wqo sur les sous-ensembles Boréliens de chaque espace quasi-Polonais.

The conditions for the reproduction of the SAGUAPAC water cooperative in the city of Santa Cruz de la Sierra, Bolivia : discourse analysis

The SAGUAPAC cooperative in the city of Santa Cruz de la Sierra (Eastern Bolivia) is regularly presented as an example of cooperative successes regarding water supply and sanitation. Its efficiency, both economic and technical, is widely considered as the main reason for its attractiveness. However, without denying its importance, we show, through a discourse analysis from and about SAGUAPAC in local media, that moral and non-instrumental factors are crucial in the reproduction of the cooperative. These factors create attachment and affection toward the cooperative, through a storytelling using a four-dimensional rhetoric (mythification, identification, emotionalisation and personification). This storytelling technique, internalized in the local media discourse and materializing the so-called new spirit of capitalism, exploits the affects and instrumentalisation of local myths and legends, as well as the 'camba' ethnic identity. In that, it tends to retain SAGUAPAC members and to canvass new ones, by providing them with recognition in their quality of local community members. However, the mobilisation of social norms and power hierarchies might end up reinforcing the social exclusion of Andean non-camba immigrants, inspite of an a priori inclusive and democratic organisation.