Intrauterine growth restriction and absent or reverse end-diastolic blood flow in umbilical artery (Doppler class II or III): A retrospective study of short- and long-term fetal morbidity and mortality.

OBJECTIVE: Absent or reverse end-diastolic flow (Doppler II/III) in umbilical artery is correlated with poor perinatal outcome, particularly in intrauterine growth restricted (IUGR) fetuses. The optimal timing of delivery is still controversial. We studied the short- and long-term morbidity and mortality among these children associated with our defined management. STUDY DESIGN: Sixty-nine IUGR fetuses with umbilical Doppler II/III were divided into three groups; Group 1, severe early IUGR, no therapeutic intervention (n = 7); Group 2, fetuses with pathological biophysical profile, immediate delivery (n = 35); Group 3, fetuses for which expectant management had been decided (n = 27). RESULTS: In Group 1, stillbirth was observed after a mean delay of 6.3 days. Group 2 delivered at an average of 31.6 weeks and two died in the neonatal period (6%). In Group 3 after a mean delay of 8 days, average gestational age at delivery was 31.7 weeks; two intra uterine and four perinatal deaths were observed (22%). Long-term follow-up revealed no sequelae in 25/31 (81%) and 15/18 (83%), and major handicap occurred in 1 (3%) and 2 patients (11%), respectively, for Groups 2 and 3. CONCLUSION: Fetal mortality was observed in 22% of this high risk group. After a mean period of follow-up of 5 years, 82% of infants showed no sequelae. According to our management, IUGR associated with umbilical Doppler II or III does not show any benefit from an expectant management in term of long-term morbidity.

Short term impact of Tribulus terrestris intake on doping control analysis of endogenous steroids.

Tribulus terrestris is a nutritional supplement highly debated regarding its physiological and actual effects on the organism. The main claimed effect is an increase of testosterone anabolic and androgenic action through the activation of endogenous testosterone production. Even if this biological pathway is not entirely proven, T. terrestris is regularly used by athletes. Recently, the analysis of two female urine samples by GC/C/IRMS (gas chromatography/combustion/isotope-ratio-mass-spectrometry) conclusively revealed the administration of exogenous testosterone or its precursors, even if the testosterone glucuronide/epitestosterone glucuronide (T/E) ratio and steroid marker concentrations were below the cut-off values defined by World Anti-Doping Agency (WADA). To argue against this adverse analytical finding, the athletes recognized having used T. terrestris in their diet. In order to test this hypothesis, two female volunteers ingested 500 mg of T. terrestris, three times a day and for two consecutive days. All spot urines were collected during 48 h after the first intake. The (13)C/(12)C ratio of ketosteroids was determined by GC/C/IRMS, the T/E ratio and DHEA concentrations were measured by GC/MS and LH concentrations by radioimmunoassay. None of these parameters revealed a significant variation or increased above the WADA cut-off limits. Hence, the short-term treatment with T. terrestris showed no impact on the endogenous testosterone metabolism of the two subjects.

Alliance patterns over the course of short-term dynamic psychotherapy: The shape of productive relationships.

The shape of alliance processes over the course of psychotherapy has already been studied in several process-outcome studies on very brief psychotherapy. The present study applies the shape-of-change methodology to short-term dynamic psychotherapies and complements this method with hierarchical linear modeling. A total of 50 psychotherapies of up to 40 sessions were included. Alliance was measured at the end of each session. The results indicate that a linear progression model is most adequate. Three main patterns were found: stable, linear, and quadratic growth. The linear growth pattern, along with the slope parameter, was related to treatment outcome. This study sheds additional light on alliance process research, underscores the importance of linear alliance progression for outcome, and also fosters a better understanding of its limitations.

Single breath-hold slice-following CSPAMM myocardial tagging.

Myocardial tagging has shown to be a useful magnetic resonance modality for the assessment and quantification of local myocardial function. Many myocardial tagging techniques suffer from a rapid fading of the tags, restricting their application mainly to systolic phases of the cardiac cycle. However, left ventricular diastolic dysfunction has been increasingly appreciated as a major cause of heart failure. Subtraction based slice-following CSPAMM myocardial tagging has shown to overcome limitations such as fading of the tags. Remaining impediments to this technique, however, are extensive scanning times (approximately 10 min), the requirement of repeated breath-holds using a coached breathing pattern, and the enhanced sensitivity to artifacts related to poor patient compliance or inconsistent depths of end-expiratory breath-holds. We therefore propose a combination of slice-following CSPAMM myocardial tagging with a segmented EPI imaging sequence. Together with an optimized RF excitation scheme, this enables to acquire as many as 20 systolic and diastolic grid-tagged images per cardiac cycle with a high tagging contrast during a short period of sustained respiration.

Functional MRI evaluation of liver tumour response after radiofrequency: short- and mid-term evolution of diffusion parameters

Purpose: To evaluate the short- and mid-term evolutions of the apparent diffusion coefficient of lesions treated with RF, in order to determine if the ADC can be used as a marker of tumour response. Methods and Materials: Twenty patients were treated for a liver malignancy with RF and were examined on a 1.5 T/3.0 T machine with T2, gadolinium-enhanced T1 and diffusion sequences: before treatment (< 1 month), just after treatment (< 1 month) and midterm (3-6 months). The ADC was measured in the whole lesion and in the area with the most restricted diffusion (MRDA). The ROI size was also measured on the diffusion map. The Pearson/ANOVA tests were used. Results: All patients were successfully treated with complete disappearance of CE. The lesional size on T2 showed a negative evolution in time (p < 0.002). The ADC in the whole lesion showed a bell-shaped evolution (increasing just after RF, then decreasing, p = 0.02). The ROI size on the diffusion map followed a similar course (p = 0.01). For the MRDA, such evolutions were also found, but they were not significant. There was a negative correlation between CE and the ADC (p < 0.02) and between the lesional size on T2 and ADC (p = 0.03) in the whole lesion. There were also positive correlations between the ROI size and ADC (p = 0.0008) and between CE and the size on T2 (p = 0.0002). The ADC in MRDA showed some non-significant correlations with other variables. Conclusion: The lesions successfully treated with RF have a clear and predictable evolution in terms of T2 size, CE and ADC.

Interactions of Adeno-associated virus Rep78 protein with the host cell

Abstract : Adeno-associated virus (AAV) is a small DNA virus belonging to the familiy of Parvoviridae. Its genome contains two genes : the rep gene encoding four non structural proteins (Rep78, 68, 52 and 40) implicated in transcription, replication and site-specific integration of the viral DNA and the cap gene encoding three capsid proteins. AAV does not cause any disease, but is studied in view of its potential use to treat several diseases. An interesting property of AAV is its antiproliferative effect. Two elements of AAV can inhibit cell growth. Firstly, the single stranded viral DNA is recognized in cells as damaged DNA leading to either a G2 block or cell death depending on p53 status. Secondly, the two larger Rep proteins (Rep78 and 68) also arrest the cell cycle when they are expressed at high levels. Rep78 in particular induces a complete cell cycle arrest in all the phases, including S phase. Such a strong S phase arrest is rarely seen in other conditions. It was thus interesting to determine how Rep78 could induce it. We found that this strong block is the consequence of Rep78's effects on at least two pathways. Rep78 induces a DNA damage response by producing nicks in the cellular chromatin. Furthermore, Rep78 can bind to the cellular phosphatase Cdc25A and prevent its binding to its substrates CDK2 and CDK1, thus inhibiting its activity. A mutational analysis of Rep78 protein determined that its endonuclease activity is responsible for the DNA damage response and its zinc finger domain for Cdc25A inhibition. The combined expression of two mutants each defective for one of these activities, or these two activities obtained independently of Rep78, could restore the complete cell cycle block, indicating that these two effects of Rep78 are likely to explain completely the cell cycle block it induces. Secondly, the lack of pathogenicity of AAV, its broad range of infection and its ability to integrate site-specifically in human chromosome 19 make it an interesting potential vector for gene therapy. However site-specific integration is only possible in the presence of Rep78/68 whose gene is removed in recombinant AAV vectors. In this part of the study, we tried to introduce Rep protein separately from recombinant AAV vectors to promote their site-specific integration. For that purpose, a fusion protein, TAT-Rep, comprising Rep78/68 joined to the human immunodeficiency virus Tat protein was produced. It had the ability to enter cells and remain active there for a short period. Its activity was sufficient to mediate transcription from the p5 promoter, second-strand synthesis of a recombinant AAV and probably site-specific integration. Résumé : Le virus associé à l'adénovirus (AAV) est un petit virus à ADN qui fait partie de la famille des Parvoviridae. Son génome contient deux gènes : le gène rep code pour quatre protéines (Rep78, 68, 52 et 40) qui participent à la transcription, la réplication et l'intégration du virus et le gène cap code pour les trois protéines de capside. AAV ne produit pas de maladie, mais pourrait au contraire être utilisé pour en soigner. Sa bénignité, sa capacité à infecter différents types de cellules et son intégration spécifique en font un vecteur potentiel pour la thérapie génique. Pour qu'il puisse s'intégrer spécifiquement, il a besoin de la protéine Rep78 ou 68, mais ce gène doit être enlevé des vecteurs pour la thérapie génique. Le but de la première partie de cette étude était d'introduire Rep78 ou 68 dans des cellules en même temps qu'un AAV recombinant, mais indépendamment afin de permettre une intégration spécifique. La stratégie utilisée était de produire une protéine de fusion (TAT-Rep) qui peut entrer dans des cellules si elle est présente dans leur milieu. Cette protéine entrait bien dans les cellules et y était active favorisant ainsi l'intégration spécifique. Une deuxième propriété d'AAV, son effet anti-prolifératif, est intéressante dans le cadre de certaines maladies comme le cancer. Deux éléments d'AAV en sont responsables. D'abord, son ADN simple brin active une réponse cellulaire à l'ADN endommagé et arrête les cellules en G2 ou provoque leur mort. De plus, la protéine Rep78 d'AAV peut fortement bloquer le cycle cellulaire à toutes les phases, même en phase S, ce qui est rare. C'est pourquoi nous avons essayé de comprendre cet effet. Nous avons remarqué que Rep78 doit agir sur deux fronts pour obtenir ce fort bloc. D'un côté, Rep78 introduit des coupures simple brin sur l'ADN de la cellule ce qui active une réponse cellulaire à l'ADN endommagé qui passe par ATM. D'un autre côté, Rep78 lie une phosphatase cellulaire, Cdc25A, et l'empêche ainsi de lier ses substrats CDK2 et CDK1 et donc d'être active. Finalement, à l'aide de mutants de Rep78, nous avons déterminé que l'activité endonuclease de Rep78 était nécessaire pour induire une réponse cellulaire via ATM et que le domaine C-terminal appelé «zinc finger » était responsable de la liaison avec Cdc25A. En co-exprimant deux mutants, qui n'ont chacun qu'un des effets de Rep78, ou en obtenant les deux effets de Rep78 indépendamment d'elle, nous avons obtenu un bloc complet du cycle cellulaire similaire à celui obtenu avec Rep78. Il est donc probable que ces deux effets de Rep78 sont suffisants pour expliquer comment elle arrive à arrêter le cycle cellulaire si efficacement.

Life-Cycle Effects on Household Expenditures: A Latent-Variable Approach

Using data from the Spanish household budget survey, we investigate life- cycle effects on several product expenditures. A latent-variable model approach is adopted to evaluate the impact of income on expenditures, controlling for the number of members in the family. Two latent factors underlying repeated measures of monetary and non-monetary income are used as explanatory variables in the expenditure regression equations, thus avoiding possible bias associated to the measurement error in income. The proposed methodology also takes care of the case in which product expenditures exhibit a pattern of infrequent purchases. Multiple-group analysis is used to assess the variation of key parameters of the model across various household life-cycle typologies. The analysis discloses significant life-cycle effects on the mean levels of expenditures; it also detects significant life-cycle effects on the way expenditures are affected by income and family size. Asymptotic robust methods are used to account for possible non-normality of the data.

The short arm of the law: judicial institutions and local governance in Brazil

This paper estimates the effect of judicial institutions on governance at the local level in Brazil. Our estimation strategy exploits a unique institutional feature of state judiciary branches which assigns prosecutors and judges to the most populous among contiguous counties forming a judiciary district. As a result of this assignment mechanism there are counties with nearly identical populations, some with and some without local judicial presence, which we exploit to impute counterfactual outcomes. Conditional on observable county characteristics, offenses per civil servant are about 35% lower in counties that have a local seat of the state judiciary. The lower incidence of infractions stems mostly from fewer violations of financial management regulations by local administrators, fewer instances of problems in project execution and project managment, fewer cases of non-existent or ineffective civil society oversight and fewer cases of improper handling of remittances to local residents.

Measurement with Some Theory: a New Approach to Evaluate Business Cycle Models

We propose a method to evaluate cyclical models which does not require knowledge of the DGP and the exact empirical specification of the aggregate decision rules. We derive robust restrictions in a class of models; use some to identify structural shocks and others to evaluate the model or contrast sub-models. The approach has good size and excellent power properties, even in small samples. We show how to examine the validity of a class of models, sort out the relevance of certain frictions, evaluate the importance of an added feature, and indirectly estimate structural parameters.

Predictable Life-Cycle Shocks, Income Risk and Consumption Inequality

Was the increase in income inequality in the US due to permanent shocks or merely to an increase in the variance of transitory shocks? The implications for consumption and welfare depend crucially on the answer to this question. We use CEX repeated cross-section data on consumption and income to decompose idiosyncratic changes in income into predictable life-cycle changes, transitory and permanent shocks and estimate the contribution of each to total inequality. Our model fits the joint evolution of consumption and income inequality well and delivers two main results. First, we find that permanent changes in income explain all of the increase in inequality in the 1980s and 90s. Second, we reconcile this finding with the fact that consumption inequality did not increase much over this period. Our results support the view that many permanent changes in income are predictable for consumers, even if they look unpredictable to the econometrician, consistent with models of heterogeneous income profiles.

Rules of origin : from analysis to reform

General Introduction This thesis can be divided into two main parts :the first one, corresponding to the first three chapters, studies Rules of Origin (RoOs) in Preferential Trade Agreements (PTAs); the second part -the fourth chapter- is concerned with Anti-Dumping (AD) measures. Despite wide-ranging preferential access granted to developing countries by industrial ones under North-South Trade Agreements -whether reciprocal, like the Europe Agreements (EAs) or NAFTA, or not, such as the GSP, AGOA, or EBA-, it has been claimed that the benefits from improved market access keep falling short of the full potential benefits. RoOs are largely regarded as a primary cause of the under-utilization of improved market access of PTAs. RoOs are the rules that determine the eligibility of goods to preferential treatment. Their economic justification is to prevent trade deflection, i.e. to prevent non-preferred exporters from using the tariff preferences. However, they are complex, cost raising and cumbersome, and can be manipulated by organised special interest groups. As a result, RoOs can restrain trade beyond what it is needed to prevent trade deflection and hence restrict market access in a statistically significant and quantitatively large proportion. Part l In order to further our understanding of the effects of RoOs in PTAs, the first chapter, written with Pr. Olivier Cadot, Celine Carrère and Pr. Jaime de Melo, describes and evaluates the RoOs governing EU and US PTAs. It draws on utilization-rate data for Mexican exports to the US in 2001 and on similar data for ACP exports to the EU in 2002. The paper makes two contributions. First, we construct an R-index of restrictiveness of RoOs along the lines first proposed by Estevadeordal (2000) for NAFTA, modifying it and extending it for the EU's single-list (SL). This synthetic R-index is then used to compare Roos under NAFTA and PANEURO. The two main findings of the chapter are as follows. First, it shows, in the case of PANEURO, that the R-index is useful to summarize how countries are differently affected by the same set of RoOs because of their different export baskets to the EU. Second, it is shown that the Rindex is a relatively reliable statistic in the sense that, subject to caveats, after controlling for the extent of tariff preference at the tariff-line level, it accounts for differences in utilization rates at the tariff line level. Finally, together with utilization rates, the index can be used to estimate total compliance costs of RoOs. The second chapter proposes a reform of preferential Roos with the aim of making them more transparent and less discriminatory. Such a reform would make preferential blocs more "cross-compatible" and would therefore facilitate cumulation. It would also contribute to move regionalism toward more openness and hence to make it more compatible with the multilateral trading system. It focuses on NAFTA, one of the most restrictive FTAs (see Estevadeordal and Suominen 2006), and proposes a way forward that is close in spirit to what the EU Commission is considering for the PANEURO system. In a nutshell, the idea is to replace the current array of RoOs by a single instrument- Maximum Foreign Content (MFC). An MFC is a conceptually clear and transparent instrument, like a tariff. Therefore changing all instruments into an MFC would bring improved transparency pretty much like the "tariffication" of NTBs. The methodology for this exercise is as follows: In step 1, I estimate the relationship between utilization rates, tariff preferences and RoOs. In step 2, I retrieve the estimates and invert the relationship to get a simulated MFC that gives, line by line, the same utilization rate as the old array of Roos. In step 3, I calculate the trade-weighted average of the simulated MFC across all lines to get an overall equivalent of the current system and explore the possibility of setting this unique instrument at a uniform rate across lines. This would have two advantages. First, like a uniform tariff, a uniform MFC would make it difficult for lobbies to manipulate the instrument at the margin. This argument is standard in the political-economy literature and has been used time and again in support of reductions in the variance of tariffs (together with standard welfare considerations). Second, uniformity across lines is the only way to eliminate the indirect source of discrimination alluded to earlier. Only if two countries face uniform RoOs and tariff preference will they face uniform incentives irrespective of their initial export structure. The result of this exercise is striking: the average simulated MFC is 25% of good value, a very low (i.e. restrictive) level, confirming Estevadeordal and Suominen's critical assessment of NAFTA's RoOs. Adopting a uniform MFC would imply a relaxation from the benchmark level for sectors like chemicals or textiles & apparel, and a stiffening for wood products, papers and base metals. Overall, however, the changes are not drastic, suggesting perhaps only moderate resistance to change from special interests. The third chapter of the thesis considers whether Europe Agreements of the EU, with the current sets of RoOs, could be the potential model for future EU-centered PTAs. First, I have studied and coded at the six-digit level of the Harmonised System (HS) .both the old RoOs -used before 1997- and the "Single list" Roos -used since 1997. Second, using a Constant Elasticity Transformation function where CEEC exporters smoothly mix sales between the EU and the rest of the world by comparing producer prices on each market, I have estimated the trade effects of the EU RoOs. The estimates suggest that much of the market access conferred by the EAs -outside sensitive sectors- was undone by the cost-raising effects of RoOs. The chapter also contains an analysis of the evolution of the CEECs' trade with the EU from post-communism to accession. Part II The last chapter of the thesis is concerned with anti-dumping, another trade-policy instrument having the effect of reducing market access. In 1995, the Uruguay Round introduced in the Anti-Dumping Agreement (ADA) a mandatory "sunset-review" clause (Article 11.3 ADA) under which anti-dumping measures should be reviewed no later than five years from their imposition and terminated unless there was a serious risk of resumption of injurious dumping. The last chapter, written with Pr. Olivier Cadot and Pr. Jaime de Melo, uses a new database on Anti-Dumping (AD) measures worldwide to assess whether the sunset-review agreement had any effect. The question we address is whether the WTO Agreement succeeded in imposing the discipline of a five-year cycle on AD measures and, ultimately, in curbing their length. Two methods are used; count data analysis and survival analysis. First, using Poisson and Negative Binomial regressions, the count of AD measures' revocations is regressed on (inter alia) the count of "initiations" lagged five years. The analysis yields a coefficient on measures' initiations lagged five years that is larger and more precisely estimated after the agreement than before, suggesting some effect. However the coefficient estimate is nowhere near the value that would give a one-for-one relationship between initiations and revocations after five years. We also find that (i) if the agreement affected EU AD practices, the effect went the wrong way, the five-year cycle being quantitatively weaker after the agreement than before; (ii) the agreement had no visible effect on the United States except for aone-time peak in 2000, suggesting a mopping-up of old cases. Second, the survival analysis of AD measures around the world suggests a shortening of their expected lifetime after the agreement, and this shortening effect (a downward shift in the survival function postagreement) was larger and more significant for measures targeted at WTO members than for those targeted at non-members (for which WTO disciplines do not bind), suggesting that compliance was de jure. A difference-in-differences Cox regression confirms this diagnosis: controlling for the countries imposing the measures, for the investigated countries and for the products' sector, we find a larger increase in the hazard rate of AD measures covered by the Agreement than for other measures.