Do Mutual Fund Managers Have Superior Skills? An Analysis of the Portfolio Deviations from a Benchmark

By construction, actively managed portfolios must differ from passively managed ones. Consequently, the manager’s problem can be viewed as selecting how to deviate from a passive portfolio composition. The purpose of this study is to see if we can infer the presence of superior skills through the analysis of the portfolio deviations from a benchmark. Based on the Black-Litterman approach, we hypothesize that positive signals should lead to an increase in weight, from which should follow that the largest deviations from a benchmark weight reveal the presence of superior skills. More precisely, this study looks at the subsequent performance of the securities corresponding to the largest deviations from different external benchmarks. We use a sample of 8385 US funds from the CRSP Survivorship bias free database from June 2003 to June 2004 to test our predictions. We use two external benchmarks to calculate the deviations: the CRSP value weighted index (consistent with the Black-Litterman model) and the investment objective of each fund. Our main result shows that a portfolio of the securities with the most important positive deviations with respect to a passive benchmark (either CRSP-VW or investment objective), would have earned a subsequent positive abnormal return (on a risk-adjusted basis) for one month after the portfolio date. The magnitude of this return is around 0.6% for all the funds, and can be as high as 2.77% for small caps value funds. This result is robust to all the performance measures used in this study

Multimodal Elastic Matching of Brain Images

This paper presents an original method for three-dimensional elastic registration of multimodal images. We propose to make use of a scheme that iterates between correcting for intensity di#erences between images and performing standard monomodal registration. The core of our contribution resides in providing a method that finds the transformation that maps the intensities of one image to those of another. It makes the assumption that there are at most two functional dependences between the intensities of structures present in the images to register, and relies on robust estimation techniques to evaluate these functions. We provide results showing successful registration between several imaging modalities involving segmentations, T1 magnetic resonance (MR), T2 MR, proton density (PD) MR and computed tomography (CT)

Analyse fonctionnelle du gène BMP-2 lors de la régénération du membre chez l’axolotl

Les amphibiens urodèles (e.g. les axolotls) possèdent la remarquable capacité de régénérer plusieurs parties de leur corps. Ils peuvent, entre autres, régénérer parfaitement un membre amputé par épimorphose, un processus biphasique comprenant une phase de préparation, spécifique à la régénération, et une phase de redéveloppement, commune à l’épimorphose et au développement embryonnaire. Durant la phase de préparation, les cellules du moignon se dédifférencient en cellules pseudo-embryonnaires, prolifèrent et migrent distalement au plan d’amputation pour former un blastème de régénération. Parmi les vertébrés, la dédifférenciation est unique aux urodèles. Afin de mieux comprendre le contrôle moléculaire de la régénération chez les urodèles, nous avons choisi d’étudier BMP-2, un facteur de croissance, en raison de son implication dans la régénération des phalanges distales chez les mammifères. Le facteur de transcription MSX-1 a également été sélectionné en raison de sa capacité à induire la dédifférenciation cellulaire in vitro et de son interaction potentielle avec la signalisation des BMPs. Les résultats présentés dans cette thèse démontrent que BMP-2 et MSX-1 sont exprimés lors des phases de préparation et de redéveloppement de l’épimorphose, et que leur profil d'expression spatio-temporel est très semblable, ce qui suggère une interaction de leurs signaux. En outre, chez les tétrapodes amniotes, l’expression de Shh est restreinte au mésenchyme postérieur des membres en développement et chevauche l’expression de BMP-2. Toutefois, l’expression de BMP-2 n’est pas restreinte à la région postérieure mais forme un gradient postéro-antérieur. Shh est le principal régulateur de la formation du patron de développement antéro-postérieur du ii membre. Étant donné les domaines d’expression chevauchants de BMP-2 et Shh et la restriction postérieure d’expression de Shh, on croit que Shh régule la formation du patron de développement de postérieur à antérieur par l’activation de l’expression de BMP-2. Fait intéressant, l’axolotl exprime également Shh dans la région postérieure, mais le développement des pattes se fait de la région antérieure à la région postérieure au lieu de postérieur à antérieur comme chez les autres tétrapodes, et ceci durant le développement et la régénération. Nous avons utilisé cette caractéristique de l’axolotl pour démontrer que la signalisation Shh ne structure pas l’autopode via BMP-2. En effet, l’expression de BMP-2 n'est pas régulée par l'inhibition de la signalisation Shh, et son expression est du côté opposé à celle de Shh durant le développement et la régénération des pattes de l’axolotl. Il a été observé durant le développement du membre chez la souris que MSX-1 est régulé par la signalisation Shh. Nos résultats ont démontrés que chez l’axolotl, MSX-1 ne semble pas régulé par l'inhibition de la signalisation Shh au cours de la régénération du membre. De plus, nous avons démontré que contrairement à l’expression de Shh, l’expression de BMP-2 est corrélée avec l’ordre de formation des phalanges, est impliquée dans la condensation cellulaire et dans l'apoptose précédant la chondrogenèse. L’ensemble de ces résultats suggère un rôle de BMP-2 dans l’initiation de l’ossification endochondrale. Enfin, nous avons démontré que la signalisation BMP est indispensable pour l’épimorphose du membre durant la phase de redéveloppement.Urodele amphibians (e.g. the axolotls) have a remarkable ability to regenerate parts of their body. They will, among other things, fully regenerate an amputated limb by epimorphosis, a biphasic process comprising a preparation phase, specific to the regeneration, and a redevelopment phase, common to epimorphosis and embryonic development. During the preparation phase, the cells of the stump dedifferentiate into embryonic-like cells, proliferate and migrate distally from the level of amputation to form a regeneration blastema. Among vertebrates, the process of dedifferentiation is unique to urodeles. To better understand the molecular control of regeneration in urodeles, we chose to study BMP-2, a growth factor, because of its involvement in mammalian digit tip regeneration. The transcription factor MSX-1 has also been selected because of its ability to induce cellular dedifferentiation in vitro and its potential interaction with BMPs signaling. The results presented in this thesis show that BMP-2 and MSX-1 are expressed during phases of preparation and redevelopment of epimorphosis, and their spatio-temporal expression profiles are very similar at each stage of epimorphosis, suggesting an interaction of their signals during regeneration. In addition, in tetrapod amniotes, the expression of Shh is restricted to the posterior mesenchyme of developing limbs and overlaps with the expression of BMP-2. However, the expression of BMP-2 is not restricted to the posterior region but forms a posterior-anterior gradient. Shh is the main regulator of the anterior-posterior pattern formation of developing limbs. Given the overlapping expression domains of Shh and BMP-2, and the expression restriction of Shh in posterior, Shh is believed to iv regulate the pattern formation of developing limbs by the activation of BMP-2 expression. Interestingly, the axolotl also expresses Shh in the posterior region, but the limb develops from anterior to posterior rather than posterior to anterior as in other tetrapods, and this, during development and epimorphosis. We used this feature of the axolotl to demonstrate that Shh signaling does not regulate pattern formation through BMP-2. Indeed, the expression of BMP-2 is not regulated by the inhibition of hh signaling, and its expression is opposite to that of Shh during development and regeneration of the axolotl limb. It was observed, during limb development in mice that MSX-1 is regulated by Shh signaling. Our results suggest that in the axolotl, MSX-1 is not regulated by the inhibition of Shh signaling during limb regeneration. Furthermore, we demonstrated that unlike the expression of Shh, the expression of BMP-2 is correlated with the order of formation of the phalanges, is involved in cell condensation and apoptosis preceding chondrogenesis. Taken together, these results suggest a role for BMP-2 in the initiation of endochondral ossification. Finally, we demonstrated that BMP signaling is essential for the redevelopment phase of limb epimorphosis

Développement et validation de contenu d’un programme de rééducation du membre supérieur post AVC en ergothérapie

Introduction. La thérapie axée sur la répétition de tâches fonctionnelles est préconisée pour la réadaptation du membre supérieur à la suite d’un accident vasculaire cérébral (AVC). Toutefois, aucun programme d’intervention n’opérationnalise l’ensemble des composantes clés du TOT en une démarche clinique valide de rééducation du membre supérieur post AVC en ergothérapie. Objectifs. 1) Établir la validité de contenu d’un programme de rééducation du membre supérieur post AVC en ergothérapie et 2) proposer un modèle logique de l’intervention qui fait consensus auprès d’experts et d’usagers. Méthodes. Un modèle logique d’un programme de rééducation du membre supérieur post AVC en ergothérapie a été développé, puis soumis à deux méthodes de recherche pour valider le contenu et obtenir un consensus d’experts et d’usagers : 1) Méthode Delphi : 14 experts ont examiné des capsules audiovisuelles illustrant le programme d’intervention et ont répondu à deux questionnaires pour valider les objectifs, la nature de l’intervention, les ressources, les activités et les extrants; 2) Technique de groupe nominal : six usagers ayant un vécu expérientiel de l’intervention ont généré les effets ciblés. L’indice de validité de contenu, deux indices d’accord interjuges et l’analyse de contenu ont été utilisés pour analyser les données. Résultats. Près de 93 % du contenu du programme de rééducation du membre supérieur post AVC en ergothérapie obtient un indice de validité satisfaisant, dont 82 % qui font consensus auprès d’experts et d’usagers dans un modèle logique révisé. Conclusion. Le modèle logique révisé propose une vision commune, quoiqu’incomplète, d’un programme de rééducation du membre supérieur post AVC en ergothérapie basé sur le TOT. Les activités et les extrants de l’évaluation devront faire l’objet de validation lors d’une phase subséquente d’implantation. Un transfert de connaissances sur les moyens pour favoriser le sentiment d’efficacité personnelle est aussi à prévoir pour réévaluer son rôle dans le programme d’intervention.Background. Task-Oriented Training (TOT) is the recommended approach for upper extremity rehabilitation after a stroke. To date, no program have operationalized all the key components of TOT into a valid upper extremity clinical rehabilitation process post stroke in occupational therapy. Objectives. 1) To determine the content validity of an upper extremity rehabilitation program post stroke in occupational therapy and 2) to propose a logic model reaching consensus among experts and patients. Methods. A logic model of an upper extremity rehabilitation program post stroke in occupational therapy was developed and validated. Two research methods were used to validate the content and to achieve a consensus of experts and patients : 1) Delphi method : 14 experts examined audiovisual capsules of the intervention and completed two questionnaires to validate the objectives, the nature of the intervention, the resources, the activities and the outputs; 2) Nominal group technique : six patients with experience of the intervention generated the outcomes. The content validity index, two interrater agreement statistics and a content analysis were used for data analysis. Results. Almost 93 % of the content of the upper extremity rehabilitation program post stroke in occupational therapy obtained a satisfactory validity index, including 82 % reaching consensus among experts and patients in a revised logic model. Conclusion. The revised logic model now offers a common, albeit incomplete, vision of an upper extremity rehabilitation program post stroke based on the TOT in occupational therapy. Activities and outputs of the evaluation should be validated during a subsequent implementation phase. Knowledge translation on the modalities to promote self-efficacy is also to be planned to reassess its role in the intervention program

BMP-2 functions independently of SHH signaling and triggers cell condensation and apoptosis in regenerating axolotl limbs

<p>Abstract</p> <p>Background</p> <p>Axolotls have the unique ability, among vertebrates, to perfectly regenerate complex body parts, such as limbs, after amputation. In addition, axolotls pattern developing and regenerating autopods from the anterior to posterior axis instead of posterior to anterior like all tetrapods studied to date. Sonic hedgehog is important in establishing this anterior-posterior axis of limbs in all tetrapods including axolotls. Interestingly, its expression is conserved (to the posterior side of limb buds and blastemas) in axolotl limbs as in other tetrapods. It has been suggested that <it>BMP-2 </it>may be the secondary mediator of sonic hedgehog, although there is mounting evidence to the contrary in mice. Since <it>BMP-2 </it>expression is on the anterior portion of developing and regenerating limbs prior to digit patterning, opposite to the expression of sonic hedgehog, we examined whether <it>BMP-2 </it>expression was dependent on sonic hedgehog signaling and whether it affects patterning of the autopod during regeneration.</p> <p>Results</p> <p>The expression of <it>BMP-2 </it>and <it>SOX-9 </it>in developing and regenerating axolotl limbs corresponded to the first digits forming in the anterior portion of the autopods. The inhibition of sonic hedgehog signaling with cyclopamine caused hypomorphic limbs (during development and regeneration) but did not affect the expression of <it>BMP-2 </it>and <it>SOX-9</it>. Overexpression of <it>BMP-2 </it>in regenerating limbs caused a loss of digits. Overexpression of <it>Noggin </it>(<it>BMP </it>inhibitor) in regenerating limbs also resulted in a loss of digits. Histological analysis indicated that the loss due to <it>BMP-2 </it>overexpression was the result of increased cell condensation and apoptosis while the loss caused by <it>Noggin </it>was due to a decrease in cell division.</p> <p>Conclusion</p> <p>The expression of <it>BMP-2 </it>and its target <it>SOX-9 </it>was independent of sonic hedgehog signaling in developing and regenerating limbs. Their expression correlated with chondrogenesis and the appearance of skeletal elements has described in other tetrapods. Overexpression of <it>BMP-2 </it>did not cause the formation of extra digits, which is consistent with the hypothesis that it is not the secondary signal of sonic hedgehog. However, it did cause the formation of hypomorphic limbs as a result of increased cellular condensation and apoptosis. Taken together, these results suggest that <it>BMP-2 </it>does not have a direct role in patterning regenerating limbs but may be important to trigger condensation prior to ossification and to mediate apoptosis.</p

Multimodal Brain Warping Using the Demons Algorithm and Adaptative Intensity Corrections

International audienceThis paper presents an original method for three-dimensional elastic registration of multimodal images. We propose to make use of a scheme that iterates between correcting for intensity differences between images and performing standard monomodal registration. The core of our contribution resides in providing a method that finds the transformation that maps the intensities of one image to those of another. It makes the assumption that there are at most two functional dependencies between the intensities of structures present in the images to register, and relies on robust estimation techniques to evaluate these functions. We provide results showing successful registration between several imaging modalities involving segmentations, T1 magnetic resonance (MR), T2 MR, proton density (PD) MR and computed tomography (CT). We also argue that our intensity modeling may be more appropriate than mutual information (MI) in the context of evaluating high-dimensional deformations, as it puts more constraints on the parameters to be estimated and, thus, permits a better search of the parameter space

Flt3L-Mediated expansion of plasmacytoid dendritic cells suppresses HIV infection in humanized mice

Plasmacytoid dendritic cells (plasmacytoid DC, pDC) are major IFN-I producers and have been shown to be affected by HIV through ill-defined mechanisms. In this study, we directly assess the role of pDC in early infection, evaluating whether modulating their abundance can alter viral replication. First, HIV infection of humanized mice induces systemic depletion of pDC, and in the presence of soluble FMS-like tyrosine kinase 3 ligand (Flt3L), pDC levels remain elevated. Flt3L significantly delays the onset of viremia and reduces viral replication via a process that is dependent on pDC and mediated through an enhanced early IFN-I response. pDC from Flt3L-treated mice are more prone to express IFN-a following TLR7 stimulation, but this propensity is gradually decreased during infection. In conclusion, maintaining pDC levels and function is key to effective early viral control, and in this context, these findings provide practical insights for anti-HIV strategies and vaccine design

Characterization of 3D PET systems for accurate quantification of myocardial blood flow

Three-dimensional (3D) mode imaging is the current standard for positron emission tomography-computed tomography (PET-CT) systems. Dynamic imaging for quantification of myocardial blood flow (MBF) with short-lived tracers, such as Rb-82- chloride (Rb-82), requires accuracy to be maintained over a wide range of isotope activities and scanner count-rates. We propose new performance standard measurements to characterize the dynamic range of PET systems for accurate quantitative imaging. Methods: 1100-3000 MBq of Rb-82 or N-13-ammonia was injected into the heart wall insert of an anthropomorphic torso phantom. A decaying isotope scan was performed over 5 half-lives on 9 different 3D PET-CT systems and 1 3D/twodimensional (2D) PET-only system. Dynamic images (28x15s) were reconstructed using iterative algorithms with all corrections enabled. Dynamic range was defined as the maximum activity in the myocardial wall with <10% bias, from which corresponding dead-time, count-rates and/or injected activity limits were established for each scanner. Scatter correction residual bias was estimated as the maximum cavity blood-tomyocardium activity ratio. Image quality was assessed via the coefficient of variation measuring non-uniformity of the left ventricle (LV) myocardium activity distribution. Results: Maximum recommended injected activity/body-weight, peak dead-time correction factor, count-rates and residual scatter bias for accurate cardiac MBF imaging were: 3-14 MBq/kg, 1.5-4.0, 22-64 Mcps singles and 4-14 Mcps prompt coincidence count-rates, and 2-10% on the investigated scanners. Non-uniformity of the myocardial activity distribution varied from 3-16%. Conclusion: Accurate dynamic imaging is possible on the 10 3D-PET systems if the maximum injected MBq/kg values are respected to limit peak dead-time losses during the bolus first-pass transit

Genetic Variation in LPA, Calcific Aortic Valve Stenosis in Patients Undergoing Cardiac Surgery, and Familial Risk of Aortic Valve Microcalcification.

IMPORTANCE: Genetic variants at the LPA locus are associated with both calcific aortic valve stenosis (CAVS) and coronary artery disease (CAD). Whether these variants are associated with CAVS in patients with CAD vs those without CAD is unknown. OBJECTIVE: To study the associations of LPA variants with CAVS in a cohort of patients undergoing heart surgery and LPA with CAVS in patients with CAD vs those without CAD and to determine whether first-degree relatives of patients with CAVS and high lipoprotein(a) (Lp[a]) levels showed evidence of aortic valve microcalcification. DESIGN, SETTING, AND PARTICIPANTS: This genetic association study included patients undergoing cardiac surgery from the Genome-Wide Association Study on Calcific Aortic Valve Stenosis in Quebec (QUEBEC-CAVS) study and patients with CAD, patients without CAD, and control participants from 6 genetic association studies: the UK Biobank, the European Prospective Investigation of Cancer (EPIC)-Norfolk, and Genetic Epidemiology Research on Aging (GERA) studies and 3 French cohorts. In addition, a family study included first-degree relatives of patients with CAVS. Data were collected from January 1993 to September 2018, and analysis was completed from September 2017 to September 2018. EXPOSURES: Case-control studies. MAIN OUTCOMES AND MEASURES: Presence of CAVS according to a weighted genetic risk score based on 3 common Lp(a)-raising variants and aortic valve microcalcification, defined as the mean tissue to background ratio of 1.25 or more, measured by fluorine 18-labeled sodium fluoride positron emission tomography/computed tomography. RESULTS: This study included 1009 individuals undergoing cardiac surgery and 1017 control participants in the QUEBEC-CAVS cohort; 3258 individuals with CAVS and CAD, 41 100 controls with CAD, 2069 individuals with CAVS without CAD, and 380 075 control participants without CAD in the UK Biobank, EPIC-Norfolk, and GERA studies and 3 French cohorts combined; and 33 first-degree relatives of 17 patients with CAVS and high Lp(a) levels (≥60 mg/dL) and 23 control participants with normal Lp(a) levels (<60 mg/dL). In the QUEBEC-CAVS study, each SD increase of the genetic risk score was associated with a higher risk of CAVS (odds ratio [OR], 1.35 [95% CI, 1.10-1.66]; P = .003). Each SD increase of the genetic risk score was associated with a higher risk of CAVS in patients with CAD (OR, 1.30 [95% CI, 1.20-1.42]; P < .001) and without CAD (OR, 1.33 [95% CI, 1.14-1.55]; P < .001). The percentage of individuals with a tissue to background ratio of 1.25 or more or CAVS was higher in first-degree relatives of patients with CAVS and high Lp(a) (16 of 33 [49%]) than control participants (3 of 23 [13%]; P = .006). CONCLUSIONS AND RELEVANCE: In this study, a genetically elevated Lp(a) level was associated with CAVS independently of the presence of CAD. These findings support further research on the potential usefulness of Lp(a) cascade screening in CAVS