Constant coefficient tests for random coefficient regression

Random coefficient regression models have been applied in differentfields and they constitute a unifying setup for many statisticalproblems. The nonparametric study of this model started with Beranand Hall (1992) and it has become a fruitful framework. In thispaper we propose and study statistics for testing a basic hypothesisconcerning this model: the constancy of coefficients. The asymptoticbehavior of the statistics is investigated and bootstrapapproximations are used in order to determine the critical values ofthe test statistics. A simulation study illustrates the performanceof the proposals.

Constant interest rate projections without the curse of indeterminacy

Constant interest rate (CIR) projections are often criticized on the grounds that they are inconsistent with the existence of a unique equilibrium in a variety of forward-looking models. This note shows howto construct CIR projections that are not subject to that criticism, using a standard New Keynesian model as a reference framework.

Reference Cluster Normalization Improves Detection of Frontotemporal Lobar Degeneration by Means of FDG-PET.

Positron emission tomography with [18F] fluorodeoxyglucose (FDG-PET) plays a well-established role in assisting early detection of frontotemporal lobar degeneration (FTLD). Here, we examined the impact of intensity normalization to different reference areas on accuracy of FDG-PET to discriminate between patients with mild FTLD and healthy elderly subjects. FDG-PET was conducted at two centers using different acquisition protocols: 41 FTLD patients and 42 controls were studied at center 1, 11 FTLD patients and 13 controls were studied at center 2. All PET images were intensity normalized to the cerebellum, primary sensorimotor cortex (SMC), cerebral global mean (CGM), and a reference cluster with most preserved FDG uptake in the aforementioned patients group of center 1. Metabolic deficits in the patient group at center 1 appeared 1.5, 3.6, and 4.6 times greater in spatial extent, when tracer uptake was normalized to the reference cluster rather than to the cerebellum, SMC, and CGM, respectively. Logistic regression analyses based on normalized values from FTLD-typical regions showed that at center 1, cerebellar, SMC, CGM, and cluster normalizations differentiated patients from controls with accuracies of 86%, 76%, 75% and 90%, respectively. A similar order of effects was found at center 2. Cluster normalization leads to a significant increase of statistical power in detecting early FTLD-associated metabolic deficits. The established FTLD-specific cluster can be used to improve detection of FTLD on a single case basis at independent centers - a decisive step towards early diagnosis and prediction of FTLD syndromes enabling specific therapies in the future.

Constant fluctuating asymmetry but not directional asymmetry along the geographic distribution of Drosophila antonietae (Diptera, Drosophilidae)

ABSTRACT The population dynamics of a species tends to change from the core to the periphery of its distribution. Therefore, one could expect peripheral populations to be subject to a higher level of stress than more central populations (the center–periphery hypothesis) and consequently should present a higher level of fluctuating asymmetry. To test these predictions we study asymmetry in wing shape of five populations of Drosophila antonietae collected throughout the distribution of the species using fluctuating asymmetry as a proxy for developmental instability. More specifically, we addressed the following questions: (1) what types of asymmetry occur in populations of D. antonietae? (2) Does the level of fluctuating asymmetry vary among populations? (3) Does peripheral populations have a higher fluctuating asymmetry level than central populations? We used 12 anatomical landmarks to quantify patterns of asymmetry in wing shape in five populations of D. antonietae within the framework of geometric morphometrics. Net asymmetry – a composite measure of directional asymmetry + fluctuating asymmetry – varied significantly among populations. However, once net asymmetry of each population is decomposed into directional asymmetry and fluctuating asymmetry, most of the variation in asymmetry was explained by directional asymmetry alone, suggesting that populations of D. antonietae have the same magnitude of fluctuating asymmetry throughout the geographical distribution of the species. We hypothesize that larval development in rotting cladodes might play an important role in explaining our results. In addition, our study underscores the importance of understanding the interplay between the biology of a species and its geographical patterns of asymmetry.

Blood pressure normalization in a large population of hypertensive patients treated with perindopril/indapamide combination: results of the OPTIMAX trial.

OBJECTIVE: To determine if the fixed-dose perindopril/indapamide combination (Per/Ind) normalizes blood pressure (BP) in the same fraction of hypertensive patients when treated in everyday practice or in controlled trials. METHODS: In this prospective trial, 17 938 hypertensive patients were treated with Per 2 mg/Ind 0.625 mg for 3-6 months. In Group 1 Per/Ind was initiated in newly diagnosed patients (n = 7032); in Group 2 Per/Ind replaced previous therapy in patients already treated but having either their BP still uncontrolled or experiencing side-effects (n = 7423); in Group 3 Per/Ind was added to previous treatment in patients with persistently high BP (n = 3483). BP was considered normalized when < or = 140/90 mm Hg. A multivariate analysis for predictors of BP normalization was performed. RESULTS: Subjects were on average 62 years old and had a baseline BP of 162.3/93.6 mm Hg. After treatment with Per/Ind, BP normalization was reached in 69.6% of patients in the Initiation group, 67.5% in the Replacement Group, and 67.4% in the Add-on Group (where patients were more frequently at risk, diabetic, or with target organ damage). Mean decreases in systolic BP of 22.8 mm Hg and in diastolic BP of 12.4 mm Hg were recorded. CONCLUSIONS: This trial was established to reflect everyday clinical practice, and a treatment strategy based on the Per/Ind combination, administered as initial, replacement, or add-on therapy, led to normalization rates that were superior to those observed in Europe in routine practice. These results support recent hypertension guidelines which encourage the use of combination therapy in the management of arterial hypertension.

Low-dose angiostatic tyrosine kinase inhibitors improve photodynamic therapy for cancer: lack of vascular normalization.

Photodynamic therapy (PDT) is an effective clinical treatment for a number of different cancers. PDT can induce hypoxia and inflammation, pro-angiogenic side effects, which may counteract its angio-occlusive mechanism. The combination of PDT with anti-angiogenic drugs offers a possibility for improved anti-tumour outcome. We used two tumour models to test the effects of the clinically approved angiostatic tyrosine kinase inhibitors sunitinib, sorafenib and axitinib in combination with PDT, and compared these results with the effects of bevacizumab, the anti-VEGF antibody, for the improvement of PDT. Best results were obtained from the combination of PDT and low-dose axitinib or sorafenib. Molecular analysis by PCR revealed that PDT in combination with axitinib suppressed VEGFR-2 expression in tumour vasculature. Treatment with bevacizumab, although effective as monotherapy, did not improve PDT outcome. In order to test for tumour vessel normalization effects, axitinib was also applied prior to PDT. The absence of improved PDT outcome in these experiments, as well as the lack of increased oxygenation in axitinib-treated tumours, suggests that vascular normalization did not occur. The current data imply that there is a future for certain anti-angiogenic agents to further improve the efficacy of photodynamic anti-cancer therapy.

Time constant of the cerebral arterial bed in normal subjects.

The time constant of cerebral arterial bed (in brief time constant) is a product of brain arterial compliance (C(a)) and resistance (CVR). We tested the hypothesis that in normal subjects, changes in end-tidal CO(2) (EtCO(2)) affect the value of the time constant. C(a) and CVR were estimated using mathematical transformations of arterial pressure (ABP) and transcranial Doppler (TCD) cerebral blood flow velocity waveforms. Responses of the time constant to controlled changes in EtCO(2) were compared in 34 young volunteers. Hypercapnia shortened the time constant (0.22 s [0.17, 0.26] vs. 0.16 s [0.13, 0.20]; p = 0.000001), while hypocapnia lengthened the time constant (0.22 s [0.17, 0.26] vs. 0.23 s [0.19, 0.32]; p < 0.0032). The time constant was negatively correlated with changes in EtCO(2) (R(partial) = -0.68, p < 0.000001). This was associated with a decrease in CVR when EtCO(2) increased (R(partial) = -0.80, p < 0.000001) and C(a) remained independent of changes in EtCO(2). C(a) was negatively correlated with mean ABP (R(partial) = -0.68, p < 0.000001). In summary, the time constant shortens with increasing EtCO(2). Its potential role in cerebrovascular investigations needs further studies.

Parole, personnage et sujet dans les récits littéraires de Benjamin Constant

Même si Alison Fairlie, Tzvetan Todorov, Han Verhoeff et Simone Balayé ont reconnu l'importance de la parole dans les récits littéraires de Benjamin Constant (Amélie et Germaine, Cécile, Ma vie et Adolphe), dans leurs commentaires ces critiques ont surtout mis en évidence les échecs et les malentendus inhérents à toute communication verbale. Au-delà de ces constatations, il restait à montrer que les récits constantiens donnent à voir et à comprendre l'intérêt que cet écrivain nourrissait pour la parole, tout particulièrement pour la parole privée -celle qu'il a choisi de mettre en scène dans ces quatre oeuvres, qui acquièrent, grâce à cette spécificité, une manière d'unité. Cette parole intime, aux antipodes de la parole publique, s'offre comme un champ d'investigation illimité tant le locuteur est alors impliqué dans sa pratique verbale. Les introspections des narrateurs-personnages constantiens font naître la peinture d'un sujet moderne, fragilisé dans sa vie personnelle et peu engagé dans la vie sociale, mais elles offrent surtout un vaste panorama des situations d'interlocution et présentent en creux les nombreuses ressources de la parole. Ces récits, qui accordent une attention tout à fait signifiante à l'écriture de la parole, mais échappent parfois à toute classification générique, parviennent à mimer les incertitudes de leur narrateur-personnage tout en révélant que c'est par la parole, originale et singulière, que le sujet s'individualise expérience rendue souvent difficile à cause de la langue conventionnelle dont usent ceux que l'on rencontre dans les lieux de sociabilité, en ce XIXe siècle naissant.