Asymptotic Results with Generalized Estimating Equations for Longitudinal data II

We consider the marginal models of Liang and Zeger (1986) for the analysis of longitudinal data and we develop a theory of statistical inference for such models. We prove the existence, weak consistency and asymptotic normality of a sequence of estimators defined as roots of pseudo-likelihood equations.Generalized estimating equations, Generalized linear model, Consistency, Asymptotic normality

Reducing Automatic Stereotype Activation: Mechanisms and Moderators of Situational Attribution Training

Individuals tend to underestimate situational causes and overly rely on trait causes in explaining negative behaviors of outgroup members, a tendency named the ultimate attribution error (Pettigrew, 1979). This attributional pattern is directly related to stereotyping, because attributing negative behaviors to internal, stable causes tends to perpetuate negative stereotypes of outgroup members. Recent research on implicit bias reduction revealed that circumventing individuals’ tendency to engage in the ultimate attribution error led to reduced stereotyping. More specifically, training White participants to consider situational factors in determining Blacks’ negative stereotypic behaviors led to decreased automatic stereotype activation. This technique was named Situational Attribution Training (Stewart, Latu, Kawakami, & Myers, 2010). In the current studies, I investigated the mechanisms and moderators of Situational Attribution Training. In Study 1, I investigated the effect of training on spontaneous situational inferences. Findings revealed that training did not increase spontaneous situational inferences: both training and control participants showed evidence of spontaneous situational inferences. In Study 2, I investigated whether correcting trait inferences by taking into account situational factors has become automatic after training. In addition, explicit prejudice, motivations to control prejudice, and cognitive complexity variables (need for cognition, personal need for structure) were investigated as moderators of training success. These findings revealed that Situational Attribution Training works best for individuals high in need for cognition, under conditions of no cognitive load, but not high cognitive load. Training increased implicit bias for individuals high in modern racism, regardless of their cognitive load. Possible explanations of these findings were discussed, including methodological limitations and theoretical implications

On Expectations-Driven Business Cycles in Economies with Production Externalities: A Comment

Eusepi (2009, International Journal of Economic Theory 5, pp. 9-23) analytically finds that a one-sector real business cycle model may exhibit positive co-movement between consumption and investment when the equilibrium wage-hours locus is positively-sloped and steeper than the household's labor supply curve. However, we show that this condition does not imply expectations-driven business cycles will emerge in Eusepi's model. Specifically, a positive news shock about future productivity improvement leads to an aggregate recession whereby output, employment, consumption and investment all fall in the announcement period.Expectations-Driven Business Cycles; Production Externalities.

Positive surgical margins in nephron-sparing surgery; the great unknown

There is a currently a general trend towards organ-preserving surgery, and urology is no exception. Specifically, nephron-sparing surgery (NSS) has gained general acceptance for T1a renal cell carcinoma (guidelines recommendations). Moreover T1b, T2 and even T3 stage tumors have been included on the nephron sparing list at some centers. An unresolved issue is that of positive surgical margins (PSM), not only their detection but also the implications for follow up and treatment. This paper highlights data available on risk factors for PSM, their clinical relevance, and possible therapeutic consequences. From the surgeon’s viewpoint, NSS is a daring and risky surgical procedure. Urological guidelines stress the importance of NSS, and thus the trend is moving in that direction. Unresolved, however, is the problem of PSM. Trifecta, MIC, and pentafecta are applicable concepts which attempt to define the optimal endpoint of NSS, but further elaboration is necessary. Specifically, research needs to focus less on the concept of definitive margins and more on their identification and avoidance. Although some studies suggest that PSMs do not influence overall survival rate, the basic idea of preserving tissue that is not cancerous leads to further medical, social, and psychological considerations

Antibody binding increases the flexibility of the prion protein

Prion diseases are associated with the conversion of the cellular prion protein (PrP) into a pathogenic conformer (PrPSc). A proposed therapeutic approach to avoid the pathogenic transformation is to develop antibodies that bind to PrP and stabilize its structure. POM1 and POM6 are two monoclonal antibodies that bind the globular domain of PrP and have different biological responses, i.e., trigger neurotoxicity mimicking prion infections (POM1) or prevent neurotoxicity (POM6). The crystal structures of PrP in complex with the two antibodies show similar epitopes which seems inconsistent with the opposite phenotypes. Here, we investigate the influence of the POM1 and POM6 antibodies on the flexibility of the mouse PrP by molecular dynamics simulations. The simulations reveal that the POM6/PrP interface is less stable than the POM1/PrP interface, ascribable to localized polar mismatches at the interface, despite the former complex having a larger epitope than the latter. In the presence of any of the two antibodies, the flexibility of the globular domain increases everywhere except for the β1-α1 loop in the POM1/PrP complex which suggests the involvement of this loop in the pathological conversion. The secondary structure of PrP is preserved whereas the polar interactions involving residues Glu146, Arg156 and Arg208 are modified upon antibody binding

Optimizing endothelin receptor antagonist use in the management of pulmonary arterial hypertension

Endothelin receptor antagonism has emerged as an important therapeutic approach in pulmonary arterial hypertension (PAH). Bench to bedside scientific research has shown that endothelin-1 (ET-1) is overexpressed in several forms of pulmonary vascular disease and may play an important pathogenetic role in the development and progression of PAH. Oral endothelin receptor antagonists (ERAs) improved exercise capacity, functional status, pulmonary hemodymanics, and delayed the time to clinical worsening in several randomized placebo-controlled trials. Two ERAs are currently approved by the US Food and Drug Administration: bosentan, a dual ERA for patients with class III and IV PAH, and ambrisentan, a selective ERA for patients with class II and III PAH. Sitaxsentan, another selective ERA, has been approved in Europe, Canada, and Australia. The objective of this review is to evaluate the available evidence describing the pharmacology, efficacy, safety, and tolerability, and patient-focused perspectives regarding the different types of endothelin receptor antagonists. Ongoing and forthcoming randomized trials are also highlighted including the approach of combining this class of drugs with other drugs that target different cellular pathways believed to be etiologically important in PAH