Continual Conscious Bioluminescent Imaging in Freely Moving Mice

In vivo bioluminescent imaging allows the detection of reporter gene expression in rodents in real time. Here we describe a novel technology whereby we can generate somatotransgenic rodents with the use of a viral vector carrying a luciferase transgene. We are able to achieve long term luciferase expression by a single injection of lentiviral or adeno-associated virus vectors to newborn mice. Further, we describe whole body bioluminescence imaging of conscious mice in a noninvasive manner, thus enforcing the 3R’s (replacement, reduction, and refinement) of biomedical animal research

CDH1 mutation distribution and type suggests genetic differences between the etiology of orofacial clefting and gastric cancer

Pathogenic variants in CDH1, encoding epithelial cadherin (E-cadherin), have been implicated in hereditary diffuse gastric cancer (HDGC), lobular breast cancer, and both syndromic and non-syndromic cleft lip/palate (CL/P). Despite the large number of CDH1 mutations described, the nature of the phenotypic consequence of such mutations is currently not able to be predicted, creating significant challenges for genetic counselling. This study collates the phenotype and molecular data for available CDH1 variants that have been classified, using the American College of Medical Genetics and Genomics criteria, as at least ‘likely pathogenic’, and correlates their molecular and structural characteristics to phenotype. We demonstrate that CDH1 variant type and location differ between HDGC and CL/P, and that there is clustering of CL/P variants within linker regions between the extracellular domains of the cadherin protein. While these differences do not provide for exact prediction of the phenotype for a given mutation, they may contribute to more accurate assessments of risk for HDGC or CL/P for individuals with specific CDH1 variants

Differential postural effects of plantar-flexor muscles fatigue under normal, altered and improved vestibular and neck somatosensory conditions

The aim of the present study was to assess the effects of plantar-flexor muscles fatigue on postural control during quiet standing under normal, altered and improved vestibular and neck somatosensory conditions. To address this objective, young male university students were asked to stand upright as still as possible with their eyes closed in two conditions of No Fatigue and Fatigue of the plantar-flexor muscles. In Experiment 1 (n=15), the postural task was executed in two Neutral head and Head tilted backward postures, recognized to degrade vestibular and neck somatosensory information. In Experiment 2 (n=15), the postural task was executed in two conditions of No tactile and Tactile stimulation of the neck provided by the application of strips of adhesive bandage to the skin over and around the neck. Centre of foot pressure displacements were recorded using a force platform. Results showed that (1) the Fatigue condition yielded increased CoP displacements relative to the No Fatigue condition (Experiment 1 and Experiment 2), (2) this destabilizing effect was more accentuated in the Head tilted backward posture than Neutral head posture (Experiment 1) and (3) this destabilizing effect was less accentuated in the condition of Tactile stimulation than that of No tactile stimulation of the neck (Experiment 2). In the context of the multisensory control of balance, these results suggest an increased reliance on vestibular and neck somatosensory information for controlling posture during quiet standing in condition of altered ankle neuromuscular function

Semiparametric Multivariate Accelerated Failure Time Model with Generalized Estimating Equations

The semiparametric accelerated failure time model is not as widely used as the Cox relative risk model mainly due to computational difficulties. Recent developments in least squares estimation and induced smoothing estimating equations provide promising tools to make the accelerate failure time models more attractive in practice. For semiparametric multivariate accelerated failure time models, we propose a generalized estimating equation approach to account for the multivariate dependence through working correlation structures. The marginal error distributions can be either identical as in sequential event settings or different as in parallel event settings. Some regression coefficients can be shared across margins as needed. The initial estimator is a rank-based estimator with Gehan's weight, but obtained from an induced smoothing approach with computation ease. The resulting estimator is consistent and asymptotically normal, with a variance estimated through a multiplier resampling method. In a simulation study, our estimator was up to three times as efficient as the initial estimator, especially with stronger multivariate dependence and heavier censoring percentage. Two real examples demonstrate the utility of the proposed method

Temporomandibular joint dysfunction and orthognathic surgery: a retrospective study

<p>Abstract</p> <p>Background</p> <p>Relations between maxillo-mandibular deformities and TMJ disorders have been the object of different studies in medical literature and there are various opinions concerning the alteration of TMJ dysfunction after orthognathic surgery. The purpose of the present study was to evaluate TMJ disorders changes before and after orthognathic surgery, and to assess the risk of creating new TMJ symptoms on asymptomatic patients.</p> <p>Methods</p> <p>A questionnaire was sent to 176 patients operated at the Maxillo-Facial Service of the Lille's 2 Universitary Hospital Center (Chairman Pr Joël Ferri) from 01.01.2006 to 01.01.2008. 57 patients (35 females and 22 males), age range from 16 to 65 years old, filled the questionnaire. The prevalence and the results on pain, sounds, clicking, joint locking, limited mouth opening, and tenseness were evaluated comparing different subgroups of patients.</p> <p>Results</p> <p>TMJ symptoms were significantly reduced after treatment for patients with pre-operative symptoms. The overall subjective treatment outcome was: improvement for 80.0% of patients, no change for 16.4% of patients, and an increase of symptoms for 3.6% of them. Thus, most patients were very satisfied with the results. However the appearance of new onset of TMJ symptoms is common. There was no statistical difference in the prevalence of preoperative TMJ symptoms and on postoperative results in class II compared to class III patients.</p> <p>Conclusions</p> <p>These observations demonstrate that: there is a high prevalence of TMJ disorders in dysgnathic patients; most of patients with preoperative TMJ signs and symptoms can improve TMJ dysfunction and pain levels can be reduced by orthognathic treatment; a percentage of dysgnathic patients who were preoperatively asymptomatic can develop TMJ disorders after surgery but this risk is low.</p

Chiral U(1) flavor models and flavored Higgs doublets: the top FB asymmetry and the Wjj

We present U(1) flavor models for leptophobic Z' with flavor dependent couplings to the right-handed up-type quarks in the Standard Model, which can accommodate the recent data on the top forward-backward (FB) asymmetry and the dijet resonance associated with a W boson reported by CDF Collaboration. Such flavor-dependent leptophobic charge assignments generally require extra chiral fermions for anomaly cancellation. Also the chiral nature of U(1)' flavor symmetry calls for new U(1)'-charged Higgs doublets in order for the SM fermions to have realistic renormalizable Yukawa couplings. The stringent constraints from the top FB asymmetry at the Tevatron and the same sign top pair production at the LHC can be evaded due to contributions of the extra Higgs doublets. We also show that the extension could realize cold dark matter candidates.Comment: 40 pages, 10 figures, added 1 figure and extended discussion, accepted for publication in JHE

Imbibition in Disordered Media

The physics of liquids in porous media gives rise to many interesting phenomena, including imbibition where a viscous fluid displaces a less viscous one. Here we discuss the theoretical and experimental progress made in recent years in this field. The emphasis is on an interfacial description, akin to the focus of a statistical physics approach. Coarse-grained equations of motion have been recently presented in the literature. These contain terms that take into account the pertinent features of imbibition: non-locality and the quenched noise that arises from the random environment, fluctuations of the fluid flow and capillary forces. The theoretical progress has highlighted the presence of intrinsic length-scales that invalidate scale invariance often assumed to be present in kinetic roughening processes such as that of a two-phase boundary in liquid penetration. Another important fact is that the macroscopic fluid flow, the kinetic roughening properties, and the effective noise in the problem are all coupled. Many possible deviations from simple scaling behaviour exist, and we outline the experimental evidence. Finally, prospects for further work, both theoretical and experimental, are discussed.Comment: Review article, to appear in Advances in Physics, 53 pages LaTe

The responsibility to protect and the use of force: remaking the procrustean bed?

The emergence of the Responsibility to Protect (R2P) owed much to the need to enhance the UN’s ability to act forcibly in the face of the most extreme cases of gross human suffering. Too often in the past such responses were emasculated or thwarted by the necessity to successfully navigate the UN Charter’s prescriptions over the use of force, by the unwillingness of member states to provide military forces, or by a combination of the two. In accepting that certain types of inhuman activity can lead to the legitimate use of force within the UN Charter framework, the adoption of R2P appeared to resolve at least some of these problems, and as such it offered hope to those wishing to see the UN adopt a more assertive response to the grossest of human rights abuses. But, using stalemate over Syria as its backdrop, this article demonstrates the dubiousness of the claim that such a normative development can ever trump the hard edged political and strategic factors which determine when states will accept and/or participate in the use of force, and it suggests a radical solution to the dangers inherent in R2P’s intimate association with military intervention

Selection Bias in a Study of Implantable Defibrillator Patients: The Role of Type D Personality

# The Author(s) 2010. This article is published with open access at Springerlink.com Background Selection bias constitutes a major issue in research using volunteers as study participants. Purpose We examined whether research in partners may affect participation rates of implantable cardioverterdefibrillator (ICD) patients with a Type D personality (joint presence of negative affectivity and social inhibition). Method Patients who underwent ICD implantation between May 2003 and November 2007, and who had a partner, were included (n=440). In September 2005, a substudy on partners of ICD patients was added (n=276 patients). Results The proportion Type D patients after the start of the partner substudy was significantly lower as compared to the proportion before this substudy (17.5 % versus 28.8%; p= 0.006). Patients who participated following the start of the partner substudy were less likely to have a Type D personality (OR=0.44; p=0.002), adjusting for possible confounders. In the partner substudy, nonparticipation was more prevalent among partners of Type D patients as compared to partners of non-Type D patients (20.4 % versus 10.1%; p=0.044). Partner nonparticipation was marginally significantly associated with Type D personality of the patient (OR=2.13; p=0.083), adjusting for confounders. Conclusions The addition of a partner substudy may be related to a decreased proportion of participants with a Type D personality. Nonparticipation was more prevalent among partners of Type D patients. These observations may influence results of studies, as Type Ds tend to be less healthy