Adaptation of an amphibian mucociliary clearance model to evaluate early effects of tobacco smoke exposure

RATIONALE: Inhaled side-stream tobacco smoke brings in all of its harmful components impairing mechanisms that protect the airways and lungs. Chronic respiratory health consequences are a complex multi-step silent process. By the time clinical manifestations require medical attention, several structural and functional changes have already occurred. The respiratory system has to undergo an iterative process of injury, healing and remodeling with every exposure. METHODS: To have a better understanding of the initial changes that take place when first exposed to environmental tobacco smoke, we have developed an exposure model, using the frog palate that closely represents the features of obstructive airways where ciliary dysfunction and mucus hypersecretion occur. RESULTS: Mucus transport was significantly reduced, even after exposure to the smoke of one cigarette (p < 0.05) and even further with 4-cigarettes exposure (p < 0.001). Morphometric and ultrastructural studies by SEM show extensive areas of tissue disruption. Gelatinase zymography shows activation of MMP9 in mucus from palates exposed to tobacco smoke. CONCLUSIONS: The clearance of mucus on the frog palate is significantly reduced after exposure to environmental tobacco smoke. Cilia and the extracellular matrix are anatomically disrupted. Tobacco smoke triggers an increased activity of matrix metalloproteinases associated with a substantial defoliation of ciliated epithelium. These studies enhance the knowledge of the changes in the mucociliary apparatus that occur initially after exposure to environmental tobacco smoke, with the goal of understanding how these changes relate to the genesis of chronic airway pathologies in humans

Comparison of techniques for handling missing covariate data within prognostic modelling studies: a simulation study

Background: There is no consensus on the most appropriate approach to handle missing covariate data within prognostic modelling studies. Therefore a simulation study was performed to assess the effects of different missing data techniques on the performance of a prognostic model. Methods: Datasets were generated to resemble the skewed distributions seen in a motivating breast cancer example. Multivariate missing data were imposed on four covariates using four different mechanisms; missing completely at random (MCAR), missing at random (MAR), missing not at random (MNAR) and a combination of all three mechanisms. Five amounts of incomplete cases from 5% to 75% were considered. Complete case analysis (CC), single imputation (SI) and five multiple imputation (MI) techniques available within the R statistical software were investigated: a) data augmentation (DA) approach assuming a multivariate normal distribution, b) DA assuming a general location model, c) regression switching imputation, d) regression switching with predictive mean matching (MICE-PMM) and e) flexible additive imputation models. A Cox proportional hazards model was fitted and appropriate estimates for the regression coefficients and model performance measures were obtained. Results: Performing a CC analysis produced unbiased regression estimates, but inflated standard errors, which affected the significance of the covariates in the model with 25% or more missingness. Using SI, underestimated the variability; resulting in poor coverage even with 10% missingness. Of the MI approaches, applying MICE-PMM produced, in general, the least biased estimates and better coverage for the incomplete covariates and better model performance for all mechanisms. However, this MI approach still produced biased regression coefficient estimates for the incomplete skewed continuous covariates when 50% or more cases had missing data imposed with a MCAR, MAR or combined mechanism. When the missingness depended on the incomplete covariates, i.e. MNAR, estimates were biased with more than 10% incomplete cases for all MI approaches. Conclusion: The results from this simulation study suggest that performing MICE-PMM may be the preferred MI approach provided that less than 50% of the cases have missing data and the missing data are not MNAR

MR Imaging Findings of a Primary Cardiac Osteosarcoma and Its Bone Metastasis with Histopathologic Correlation

An osteosarcoma of cardiac origin is extremely rare, and a comprehensive description of MR imaging (MRI) findings of cardiac osteosarcoma and its metastasis in the femur have not been reported in the literature. We present a case of cardiac osteosarcoma in a 47-year-old woman and its metastasis to the femur, focusing on the description of MRI findings of the cardiac and metastatic bony osteosarcoma with a histopathologic correlation

Rotation Curves of Spiral Galaxies

Rotation curves of spiral galaxies are the major tool for determining the distribution of mass in spiral galaxies. They provide fundamental information for understanding the dynamics, evolution and formation of spiral galaxies. We describe various methods to derive rotation curves, and review the results obtained. We discuss the basic characteristics of observed rotation curves in relation to various galaxy properties, such as Hubble type, structure, activity, and environment.Comment: 40 pages, 6 gif figures; Ann. Rev. Astron. Astrophys. Vol. 39, p.137, 200

Analysis of different characteristics of smile

Introduction: Analysis of smile is imperative in the diagnosis and treatment planning phases of aesthetic dentistry.Aim: To evaluate the components of smile among students of a dental institution.Methods: Frontal view digital photographs with posed smile of 157 dental students were assessed using Adobe Photoshop7.0. Smile characteristics evaluated included; smile line, smile arc, smile design, upper lip curvature, labiodental relationship and number of teeth displayed. Data were analyzed using SPSS version 23.0. Pearson chi-square test was used to determine the gender based differences for various parameters.Results: Average smile line (43.3%), consonant smile arcs (45.2%), cuspid smiles (45.9%), upward lip curvature (43.9%), maxillary anterior teeth not covered by lower lip (60.5%) and teeth displayed up to first premolars (35.7%). Gender based differences were not statistically significant except for smile arc (p value = 0.02) and number of teeth displayed (p value \u3c 0.001). There was a significant relationship between lip curvature and smile pattern (p value \u3c 0.001) and lip curvature and smile arc (p value = 0.01) revealing that upward lip curvature was associated with commissure type smiles and consonant smile arcs.Conclusions: The smile characteristics should be considered before beginning the aesthetic treatment of the patient to obtain adequate results in oral rehabilitation

Endothelin-1 Predicts Hemodynamically Assessed Pulmonary Arterial Hypertension in HIV Infection.

BackgroundHIV infection is an independent risk factor for PAH, but the underlying pathogenesis remains unclear. ET-1 is a robust vasoconstrictor and key mediator of pulmonary vascular homeostasis. Higher levels of ET-1 predict disease severity and mortality in other forms of PAH, and endothelin receptor antagonists are central to treatment, including in HIV-associated PAH. The direct relationship between ET-1 and PAH in HIV-infected individuals is not well described.MethodsWe measured ET-1 and estimated pulmonary artery systolic pressure (PASP) with transthoracic echocardiography (TTE) in 106 HIV-infected individuals. Participants with a PASP ≥ 30 mmHg (n = 65) underwent right heart catheterization (RHC) to definitively diagnose PAH. We conducted multivariable analysis to identify factors associated with PAH.ResultsAmong 106 HIV-infected participants, 80% were male, the median age was 52 years and 77% were on antiretroviral therapy. ET-1 was significantly associated with higher values of PASP [14% per 0.1 pg/mL increase in ET-1, p = 0.05] and PASP ≥ 30 mmHg [PR (prevalence ratio) = 1.24, p = 0.012] on TTE after multivariable adjustment for PAH risk factors. Similarly, among the 65 individuals who underwent RHC, ET-1 was significantly associated with higher values of mean pulmonary artery pressure and PAH (34%, p = 0.003 and PR = 2.43, p = 0.032, respectively) in the multivariable analyses.ConclusionsHigher levels of ET-1 are independently associated with HIV-associated PAH as hemodynamically assessed by RHC. Our findings suggest that excessive ET-1 production in the setting of HIV infection impairs pulmonary endothelial function and contributes to the development of PAH

Non-global Structure of the O({\alpha}_s^2) Dijet Soft Function

High energy scattering processes involving jets generically involve matrix elements of light- like Wilson lines, known as soft functions. These describe the structure of soft contributions to observables and encode color and kinematic correlations between jets. We compute the dijet soft function to O({\alpha}_s^2) as a function of the two jet invariant masses, focusing on terms not determined by its renormalization group evolution that have a non-separable dependence on these masses. Our results include non-global single and double logarithms, and analytic results for the full set of non-logarithmic contributions as well. Using a recent result for the thrust constant, we present the complete O({\alpha}_s^2) soft function for dijet production in both position and momentum space.Comment: 55 pages, 8 figures. v2: extended discussion of double logs in the hard regime. v3: minor typos corrected, version published in JHEP. v4: typos in Eq. (3.33), (3.39), (3.43) corrected; this does not affect the main result, numerical results, or conclusion

Types of problems elicited by verbal protocols for blind and sighted participants

Verbal protocols are often used in user-based studies of interactive technologies. This study investigated whether different types of problems are revealed by concurrent and retrospective verbal protocols (CVP and RVP) for blind and sighted participants. Eight blind and eight sighted participants undertook both CVP and RVP on four websites. Overall, interactivity problems were significantly more frequent in comparison to content or information architecture problems. In addition, RVP revealed significantly more interactivity problems than CVP for both user groups. Finally, blind participants encountered significantly more interactivity problems than sighted participants. The findings have implications for which protocol is appropriate, depending on the purpose of a particular study and the user groups involved

Non-Global Logarithms in Filtered Jet Algorithms

We analytically and numerically study the effect of perturbative gluons emission on the "Filtering analysis", which is part of a subjet analysis procedure proposed two years ago to possibly identify a low-mass Higgs boson decaying into b\bar{b} at the LHC. This leads us to examine the non-global structure of the resulting perturbative series in the leading single-log large-N_c approximation, including all-orders numerical results, simple analytical approximations to them and comments on the structure of their series expansion. We then use these results to semi-analytically optimize the parameters of the Filtering analysis so as to suppress as much as possible the effect of underlying event and pile-up on the Higgs mass peak reconstruction while keeping the major part of the perturbative radiation from the b\bar{b} dipole.Comment: 47 pages, 25 figures, 1 figure and a few comments added, version accepted for publication in JHE

Transient peak-strain matching partially recovers the age-impaired mechanoadaptive cortical bone response

Mechanoadaptation maintains bone mass and architecture; its failure underlies age-related decline in bone strength. It is unclear whether this is due to failure of osteocytes to sense strain, osteoblasts to form bone or insufficient mechanical stimulus. Mechanoadaptation can be restored to aged bone by surgical neurectomy, suggesting that changes in loading history can rescue mechanoadaptation. We use non-biased, whole-bone tibial analyses, along with characterisation of surface strains and ensuing mechanoadaptive responses in mice at a range of ages, to explore whether sufficient load magnitude can activate mechanoadaptation in aged bone. We find that younger mice adapt when imposed strains are lower than in mature and aged bone. Intriguingly, imposition of short-term, high magnitude loading effectively primes cortical but not trabecular bone of aged mice to respond. This response was regionally-matched to highest strains measured by digital image correlation and to osteocytic mechanoactivation. These data indicate that aged bone’s loading response can be partially recovered, non-invasively by transient, focal high strain regions. Our results indicate that old murine bone does respond to load when the loading is of sufficient magnitude, and bones’ age-related adaptation failure may be due to insufficient mechanical stimulus to trigger mechanoadaptation