Effects of Varenicline in Adult Smokers: A Multinational, 24-Week, Randomized, Double-Blind, Placebo-Controlled Study

Background: Prevalence rates of smoking are rising in developing countries. Previous trials evaluating the efficacy and tolerability of the smoking-cessation medication varenicline have used largely participants of Caucasian origin. Objective: This study was conducted to evaluate the efficacy and tolerability of varenicline in populations of participants from Latin America, Africa, and the Middle East to investigate potential differences in the therapeutic response to varenicline. Methods: This multinational, randomized, double-blind, placebo-controlled trial was conducted at 42 centers in 11 countries (Latin America: Brazil, Colombia, Costa Rica, Mexico, and Venezuela; Africa: Egypt and South Africa; Middle East: Jordan, Lebanon, Saudi Arabia, and the United Arab Emirates). Participants were male and female smokers aged 18 to 75 years who were motivated to stop smoking; smoked >= 10 cigarettes/d, with no cumulative period of abstinence >3 months in the previous year; and who had no serious or unstable disease within the previous 6 months. Subjects were randomized in a 2:1 ratio to receive varenicline 1 mg or placebo, BID for 12 weeks, with a 12-week nontreatment follow-up. Brief smoking-cessation counseling was provided. The main outcome measures were carbon monoxide confirmed continuous abstinence rate (CAR) at weeks 9 to 12 and weeks 9 to 24. Adverse events (AEs) were recorded for tolerability assessment. Results: Overall, 588 subjects (varenicline, 390; placebo, 198) were randomized and treated. The mean (SD) ages of subjects in the varenicline and placebo groups were 43.1 (10.8) and 43.9 (10.8) years, respectively; 57.7% and 65.7% were male; and the mean (SD) weights were 75.0 (16.0) and 76.7 (16.3) kg (range, 40.0-130.0 and 45.6-126.0 kg). CAR at weeks 9 to 12 was significantly higher with varenicline than with placebo (53.59% vs 18.69%; odds ratio [OR] = 5.76; 95% CI, 3.74-8.88; P < 0.0001), and this rate was maintained during weeks 9 to 24 (39.74% vs 13.13%; OR = 4.78; 95% CI, 2.97-7.68; P < 0.0001). Nausea, headache, and insomnia were the most commonly reported AEs with varenicline and were reported numerically more frequently in the varenicline group compared with the placebo group. Serious AEs (SAEs) were reported in 2.8% of varenicline recipients compared with 1.0% in the placebo group, with 6 subjects reporting psychiatric SAEs compared with none in the placebo group. Conclusion: Based on these data, varenicline was apparently efficacious and generally well tolerated as a smoking-cessation aid in smokers from selected sites in Latin America, Africa, and the Middle East. ClinicalTrials. gov identifier: NCT00594204. (Clin Ther. 2011;33:465-477) (C) 2011 Published by Elsevier HS Journals, Inc.

The cultural adaptation and validation of the ""Burn Specific Health Scale-Revised"" (BSHS-R): Version for Brazilian burn victims

Background: The Burns Specific Health Scale-Revised (BSHS-R) is of easy application, can be self-administered, and it is considered a good scale to evaluate various important life aspects of burn victims. Objectives: To translate and culturally adapt the BSHS-R into the Brazilian-Portuguese language and to evaluate the internal consistency and convergent validity of the translated BSHS-R. Methods: The cultural adaptation of the BSHS-R included translation and back-translation, discussions with professionals and patients to ensure conceptual equivalence, semantic evaluation, and pre-test of the instrument. The Final Brazilian-Portuguese Version (FBPV) of the BSHS-R was tested on a group of 115 burn patients for internal consistency and validity of construct (using the Rosenberg Self-Esteem Scale (RSES) and the Beck Depression Inventory (BDI)). Results: All values of Cronbach`s alpha were greater than. 8, demonstrating that the internal consistency of the FBPV was very high. Self-esteem was highly correlated with affect and body image (r = .59, p < .001), and with interpersonal relationships (T = .51, p < .001). Correlations between the domains of the FBPV and the BDI were all negative but larger in magnitude than the correlations with RSES. Depression was highly correlated with affect and body image (r = -77, p < .001), and with interpersonal relationships (r = -67, p < .001). Conclusions: The results showed that the adapted version of the BSHS-R into Brazilian-Portuguese fulfills the validity and reliability criteria required from an instrument of health status assessment for burn patients. (C) 2008 Elsevier Ltd and ISBI. All rights reserved.

Modeling associations between genetic markers using Bayesian networks

Motivation: Understanding the patterns of association between polymorphisms at different loci in a population ( linkage disequilibrium, LD) is of fundamental importance in various genetic studies. Many coefficients were proposed for measuring the degree of LD, but they provide only a static view of the current LD structure. Generative models (GMs) were proposed to go beyond these measures, giving not only a description of the actual LD structure but also a tool to help understanding the process that generated such structure. GMs based in coalescent theory have been the most appealing because they link LD to evolutionary factors. Nevertheless, the inference and parameter estimation of such models is still computationally challenging. Results: We present a more practical method to build GM that describe LD. The method is based on learning weighted Bayesian network structures from haplotype data, extracting equivalence structure classes and using them to model LD. The results obtained in public data from the HapMap database showed that the method is a promising tool for modeling LD. The associations represented by the learned models are correlated with the traditional measure of LD D`. The method was able to represent LD blocks found by standard tools. The granularity of the association blocks and the readability of the models can be controlled in the method. The results suggest that the causality information gained by our method can be useful to tell about the conservability of the genetic markers and to guide the selection of subset of representative markers.

Positioning of Deadeners for Vibration Reduction in Vehicle Roof Using Embedded Sensitivity

The noise, vibration and harshness (NVH) performance of passenger vehicles strongly depends on the fluid-structure interaction between the air in the vehicle cavity and the sheet metal structure of the vehicle. Most of the noise and vibration problems related to this interaction come from resonance peaks of the sheet metal, which are excited by external forces (road, engine, and wind). A reduction in these resonance peaks can be achieved by applying bitumen damping layers, also called deadeners, in the sheet metal. The problem is where these deadeners shall be fixed, which is usually done in a trial-and-error basis. In this work, one proposes the use of embedded sensitivity to locate the deadeners in the sheet metal of the vehicle, more specifically in the vehicle roof. Experimental frequency response functions (FRFs) of the roof are obtained and the data are processed by adopting the embedded sensitivity method, thus obtaining the sensitivity of the resonance peaks on the local increase in damping due to the deadeners. As a result, by examining the sensitivity functions, one can find the optimum location of the deadeners that maximize their effect in reducing the resonance peaks of interest. After locating the deadeners in the optimum positions, it was possible to verify a strong reduction in resonance peaks of the vehicle roof, thus showing the efficiency of the procedure. The main advantage of this procedure is that it only requires FRF measurements of the vehicle in its original state not needing any previous modification of the vehicle structure to find the sensitivity functions. [DOI: 10.1115/1.4000769]

Active sound quality control of engine induced cavity noise

Active control solutions appear to be a feasible approach to cope with the steadily increasing requirements for noise reduction in the transportation industry. Active controllers tend to be designed with a target on the sound pressure level reduction. However, the perceived control efficiency for the occupants can be more accurately assessed if psychoacoustic metrics can be taken into account. Therefore, this paper aims to evaluate, numerically and experimentally, the effect of a feedback controller on the sound quality of a vehicle mockup excited with engine noise. The proposed simulation scheme is described and experimentally validated. The engine excitation is provided by a sound quality equivalent engine simulator, running on a real-time platform that delivers harmonic excitation in function of the driving condition. The controller performance is evaluated in terms of specific loudness and roughness. It is shown that the use of a quite simple control strategy, such as a velocity feedback, can result in satisfactory loudness reduction with slightly spread roughness, improving the overall perception of the engine sound. (C) 2008 Elsevier Ltd. All rights reserved.

Lifecycle assessment of fuel ethanol from sugarcane in Brazil

This paper presents the lifecycle assessment (LCA) of fuel ethanol, as 100% of the vehicle fuel, from sugarcane in Brazil. The functional unit is 10,000 km run in an urban area by a car with a 1,600-cm(3) engine running on fuel hydrated ethanol, and the resulting reference flow is 1,000 kg of ethanol. The product system includes agricultural and industrial activities, distribution, cogeneration of electricity and steam, ethanol use during car driving, and industrial by-products recycling to irrigate sugarcane fields. The use of sugarcane by the ethanol agribusiness is one of the foremost financial resources for the economy of the Brazilian rural area, which occupies extensive areas and provides far-reaching potentials for renewable fuel production. But, there are environmental impacts during the fuel ethanol lifecycle, which this paper intents to analyze, including addressing the main activities responsible for such impacts and indicating some suggestions to minimize the impacts. This study is classified as an applied quantitative research, and the technical procedure to achieve the exploratory goal is based on bibliographic revision, documental research, primary data collection, and study cases at sugarcane farms and fuel ethanol industries in the northeast of SA o pound Paulo State, Brazil. The methodological structure for this LCA study is in agreement with the International Standardization Organization, and the method used is the Environmental Design of Industrial Products. The lifecycle impact assessment (LCIA) covers the following emission-related impact categories: global warming, ozone formation, acidification, nutrient enrichment, ecotoxicity, and human toxicity. The results of the fuel ethanol LCI demonstrate that even though alcohol is considered a renewable fuel because it comes from biomass (sugarcane), it uses a high quantity and diversity of nonrenewable resources over its lifecycle. The input of renewable resources is also high mainly because of the water consumption in the industrial phases, due to the sugarcane washing process. During the lifecycle of alcohol, there is a surplus of electric energy due to the cogeneration activity. Another focus point is the quantity of emissions to the atmosphere and the diversity of the substances emitted. Harvesting is the unit process that contributes most to global warming. For photochemical ozone formation, harvesting is also the activity with the strongest contributions due to the burning in harvesting and the emissions from using diesel fuel. The acidification impact potential is mostly due to the NOx emitted by the combustion of ethanol during use, on account of the sulfuric acid use in the industrial process and because of the NOx emitted by the burning in harvesting. The main consequence of the intensive use of fertilizers to the field is the high nutrient enrichment impact potential associated with this activity. The main contributions to the ecotoxicity impact potential come from chemical applications during crop growth. The activity that presents the highest impact potential for human toxicity (HT) via air and via soil is harvesting. Via water, HT potential is high in harvesting due to lubricant use on the machines. The normalization results indicate that nutrient enrichment, acidification, and human toxicity via air and via water are the most significant impact potentials for the lifecycle of fuel ethanol. The fuel ethanol lifecycle contributes negatively to all the impact potentials analyzed: global warming, ozone formation, acidification, nutrient enrichment, ecotoxicity, and human toxicity. Concerning energy consumption, it consumes less energy than its own production largely because of the electricity cogeneration system, but this process is highly dependent on water. The main causes for the biggest impact potential indicated by the normalization is the nutrient application, the burning in harvesting and the use of diesel fuel. The recommendations for the ethanol lifecycle are: harvesting the sugarcane without burning; more environmentally benign agricultural practices; renewable fuel rather than diesel; not washing sugarcane and implementing water recycling systems during the industrial processing; and improving the system of gases emissions control during the use of ethanol in cars, mainly for NOx. Other studies on the fuel ethanol from sugarcane may analyze in more details the social aspects, the biodiversity, and the land use impact.

An exploratory analysis of relationships between socioeconomic, land use, activity participation variables and travel patterns

This paper aims to find relations between the socioeconomic characteristics, activity participation, land use patterns and travel behavior of the residents in the Sao Paulo Metropolitan Area (SPMA) by using Exploratory Multivariate Data Analysis (EMDA) techniques. The variables influencing travel pattern choices are investigated using: (a) Cluster Analysis (CA), grouping and characterizing the Traffic Zones (17), proposing the independent variable called Origin Cluster and, (b) Decision Tree (DT) to find a priori unknown relations among socioeconomic characteristics, land use attributes of the origin TZ and destination choices. The analysis was based on the origin-destination home-interview survey carried out in SPMA in 1997. The DT application revealed the variables of greatest influence on the travel pattern choice. The most important independent variable considered by DT is car ownership, followed by the Use of Transportation ""credits"" for Transit tariff, and, finally, activity participation variables and Origin Cluster. With these results, it was possible to analyze the influence of a family income, car ownership, position of the individual in the family, use of transportation ""credits"" for transit tariff (mainly for travel mode sequence choice), activities participation (activity sequence choice) and Origin Cluster (destination/travel distance choice). (c) 2010 Elsevier Ltd. All rights reserved.

Vehicle Dynamic Safety in Measured Rough Pavement

Dynamic vehicle behavior is used to identify safe traffic speed limits. The proposed methodology is based on the vehicle vertical wheel contact force response excited by measured pavement irregularities on the frequency domain. A quarter-car model is used to identify vehicle dynamic behavior. The vertical elevation of an unpaved road surface has been measured. The roughness spectral density is quantified as ISO Level C. Calculations for the vehicle inertance function were derived by using the vertical contact force transfer function weighed by the pavement spectral density roughness function in the frequency domain. The statistical contact load variation is obtained from the vehicle inertance density function integration. The vehicle safety behavior concept is based on its handling ability properties. The ability to generate tangential forces on the wheel/road contact interface is the key to vehicle handling. This ability is related to tire/pavement contact forces. A contribution to establish a traffic safety speed limit is obtained from the likelihood of the loss of driveability. The results show that at speeds faster than 25 km/h the likelihood of tire contact loss is possible when traveling on the measured road type. DOI: 10.1061/(ASCE)TE.19435436.0000216. (C) 2011 American Society of Civil Engineers.

Mechanical strength evaluation for Nd-YAG laser and electric resistance spot weld (ERSW) joint under multiaxial loading

This work presents a comparison between laser weld (LBW) and electric resistance spot weld (ERSW) processes used for assemblies of components in a body-in-white (BIW) at a world class automotive industry. It is carried out by evaluating the mechanical strength modeled both by experimental and numerical methods. An ""Arcan"" multiaxial test was designed and manufactured in order to enable 0 degrees, 45 degrees and 90 degrees directional loadings. The welded specimens were uncoated low carbon steel sheets (S-y = 170 MPa) used currently at the automotive industry, with two different thicknesses: 0.80 and 1.20 mm. A numerical analysis was carried out using the finite element method (FEM) through LS-DYNA code. (c) 2007 Elsevier B.V. All rights reserved.

Emissions from the premixed combustion of gasified polyethylene

An investigation was conducted on pollutants emitted from steady-state, steady-flow gasification and combustion of polyethylene (PE) in a two-stage furnace. The polymer, in pulverized form, was first pyrolyzed at 1000 degrees C, and subsequently, its gaseous pyrolyzates were burned, upon mixing with air at high temperatures (900-1100 degrees C). The motivation for this indirect type of burning PE was to attain nominally premixed combustion of the pyrolyzate gases with air, thereby achieving lower pollutant emissions than those emanating from the direct burning of the solid PE polymer. This work assessed the effluents of the two-stage furnace and examined the effects of the combustion temperature, as well as the polymer feed rate and the associated fuel/air equivalence ratio (0.3 < phi < 1.4). It was found that, whereas the yield of pyrolysis gas decreased with an increasing polymer feed rate, its composition was nearly independent of the feed rate. CO2 emissions peaked at an equivalence ratio near unity, while the CO emissions increased with an increasing equivalence ratio. The total light volatile hydrocarbon and semivolatile polycyclic aromatic hydrocarbon (PAH) emissions of combustion increased with an increasing equivalence ratio. The generated particulates were mostly submicrometer in size. Overall, PAH and soot emissions from this indirect burning of PE were an order of magnitude lower than corresponding emissions from the direct burning of the solid polymer, obtained previously in this laboratory using identical sampling and analytical techniques. Because pyrolysis of this polymer requires a nominal heat input that amounts to only a diminutive fraction of the heat released during its combustion, implementation of this technique is deemed advantageous.

Instrumented indentation testing of an epoxy adhesive used in automobile body assembling

Instrumented indentation has been used to investigate the mechanical properties of BETAMATE 1496 (R) Epoxy adhesive. The properties of the adhesive were analyzed by measuring its hardness and its Young`s modulus in samples extracted from six different positions of the front door of a commercial passenger vehicle in two phases of processing: after application of the adhesive in the door assembling (""pre-cured"" state) and after final cure in the painting oven (""cured"" state). Special attention was given to setting the optimal parameters (""creep"" time and unloading time step) for the instrumented indentation testing for the present application. Young`s modulus values around 1.1 +/- 0.2 GPa and hardness values around 0.15 +/- 0.05 GPa were obtained for all samples, irrespective of the variation of the indentation parameters in the testing procedure and of the relative position of the adhesive in the door frame in both states. (C) 2008 Elsevier Ltd. All rights reserved.

On state representations of nonlinear implicit systems

This work considers a semi-implicit system A, that is, a pair (S, y), where S is an explicit system described by a state representation (x)over dot(t) = f(t, x(t), u(t)), where x(t) is an element of R(n) and u(t) is an element of R(m), which is subject to a set of algebraic constraints y(t) = h(t, x(t), u(t)) = 0, where y(t) is an element of R(l). An input candidate is a set of functions v = (v(1),.... v(s)), which may depend on time t, on x, and on u and its derivatives up to a Finite order. The problem of finding a (local) proper state representation (z)over dot = g(t, z, v) with input v for the implicit system Delta is studied in this article. The main result shows necessary and sufficient conditions for the solution of this problem, under mild assumptions on the class of admissible state representations of Delta. These solvability conditions rely on an integrability test that is computed from the explicit system S. The approach of this article is the infinite-dimensional differential geometric setting of Fliess, Levine, Martin, and Rouchon (1999) (`A Lie-Backlund Approach to Equivalence and Flatness of Nonlinear Systems`, IEEE Transactions on Automatic Control, 44(5), (922-937)).

Some remarks on static-feedback linearization for time-varying systems

This work summarizes some results about static state feedback linearization for time-varying systems. Three different necessary and sufficient conditions are stated in this paper. The first condition is the one by [Sluis, W. M. (1993). A necessary condition for dynamic feedback linearization. Systems & Control Letters, 21, 277-283]. The second and the third are the generalizations of known results due respectively to [Aranda-Bricaire, E., Moog, C. H., Pomet, J. B. (1995). A linear algebraic framework for dynamic feedback linearization. IEEE Transactions on Automatic Control, 40, 127-132] and to [Jakubczyk, B., Respondek, W. (1980). On linearization of control systems. Bulletin del` Academie Polonaise des Sciences. Serie des Sciences Mathematiques, 28, 517-522]. The proofs of the second and third conditions are established by showing the equivalence between these three conditions. The results are re-stated in the infinite dimensional geometric approach of [Fliess, M., Levine J., Martin, P., Rouchon, P. (1999). A Lie-Backlund approach to equivalence and flatness of nonlinear systems. IEEE Transactions on Automatic Control, 44(5), 922-937]. (C) 2008 Elsevier Ltd. All rights reserved.

New simple and efficient heuristics for the uncapacitated single allocation hub location problem

Hub-and-spoke networks are widely studied in the area of location theory. They arise in several contexts, including passenger airlines, postal and parcel delivery, and computer and telecommunication networks. Hub location problems usually involve three simultaneous decisions to be made: the optimal number of hub nodes, their locations and the allocation of the non-hub nodes to the hubs. In the uncapacitated single allocation hub location problem (USAHLP) hub nodes have no capacity constraints and non-hub nodes must be assigned to only one hub. In this paper, we propose three variants of a simple and efficient multi-start tabu search heuristic as well as a two-stage integrated tabu search heuristic to solve this problem. With multi-start heuristics, several different initial solutions are constructed and then improved by tabu search, while in the two-stage integrated heuristic tabu search is applied to improve both the locational and allocational part of the problem. Computational experiments using typical benchmark problems (Civil Aeronautics Board (CAB) and Australian Post (AP) data sets) as well as new and modified instances show that our approaches consistently return the optimal or best-known results in very short CPU times, thus allowing the possibility of efficiently solving larger instances of the USAHLP than those found in the literature. We also report the integer optimal solutions for all 80 CAB data set instances and the 12 AP instances up to 100 nodes, as well as for the corresponding new generated AP instances with reduced fixed costs. Published by Elsevier Ltd.

On state representations of time-varying nonlinear systems

This work considers a nonlinear time-varying system described by a state representation, with input u and state x. A given set of functions v, which is not necessarily the original input u of the system, is the (new) input candidate. The main result provides necessary and sufficient conditions for the existence of a local classical state space representation with input v. These conditions rely on integrability tests that are based on a derived flag. As a byproduct, one obtains a sufficient condition of differential flatness of nonlinear systems. (C) 2009 Elsevier Ltd. All rights reserved.