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Abstract A 3-D printing method to produce dental prostheses of complex shapes from a commercial, photocurable resin-ceramic slurry is developed and optimized. The microstructure, mechanical properties and wear behavior of the resulting material are evaluated and compared with a conventional/control sample and other ceramic-polymer dental composites. Commercial resin-ceramic dental slurries can be successfully extruded and appropriately photocured in a low cost 3-D printing system to produce cost-efficient complex dental parts that could be used in indirect restorations. The printing process does not appreciably introduce defects in the material and the 3-D printed composites exhibit mechanical properties (hardness, elastic modulus) and wear resistance comparable to the control material and analogous, conventional dental composites. The main wear mechanisms under sliding contact against a hard antagonist are plastic deformation at the asperity level and ceramic particle pull-out due to filler/matrix interfacial weakness. Graphical Abstract 3-D printing commercial resin-filler slurries creates cost-efficient tooth prostheses with properties akin to conventional dental composites

Abstract Background Modulator therapies that seek to correct the underlying defect in cystic fibrosis (CF) have revolutionized the clinical landscape. Given the heterogeneous nature of lung disease progression in the post-modulator era, there is a need to develop prediction models that are robust to modulator uptake. Methods We conducted a retrospective longitudinal cohort study of the CF Foundation Patient Registry (N = 867 patients carrying the G551D mutation who were treated with ivacaftor from 2003 to 2018). The primary outcome was lung function (percent predicted forced expiratory volume in 1 s or FEV1pp). To characterize the association between ivacaftor initiation and lung function, we developed a dynamic prediction model through covariate selection of demographic and clinical characteristics. The ability of the selected model to predict a decline in lung function, clinically known as an FEV1-indicated exacerbation signal (FIES), was evaluated both at the population level and individual level. Results Based on the final model, the estimated improvement in FEV1pp after ivacaftor initiation was 4.89% predicted (95% confidence interval [CI]: 3.90 to 5.89). The rate of decline was reduced with ivacaftor initiation by 0.14% predicted/year (95% CI: 0.01 to 0.27). More frequent outpatient visits prior to study entry and being male corresponded to a higher overall FEV1pp. Pancreatic insufficiency, older age at study entry, a history of more frequent pulmonary exacerbations, lung infections, CF-related diabetes, and use of Medicaid insurance corresponded to lower FEV1pp. The model had excellent predictive accuracy for FIES events with an area under the receiver operating characteristic curve of 0.83 (95% CI: 0.83 to 0.84) for the independent testing cohort and 0.90 (95% CI: 0.89 to 0.90) for 6-month forecasting with the masked cohort. The root-mean-square errors of the FEV1pp predictions for these cohorts were 7.31% and 6.78% predicted, respectively, with standard deviations of 0.29 and 0.20. The predictive accuracy was robust across different covariate specifications. Conclusions The methods and applications of dynamic prediction models developed using data prior to modulator uptake have the potential to inform post-modulator projections of lung function and enhance clinical surveillance in the new era of CF care.

Within the phenomenology of particle physics, the theoretical model of 4-zero textures is validated using a chi-square criterion that compares experimental data with the computational results of the model. Traditionally, analytical methods that often imply simplifications, combined with computational analysis, have been used to validate texture models. In this paper, we propose a new meta-heuristic variant of the differential evolution algorithm that incorporates aspects of the particle swarm optimization algorithm called “HE-DEPSO” to obtain chi-squared values that are less than a bound value, which exhaustive and traditional algorithms cannot obtain. The results show that the proposed algorithm can optimize the chi-square function according to the required criteria. We compare simulated data with experimental data in the allowed search region, thereby validating the 4-zero texture model.

ABSTRACT Objective: To evaluate the advantages and disadvantages of bone reconstruction and lengthening compared to amputation in the treatment of tibial hemimelia for patients and their families. Methods: Systematic review of articles published in English and Portuguese between 1982 and 2022 in the MEDLINE, PubMed, Cochrane and SciELO databases. The variables of interest were: year of publication, sample characteristics, classification of tibial hemimelia according to Jones, treatment outcome and follow-up time. Results: A total of eleven articles were included in the scope of this review. The studies involved 131 patients, 53.4% male and 46.6% female. The age of the patients who underwent a surgical procedure ranged from 1 year and 10 months to 15 years. The most common type was Jones’ I (40.9%). The most recurrent complications in the reconstruction treatment were: infection of the external fixator path, flexion contracture (mainly of the knee), reduction in the range of motion of the knee and ankle. Conclusion: We did not find enough relevant studies in the literature to prove the superiority of reconstruction. Amputation remains the gold standard treatment for tibial hemimelia to this day. Level of Evidence III, systematic review of level III studies

Alemtuzumab is used as lymphocyte-depleting therapy for severe or glucocorticoid-resistant kidney transplant rejection. However, the long-term efficacy and toxicity of alemtuzumab therapy are unclear. Therefore, all cases of alemtuzumab anti-rejection therapy between 2012 and 2022 in our institution were investigated. Graft survival, graft function, lymphocyte depletion, serious infections, malignancies, and patient survival were analyzed and compared with a reference cohort of transplanted patients who did not require alemtuzumab anti-rejection therapy. A total of 225 patients treated with alemtuzumab were identified and compared with a reference cohort of 1,668 patients. Over 60% of grafts was salvaged with alemtuzumab therapy, but graft survival was significantly poorer compared to the reference cohort. The median time of profound T- and B lymphocyte depletion was 272 and 344 days, respectively. Serious infection rate after alemtuzumab therapy was 54.1/100 person-years. The risk of death (hazard ratio 1.75, 95%-CI 1.28–2.39) and infection-related death (hazard ratio 2.36, 95%-CI 1.35–4.11) were higher in the alemtuzumab-treated cohort. In conclusion, alemtuzumab is an effective treatment for severe kidney transplant rejection, but causes long-lasting lymphocyte depletion and is associated with frequent infections and worse patient survival outcomes.

Solar flares are broadly classified as impulsive or gradual. Ions accelerated in a gradual flare are thought to be accelerated through a shock acceleration mechanism, but the particle acceleration process in an impulsive flare is still largely unexplored. To understand the acceleration process, it is necessary to measure the high-energy gamma rays and neutrons produced by the impulsive flare. Under such circumstances, on 7 November 2004, a huge X2.0 flare occurred on the solar surface, where ions were accelerated to energies greater than 10 GeV. The accelerated primary protons collided with the solar atmosphere and produced line gamma rays and neutrons. These particles were received as neutrons and line gamma rays, respectively. Neutrons of a few GeV, on the other hand, decay to produce secondary protons while traveling 0.06 au in the solar–terrestrial space. These secondary protons arrive at the magnetopause. Although the flux of secondary protons is very low, the effect of collecting secondary protons arriving in a wide region of the magnetosphere (the Funnel or Horn effect) has resulted in significant signals being received by the solar neutron telescope at Mt. Sierra Negra (4600 m). This information suggests that ions on the solar surface are accelerated to over 10 GeV with an impulsive flare.

In this work, we propose a variation of the cellular particle swarm optimization algorithm with differential evolution hybridization (CPSO-DE) to include constrained optimization, named Ts-CPD. It is implemented as a kernel of electronic design automation (EDA) tool capable of sizing circuit components considering a single-objective design with restrictions and constraints. The aim is to improve the optimization solutions in the sizing of analog circuits. To evaluate our proposal’s performance, we present the design of three analog circuits: a differential amplifier, a two-stage operational amplifier (op-amp), and a folded cascode operational transconductance amplifier. Numerical simulation results indicate that Ts-CPD can find better solutions, in terms of the design objective and the accomplishment of constraints, than those reported in previous works. The Ts-CPD implementation was performed in Matlab using Ngspice and can be found on GitHub (see Data Availability Statement).

Digital Light Processing was used to fabricate bioactive ceramic scaffolds for bone regeneration using β-tricalcium phosphate (β-TCP) powder as a starting material. The 3D structures were de-binded in vacuum and divided in two batches: Carbon Containing samples and Carbon Free samples (obtained by firing at 750 °C in air after de-binding). All samples were then sintered in pressure-less SPS either at 1200 °C or 1500 °C, resulting in two different polymorphs (β and α -TCP). The influence of the de-binding method, the in-situ formation of a carbonaceous phase and different phase composition of resulting scaffolds was evaluated in terms of mechanical performance and in vitro bioactivity and solubility in simulated body fluid (SBF). All scaffolds exhibited compressive strengths within the range of cancellous bone and bone-like apatite precipitates were visible on their surface after 21 days of immersion in SBF, with the exception of carbon-free samples sintered at 1200 °C.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare CD30 positive T cell lymphoma whose incidence has recently increased. Until 2020, 733 cases of BIA-ALCL and 36 deaths have been reported around the world, with only one confirmed case in Portugal. The authors describe two clinical cases of BIA-ALCL after breast cancer reconstruction using macrotextured implants. Case 1: A 45-year-old patient, who presented with a typical late-onset seroma five years after breast reconstruction and underwent capsulectomy, confirming localized disease to the capsule. Case 2: A 43-year-old patient presented with an atypical presentation of pleural effusion and tumor mass, 14 years after reconstruction. She underwent implant removal and chemotherapy, due to metastatic disease. These clinical cases illustrate two very distinct clinical presentations of BIA-ALCL. Early diagnosis of this entity allows for effective treatment of the disease, which should be approached in a multidisciplinary setting.

Canonical Correlation Analysis (CCA) infers a pairwise linear relationship between two groups of random variables, X and Y. In this paper, we present a new procedure based on Rényi’s pseudodistances (RP) aiming to detect linear and non-linear relationships between the two groups. RP canonical analysis (RPCCA) finds canonical coefficient vectors, a and b, by maximizing an RP-based measure. This new family includes the Information Canonical Correlation Analysis (ICCA) as a particular case and extends the method for distances inherently robust against outliers. We provide estimating techniques for RPCCA and show the consistency of the proposed estimated canonical vectors. Further, a permutation test for determining the number of significant pairs of canonical variables is described. The robustness properties of the RPCCA are examined theoretically and empirically through a simulation study, concluding that the RPCCA presents a competitive alternative to ICCA with an added advantage in terms of robustness against outliers and data contamination.

In this paper, we introduce the restricted minimum density power divergence Gaussian estimator (MDPDGE) and study its main asymptotic properties. In addition, we examine it robustness through its influence function analysis. Restricted estimators are required in many practical situations, such as testing composite null hypotheses, and we provide in this case constrained estimators to inherent restrictions of the underlying distribution. Furthermore, we derive robust Rao-type test statistics based on the MDPDGE for testing a simple null hypothesis, and we deduce explicit expressions for some main important distributions. Finally, we empirically evaluate the efficiency and robustness of the method through a simulation study.

Nature has evolved ingenious armour designs, like the flexible carapaces of armadillo and boxfish consisting of hexagonal segments connected by collagen fibres, that serve as bioinspiration for modern ballistic armours. Here, Finite element modelling (FEM) used to analyze the effect of scale geometry and other impact parameters on the ballistic protection provided by a bioinspired segmented ceramic armour. For this purpose, the impact of cylindrical fragment simulating projectiles (FSPs) onto alumina-epoxy non-overlapping scaled plates was simulated. Scale geometrical parameters (size, thickness and shape) and impact conditions (FSP diameter, speed, location) are varied and the amount of damage produced in the ceramic tiles and the final residual velocity of the FSP after the impact are evaluated. It is found that segmentation drastically reduces the size of the damaged area without significantly reducing the ballistic protection in centred impact, provided the tile size is kept over a critical value. Such critical tile size (∼20 mm, inscribed diameter, for impacts at 650 m/s) is independent of the scale thickness, but decreases with projectile speed, although never below the diameter of the projectile. Off-centred impacts reduce the ballistic protection and increase the damaged area, but this can be minimized with an appropriate tile shape. In this sense and in agreement with the natural hexagonal tiles of the boxfish and armadillo, hexagonal scales are found to be optimal, exhibiting a variation of ballistic protection—measured as reduction of projectile speed—with impact location under 12%. Design guidelines for the fabrication of segmented protection systems are proposed in the light of these numerical results. Keywords: Scaled armour, Ballistic impact, Alumina, Epoxy, Finite element analysis, Bioinspiration

The Rao’s score, Wald and likelihood ratio tests are the most common procedures for testing hypotheses in parametric models. None of the three test statistics is uniformly superior to the other two in relation with the power function, and moreover, they are first-order equivalent and asymptotically optimal. Conversely, these three classical tests present serious robustness problems, as they are based on the maximum likelihood estimator, which is highly non-robust. To overcome this drawback, some test statistics have been introduced in the literature based on robust estimators, such as robust generalized Wald-type and Rao-type tests based on minimum divergence estimators. In this paper, restricted minimum Rényi’s pseudodistance estimators are defined, and their asymptotic distribution and influence function are derived. Further, robust Rao-type and divergence-based tests based on minimum Rényi’s pseudodistance and restricted minimum Rényi’s pseudodistance estimators are considered, and the asymptotic properties of the new families of tests statistics are obtained. Finally, the robustness of the proposed estimators and test statistics is empirically examined through a simulation study, and illustrative applications in real-life data are analyzed.

Migrant students tend to underperform in Science, Technology, Engineering, and Mathematics (STEM) subjects and are less likely to pursue higher education in STEM when compared with their nonmigrant peers. Given the substantial increase in migration, this disparity has been a central concern in science education in many European countries. The purpose of this study was to investigate the effectiveness of an innovative science outreach program that brings together migrant students and STEM professionals with the same linguistic and cultural backgrounds. The program consists of one-off workshops that follow an inquiry-based approach and include hands-on activities and science communication in the students' heritage language. Using surveys with adapted scales and open-ended questions, we applied a randomized block design with waitlist control groups and repeated measures. Eighty-three Portuguese-speaking migrant students aged 6-17 years participated in the workshops in Germany and the United Kingdom. Results indicate that both the students and STEM professionals evaluated the program positively and that students who participated in the workshops tended to demonstrate an increase in their attainment value for science and an increase in their self-concept of ability for the heritage language 4 weeks after the intervention when compared with students in the control condition. These effects were particularly pronounced for students with low prior motivation to study science or speak the heritage language. Our results thus show that it is possible to foster migrant students' attainment value for science and increase their self-concept of ability regarding the heritage language through a brief science outreach intervention.

Systemic lupus erythematosus (SLE) is an autoimmune disease with a strong ethnic and gender bias. In a transancestral genetic association study, Langefeldet al. identify 24 novel regions associated with risk to lupus and propose a cumulative hits hypothesis for loci conferring risk to SLE.

Esse trabalho tem por objetivos analisar potencialidades e desafios de uma sequência didática (SD) elaborada sob a perspectiva CTS (Ciência–Tecnologia-Sociedade) com enfoque investigativo para o ensino de Química na educação básica, utilizando o tema sociocientífico Água – medição de pH. A SD foi aplicada em uma turma da 2ª série do Ensino Médio de uma escola estadual pública localizada no interior do estado de São Paulo, Brasil. A pesquisa foi desenvolvida em uma abordagem qualitativa, utilizando-se do método da pesquisa-ação. Os dados da pesquisa, coletados por meio de observação participante, registro em caderno de campo, produção dos estudantes e questionários, foram analisados a partir dos pressupostos da análise de conteúdo de Bardin. Como potencialidades da SD para o ensino de química, destacam-se o aumento de interesse e motivação dos alunos durante as aulas e a conscientização ambiental. Como desafios destacam-se a escassa disponibilidade de tempo do professor da escola pública sobrecarregado de aulas, comprometendo o planejamento criterioso de atividades desta natureza e a superação da falta de conhecimentos prévios e da deficiência na capacidade leitora e escritora dos alunos, decorrentes de uma educação básica pouco valorizada na sociedade e carente de investimentos públicos.

This article describes the solution proposed through physical modules and software for treating attention deficit hyperactivity disorder - ADHD; proposed project in order to provide alternative low-cost therapy in order to enhance skills in children with this condition.

The management of downy mildew (Plasmopara halstedii) in sunflower, is heavily dependent on genetic resistance, whilst entomopathogenic fungi (EF) can reduce other sunflower diseases. In this work, we characterized P. halstedii from Spain and other countries collected in the past few years. Twenty-three races were identified (the most frequent in Spain being 310, 304, 705 and 715), with an increasing proportion of highly virulent races. Five isolates from countries other than Spain overcame the resistance in RHA-340. In addition, we assessed the efficacy of five EF against downy mildew and their effects on sunflower growth in axenic conditions. None of the entomopathogens reduced disease severity, nor did they have any effect on plant growth when applied together with P. halstedii. In contrast, three EF reduced some of the plant growth variables in the absence of the pathogen. Microbiological and molecular diagnostics suggest that the axenic system and the short experimental time used in this study did not favor the successful establishment of EF in the plants or their potential biocontrol effect. Our results show a shift in P. halstedii racial patterns and suggest that soil as a growth substrate and long infection times are needed for EF effectiveness against downy mildew.

Verticillium wilt and leaf mottle of sunflower, caused by the fungus Verticillium dahliae (Vd) has become a major constraint to sunflower oil production in temperate European countries. Information about Vd from sunflower is very scarce despite genetics, molecular traits and pathogenic abilities of fungal strains affecting many other crops being widely known. Understanding and characterizing the diversity of Vd populations in those countries where sunflowers are frequent and severely affected by the fungus are essential for efficient breeding for resistance. In this study, we have analyzed genetic, molecular and pathogenic traits of Vd isolates affecting sunflower in European countries. When their genetics was investigated, almost all the isolates from France, Italy, Spain, Argentina, and Ukraine were assigned to vegetative compatibility group (VCG) 2B. In Bulgaria, Turkey, Romania, and Ukraine, some isolates were assigned to VCG6, but some others could not be assigned to any VCG. Genotyping markers used for Vd affecting crops other than sunflower showed that all the isolates were molecularly identified as race 2 and that markers of defoliating (D) and non-defoliating (ND) pathotypes distinguished two well-differentiated clusters, one (E) grouping those isolates from Eastern Europe and the other (W) all those from the Western Europe and Argentina. All the isolates in cluster W were VCG2B, while the isolates in cluster E belonged to an unknown VCG or to VCG6. When the host range was investigated in the greenhouse, the fungus was highly pathogenic to artichoke, showing the importance of farming alternatives in the management of Verticillium attacks. Sunflower genotypes were inoculated with a selection of isolates in two experiments. Two groups were identified, one including the isolates from Western Europe, Argentina, and Ukraine, and the other including isolates from Bulgaria, Romania, and Turkey. Three pathogenic races were differentiated: V1, V2-EE (Eastern Europe) and V2-WE (Western Europe). Similarly, three differentials are proposed for race identification: HA 458 (universal susceptible), HA 89 (resistant to V2-EE, susceptible to V2-WE) and INRA2603 (susceptible to V2-EE, resistant to V2-WE). The diversity found in Vd affecting sunflower must be taken into account in the search for resistance to the pathogen for European environments of sunflower production.

Las innovaciones tecnológicas del siglo xix contribuyeron al desarrollo del ferrocarril, incidiendo en la circulación de bienes y personas hacia destinos lejanos. Esta moda común de las sociedades europeas se desplazó a otras latitudes y Yucatán no fue la excepción. El ferrocarril propició cambios significativos porque la élite local se aficionó a los viajes hacia las recién descubiertas playas como lugares de veraneo y espacios exclusivos. No obstante, cuando el pueblo fracturó la división social en las playas, la élite se trasladó a nuevos lugares de sociabilidad (haciendas y pueblos) como lugares exóticos. Las exclusividades se ampliaron a finales del siglo xix con los vapores y nuevos destinos: Estados Unidos y Europa. Este trabajo analiza el papel que desempeñó el espacio de exclusividad elitista como referente en la elección de sus destinos y en su diferenciación social con el pueblo. Abstract The technological innovations of the 19th century contributed to the development of the railway, affecting the movement of goods and people to distant destinations. This common trend of European societies moved to other latitudes and Yucatan was no exception. Railroad led to significant changes because local elite encroached to travel towards the newly discovered beaches as holiday venues and exclusive spaces. However, when the town fractured the social division in the beaches, the elite moved to new places of sociability (haciendas and towns) as exotic locations. The exclusives were expanded at the end of the 19th century with fumes and new destinations: United States and Europe. This paper analyzes the role played by space of elitist exclusivity as a reference point in the choice of their destiny and their social differentiation with the people.

Este trabalho discute uma intervenção didática sob a perspectiva Ciência-Tecnologia-Sociedade (CTS) com o tema sociocientífico “uso e abuso de substâncias psicoativas” para o ensino de Química, utilizando como estratégia de ensino o Seminário em grupo. Foi utilizada a modalidade pesquisa-ação numa abordagem qualitativa, objetivando verificar possíveis contribuições do Seminário para o ensino de química com enfoque CTS. O Seminário, assumido em uma perspectiva de educação CTS, mostrou-se estratégia didática favorável à participação do estudante de forma ativa no processo ensino-aprendizagem, à valorização do papel de mediador do professor, à promoção de uma educação voltada à cidadania e à participação social.

A evasão de impostos, sobretudo por meio de subfaturamento das importações, sempre foi motivo de preocupação da administração aduaneira. Além da redução de receita tributária, a sonegação impõe perdas de competitividade aos importadores que assumem todos os encargos tributários, e reduz o grau de proteção à produção doméstica. O objetivo deste trabalho é verificar empiricamente a relação entre os níveis de tarifa aduaneira e o subfaturamento das importações no Brasil, e se este resultado é influenciado pelas características específicas de determinados bens (produtos diferenciados), bem como pela presença de produtos similares com tarifas menores. Entre outros fatos, os resultados apontam que o aumento de um ponto de percentagem na alíquota da tarifa implica uma elevação de 3,1% no nível de sonegação. Na comparação entre bens diferenciados e homogêneos, as estimativas indicam uma elasticidade maior para os primeiros.Tax evasion in Brazilian imports has been an issue of concern for the customs authorities. This problem is addressed here using the theoretical approach of defining evasion as the difference between the value of exports of other countries to country-regionBrazil and value of imports reported by country-regionplaceBrazil. This makes it possible to quantify the effects of high import tariff rates on tax evasion due mainly to underreporting of value. The main empirical result of the paper is that a one-percentage-point increase in the tariff rate implies a 3.1% increase in evasion. Furthermore, we identify an also robust elasticity of evasion of 3.2%for differentiated products in contrast with a lower value of 2.2% for homogeneous products.

The phenomena of ‘herding’ or herd behavior can have important effects when it manifests in equity markets as co-movement in trades of institutional money managers. On one hand, the assetsunder management are so large in comparison with the size of themarket that the trades of these managers affect asset prices, evenmore so if many managers trade in the same direction. On the otherhand, commissions and fees paid by investors are supposedly leviedin exchange for an expert management of the investors’ capital.Thus, a manager that simply imitates the behavior of others does notadd value with her work. The present study is the first to report theresults of two measures of herding used to study this phenomenon inthe equity portions of Chilean AFP (pension) funds. One measure isthe widely used Lakonishok, Vishny y Shleifer (1992) metric, theother is a relatively newer measure presented in Sias (2004). Using adataset of monthly fund trades during the period 2003-2011, bothmeasures find herding in the Chilean market which, while moderatein intensity, is still higher than that reported in the stock markets ofdeveloped countries. More interesting is the asymmetry of results:herding is stronger during times of market crisis, and almostdisappears during periods when the economy expands. These resultshave important implications for performance evaluation and valueadded of the pension funds managed by the AFPs, as well as theimpact of their trades in the stability of the stock market.

Este trabalho tem como objetivo avaliar os efeitos de cotas tarifárias adicionais para as exportações brasileiras de produtos agrícolas, com base na proposta européia de maio de 2004 no âmbito das negociações para um acordo de livre-comércio Mercosul- União Européia. A análise teórica do funcionamento dos três instrumentos da cota tarifária (seu volume e as tarifas intra e extracota) revela que, dependendo da demanda, apenas um deles efetivamente restringe as importações. Assim, a oferta de cotas adicionais não implica necessariamente um aumento equivalente na quantidade exportada. Na estimativa de ganho de receita deve ser considerada também a variação na renda da cota. Além disso, a administração da cota terá um papel crucial na alocação dessa renda. Caso seja o Mercosul a fazê-la, as estimativas indicam um aumento de US$ 728 milhões na receita de divisas, bastante próximo do valor da cota total oferecida a preços correntes, sendo US$ 252 milhões resultantes da apropriação das rendas das cotas e US$ 476 milhões do incremento nas exportações. Se o controle das cotas for realizado pela União Européia, o ganho do Brasil decorrerá exclusivamente do aumento das exportações, atingindo apenas 63,7% do valor da cota citada.This paper aims to evaluate the effects of additional tariff quotas on some Brazilian agricultural exports. The study focuses on the European offer in the negotiations for a Mercosur-European Union free trade agreement in May 2004. The economic analysis of the tariff quota shows that - given the demand curve - only one of the three components (the volume and the intra and extra tariffs rates) will effectively pose a restriction to the imports. So, the concession of an additional quota does not necessarily imply an equivalent increase in exports. In the estimation of the gains, one must consider the change in the quota rent. Besides the administration of the quota systems will play crucial role on the allocation of the quota rent. If Mercosur gets in charge, the estimates indicate an addition of US$ 728 million in exports, of which US$ 525 million result from the appropriation of the quota rents and US$ 476 million from exports. The sum of both is indeed close to the value of the additional quotas at current prices. If the administration goes to the EU, the gains will derive exclusively from the expansion in exports, which corresponds to 63.7% to the value of the quota.

South America has a complex demographic history shaped by multiple migration and admixture events in pre- and post-colonial times. Settled over 14,000 years ago by Native Americans, South America has experienced migrations of European and African individuals, similar to other regions in the Americas. However, the timing and magnitude of these events resulted in markedly different patterns of admixture throughout Latin America. We use genome-wide SNP data for 437 admixed individuals from 5 countries (Colombia, Ecuador, Peru, Chile, and Argentina) to explore the population structure and demographic history of South American Latinos. We combined these data with population reference panels from Africa, Asia, Europe and the Americas to perform global ancestry analysis and infer the subcontinental origin of the European and Native American ancestry components of the admixed individuals. By applying ancestry-specific PCA analyses we find that most of the European ancestry in South American Latinos is from the Iberian Peninsula; however, many individuals trace their ancestry back to Italy, especially within Argentina. We find a strong gradient in the Native American ancestry component of South American Latinos associated with country of origin and the geography of local indigenous populations. For example, Native American genomic segments in Peruvians show greater affinities with Andean indigenous peoples like Quechua and Aymara, whereas Native American haplotypes from Colombians tend to cluster with Amazonian and coastal tribes from northern South America. Using ancestry tract length analysis we modeled post-colonial South American migration history as the youngest in Latin America during European colonization (9-14 generations ago), with an additional strong pulse of European migration occurring between 3 and 9 generations ago. These genetic footprints can impact our understanding of population-level differences in biomedical traits and, thus, inform future medical genetic studies in the region.

Durante el siglo XIX la sociedad mexicana emprendió la constitución de un nuevo modelo de nación que incorporó el valor moral por el trabajo. La modernización y el progreso figuraron como elementos configuradores y se estimó al individuo según su grado de capacidades de contribución nacional. La imagen de ciudadano se vincula estrechamente con el trabajo y, por este motivo, las personas ociosas, jugadoras o sin oficio pertenecían al rango de los inútiles.During the nineteenth century Mexican society began the constitution of a new model of Nation which has incorporated the moral value related to work. Modernization and progress were pivotal elements for that, and the individual has started to be considered for his capacity of contributing with the Nation. The citizen image was closely related to work. In consequence, idlers, gamblers, and unemployed were classified as useless.

Durante o século XIX as nações começaram a desenvolver um conjunto de políticas que visem promover mecanismos de progresso social e um dos meios para alcançar este objectivo foi através do trabalho. Feriados religiosos foram um dos obstáculos mais graves porque o ano do calendário de festas ocupou um significativo número de dias úteis. Perante esta grave situação, as autoridades políticas tentaram promover uma série de medidas destinadas a reduzir progressivamente o número de dias de férias no exercício das suas actividades profissionais, que afetam a produtividade e o indivíduo.

OBJECTIVES:Active immunization, or vaccination, with tumor necrosis factor (TNF)-Kinoid (TNF-K) is a novel approach to induce polyclonal anti-TNF antibodies in immune-mediated inflammatory diseases. This study was performed to transfer the proof of concept obtained in mice model of rheumatoid arthritis (RA) into human. We designed a pilot study to demonstrate the feasibility of therapeutic vaccination in RA. METHODS:This was a phase IIa, placebo-controlled, multicenter study in adults with RA who previously experienced secondary failure of TNF antagonists. Patients were immunized intramuscularly with 2 or 3 doses of placebo (n = 10) or 90 (n = 6), 180 (n = 12), or 360 µg TNF-K (n = 12). The primary objective was to identify the best dose and schedule based on anti-TNF antibody titers. Clinical symptoms and safety were assessed during 12 months and solicited reactions for 7 days after each injection. RESULTS:The highest anti-TNF antibody response was detected in patients immunized with 360 µg TNF-K and with 3 injections, although this difference was not significant with all other groups. Similar proportions of patients receiving TNF-K and placebo reported adverse events up to month 12. Serious adverse events were reported by 4 patients treated with TNF-K (13.3%) and 3 treated with placebo (30.0%), all unrelated to treatment. At month 12, DAS28-CRP, tender and swollen joint counts, and HAQ scores decreased significantly more in patients who exhibited anti-TNF antibody response than in patients who did not. CONCLUSIONS:TNF-K therapeutic vaccination induced dose- and schedule-dependent anti-TNF antibodies in RA patients and was well tolerated. Patients who developed anti-TNF antibodies showed a trend toward clinical improvement. Although the most aggressive dose and schedule, i.e. 360 mg dose administered 3 times, did show a strong trend of higher antibody response, further studies are warranted to examine even higher and more frequent doses in order to establish the best conditions for clinical improvement. TRIAL REGISTRATION:ClinicalTrials.gov NCT01040715.

La comisaría definió distintos grados de penetración en la territorialidad colonial de acuerdo al funcionamiento de los distintos modelos aplicados por el Tribunal del Santo Oficio en la Nueva España. De las inmensas jurisdicciones territoriales, las dimensiones de las comisarias gradualmente fueron reduciéndose con la intención de que hubiera una mayor presencia del Santo Oficio y, así, acortar las distancias que favorecieran la realización de las visitas de distrito. El objetivo de este trabajo consiste en analizar cómo se fueron organizando y reorganizando las comisarías de la provincia de Yucatán durante los siglos XVI-XIX.

Porous ceramic scaffolds are widely studied in the tissue engineering field due to their potential in medical applications as bone substitutes or as bone-filling materials. Solid free form (SFF) fabrication methods allow fabrication of ceramic scaffolds with fully controlled pore architecture, which opens new perspectives in bone tissue regeneration materials. However, little experimentation has been performed about real biological properties and possible applications of SFF designed 3D ceramic scaffolds. Thus, here the biological properties of a specific SFF scaffold are evaluated first, both in vitro and in vivo, and later scaffolds are also implanted in pig maxillary defect, which is a model for a possible application in maxillofacial surgery. In vitro results show good biocompatibility of the scaffolds, promoting cell ingrowth. In vivo results indicate that material on its own conducts surrounding tissue and allow cell ingrowth, thanks to the designed pore size. Additional osteoinductive properties were obtained with BMP-2, which was loaded on scaffolds, and optimal bone formation was observed in pig implantation model. Collectively, data show that SFF scaffolds have real application possibilities for bone tissue engineering purposes, with the main advantage of being fully customizable 3D structures.