bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of educational programs on reducing the burden of caregivers of elderly individuals with dementia: a systematic review
Authors: Marim Camila Manuela , Silva Valter , Taminato Mônica , Barbosa Dulce Aparecida
Published: March 2013

OBJECTIVE: This study's objective was to analyze the effectiveness of educational and support programs for caregivers on reducing their burden. METHOD: The method used was a systematic review. The following were searched; MEDLINE, LILACS, Embase, Cochrane, Web of Science, SciELO and CINAHL. RESULTS: Seven randomized clinical studies were included. These studies compared an educational program with standard care delivery, assessing the burden of caregivers through the Zarit Burden Interview. After the analysis of sensitivity, four studies were grouped in the meta-analysis showing a statistically significant reduction in caregiver burden among the participants of educational and support programs. CONCLUSION: The evidence obtained in this study suggests that educational and support programs have a positive impact on the reduction of caregiver burden when compared to standard care. Therefore, the inclusion of these programs in institutions providing care to the elderly is effective and should be encouraged. These programs should also share non-pharmacological management strategies for the behavioral and psychological symptoms of dementia.
Construction and transformation of social representations of AIDS and implications for health care
Authors: Oliveira Denize Cristina de
Published: March 2013

OBJECTIVES: to analyze the process of the constitution and evolution of social representations and practices referent to aids, based on studies carried out in the last eleven years among health professionals. METHOD: a comparison of representational structures of aids in different decades was undertaken, accompanied by a study of the silent zone, involving health professionals. Data collection and analysis included techniques of free association, structural analysis, and study of the silent zone. RESULTS: the existence of a process of change was observed in the social representations of aids, with the introduction of the possibility of co-existence with the disease and the reduction of the importance of death. CONCLUSIONS: this process is presented as the result of a complex movement of symbolic constructions arising from human interactions, contributing to knowledge of ways of thinking associated with the syndrome and to professional practices in healthcare.
Parâmetros curriculares nacionais: uma revisita aos temas transversais meio ambiente e saúde
Authors: Bomfim Alexandre Maia do , Anjos Maylta Brandão dos , Floriano Marcio Douglas , Figueiredo Carmen Simone Macedo , Santos Denise Azevedo dos , Silva Carolina Luiza de Castro da
Published: March 2013

Nosso estudo parte do legado dos temas transversais deixado pelos Parâmetros Curriculares Nacionais, especificamente os de meio ambiente e saúde, procurando entender como foram processados em documentos oficiais - como as Diretrizes Curriculares Nacionais, as Orientações Curriculares para o Ensino Médio etc. - e como foram absorvidos e ressignificados no interior das escolas, principalmente nos projetos político-pedagógicos. Procurou-se problematizar esses temas com base no momento atual, sem desconsiderar, no entanto, o contexto em que foram criados. Para essa releitura, o suporte veio de autores que trabalham com análise de textos e pesquisa qualitativa. O estudo das partes 'meio ambiente' e 'saúde' mostrou que os textos, de maneira geral, são pouco atraentes; pouco práticos; apresentam dificuldades em dar pistas de ação; não mostram bem as diferentes interfaces com as diferentes áreas; não facilitam a visualização do sentido em que ocorre a trans e a interdisciplinaridade; apresentam-se em alguns momentos lacunares ou superficiais; e têm uma proposta de educação comportamentalista. Nesse limite, a educação serve mais à conformação do que à transformação da realidade; responsabiliza demasiadamente o indivíduo e isenta o Estado; promove uma cidadania passiva, que alcança a compreensão do direito, mas não a sua realização.
Brasil: nova classe média ou novas formas de superexploração da classe trabalhadora?
Authors: Luce Mathias Seibel
Published: March 2013

Com base na categoria da superexploração da força de trabalho, formulada no âmbito da teoria marxista da dependência, apresentamos uma crítica à tese de que o Brasil estaria se tornando 'país de classe média' e sustentamos que um contingente substancial dentre o que vem sendo nomeado de 'nova classe média' consiste, na verdade, de trabalhadores - e suas famílias - vivendo em condições de superexploração. O texto encontra-se dividido em três seções. Na primeira, questionamos os pressupostos básicos da tese Brasil, país de classe média. Na segunda, expomos os fundamentos da categoria da superexploração e demonstramos seu incremento nas relações de produção do capitalismo brasileiro na década de 2000. Na terceira, demonstramos como o acesso da população trabalhadora ao consumo de bens duráveis no período recente, antes que a ascensão de uma suposta 'nova classe média', configura uma forma renovada de superexploração. Por fim, salientamos os nexos entre as condições de trabalho, saúde e direitos da classe trabalhadora no Brasil e as tendências do capitalismo mundial, questionando o falso dilema neoliberalismo e neodesenvolvimentismo no debate atual e colocando a real disjuntiva do ponto de vista da emancipação da classe trabalhadora em relação ao poder despótico do capital.
RC T beams strengthened to shear with carbon fiber composites
Authors: Spagnolo JR L. A. , Sánchez Filho E. S. , Velasco M. S. L.
Published: March 2013

This paper presents the experimental data of the behavior of reinforced concrete beams strengthened to shear with carbon fiber composites. The tests were composed of eight T beams, b w=15 cm, h=40 cm, flange width 40 cm, flange height 8 cm, and length 300 cm, divided into two series with the same longitudinal steel reinforcement and a reference beam without strengthening in each series. The beams had two types of arrangement of internal steel stirrups. The test variables were the internal and external geometric ratio of the transverse reinforcement and the mechanical ratio of carbon fiber composites stirrups. All the beams were loaded at two points. The strengthened beams were submitted to a preloading and the strengthening was applied to the cracked beam. All the beams were designed in order to guarantee shear failure, and the ultimate load of the strengthened beams was 36% to 54% greater than the reference beams. The Cracking Sliding Model applied to the strengthened beams was evaluated and showed good agreement with the experimental results.
Automation of the evaluation of bonded and unbonded prestressed concrete beams, according to brazilian and french code specifications
Authors: Lazzari P. M. , Campos Filho A. , Gastal F. P. S. L. , Barbieri R. A. , Schwingel R. C.
Published: March 2013

This paper presents a suggestion for the automation of the design procedures of bonded and unbonded prestressed concrete flexural members, according to the Brazilian (NBR 6118:2007) and French (Règles BPEL 91) norm specifications. Prestressing of concrete structures has been increasingly used, mainly due to its building advantages, as well as allowing reducing crack incidence and element dimensions by the use of more resistant materials. Structure is analyzed by a numerical model that employs a hybrid type finite element for planar frames, considering geometric nonlinearity, cyclic loading and composite construction. The computational algorithm implemented considers full, partial and limited prestressing situations, evaluating in each case decompression limit state, limit state of cracking, ultimate limit state and final prestressing state. Finally, two examples comparing design situations according to the Brazilian and French norms are presented.
Concrete compressive characteristic strength analysis of pile caps with three piles
Authors: Buttignol T. E.T. , Almeida L.C.
Published: March 2013

In this paper a numerical analysis of three-pile caps is developed to study the influence of concrete compressive characteristic strength in pile caps resistance capacity. A three-pile cap model derived from Miguel's [1] work was adopted. From this model, variations on the compressive characteristic strength were made in order to observe modifications in its structural behavior. The numerical analysis was developed with finite element software ATENA 3D [2]. The results demonstrated that an increase in the compressive characteristic strength was not followed by a significant increment in pile cap's strength, since models' ruin were due to concrete splitting (opening cracks parallel to principal compressive stresses as a result of perpendicular tension stresses within the structure) and ties steel bars yielding. In the models analyzed high-tension stresses were developed along the struts and at the bottom of the pile cap's section, demonstrating that pile cap's ultimate resistance is not influenced by the compressive strength.
A escrita nas práticas de letramento acadêmico
Authors: Marinho Marildes
Published: March 2013

São inúmeros os trabalhos sobre o ensino-aprendizagem da escrita no ensino fundamental e médio. No entanto, a escrita acadêmica ainda não tem recebido a merecida atenção, no Brasil. Serão analisados aqui alguns elementos próprios das condições de produção de escrita de alunos de um curso de graduação. A concepção bakhtiniana, para a qual o domínio de um gênero é um comportamento social, articulada com uma abordagem etnográfica, delineia o referencial teórico-metodológico principal. Abordar o texto etnograficamente significa tratá-lo como um traço ou um elemento de uma situação social, que inclui igualmente os valores, regras, significados e atitudes, assim como modelos de comportamento dos participantes da interação. Conclui-se que o envolvimento da universidade com o ensino-aprendizagem da escrita acadêmica demanda pesquisas sobre habilidades e competências linguísticas e também sobre fundamentos e estratégias que permitam refazer princípios e crenças que têm levado nossos alunos a uma relação "tímida", "deficiente", "inadequada" e tensa com as práticas acadêmicas letradas.
Analysis of Dermatologic Events in Vemurafenib-Treated Patients With Melanoma
Authors: Lacouture Mario E. , Duvic Madeleine , Hauschild Axel , Prieto Victor G. , Robert Caroline , Schadendorf Dirk , Kim Caroline C. , McCormack Christopher J. , Myskowski Patricia L. , Spleiss Olivia , Trunzer Kerstin , Su Fei , Nelson Betty , Nolop Keith B. , Grippo Joseph F. , Lee Richard J. , Klimek Matthew J. , Troy James L. , Joe Andrew K.
Published: March 2013

Background.

Vemurafenib has been approved for the treatment of patients with advanced BRAFV600E-mutant melanoma. This report by the Vemurafenib Dermatology Working Group presents the characteristics of dermatologic adverse events (AEs) that occur in vemurafenib-treated patients, including cutaneous squamous cell carcinoma (cuSCC).

Methods.

Dermatologic AEs were assessed from three ongoing trials of BRAFV600E mutation-positive advanced melanoma. Histologic central review and genetic characterization were completed for a subset of cuSCC lesions.

Results.

A total of 520 patients received vemurafenib. The most commonly reported AEs were dermatologic AEs, occurring in 92%–95% of patients. Rash was the most common AE (64%–75% of patients), and the most common types were rash not otherwise specified, erythema, maculopapular rash, and folliculitis. Rash development did not appear to correlate with tumor response. Photosensitivity occurred in 35%–63% of patients, and palmar-plantar erythrodysesthesia (PPE) occurred in 8%–10% of patients. The severity of rash, photosensitivity, and PPE were mainly grade 1 or 2. In all, 19%–26% of patients developed cuSCC, mostly keratoacanthomas (KAs). The majority of patients with cuSCC continued therapy without dose reduction after resection. Genetic analysis of 29 cuSCC/KA samples demonstrated HRAS mutations in 41%.

Conclusions.

Dermatologic AEs associated with vemurafenib treatment in patients with melanoma were generally manageable with supportive care measures. Dose interruptions and/or reductions were required in <10% of patients.
The fate of medieval English bridges since 1770: demolition, survival and preservation
Authors: Harrison David
Published: March 2013

Until 1770 England had a huge road network making use of medieval bridges. Now, only about 100 major medieval bridges survive. Although no accurate survey has yet been undertaken, it is estimated that over 80% of the major medieval bridges were demolished during the period 1770–1830. The paper looks at the reasons for this widespread demolition programme. The pattern of demolition was varied: over some rivers most medieval bridges were replaced; over others, many remain. Apart from a poor state of repair, the main reason for demolition was that they were inadequate for new wheeled transport. However, many bridges could have been repaired and widened, as some indeed were. Many were demolished because of a shift in attitudes – a desire for modern, fashionable structures. Only in the 1870s did the option to preserve and restore old bridges start to gain popularity and few ancient bridges have been demolished since that time. This study of the post-medieval history of ancient bridges provides valuable insights and background knowledge for civil engineers dealing with old bridges.
Steel fibres as minimum shear reinforcement in reinforced concrete beams
Authors: Jain Kranti , Singh Bhupinder
Published: March 2013

The results of an experimental appraisal of the ACI Building Code provisions allowing the use of deformed steel fibres as minimum shear reinforcement in reinforced concrete beams are presented. Two types of hooked-end steel fibres of lengths 35 mm and 60 mm were used in the fibrous concretes at volume fractions in the range of 0·75 to 1·5% and 0·5 to 1%, respectively. The performance of the fibrous concrete beams was compared to that of beams detailed with code-specified minimum web reinforcement. The results indicate that the use of hooked-end steel fibres even at a volume fraction (0·5%) lower than the ACI Code-specified minimum of 0·75% led to multiple diagonal cracking with crack widths significantly smaller than permissible values. The measured shear strengths across all fibre aspect ratios and volume fractions were higher than a lower bound limit for fibrous concrete beams reported in the literature as well as predicted values of the beams with code-specified conventional minimum web reinforcement. The results of this investigation support the use of the steel fibres used in the experiments as minimum shear reinforcement in normal-strength reinforced concrete beams with depths equal to those of the tested beams.
Central Activating Transcription Factor 4 (ATF4) Regulates Hepatic Insulin Resistance in Mice via S6K1 Signaling and the Vagus Nerve
Authors: Zhang Qian , Yu Junjie , Liu Bin , Lv Ziquan , Xia Tingting , Xiao Fei , Chen Shanghai , Guo Feifan
Published: March 2013

Recent studies have revealed that the central nervous system, particularly the hypothalamus, is critical for regulating insulin sensitivity in peripheral tissues. The aim of our current study is to investigate the possible involvement of hypothalamic activating transcription factor 4 (ATF4) in the regulation of insulin sensitivity in the liver. Here, we show that overexpression of ATF4 in the hypothalamus resulting from intracerebroventricular injection of adenovirus expressing ATF4 induces hepatic insulin resistance in mice and that inhibition of hypothalamic ATF4 by intracerebroventricular adenovirus expressing a dominant-negative ATF4 variant has the opposite effect. We also show that hypothalamic ATF4-induced insulin resistance is significantly blocked by selective hepatic vagotomy or by inhibiting activity of the mammalian target of rapamycin (mTOR) downstream target S6K1. Finally, we show that inhibition of hypothalamic ATF4 reverses hepatic insulin resistance induced by acute brain endoplasmic reticulum (ER) stress. Taken together, our study describes a novel central pathway regulating hepatic insulin sensitivity that is mediated by hypothalamic ATF4/mTOR/S6K1 signaling and the vagus nerve and demonstrates an important role for hypothalamic ATF4 in brain ER stress–induced hepatic insulin resistance. These results may lead to the identification of novel therapeutic targets for treating insulin resistance and associated metabolic diseases.
Concentration and Activity of the Soluble Form of the Interleukin-7 Receptor α in Type 1 Diabetes Identifies an Interplay Between Hyperglycemia and Immune Function
Authors: Monti Paolo , Brigatti Cristina , Krasmann Miriam , Ziegler Anette G. , Bonifacio Ezio
Published: March 2013

Soluble interleukin-7 (IL-7) receptor α (sCD127) is implicated in the pathogenesis of autoimmune diseases. We show that serum sCD127 concentrations are increased at the onset of type 1 diabetes (T1D; n = 390) as compared with concentrations in age-matched islet autoantibody–negative first-degree relatives of patients (n = 392; P = 0.00001). sCD127 concentration in patients was influenced by islet autoantibody status (P = 0.003) and genotype of the rs6897932 single nucleotide polymorphism within the IL-7RA gene (P = 0.006). Release of sCD127 in vitro was strongly upregulated by activation of T lymphocytes and affected by exposure to cytokines. sCD127 bound IL-7 and was antagonistic to IL-7 signaling and IL-7–mediated T-cell proliferation, suggesting a regulatory feedback mechanism on T-cell expansion. Remarkably, high glucose led to a glycated form of sCD127 that was ineffective as an IL-7 antagonist. The finding of glycated sCD127 in the circulation of patients at onset of T1D suggested that physiological regulation of IL-7–mediated T-cell survival and expansion by sCD127 may be compromised in T1D. The findings indicate that genetic, immunologic, and metabolic factors contribute to a dysregulation of the IL-7/IL-7 receptor pathway in T1D and identify a novel hyperglycemia-mediated interference of immune regulatory networks.
Nonexistence Results for Semilinear Equations in
Carnot Groups
Authors: Ferrari Fausto , Pinamonti Andrea
Published: March 2013

In this paper, following [3], we provide some nonexistence results
for semilinear equations in the the class of Carnot groups
of type ★.This class, see [20], contains, in particular, all groups
of step 2; like the Heisenberg group, and also Carnot groups
of arbitrarly large step. Moreover, we prove some nonexistence
results for semilinear equations in the Engel group,
which is the simplest Carnot group that is not of type ★.
Liquid-solid equilibrium for the NaCl-NaHCO3-Na2CO3-H2O system at 45°C. Validation of mixed solvent electrolyte model
Authors: Jaworski Zdzisław , Czernuszewicz Małgorzata
Published: March 2013

The main objective of this work was to verify the mixed solvent electrolyte (MSE) thermodynamic model for the prediction of the liquid-solid equilibrium in the soda system. The full quaternary system NaCl-NaHCO3-Na2CO3-H2O and its three subsystems were considered. Validation of the thermodynamic model was based on experimental data from literature. Phase diagrams for the soda system are plotted for isotherms of 45°C. Good agreement of the MSE results with those from experiments was found at 45°C. Similar phase diagrams for other temperature levels can be constructed based on the validated MSE model.
Fastener effect on magnetic properties of chain compounds of dinuclear ruthenium carboxylates
Authors: Ishida Hideaki , Handa Makoto , Hiromitsu Ichiro , Mikuriya Masahiro
Published: March 2013

Chlorido-bridged chain complexes of dinuclear ruthenium benzoate analogues, [Ru2{3,4,5-(CmH2m+1O)3C6H2CO2}4Cl]n (mCl) (m = 3, 5–7, 9, 11, 13, 15, 17), were synthesised and the crystal structure of 3Cl · 2nH2O was revealed. The magnetic measurements for a series of the complexes mCl (m = 2–18) revealed that all the complexes show an antiferromagnetic interaction between the dinuclear unit, with a fastener effect giving the stronger interaction as the alkyl-chain length m increases.
d-Glucosamine as an efficient and green additive for palladium-catalyzed Heck reaction
Authors: Amini Mojtaba , Etemadi Hossein
Published: March 2013

The Heck coupling of haloarenes with various alkenes was successfully performed in the presence of 0.5 mole % Pd(OAc)2 and 1.0 mole % d-glucosamine as an additive with K2CO3 as the optimal base in a mixture of H2O/iPrOH (φ r = 2: 1) as the reaction solvent at 80°C after 6 h. d-Glucosamine was found to be an inexpensive, air-stable, easy to available, and efficient additive in palladium-catalyzed Heck reactions of aryl iodides (67–95 % conversion) and bromides (38–72 % conversion).
Solvent-free acetylation and tetrahydropyranylation of alcohols catalyzed by recyclable sulfonated ordered nanostructured carbon
Authors: Zareyee Daryoush , Alizadeh Parastoo , Ghandali Mohammad , Khalilzadeh Mohammad
Published: March 2013

Rapid and practical green acetylation and tetrahydropyranylation routes of structurally diverse alcohols and phenols were applied under solvent-free reaction conditions providing excellent yields, using catalytic amounts of environmentally friendly sulfonated ordered nanoporous carbon (CMK-5-SO3H). Non-toxic nature of the catalyst, its easy handling, recovery and reusability, and the absence of any solvent characterize the presented procedures as efficient methods. These procedures provide methods for the separation of the product by simple filtration.
Scientific Concepts and Their Policy Affordances: How a Focus on Compatibility Can Improve Science-Policy Interaction and Outcomes
Authors: Hirsch Paul D. , Luzadis Valerie A.
Published: March 2013

We develop a twofold approach to the development and utilization of policy-relevant knowledge. First, we propose that moving beyond competition to focus on compatibility may promote more effective interdisciplinary collaborations in the context of complex social-ecological problems. Second, we propose that attention to the policy affordances of a set of compatible hypotheses may inform the development of a more holistic and robust set of policy options. This twofold approach is modeled in our methodological approach, in which we have sought to discover how the concepts each of us have been developing are compatible with each other, and what affordances they might offer for improving translation across the science-policy boundary. We illustrate and apply our approach to the complex milieu surrounding the issue of lead paint toxicity. In addition, we draw on findings from focus groups with researchers involved in collaborations at the science-policy boundary to develop recommendations for productive and policy-relevant interdisciplinary collaboration.
Atypical tumors of the facial nerve: case series and review of the literature
Authors: Ross Lindsey , Drazin Doniel , Eboli Paula , Lekovic Gregory P.
Published: March 2013

Object

The authors present a series of 4 patients with rare facial nerve tumors. The relevant literature is reviewed and is discussed regarding diagnostic features, the role of operative management, and surgical approach.

Methods

A retrospective chart review was conducted for patients with tumors of the facial nerve that were treated between 2008 and 2011. Patients undergoing observation with serial MRI and those who were treated with up-front radiosurgery and for whom tissue diagnosis was not available were excluded. In addition, patients with suspected vestibular schwannoma, facial nerve schwannoma, neurofibromatosis Type 2, and metastatic disease were also excluded. The charts of 4 patients (2 men and 2 women) with “atypical” tumors were reviewed and analyzed.

Results

A total of 12 patients with tumors of the facial nerve were identified during the study period. Patient characteristics, preoperative imaging, operative approach, tumor histology, and outcomes are described.

Conclusions

Atypical facial nerve tumors must be distinguished from the more common facial nerve schwannoma. How the authors of this study treat rare facial nerve tumors is based on their experience with the more common facial nerve schwannomas, characterized by a slow progression of symptoms and growth. Less is known about the rare lesions, and thus a conservative approach may be warranted. Open questions include the role of radiosurgery, facial nerve decompression, and indications for resection of tumor and cable grafting for these rare lesions.
Neurosurgical management of neurenteric cysts in children
Authors: Al-Ahmed Ibrahim H. , Boughamoura Mohamed , Dirks Peter , Kulkarni Abhaya V. , Rutka James T. , Drake James M.
Published: March 2013

Object

Neurenteric cysts (NCs) are endothelium-lined structures of presumed endodermal origin. There have been few pediatric series of intracranial NCs reported previously. The authors present their experience in the management of these lesions.

Methods

A retrospective chart review of all cases of NCs identified between 1977 and 2007 was carried out. Demographics, details of clinical presentation, surgical therapy, and outcome data were extracted.

Results

Eleven cases were identified, involving 6 girls and 5 boys. The patients' average age was 4.6 years (range 1 day–14 years). Limb weakness was the most common presenting symptom. The location of the cysts was cervical in 2 cases, cervicothoracic in 4 cases, and thoracic in 3 cases. One cyst was anterior to the pons with extension to the left cerebellopontine angle and 1 cyst was at the craniocervical junction. Five patients had an apparently complete initial excision, with 1 recurrence. Four patients were initially treated with incomplete excision and/or cyst drainage, usually into an Ommaya reservoir. A neonate with a large cervicothoracic cyst died of multiple congenital anomalies without any intervention. All other patients were alive at last follow-up. One patient with a radiologically identified presumed cyst, which remained stable, was simply followed up. Several patients required multiple procedures and 1 patient developed hydrocephalus after aseptic meningitis and was treated with CSF shunting.

Conclusions

Neurenteric cysts are rare in the pediatric population. Total resection, if possible, provides the best long-term outcome. Incomplete excision may lead to multiple procedures, including cyst drainage, but can lead to long-term stability.
Longterm Safety and Efficacy of Tocilizumab in Patients with Rheumatoid Arthritis: A Cumulative Analysis of Up to 4.6 Years of Exposure
Authors: Genovese Mark C. , Rubbert-Roth Andrea , Smolen Josef S. , Kremer Joel , Khraishi Majed , Gómez-Reino Juan , Sebba Anthony , Pilson Robert , Williams Sarah , Van Vollenhoven Ronald
Published: March 2013

Objective.

To assess the longterm safety and efficacy of tocilizumab (TCZ) in patients with moderate to severe rheumatoid arthritis (RA).

Methods.

Patient data were from 5 randomized controlled TCZ trials (n = 4211), their open-label extension phases (n = 3512), and a drug interaction study (n = 23). All randomly assigned patients, regardless of previous RA treatment, were analyzed. Measures of safety included number of adverse events (AE), serious AE (SAE), AE leading to treatment discontinuation, laboratory tests, and deaths. Efficacy measures included American College of Rheumatology (ACR) 20/50/70 responses, tender joint count (TJC), swollen joint count (SJC), ACR core set components, and low disease activity (LDA) or Disease Activity Score in 28 joints (DAS28) remission. ACR/European League Against Rheumatism (EULAR) disease remission was a posthoc exploratory analysis.

Results.

Total duration of observation was 12,293 patient-years (PY). No new safety signals were identified; infections were the most common AE and SAE. The rate of serious infections was 4.5/100 PY. Improvements from baseline in clinical efficacy, measured as ACR20/50/70 responses, TJC, SJC, ACR core set components, and LDA and DAS28 remission, were generally sustained through at least 216 weeks of followup. ACR/EULAR disease remission was attained by 16.5% (Boolean) and 22.7% (index) of patients at Week 216.

Conclusion.

TCZ has to date been studied for up to 4.6 years (240 weeks) of treatment in patients with RA. Our analysis reveals a longer-term safety profile consistent with previous observations, no new safety signals, and durable efficacy of TCZ in a large clinical trial program.
RANKL/OPG Ratio and DKK-1 Expression in Primary Osteoblastic Cultures from Osteoarthritic and Osteoporotic Subjects
Authors: Corrado Addolorata , Neve Anna , Macchiarola Antonio , Gaudio Annamaria , Marucci Arcangela , Cantatore Francesco Paolo
Published: March 2013

Objective.

To evaluate the expression of Dickkopf-1 protein factor (DKK-1), DKK-2, and β-catenin, components of the Wnt pathway, in human osteoarthritic (OA) and osteoporotic (OP) osteoblasts and to correlate it to cell metabolic activity, proliferation, and receptor activator of nuclear factor-κB ligand/osteoprotegerin (RANKL/OPG) expression.

Methods.

Primary human osteoblast cultures were obtained from healthy, OA, and OP donors. In each cell population we evaluated DKK-1, DKK-2, nonphosphorylated β-catenin and RANKL/OPG expression, osteocalcin and alkaline phosphatase (ALP) synthesis, and cell proliferation, both in basal condition and after vitamin D3 stimulation.

Results.

DKK-1 and DKK-2 showed opposite patterns of expression in OA and OP osteoblasts. The RANKL/OPG ratio was significantly higher in the OP group because of a greater expression of RANKL, whereas it was significantly lower in the OA group because of a higher expression of OPG. Treatment with vitamin D3 increased the RANKL/OPG ratio and DKK-2 expression and reduced DKK-1 expression in each cell population, but did not affect β-catenin levels. Both osteocalcin and ALP production and cell proliferation were enhanced in OA cells and reduced in the OP ones.

Conclusion.

These data confirm that OA and OP are characterized by opposite bone changes, consisting of reduced bone remodeling processes with increased osteoblast activity in OA, and enhanced bone resorptive activity with reduction of osteoblast metabolism in OP, and suggest that the Wnt pathway is involved in the pathogenesis of both diseases.
Recommendations for Frequency of Visits to Monitor Systemic Lupus Erythematosus in Asymptomatic Patients: Data from an Observational Cohort Study
Authors: Gladman Dafna D. , Ibañez Dominique , Ruiz Ioana , Urowitz Murray B.
Published: March 2013

Objective.

The aim of our study was to determine the optimal frequency of followup visits in patients with systemic lupus erythematosus (SLE).

Methods.

Patients followed in the lupus clinic over a 2-year period who had at least 3 visits and at least 18 months of followup were included. At each visit patients undergo a complete history, physical examination, and laboratory evaluation. The following variables that would not have been recognized by the patient were identified: proteinuria, hematuria, pyuria, casts, low hemoglobin, leukopenia, thrombocytopenia, elevated serum creatinine, positive anti-DNA antibodies, and low complement. When one of these variables was detected, it was determined whether it was new, and whether other features of activity were present. Thus isolated new variables of interest were identified. Descriptive statistics were used.

Results.

A total of 515 patients (89% female, 61% white) met the inclusion criteria, with an average of 6.1 ± 1.5 for a total of 3126 visits. The average length of time between visits was 3.8 ± 1.0 months. In the 515 patients, the variables of interest were the sole manifestation of SLE in 126 (24.5%) patients (in a total of 175 visits). The commonest manifestations were renal, low complement, and DNA antibodies followed by thrombocytopenia, low hemoglobin, and elevated creatinine.

Conclusion.

One in 4 patients with SLE seen over a 2-year period will have a solitary silent variable of interest that could be detected only by routine laboratory followup. Patients with mild or inactive disease should be followed with clinical and laboratory measures at 3–4 month intervals.
Effect of All-transretinoic Acid on Th17 and T Regulatory Cell Subsets in Patients with Ankylosing Spondylitis
Authors: Bidad Katayoon , Salehi Eisa , Jamshidi Ahmadreza , Saboor-Yaraghi Ali Akbar , Oraei Mona , Meysamie Alipasha , Mahmoudi Mahdi , Nicknam Mohammad Hossein
Published: March 2013

Objective.

We compared Th17 and T regulatory cells in patients with ankylosing spondylitis (AS) and in healthy controls. The effect of all-transretinoic acid (ATRA) was studied on cultured CD4+ T cells of patients with AS compared to controls.

Methods.

Eighteen patients with AS and 18 age- and sex-matched healthy controls were included. CD4+ T cells were separated and cultured in conditions of anti-CD3 and anti-CD28 stimulation with and without ATRA. Intracellular and secreted cytokines, transcription factors, and gene expression were evaluated after 72 h.

Results.

The frequency of CD4+IL-17+ T cells was significantly higher in patients with AS compared to controls, and ATRA could significantly decrease it. The frequency of forkhead box protein 3 (FOXP3)+ retinoic acid-related orphan receptor γt (RORγt) negative T-bet negative CD4+ cells was significantly lower in cases compared to controls. Intracellular and secreted interferon-γ (IFN-γ) was not significantly different between cases and controls. ATRA significantly increased intracellular IFN-γ in cases but not in controls. Tumor necrosis factor-α (TNF-α) secretion was significantly higher and interleukin 10 secretion was significantly lower in culture supernatant of cases compared to controls. ATRA could significantly decrease TNF-α secretion in cases.

Conclusion.

Our findings favor a pathogenic role for Th17 cells in AS. Th1 cells did not seem to contribute in the pathogenesis of this disease. The effect of ATRA as an immunomodulator on deviated immune cells was associated with decreased inflammatory markers. This association could be a reason for a clinical trial of ATRA in patients with AS.
Presencia y actuación española en la 30 Reunión de Técnicos de la Industria del Cemento del Brasil
Authors: Calleja José
Published: March 2013

Not available
Identificación de incrustaciones en ciclones recuperadores de calor de hornos DOPOL
Authors: Triviño Vázquez Fernando
Published: March 2013

Not avaible
Host B7x Promotes Pulmonary Metastasis of Breast Cancer
Authors: Abadi Yael M. , Jeon Hyungjun , Ohaegbulam Kim C. , Scandiuzzi Lisa , Ghosh Kaya , Hofmeyer Kimberly A. , Lee Jun Sik , Ray Anjana , Gravekamp Claudia , Zang Xingxing
Published: March 2013

B7x (B7-H4 or B7S1) is an inhibitory member of the B7 family of T cell costimulation. It is expressed in low levels in healthy peripheral tissues, such as the lung epithelium, but is overexpressed in a variety of human cancers with negative clinical associations, including metastasis. However, the function of B7x in the context of cancer, whether expressed on cancer cells or on surrounding “host” tissues, has not been elucidated in vivo. We used the 4T1 metastatic breast cancer model and B7x knockout (B7x −/−) mice to investigate the effect of host tissue–expressed B7x on cancer. We found that 4T1 cells were B7x negative in vitro and in vivo, and B7x−/− mice had significantly fewer lung 4T1 tumor nodules than did wild-type mice. Furthermore, B7x−/− mice showed significantly enhanced survival and a memory response to tumor rechallenge. Mechanistic studies revealed that the presence of B7x correlated with reduced general and tumor-specific T cell cytokine responses, as well as with an increased infiltration of immunosuppressive cells, including tumor-associated neutrophils, macrophages, and regulatory T cells, into tumor-bearing lungs. Importantly, tumor-associated neutrophils strongly bound B7x protein and inhibited the proliferation of both CD4 and CD8 T cells. These results suggest that host B7x may enable metastasizing cancer cells to escape local antitumor immune responses through interactions with the innate and adaptive immune systems. Thus, targeting the B7x pathway holds much promise for improving the efficacy of immunotherapy for metastatic cancer.
Expression of CXCR3 on Specific T Cells Is Essential for Homing to the Prostate Gland in an Experimental Model of Chronic Prostatitis/Chronic Pelvic Pain Syndrome
Authors: Breser Maria L. , Motrich Ruben D. , Sanchez Leonardo R. , Mackern-Oberti Juan P. , Rivero Virginia E.
Published: March 2013

Experimental autoimmune prostatitis (EAP) is considered a valid model for the human disease chronic prostatitis/chronic pelvic pain syndrome. In this report, we analyzed phenotypic characteristics of T cells that gain access to the prostate and induce leukocyte recruitment in mice with different susceptibility to EAP. After EAP induction, NOD mice developed a specific cellular response characterized by a mixed Th1/Th17 pattern with specific T cells mainly expressing CXCR3 that infiltrated and damaged the prostate. In contrast, BALB/c mice, as well as NOD-IFN-γ−/−, exhibited only Th17 cells mainly expressing CCR6 that were not capable of infiltrating the prostate gland. Adoptive transfer experiments of T cells from NOD or NOD–IFN-γ−/− mice to NOD-SCID recipients showed that only T cells from NOD mice successfully infiltrated the prostate. However, after “in vitro” or “in vivo” treatment with rIFN-γ, T cells from NOD–IFN-γ−/− mice became capable of homing to the prostate and induced leukocyte recruitment. Chemokine levels in prostate tissue from NOD mice showed increased expression levels of CXCR3 ligands. Additional experiments using adoptive transfer of sorted CXCR3+CD3+ T cells or administrating a CXCR3 antagonist treatment confirmed these previous results. Altogether, our results demonstrate that the expression of CXCR3 on effector T cells is essential for their homing to the prostate gland in EAP. CXCR3 emerges as a potential therapeutic target to control chronic prostatitis/chronic pelvic pain syndrome.
A Nonsense Polymorphism (R392X) in TLR5 Protects from Obesity but Predisposes to Diabetes
Authors: Al-Daghri Nasser M. , Clerici Mario , Al-Attas Omar , Forni Diego , Alokail Majed S. , Alkharfy Khalid M. , Sabico Shaun , Mohammed Abdul Khader , Cagliani Rachele , Sironi Manuela
Published: March 2013

The TLR5 gene encodes an innate immunity receptor. Mice lacking Tlr5 (T5KO) develop insulin resistance and increased adiposity. Owing to the segregation of a dominant nonsense polymorphism (R392X, rs5744168), a portion of humans lack TLR5 function. We investigated whether the nonsense polymorphism influences obesity and susceptibility to type 2 diabetes (T2D). R392X was genotyped in two cohorts from Saudi Arabia, a region where obesity and type 2 diabetes (T2D) are highly prevalent. The nonsense allele was found to protect from obesity (pcombined = 0.0062; odds ratio, 0.51) and to associate with lower body mass index (BMI) (pcombined = 0.0061); this allele also correlated with a reduced production of proinflammatory cytokines. A significant interaction was noted between rs5744168 and sex in affecting BMI (pinteraction = 0.006), and stratification by gender revealed that the association is driven by females (pcombined = 0.0016 and 0.0006 for obesity and BMI, respectively). The nonsense polymorphism also associated with BMI in nonobese women. After correction for BMI, the 392X allele was found to represent a risk factor for T2D with a sex-specific effect (pinteraction = 0.023) mediated by females (p = 0.021; odds ratio, 2.60). Fasting plasma glucose levels in nondiabetic individuals were also higher in women carrying the nonsense allele (p = 0.012). Thus, in contrast to T5KO mice, loss of human TLR5 function protects from weight gain, but in analogy to the animal model, the nonsense allele predisposes to T2D. These effects are apparently sex-specific. Data in this study reinforce the hypothesis that metabolic diseases, including T2D, are associated with immune dysregulation.
Reversion of Somatic Mutations of the Respiratory Syncytial Virus–Specific Human Monoclonal Antibody Fab19 Reveal a Direct Relationship between Association Rate and Neutralizing Potency
Authors: Bates John T. , Keefer Christopher J. , Utley Thomas J. , Correia Bruno E. , Schief William R. , Crowe James E.
Published: March 2013

The role of affinity in determining neutralizing potency of mAbs directed against viruses is not well understood. We investigated the kinetic, structural, and functional advantage conferred by individual naturally occurring somatic mutations in the Ab H chain V region of Fab19, a well-described neutralizing human mAb directed to respiratory syncytial virus. Comparison of the affinity-matured Ab Fab19 with recombinant Fab19 Abs that were variants containing reverted amino acids from the inferred unmutated ancestor sequence revealed the molecular basis for affinity maturation of this Ab. Enhanced binding was achieved through mutations in the third H chain CDR (HCDR3) that conferred a markedly faster on-rate and a desirable increase in antiviral neutralizing activity. In contrast, most somatic mutations in the HCDR1 and HCDR2 regions did not significantly enhance Ag binding or antiviral activity. We observed a direct relationship between the measured association rate (Kon) for F protein and antiviral activity. Modeling studies of the structure of the Ag–Ab complex suggested the HCDR3 loop interacts with the antigenic site A surface loop of the respiratory syncytial virus F protein, previously shown to contain the epitope for this Ab by experimentation. These studies define a direct relationship of affinity and neutralizing activity for a viral glycoprotein–specific human mAb.
Competition for Antigen at the Level of the APC Is a Major Determinant of Immunodominance during Memory Inflation in Murine Cytomegalovirus Infection
Authors: Farrington Lila A. , Smith Tameka A. , Grey Finn , Hill Ann B. , Snyder Christopher M.
Published: March 2013

The unique ability of CMV to drive the expansion of virus-specific T cell populations during the course of a lifelong, persistent infection has generated interest in the virus as a potential vaccine strategy. When designing CMV-based vaccine vectors to direct immune responses against HIV or tumor Ags, it becomes important to understand how and why certain CMV-specific populations are chosen to inflate over time. To investigate this, we designed recombinant murine CMVs (MCMVs) encoding a SIINFEKL-enhanced GFP fusion protein under the control of endogenous immediate early promoters. When mice were infected with these viruses, T cells specific for the SIINFEKL epitope inflated and profoundly dominated T cells specific for nonrecombinant (i.e., MCMV-derived) Ags. Moreover, when the virus encoded SIINFEKL, T cells specific for nonrecombinant Ags displayed a phenotype indicative of less frequent exposure to Ag. The immunodominance of SIINFEKL-specific T cells could not be altered by decreasing the number of SIINFEKL-specific cells available to respond, or by increasing the number of cells specific for endogenous MCMV Ags. In contrast, coinfection with viruses expressing and lacking SIINFEKL enabled coinflation of T cells specific for both SIINFEKL and nonrecombinant Ags. Because coinfection allows presentation of SIINFEKL and MCMV-derived Ags by different cells within the same animal, these data reveal that competition for, or availability of, Ag at the level of the APC determines the composition of the inflationary response to MCMV. SIINFEKL’s strong affinity for H-2Kb, as well as its early and abundant expression, may provide this epitope’s competitive advantage.
The Mechanism of Tissue-Restricted Antigen Gene Expression by AIRE
Authors: Žumer Kristina , Saksela Kalle , Peterlin B. Matija
Published: March 2013

The autoimmune regulator is a critical transcription factor for generating central tolerance in the thymus. Recent studies have revealed how the autoimmune regulator targets many otherwise tissue-restricted Ag genes to enable negative selection of autoreactive T cells.
Intercomparison of shortwave radiative transfer schemes in global aerosol modeling: results from the AeroCom Radiative Transfer Experiment
Authors: Randles C. A. , Kinne S. , Myhre G. , Schulz M. , Stier P. , Fischer J. , Doppler L. , Highwood E. , Ryder C. , Harris B. , Huttunen J. , Ma Y. , Pinker R. T. , Mayer B. , Neubauer D. , Hitzenberger R. , Oreopoulos L. , Lee D. , Pitari G. , Di Genova G. , Quaas J. , Rose F. G. , Kato S. , Rumbold S. T. , Vardavas I. , Hatzianastassiou N. , Matsoukas C. , Yu H. , Zhang F. , Zhang H. , Lu P.
Published: March 2013

Abstract. In this study we examine the performance of 31 global model radiative transfer schemes in cloud-free conditions with prescribed gaseous absorbers and no aerosols (Rayleigh atmosphere), with prescribed scattering-only aerosols, and with more absorbing aerosols. Results are compared to benchmark results from high-resolution, multi-angular line-by-line radiation models. For purely scattering aerosols, model bias relative to the line-by-line models in the top-of-the atmosphere aerosol radiative forcing ranges from roughly −10 to 20%, with over- and underestimates of radiative cooling at lower and higher solar zenith angle, respectively. Inter-model diversity (relative standard deviation) increases from ~10 to 15% as solar zenith angle decreases. Inter-model diversity in atmospheric and surface forcing decreases with increased aerosol absorption, indicating that the treatment of multiple-scattering is more variable than aerosol absorption in the models considered. Aerosol radiative forcing results from multi-stream models are generally in better agreement with the line-by-line results than the simpler two-stream schemes. Considering radiative fluxes, model performance is generally the same or slightly better than results from previous radiation scheme intercomparisons. However, the inter-model diversity in aerosol radiative forcing remains large, primarily as a result of the treatment of multiple-scattering. Results indicate that global models that estimate aerosol radiative forcing with two-stream radiation schemes may be subject to persistent biases introduced by these schemes, particularly for regional aerosol forcing.
Black carbon vertical profiles strongly affect its radiative forcing uncertainty
Authors: Samset B. H. , Myhre G. , Schulz M. , Balkanski Y. , Bauer S. , Berntsen T. K. , Bian H. , Bellouin N. , Diehl T. , Easter R. C. , Ghan S. J. , Iversen T. , Kinne S. , Kirkevåg A. , Lamarque J.-F. , Lin G. , Liu X. , Penner J. E. , Seland Ø. , Skeie R. B. , Stier P. , Takemura T. , Tsigaridis K. , Zhang K.
Published: March 2013

Abstract. The impact of black carbon (BC) aerosols on the global radiation balance is not well constrained. Here twelve global aerosol models are used to show that at least 20% of the present uncertainty in modeled BC direct radiative forcing (RF) is due to diversity in the simulated vertical profile of BC mass. Results are from phases 1 and 2 of the global aerosol model intercomparison project (AeroCom). Additionally, a significant fraction of the variability is shown to come from high altitudes, as, globally, more than 40% of the total BC RF is exerted above 5 km. BC emission regions and areas with transported BC are found to have differing characteristics. These insights into the importance of the vertical profile of BC lead us to suggest that observational studies are needed to better characterize the global distribution of BC, including in the upper troposphere.