Intelligent transportation systems are designed to provide innovative applications and services relating to traffic management, as well as to facilitate the access to information for other systems ...and users. The compelling motivation for employing underutilized onboard resources for transportation systems and the advancements in management technology for Cloud computing resources has promoted the concept of Vehicular Clouds. This work gathers and describes the most recent approaches and solutions for Vehicular Clouds, featuring applications, services, and traffic models that can enable Vehicular Cloud in a more dynamic environment. We have considered a large number of applications and services that showed relevance in the scope of the transportation system, benefiting its management, drivers, passengers, and pedestrians. Nevertheless, the high traffic mobility imposes as a significant challenge in implementing a Vehicular Cloud on continually changing physical resources. The dynamics of the environment bring fundamental issues and increase the complexity of building this new type of Cloud. By analyzing the existing traffic models, we found that Vehicular Cloud computing is technologically feasible not just in the static environment, like a parking lot or garage where vehicles are stationary, but also the dynamic scenarios, such as highways or streets where vehicles move.
Mobile Cloud Computing (MCC) has been extensively explored to be applied as a vital tool to enhance the capabilities of mobile devices, increasing computing power, expanding storage capacity, and ...prolonging battery life. Offloading works as the fundamental feature that enables MCC to relieve task load and extend data storage through an accessible cloud resource pool. Several initiatives have drawn attention to delivering MCC-supported energy-oriented offloading as a method to cope with a lately steep increase in the number of rich mobile applications and the enduring limitations of battery technologies. However, MCC offloading relieves only the burden of energy consumption of mobile devices; performance concerns about Cloud resources, in most cases, are not considered when dynamically allocating them for dealing with mobile tasks. The application context of MCC, encompassing urban computing, aggravates the situation with very large-scale scenarios, posing as a challenge for achieving greener solutions in the scope of Cloud resources. Thus, this article gathers and analyzes recent energy-aware offloading protocols and architectures, as well as scheduling and balancing algorithms employed toward Cloud green computing. This survey provides a comparison among system architectures by identifying their most notable advantages and disadvantages. The existing enabling frameworks are categorized and compared based on the stage of the task offloading process and resource management types, describing current open challenges and future research directions.
The ATLAS trial compared axitinib versus placebo in patients with locoregional renal cell carcinoma (RCC) at risk of recurrence after nephrectomy.
In a phase III, randomized, double-blind trial, ...patients had >50% clear-cell RCC, had undergone nephrectomy, and had no evidence of macroscopic residual or metastatic disease independent review committee (IRC) confirmed. The intent-to-treat population included all randomized patients ≥pT2 and/or N+, any Fuhrman grade (FG), Eastern Cooperative Oncology Group status 0/1. Patients (stratified by risk group/country) received (1 : 1) oral twice-daily axitinib 5 mg or placebo for ≤3 years, with a 1-year minimum unless recurrence, occurrence of second primary malignancy, significant toxicity, or consent withdrawal. The primary end point was disease-free survival (DFS) per IRC. A prespecified DFS analysis in the highest-risk subpopulation (pT3, FG ≥ 3 or pT4 and/or N+, any T, any FG) was conducted.
A total of 724 patients (363 versus 361, axitinib versus placebo) were randomized from 8 May 2012, to 1 July 2016. The trial was stopped due to futility at a preplanned interim analysis at 203 DFS events. There was no significant difference in DFS per IRC hazard ratio (HR) = 0.870; 95% confidence interval (CI) : 0.660–1.147; P = 0.3211). In the highest-risk subpopulation, a 36% and 27% reduction in risk of a DFS event (HR; 95% CI) was observed per investigator (0.641; 0.468–0.879; P = 0.0051), and by IRC (0.735; 0.525–1.028; P = 0.0704), respectively. Overall survival data were not mature. Similar adverse events (AEs; 99% versus 92%) and serious AEs (19% versus 14%), but more grade 3/4 AEs (61% versus 30%) were reported for axitinib versus placebo.
ATLAS did not meet its primary end point; however, improvement in DFS per investigator was seen in the highest-risk subpopulation. No new safety signals were reported.
NCT01599754
Highlights • BTK is a TEC-family kinases member, expressed in lymphocytes and other cell subtypes. • TEC kinases inhibition by Ibrutinib has promising results in cancer cellular models. • Ibrutinib ...is able to modify the tumor microenvironment with therapeutic implications. • BTK inhibitors may have synergistic effect with other active drugs in solid tumors.
The present paper aims at developing a simple but effective numerical model for the study of the bond behavior of Fiber Reinforced Strengthening systems (FRP) externally applied on curved masonry ...substrates. The main peculiarities of the proposed model are its simplicity and the possibility to straightforwardly introduce at the interface level coupled cohesive laws for accounting a mixed mode debonding mechanism. Indeed, the model relies on a discretization based on in-series and in-parallel springs for modeling the substrate, the reinforcement and the reinforcement/substrate interface layer. In particular, while both the substrate and the reinforcement springs are assumed linear-elastic, nonlinear constitutive laws are accounted for the interface springs where, in addition, a coupled behavior between normal and shear springs is assumed considering the Mohr-Coulomb failure domain. The proposed numerical model is used in the paper as a tool for the assessment of formulas specifically devoted to the evaluation of the bond resistance of curved masonry samples strengthened with FRPs. In particular, both formulas derived from the closed form solution of equilibrium equations and a formula derived by approximating the closed form solution through an exponential law are here presented. With the main purpose to validate the proposed model, numerical analyses are preliminary presented in the paper with reference to experimental bond tests on masonry samples with concave and convex substrate configurations strengthened by glass FRP strips. Then, further numerical analyses developed by considering different values of the geometry curvature and mechanical properties of the interface, are subsequently developed with the main goal to check the reliability of the proposed formulas.
The management of advanced neuroendocrine tumors (NETs) has recently changed. We assessed the activity of pazopanib after failure of other systemic treatments in advanced NETs.
This was a ...multicenter, open-label, phase II study evaluating pazopanib as a single agent in advanced NETs (PAZONET study). The clinical benefit rate (CBR) at 6 months was the primary end point. Translational correlation of radiological response and progression-free survival (PFS) with circulating and tissue biomarkers was also evaluated.
A total of 44 patients were enrolled. Twenty-five patients (59.5%) were progression-free at 6 months (4 partial responses, 21 stable diseases) with a median PFS of 9.5 months 95% confidence interval (CI) 4.8-14.1. The CBR varied according to prior therapy received, with 73%, 60% and 25% in patients treated with prior multitarget inhibitors, prior mTOR inhibitors and both agents, respectively. A nonsignificant increase in PFS was observed in patients presenting lower baseline circulating tumor cell (CTC) counts (9.1 versus 5.8 months; P = 0.22) and in those with decreased levels of soluble-vascular endothelial growth factor receptor-2 (sVEGFR-2) (12.6 versus 9.1 months; P = 0.067). A trend toward reduced survival was documented in patients with VEGFR3 rs307821 and rs307826 missense polymorphisms hazard ratio (HR): 12.3; 95% CI 1.09-139.2; P = 0.042 and HR: 6.9; 95% CI 0.96-49.9; P = 0.055, respectively.
Pazopanib showed clinical activity in patients with advanced NETs regardless of previous treatments. Additionally, CTCs, soluble-s VEFGR-2 and VEGFR3 gene polymorphisms constitute potential biomarkers for selecting patients for pazopanib (NCT01280201).
NCT01280201.
Recombinant adeno-associated virus (rAAV) is a leading gene therapy vector. However, neutralizing antibodies reduce its efficacy. Traditional methods used to investigate antibody binding provide ...limited information. Here, charge detection mass spectrometry (CD-MS) was used to investigate the binding of monoclonal antibody ADK8 to AAV serotype 8 (AAV8). CD-MS provides a label-free approach to antibody binding. Individual binding events can be monitored as each event is indicated by a shift of the antibody–antigen complex to a higher mass. Unlike other methods, the CD-MS approach reveals the distribution of antibodies bound on capsids, allowing AAV8 subpopulations with different affinities to be identified. The charge state generated by the electrospray of large ions is normally correlated with the structure, and the charge is expected to increase when an antibody binds to the capsid exterior. Surprisingly, binding of the first ADK8 to AAV8 causes a substantial decrease in the charge, suggesting that the first antibody binding event causes a significant structural change. The charge increases for subsequent binding events. Finally, high ADK8 concentrations cause agglutination, where ADK8 links AAV capsids to form dimers and higher order multimers.
Doenças do sistema nervoso de bovinos no semiárido nordestino Galiza, Glauco J.N.(Universidade Federal de Campina Grande Centro de Saúde e Tecnologia Rural); Silva, Maria L.C.R.(Universidade Federal de Campina Grande Centro de Saúde e Tecnologia Rural); Dantas, Antônio F.M.(Universidade Federal de Campina Grande Centro de Saúde e Tecnologia Rural) ...
Pesquisa Veterinária Brasileira,
2010, Volume:
30, Issue:
3
Journal Article
Peer reviewed
Open access
Para determinar as doenças que ocorrem no sistema nervoso de bovinos no semiárido nordestino, foi realizado um estudo retrospectivo em 411 necropsias de bovinos realizadas no Hospital Veterinário da ...Universidade Federal de Campina Grande, Patos, Paraíba, entre janeiro de 2000 a dezembro de 2008. Dos 411 casos analisados 139 (33,81%) apresentaram alterações clínicas do sistema nervoso e as fichas foram revisadas para determinar os principais achados referentes à epidemiologia, aos sinais clínicos e às alterações macroscópicas e microscópicas. Em 28 (20,14%) casos o diagnóstico foi inconclusivo. As principais enfermidades foram raiva (48,7% dos casos com sinais nervosos), abscessos cerebrais (7,2%) incluindo três casos de abscesso da pituitária, febre catarral maligna (6,3%), botulismo (6,3%), alterações congênitas (4,5%), traumatismo (4,5%), tuberculose (2,7%), tétano (2,7%), infecção por herpesvírus bovino-5 (2,7%), encefalomielite não supurativa (2,7%), intoxicação por Prosopis juliflora (2,7%), status spongiosus congênito de causa desconhecida (1,8%) e polioencefalomalacia (1,8%). Outras doenças diagnosticadas numa única oportunidade (0,9%) foram criptococose, listeriose, encefalite tromboembólica, linfossarcoma, tripanossomíase e babesiose por Babesia bovis.
Diseases of the nervous system of cattle in the semiarid region of northeastern Brazil were evaluated by a retrospective study of 411 cattle necropsies performed in the Veterinary Hospital of the Federal University of Campina Grande, Patos, Paraíba, from January 2000 to December 2008. Of the 411 cases analyzed, 139 (33.81%) were from cattle that presented nervous signs and the records were reviewed to determine the epidemiological, clinical, and macroscopic and histologic main features. Diagnosis was inconclusive in 28 cases (20.14%). In cases with diagnosis the main diseases were rabies (48.7% of the cases with nervous signs), brain abscesses (7.2%) including three cases of pituitary abscesses, malignant catarrhal fever (6.3%), botulism (6.3%), congenital malformations (4.5%), trauma (4.5%), tuberculosis (2.7%), tetanus (2.7%), infection by bovine hervesvirus-5 (2.7%), non-suppurative encephalomyelitis (2.7%), intoxication by Prosopis juliflora (2.7%), congenital status spongiosus of unknown etiology (1.8%), and polioencephalomalacia (1.8%). Other diseases diagnosed only once (0.9%) were cryptococcosis, listeriosis, thromboembolic encephalitis, lymphosarcoma, trypanosso-miasis, and babesiosis by Babesia bovis.
Resumen: Objetivo: Determinar si existen diferencias en la prevalencia del uso de fármacos para la osteoporosis entre pacientes diabéticos tipo 2 (DM2) y no diabéticos. Material y método: Estudio de ...cohortes retrospectivas con datos del Sistema de Información para el Desarrollo de la Investigación en Atención Primaria (SIDIAP), que contiene información clínica anonimizada de más de 5 millones de pacientes de Cataluña. Se seleccionaron todos los pacientes de ≥50 años de edad con diagnóstico de DM2, que fueron apareados con dos sujetos sin diabetes. Se recogió información sobre variables descriptivas, fracturas prevalentes y el uso de fármacos para la osteoporosis agrupados en bifosfonatos (BF), suplementos calcio y vitamina D (CaD), y cualquier fármaco para la osteoporosis (FPO). Mediante regresión logística se calculó la asociación entre la presencia de DM2 y el uso de FPO, ajustando por variables confusoras. Resultados: Se identificaron 166.106 pacientes con DM2 y 332.212 no diabéticos. Los DM2 tenían mayor prevalencia de fractura que los no diabéticos (1,3% vs. 0,3%). El uso de BF en los pacientes con DM2 era del 6,6%, frente al 9,3% en los no diabéticos (p<0,001); de CaD, 9,7% vs. 12,3% (p <0,001); y de FPO, 7,6% vs. 10,7% (p<0,001). Tras ajustar por variables confusoras, los pacientes con DM2 presentaban menor probabilidad de ser tratados con BF (OR=0,67; IC95%: 0,64-0,68), con CaD (OR=0,71; IC95 %: 0,70-0,73) o con FPO (OR=0,66; IC95%: 0,64-0,67) que los no diabéticos. Conclusiones: A pesar de presentar una mayor prevalencia de fracturas previas, los pacientes con DM2 tienen más del 30% de probabilidad de no recibir un FPO que los no diabéticos. Esto podría ser debido a una infravaloración del riesgo en estos pacientes.
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