Treatment of Open-Angle Glaucoma and Ocular Hypertension with Preservative-Free Tafluprost/Timolol Fixed-Dose Combination Therapy : The VISIONARY Study

Funding Information: Funding was provided by Santen SA for the study, medical writing services and Rapid Service Fees. All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis. The contribution of IRCCS Fondazione Bietti to this work was supported by the Italian Ministry of Health and by Fondazione Roma. Publisher Copyright: © 2020, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Introduction: A non-interventional, multicenter, European, prospective evaluation of the effectiveness, tolerability, and safety of a topical preservative-free tafluprost (0.0015%) and timolol (0.5%) fixed-dose combination (PF tafluprost/timolol FC) in adults with open-angle glaucoma (OAG) and ocular hypertension (OHT) demonstrating insufficient response to topical beta-receptor blockers or prostaglandin analogue (PGA) monotherapy. Methods: Mean intraocular pressure (IOP) change from baseline was measured at study visits following a switch to PF tafluprost/timolol FC. Primary endpoint was absolute mean IOP change at month 6. Change from baseline concerning ocular signs and symptoms was also explored. Results: Analyses included 577 patients (59.6% female). Mean age (SD) was 67.8 (11.67) years. Mean (SD) IOP reduction from baseline was significant at all study visits; 5.4 (3.76) mmHg (23.7%) at week 4, 5.9 (3.90) mmHg (25.6%) at week 12, and 5.7 (4.11) mmHg (24.9%) at month 6 (p < 0.0001 for all visits). At month 6, 69.2%, 53.6%, 40.0%, and 25.8% were responders based on ≥ 20%, ≥ 25%, ≥ 30%, and ≥ 35% cutoff values for mean IOP, respectively. Significant reductions were observed concerning corneal fluorescein staining (p < 0.0001), dry eye symptoms, irritation, itching, and foreign body sensation (p < 0.001 for each parameter). Conjunctival hyperemia was significantly reduced at all study visits (p < 0.0001 at each visit). Overall, 69 treatment-related adverse events (AEs) were reported, one of which was serious (status asthmaticus). Most AEs were mild to moderate in severity, and the majority had resolved or were resolving at the end of the study period. Conclusion: In clinical practice, PF tafluprost/timolol FC provided statistically and clinically significant IOP reductions in patients with OAG and OHT insufficiently controlled on or intolerant to PGA or beta-receptor blocker monotherapy. The full IOP reduction appeared at week 4 and was maintained over the 6-month study period. Key symptoms of ocular surface health improved. Trial Registration: European Union electronic Register of Post-Authorisation Studies (EU PAS) register number, EUPAS22204.publishersversionPeer reviewe

State of the art in the determination of the fine structure constant and the ratio h/muh/m_\mathrm{u}

The fine structure constant $\alpha$ and the ratio $h/m_{\mathrm{u}}$ between the Planck constant and the unified atomic mass are keystone constants for the determination of other fundamental physical constants, especially the ones involved in the framework of the future International System of units. This paper presents how these two constants, which can be deduced from one another, are measured. We will present in detail the measurement of $h/m_\mathrm{Rb}$ performed by atomic interferometry at the Laboratoire Kastler Brossel in Paris. This type of measurement also allows a test of the standard model to be carried out with unparalleled accuracy.Comment: arXiv admin note: text overlap with arXiv:1309.339

X86_64 vs Aarch64 Performance Validation with COTSon

In this study, we provide a set of architectural parameters for the HPLabs COTSon simulator that can be used to model existing processors, such as the Intel i7700 (X86_64 architecture) and the ARM A53 (Aarch64 architecture). We carry out an initial validation, by comparing the execution time while performing the weak scaling of the architecture, in the case of two common benchmarks. We use the Recursive Fibonacci and Matrix Multiplication benchmarks for simplicity. By using the simulator, we can then further study the sensitivity of the architecture and derive which features may matter most to evaluate the performance. Our goal here is to verify that the COTSon simulator can be used to model both the X86_64 and Aarch64 architectures. Based on this validation study, we have the possibility to analyze the bottlenecks and desirable microarchitectural features of modern architectures

O ESTÁGIO CURRICULAR DO CURSO DE BACHARELADO EM EDUCAÇÃO FÍSICA NA PERCEPÇÃO DE ACADÊMICOS

A pesquisa teve por objetivo verificar a percepção de acadêmicos de um curso de bacharelado em Educação Física acerca de suas intervenções no estágio curricular. Trata-se de um estudo de caso e a opção metodológica foi pela pesquisa descritiva. A amostra contou com 56 acadêmicos da Universidade Estadual de Maringá (UEM) – Campos Sede. Foi empregado um questionário, e os dados foram tratados com base na estatística descritiva e a partir dos indicativos da análise de conteúdo. Como resultados, verificaram-se saberes abordados na graduação que precisam ser mais bem desenvolvidos por serem considerados pertinentes à atuação no estágio curricular, como os recursos metodológicos e a coordenação das relações profissionais. Outras dimensões que foram indicadas como relevantes são o planejamento e os elementos conceituais e didáticos. Conclui-se que há necessidade de os cursos analisarem continuamente suas propostas curriculares, tendo em vista um processo formativo condizente com as demandas profissionais

Divergent Trends of Anti-JCPyV Serum Reactivity and Neutralizing Activity in Multiple Sclerosis (MS) Patients during Treatment with Natalizumab

The association between natalizumab and progressive multifocal leukoencephalopathy (PML) is established, but a reliable clinical risk stratification flow-chart is lacking. New risk factors are needed, such as the possible role of the anti-JC polyomavirus (JCPyV) neutralizing antibody. In this pilot study, we analyzed this parameter during natalizumab treatment. Sequential sera of 38 multiple sclerosis patients during their first year of natalizumab treatment were collected, and grouped according to the number of infusions. For 11 patients, samples were also available after 24 infusions (T24), when progressive multifocal leukoencephalopathy (PML) risk is higher. The reactivity against VP1, the main JCPyV surface protein, and the anti-JCPyV neutralizing activity were evaluated. During the first year, a lack of correlation between anti-JCPyV antibody response and its neutralizing activity was observed: a significant decrease in anti-JCPyV antibody response was observed (p = 0.0039), not paralleled by a similar trend in the total anti-JCPyV neutralizing activity (p = 0.2239). This lack of correlation was even more evident at T24 when, notwithstanding a significant increase in the anti-JCPyV response (p = 0.0097), a further decrease of the neutralizing activity was observed (p = 0.0062). This is the first study evidencing, prospectively, the lack of correlation between the anti-JCPyV antibody response and its neutralizing activity during natalizumab treatment

PreserFlo® MicroShunt: an overview of this minimally invasive device for open-angle glaucoma

For moderate-to-severe glaucoma, trabeculectomy remains the “gold standard” intraocular pressure (IOP)-lowering treatment; nonetheless, this method requires extensive post-operative maintenance. Microinvasive glaucoma surgery (MIGS) treatments are designed to lessen intra- and post-operative care burden while offering an acceptable IOP decrease for individuals with mild to moderate glaucoma. The PreserFlo® MicroShunt (previously InnFocus MicroShunt) is an 8.5 mm glaucoma drainage device manufactured from poly(styrene-block-isobutylene-block-styrene) (SIBS), an extremely biocompatible and bioinert material. The lumen is narrow enough to prevent hypotony, but big enough to avoid being obstructed by sloughed cells or pigment. The device is implanted ab externo, as a stand-alone procedure or in conjunction with cataract surgery, with intraoperative mitomycin C, and a bleb is produced under the conjunctiva and Tenon’s capsule. The MicroShunt was CE-marked in 2012 and designed for primary open-angle glaucoma, the IOP of which remains uncontrolled after maximally tolerated topical treatment. Several clinical trials evaluating the MicroShunt’s long-term safety and effectiveness have been conducted, highlighting the effectiveness of the device over time, along with a tolerable safety profile. The present review aims to gather evidence of PreserFlo’s effectiveness and safety results almost 10 years after its introduction, and furthermore, to compare it with other MIGS and with the gold-standard trabeculectomy for glaucoma management