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The outcomes of patients with metastatic melanoma (MM) have significantly improved after the introduction of BRAF-specific inhibitors. Herein is reported a patient with MM and non-V600-BRAF mutation who responded to iBRAF/iMEK therapy. In July 2014, a 63-year-old man presented with a 4.1mm-thick V600E-BRAF wild type melanoma on the back. Metastases were identified in one sentinel node and two of 11 subsequently excised lymph nodes, with no signs of distant metastatic disease. In September 2017, lung metastasis was observed and pembrolizumab was started. Progressive disease was apparent at cycle 10 and therapy was switched to ipilimumab. After four cycles, an asymmetric response was observed. In November 2017, next generation sequencing genomic profiling disclosed a rare L597K-BRAF mutation and vemurafenib plus cobimetinib therapy was initiated in January 2018. Seven days after treatment start, a remarkable clinical improvement was observed. In April 2018, the patient achieved partial response, which was sustained until October 2018. Cases of patients with non-V600-BRAF mutations responding to iBRAF/iMEK therapy have been reported over the last years. To the best of our knowledge, this is the first case reporting response to combined iBRAF/iMEK therapy in a patient with metastatic melanoma harboring L597K mutation.

Rickettsia monacensis, spotted fever group rickettsiae (SFGR), are bacteria transmitted by Ixodes spp. ticks and are rarely reported as causing disease in humans. Few cases have been documented and laboratory [...]

The aim of this study was to determine the liquid-liquid equilibrium data for a ternary system of water, ethyl acetate and oil from the microalgae Scenedesmus obliquus at 298.15, 308.15, and 318.15 K. The potential of the ternary system was also investigated for the selective extraction of free fatty acids and neutral lipids from crude microalgae oil. The equilibrium data were obtained using a model oil formulated from a mixture of refined vegetable oils, with a fatty acid profile analogous to the dark and opaque algae oil. The experimental equilibrium curves and tie lines were provided as a function of temperature for a free fatty acid content of 2%, 20% and 40% (w/w). The free fatty acids in the model oil migrated preferentially to the ethyl acetate-rich phase in each of the systems under study, with extraction efficiencies ranging from 79.4% to 97.1%. However, the extraction efficiencies for the neutral lipids were lower (51.5–70.1%), indicating the preferential extraction of free fatty acids. The distribution coefficients of neutral lipids (1.06–2.34) and free fatty acids (3.85–33.2) were determined in order to better understand the selectivity of the green solvent, ethyl acetate, in the purification of crude oil from algae. The selectivity values varied from 1.84 to 28.6, indicating that the solvent was effective in concentrating neutral lipids and free fatty acids in the ethyl acetate-rich phase. The increase in free fatty acid content therefore reduced the partition coefficient for neutral lipids, improving its selectivity, and making it possible to concentrate this lipid class by liquid-liquid separation with ethyl acetate. [ABSTRACT FROM AUTHOR]

In recent decades, neoliberal logics have affected the teaching profession and, consequently, had a direct impact on teachers' professionalism. The aim of this paper was to conduct a literature review to determine the most significant arguments and debates about teacher professionalism in the last 10 years and its relation to a transformative teacher attitude. Therefore, relevant review studies from 2011 to 2021 were analysed in order to respond to the following questions: "how can current scholarly publishing within teacher professionalism inform a transformative vision of education? What are the main themes identified and how do they relate in order to inform teachers' professionalism?". The themes of 'professionalism' and 'agency' are central to the current scientific debate, interconnected with the issues of professional development, leadership, and research. This paper hereby provides insight into alternative paths towards the (re)professionalisation of teachers, which response can be a 'transformative professionalism' framed by the interconnection of professionalism and agency. The process of continuous professional development in the context of autonomy appears as the elected form for this process of re-professionalisation and agency. School leadership and teachers' research emerge as opportunities for professional development with these characteristics. [ABSTRACT FROM AUTHOR]

Objective: We assessed and compared molecular tissue changes at the entheses in patients with psoriasis (PsO) and psoriatic arthritis (PsA) and in healthy controls (HCs) in vivo using multispectral optoacoustic tomography (MSOT) and described their relationship with clinical and ultrasound findings of enthesitis. Methods: A cross‐sectional study (MSOT and Arthrosonography in PsA) in biologic disease‐modifying antirheumatic drug–naïve patients with PsA and PsO and HCs was performed. Participants underwent clinical, ultrasonographic, and MSOT examination of six entheses (lateral humeral epicondyle, distal patellar tendon attachment, and Achilles tendon attachment). MSOT‐measured hemoglobin (Hb), oxygen saturation (SO2), collagen, and lipid levels were quantified, and mean differences between groups were calculated using linear mixed effects models. MSOT‐measured analytes were compared between entheses with and without clinical and ultrasound anomalies. Results: Ninety participants were included (30 PsO, 30 PsA, and 30 HCs), 540 entheses were clinically assessed, and 540 ultrasound and 830 MSOT scans were obtained. Patients with PsA and PsO showed increased oxygenated Hb (PsA: P = 0.003; PsO: P = 0.054) and SO2 (PsA: P < 0.001; PsO: P = 0.001) levels and decreased collagen signals (PsA: P < 0.001; PsO: P < 0.001) compared with HCs, with more pronounced changes in PsA. Significantly lower collagen levels (P = 0.01) and increased lipids (P = 0.03) were recorded in tender entheses compared with nontender ones. Erosions and enthesophytes on ultrasound were associated with significant differences in SO2 (P = 0.014) and lipid signals (P = 0.020), respectively. Conclusion: Patients with PsA and PsO exhibit an analogous metabolic pattern at the entheses that is exacerbated in the presence of inflammation. These findings support the notion of a psoriatic disease spectrum characterized by common immunometabolic tissue changes. [ABSTRACT FROM AUTHOR]

This study aimed to emphasize the significance of spatial variability in soil strength parameters on the behavior of nailed walls, highlighting the necessity of probabilistic design approaches. The investigation involved a 7.2-m nailed wall reinforced with five nails, simulated using the local average subdivision random field theory combined with the limit equilibrium method and the FEM, known as the random limit equilibrium method (RLEM) and the random finite-element method (RFEM) approaches. Initially, the wall stability was evaluated by RLEM using 10,000 Latin hypercube sampling realizations. The wall was globally stable among all samples for a correlation length equal to its height (7.2 m). The wall behavior, associated displacements, moments, wall shear forces, nail axial forces, and ground settlements were examined using RFEM. The RFEM analysis reveals that different random fields influence the maximum displacement (Hmax), maximum moment (Mmax), and maximum shear force (Vmax) experienced by the wall. The cumulative distribution function plots were generated for the wall critical parameters, including Hmax, Mmax, and Vmax. Leveraging the simple weighted averaging and ordered weighted averaging techniques, different combinations of Hmax, Mmax, and Vmax were assessed with varying weight assumptions. This allowed us to identify critical random field realizations and estimate the level of risk using a newly introduced parameter, the decision index. Finally, the effect of different correlation lengths (isotropic and anisotropic) for two different coefficients of variation of soil strength parameters on the distribution of Hmax, Mmax, and Vmax was studied. The findings highlight the importance of considering the spatial variability of soil properties to achieve a reliable design of nailed walls. [ABSTRACT FROM AUTHOR]

The quality of how teachers are being prepared is seen as a priority in the twenty-first century and engagement with research is often considered a crucial element of initial teacher education programmes. Institutional and national contexts have an impact in the way research is valued. This paper investigates the perspectives of Portuguese and English teacher educators towards the value given to research in initial teacher education. Interviews were completed with teacher educators working within different kinds of higher education institutions--university, polytechnic and teaching-led university. Results suggest that research has a significant presence and relevance in all cases but is valued differently.