Transdisciplinarity in strategic decisions for oncological treatments

The current models for equity and access to new oncological treatments are under strain due to the economic and demographic crisis in Europe as well as the rising costs of innovative drugs. Cancer treatment needs a model of patient-centered care in which an interdisciplinary care plan, based on evidence-based practice is essential for patient wellbeing. Physicians should be focused in the doctor-patient relationship and informed consent is important, especially when new medicines are prescribed. Related with informed consent, there is therapeutic privilege. Moreover, utilitarianism and social justice have to be considered without compromising human dignity and the principle of economy cannot be ignored in the provision of public services. An interdisciplinary approach is essential for the new oncological drugs approval. Therefore, transdisciplinary decision between civil society, pharmaceuticals, healthcare professionals and policy makers is essential in order to assure quality, access to innovation and equity in oncological care.info:eu-repo/semantics/acceptedVersio

Impact of the economic crisis in the approval of new oncological drugs:the Portuguese paradigm

Background: The European crisis lead to funding restrains in healthcare, already under pressure due to the ageing of the population and the increase of demands from innovation. Portugal is the paradigm of the European crisis since has both an economic and demographic crisis. The researchers aimed to evaluate the impact of economic restrains in Portugal for access and reimbursement of new oncological drugs. Methodology: A qualitative approach was used, supported by 27 formal, tape recorded, semi-structured interviews to representatives of the different healthcare stakeholders and policymakers. The content analysis with semantic associations through co-occurrence analysis were done with the support of Tropes® software. Results: The results of the content analysis showed that economic restrains are leading to a policy of cost control with lower prices and reduced access to innovation; an excessive delay in the approval of new drugs; lack of transparency; serious limitations and inequity between hospitals. Contractual boundaries to national prescription was established and agreements with pharmaceuticals were made. Changes in the reimbursement process are being implemented with an increase of risk sharing mechanisms and implementation of a new system of health technological evaluation (SINATS). Treatment protocols are also being revised and public hospitals are trying to increase the number of clinical trials but there is still much bureaucracy. In this qualitative approach, the following factors with impact on survival were identified: Innovation and technological development, government funding, the price of drugs and type of oncological diseases. Conclusions: The economic crisis is leading to a very serious problem of inequity. However, it is also an opportunity for a structural reform. In Portugal, an attempt of reform is being made with the implementation of SINATS since it is important to distinguish molecules that effectively bring added value. In order to consider the strategic vision in which the patient is the center of all efforts, the process of reimbursement approval for new medicines should be faster, more transparent and interdisciplinary. Moreover, the decisions must be done triangulating evidence based medicine, economics, health policy and ethical and legal issues. For National Health Service sustainability, efficiency and efficacy, clinical and economic reassessments must be done after market introduction of new medicines, with subsequent renegotiations.info:eu-repo/semantics/publishedVersio

Understanding the complex phase diagram of uranium: the role of electron-phonon coupling

We report an experimental determination of the dispersion of the soft phonon mode along [1,0,0] in uranium as a function of pressure. The energies of these phonons increase rapidly, with conventional behavior found by 20 GPa, as predicted by recent theory. New calculations demonstrate the strong pressure (and momentum) dependence of the electron-phonon coupling, whereas the Fermi-surface nesting is surprisingly independent of pressure. This allows a full understanding of the complex phase diagram of uranium, and the interplay between the charge-density wave and superconductivity

Temperature and pressure-induced spin-state transitions in LaCoO3

We report the continuous variation of the spin moment of cobalt in LaCoO3 across its temperature and pressure-induced spin transitions evidenced with K\beta emission spectra. The first thermal transition is best described by a transition to an orbitally nondegenerate intermediate spin (S=1) state. In parallel, continuous redistribution of the 3d electrons is also indicated by partial fluorescence yield X-ray absorption spectra. At high pressure, our study confirms that the material becomes low spin between 40 and 70 kbar at room temperature

K-edge X-ray absorption spectra in transition metal oxides beyond the single particle approximation: shake-up many body effects

The near edge structure (XANES) in K-edge X-ray absorption spectroscopy (XAS) is a widely used tool for studying electronic and local structure in materials. The precise interpretation of these spectra with the help of calculations is hence of prime importance, especially for the study of correlated materials which have a complicated electronic structure per se. The single particle approach, for example, has generally limited itself to the dominant dipolar cross-section. It has long been known however that effects beyond this approach should be taken into account, both due to the inadequacy of such calculations when compared to experiment and the presence of shake-up many-body satellites in core-level photoemission spectra of correlated materials. This effect should manifest itself in XANES spectra and the question is firstly how to account for it theoretically and secondly how to verify it experimentally. By using state-of-the-art first principles electronic structure calculations and 1s photoemission measurements we demonstrate that shake-up many-body effects are present in K-edge XAS dipolar spectra of NiO, CoO and CuO at all energy scales. We show that shake-up effects can be included in K-edge XAS spectra in a simple way by convoluting the single-particle first-principles calculations including core-hole effects with the 1s photoemission spectra. We thus describe all features appearing in the XAS dipolar cross-section of NiO and CoO and obtain a dramatic improvement with respect to the single-particle calculation in CuO. These materials being prototype correlated magnetic oxides, our work points to the presence of shake-up effects in K-edge XANES of most correlated transition metal compounds and shows how to account for them, paving the way to a precise understanding of their electronic structure.Comment: 6 pages, 4 picture

The influence of dna repair genes variants

Funding: This research was funded by FCT—Fundação para a Ciência e a Tecnologia (Portuguese Foundation for Science and Technology) through Project UID/BIM/00009/2019—Centre for Toxicogenomics and Human Health.Radioiodine therapy with131I remains the mainstay of standard treatment for well-differentiated thyroid cancer (DTC). Prognosis is good but concern exists that131I-emitted ionizing radiation may induce double-strand breaks in extra-thyroidal tissues, increasing the risk of secondary malignancies. We, therefore, sought to evaluate the induction and 2-year persistence of micronuclei (MN) in lymphocytes from 26131I-treated DTC patients and the potential impact of nine homologous recombination (HR), non-homologous end-joining (NHEJ), and mismatch repair (MMR) polymorphisms on MN levels. MN frequency was determined by the cytokinesis-blocked micronucleus assay while genotyping was performed through pre-designed TaqMan® Assays or conventional PCR-restriction fragment length polymorphism (RFLP). MN levels increased significantly one month after therapy and remained persistently higher than baseline for 2 years. A marked reduction in lymphocyte proliferation capacity was also apparent 2 years after therapy. MLH1 rs1799977 was associated with MN frequency (absolute or net variation) one month after therapy, in two independent groups. Significant associations were also observed for MSH3 rs26279, MSH4 rs5745325, NBN rs1805794, and tumor histotype. Overall, our results suggest that131I therapy may pose a long-term challenge to cells other than thyrocytes and that the individual genetic profile may influence131I sensitivity, hence its risk-benefit ratio. Further studies are warranted to confirm the potential utility of these single nucleotide polymorphisms (SNPs) as radiogenomic biomarkers in the personalization of radioiodine therapy.publishersversionpublishe

Valence state of Mn in Ca-doped LaMnO3 studied by high-resolution Mn K ß emission spectroscopy

Mn K ß x-ray emission spectra provide a direct method to probe the effective spin state and charge density on the Mn atom and is used in an experimental study of a class of Mn oxides. Specifically, the Mn K ß line positions and detailed spectral shapes depend on the oxidation and the spin state of the Mn sites as well as the degree of d covalency/itinerancy. Theoretical calculations including atomic charge and multiplet effects, as well as crystal-field splittings and covalency effects, are used as a guide to the experimental results. Direct comparison of the ionic system MnF2 and the covalent system MnO reveals significant changes due to the degree of covalency of Mn within atomic-type Mn K ß simulations. Moreover, comparisons of measurement with calculations support the assumed high spin state of Mn in all of the systems studied. The detailed shape and energy shift of the spectra for the perovskite compounds, LaMnO3 and CaMnO3, are, respectively, found to be very similar to the covalent Mn^(3+)-Mn2O3 and Mn^(4+)-MnO2 compounds thereby supporting the identical Mn-state assignments. Comparison to the theoretical modeling emphasizes the strong covalency in these materials. Detailed Mn K b x-ray emission results on the La1_xCaxMnO3 system can be well fit by linear superpositions of the end member spectra, consistent with a mixed-valent character for the intermediate compositions. However, an arrested Mn-valence response to the doping in the x<0.3 range is found. No evidence for Mn^2+ is observed at any x values seemingly ruling out proposals regarding Mn^3+ disproportionation

The First Ultra-cool Brown Dwarf Discovered by the Wide-field Infrared Survey Explorer

We report the discovery of the first new ultra-cool brown dwarf (BDs) found with the Wide-field Infrared Survey Explorer (WISE). The object’s preliminary designation is WISEPC J045853.90+643451.9. Follow-up spectroscopy with the LUCIFER instrument on the Large Binocular Telescope indicates that it is a very late-type T dwarf with a spectral type approximately equal to T9. Fits to an IRTF/SpeX 0.8–2.5 μm spectrum to the model atmospheres of Marley and Saumon indicate an effective temperature of approximately 600 K as well as the presence of vertical mixing in its atmosphere. The new BD is easily detected by WISE, with a signal-to-noise ratio of ~36 at 4.6 μm. Current estimates place it at a distance of 6–10 pc. This object represents the first in what will likely be hundreds of nearby BDs found by WISE that will be suitable for follow-up observations, including those with the James Webb Space Telescope. One of the two primary scientific goals of the WISE mission is to find the coolest, closest stars to our Sun; the discovery of this new BD proves that WISE is capable of fulfilling this objective