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A panel of Brazilian experts convened in order to provide recommendations regarding staging methods, antineoplastic therapy, osteoclast-targeted therapy, and patient follow-up in non-metastatic, castrationresistant prostate cancer. Key points include the reliance on prostate-specific antigen doubling time for treatment decisions, the absence of a clear preference between conventional and novel imaging techniques, and the increasing role of novel androgen-receptor signaling inhibitors. Introduction: Non-metastatic, castration-resistant prostate cancer (nmCRPC) is an important clinical stage of prostate cancer, prior to morbidity and mortality from clinical metastases. In particular, the introduction of novel androgenreceptor signaling inhibitors (ARSi) has changed the therapeutic landscape in nmCRPC. Given recent developments in this field, we update our recommendations for the management of nmCRPC. Methods: A panel of 51 invited medical oncologists and urologists convened in May of 2021 with the aim of discussing and providing recommendations regarding the most relevant issues concerning staging methods, antineoplastic therapy, osteoclast-targeted therapy, and patient follow-up in nmCRPC. Panel members considered the available evidence and their practical experience to address the 73 multiple-choice questions presented. Results: Key recommendations and findings include the reliance on prostate-specific antigen doubling time for treatment decisions, the absence of a clear preference between conventional and novel (i.e., positron-emission tomography-based) imaging techniques, the increasing role of ARSis in various settings, the general view that ARSis have similar efficacy. Panelists highlighted the slight preference for darolutamide, when safety is of greater concern, and a continued need to develop high-level evidence to guide the intensity of followup in this subset of prostate cancer. Discussion: Despite the limitations associated with a consensus panel, the topics addressed are relevant in current practice, and the recommendations can help practicing clinicians to provide state-of-the-art treatment to patients with nmCRPC in Brazil and other countries with similar healthcare settings. [ABSTRACT FROM AUTHOR]

En exposant sur la scène institutionnelle les souffrances de son présent, l'adolescent(e) vient nous parler du passé de son histoire, des liens abimés, anéantis, ou inhabités, qui jalonnent sa trajectoire de vie et surgissent dans cet « entre-temps » de son existence en autant d'éclats douloureux dans le monde interne de sa psyché et dans le corps. Lors de leur traversée de l'institution de soins, nous travaillons, avec ces adolescent(e)s et leur famille, dans cet espace-temps, sur ce qui pourrait venir aider à réduire les lignes de brisure internes afin que se remettent en mouvement les capacités subjectives à penser et à agir dans le monde. Notre éthique de travail s'appuie sur la capacité propre à chaque acteur institutionnel de déployer leurs enveloppes psychiques contenantes autour des jeunes patients ; déploiement symbolisé de la fonction contenante par le temps de penser le soin pour le soignant, le temps d'y consentir de manière sécure pour l'adolescent, puis pour celui-ci le temps redevenu acceptable d'explorer le champ des possibles. By exposing on the institutional level the sufferings of his present, the adolescent talks to us about his history, the damaged, destroyed or uninhabited links which mark out his life trajectory and arise in this "meantime" of his existence in so many painful shards in the internal world of his psyche and in the body. During their journey through the care institution, we work with these adolescents and their families, in this space-time, on what could help to reduce the internal breaking lines so that they can again start moving their subjective capacities to think and act in the world. Our work ethic is based on the specific capacity of each institutional actor to deploy his/her containing psychic envelopes around young patients; symbolized deployment of the containing function by the time to think about the care for the caregiver, the time to consent to it in a safe way for the adolescent, then for the latter the time once again acceptable to explore the field of possibilities. [ABSTRACT FROM AUTHOR]

Background: We aimed to describe the reasons for failure of experimental anticancer drugs in late-stage clinical development.Material and Methods: We searched the PharmaProjects database (https://citeline.com/products/pharmaprojects/) for anticancer drugs discontinued between 01/01/2009 and 06/30/2014. Drug programs that reached phase III trials, but never gained Food and Drug Administration (FDA) approval were compared to 37 anti-cancer drugs achieving FDA approval in this time period.Results: Forty-two drugs fit our criteria for development failures. These failed drugs (49% targeted, 23% cytotoxics, and 28% other) were tested in 43 cancer indications (drug programs). Only 16% (7/43) of failed drug programs adopted a biomarker-driven rationale for patient selection versus 57% (21/37) of successful drug programs (P<0.001). Phase II trial information was available in 32 of 43 failed drug programs and in 32 of 37 successful programs. Nine of the 32 trials (28%) of failed drugs versus 28 of 32 trials (87%) of successful drugs (P<0.001) achieved proof of concept (single agent response rate (RR) ⩾20% or combination therapy showing a ⩾20% RR increase above the median historical RR without the experimental agent (with a minimal absolute increase of 5%) or a randomized phase II trial showing significance (P⩽0.05) for its primary outcome). No pattern of study sites, trial design or funding characteristics emerged from the failed drug analysis.Conclusion: For drugs that reached Phase III, lack of a biomarker-driven strategy and failure to attain proof of concept in phase II are potential risk factors for later discontinuation, especially for targeted agents. [ABSTRACT FROM AUTHOR]

The Lofoten Basin of the Norwegian Sea is characterized by a local maximum of eddy kinetic energy and it is an important transit region for the warm and saline Atlantic waters on their way towards the Arctic Ocean. Eddies are generated by the Norwegian Atlantic Current and propagate anticlockwise around the center of the basin. In situ and satellite observations have discovered a rather small (with a radius of a few tens of km), but strong quasi-permanent anticyclonic vortex that resides in the center of the Lofoten Basin near 3°E, 69.8°N. The objective of this paper is to understand how and why the vortex is formed and to investigate what processes support its stability and drive its variability. To achieve this objective, we have conducted three high-resolution numerical experiments with the mean horizontal grid spacing of 18 km, 9 km, and 4 km. The Lofoten Vortex did not form in the 18-km experiment. The most realistic (compared to available observations) simulation of the vortex is provided by the 4-km experiment, which better reproduces eddy variability in the region. The experiments thus provide experimental evidence of the importance of eddies in the formation and stability of the vortex. We demonstrate how anticyclonic eddies, that are usually stronger and more numerous in the basin than cyclonic eddies, contribute to the intensification of the Lofoten Vortex. The Lofoten Vortex itself is not stationary and drifts cyclonically within the area bounded by approximately the 3250 m isobath. The analysis of the barotropic vorticity budget in the 4-km experiment shows that the advection of the relative vorticity gradient by eddies is the main mechanism that drives the variability of the Lofoten Vortex. The direct impact of wind/buoyancy forcing is found to be small to negligible. [ABSTRACT FROM AUTHOR]

Abstract: The regional variability of sea level is an integral indicator of changing oceanographic conditions due to different processes of oceanic, atmospheric, and terrestrial origin. The present study explores the nature of sea level variability in the Barents Sea—a marginal shelf sea of the Arctic Ocean. A characteristic feature that distinguishes this sea from other Arctic shelf seas is that it is largely ice free throughout the year. This allows continuous monitoring of sea level by space-borne altimeters. In this work we combine satellite altimetry, ocean gravity measurements by GRACE satellites, available hydrography data, and a high-resolution ocean data synthesis product to estimate the steric and mass-related components of sea level in the Barents Sea. We present one of the first observational evidence of the local importance of the mass-related sea level changes. The observed 1–3 month phase lag between the annual cycles of sea level in the Barents Sea and in the Nordic seas (Norwegian, Iceland, Greenland seas) is explained by the annual mass-related changes. The analysis of the barotropic vorticity budget shows that the mass-related sea level variability in the central part of the Barents Sea is determined by the combined effect of wind stress, flow over the varying bottom topography, and dissipation, while the impact of vorticity fluxes is negligible. Overall, the steric sea level has smaller amplitudes and mainly varies on the seasonal time scale. The thermosteric sea level is the main contributor to the steric sea level along the pathways of the Atlantic inflow into the Barents Sea. The relative contribution of the halosteric sea level is dominant in the southeastern, eastern, and northern parts of the Barents Sea, modulated by the seasonal sea ice formation/melt as well as by continental runoff. The variability of the thermosteric sea level in the Barents Sea is mostly driven by variations in the net surface heat flux, whereas the contribution of heat advection becomes as important as the ocean-atmosphere heat exchange at interannual time scales. [Copyright &y& Elsevier]

Phonons – quanta of crystal lattice vibrations – reveal themselves in all electrical, thermal, and optical phenomena in materials. Nanostructures open exciting opportunities for tuning the phonon energy spectrum and related material properties for specific applications. The possibilities for controlled modification of the phonon interactions and transport – referred to as phonon engineering or phononics – increased even further with the advent of graphene and two-dimensional van der Waals materials. We describe methods for tuning the phonon spectrum and engineering the thermal properties of the low-dimensional materials via ribbon edges, grain boundaries, isotope composition, defect concentration, and atomic-plane orientation. [Copyright &y& Elsevier]

Abstract: Kaolinite clay samples from Amazon region, Pará state, Brazil, were first intercalated with dimethylsulfoxide (DS) followed by immobilization of (3-aminopropyl)triethoxysilane (APS). The samples were characterized by X-ray diffraction, and zero point charge determination. The chemically modified kaolinite samples showed modification of its physical–chemical properties including: specific area of 25.2–421.5m2 g−1 for K 1 and K 1-DS/APS, and 24.7–425.9m2 g−1 for K 2 and K 2-DS/APS. New d 001 values of 1.313 and 1.319nm for the modified kaolinites K 1-DS/APS and K 2-DS/APS, respectively, were obtained. From electrical property investigations an increase in electric permittivity was observed for real (ɛ |) and imaginary (ɛ ||) at low frequencies, which are probably related to the interlayer molecules. The energetic effect caused by mercury cation adsorption was determined through calorimetric titration at the solid–liquid interface and gave net thermal effects that enabled the calculation of the exothermic enthalpic values and the equilibrium constant. From these values negative Gibbs free energy and positive entropy were calculated and this set of thermodynamic data is favorable for mercury/basic center interaction at the solid/liquid interface. [Copyright &y& Elsevier]

Abstract: In this study, the original tourmaline and beryl mineral samples have been collected from a Brazilian pegmatite. The objective of this study was to examine the adsorption behavior of uranyl from aqueous solution on Brazilian cyclosilicate samples. The cyclosilicate samples were characterized by elemental analysis, X-ray diffraction, and nitrogen adsorption–desorption. The ability of these minerals to remove the U(VI) from aqueous solution was followed by a series of adsorption isotherms, using a batchwise process. The adsorption maximum was determined to be 2.95 and 2.60×10−4molg−1 for beryl and tourmaline mineral samples, respectively. The energetic effects caused by radionuclide cation adsorption were determined through calorimetric titrations. Thermodynamics indicated the existence of favorable conditions for such U(VI)–OH interactions. [Copyright &y& Elsevier]

Abstract: Mixed quantum mechanical/molecular mechanics calculations were used to explore the electron pathway of the terminal electron transfer enzyme, cytochrome c oxidase. This enzyme catalyzes the reduction of molecular oxygen to water in a multiple step process. Density functional calculations on the three redox centers allowed for the characterization of the electron transfer mechanism, following the sequence CuA →heme a →heme a 3. This process is largely affected by the presence of positive charges, confirming the possibility of a proton coupled electron transfer. An extensive mapping of all residues involved in the electron transfer, between the CuA center (donor) and the O2 reduction site heme a 3-CuB (receptor), was obtained by selectively activating/deactivating different quantum regions. The method employed, called QM/MM e-pathway, allowed the identification of key residues along the possible electron transfer paths, consistent with experimental data. In particular, the role of arginines 481 and 482 appears crucial in the CuA →heme a and in the heme a →heme a 3 electron transfer processes. This article is part of a Special Issue entitled: Allosteric cooperativity in respiratory proteins. [Copyright &y& Elsevier]

Abstract: Imogolite is an important paracrystalline hydrous aluminosilicate with a unique nanofiber structure. The synthetic imogolite sample was used for organofunctionalization process with 2-mercaptothiazoline and 2-mercaptobenzimidazole. Due to the increment of basic centers attached to the pendant chains, the metal adsorption capability of the final chelating materials, was found to be higher than is precursor. The ability of these materials to remove rubidium from aqueous solution was followed by a series of adsorption isotherms at room temperature and pH 4.0, in batch adsorption experiments in order to explain the adsorption mechanism. The maximum number of moles adsorbed was determined to be 17.89×10−2, 29.89×10−2, and 30.55×10−2 mmolg−1 for IMO, IMOMBI, and IMOMTZ, respectively. In order to evaluate the aluminosilicate samples as adsorbents in dynamic system, a glass column was fulfilled with aluminosilicate samples (1.0g) and it was fed with 1.9×10−3 moldm−3 rubidium at pH 4.0. The energetic effects caused by metal cations adsorption were determined through calorimetric titrations. The enthalpic and entropic values indicated the existence of favorable reaction between rubidium-nitrogen and sulfur center atoms on pendant chain covalent bonded to the inorganic backbone. [Copyright &y& Elsevier]

Abstract: Hectorite (H) clay sample from the Amazon region, Brazil, has been modified with 2-mercaptobenzimidazole (MBI) using homogeneous and heterogeneous routes. The natural and modified materials were characterized through elemental analyses, nuclear magnetic nuclei of carbon-13 and silicon-29, and SEM. The well-defined peaks obtained in the 13C NMR spectra in the 112–129ppm region confirmed the attachment of organic functional groups as pendant chains bonded into the hectorite clay. Due to the increment of basic centers attached to the pendant chains the metal adsorption capability of the final chelating materials, was found to be higher than its precursor. The adsorption of metal ions from aqueous solution follows the order Eu3+ >U6+ >Th4+ for all systems. The maximum number of moles adsorbed was determined to be 11.63, 12.85 and 14.01mmolg−1 (HHET) for Th4+, U6+ and Eu3+, respectively. The competitive sorption behavior, with variation of pH, was favorable for the separation of thorium(IV) from binary mixtures with uranium(VI) and europium(III). The energetic effects (∆int H°, ∆int G° and ∆int S°) caused by metal cation adsorption were determined through calorimetric titrations. [Copyright &y& Elsevier]

Abstract: In order to quantify the spatial and seasonal variations of sediment oxygen consumption and nutrient fluxes, we performed a spatial survey in the south west lagoon of New Caledonia during the two major seasons (dry and wet) based on a network of 11 sampling stations. Stations were selected along two barrier reef to land transects representing most types of sediments encountered in the lagoon. Fluxes were measured using ex-situ sediment incubations and compared to sediment characteristics. Sediment oxygen consumption (SOC) varied between 500 and 2000μmolm−2 h−1, depending on season and stations. Nutrient effluxes from sediment were highly variable with highest fluxes measured in muddy sediments near the coast. Inter-sample variability was as high as seasonal differences so that no seasonally driven temperature effect could be observed on benthic nutrient fluxes in our temperature range. Nutrient fluxes, generally directed from the sediment to the water column, varied between −5.0 and 70.0μmolm−2 h−1 for ammonia and between −2.5 and+12.5μmolm−2 h−1 for PO4 and NO2+3. SOC and nutrient fluxes were compared to pelagic primary production rates in order to highlight the tight coupling existing between the benthic and pelagic compartments in this shallow tropical lagoon. Under specific occasions of low pelagic productivity, oxygen sediment consumption and related carbon and nutrient fluxes could balance nearly all net primary production in the lagoon. These biogeochemical estimates point to the functional importance of sediment biogeochemistry in the lagoon of New Caledonia. [ABSTRACT FROM AUTHOR]

Abstract: A Hectorite sample (H) has been chemically modified with N-propyldiethylenetrimethoxysilane and bis[3-(triethoxysilyl)propyl]tetrasulfide. The resulting materials (H3TPT and HNPTM) have been characterized through elemental analysis, X-ray diffractometry, carbon nuclear magnetic resonance in the solid state, textural analysis, and thermogravimetric analysis. The adsorption experiments were performed under batch process with pH, ionic strength, contact time, and uranyl concentration as variables. The attached basic centers adsorbed uranyl cation to give maxima adsorption capacity of 5.55±0.21, 14.86±0.05, and 18.99±0.05×10−3 mmolg−1 for H, H3TPT, and HNPTM, respectively. From calorimetric determinations the quantitative thermal effects for UO2 2+/center interactions gave exothermic enthalpy (ΔintH=−6.90 to −7.88kJmol−1), negative Gibbs free energy (ΔintG=−22.34 to −24.56kJmol−1), and positive entropy (ΔintS=51.80–56.00JK−1 mol−1). These thermodynamic data confirmed the energetically favorable condition of such interaction solid/liquid for all systems. [Copyright &y& Elsevier]

Abstract: A hectorite (H) clay sample has been modified with 2-mercaptobenzimidazole (MBI) using homogeneous and heterogeneous routes. Both modification methodologies resulted in similar products, named HHOM and HHET, respectively. These materials were characterized by CO2 gas adsorption, elemental analysis, nuclear magnetic nuclei of carbon-13 and silicon-29. The effect of two variables (contact time and metal concentration) has been studied using batch technique at room temperature and pH 2.0. After achieving the best conditions for Cr(VI) adsorption, isotherms of this adsorbate on using the chosen adsorbents were obtained, which were fitted to non-linear Sips isotherm model. The maximum number of moles adsorbed was determined to be 11.63, 12.85 and 14.01mmolg−1 for H, HHOM and HHET, respectively, reflecting the maximum adsorption order of HHET >HHOM >H. The energetic effects (Δint H°, Δint G° and Δint S°) caused by chromium ion adsorption were determined through calorimetric titrations. [Copyright &y& Elsevier]

Abstract: A synthetic Na-magadiite sample has been modified by organofunctionalization process using synthetic route involved the reaction of 2-mercaptopyrimidine with 3-chloropropyltriethoxysilane. The ability of these materials to remove As(V) from aqueous solution was followed by a series of adsorption isotherms adjusted to the Langmuir equation at room temperature and pH 2.0. The kinetic parameters analyzed by the Lagergren and Elovich models gave a good fit for a pseudo-second-order reaction with k 2 in the 4.9–14.0mmol−1 min−1 range for MMPY. The adsorption process was exothermic (Δint H =−4.09 to −5.79kJmol−1) accompanied by increase in entropy (Δint S =41.29–61.80JK−1 mol−1) and Gibbs energy (Δint G =−22.34 to −24.19kJmol−1). The energetic effect caused by arsenic(V) cation adsorption was determined through calorimetric titration at the solid–liquid interface and gave a net thermal effect that enabled the calculation of the exothermic values and the equilibrium constant. [Copyright &y& Elsevier]

Abstract: Natural montmorillonite (M) and synthetic kanemite (K) have been functionalized with 1,4-bis(3-aminopropyl)piperazine reacted with methylacrylate to yield new inorganic–organic chelating materials. The original and modified materials were characterized by X-ray diffractometry, textural analysis, SEM and nuclear magnetic nuclei of carbon-13 and silicon-29. The chemically modified clay samples (M-APPMA and K-APPMA) showed modification of its physical–chemical properties including: specific area 45.0m2 g−1 (M) to 978.8m2 g−1 (M-APPMA) and 23.5m2 g−1 (K) to 898.9m2 g−1 (K-APPMA). The ability of these materials to remove thorium(IV), uranyl(VI) and europium(III) from aqueous solution was followed by a series of adsorption isotherms, which were fitted to non-linear Sips adsorption isotherm model. To achieve the best adsorption conditions the influence of pH and variation of metal concentration were investigated. The energetic effects (Δint H°, Δint G° and Δint S°) caused by metal ions adsorption were determined through calorimetric titrations. [Copyright &y& Elsevier]

Abstract: The compound 5-amino-1,3,4-thiadiazole-thiol was anchored onto analogue of heulandite by heterogeneous route. The original (HEU) and modified heulandite (HEUATT) samples were characterized through elemental analysis and nuclear magnetic nuclei of carbon-13 and silicon-29. The ability of these materials to remove Mn(II), Zn(II) and Pb(II) from aqueous solution was followed by a series of adsorption isotherms adjusted to a Sips equation. To achieve the best adsorption conditions the influence of pH and contact time were investigated. Based on the capacity of adsorption of HEUATT to interact with metal ions, the following results were obtained 13.0, 10.1 and 7.4mmolg−1 for Pb(II), Zn(II) and Mn(II), respectively, reflecting a maximum adsorption order of Pb(II)>Zn(II)>Mn(II). The energetic effects caused by metal cation adsorption were determined through calorimetric titrations. [Copyright &y& Elsevier]