Fabrication andin vitro characterization of three-dimensional organic/inorganic scaffolds by robocasting

International audienceA key issue for the fabrication of scaffolds for tissue engineering is the development of processing techniques flexible enough to produce materials with a wide spectrum of solubility (bioresorption rates) and mechanical properties matching those of calcified tissues. These techniques must also have the capability of generating adequate porosity to further serve as a framework for cell penetration, new bone formation, and subsequent remodeling. In this study, we show how hybrid organic/inorganic scaffolds with controlled microstructures can be built using robotic assisted deposition at room temperature. Polylactide or polycaprolactone scaffolds with pore sizes ranging between 200–500 μm and hydroxyapatite contents up to 70 wt % were fabricated. Compressive tests revealed an anisotropic behavior of the scaffolds, strongly dependent on their chemical composition. The inclusion of an inorganic component increased their stiffness but they were not brittle and could be easily machined even for ceramic contents up to 70 wt %. The mechanical properties of hybrid scaffolds did not degrade significantly after 20 days in simulated body fluid. However, the stiffness of pure polylactide scaffolds increased drastically due to polymer densification. Scaffolds containing bioactive glasses were also printed. After 20 days in simulated body fluid they developed an apatite layer on their surface

Antimony substituted lanthanum orthoniobate proton conductor - Structure and electronic properties

X‐ray and neutron diffraction have been utilized to analyze the crystalline and electronic structure of lanthanum orthoniobate substituted by antimony. Using X‐ray absorption spectroscopy and photoelectron spectroscopy, changes in the electronic structure of the material upon substitution have been analyzed. The structural transition temperature between fergusonite and scheelite phases for 30 mol% antimony substitution was found to be 15°C. Based on the neutron data, the oxygen nonstoichiometry was found to be relatively low. Moreover no influence on the position of the valence band maximum was observed. The influence of the protonation on the electronic structure of constituent oxides has been studied. Absorption data show that the incorporation of protonic defects into the lanthanum orthoniobate structure leads to changes in lanthanum electronic structure and a decrease in the density of unoccupied electronic states

Relationships between Endogenous Plasma Biomarkers of Constitutive Cytochrome P450 3A Activity and Single-Time-Point Oral Midazolam Microdose Phenotype in Healthy Subjects

Due to high basal interindividual variation in cytochrome P450 3A (CYP3A) activity and susceptibility to drug interactions, there has been interest in the application of efficient probe drug phenotyping strategies, as well as endogenous biomarkers for assessment of in vivo CYP3A activity. The biomarkers 4β-hydroxycholesterol (4βHC) and 6β-hydroxycortisol (6βHCL) are sensitive to CYP3A induction and inhibition. However, their utility for the assessment of constitutive CYP3A activity remains uncertain. We investigated whether endogenous plasma biomarkers (4βHC and 6βHCL) are associated with basal CYP3A metabolic activity in healthy subjects assessed by a convenient single-time-point oral midazolam (MDZ) phenotyping strategy. Plasma 4βHC and 6βHCL metabolic ratios (MRs) were analysed in 51 healthy adult participants. CYP3A activity was determined after administration of an oral MDZ microdose (100 μg). Simple linear and multiple linear regression analyses were performed to assess relationships between MDZ oral clearance, biomarkers and subject covariates. Among study subjects, basal MDZ oral clearance, 4βHC and 6βHCL MRs ranged 6.5-, 10- and 13-fold, respectively. Participant age and alcohol consumption were negatively associated with MDZ oral clearance (p = 0.03 and p = 0.045, respectively), while weight and female sex were associated with lower plasma 4βHC MR (p = 0.0003 and p = 0.032, respectively). Neither 4βHC nor 6βHCL MRs were associated with MDZ oral clearance. Plasma 4βHC and 6βHCL MRs do not relate to MDZ single-time-point metabolic phenotype in the assessment of constitutive CYP3A activity among healthy individuals

Apixaban Concentrations with Lower than Recommended Dosing in Older Adults with Atrial Fibrillation

OBJECTIVES: Lower than recommended doses of direct-acting oral anticoagulants are often prescribed to older adults with nonvalvular atrial fibrillation (NVAF). Our goal was to determine the consequences of lower than recommended dosing on plasma apixaban concentrations during the clinical care of older adults with NVAF. DESIGN: Convenience sample of patients receiving anticoagulation during 2017. SETTING: Academic medical center. PARTICIPANTS: Stable adults older than 65 years with NVAF receiving apixaban on a chronic basis. MEASUREMENTS: Patient age, weight, creatinine, co-medications, and apixaban concentrations. RESULTS: A total of 110 older adults with NVAF (mean age = 80.4 y; range = 66-100 y with 45% women) were studied. Overall, 48 patients received recommended dosing of 5 mg twice/day, and 42 received lower than recommended dosing. One patient in each category had concentrations below the expected 5% to 95% range at time of peak concentrations. Differences in proportion of apixaban concentrations within or outside expected ranges were not significant between patients receiving lower than recommended doses and those dosed as recommended at 5 mg twice/day (P =.35). However, in patients dosed as recommended with 5 mg twice/day, four had concentrations above the 5% to 95% range for peak levels expected at 3 to 4 hours after dosing; in two, this occurred around the midpoint of the dosing interval. Twenty patients received 2.5 mg twice/day as recommended. One-third had apixaban concentrations higher than expected peak concentrations compared with the clinical trials, and more than two-thirds had levels above the reported median for peak concentrations. CONCLUSIONS: Apixaban concentrations in older adults with NVAF seen clinically were higher than expected based on clinical trial data. The findings raise questions about the optimal dosing of apixaban in older adults with NVAF encountered outside of clinical trials and suggest a role for the monitoring of apixaban concentrations during care of patients that differ from those in randomized trials or when considering dosing outside of published guidelines. J Am Geriatr Soc 67:1902–1906, 2019

Crustal and Upper Mantle Velocity Model along the DOBRE-4 Profile from North Dobruja to the Central Region of the Ukrainian Shield : 2. Geotectonic Interpretation

Peer reviewe

Сейсмічний експеримент TTZ-South

The wide-angle reflection and refraction (WARR) TTZ-South transect carried out in 2018 crosses the SW region of Ukraine and the SE region of Poland. The TTZ-South profile targeted the structure of the Earth’s crust and upper mantle of the Trans-European Suture Zone, as well as the southwestern segment of the East European Craton (slope of the Ukrainian Shield). The ~550 km long profile (~230 km in Poland and ~320 km in western Ukraine) is an extension of previously realized projects in Poland, TTZ (1993) and CEL03 (2000). The deep seismic sounding study along the TTZ-South profile using TEXAN and DATA-CUBE seismic stations (320 units) made it possible to obtain high-quality seismic records from eleven shot points (six in Ukraine and five in Poland). This paper presents a smooth P-wave velocity model based on first-arrival travel-time inversion using the FAST (First Arrival Seismic Tomography) code.The obtained image represents a preliminary velocity model which, according to the P-wave velocities, consists of a sedimentary layer and the crystalline crust that could comprise  upper, middle and lower crustal layers. The Moho interface, approximated by the 7.5 km/s isoline, is located at 45—47 km depth in the central part of the profile, shallowing to 40 and 37 km depth in the northern (Radom-Łysogóry Unit, Poland) and southern (Volyno-Podolian Monocline, Ukraine) segments of the profile, respectively. A peculiar feature of the velocity cross-section is a number of high-velocity bodies distinguished in the depth range of 10—35 km. Such high-velocity bodies were detected previously in the crust of the Radom-Łysogóry Unit. These bodies, inferred at depths of 10—35 km, could be allochthonous fragments of what was originally a single mafic body or separate mafic bodies intruded into the crust during the break-up of Rodinia in the Neoproterozoic, which was accompanied by considerable rifting. The manifestations of such magmatism are known in the NE part of the Volyno-Podolian Monocline, where the Vendian trap formation occurs at the surface.Сейсмический профиль TTZ-South с использованием преломленных и отраженных в закритической области преломленных волн, отработанный в 2018 г., пересекает юго-западный район Украины и юго-восточный регион Польши. Профиль TTZ-South был направлен на изучение структуры земной коры и верхней мантии Трансъевропейской шовной зоны (ТЕШЗ) и юго-западного сегмента Восточно-Европейского кратона (склона Украинского щита). Профиль длиной ~550 км (~230 км в Польше и ~320 км на западе Украины) является продолжением ранее реализованных проектов в Польше — профиля TTZ (1993 г.) и CEL03 (2000 г.). Глубинное сейсмическое зондирование по профилю TTZ-South, выполненное с использованием 320 сейсмических станций TEXAN и DATA-CUBE, позволило получить сейсмические записи высокого качества из одиннадцати пунктов взрыва (шесть в Украине и пять в Польше). В данной статье представлена упрощенная Р-скоростная модель, основанная на инверсии времен пробега первых вступлений Р-волн, построенная с использованием программы сейсмической томографии первых вступлений FAST. Полученное изображение представляет собой предварительную скоростную модель, которая состоит из осадочного слоя и кристаллической коры, включающей верхний, средний и нижний ее слои. Поверхность Мохо, аппроксимируемая изолинией 7,5 км/с, расположена на глубине 45—47 км в центральной части профиля, воздымаясь до 40 и 37 км в северной (Радом-Лысогорский блок в Польше) и южной (Волыно-Подольская моноклиналь в Украине) частях профиля соответственно. Особенностью скоростного разреза является ряд высокоскоростных тел, выявленных в диапазоне глубин 10—35 км. Аналогичные высокоскоростные тела ранее были обнаружены в коре Радом-Лысогорского блока. Тела, обнаруженные на глубине 10—35 км, могут быть аллохтонными фрагментами изначально единого массива основных пород или отдельными телами основного состава, внедрившимися в кору в неопротерозое во время раскола суперконтинета Родиния, который сопровождался мощным рифтогенезом. Проявления рифтогенного магматизма известны в северо-восточной части Волыно-Подольской моноклинали, где на поверхность выходят вендские трапы.Сейсмічний профіль TTZ-South з використанням заломлених і відбитих у за критичній зоні заломлених хвиль, відпрацьований у 2018 р., перетинає південно-західний район України і південно-східний регіон Польщі. Профіль TTZ-South був спрямований на вивчення структури земної кори і верхньої мантії Транс'єв ропейської шовної зони (ТЄШЗ) і південно-західного сегмента Східно-Європейського кратона (схила Українського щита). Профіль довжиною ~550 км (~230 км в Польщі і ~320 км на заході України) є продовженням раніше реалізованих проєктів у Польщі — профілю TTZ (1993 р.) і CEL03 (2000 р). Глибинне сейсмічне зондування за профілем TTZ-South, виконане з використанням 320 сейсмічних станцій TEXAN і DATA-CUBE, дало змогу отримати сейсмічні записи високої якості з одинадцяти пунктів вибуху (шість в Україні і п'ять у Польщі). У даній статті представлена спрощена Р-швидкісна модель, що базується на інверсії часів пробігу перших вступів Р-хвиль, побудована з використанням програми сейсмічної томографії перших вступів FAST. Отримане зображення являє собою попередню швидкісну модель, яка складається з осадового шару і кристалічної кори, що включає верхній, середній і нижній її шари. Поверхня Мохо, що апроксимується ізолінією 7,5 км/с, розташована на глибині 45—47 км у центральній частині профілю, здіймається до 40 і 37 км у північній (Радом-Лисогорський блок у Польщі) і південній (Волино-Подільська монокліналь в Україні) частинах профілю відповідно. Особливістю швидкісного розрізу є ряд високошвидкісних тіл, виявлених у діапазоні глибин 10—35 км. Подібні високошвидкісні тіла раніше були виявлені в корі Радом-Лисогірського блоку. Тіла, виявлені на глибині 10—35 км, можуть бути алохтонними фрагментами спочатку єдиного масиву основних порід або окремими тілами основного складу, що впровадилися в кору в неопротерозої під час розколу суперконтінета Родінія, який супроводжувався потужним рифтогенезом. Прояви рифтогенного магматизму відомі в північно-східній частині Волино-Подільської моноклінали, де на поверхню виходять вендські трапи

Lithospheric structure along wide-angle seismic profile GEORIFT 2013 in Pripyat–Dnieper–Donets Basin (Belarus and Ukraine)

The GEORIFT 2013 (GR'13) WARR (wide-angle reflection and refraction) experiment was carried out in 2013 in the territory of Belarus and Ukraine with broad international co-operation. The aim of the work is to study basin architecture and deep structure of the Pripyat-Dnieper-Donets Basin (PDDB), which is the deepest and best studied Palaeozoic rift basin in Europe. The PDDB is located in the southern part of the East European Craton (EEC) and crosses Sarmatia-one of the three segments of the EEC. The PDDB was formed by Late Devonian rifting associated with domal basement uplift and magmatism. The GR'13 extends in NW SE direction along the PDDB strike and crosses the Pripyat Trough (PT) and Dnieper Graben (DG) separated by the Bragin Uplift (BU) of the basement. The field acquisition along the GR'13 (of 670 km total length) involved 14 shots and recorders deployed every similar to 2.2 km for several shot points. The good quality of the data, with first arrivals visible up to 670 km for several shot points, allowed for construction of a velocity model extending to 80 km depth using ray-tracing modelling. The thickness of the sediments (Vp <6.0 km s(-1)) varies from 1-4 km in the PT, to 5 km in the NW part of the DG, to 10-13 km in the SE part of the profile. Below the DG, at similar to 330-530 km distance, we observed an upwarping of the lower crust (with Vp of similar to 7.1 km s(-1)) to 25 km depth that represents a rift pillow or mantle underplate. The Moho shallows southeastwards from similar to 47 km in the PT to 40-38 km in the DG with mantle velocities of 8.35 and similar to 8.25 km s(-1) in the PT and DG, respectively. A near-horizontal mantle discontinuity was found beneath BU (a transition zone from the PT to the DG) at the depth of 50-47 km. It dips to the depth of similar to 60 km at distances of 360-405 km, similar to the intersecting EUROBRIDGE'97 profile. The crust and upper mantle structure on the GR'13 may reflect varying intensity of rifting in the PDDB from a passive stage in the PT to active rifting in the DG. The absence of Moho uplift and relatively thick crystalline crust under the PT is explained by its tectonic position as a closing unit of the PDDB, with a gradual attenuation of rifting from the southeast to the northwest. The most active stage of rifting is evidenced in the DG by a shallower Moho and by a presence of a rift pillow caused by mafic and ultramafic intrusions during the active phase. The junction of the PT and the DG (the BU) locates just at its intersection with the NS regional tectonic zone Odessa-Gomel. Most likely, the 'blocking' effect of this zone did not allow for further propagation of active rifting to the NW.Peer reviewe

Crustal and Upper Mantle Velocity Model along the DOBRE-4 Profile from North Dobruja to the Central Region of the Ukrainian Shield : 1. Seismic Data

For studying the structure of the lithosphere in southern Ukraine, wide-angle seismic studies that recorded the reflected and refracted waves were carried out under the DOBRE-4 project. The field works were conducted in October 2009. Thirteen chemical shot points spaced 35-50 km apart from each other were implemented with a charge weight varying from 600 to 1000 kg. Overall 230 recording stations with an interval of 2.5 km between them were used. The high quality of the obtained data allowed us to model the velocity section along the profile for P-and S-waves. Seismic modeling was carried out by two methods. Initially, trial-and-error ray tracing using the arrival times of the main reflected and refracted P-and S-phases was conducted. Next, the amplitudes of the recorded phases were analyzed by the finite-difference full waveform method. The resulting velocity model demonstrates a fairly homogeneous structure from the middle to lower crust both in the vertical and horizontal directions. A drastically different situation is observed in the upper crust, where the Vp velocities decrease upwards along the section from 6.35 km/s at a depth of 15-20 km to 5.9-5.8 km/s on the surface of the crystalline basement; in the Neoproterozoic and Paleozoic deposits, it diminishes from 5.15 to 3.80 km/s, and in the Mesozoic layers, it decreases from 2.70 to 2.30 km/s. The sub-crustal Vp gradually increases downwards from 6.50 to 6.7-6.8 km/s at the crustal base, which complicates the problem of separating the middle and lower crust. The Vp velocities above 6.80 km/s have not been revealed even in the lowermost part of the crust, in contrast to the similar profiles in the East European Platform. The Moho is clearly delineated by the velocity contrast of 1.3-1.7 km/s. The alternating pattern of the changes in the Moho depths corresponding to Moho undulations with a wavelength of about 150 km and the amplitude reaching 8 to 17 km is a peculiarity of the velocity model.Peer reviewe

Introduction to "Working Across Species"

Comparison between different animal species is omnipresent in the history of science and medicine but rarely subject to focussed historical analysis. The articles in the ‘‘Working Across Species’’ topical collection address this deficit by looking directly at the practical and epistemic work of cross-species comparison. Drawn from papers presented at a Wellcome-Trust-funded workshop in 2016, these papers investigate various ways that comparison has been made persuasive and successful, in multiple locations, by diverse disciplines, over the course of two centuries. They explore the many different animal features that have been considered to be (or else made) comparable, and the ways that animals have shaped science and medicine through the use of comparison. Authors demonstrate that comparison between species often transcended the range of practices typically employed with experimental animal models, where standardised practises and apparatus were applied to standardised bodies to produce generalizable, objective data; instead, comparison across species has often engaged diverse groups of nonstandard species, made use of subjective inferences about phenomena that cannot be directly observed, and inspired analogies that linked physiological and behavioural characteristics with the apparent affective state of non-human animals. Moreover, such comparative practices have also provided unusually fruitful opportunities for collaborative connections between different research traditions and disciplines