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Introduction: A phase I, open-label clinical trial in healthy male subjects was conducted to assess the pharmacokinetic and safety profile of an oromucosal cannabinoid spray (AP701) containing a lipid-based nanoparticular drug formulation standardized to â-9-tetrahydrocannabinol (THC). Methods: Twelve healthy male subjects received a single dose of AP701 (12 sprays) containing 3.96 mg THC. Plasma samples were drawn 10 min-30 h post dose for analysis of THC and the active metabolite 11-hydroxy-â-9-THC (11-OH-THC). Results: The single dose of the applied oromucosal cannabinoid spray AP701 (12 sprays, 3.96 mg THC) resulted in a mean maximum plasma concentration (C[sub.max]) of 2.23 ng/mL (90% CI 1.22-3.24) and a mean overall exposure (area under the concentration-time curve from time 0 to last measurable concentration [AUC[sub.0-t]]) of 7.74 h × ng/mL (90% CI 5.03-10.45) for THC. For the active metabolite 11-OH-THC, a C[sub.max] of 2.09 mg/mL (90% CI 1.50-2.68) and AUC[sub.0-t] of 10.4 h × ng/mL (90% CI 7.03-13.77) was found. The oromucosal cannabinoid spray AP701 caused only minor psychotropic effects despite the relatively high dosage applied by healthy subjects. No serious adverse effects occurred. Overall, the oromucosal cannabinoid spray AP701 was well tolerated. Conclusion: Compared to currently available drugs on the market, higher AUC values could be detected for the oromucosal cannabinoid spray AP701 despite administration of a lower dose. These comparatively higher blood levels caused only minor psychotropic adverse effects. The oromucosal cannabinoid spray AP701 was well tolerated at a single dose of 3.96 mg THC. The oromucosal administration may provide an easily applicable and titratable drug formulation with a high safety and tolerability profile. Keywords: Pharmacokinetics, Safety, Cannabinoids, Oromucosal spray, Nanoparticles, Author(s): Stefan Lorenzl [a,b,c]; Franz Gottwald [d]; Angelika Nistler [e]; Laura Brehm [e]; Renate Grötsch [f]; Georg Haber [c]; Christian Bremm [g]; Christiane Weck [a,c]; Carina Trummer [d]; Werner Brand [...]

Maryanne Wolf's early literacy knowledge is based on her research into deep reading and on periods of enlightened linguistic processes. In her own rich language of conveyance, she brought great inspiration to the Montessori teachers at the Columbia, South Carolina conference. Her presentation on the research of early reading, the acquisition of cognitive and affective skills, optimal exposure to books, and the benefits of reading out-loud corroborates precisely with Montessori theory and practice. She also documented the power of focused, joint attention between the adult reader and child as a key developmental force in the formation of early literacy. In this extract from her newest book, Wolf writes of the developmental phases a child goes through, from prereading to linguistic awareness, and the importance of a literate environment to increasing the scope of early reading. Literacy expands the child's world beyond cognitive ability as it opens communication, symbolism, and immersion into the imagination of literature. [Reprinted, with permission, from Chapter 3 of "Tales of Literacy for the 21st Century" by Maryanne Wolf with Stephanie Gottwald, 2016, Oxford University Press.]

The article’s focus is on the postal services sector. The sector plays an important role in a process of delivering packages to the customers. Over the last few years, there has been a significant growth in volume of shipments transported. The aim of the article is to demonstrate the current development and subsequent prediction of two selected indicators that play an important role in the context of e-commerce development in the V4 states. One of the indicators is the number of shipments; the other is the indicator of CO2 emissions. While the values of the CO2 emission in the predictive analysis in comparison with the growing e-commerce turnover indicator stagnate, the number of shipments is growing alongside the e-commerce turnover values. In the light of these findings, it is clear that the growing number of shipments will result in the need to change the approach to the organisation of the parcel delivery process, especially in big cities and agglomerations. It is also necessary to mention that organisational changes in the parcel delivery process in big cities and agglomerations must be carried out in an environmentally friendly way.

The thyroid operates within a complex system of homeostatic regulation, where the level of thyrotropin (TSH) influences the rate of secretion of the principal thyroid hormones, thyroxine (T4) and triiodothyronine (T3). The devastating consequences of untreated thyroid dysfunction have been evident for centuries. Indeed, sources from antiquity described goitre and cretinism, two of the clinical sequelae of untreated overt thyroid disease. It was not until the first part of the 19th century that goitre and cretinism were first associated with iodine status; however, the endocrine function of the thyroid was not clearly identified until the early part of the 20th century. Three principal innovations in the 20th century supported the use of levothyroxine (LT4) replacement therapy for the management of hypothyroidism: a practical technique for the synthesis of LT4 suitable to support pharmaceutical use (late 1940s), the discovery that LT4 is converted to the active thyroid hormone, T3, in the peripheral tissues (1970), and the development of robust and sensitive assay methodology for measuring thyroid hormones in the blood (1960 onwards). Synthetic LT4, titrated to bring the level of TSH within a predefined “normal” reference range, is now established as the mainstay of treatment for hypothyroidism, and provides adequate restoration of thyroid hormone function for most people with this condition. Future research will explore further the nuances of the hypothalamic-pituitary-thyroid axis, and the place, if any, for T3 within the management of thyroid dysfunction.

Background: Fibrosis limits the success of filtering glaucoma surgery. We employed 2D and 3D in vitro models to assess the effects of fluid flow on human tenon fibroblasts (HTF). Methods: HTF were exposed to continuous or pulsatile fluid flow for 48 or 72 h, at rates expected at the transscleral outflow site after filtering surgery. In the 2D model, the F-actin cytoskeleton and fibronectin 1 (FN1) were visualized by confocal immunofluorescence microscopy. In the 3D model, mRNA and whole cell lysates were extracted to analyze the expression of fibrosis-associated genes by qPCR and Western blot. The effects of a small-molecule inhibitor of the TGF-β receptor ALK5 were studied. Results: Slow, continuous fluid flow induced fibrotic responses in the 2D and 3D models. It elicited changes in cell shape, the F-actin cytoskeleton, the deposition of FN1 and activated the intracellular TGF-β signaling pathway to induce expression of fibrosis-related genes, such as CTGF, FN1 and COL1A1. ALK5-inhibition reduced this effect. Intermittent fluid flow also induced fibrotic changes, which decreased with increasing pause duration. Conclusions: Slow interstitial fluid flow is sufficient to induce fibrosis, could underlie the intractable nature of fibrosis following filtering glaucoma surgery and might be a target for antifibrotic therapy.

Angle-resolved photoemission spectroscopy (ARPES) is a method that measures orbital and band structure contrast through the momentum distribution of photoelectrons. Its simplest interpretation is obtained in the plane-wave approximation, according to which photoelectrons propagate freely to the detector. The photoelectron momentum distribution is then essentially given by the Fourier transform of the real-space orbital. While the plane-wave approximation is remarkably successful in describing the momentum distributions of aromatic compounds, it generally fails to capture kinetic-energy-dependent final-state interference and dichroism effects. Focusing our present study on quasi-freestanding monolayer graphene as the archetypical two-dimensional (2D) material, we observe an exemplary E_{kin}-dependent modulation of, and a redistribution of spectral weight within, its characteristic horseshoe signature around the K[over ¯] and K[over ¯]^{′} points: both effects indeed cannot be rationalized by the plane-wave final state. Our data are, however, in remarkable agreement with ab initio time-dependent density functional simulations of a freestanding graphene layer and can be explained by a simple extension of the plane-wave final state, permitting the two dipole-allowed partial waves emitted from the C 2p_{z} orbitals to scatter in the potential of their immediate surroundings. Exploiting the absolute photon flux calibration of the Metrology Light Source, this scattered-wave approximation allows us to extract E_{kin}-dependent amplitudes and phases of both partial waves directly from photoemission data. The scattered-wave approximation thus represents a powerful yet intuitive refinement of the plane-wave final state in photoemission of 2D materials and beyond.

Triboelectric nanogenerators (TENGs) are energy converters or energy harvesters that convert mechanical motion into electrical energy on the basis of their material properties. A particular advantage of the TENG is its ability to convert small, low-frequency and random mechanical movements that are relevant for body movements and wearable applications. Within the presented study, different Parylene types were analysed as the dielectric material in TENG and found to be promising with respect to providing high output voltages and powers, respectively. Besides the verification of the usability of Parylene for TENG and its superior triboelectric properties, also significant differences were found between the Parylene types.

Abstract Bats represent a highly diverse group of mammals and are essential for ecosystem functioning. However, knowledge about their behaviour, ecology and conservation status is limited. Direct observation of marked individuals (commonly applied to birds) is not possible for bats due to their small size, rapid movement and nocturnal lifestyle, while neither popular observation methods such as camera traps nor conventional tracking technologies sufficiently capture the behaviour of individuals. The combination and networking of different sensors in a single system can overcome these limitations, but this potential has been explored only to a limited extent. We present BatRack, a multi‐sensor device that combines ultrasonic audio recordings, automatic radio telemetry and video camera recordings in a single modular unit. BatRack facilitates the individual or combined scheduling of sensors and includes a mutual triggering mode. It consists of off‐the‐shelf hardware and both its hardware blueprints and the required software have been published under an open license to allow scientists and practitioners to replicate the system. We tested the suitability of radio telemetry and audio sensors as camera triggers and evaluated the detection of individuals in video recordings compared to radio telemetry signals. Specifically, BatRack was used to monitor the individual swarming behaviour of six members of a maternity colony of Bechstein's bat. Preliminary anecdotal results indicate that swarming intensity is related to reproductive state and roost switching. BatRack allows researchers to recognize individual bats and monitor their behavioural patterns using an easily deployed and scalable system. BatRack is thus a promising approach to obtaining detailed insights into the behavioural ecology of bats.

Recent expertise development studies have used retrospective recall methods to explore developmental biographies and/or practice histories of current or past athletes. This methodological approach limits the generalizability and trustworthiness of findings. As such, a gap exists for research exploring key multidisciplinary features in athlete development using prospective longitudinal research designs. The present research aimed to holistically model the development of talent in Olympic Weightlifting using such a design. We observed the holistic profiles of 29 junior weightlifting athletes longitudinally over a 10-month period, and subsequently classified six of the 23 athletes as high performing based on their performances in competitions up to 12 months following the study. This holistic profile was based on a framework of expertise development themes: (1) demographics and family sport participation, (2) anthropometrics and physiological factors, (3) psychosocial profiling, (4) sport participation history, and (5) weightlifting specific practice activities. A summary model was produced which selected a critical set of nine features that classified group membership with 91% average accuracy. Odds ratio calculations uncovered discriminating features in the holistic profiles of performance groups, from which empirically derived logical statements could inform the description of high-performance attainment.

In oral and maxillofacial bone reconstruction, autografts from the iliac crest represent the gold standard due to their superior clinical performance, compared to autografts derived from other extraoral regions. Thus, the aim of our study was to identify putative differences between osteoblasts derived from alveolar (hOB-A) and iliac crest (hOB-IC) bone of the same donor (nine donors) by means of their molecular properties in 2D and 3D culture. We thereby focused on the gene expression of biomarkers involved in osteogenic differentiation, matrix formation and osteoclast modulation. Furthermore, we examined the transcriptional response to Vit.D3 in hOB-A and hOB-IC. Our results revealed different modulation modes of the biomarker expression in osteoblasts, namely cell origin/bone entity-dependent, and culture configuration- and/or time-dependent modulations. SEMA3A, SPP1, BGLAP and PHEX demonstrated the strongest dependence on cell origin. With respect to Vit.D3-effects, BGLAP, SPP1 and ALPL displayed the highest Vit.D3-responsiveness. In this context we demonstrated that the transcriptional Vit.D3-response concerning SPP1 and ALPL in human osteoblasts depended on the cell origin. The results indicate a higher bone remodeling activity of iliac crest than alveolar osteoblasts and support the growing evidence that a high osteoclast activity at the host-/donor bone interface may support graft integration.