Excipient Risk Analysis: A new ERA

Non

Master of Science

thesisEssential amino acids (EAA) are a potent stimulator of mammalian target of rapamycin complex 1 (mTORC1) signaling and muscle protein synthesis. However, the molecular regulators upstream of mTORC1 signaling that are stimulated by EAA are not well described in human skeletal muscle. Leucyl tRNA synthetase (LRS) and RagB have recently been shown to be important in mTORC1 activation, but their role in human skeletal muscle following EAA ingestion is unknown. The purpose of this study was to determine changes in protein expression and the association of the LRS- and RagB RagBmTORC1 complexes following acute EAA ingestion in healthy human skeletal muscle. Muscle biopsies (vastus lateralis) were obtained from 13 young adults (7M, 6F, 22.9 ± 0.9y, 21.7 ± 0.9 BMI) in the fasted state (basal) and 1 and 3 h after EAA (13g; 2.4g Leu) ingestion. Co-immunoprecipitation and western blotting were used to determine LRSand RagB-mTORC1 protein complexes and LRS and RagB protein expression, respectively. We report that EAA ingestion did not alter LRS- or RagB-mTORC1 association or LRS protein expression (P > 0.05) contrary to the robust increase in mTOR phosphorylation (P < 0.05). However, we found that EAA increased RagB protein abundance following EAA ingestion (P < 0.05). We conclude that LRS- and RagBmTORC1 complexes are not altered 1 and 3 h following EAA ingestion in healthy young adult skeletal muscle. However, the transient increase in RagB protein expression afterEAA ingestion may be an important mechanism to promote protein anabolism

Paediatricians’ Engagement with Reflective Practice: A Scoping Review

Introduction: This scoping review identified literature describing reflective practice amongst paediatricians and then aligned the reflective concepts with Wellington and Austin’s Orientations to Reflection: Immediate, Technical, Deliberative, Dialectical and Transpersonal. These distinctions present concepts for paediatricians to contemplate in their reflective practice. Methods: OVID MEDLINE and APA PsycInfo databases were searched for English language articles in peer-reviewed journals using the terms “paediatric*” AND “pediatric*” AND “doctor*” and “physician*” AND “reflect*”. A data capture form was created and populated. Results: Twenty-one articles describing reflective practice amongst paediatricians were identified. Most articles (43%; n = 9) described the immediate orientation to reflection. One article, a personal perspective from a late-career stage paediatrician, aligned with a transpersonal orientation to reflection. Conclusions: Reflective practice of the immediate orientation is accepted by paediatricians during education initiatives. It often takes place accidentally but can be developed through awareness of reflection, role-modelling, goal-setting, and feedback. Enhancing factors include a friendly, flexible learning environment, faculty support, protected time, and sharing significant experiences. Positive effects of promoting reflection include enhancing clinical practice, increasing resilience, and entrustment. Barriers include emphasis on efficiency, lack of continuity or awareness, negative emotions, and burnout. Reflective practice should be encouraged. One should not assume “it just happens”

Rings and Radial Waves in the Disk of the Milky Way

We show that in the anticenter region, between Galactic longitudes of $110^\circ<l<229^\circ$, there is an oscillating asymmetry in the main sequence star counts on either side of the Galactic plane using data from the Sloan Digital Sky Survey. This asymmetry oscillates from more stars in the north at distances of about 2 kpc from the Sun to more stars in the south at 4-6 kpc from the Sun to more stars in the north at distances of 8-10 kpc from the Sun. We also see evidence that there are more stars in the south at distances of 12-16 kpc from the Sun. The three more distant asymmetries form roughly concentric rings around the Galactic center, opening in the direction of the Milky Way's spiral arms. The northern ring, 9 kpc from the Sun, is easily identified with the previously discovered Monoceros Ring. Parts of the southern ring at 14 kpc from the Sun (which we call the TriAnd Ring) have previously been identified as related to the Monoceros Ring and others have been called the Triangulum Andromeda Overdensity. The two nearer oscillations are approximated by a toy model in which the disk plane is offset by of the order 100 pc up and then down at different radii. We also show that the disk is not azimuthally symmetric around the Galactic anticenter and that there could be a correspondence between our observed oscillations and the spiral structure of the Galaxy. Our observations suggest that the TriAnd and Monoceros Rings (which extend to at least 25 kpc from the Galactic center) are primarily the result of disk oscillations.Comment: 19figures, 2tables, ApJ accepte

Excipient risk analysis: A new ERA?

Excipient risk management must address the three sources of excipient-related risk; namely, safety, supply chain integrity and technological risk

Inclusion of relevant tests in the Pharmacopoeia to improve supply chain integrity

Because current compendial methods are not sufficiently robust, specific or rapid enough for many excipients, compliance with specifications is a complement, not a substitute for supply chain security. Multiple and more specific tests will hinder economically motivated adulteration. Specifications should be improved, supply chain oversight tightened, and caveat emptor

The First Hypervelocity Star from the LAMOST Survey

We report the first hypervelocity star (HVS) discovered from the LAMOST spectroscopic survey. It is a B-type star with a heliocentric radial velocity about 620 km/s, which projects to a Galactocentric radial velocity component of ~477 km/s. With a heliocentric distance of ~13 kpc and an apparent magnitude of ~13 mag, it is the nearest bright HVS currently known. With a mass of ~9Msun, it is one of the three most massive HVSs discovered so far. The star is clustered on the sky with many other known HVSs, with the position suggesting a possible connection to Galactic center structures. With the current poorly-determined proper motion, a Galactic center origin of this HVS remains consistent with the data at the 1sigma level, while a disk run-away origin cannot be excluded. We discuss the potential of the LAMOST survey to discover a large statistical sample of HVSs of different types.Comment: 5 pages, 5 figures, accepted for publication in ApJL, updated contour plot for the ejection positions after correcting a mistake in the calculatio