Patient acceptability, safety and access : A balancing act for selecting age-appropriate oral dosage forms for paediatric and geriatric populations

© 2017 Elsevier B.V. All rights reserved.The selection and design of age-appropriate formulations intended for use in paediatric and geriatric patients are dependent on multiple factors affecting patient acceptability, safety and access. The development of an economic and effective product relies on a balanced consideration of the risks and benefits of these factors. This review provides a comprehensive and up-to-date analysis of oral dosage forms considering key aspects of formulation design including dosage considerations, ease of use, tolerability and safety, manufacturing complexity, stability, supply and cost. Patient acceptability has been examined utilising an evidence-based approach to evaluate regulatory guidance and literature. Safety considerations including excipients and potential risk of administration errors of the different dosage forms are also discussed, together with possible manufacturing and supply challenges. Age appropriate drug product design should consider and compare i) acceptability ii) safety and iii) access, although it is important to recognise that these factors must be balanced against each other, and in some situations a compromise may need to be reached when selecting an age-appropriate formulation.Peer reviewedFinal Accepted Versio

Observations of Global and Local Infall in NGC 1333

We report ``infall asymmetry'' in the HCO$^+$ (1--0) and (3--2) lines toward NGC 1333, extended over $\sim 0.39 {\rm pc}^2$, a larger extent than has been reported be fore, for any star-forming region. The infall asymmetry extends over a major portion of the star-forming complex, and is not limited to a single protostar, or to a single dense core, or to a single spectral line. It seems likely that the infall asymmetry represents inward motions, and that these motions are physically associated with the complex. Both blue-asymmetric and red-asymmetric lines are seen, but in both the (3--2) and (1--0) lines of HCO$^+$ the vast majority of the asymmetric lines are blue, indicating inward motions. The (3--2) line, tracing denser gas, has the spectra with the strongest asymmetry and these spectra are associated with the protostars IRAS 4A and 4B, which most likely indicates a warm central source is affecting the line profiles. The (3--2) and (1--0) lines usually have the same sense of asymmetry in common positions, but their profiles differ significantly, and the (1--0) line appears to trace motions on much larger spatial scales than does the (3--2) line. Line profile models fit the spectra well, but do not strongly constrain their parameters. The mass accretion rate of the inward motions is of order 10$^{-4}$ M$_\odot$/yr, similar to the ratio of stellar mass to cluster age.Comment: 28 pages, 11 figures, 1 colour figur

Hydraulic Fracture

We consider a variation of Griffith's analysis of rupture, one which simulates the process of hydrofracturing, where fluid forced into a crack raises the fluid pressure until the crack begins to grow. Unlike that of Griffith, in this analysis fluid pressure drops as a hydrofracture grows. We find that growth of the fracture depends on the ratio of the compliances of the fluid and the fracture, a non-dimensional parameter called $\alpha_0$ here. The pressure needed to initiate a hydrofracture is found to be the same as that derived by Griffith. Once a fracture initiates, for relatively low values of the model parameter $\alpha_0$ ($\alpha_0 \leq 0.2$) the fracture advances spontaneously to a new radius which depends on the value of $\alpha_0$. For $\alpha_0 \leq 0.2$ further fluid injection is required to increase the fracture radius after spontaneous growth stops. For the case where $\alpha_0 > 0.2$ each increment of fracture growth requires injection of more fluid. For the extreme case where $\alpha_0 = 0$ our results are the same as Griffith's, i.e., a fracture once initiated grows without limit.Comment: 10 pages, 4 figure

The Phase Diagram of 1-in-3 Satisfiability Problem

We study the typical case properties of the 1-in-3 satisfiability problem, the boolean satisfaction problem where a clause is satisfied by exactly one literal, in an enlarged random ensemble parametrized by average connectivity and probability of negation of a variable in a clause. Random 1-in-3 Satisfiability and Exact 3-Cover are special cases of this ensemble. We interpolate between these cases from a region where satisfiability can be typically decided for all connectivities in polynomial time to a region where deciding satisfiability is hard, in some interval of connectivities. We derive several rigorous results in the first region, and develop the one-step--replica-symmetry-breaking cavity analysis in the second one. We discuss the prediction for the transition between the almost surely satisfiable and the almost surely unsatisfiable phase, and other structural properties of the phase diagram, in light of cavity method results.Comment: 30 pages, 12 figure

3D Spectrophotometry of Planetary Nebulae in the Bulge of M31

We introduce crowded field integral field (3D) spectrophotometry as a useful technique for the study of resolved stellar populations in nearby galaxies. As a methodological test, we present a pilot study with selected extragalactic planetary nebulae (XPN) in the bulge of M31, demonstrating how 3D spectroscopy is able to improve the limited accuracy of background subtraction which one would normally obtain with classical slit spectroscopy. It is shown that due to the absence of slit effects, 3D is a most suitable technique for spectrophometry. We present spectra and line intensities for 5 XPN in M31, obtained with the MPFS instrument at the Russian 6m BTA, INTEGRAL at the WHT, and with PMAS at the Calar Alto 3.5m Telescope. Using 3D spectra of bright standard stars, we demonstrate that the PSF is sampled with high accuracy, providing a centroiding precision at the milli-arcsec level. Crowded field 3D spectrophotometry and the use of PSF fitting techniques is suggested as the method of choice for a number of similar observational problems, including luminous stars in nearby galaxies, supernovae, QSO host galaxies, gravitationally lensed QSOs, and others.Comment: (1) Astrophysikalisches Institut Potsdam, (2) University of Durham. 18 pages, 11 figures, accepted for publication in Ap

Star Formation in Bright Rimmed Clouds. I. Millimeter and Submillimeter Molecular Line Surveys

We present the results of the first detailed millimeter and submillimeter molecular line survey of bright rimmed clouds, observed at FCRAO in the CO (J=1-0), C18O (J=1-0), HCO+ (J=1-0), H13CO+ (J=1-0), and N2H+ (J=1-0) transitions, and at the HHT in the CO (J=2-1), HCO+ (J=3-2), HCO+ (J=4-3), H13CO+ (J=3-2), and H13CO+ (J=4-3) molecular line transitions. The source list is composed of a selection of bright rimmed clouds from the catalog of such objects compiled by Sugitani et al. (1991). We also present observations of three Bok globules done for comparison with the bright rimmed clouds. We find that the appearance of the millimeter CO and HCO+ emission is dominated by the morphology of the shock front in the bright rimmed clouds. The HCO+ (J=1-0) emission tends to trace the swept up gas ridge and overdense regions which may be triggered to collapse as a result of sequential star formation. Five of the seven bright rimmed clouds we observe seem to have an outflow, however only one shows the spectral line blue-asymmetric signature that is indicative of infall, in the optically thick HCO+ emission. We also present evidence that in bright rimmed clouds the nearby shock front may heat the core from outside-in thereby washing out the normally observed line infall signatures seen in isolated star forming regions. We find that the derived core masses of these bright rimmed clouds are similar to other low and intermediate mass star forming regions.Comment: 67 pages, including 35 figures and 6 tables. Accepted for publication in ApJ. Version with embedded full-resolution figures available at http://www.astro.umass.edu/~devries/brc1

How do people with chronic pain choose their music for pain management? Examining the external validity of the cognitive vitality model

Music interventions for pain are more successful when patients choose the music themselves. But little is known about the attentional strategies used by chronic pain patients when choosing or using music for pain management, and the degree to which these attentional strategies align with the cognitive mechanisms outlines in the cognitive vitality model (CVM, a recently developed theoretical framework that outlines five cognitive mechanisms that mediate the analgesic effects of music for pain management). To investigate this question, we used a sequential explanatory mixed method approach, which included a survey, online music listening experiment, and qualitative data collection, with chronic pain patients (n=70). First, we asked chronic pain patients to name a piece of music that they would use to manage their chronic pain, and answer 19 questions about why they chose that particular piece of music using a questionnaire based on the CVM. Next, we asked chronic pain patients to listen to high energy and low energy pieces of music, to understand aesthetic music preferences and emotional responses at the group level. Finally, participants were asked to qualitatively tell us how they used music to manage their pain. Factor Analysis was completed on the survey data, and identified a five-factor structure in participant responses that was consistent with five mechanisms identified in the CVM. Regression analysis indicated that chronic pain patients choose music for pain management if they think it will facilitate Musical Integration and Cognitive Agency. Musical Integration refers to the degree to which the music can provide an immersive and absorbing experience. Cognitive Agency refers to having an increased feeling of control. At the group level, participants reported a preference for low energy music, and reported that they found high energy music more irritating. However, is it important to note that individual people had different music preferences. Thematic synthesis of patient responses highlighted how these processes mediate the analgesic benefits of music listening from the perspective of chronic pain patients, and highlighted the wide range of music used by participants for chronic pain management including electronic dance music, heavy metal and Beethoven. These findings demonstrate that chronic pain patients use specific attentional strategies when using music for pain management, and these strategies align with the cognitive vitality model

Space station automation of common module power management and distribution

The purpose is to automate a breadboard level Power Management and Distribution (PMAD) system which possesses many functional characteristics of a specified Space Station power system. The automation system was built upon 20 kHz ac source with redundancy of the power buses. There are two power distribution control units which furnish power to six load centers which in turn enable load circuits based upon a system generated schedule. The progress in building this specified autonomous system is described. Automation of Space Station Module PMAD was accomplished by segmenting the complete task in the following four independent tasks: (1) develop a detailed approach for PMAD automation; (2) define the software and hardware elements of automation; (3) develop the automation system for the PMAD breadboard; and (4) select an appropriate host processing environment

Invertible Dirac operators and handle attachments on manifolds with boundary

For spin manifolds with boundary we consider Riemannian metrics which are product near the boundary and are such that the corresponding Dirac operator is invertible when half-infinite cylinders are attached at the boundary. The main result of this paper is that these properties of a metric can be preserved when the metric is extended over a handle of codimension at least two attached at the boundary. Applications of this result include the construction of non-isotopic metrics with invertible Dirac operator, and a concordance existence and classification theorem.Comment: Accepted for publication in Journal of Topology and Analysi

Post-transplantation cutaneous and renal Aspergillus infection

A 68-year old renal transplant recipient suffered multiple complications following initial good graft function from a deceased-donor transplant. Late in the first week he was oliguric with haematuria; the graft failed in week 2 following development of a haematoma from rupture of a renal artery aneurysm. He had a recurrent bleed from the internal iliac graft site and subsequently developed painful dark patches on his leg, distal to where the transplant had been. Histology from the explanted graft and skin biopsies demonstrated Aspergillus flavus; this was also grown in culture of the external iliac artery tissue. Systemic aspergillosis is rare but well recognised, especially in the immunocompromised. Presentations include mycotic aneurysms and secondary cutaneous aspergillosis from haematogenous spread. Diagnosis requires confirmation by histology or direct culture, but a high beta-glucan concentration and positive galactomannan antigen can suggest invasive fungal infection in the early stages of the disease. Cases should be managed with systemic antifungals and involvement of local microbiology services; unfortunately, prognosis is poor