Evaluation of the Utility of Decomposition-Enhanced Spike-Triggered Averaging Motor Unit Number Estimation as an Outcome Measure for the Study of Amyotrophic Lateral Sclerosis

OBJECTIVES: The objectives of this thesis were to review the use of outcome measures systematically across amyotrophic lateral sclerosis (ALS) clinical trials, and evaluate the utility of decomposition-enhanced spike-triggered averaging (DE-STA) motor unit number estimation (MUNE) as an outcome measure, with a particular focus on its application to the upper trapezius (UT). METHODS: First, a systematic review quantified the frequency of use of outcome measures in ALS randomized controlled trials (Chapter 2). Next, the intra- and inter-rater reliability of DE-STA MUNE was evaluated in the UT of control subjects (Chapter 3), followed by the intra-rater reliability of the technique in the UT and biceps brachii of subjects with ALS (Chapter 4). To assess validity, the results of the technique in the UT were compared between subjects with ALS and control subjects (Chapter 4). The sensitivity to change of DE-STA MUNE in the UT was compared with that of various clinical outcome measures in a longitudinal study of subjects with ALS (Chapter 5). Finally, the influence of needle electrode depth on the results of the technique in the UT was evaluated in control subjects (Chapter 6). RESULTS: The heterogeneity in the use of outcome measures across ALS randomized controlled trials was demonstrated, in addition to the infrequent use of MUNE. MUNE results demonstrated moderate intra- and inter-rater reliability for control subjects in the UT, although less favorable results were found overall for inter-rater reliability. Application of DE-STA MUNE to the UT in subjects with ALS demonstrated consistently high intra-rater reliability, the ability to detect the underlying pathophysiology of the disease, and a moderate degree of sensitivity to change for MUNE results. Further evaluation found needle electrode depth to significantly influence the results of the technique, with suggestions made for improved standardization of the protocol. SIGNIFICANCE: These studies were novel in their evaluation of MUNE in the proximal, potentially clinically relevant UT. The studies mark the first evaluations of the reliability and sensitivity to change of DE-STA MUNE in subjects with ALS, finding application to the UT to be practical and promising for use as an outcome measure. Implementation of proposed improvements to the protocol may aid in further establishing DE-STA MUNE for use as an outcome measure in studies of ALS

Continued development of a detailed model of arc discharge dynamics

Using a previously developed set of codes (SEMC, CASCAD, ACORN), a parametric study was performed to quantify the parameters which describe the development of a single electron indicated avalanche into a negative tip streamer. The electron distribution function in Teflon is presented for values of the electric field in the range of four-hundred million volts/meter to four billon volts/meter. A formulation of the scattering parameters is developed which shows that the transport can be represented by three independent variables. The distribution of ionization sites is used to indicate an avalanche. The self consistent evolution of the avalanche is computed over the parameter range of scattering set

Caregivers' experiences with the new family‐centred paediatric physiotherapy programme COPCA : a qualitative study

Caregivers' experiences during early intervention of their infant with special needs have consequences for their participation in the intervention. Hence, it is vital to understand caregivers' view. This study explored caregivers' experiences with the family-centred early intervention programme "COPing with and CAring for infants with special needs" (COPCA)

Teaching Medical Humanities in Medical Schools with Open Education Resources

In this chapter we will explore various ways in which open education resources might be utilised in the teaching of medical humanities in medical schools. Open education resources are generic open access materials in a particular field, which can be used by educators and students alike to support teaching and learning. They might be particularly useful when an institution lacks staff with specific expertise to teach essential but ‘minority’ subjects. The open and generic nature of these resources almost always means that they can be used flexibly to suit the teaching and learning contexts in which they are used. However, that same generic character means that they will be rarely directed towards specific learning outcomes, and therefore educators might struggle to fit them into teaching programmes, or have to alter their own learning outcomes and curricula in order to fit the resources available.Here, we outline and reflect upon different ways we have used open access medical humanities materials developed by the ALCMAEON project to support teaching in UK medical programmes the medical schools at the University of Bristol and University of St Andrews respectively. We begin by discussing the difficulties often encountered in teaching medical humanities in the crowded medical curriculum, before outlining what open education resources are and how they can help, with particular reference to the ALCMAEON project. We then outline and reflect on three different ways in which the ALCMAEON resources have been used to support teaching and learning with medical humanities, and consider the wider lessons we can draw from that experience about the use and development of open education resources to support learning and teaching of ‘minority’ subjects in medical curricula.<br/

Comprehensive design and whole-cavity simulation of a multi-beam inductive output tube using a 3rd harmonic drive on the grid

In this paper, we discuss the design and whole-cavity simulation of a Multi-Beam Inductive Output Tube (MBIOT) that uses a 3rd harmonic component to the drive voltage on the grid. High-efficiency inductive output tubes (IOTs) are typically characterized by efficiencies up to 70 - 75%. However, the achievement of efficiencies greater than 80% would substantially reduce the operating costs of next-generation accelerators. To achieve this goal, we consider the addition of a 3rd harmonic component to the drive signal on the grid. We anticipate that the MBIOT will be used to provide the rf power to drive RF linacs. We discuss and model an 8-beam MBIOT with a 700 MHz resonant cavity using beams with a voltage of 35 kV and an average current of 7.25 A yielding a perveance of about 1.1 microP. We simulate this MBIOT using the NEMESIS simulation code which has been extended using a three-dimensional Poisson solver based upon the Petsc package from Argonne National Laboratory. The effect of the 3rd harmonic on the efficiency is greatest when the phase of the 3rd harmonic is shifted by pi radians with respect to the fundamental drive signal and with 3rd harmonic powers greater than about 50% of the fundamental drive power. For the present example, we show that efficiencies approaching 82% are possible. Designs for the MBIOT input coupler, grids and output cavity have been developed based on these simulations and will be discussed.Comment: 12 pages, 30 figure

Weaving Indigenous and Western Science Knowledges Through a Land-Based Field Course at Bkejwanong Territory (Laurentian Great Lakes)

In response to a growing interest in building Indigenous-led educational experiences, we codeveloped a land-based field course that wove Indigenous ways of knowing together with Western ecological concepts. The spirit of the course was the one rooted in varied ways of knowing nature, on the land, the water, and the culture—to see the Great Lakes from an Anishinaabe perspective. Situated in the heart of the Laurentian Great Lakes Basin at Bkejwanong Territory (Walpole Island First Nation), in the Traditional Territory of the Three Fires Confederacy of First Nations (Ojibwe, Odawa, and Potawatomi) on Turtle Island (North America), this inaugural undergraduate university course was led by an Indigenous instructor with contributions from non-Indigenous science faculty from the university and local community knowledge keepers. Here, we describe our journey in cocreating land-based teaching modules with Indigenous scholars and scholars at the University of Windsor, Ontario, Canada. We focused on experiences that exposed students to traditional ways of knowing nature, and reflections were used as the main teaching pedagogy. The course offered daily perspectives and activities across land and water and examined dimensions of biodiversity as sacred beings and medicine. Outcomes and indicators of success were driven by the individual’s reflection and evaluation on their own growth, as expressed through a final project aimed at bridging knowledges, supporting community initiatives or both. This case is designed to offer an example that has potential for application to many other contexts where community-faculty partnerships and land-based learning opportunities are availabl

Advanced Practice Pharmacists: a retrospective evaluation of the efficacy and cost of ClinicaL Pharmacist PractitionErs managing ambulatory Medicare patients in North Carolina (APPLE-NC)

Abstract Background Clinical Pharmacist Practitioners are advanced practicing pharmacists in North Carolina that provide disease-specific management. The purpose of this retrospective cohort study was to compare the efficacy and charges from referrals to a Clinical Pharmacist Practitioner by the primary care provider, to those managed by a primary care provider alone. Methods Patients were separated into cohorts depending if they had at least two appointments with a Clinical Pharmacist Practitioner from November 2008 to November 2011. A primary care provider saw all patients at least twice during the study period. Cohorts were then matched by age, gender, and disease states. Medicare billed data was evaluated from outpatient visits related to hypertension, diabetes mellitus, and peripheral neuropathy, as well as emergency department visits and inpatient admissions. Cost of medications was estimated using 2009 AWP data corresponding to medication histories within the electronic medical record. Efficacy was defined as ability to reach disease state goal determined using national guidelines and reduction in pain score. Efficacy was analyzed by difference-in-differences test and all other numerical data tested by paired t-tests. Results The Clinical Pharmacist Practitioners cohort experienced more outpatient visits (1338 vs. 858, p < 0.001), fewer emergency department visits (115 vs. 190, p < 0.05), and similar inpatient admissions (88 vs. 117, p > 0.05) than the primary care providers cohort, respectively. The Clinical Pharmacist Practitioners cohort showed changes in charges of +22.6 % for outpatient visits, −45.5 % emergency department visits, and −13.2 % inpatient admissions relative to the primary care provider cohort. There was no difference in average daily medication cost (Clinical Pharmacist Practitioners $38.52 vs. primary care providers$38.23, p = 0.97) or achievement of disease state goals. Conclusion APPLE-NC demonstrated that through referrals, Clinical Pharmacist Practitioners provide services comparable in charges and efficacy to primary care providers. Consequently, the current increased need for primary care practitioners can be met in part by increasing the utilization of advanced practice pharmacists for chronic disease management. Trial registration This does not apply for this retrospective cohort study

Statistical analysis plan for the Stroke Oxygen Study (SO₂S): a multi-center randomized controlled trial to assess whether routine oxygen supplementation in the first 72 hours after a stroke improves long-term outcome.

BACKGROUND: The Stroke Oxygen Study (SO₂S) is a multi-center randomized controlled trial of oxygen supplementation in patients with acute stroke. The main hypothesis for the trial is that fixed-dose oxygen treatment during the first 3 days after an acute stroke improves outcome. The secondary hypothesis is that restricting oxygen supplementation to night time only is more effective than continuous supplementation. This paper describes the statistical analysis plan for the study. METHODS AND DESIGN: Patients (n = 8000) are randomized to three groups: (1) continuous oxygen supplementation for 72 hours; (2) nocturnal oxygen supplementation for three nights; and (3) no routine oxygen supplementation. Outcomes are recorded at 7 days, 90 days, 6 months, and 12 months. The primary outcome measure is the modified Rankin scale at 90 days. Data will be analyzed according to the intention-to-treat principle. Methods of statistical analysis are described, including the handling of missing data, the covariates used in adjusted analyses, planned subgroups analyses, and planned sensitivity analyses. TRIAL REGISTRATION: This trial is registered with the ISRCTN register, number ISRCTN52416964 (30 September 2005)

Shape, size, and maturity trajectories of the human ilium

Morphological traits of the ilium have consistently been more successful for juvenile sex determination than have techniques applied to other skeletal elements, however relatively little is known about the ontogeny and maturation of size and shape dimorphism in the ilium. We use a geometric morphometric approach to quantitatively separate the ontogeny of size and shape of the ilium, and analyze interpopulation differences in the onset, rate and patterning of sexual dimorphism. We captured the shape of three traits for a total of 191 ilia from Lisbon (Portugal) and London (UK) samples of known age and sex (0-17 years). Our results indicate that a) there is a clear dissociation between the ontogeny of size and shape in males and females, b) the ontogeny of size and shape are each defined by nonlinear trajectories that differ between the sexes, c) there are interpopulation differences in ontogenetic shape trajectories, which point to population-specific patterning in the attainment of sexual dimorphism, and d) the rate of shape maturation and size maturation is typically higher for females than males. Male and female shape differences in the ilium are brought about by trajectory divergence. Differences in size and shape maturation between the sexes suggest that maturity may confound our ability to discriminate between the sexes by introducing variation not accounted for in age-based groupings. The accuracy of sex determination methods using the ilium may be improved by the use of different traits for particular age groups, to capture the ontogenetic development of shape in both sexes