Parathyroid Hormone (1-84): Assay Development and Application to the Physiology and Pathophysiology of Calcium Homeostasis

1. The initial aim of the thesis was the production of monoclonal antibodies for use in the development of an assay for PTH (1-84). The response to immunisation, using chemically synthesised PTH peptides as immunogen, was species and strain specific with DA rats consistently responding with high titre antibodies to PTH (1-34). Five monoclonal antibodies were produced to PTH (1-34), three of which (3B3, 4G3 and 6E3) were considered to be of potential use in assay systems. 2. A two-site immunometric assay specific for PTH (1-84) has been developed using 3B3 and a C-terminal monoclonal antibody - ESQ1. The assay development studies revealed 3B3 to be sensitive to the oxidation state of PTH. Hydrogen peroxide is therefore included in the assay to convert endogenous PTH (1-84) to the oxidised form prior to measurement. The validation studies confirmed the assay to be unaffected by PTH fragments. The assay has a minimum detection limit of 0.5 pmol/1, sufficient to measure PTH (1-84) in all normal subjects, and a range of 1. 5-250 pmol/1 with an intra-assay CV of less than 10% (2.8-250 pmol/1 less than 5% CV). Studies on clinical samples indicate good discrimination between normal subjects (mean 2. 1; range 1.0-5.0 pmol/1) and patients with primary hyperparathyroidism (mean 21.; range 5.8-100 pmol/1) who in turn are well separated from patients with hypercalcaemia of malignancy (14/180.5 pmol/1). 3. The measurement of PTH(1-84) over a 24 h period has shown the existence of circadian rhythm, characterised by an early evening rise and a broad peak through the night, in normal subjects which is absent in patients with primary hyperparathyroidism. The physiological significance of this observation is reflected in the presence of parallel changes in nephrogenous cyclic adenosine monophosphate in the normal subjects which are also absent in the hyperparathyroid patients. Although transient falls in calcium were observed these studies the changes in PTH (1-84) over the 24 h period could not be fully accounted for by changes in serum adjusted calcium concentrations. An important observation from these studies was that discrimination between normal subjects and patients with primary hyperparathyroidism is time dependent. Thus for optimal discrimination between normal subjects and patients with primary hyperparathyroidism PTH (1-84) samples should be taken, and reference ranges established, between 1000 and 1600 h. The most significant finding of the circadian studies was that PTH (1-84) concentrations in normal subjects over a 24 h period show a stronger temporal correlation with other circadian hormones, notably prolactin, than with adjusted calcium concentrations. This observation suggests that factors other than plasma ionised calcium are involved in the tonic control of PTH (1-84) secretion. 4. PTH (1-84) concentrations in the circulation vary in a manner consistent with pulsatile secretion. The estimates of pulsatility obtained in normal subjects, pulses every 10-15 minutes, are in agreement with the frequency of pulsatility previously reported for bioactive PTH. This supports the concept of PTH (1-84) being the major bioactive form of PTH in the circulation. The response to an acute lowering of serum calcium confirms that, in common with other hormones, modulations of the amplitude and frequency of pulses are an integral part of the control of PTH (1-84) secretion. However, the pattern of pulsatility observed, at the frequencies studied, appears to be characteristic of the individual and does not correlate with the presence of primary hyperparathyroidism. 5. The response to treatment, with the bisphosphonate Pamidronate, was compared in patients with either Paget's disease of bone or hypercalcaemia associated with malignancy. In the patients with Paget's disease therapy with Pamidronate produced a small but significant drop in serum adjusted calcium which was sustained throughout the study. This was accompanied by a significant rise in PTH (1-84). The concentration of PTH (1-84) continued to rise progressively despite no further fall in serum calcium. In patients with hypercalcaemia of malignancy Pamidronate produced the expected and prolonged decrease in serum adjusted calcium such that at the end of the study the mean calcium in these patients was within the reference interval. The PTH (1-84) concentrations rose progressively throughout the study to a mean concentration above the reference interval. More interestingly the initial increase occurred when the mean adjusted calcium was above the reference interval with no patient hypocalcaemic. The results suggest a resetting of the 'trigger' point for PTH (1-84) secretion in patients with hypercalcaemia of malignancy. An important conclusion from this study is that in the assessment of PTH (1-84) concentrations in the hypercalcaemic patient samples should be obtained prior to treatment being initiated

Perceptions of Graduates from a Canadian Bachelor of Nursing Program: Preparing for the Registered Nurse National Council Licensure Examination (NCLEX-RN) (Perceptions des diplômées d’un programme canadien de baccalauréat en sciences infirmières : préparation à l’examen pour infirmières autorisées du National Council Licensure Examination (NCLEX-RN)

Perceptions of Graduates from a Canadian Bachelor of Nursing Program: Preparing for the Registered Nurse National Council Licensure Examination (NCLEX-RN) As a self-regulated profession, nursing in Canada is based on legislation enacted by provincial and territorial associations with the purpose of protecting the public from harm (Marquis & Trajan, 2012). Since 1970 most Canadian jurisdictions required completion of national examinations to obtain professional licensure (Elliott, Rutty & Villeneuve, 2013; Kovner & Spetz, 2013). In 2011 the Canadian Council of Registered Nurse Regulators (CCRNR) announced the Canadian Registered Nurse Examination (CRNE) would be replaced with the National Council Licensure Examination-Registered Nurse (NCLEX-RN) developed in the United States as the new requirement for registered nurses (RN) to enter practice in Canada. The implementation of the NCLEX-RN in 2015 stimulated extensive dialogue among nursing stakeholders in Canada. Preliminary exam results indicated that the first cohort of Canadian NCLEX-RN writers had lower scores than both previous CRNE results and the NCLEX-RN pass rates of writers in the United States (Hobbins & Bradley, 2013; PennellSebekos, 2015). A key factor impacting NCLEX-RN success is strategies used by candidates to prepare for the exam. This paper describes research undertaken to investigate the perceptions of the first cohort of graduates from an Atlantic Canada Bachelor of Nursing (BN) program about their NCLEX-RN preparations. The investigation focused on strategies employed by participants prior to, and after program completion, and how these preparations aligned with their experiences in writing the exam. Résumé La profession infirmière au Canada étant autorégulée, elle se fonde sur la législation adoptée par les ordres professionnels des provinces et territoires afin de protéger le public de tout danger (Marquis & Trajan, 2012). Depuis 1970, la plupart des autorités canadiennes en la matière exigent la réussite d’un examen national en vue de l’obtention du permis d’exercer professionnellement (Elliott, Rutty & Villeneuve, 2013; Kovner & Spetz, 2013). En 2011, le Conseil canadien des organismes de réglementation de la profession infirmière (CCORPI) a annoncé que l’Examen d’autorisation infirmière au Canada (EAIC) serait remplacé par l’examen américain pour infirmières autorisées du National Council Licensure Examination (NCLEX-RN), à titre de nouvelle exigence d’entrée dans la pratique des infirmières autorisées au Canada. L’implantation du NCLEX-RN, en 2015, a engendré de nombreuses discussions parmi les diverses parties prenantes du domaine infirmier au pays. Les résultats de l’examen préliminaire indiquaient que la première cohorte de diplômées canadiennes à passer le NCLEX-RN a obtenu des notes inférieures aux deux EAIC précédents et un taux plus faible de réussite que les candidates américaines au NCLEX-RN (Hobbins & Bradley, 2013; Pennell-Sebekos, 2015). Un facteur essentiel de réussite du NCLEX-RN est le suivant: les stratégies adoptées par les candidates pour se préparer à l’examen. Cet article décrit la recherche entreprise pour examiner les perceptions de la première cohorte de diplômées d’un programme de baccalauréat en sciences infirmières dans la région atlantique en ce qui concerne leur préparation à l’examen NCLEX-RN. La recherche portait sur les stratégies employées par les participantes avant et après la fin de leur programme, et sur le parallèle entre cette préparation et leur expérience en cours d’examen

A Study of the Use of Social Media Marketing in the Football Industry.

Football clubs across the globe are realising that the use of social media is the future in terms of improving and expanding their business, whether this be for marketing purposes or as a medium for directly communicating with their fans. Although this study found that the majority of European teams researched have a social network presence, there was a difference in how effectively social media was used between the various leagues. This study demonstrates that most football clubs have some social media presence, such as the number of Facebook likes, Twitter tweets and YouTube videos. However, the findings indicate that well-known world-wide clubs don’t always use this commercial potential as effectively as they might and that teams with lesser prominence sometimes use social media in a more effective way in order to market effectively to their fan base

Factors Influencing Parents’ Decision to Use Public Pre-K Programs in Maine: Results of a Parent Survey

This report presents the findings of a parent survey conducted in January-February 2016 by the Maine Education Policy Research Institute (MEPRI) at the request of the Maine State Legislature, to investigate barriers to participation in public pre-K programs for four year olds and other factors that influence parents’ decisions to use preschool programs (public or private) or no preschool. The report builds on earlier MEPRI research on preschool programs in Maine conducted through surveys and case study interviews in 2015. Together, the MEPRI data serve to inform state and local decisions about public preschool and specifically the proposed legislation LD 1394 “An Act to Implement the Recommendations of the Commission to Strengthen the Adequacy and Equity of Certain Cost Components of the School Funding Formula”

National Health Service healthcare staff experience and practices regarding complementary and alternative medicine: an online survey.

The use of complementary and alternative medicine (CAM) is increasing. The most common reported reason for CAM use is dissatisfaction with conventional healthcare. Several studies have reported factors influencing CAM usage and beliefs in the general public but the beliefs of healthcare staff are less well known. This paper reports the results of an online survey of 537 healthcare staff. Our study demonstrated an increased rate of patient referral for CAM from both personal CAM users and those trained in CAM. There was a high level of optimism amongst respondents as to the role CAM may play in patient care with mental health, depression and palliative care cited as the areas with highest expected benefit. Doctors were generally less optimistic about the likelihood of benefit compared to other healthcare staff. Implications for clinical practice, future research and staff education are discussed

Inferring Core-Collapse Supernova Physics with Gravitational Waves

Stellar collapse and the subsequent development of a core-collapse supernova explosion emit bursts of gravitational waves (GWs) that might be detected by the advanced generation of laser interferometer gravitational-wave observatories such as Advanced LIGO, Advanced Virgo, and LCGT. GW bursts from core-collapse supernovae encode information on the intricate multi-dimensional dynamics at work at the core of a dying massive star and may provide direct evidence for the yet uncertain mechanism driving supernovae in massive stars. Recent multi-dimensional simulations of core-collapse supernovae exploding via the neutrino, magnetorotational, and acoustic explosion mechanisms have predicted GW signals which have distinct structure in both the time and frequency domains. Motivated by this, we describe a promising method for determining the most likely explosion mechanism underlying a hypothetical GW signal, based on Principal Component Analysis and Bayesian model selection. Using simulated Advanced LIGO noise and assuming a single detector and linear waveform polarization for simplicity, we demonstrate that our method can distinguish magnetorotational explosions throughout the Milky Way (D <~ 10kpc) and explosions driven by the neutrino and acoustic mechanisms to D <~ 2kpc. Furthermore, we show that we can differentiate between models for rotating accretion-induced collapse of massive white dwarfs and models of rotating iron core collapse with high reliability out to several kpc.Comment: 22 pages, 9 figure