Haemodialysis work environment contributors to job satisfaction and stress: A sequential mixed methods study

Background: Haemodialysis nurses form long term relationships with patients in a technologically complex work environment. Previous studies have highlighted that haemodialysis nurses face stressors related to the nature of their work and also their work environments leading to reported high levels of burnout. Using Kanters (1997) Structural Empowerment Theory as a guiding framework, the aim of this study was to explore the factors contributing to satisfaction with the work environment, job satisfaction, job stress and burnout in haemodialysis nurses. Methods: Using a sequential mixed-methods design, the first phase involved an on-line survey comprising demographic and work characteristics, Brisbane Practice Environment Measure (B-PEM), Index of Work Satisfaction(IWS), Nursing Stress Scale (NSS) and the Maslach Burnout Inventory (MBI). The second phase involved conducting eight semi-structured interviews with data thematically analyzed. Results: From the 417 nurses surveyed the majority were female (90.9 %), aged over 41 years of age (74.3 %), and 47.4 % had worked in haemodialysis for more than 10 years. Overall the work environment was perceived positively and there was a moderate level of job satisfaction. However levels of stress and emotional exhaustion (burnout) were high. Two themes, ability to care and feeling successful as a nurse, provided clarity to the level of job satisfaction found in phase 1. While two further themes, patients as quasi-family and intense working teams, explained why working as a haemodialysis nurse was both satisfying and stressful. Conclusions: Nurse managers can use these results to identify issues being experienced by haemodialysis nurses working in the unit they are supervising.

Early stopping by using stochastic curtailment in a three-arm sequential trial

Summary. Interim analysis is important in a large clinical trial for ethical and cost considerations. Sometimes, an interim analysis needs to be performed at an earlier than planned time point. In that case, methods using stochastic curtailment are useful in examining the data for early stopping while controlling the inflation of type I and type II errors. We consider a three-arm randomized study of treatments to reduce perioperative blood loss following major surgery. Owing to slow accrual, an unplanned interim analysis was required by the study team to determine whether the study should be continued. We distinguish two different cases: when all treatments are under direct comparison and when one of the treatments is a control. We used simulations to study the operating characteristics of five different stochastic curtailment methods. We also considered the influence of timing of the interim analyses on the type I error and power of the test. We found that the type I error and power between the different methods can be quite different. The analysis for the perioperative blood loss trial was carried out at approximately a quarter of the planned sample size. We found that there is little evidence that the active treatments are better than a placebo and recommended closure of the trial.

Sequential allocation in clinical trials

Suppose two treatments with binary responses are available for patients with some disease and that each patient will receive one of the two treatments. In this paper we consider the interests of patients both within and outside a trial using a Bayesian bandit approach and conclude that equal allocation is not appropriate for either group of patients. It is suggested that Gittins indices should be used (using an approach called dynamic discounting by choosing the discount rate based on the number of future patients in the trial) if the disease is rare, and the least failures rule if the disease is common. Some analytical and simulation results are provided.

Preparation and in vitro release of drug-loaded microparticles for oral delivery using wholegrain sorghum kafirin protein

Kafirin microparticles have been proposed as an oral nutraceutical and drug delivery system. This study investigates microparticles formed with kafirin extracted from white and raw versus cooked red sorghum grains as an oral delivery system. Targeted delivery to the colon would be beneficial for medication such as prednisolone, which is used in the management of inflammatory bowel disease. Therefore, prednisolone was loaded into microparticles of kafirin from the different sources using phase separation. Differences were observed in the protein content, in vitro protein digestibility, and protein electrophoretic profile of the various sources of sorghum grains, kafirin extracts, and kafirin microparticles. For all of the formulations, the majority of the loaded prednisolone was not released in in vitro conditions simulating the upper gastrointestinal tract, indicating that most of the encapsulated drug could reach the target area of the lower gastrointestinal tract. This suggests that these kafirin microparticles may have potential as a colon-targeted nutraceutical and drug delivery system.

Optimal adaptive sequential spatial sampling of soil using pair-copulas

A spatial sampling design that uses pair-copulas is presented that aims to reduce prediction uncertainty by selecting additional sampling locations based on both the spatial configuration of existing locations and the values of the observations at those locations. The novelty of the approach arises in the use of pair-copulas to estimate uncertainty at unsampled locations. Spatial pair-copulas are able to more accurately capture spatial dependence compared to other types of spatial copula models. Additionally, unlike traditional kriging variance, uncertainty estimates from the pair-copula account for influence from measurement values and not just the configuration of observations. This feature is beneficial, for example, for more accurate identification of soil contamination zones where high contamination measurements are located near measurements of varying contamination. The proposed design methodology is applied to a soil contamination example from the Swiss Jura region. A partial redesign of the original sampling configuration demonstrates the potential of the proposed methodology.

The gradual release of responsibility: A case study of teaching science inquiry skills

This thesis investigated how a year-4 teacher used a pedagogical approach referred to as the Gradual Release of Responsibility (GRR) model of instruction for teaching Science Inquiry Skills in a primary classroom. Through scaffolding her students' learning using the GRR, the teacher guided her students towards developing an understanding about Scientific Inquiry leading to the foundations of scientific literacy. A learning environment was established in which students engaged in rich conversations, designed and conducted experiments using fair testing procedures, analysed and offered justifications for results, and negotiated knowledge claims in ways similar to some of those in the scientific community.

Occupational release of engineered nanoparticles: A review

Characterising the release of different types of Engineered Nanoparticles (ENPs) from various processes is of critical importance for the assessment of human exposure, as well as understanding the possible health effects of these particles. Therefore, the main aim of this chapter is to present a comprehensive review of studies which report on the release of airborne ENPs in different nanotechnology workplaces. The chapter will cover topics of relevance to the occupational characterisation of ENP emissions, ranging from the identification of different particle release sources and scenarios, to measurement methods and working towards a more uniform approach to characterisation. Furthermore, a brief review of ENP exposure control strategies, together with the application of mathematical modelling as an effective tool for the characterisation of emissions at nanotechnology workplaces is included.

Inflammation-driven bone formation in a mouse model of ankylosing spondylitis: Sequential not parallel processes

Background Ankylosing spondylitis (AS) is an immune-mediated arthritis particularly targeting the spine and pelvis and is characterised by inflammation, osteoproliferation and frequently ankylosis. Current treatments that predominately target inflammatory pathways have disappointing efficacy in slowing disease progression. Thus, a better understanding of the causal association and pathological progression from inflammation to bone formation, particularly whether inflammation directly initiates osteoproliferation, is required. Methods The proteoglycan-induced spondylitis (PGISp) mouse model of AS was used to histopathologically map the progressive axial disease events, assess molecular changes during disease progression and define disease progression using unbiased clustering of semi-quantitative histology. PGISp mice were followed over a 24-week time course. Spinal disease was assessed using a novel semi-quantitative histological scoring system that independently evaluated the breadth of pathological features associated with PGISp axial disease, including inflammation, joint destruction and excessive tissue formation (osteoproliferation). Matrix components were identified using immunohistochemistry. Results Disease initiated with inflammation at the periphery of the intervertebral disc (IVD) adjacent to the longitudinal ligament, reminiscent of enthesitis, and was associated with upregulated tumor necrosis factor and metalloproteinases. After a lag phase, established inflammation was temporospatially associated with destruction of IVDs, cartilage and bone. At later time points, advanced disease was characterised by substantially reduced inflammation, excessive tissue formation and ectopic chondrocyte expansion. These distinct features differentiated affected mice into early, intermediate and advanced disease stages. Excessive tissue formation was observed in vertebral joints only if the IVD was destroyed as a consequence of the early inflammation. Ectopic excessive tissue was predominantly chondroidal with chondrocyte-like cells embedded within collagen type II- and X-rich matrix. This corresponded with upregulation of mRNA for cartilage markers Col2a1, sox9 and Comp. Osteophytes, though infrequent, were more prevalent in later disease. Conclusions The inflammation-driven IVD destruction was shown to be a prerequisite for axial disease progression to osteoproliferation in the PGISp mouse. Osteoproliferation led to vertebral body deformity and fusion but was never seen concurrent with persistent inflammation, suggesting a sequential process. The findings support that early intervention with anti-inflammatory therapies will be needed to limit destructive processes and consequently prevent progression of AS.

Effect of deletion of Ghrelin-O-Acyltransferase on the pulsatile release of growth hormone in mice

Ghrelin, a gut hormone originating from the post-translational cleavage of preproghrelin, is the endogenous ligand of growth hormone secretagogue receptor 1a (GHS-R1a). Within the growth hormone (GH) axis, the biological activity of ghrelin requires octanoylation by ghrelin-O-acyltransferase (GOAT), conferring selective binding to the GHS-R1a receptor via acylated ghrelin. Complete loss of preproghrelin-derived signalling (through deletion of the Ghrl gene) contributes to a decline in peak GH release; however, the selective contribution of endogenous acyl-ghrelin to pulsatile GH release remains to be established. We assessed the pulsatile release of GH in ad lib. fed male germline goat−/− mice, extending measures to include mRNA for key hypothalamic regulators of GH release, and peripheral factors that are modulated relative to GH release. The amount of GH released was reduced in young goat−/− mice compared to age-matched wild-type mice, whereas pulse frequency and irregularity increased. Altered GH release did not coincide with alterations in hypothalamic Ghrh, Srif, Npy or Ghsr mRNA expression, or pituitary GH content, suggesting that loss of Goat does not compromise canonical mechanisms that contribute to pituitary GH production and release. Although loss of Goat resulted in an irregular pattern of GH release (characterised by an increase in the number of GH pulses observed during extended secretory events), this did not contribute to a change in the expression of sexually dimorphic GH-dependent liver genes. Of interest, circulating levels of insulin-like growth factor (IGF)-1 were elevated in goat−/− mice. This rise in circulating levels of IGF-1 was correlated with an increase in GH pulse frequency, suggesting that sustained or increased IGF-1 release in goat−/− mice may occur in response to altered GH release patterning. Our observations demonstrate that germline loss of Goat alters GH release and patterning. Although the biological relevance of altered GH secretory patterning remains unclear, we propose that this may contribute to sustained IGF-1 release and growth in goat−/− mice.