“It’s trying to manage the work” : A qualitative evaluation of recruitment processes within a UK multi-centre trial

Acknowledgments The authors would like to thank all interviewees who agreed to take part in this study. The authors would like to thank the TISU Trial Group for their support with this project. In particular, the authors would like to thank Sarah Cameron (TISU Trial Manager) for her help in identifying and recruiting staff from the various TISU trial study sites. Funding ZCS was supported by a core grant from the CSO (reference CZU/3/3) and a Wellcome Trust Institutional Strategic Support Fund award (reference RG12724-18). KG was supported by an MRC Methodology Research Fellowship (MR/L01193X/1). Transcription costs were supported by the National Institute for Health Research (NIHR), HTA programme (TISU project number 10/137/01). The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the HTA programme, NIHR, National Health Service or the Department of Health.Peer reviewedPublisher PD

Nitrogen leaching from effluent irrigated pasture

The surface waters of the Taupo region are of high quality and are sensitive to inputs of nitrogen. To reduce the amount of nitrogen discharged to surface water, the Taupo District Council (TDC) has employed a land treatment scheme (LTS), where treated municipal wastewater is irrigated onto ryegrass pasture. To limit the possibility of nitrogen pollution, regulations govern the amount of effluent that TDC may irrigate. This study reports the results from the first year of a five year trial where nitrogen leaching from the Taupo LTS was measured. To measure nitrogen leaching from the Taupo LTS, 48 intact monolith lysimeters were installed beneath effluent irrigation from two centre pivot irrigators. Four treatments based on nitrogen loading rates were trialled, nominally no-N (0 kg N ha-¹yr-¹), low-N (350 kg N ha-¹yr-¹ or less), mid-N (between 350 and 450 kg N ha-¹yr-¹), and high-N (greater than 450 kg N ha-¹yr-¹). Leachate was collected at least monthly and analysed for total nitrogen (TN), nitrate/nitrite nitrogen (NO₃-N), ammoniacal nitrogen (NH₄-N), dissolved organic nitrogen (DON), and total Kjeldahl nitrogen (TKN). The pasture was removed from the lysimeters to determine dry-matter production and pasture nitrogen concentration to calculate nitrogen uptake. Effluent irrigation significantly increased pasture growth and nitrogen leaching compared to the un-irrigated treatments (P<0.001). The mean rate of pasture growth from the irrigated treatments was 15,800 ± 1,700 kg DM ha-¹yr-¹, but there were no significant difference between the rate of pasture growth between the irrigated treatments. The pasture of the high-N treatments had a significantly higher nitrogen concentration than the low-N treatments (P<0.001), consequently the high-N treatment removed 390 kg N ha-¹, compared to 310 kg N ha-¹ removed from the mid-N and low-N treatments. On average, the pasture removed 84 % of the nitrogen that was irrigated. After 12 months, the no-N treatments leached 5 ± 3 kg TN ha-¹, the low-N treatment leached 15 ± 1 kg TN ha-¹, the mid-N treatment leached 17 ± 8 kg TN ha-¹, and the high-N treatment leached 26 ± 4 kg TN ha-¹. The high-N treatments leached significantly more TN than the low-N (P<0.005), but there was no significant difference in TN leached between the high-N and mid-N, or the mid-N and low-N treatments. The TN leached was poorly correlated with the rate of effluent irrigation. TN leached was positively correlated with the volume of water that drained through the soil (R2=0.7). The nitrogen in the leachate of the irrigated treatments comprised on average, 53 % NO₃-N, and 45 % DON, while the leachate of the un-irrigated treatments comprised, on average, 26 % NO₃-N and 72 % DON. NH₄-N accounted for approximately 2% of all nitrogen leached. Most of the NO₃-N leached throughout the year was leached after rain during summer and autumn. The mean concentration of NO₃-N leached from the irrigated treatments was 1.3 g N m-³. The concentration of NO₃-N in the leachate never exceeded Ministry of Health guidelines (11.3 g N m-³). The mean concentration of DON leached from the irrigated treatments was 1.2 g N m-³. Removing nitrogen in the pasture is the solution to avoid excess nitrogen leaching from the Taupo LTS. There is potential to recover more nitrogen in the pasture by improving the pasture cover and frequency of harvest

Small heat-shock proteins: important players in regulating cellular proteostasis

Small heat-shock proteins (sHsps) are a diverse family of intra-cellular molecular chaperone proteins that play a critical role in mitigating and preventing protein aggregation under stress conditions such as elevated temperature, oxidation and infection. In doing so, they assist in the maintenance of protein homeostasis (proteostasis) thereby avoiding the deleterious effects that result from loss of protein function and/or protein aggregation. The chaperone properties of sHsps are therefore employed extensively in many tissues to prevent the development of diseases associated with protein aggregation. Significant progress has been made of late in understanding the structure and chaperone mechanism of sHsps. In this review, we discuss some of these advances, with a focus on mammalian sHsp hetero-oligomerisation, the mechanism by which sHsps act as molecular chaperones to prevent both amorphous and fibrillar protein aggregation, and the role of post-translational modifications in sHsp chaperone function, particularly in the context of disease.SM was supported by a Royal Society Dorothy Hodgkin Fellowship, HE is supported by an Australian Research Council Future Fellowship (FT110100586) and JC is supported by a National Health and Medical Research Council Project Grant (#1068087)

Alpha-Casein as a Molecular Chaperone

Alpha-casein, more specifically known as αS-casein, is a predominant milk protein with important nutritional properties. αS-Casein, composed of two individual gene products, αS1- and αS2-casein, has been described in the past few decades as having molecular chaperone properties. In performing as molecular chaperones, αS-casein and its purified constituent proteins, αS1- and αS2-casein, stabilise a wide range of proteins from milk and non-milk sources against aggregation and precipitation under conditions of stress (e.g. heat, reduction). Investigations into the chaperone action of αS-casein have revealed that it stabilises its partially unfolded ‘target’ proteins by interacting with them and forming a soluble, high molecular weight complex similar to that formed by the small heat-shock proteins (sHsps) and another unrelated chaperone, clusterin. In addition, it has been shown that αS-casein is able to protect target proteins from aggregation when forming either amorphous or fibrillar aggregates, and that its chaperone activity is dependent on the target protein present, the stress conditions applied, the mode of protein aggregation (i.e. amorphous versus fibrillar), the speed of aggregation, and the presence of competing ions. Like the sHsps and clusterin, αS-casein is ATP-independent in its action, is unable to refold partially unfolded proteins and cannot prevent loss of enzyme activity under heat stress. Unlike the sHsps and clusterin, however, αS-casein binds its target proteins in a way that does not facilitate interaction with Hsp70 which in the presence of ATP can refold partially unfolded target proteins. The exploration of αS-casein’s relatively new role as a molecular chaperone in milk is of great interest to the food industry as it opens up new avenues for the stabilisation of milk and milk products under a range of environmental conditions (e.g. elevated temperature) and provides new possibilities for the development of dairy foods with unique properties and textures

A Study of the Chemical Factors Affecting the Rheological Properties of a Quartz-Bentonite Suspension in Water

Frequently, difficulties are encountered with mineral pulps in a mineral-processing plant, which are not alleviated or minimized by the application of such simple measures as varying fineness of grind of solid material, changing pulp density, or altering equipment operation (within practical limits). The basis of the difficulty in such a situation may be found in the very nature of the pulp-- its flow characteristics and behavior. Recognition of the problem followed by one-point viscometric measurement to determine fluidity can lead an operator to erroneous conclusions. Underlying this difficulty is the lack of technical literature concerning the application of ion exchange to rheological control of a mineral pulp. In this study, an attempt has been made to add to the available, useful literature regarding such application

Developing and evaluating interventions to reduce inappropriate prescribing by general practitioners of antibiotics for upper respiratory tract infections: a randomised controlled trial to compare paper-based and web-based modelling experiments

Background: Much implementation research is focused on full-scale trials with little evidence of preceding modelling work. The Medical Research Council Framework for developing and evaluating complex interventions has argued for more and better theoretical and exploratory work prior to a trial as a means of improving intervention development. Intervention modelling experiments (IMEs) are a way of exploring and refining an intervention before moving to a full-scale trial. They do this by delivering key elements of the intervention in a simulation that approximates clinical practice by, for example, presenting general practitioners (GPs) with a clinical scenario about making a treatment decision. Methods: The current proposal will run a full, web-based IME involving 250 GPs that will advance the methodology of IMEs by directly comparing results with an earlier paper-based IME. Moreover, the web-based IME will evaluate an intervention that can be put into a full-scale trial that aims to reduce antibiotic prescribing for upper respiratory tract infections in primary care. The study will also include a trial of email versus postal invitations to participate. Discussion: More effective behaviour change interventions are needed and this study will develop one such intervention and a system to model and test future interventions. This system will be applicable to any situation in the National Health Service where behaviour needs to be modified, including interventions aimed directly at the public. Trial registration: ClinicalTrials (NCT): NCT0120673

Discourse, care and control : an ethnography of residential and nursing home elder care work

Metadata merged with duplicate record (http://hdl.handle.net/10026.1/877) on 20.12.2016 by CS (TIS).This is a digitised version of a thesis that was deposited in the University Library. If you are the author please contact PEARL Admin ([email protected]) to discuss options.This thesis presents the notion that paid elder care work is often more involved with ordering individuals, than caring for them. It discusses this issue via ethnographic data about care assistant and nursing auxiliary work, which was collected in two elder care homes: Hazelford Lodge residential home and Bracken Court nursing home. The thesis uses care, control, and knowledge as the main themes for the discussion of work in both homes. The first chapter sites the thesis within the context of the academic literature on the discourses of the body, the nature of care work and residential care. It focuses especially upon care work as body labour. Chapter two presents the ethnographic methodological approach of the thesis, in two sections. Firstly, the use of the Foucauldian notion of discourse is explained, and secondly, the research process and research relationships are explored through a reflexive account. Chapters two and three present social, structural and spatial aspects of the two settings. They discuss the different ways in which the homes were organised, and that spaces were utilised and had different meanings, within the homes. Chapters four and five are based upon data from Hazelford Lodge residential home, and illustrate the care assistants' work as centred upon created order in the home, based upon the typification of residents and others. Chapters six and seven explore the auxiliaries' work in Bracken Court and present three control issues as central to their jobs. Firstly the overt ordering of patients around spaces in the home. Secondly, the normalisation of individuals into patient, and objects, of body work. Thirdly, the auxiliaries' resistance to heir role and status. Chapter eight compares the work of the assistants and auxiliaries in terms of resident and patient construction, the nature of the two forms of work, their knowledge, and lastly, their constructions of place and status. The thesis argues that both groups of workers are involved in ordering bodies that they perceive to be problematic and degenerating. In Hazelford Lodge order and discipline is practised as care and in Bracken Court the auxiliaries use more overt forms of control, but both 'caring' and controlling are effective methods of creating order. By introducing notions of body labour and ordering, the thesis presents a unique critique of paid care

Digital tools for trial recruitment and retention - Plenty of tools but rigorous evaluation is in short supply

Peer reviewedPublisher PD

Protocol for the effective feedback to improve primary care prescribing safety (EFIPPS) study : a cluster randomised controlled trial using ePrescribing data

High-risk prescribing in primary care is common and causes considerable harm. Feedback interventions to improve care are attractive because they are relatively cheap to widely implement. There is good evidence that feedback has small to moderate effects, but the most recent Cochrane review called for more high-quality, large trials that explicitly test different forms of feedback. The study is a three-arm cluster-randomised trial with general practices being randomised and outcomes measured at patient level. 262 practices in three Scottish Health Board areas have been randomised (94% of all possible practices). The two active arms receive different forms of prescribing safety data feedback, with rates of high-risk prescribing compared with a ‘usual care’ arm. Sample size estimation used baseline data from participating practices. With 85 practices randomised to each arm, then there is 93% power to detect a 25% difference in the percentage of high-risk prescribing (from 6.1% to 4.5%) between the usual care arm and each intervention arm. The primary outcome is a composite of six high-risk prescribing measures (antipsychotic prescribing to people aged ≥75 years; non-steroidal anti-inflammatory drug (NSAID) prescribing to people aged ≥75 without gastroprotection; NSAID prescribing to people prescribed aspirin/clopidogrel without gastroprotection; NSAID prescribing to people prescribed an ACE inhibitor/angiotensin receptor blocker and a diuretic; NSAID prescription to people prescribed an oral anticoagulant without gastroprotection; aspirin/clopidogrel prescription to people prescribed an oral anticoagulant without gastroprotection). The primary analysis will use multilevel modelling to account for repeated measurement of outcomes in patients clustered within practices. The study was reviewed and approved by the NHS Tayside Committee on Medical Research Ethics B (11/ES/0001). The study will be disseminated via a final report to the funder with a publicly available research summary, and peer reviewed publications