Confirmation of the Electrostatic Self-Assembly of Nanodiamonds

A reliable explanation for the underlying mechanism responsible for the persistent aggregation and self-assembly of colloidal 5 nm diamond nanoparticles is critical to the development of nanodiamond-based technologies. Although a number of mechanisms have been proposed, validation has been hindered by the inherent difficulty associated with the identification and characterisation of the inter-particle interfaces. In this paper we present results of high resolution aberration corrected electron microscopy and complementary computer simulations to explicate the features involved, and confirm the electrostatic interaction mechanism as the most probable cause for the formation of agglutinates and agglomerates of primary particles.Comment: 9 pages (including Supplementary Information), accepted for publication by Nanoscal

The learner’s perspective in GP teaching practices with multi-level learners: a qualitative study

BACKGROUND Medical students, junior hospital doctors on rotation and general practice (GP) registrars are undertaking their training in clinical general practices in increasing numbers in Australia. Some practices have four levels of learner. This study aimed to explore how multi-level teaching (also called vertical integration of GP education and training) is occurring in clinical general practice and the impact of such teaching on the learner. METHODS A qualitative research methodology was used with face-to-face, semi-structured interviews of medical students, junior hospital doctors, GP registrars and GP teachers in eight training practices in the region that taught all levels of learners. Interviews were audio-recorded and transcribed. Qualitative analysis was conducted using thematic analysis techniques aided by the use of the software package N-Vivo 9. Primary themes were identified and categorised by the co-investigators. RESULTS 52 interviews were completed and analysed. Themes were identified relating to both the practice learning environment and teaching methods used.A practice environment where there is a strong teaching culture, enjoyment of learning, and flexible learning methods, as well as learning spaces and organised teaching arrangements, all contribute to positive learning from a learners' perspective.Learners identified a number of innovative teaching methods and viewed them as positive. These included multi-level learner group tutorials in the practice, being taught by a team of teachers, including GP registrars and other health professionals, and access to a supernumerary GP supervisor (also termed "GP consultant teacher"). Other teaching methods that were viewed positively were parallel consulting, informal learning and rural hospital context integrated learning. CONCLUSIONS Vertical integration of GP education and training generally impacted positively on all levels of learner. This research has provided further evidence about the learning culture, structures and teaching processes that have a positive impact on learners in the clinical general practice setting where there are multiple levels of learners. It has also identified some innovative teaching methods that will need further examination. The findings reinforce the importance of the environment for learning and learner centred approaches and will be important for training organisations developing vertically integrated practices and in their training of GP teachers.This project was supported by a grant from General Practice Education and Training through Coast City Country General Practice Training. This project was approved for conduct by the ANU Human Research Ethics Committee (protocol number 2011/415)

Modeling the iron oxides and oxyhydroxides for the prediction of environmentally sensitive phase transformations

Iron oxides and oxyhydroxides are challenging to model computationally as competing phases may differ in formation energies by only several kJ/mol, they undergo magnetization transitions with temperature, their structures may contain partially occupied sites or long-range ordering of vacancies, and some loose structures require proper description of weak interactions such as hydrogen bonding and dispersive forces. If structures and transformations are to be reliably predicted under different chemical conditions, each of these challenges must be overcome simultaneously, while preserving a high level of numerical accuracy and physical sophistication. Here we present comparative studies of structure, magnetization, and elasticity properties of iron oxides and oxyhydroxides using density functional theory calculations with plane-wave and locally-confined-atomic-orbital basis sets, which are implemented in VASP and SIESTA packages, respectively. We have selected hematite, maghemite, goethite, lepidocrocite, and magnetite as model systems from a total of 13 known iron oxides and oxyhydroxides; and use same convergence criteria and almost equivalent settings in order to make consistent comparisons. Our results show both basis sets can reproduce the energetic stability and magnetic ordering, and are in agreement with experimental observations. There are advantages to choosing one basis set over the other, depending on the intended focus. In our case, we find the method using PW basis set most appropriate, and combine our results to construct the first phase diagram of iron oxides and oxyhydroxides in the space of competing chemical potentials, generated entirely from first principlesComment: 46 pages - Accepted for publication in PRB (19 journal pages), January 201

Intensive care nurse-family engagement from a global perspective: A qualitative multi-site exploration

Background: Critical illness is distressing for families, and often results in negative effects on family health that influence a family\u27s ability to support their critically ill family member. Although recent attention has been directed at improving care and outcomes for families of critically ill patients, the manner in which nurses engage with families is not fully understood. Objectives: To describe nurses’ perceptions and practices of family engagement in adult intensive care units from a global perspective. Design: A qualitative-descriptive multi-site design using content analysis. Settings: The study was conducted in 26 intensive care units of 12 urban, metropolitan, academic medical centers in ten countries, spanning five continents. Participants: A total of 65 registered nurses (77% women, age of M = 39.5, SD = 11.4 years) participated. Most held intensive care certification (72%) and had worked on average 10 (SD = 9.6) years in the ICU. Methods: Semi-structured, individual interviews (M = 38.4 min, SD = 12.0) were held with ICU nurses at the hospital (94%) or their home using an interview guide. Qualitative interview data were analysed using inductive content analysis. Results: We found that nurse-family engagement was an ebb and flow of relational power that needed to be carefully negotiated and balanced, with nurses holding and often exerting more power than families. Constant fluctuations in nurses’ practices of engagement occurred in day-to-day practice from shift-to-shift and from nurse-to-nurse. Family engagement was dependent on individual nurses’ attitudes and perceptions of family, the patient\u27s condition, and workload. Lastly, family engagement was shaped by the ICU context, with team culture, collaborative relationships, unit structures and organizational resources either enabling or limiting nurses’ ability to engage with families. Conclusions: This global study provides an in-depth understanding of the way nurses engage with families in ICU and reflects many different cultures and health systems. We found that nurse-family engagement was marked by a shifting, yet often unequal power distribution in the nurse-family relationship, inconsistent nurse engagement practices, both of which resulted in variable family engagement in intensive care. Our research contributes a detailed description of engagement as practiced in the everyday delivery of health care. A more concentrated team effort, based on a shared culture and defined framework of family care is needed to ensure that families of critically ill persons are fully engaged in all aspects of intensive care

Developing a matrix to identify and prioritise research recommendations in HIV Prevention

BACKGROUND: HIV prevention continues to be problematic in the UK, as it does globally. The UK Department of Health has a strategic direction with greater focus on prevention as part of its World Class Commissioning Programme. There is a need for targeted evidence-based prevention initiatives. This is an exploratory study to develop an evidence mapping tool in the form of a matrix: this will be used to identify important gaps in contemporary HIV prevention evidence relevant to the UK. It has the potential to aid prioritisation in future research.METHODS: Categories for prevention and risk groups were developed for HIV prevention in consultation with external experts. These were used as axes on a matrix tool to map evidence. Systematic searches for publications on HIV prevention were undertaken using electronic databases for primary and secondary research undertaken mainly in UK, USA, Canada, Australia and New Zealand, 2006-9. Each publication was screened for inclusion then coded. The risk groups and prevention areas in each paper were counted: several publications addressed multiple risk groups. The counts were exported to the matrix and clearly illustrate the concentrations and gaps of literature in HIV prevention.RESULTS: 716 systematic reviews, randomised control trials and other primary research met the inclusion criteria for HIV prevention. The matrix identified several under researched areas in HIV prevention.CONCLUSIONS: This is the first categorisation system for HIV prevention and the matrix is a novel tool for evidence mapping. Some important yet under-researched areas have been identified in HIV prevention evidence: identifying the undiagnosed population; international adaptation; education; intervention combinations; transgender; sex-workers; heterosexuals and older age groups.<br/

COVID-19: Third dose booster vaccine effectiveness against breakthrough coronavirus infection, hospitalisations and death in patients with cancer: A population-based study

Purpose: People living with cancer and haematological malignancies are at increased risk of hospitalisation and death following infection with acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coronavirus third dose vaccine boosters are proposed to boost waning immune responses in immunocompromised individuals and increase coronavirus protection; however, their effectiveness has not yet been systematically evaluated. Methods: This study is a population-scale real-world evaluation of the United Kingdom’s third dose vaccine booster programme for cancer patients from 8th December 2020 to 7th December 2021. The cancer cohort comprises individuals from Public Health England’s national cancer dataset, excluding individuals less than 18 years. A test-negative case-control design was used to assess third dose booster vaccine effectiveness. Multivariable logistic regression models were fitted to compare risk in the cancer cohort relative to the general population. Results: The cancer cohort comprised of 2,258,553 tests from 361,098 individuals. Third dose boosters were evaluated by reference to 87,039,743 polymerase chain reaction (PCR) coronavirus tests. Vaccine effectiveness against breakthrough infections, symptomatic infections, coronavirus hospitalisation and death in cancer patients were 59.1%, 62.8%, 80.5% and 94.5% respectively. Lower vaccine effectiveness was associated with a cancer diagnosis within 12 months, lymphoma, recent systemic anti-cancer therapy (SACT) or radiotherapy. Lymphoma patients had low levels of protection from symptomatic disease. In spite of third dose boosters, following multivariable adjustment, individuals with cancer remain at increased risk of coronavirus hospitalisation and death compared to the population control (OR 3.38, 3.01 respectively. p<0.001 for both). Conclusions: Third dose boosters are effective for most individuals with cancer, increasing protection from coronavirus. However, their effectiveness is heterogenous, and lower than the general population. Many patients with cancer will remain at increased risk of coronavirus infections, even after 3 doses. In the case of patients with lymphoma, there is a particularly strong disparity of vaccine effectiveness against breakthrough infection and severe disease. Breakthrough infections will disrupt cancer care and treatment with potentially adverse consequences on survival outcomes. The data support the role of vaccine boosters in preventing severe disease, and further pharmacological intervention to prevent transmission and aid viral clearance to limit disruption of cancer care as the delivery of care continues to evolve during the coronavirus pandemic

20 years of research on the Alcator C-Mod tokamak

The object of this review is to summarize the achievements of research on the Alcator C-Mod tokamak [Hutchinson et al., Phys. Plasmas 1, 1511 (1994) and Marmar, Fusion Sci. Technol. 51, 261 (2007)] and to place that research in the context of the quest for practical fusion energy. C-Mod is a compact, high-field tokamak, whose unique design and operating parameters have produced a wealth of new and important results since it began operation in 1993, contributing data that extends tests of critical physical models into new parameter ranges and into new regimes. Using only high-power radio frequency (RF) waves for heating and current drive with innovative launching structures, C-Mod operates routinely at reactor level power densities and achieves plasma pressures higher than any other toroidal confinement device. C-Mod spearheaded the development of the vertical-target divertor and has always operated with high-Z metal plasma facing components—approaches subsequently adopted for ITER. C-Mod has made ground-breaking discoveries in divertor physics and plasma-material interactions at reactor-like power and particle fluxes and elucidated the critical role of cross-field transport in divertor operation, edge flows and the tokamak density limit. C-Mod developed the I-mode and the Enhanced Dα H-mode regimes, which have high performance without large edge localized modes and with pedestal transport self-regulated by short-wavelength electromagnetic waves. C-Mod has carried out pioneering studies of intrinsic rotation and demonstrated that self-generated flow shear can be strong enough in some cases to significantly modify transport. C-Mod made the first quantitative link between the pedestal temperature and the H-mode's performance, showing that the observed self-similar temperature profiles were consistent with critical-gradient-length theories and followed up with quantitative tests of nonlinear gyrokinetic models. RF research highlights include direct experimental observation of ion cyclotron range of frequency (ICRF) mode-conversion, ICRF flow drive, demonstration of lower-hybrid current drive at ITER-like densities and fields and, using a set of novel diagnostics, extensive validation of advanced RF codes. Disruption studies on C-Mod provided the first observation of non-axisymmetric halo currents and non-axisymmetric radiation in mitigated disruptions. A summary of important achievements and discoveries are included.United States. Dept. of Energy (Cooperative Agreement DE-FC02-99ER54512)United States. Dept. of Energy (Cooperative Agreement DE-FG03-94ER-54241)United States. Dept. of Energy (Cooperative Agreement DE-AC02-78ET- 51013)United States. Dept. of Energy (Cooperative Agreement DE-AC02-09CH11466)United States. Dept. of Energy (Cooperative Agreement DE-FG02-95ER54309)United States. Dept. of Energy (Cooperative Agreement DE-AC02-05CH11231)United States. Dept. of Energy (Cooperative Agreement DE-AC52-07NA27344)United States. Dept. of Energy (Cooperative Agreement DE-FG02- 97ER54392)United States. Dept. of Energy (Cooperative Agreement DE-SC00-02060

An intervention to support stroke survivors and their carers in the longer term (LoTS2Care): study protocol for a cluster randomised controlled feasibility trial

Background Despite the evidence that many stroke survivors report longer term unmet needs, the provision of longer term care is limited. To address this, we are conducting a programme of research to develop an evidence-based and replicable longer term care strategy. The developed complex intervention (named New Start), which includes needs identification, exploration of social networks and components of problem solving and self-management, was designed to improve quality of life by addressing unmet needs and increasing participation. Methods/Design A multicentre, cluster randomised controlled feasibility trial designed to inform the design of a possible future definitive cluster randomised controlled trial (cRCT) and explore the potential clinical and cost-effectiveness of New Start. Ten stroke services across the UK will be randomised on a 1:1 basis either to implement New Start or continue with usual care only. New Start will be delivered by trained facilitators and will be offered to all stroke survivors within the services allocated to the intervention arm. Stroke survivors will be eligible for the trial if they are 4–6 months post-stroke and residing in the community. Carers (if available) will also be invited to take part. Invitation to participate will be initiated by post and outcome measures will be collected via postal questionnaires at 3, 6 and 9 months after recruitment. Outcome data relating to perceived health and disability, wellbeing and quality of life as well as unmet needs will be collected. A ‘study within a trial’ (SWAT) is planned to determine the most acceptable format in which to provide the postal questionnaires. Details of health and social care service usage will also be collected to inform the economic evaluation. The feasibility of recruiting services and stroke survivors to the trial and of collecting postal outcomes will be assessed and the potential for effectiveness will be investigated. An embedded process evaluation (reported separately) will assess implementation fidelity and explore and clarify causal assumptions regarding implementation. Discussion This feasibility trial with embedded process evaluation will allow us to gather important and detailed data regarding methodological and implementation issues to inform the design of a possible future definitive cRCT of this complex intervention. Trial Registration ISRCTN38920246. Registered 22 June 2016

Ondansetron for irritable bowel syndrome with diarrhoea: randomised controlled trial

Background: Irritable bowel syndrome with diarrhoea is characterised by frequent, loose or watery stools with associated urgency, resulting in marked reduction of quality of life. Ondansetron, a 5-hydroxytryptamine-3 receptor antagonist, has been shown to benefit patients with irritable bowel syndrome with diarrhoea.Objective: To evaluate the effect of ondansetron in irritable bowel syndrome with diarrhoea.Design: Phase III, parallel-group, randomised, double-blind, multicentre, placebo-controlled trial in 400 patients, with embedded mechanistic studies.Setting: Hospital, primary care and community.Participants: Eighty participants meeting Rome IV criteria for irritable bowel syndrome with diarrhoea.Intervention: Ondansetron 4 mg (dose titrated up to two tablets three times a day) or matched placebo for 12 weeks.Main outcome measures: Clinical – Primary patient-reported end point was % ‘Food and Drug Administration-defined responders’ over 12 weeks. Secondary end points were worst abdominal pain intensity, worst urgency, stool consistency, stool frequency, anxiety, depression and dyspepsia at 12 and 16 weeks.Main outcome measures: Mechanistic – Whole gut transit time, faecal water, protease (FP), bile acids and assessment of rectal sensitivity using a barostat.Results: Clinical – The study closed early due to slow recruitment. Between 1 January 2018 and 11 May 2020, 80 patients were recruited and randomised (20% of target), 37 to ondansetron, 43 to placebo. Discontinuations (4 ondansetron; 2 placebo) meant 75 completed the 12-week trial treatment. There were four protocol violations. In the intention-to-treat analysis, 15 (40.5%) on ondansetron were primary end-point responders (95% CI 24.7% to 56.4%), and 12 (27.9%) on placebo (95% CI 14.5% to 41.3%), p = 0.19, adjusted OR 1.93 (0.73, 5.11). Pain intensity reduction occurred in 17 (46.0%) on ondansetron (95% CI 29.9% to 62.0%) and 16 (37.2%) on placebo (95% CI 22.8% to 51.7%), p = 0.32. Improvement in stool consistency occurred in 25 (67.6%) on ondansetron (95% CI 52.5% to 82.7%) and 22 (51.2%) on placebo (95% CI 36.2% to 66.1%), p = 0.07. Use of rescue medication, loperamide, was lower on ondansetron [7 (18.9%) vs. 17 (39.5%)]. Average stool consistency in the final month of treatment reduced significantly more on ondansetron, adjusted mean difference –0.5 [standard error (SE) 0.25, 95% CI (–1.0 to –0.02), p = 0.042]. Ondansetron improved dyspepsia score (SFLDQ), adjusted mean difference –3.2 points [SE 1.43, 95% CI (–6.1 to –0.4), p = 0.028]. There were no serious adverse events.Mechanistic – mean (SD). Ondansetron increased whole gut transit time between baseline and week 12 by 3.8 (9.1) hours on ondansetron, significantly more than on placebo –2.2 (10.3), p = 0.01. Mean volume to reach urgency threshold using the barostat increased on ondansetron by 84 (61) ml and 38 (48) ml on placebo, n = 8, p = 0.26. Ondansetron did not significantly alter protease, faecal water or bile acids. Changes in referral pathways substantially reduced referrals, impairing recruitment, which meant the study was underpowered.Conclusion: Our results are consistent with previous studies and confirmed ondansetron improves stool consistency and urgency but showed minor effect on pain. We plan to undertake a simplified version of this trial overcoming the changed referral pathways by recruiting in primary care, using software linked to primary care records to identify and randomise patients with irritable bowel syndrome with diarrhoea to ondansetron or placebo and remotely follow their progress; thus minimising barriers to recruitment.Trial registration: This trial is registered as ISRCTN17508514.Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation programme and will be published in full in Efficacy and Mechanism Evaluation; Vol. 10, No. 9. See the NIHR Journals Library website for further project information

Alcator C-Mod: research in support of ITER and steps beyond

This paper presents an overview of recent highlights from research on Alcator C-Mod. Significant progress has been made across all research areas over the last two years, with particular emphasis on divertor physics and power handling, plasma–material interaction studies, edge localized mode-suppressed pedestal dynamics, core transport and turbulence, and RF heating and current drive utilizing ion cyclotron and lower hybrid tools. Specific results of particular relevance to ITER include: inner wall SOL transport studies that have led, together with results from other experiments, to the change of the detailed shape of the inner wall in ITER; runaway electron studies showing that the critical electric field required for runaway generation is much higher than predicted from collisional theory; core tungsten impurity transport studies reveal that tungsten accumulation is naturally avoided in typical C-Mod conditions.United States. Department of Energy (DE-FC02-99ER54512-CMOD)United States. Department of Energy (DE-AC02-09CH11466)United States. Department of Energy (DE-FG02-96ER-54373)United States. Department of Energy (DE-FG02-94ER54235