Microfluidic platforms for biomarker analysis

Biomarkers have been described as characteristics, most often molecular, that provide information about biological states, whether normal, pathological, or therapeutically modified. They hold great potential to assist diagnosis and prognosis, monitor disease, and assess therapeutic effectiveness. While a few biomarkers are routinely utilised clinically, these only reflect a very small percentage of all biomarkers discovered. Numerous factors contribute to the slow uptake of these new biomarkers, with challenges faced throughout the biomarker development pipeline. Microfluidics offers two important opportunities to the field of biomarkers: firstly, it can address some of these developmental obstacles, and secondly, it can provide the precise and complex platform required to bridge the gap between biomarker research and the biomarker-based analytical device market. Indeed, adoption of microfluidics has provided a new avenue for advancement, promoting clinical utilisation of both biomarkers and their analytical platforms. This review will discuss biomarkers and outline microfluidic platforms developed for biomarker analysis.

Mimtags: the use of phage display technology to produce novel protein-specific probes

In recent times the use of protein-specific probes in the field of proteomics has undergone evolutionary changes leading to the discovery of new probing techniques. Protein-specific probes serve two main purposes: epitope mapping and detection assays. One such technique is the use of phage display in the random selection of peptide mimotopes (mimtags) that can tag epitopes of proteins, replacing the use of monoclonal antibodies in detection systems. In this study, phage display technology was used to screen a random peptide library with a biologically active purified human interleukin-4 receptor (IL-4R) and interleukin-13 (IL-13) to identify mimtag candidates that interacted with these proteins. Once identified, the mimtags were commercially synthesised, biotinylated and used for in vitro immunoassays. We have used phage display to identify M13 phage clones that demonstrated specific binding to IL-4R and IL-13 cytokine. A consensus in binding sequences was observed and phage clones characterised had identical peptide sequence motifs. Only one was synthesised for use in further immunoassays, demonstrating significant binding to either IL-4R or IL-13. We have successfully shown the use of phage display to identify and characterise mimtags that specifically bind to their target epitope. Thus, this new method of probing proteins can be used in the future as a novel tool for immunoassay and detection technique, which is cheaper and more rapidly produced and therefore a better alternative to the use of monoclonal antibodies.

Encountering the ‘other’: interpreting student experiences of a multi-sensory museum exhibition

The Immigration Museum Melbourne, Australia, launched the Identity: Yours, Mine, Ours exhibition in 2011. Aimed primarily at secondary school students, this long-term installation seeks to foster reflection on identity and belonging, as well as dialogue about racism, through an interactive, immersive museum experience. This paper describes a multi-method research project, which included narrative interviews, focus groups and video diaries with 47 Year 11–12 students from three secondary schools in Victoria, Australia, and discusses each method's contribution to an overall empirical understanding of the installation's impact on students' experiences. Emerging findings suggest the ways in which the exhibition space supports students to encounter and engage with individual stories and experiences, thus moving beyond an abstract tolerance of cultural diversity by unsettling the self and destabilising stereotyped and prejudiced interpretations of the ‘other’. The paper concludes by discussing the potential for triangulated qualitative approaches to provide rich emic perspectives on multi-sensory exhibitions.

Intradialytic Laughter Yoga therapy for haemodialysis patients: a pre-post intervention feasibility study.

BACKGROUND: Laughter Yoga consists of physical exercise, relaxation techniques and simulated vigorous laughter. It has been associated with physical and psychological benefits for people in diverse clinical and non-clinical settings, but has not yet been tested in a haemodialysis setting. The study had three aims: 1) to examine the feasibility of conducting Laughter Yoga for patients with end stage kidney disease in a dialysis setting; 2) to explore the psychological and physiological impact of Laughter Yoga for these patients; and 3) to estimate the sample size required for future research. METHODS: Pre/post intervention feasibility study. Eighteen participants were recruited into the study and Laughter Yoga therapists provided a four week intradialytic program (30-min intervention three times per week). Primary outcomes were psychological items measured at the first and last Laughter Yoga session, including: quality of life; subjective wellbeing; mood; optimism; control; self-esteem; depression, anxiety and stress. Secondary outcomes were: blood pressure, intradialytic hypotensive episodes and lung function (forced expiratory volume). Dialysis nurses exposed to the intervention completed a Laughter Yoga attitudes and perceptions survey (n = 11). Data were analysed using IBM SPSS Statistics v22, including descriptive and inferential statistics, and sample size estimates were calculated using G*Power. RESULTS: One participant withdrew from the study for medical reasons that were unrelated to the study during the first week (94 % retention rate). There were non-significant increases in happiness, mood, and optimism and a decrease in stress. Episodes of intradialytic hypotension decreased from 19 pre and 19 during Laughter Yoga to 4 post Laughter Yoga. There was no change in lung function or blood pressure. All nurses agreed or strongly agreed that Laughter Yoga had a positive impact on patients' mood, it was a feasible intervention and they would recommend Laughter Yoga to their patients. Sample size calculations for future research indicated that a minimum of 207 participants would be required to provide sufficient power to detect change in key psychological variables. CONCLUSIONS: This study provides evidence that Laughter Yoga is a safe, low-intensity form of intradialytic physical activity that can be successfully implemented for patients in dialysis settings. Larger studies are required, however, to determine the effect of Laughter Yoga on key psychological variables. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry - ACTRN12614001130651 . Registered 23 October 2014.

Systematic review and quality appraisal of economic evaluation publications in dentistry

Economic evaluation (EE) studies have been undertaken in dentistry since the late 20th century because economic data provide additional information to policy makers to develop guidelines and set future direction for oral health services. The objectives of this study were to assess the methodological quality of EEs in oral health. Electronic searching of Ovid MEDLINE, the Cochrane Library, and the NHS Economic Evaluation Database from 1975 to 2013 were undertaken to identify publications that include costs and outcomes in dentistry. Relevant reference lists were also searched for additional studies. Studies were retrieved and reviewed independently for inclusion by 3 authors. Furthermore, to appraise the EE methods, 1 author applied the Drummond 10-item (13-criteria) checklist tool to each study. Of the 114 publications identified, 79 studies were considered full EE and 35 partial. Twenty-eight studies (30%) were published between the years 2011 and 2013. Sixty-four (53%) studies focused on dental caries prevention or treatment. Median appraisal scores calculated for full and partial EE studies were 11 and 9 out of 13, respectively. Quality assessment scores showed that the quality of partial EE studies published after 2000 significantly improved (P = 0.02) compared to those published before 2000. Significant quality improvement was not found in full EE studies. Common methodological limitations were identified: absence of sensitivity analysis, discounting, and insufficient information on how costs and outcomes were measured and valued. EE studies in dentistry increased over the last 40 y in both quantity and quality, but a number of publications failed to satisfy some components of standard EE research methods, such as sensitivity analysis and discounting.

Patients' perceptions of participation in nursing care on medical wards

BACKGROUND: Patient participation benefits the patient and is a core concept of patient-centred care. Patients believe in their ability to prevent errors; thus, they may play a vital role in combating adverse event rates in hospitals. AIMS AND OBJECTIVES: To explore hospitalised medical patients' perceptions of participating in nursing care, including the barriers and facilitators for this activity. RESEARCH METHODS: This interpretive study was conducted on four medical wards, in two hospitals. Purposeful maximum variation sampling was operationalised to recruit patients that differed in areas such as age, gender and mobility status. In-depth semi-structured audiotaped interviews were undertaken and analysed using inductive content analysis. RESULTS: Twenty patients participated in the study. Four categories were uncovered in the data. First, valuing participation showed patients' willingness to participate, viewing it as a worthwhile task. Second, exchanging intelligence was a way of participating where patients' knowledge was built and shared with health professionals. Third, on the lookout was a type of participation where patients monitored their care, showing an attentive approach towards their own safety. Fourth, power imbalance was characterised by patients feeling their opportunities for participation were restricted. CONCLUSIONS: Patients were motivated to participate and valued participation. Cultivating this motivation may be crucial to patient empowerment and practices of safety monitoring, a fundamental strategy to addressing patient safety issues in hospitals. Engaging nurse-patient relationships, inclusive of knowledge sharing, is required in practice to empower patients to participate. Educating patients on the consequences of non-participation may motivate them, while nurses may benefit from training on patient-centred approaches. Future research should address ways to increase patient motivation and opportunities to participate.

Mutational interference mapping experiment (MIME) for studying RNA structure and function

RNA regulates many biological processes; however, identifying functional RNA sequences and structures is complex and time-consuming. We introduce a method, mutational interference mapping experiment (MIME), to identify, at single-nucleotide resolution, the primary sequence and secondary structures of an RNA molecule that are crucial for its function. MIME is based on random mutagenesis of the RNA target followed by functional selection and next-generation sequencing. Our analytical approach allows the recovery of quantitative binding parameters and permits the identification of base-pairing partners directly from the sequencing data. We used this method to map the binding site of the human immunodeficiency virus-1 (HIV-1) Pr55(Gag) protein on the viral genomic RNA in vitro, and showed that, by analyzing permitted base-pairing patterns, we could model RNA structure motifs that are crucial for protein binding.

Chemiluminescence detection of MDMA in street drug samples using tris (2,2'-bipyridine) ruthenium (III)

Tris(2,2'-bipyridine)ruthenium(II) chemiluminescence was investigated for the detection of 3,4-methylenedioxymethamphetamine (MDMA) and several related compounds in street drug samples. Optimization using flow injection analysis showed that the selectivity of the reagent can be targeted towards the detection of secondary amines by altering the pH of the reaction environment. The greater selectivity of this mode of detection, compared to UV-absorbance, reduces the probability of false positive results from interfering compounds. The detection limit for MDMA under these conditions was 0.48 μM. A HPLC method incorporating post-column tris(2,2'-bipyridine)ruthenium(II) chemiluminescence detection was applied to the determination of MDMA in five street drug samples. The results obtained were in good agreement with quantification performed using traditional UV-absorbance detection, which demonstrates the viability of this method for confirmatory analysis of drug samples. This is the first report of tris(2,2'-bipyridine)ruthenium(II) chemiluminescence for the detection of MDMA and related amphetamine derivatives.

Obesity management: Australian general practitioners' attitudes and practices

Objectives: To document general practitioners’ (GPs) attitudes and practices regarding the prevention and management of overweight and obesity.

Research Methods and Procedures: A cross-sectional survey of a randomly selected sample of 1500 Australian GPs was conducted, of which 752 questionnaires were returned. The measures included views on weight management, definitions of success, views regarding the usefulness of drugs, approaches to and strategies recommended for weight management, and problems and frustrations in managing overweight and obesity.

Results: GPs view weight management as important and feel they have an important role to play. Although they consider themselves to be well prepared to treat overweight patients, they believe that they have limited efficacy in weight management and find it professionally unrewarding. GPs view the assessment of a patient's dietary and physical activity habits and the provision of dietary and physical activity advice as very important. The approaches least likely to be considered important and/or least likely to be practiced were those that would support the patient in achieving and maintaining lifestyle change.

Discussion: There remains considerable opportunity to improve the practice of GPs in their management of overweight and obesity. Although education is fundamental, it is important to acknowledge the constraints of the GPs’ existing working environment.

Obesity impacts on general practice appointments

Objective: To quantify the impact of obesity on the number of visits to both primary and secondary care teams.

Research Methods and Procedures: The adult populations of 80 general practices throughout the United Kingdom were classified according to their BMI. We undertook a cross-sectional survey of computer-generated and handwritten records of 6150 obese people (BMI ≥ 30 kg/m2) and 1150 normal weight (BMI = 18.5 to 24.9 kg/m2) control subjects over an 18-month retrospective period.

Results: Obese patients made significantly more visits to the general practitioner (GP), practice nurse (PN), and hospital outpatient units than normal weight patients (all p < 0.001), and they were admitted to the hospital more often (p = 0.034). For both GP and PN visits, the relationship remained after adjusting for age, sex, social deprivation category, country, and number of comorbidities. Among obese patients, there was an increasing relationship between frequent GP visits (at least four appointments) and greater BMI, which remained significant after adjustment had been made for age, sex, deprivation, country, and number of comorbidities.

Discussion: The human resource burden to general practice is significantly higher in the obese population than in the normal weight population, even when adjusted for confounding factors. The increase in prevalence of obesity will continue to put pressure on GP and PN time unless appropriate action is taken.

A square peg in a round hole? Approaches to incorporating lifestyle counselling into routine primary health care

Few studies have explored how lifestyle counselling can be integrated into routine practice for primary health care (PHC) clinicians working outside general practice. This paper describes the feasibility of models of lifestyle counselling developed for PHC clinicians working in community health services and the congruence with routine practice. Action research methods were used to develop and implement models of lifestyle counselling in three community health teams. Following a six-month implementation period, semi-structured interviews were conducted with a purposeful sample of participants (n = 30) to explore the appropriateness of implementing risk factor management models in practice. Models were considered appropriate if they fitted the clinician’s philosophy of practice, were relevant to existing work tasks, could easily be integrated into workflow and were perceived as being acceptable to the client. The approach to service delivery and team priorities were also important in influencing which models suited particular teams. Models of lifestyle counselling for PHC clinicians outside general practice should be tailored to the clinicians’ and teams’ way of working and thus may need to be discipline-specific. Engaging PHC clinicians and teams is important in developing models that are acceptable and feasible in everyday practice.