The development of a family-based wearable intervention using behaviour change and co-design approaches: move and connect.

BACKGROUND: Previous research has explored the effectiveness of wearable activity trackers (wearables) for increasing child physical activity (PA) levels, but there have been mixed results. The use of theoretical frameworks and co-design techniques are recognised ways of increasing an intervention's acceptability and effectiveness. AIMS: This study aims to use co-design workshops and an evidence-based theoretical framework (the Behaviour Change Wheel) to develop a family-based PA intervention using wearables. METHODS: Three stages of intervention development outlined by the Behaviour Change Wheel were used. Co-design workshops with seven families (11 parents and 12 children) and seven PA experts were conducted where stakeholders discussed how to overcome previously identified barriers to families being active and using wearables. This resulted in the intervention's components being developed, with each component's mechanisms of action (e.g. intervention functions and behaviour change techniques) being retrospectively identified. RESULTS: The 'Move & Connect' intervention was developed, which targets family PA and wearable use. The intervention takes a flexible approach and includes eight components, including wearable devices (Fitbit Alta HR), support resources, an introductory workshop, collective challenges, goal setting and reviewing, engagement prompts, social support and health-related resources (e.g. educational videos). The intervention incorporates six intervention functions targeting PA and wearable use: education, training, modelling, persuasion, incentivisation and environmental restructuring and 24 behaviour change techniques, including goal setting, social comparison, feedback on behaviour and graded task. CONCLUSIONS: This is the first known study to use an evidence-based framework and co-design to develop a family-based wearable intervention. The identification of the intervention's mechanisms of action will prove useful when implementing and evaluating the 'Move & Connect' intervention and allow researchers to replicate its components.

Waveshape distortion of high frequency acoustic waves in gas media.

In molecular dynamics simulations of an acoustic domain excited by a sinusoidally oscillating plane acoustic source in the frequency range of hundreds of megahertz, the density and velocity perturbations adjacent to the source are observed to be non-sinusoidal in shape. This distortion in the shape of the waves is investigated using a number of simulations of frequencies in the hundred of megahertz range and velocities up to 0.50 Å/ps. The relative distortion of the wave shape is characterised by a developed nested trigonometric function. The distortion is shown to be a function of the Mach number of the acoustic source rather than the source velocity amplitude. Trends in the distortion with source amplitude and frequency indicate that distortion of the velocity and density are independent of frequency. It is shown that the density and velocity perturbation can be approximated for any sound source Mach number within the range examined using the parametrised developed equation. The developed approximation could be used to accurately simulate the influence of an oscillating plane using a stationary analytical source. This could be used to develop a hybrid molecular/continuum model that will allow lower frequency simulations. The improved understanding of the causes of the distorted high frequency waveshape could also improve the fidelity of parametric arrays.

Evaluation of the reliability and validity of the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) in paediatric cutaneous lupus among paediatric dermatologists and rheumatologists.

BACKGROUND: The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) is a reliable outcome measure for cutaneous lupus erythematosus (CLE) in adults used in clinical trials. However, it has not been validated in children, limiting clinical trials for paediatric CLE. OBJECTIVES: This study aimed to validate the CLASI in paediatrics. METHODS: Eleven paediatric patients with CLE, six dermatologists and six rheumatologists participated. The physicians were trained to use the CLASI and Physician's Global Assessment (PGA), and individually rated all patients using both tools. Each physician reassessed two randomly selected patients. Within each physician group, the intraclass correlation coefficient (ICC) was calculated to assess the reliability of each measure. RESULTS: CLASI activity scores demonstrated excellent inter- and intrarater reliability (ICC > 0·90), while the PGA activity scores had good inter-rater reliability (ICC 0·73-0·77) among both specialties. PGA activity scores showed excellent (ICC 0·89) and good intrarater reliability (ICC 0·76) for dermatologists and rheumatologists, respectively. Limitations of this study include the small sample size of patients and potential recall bias during the physician rerating session. CONCLUSIONS: CLASI activity measurement showed excellent inter- and intrarater reliability in paediatric CLE and superiority over the PGA. These results demonstrate that the CLASI is a reliable and valid outcome instrument for paediatric CLE.

Network meta-analysis of treatments for type 2 diabetes mellitus following failure with metformin plus sulfonylurea.

UNLABELLED: Aims The efficacy and safety of sodium-glucose linked transporters (SGLT2s) plus metformin and a sulfonylurea (MET + SU) for the treatment of type 2 diabetes mellitus (T2DM) in patients who fail to achieve glycemic control with MET + SU, relative to other triple therapies licensed in the EU, were estimated. Methods A systematic literature review and network meta-analysis (NMA) of randomized controlled trials (RCTs) involving anti-diabetes treatments added to MET + SU were conducted. RESULTS: Of 2236 abstracts identified through a systematic literature review, 30 RCTs published between 2003 and 2013 were included. RCTs ranged from 12 to 52 weeks in duration, included 28 to 1274 patients, were of parallel design, and most were open-label. Comparators included placebo (reference treatment), SGLT2 inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, thiazolidinediones (TZDs), alpha-glucosidase inhibitors (AGIs), meglitinides, glucagon-like peptide 1 (GLP-1) analogues, and basal, bolus, and biphasic insulin, all added on to MET + SU, as well as basal and biphasic insulin added to MET and monotherapy. The mean change (%) in HbA1c levels compared to placebo was -0.86 for SGLT2 inhibitors, -0.68 for DPP-4 inhibitors, -0.93 for TZDs, and -1.07 for GLP-1 analogues, respectively. Only SGLT2 inhibitors and GLP-1 analogues led to a weight loss (-1.71 kg and -1.14 kg, respectively) and decrease in systolic blood pressure (SBP; -3.73 mmHg and -2.90 mmHg, respectively), while all other treatments showed either an increase or no changes in weight or SBP. Conclusion SGLT2 inhibitors are at least as effective as other classes of antidiabetic agents at controlling HbA1c levels, while providing the additional benefits of weight loss and reducing SBP. Additionally, since the risk of hypoglycemia is similar or reduced with SGLT2 inhibitors, patients do not have to trade off efficacy for tolerability. Similar findings were observed for GLP-1 analogues.

Functional discovery via a compendium of expression profiles.

Ascertaining the impact of uncharacterized perturbations on the cell is a fundamental problem in biology. Here, we describe how a single assay can be used to monitor hundreds of different cellular functions simultaneously. We constructed a reference database or "compendium" of expression profiles corresponding to 300 diverse mutations and chemical treatments in S. cerevisiae, and we show that the cellular pathways affected can be determined by pattern matching, even among very subtle profiles. The utility of this approach is validated by examining profiles caused by deletions of uncharacterized genes: we identify and experimentally confirm that eight uncharacterized open reading frames encode proteins required for sterol metabolism, cell wall function, mitochondrial respiration, or protein synthesis. We also show that the compendium can be used to characterize pharmacological perturbations by identifying a novel target of the commonly used drug dyclonine.

Signaling and circuitry of multiple MAPK pathways revealed by a matrix of global gene expression profiles.

Genome-wide transcript profiling was used to monitor signal transduction during yeast pheromone response. Genetic manipulations allowed analysis of changes in gene expression underlying pheromone signaling, cell cycle control, and polarized morphogenesis. A two-dimensional hierarchical clustered matrix, covering 383 of the most highly regulated genes, was constructed from 46 diverse experimental conditions. Diagnostic subsets of coexpressed genes reflected signaling activity, cross talk, and overlap of multiple mitogen-activated protein kinase (MAPK) pathways. Analysis of the profiles specified by two different MAPKs-Fus3p and Kss1p-revealed functional overlap of the filamentous growth and mating responses. Global transcript analysis reflects biological responses associated with the activation and perturbation of signal transduction pathways.

Drug target validation and identification of secondary drug target effects using DNA microarrays.

We describe here a method for drug target validation and identification of secondary drug target effects based on genome-wide gene expression patterns. The method is demonstrated by several experiments, including treatment of yeast mutant strains defective in calcineurin, immunophilins or other genes with the immunosuppressants cyclosporin A or FK506. Presence or absence of the characteristic drug 'signature' pattern of altered gene expression in drug-treated cells with a mutation in the gene encoding a putative target established whether that target was required to generate the drug signature. Drug dependent effects were seen in 'targetless' cells, showing that FK506 affects additional pathways independent of calcineurin and the immunophilins. The described method permits the direct confirmation of drug targets and recognition of drug-dependent changes in gene expression that are modulated through pathways distinct from the drug's intended target. Such a method may prove useful in improving the efficiency of drug development programs.