Framework to assess the quality of mHealth apps: a mixed-method international case study protocol

Introduction: Healthcare professionals (HCPs) often recommend their patients to use a specific mHealth app as part of health promotion, disease prevention and patient self-management. There has been a significant growth in the number of HCPs downloading and using mobile health (mHealth) apps. Most mHealth apps that are available in app stores employ a ‘star rating’ system. This is based on user feedback on an app, but is highly subjective. Thus, the identification of quality mHealth apps which are deemed fit for purpose can be a difficult task for HCPs. Currently, there is no unified, validated standard guidelines for assessment of mHealth apps for patient safety, which can be used by HCPs. The Modified Enlight Suite (MES) is a quality assessment framework designed to provide a means for HCPs to evaluate mHealth apps before they are recommended to patients. MES was adapted from the original Enlight Suite for international use through a Delphi method, followed by preliminary validation process among a population predominantly consisting of medical students. This study aims to evaluate the applicability and validity of the MES, by HCPs, in low, middle and high income country settings. Methods and analysis: MES will be evaluated through a mixed-method study, consisting of qualitative (focus group) and quantitative (survey instruments) research, in three target countries: Malaŵi (low income), South Africa (middle income) and Ireland (high income). The focus groups will be conducted through Microsoft Teams (Microsoft, Redmond, Washington, USA) and surveys will be conducted online using Qualtrics (Qualtrics International, Seattle, Washington, USA). Participants will be recruited through the help of national representatives in Malawi (Mzuzu University), South Africa (University of Fort Hare) and Ireland (University College Cork) by email invitation. Data analysis for the focus group will be by the means of thematic analysis. Data analysis for the survey will use descriptive statistics and use Cronbach alpha as an indicator of internal consistency of the MES. The construct validity of the mHealth app will be assessed by computing the confirmatory factor analysis using Amos. Ethics and dissemination: The study has received ethical approval from the Social Research Ethics Committee (SREC) SREC/SOM/03092021/1 at University College Cork, Ireland, Malaŵi Research Ethics Committee (MREC), Malaŵi MZUNIREC/DOR/21/59 and Inter-Faculty Research Ethics Committee (IFREC) of University of Fort Hare (REC-2 70 710-028-RA). The results of the study will be disseminated through the internet, peer-reviewed journals and conference presentations

Regulation of mammary gland branching morphogenesis by the extracellular matrix and its remodeling enzymes.

A considerable body of research indicates that mammary gland branching morphogenesis is dependent, in part, on the extracellular matrix (ECM), ECM-receptors, such as integrins and other ECM receptors, and ECM-degrading enzymes, including matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). There is some evidence that these ECM cues affect one or more of the following processes: cell survival, polarity, proliferation, differentiation, adhesion, and migration. Both three-dimensional culture models and genetic manipulations of the mouse mammary gland have been used to study the signaling pathways that affect these processes. However, the precise mechanisms of ECM-directed mammary morphogenesis are not well understood. Mammary morphogenesis involves epithelial 'invasion' of adipose tissue, a process akin to invasion by breast cancer cells, although the former is a highly regulated developmental process. How these morphogenic pathways are integrated in the normal gland and how they become dysregulated and subverted in the progression of breast cancer also remain largely unanswered questions

Safety and acceptability of an organic light-emitting diode sleep mask as a potential therapy for retinal disease

Purpose The purpose of the study was to study the effect of an organic light-emitting diode sleep mask on daytime alertness, wellbeing, and retinal structure/function in healthy volunteers and in diabetic macular oedema (DMO). Patients and methods Healthy volunteers in two groups, 18–30 yrs (A), 50–70 yrs (B) and people with DMO (C) wore masks (504 nm wavelength; 80 cd/m2 luminance; ≤8 h) nightly for 3 months followed by a 1-month recovery period. Changes from baseline were measured for (means): psychomotor vigilance task (PVT) (number of lapses (NL), response time (RT)), sleep, depression, psychological wellbeing (PW), visual acuity, contrast sensitivity, colour, electrophysiology, microperimetry, and retinal thickness on OCT. Results Of 60 participants, 16 (27%) withdrew, 8 (13%) before month 1, due to sleep disturbances and mask intolerance. About 36/55 (65%) who continued beyond month 1 reported ≥1 adverse event. At month 3 mean PVT worsened in Group A (RT (7.65%, P<0.001), NL (43.3%, P=0.005)) and mean PW worsened in all groups (A 28.0%, P=0.01, B 21.2%, P=0.03, C 12.8%, P<0.05). No other clinically significant safety signal was detected. Cysts reduced/resolved in the OCT subfield of maximal pathology in 67% Group C eyes. Thinning was greater at 3 and 4 months for greater baseline thickness (central subfield P<0.001, maximal P<0.05). Conclusion Sleep masks showed no major safety signal apart from a small impairment of daytime alertness and a moderate effect on wellbeing. Masks were acceptable apart from in some healthy participants. Preliminary data suggest a beneficial effect on retinal thickness in DMO. This novel therapeutic approach is ready for large clinical trials

Brain Rhythms Reveal a Hierarchical Network Organization

Recordings of ongoing neural activity with EEG and MEG exhibit oscillations of specific frequencies over a non-oscillatory background. The oscillations appear in the power spectrum as a collection of frequency bands that are evenly spaced on a logarithmic scale, thereby preventing mutual entrainment and cross-talk. Over the last few years, experimental, computational and theoretical studies have made substantial progress on our understanding of the biophysical mechanisms underlying the generation of network oscillations and their interactions, with emphasis on the role of neuronal synchronization. In this paper we ask a very different question. Rather than investigating how brain rhythms emerge, or whether they are necessary for neural function, we focus on what they tell us about functional brain connectivity. We hypothesized that if we were able to construct abstract networks, or “virtual brains”, whose dynamics were similar to EEG/MEG recordings, those networks would share structural features among themselves, and also with real brains. Applying mathematical techniques for inverse problems, we have reverse-engineered network architectures that generate characteristic dynamics of actual brains, including spindles and sharp waves, which appear in the power spectrum as frequency bands superimposed on a non-oscillatory background dominated by low frequencies. We show that all reconstructed networks display similar topological features (e.g. structural motifs) and dynamics. We have also reverse-engineered putative diseased brains (epileptic and schizophrenic), in which the oscillatory activity is altered in different ways, as reported in clinical studies. These reconstructed networks show consistent alterations of functional connectivity and dynamics. In particular, we show that the complexity of the network, quantified as proposed by Tononi, Sporns and Edelman, is a good indicator of brain fitness, since virtual brains modeling diseased states display lower complexity than virtual brains modeling normal neural function. We finally discuss the implications of our results for the neurobiology of health and disease

KeV Warm Dark Matter and Composite Neutrinos

Elementary keV sterile Dirac neutrinos can be a natural ingredient of the composite neutrino scenario. For a certain class of composite neutrino theories, these sterile neutrinos naturally have the appropriate mixing angles to be resonantly produced warm dark matter (WDM). Alternatively, we show these sterile neutrinos can be WDM produced by an entropy-diluted thermal freeze-out, with the necessary entropy production arising not from an out-of-equilibrium decay, but rather from the confinement of the composite neutrino sector, provided there is sufficient supercooling.Comment: 12 pages, 2 figures, published versio

Complement-Mediated Virus Infectivity Neutralisation by HLA Antibodies Is Associated with Sterilising Immunity to SIV Challenge in the Macaque Model for HIV/AIDS.

Sterilising immunity is a desired outcome for vaccination against human immunodeficiency virus (HIV) and has been observed in the macaque model using inactivated simian immunodeficiency virus (SIV). This protection was attributed to antibodies specific for cell proteins including human leucocyte antigens (HLA) class I and II incorporated into virions during vaccine and challenge virus preparation. We show here, using HLA bead arrays, that vaccinated macaques protected from virus challenge had higher serum antibody reactivity compared with non-protected animals. Moreover, reactivity was shown to be directed against HLA framework determinants. Previous studies failed to correlate serum antibody mediated virus neutralisation with protection and were confounded by cytotoxic effects. Using a virus entry assay based on TZM-bl cells we now report that, in the presence of complement, serum antibody titres that neutralise virus infectivity were higher in protected animals. We propose that complement-augmented virus neutralisation is a key factor in inducing sterilising immunity and may be difficult to achieve with HIV/SIV Env-based vaccines. Understanding how to overcome the apparent block of inactivated SIV vaccines to elicit anti-envelope protein antibodies that effectively engage the complement system could enable novel anti-HIV antibody vaccines that induce potent, virolytic serological response to be developed

Clinical Outcomes Associated with Changes in a Chronic Disease Treatment Program in an Australian Aboriginal Community

In late 1995, a treatment program for renal disease and hypertension was introduced into a remote Aboriginal community. Over the next 3.5 years, mean blood pressure levels were markedly reduced, renal function stabilised, and rates of both renal and non-renal deaths declined significantly. In 1999-2000, responsibility for the program was passed to the community's local Health Board, which subsequently faced deficiencies in clinical information systems and a shortfall in funding. After the handover, the intensity of the program declined, and compliance with medicines fell. Blood pressures in the treatment cohort increased, renal function deteriorated, and rates of deaths from natural causes subsequently rose. From 2002 to mid-2003, the adjusted risks of renal and non-renal deaths in the treatment cohort were three and 9.5 times the respective risks of people during the first 18 months of treatment in the systematic phase of the program. Sustained vigorous activity, both in treatment of people already identified and in community screening for treatment eligibility, is required to maintain good results in any chronic disease program. Adequate resources and well supported staff are essential, and constant evaluation is needed to follow outcomes and modify strategies as necessary

A novel class of microRNA-recognition elements that function only within open reading frames.

MicroRNAs (miRNAs) are well known to target 3' untranslated regions (3' UTRs) in mRNAs, thereby silencing gene expression at the post-transcriptional level. Multiple reports have also indicated the ability of miRNAs to target protein-coding sequences (CDS); however, miRNAs have been generally believed to function through similar mechanisms regardless of the locations of their sites of action. Here, we report a class of miRNA-recognition elements (MREs) that function exclusively in CDS regions. Through functional and mechanistic characterization of these 'unusual' MREs, we demonstrate that CDS-targeted miRNAs require extensive base-pairing at the 3' side rather than the 5' seed; cause gene silencing in an Argonaute-dependent but GW182-independent manner; and repress translation by inducing transient ribosome stalling instead of mRNA destabilization. These findings reveal distinct mechanisms and functional consequences of miRNAs that target CDS versus the 3' UTR and suggest that CDS-targeted miRNAs may use a translational quality-control-related mechanism to regulate translation in mammalian cells

Identifying differential exon splicing using linear models and correlation coefficients

Background: With the availability of the Affymetrix exon arrays a number of tools have been developed to enable the analysis. These however can be expensive or have several pre-installation requirements. This led us to develop an analysis workflow for analysing differential splicing using freely available software packages that are already being widely used for gene expression analysis. The workflow uses the packages in the standard installation of R and Bioconductor (BiocLite) to identify differential splicing. We use the splice index method with the LIMMA framework. The main drawback with this approach is that it relies on accurate estimates of gene expression from the probe-level data. Methods such as RMA and PLIER may misestimate when a large proportion of exons are spliced. We therefore present the novel concept of a gene correlation coefficient calculated using only the probeset expression pattern within a gene. We show that genes with lower correlation coefficients are likely to be differentially spliced.Results: The LIMMA approach was used to identify several tissue-specific transcripts and splicing events that are supported by previous experimental studies. Filtering the data is necessary, particularly removing exons and genes that are not expressed in all samples and cross-hybridising probesets, in order to reduce the false positive rate. The LIMMA approach ranked genes containing single or few differentially spliced exons much higher than genes containing several differentially spliced exons. On the other hand we found the gene correlation coefficient approach better for identifying genes with a large number of differentially spliced exons.Conclusion: We show that LIMMA can be used to identify differential exon splicing from Affymetrix exon array data. Though further work would be necessary to develop the use of correlation coefficients into a complete analysis approach, the preliminary results demonstrate their usefulness for identifying differentially spliced genes. The two approaches work complementary as they can potentially identify different subsets of genes (single/few spliced exons vs. large transcript structure differences)

Transforming growth factor-β and breast cancer: Lessons learned from genetically altered mouse models

Transforming growth factor (TGF)-βs are plausible candidate tumor suppressors in the breast. They also have oncogenic activities under certain circumstances, however. Genetically altered mouse models provide powerful tools to analyze the complexities of TGF-βaction in the context of the whole animal. Overexpression of TGF-β can suppress tumorigenesis in the mammary gland, raising the possibility that use of pharmacologic agents to enhance TGF-β function locally might be an effective method for the chemoprevention of breast cancer. Conversely, loss of TGF-β response increases spontaneous and induced tumorigenesis in the mammary gland. This confirms that endogenous TGF-βs have tumor suppressor activity in the mammary gland, and suggests that the loss of TGF-β receptors seen in some human breast hyperplasias may play a causal role in tumor development