Diabetes and Technology.

The management of diabetes in clinical practice has many challenges: quickly interpreting a large volume of self-monitoring of blood glucose data, ensuring safe and accurate titration of basal insulin, managing patients on insulin pump therapy, and synthesizing glycemic data into actionable reports to improve patient outcomes. Technological advancements are emerging as a solution to some of these challenges. This article reviews mobile applications for insulin dosing, continuous glucose monitoring, insulin pump therapy, and smart insulin pens available for patients with type 1 and type 2 diabetes.

Operationalising health systems thinking: a pathway to high effective coverage.

BACKGROUND: The global health community has recognised the importance of defining and measuring the effective coverage of health interventions and their implementation strength to monitor progress towards global mortality and morbidity targets. Existing health system models and frameworks guide thinking around these measurement areas; however, they fall short of adequately capturing the dynamic and multi-level relationships between different components of the health system. These relationships must be articulated for measurement and managed to effectively deliver health interventions of sufficient quality to achieve health impacts. Save the Children's Saving Newborn Lives programme and EnCompass LLC, its evaluation partner, developed and applied the Pathway to High Effective Coverage as a health systems thinking framework (hereafter referred to as the Pathway) in its strategic planning, monitoring and evaluation. METHODS: We used an iterative approach to develop, test and refine thinking around the Pathway. The initial framework was developed based on existing literature, then shared and vetted during consultations with global health thought leaders in maternal and newborn health. RESULTS: The Pathway is a robust health systems thinking framework that unpacks system, policy and point of intervention delivery factors, thus encouraging specific actions to address gaps in implementation and facilitate the achievement of high effective coverage. The Pathway includes six main components - (1) national readiness; (2) system structures; (3) management capacity; (4) implementation strength; (5) effective coverage; and (6) impact. Each component is comprised of specific elements reflecting the range of facility-, community- and home-based interventions. We describe applications of the Pathway and results for in-country strategic planning, monitoring of progress and implementation strength, and evaluation. CONCLUSIONS: The Pathway provides a cohesive health systems thinking framework that facilitates assessment and coordinated action to achieve high coverage and impact. Experiences of its application show its utility in guiding strategic planning and in more comprehensive and effective monitoring and evaluation as well as its potential adaptability for use in other health areas and sectors.

Bidirectional Interference Between Simulated Driving and Speaking.

Purpose This study relied on acoustic measures of connected speech and several indices of driving performance to quantify interference between speaking and simulated driving. Method Three groups of 20 younger (ages 20-30 years), middle-age (ages 40-50 years), and older (ages 60-71 years) adults produced monologues and completed a simulated driving task, which involved maintaining a constant speed and lane position on a freeway. Both tasks were completed separately and concurrently. Results There were significant divided attention effects, with a reduced speaking time ratio, and increases in vocal intensity, speed variability, and steering wheel adjustments. There was a significant between-subjects age effect for intensity and fundamental frequency as the younger group had less variation with these variables compared to the other age groups across conditions. There was a significant between-subjects age effect for lane position, steering wheel position, and speed as the younger group had less variation in lane position compared to the other 2 groups, and the older group had more variation in speed and steering wheel position compared to the other 2 groups across the experimental conditions. Conclusion These findings reveal that divided attention conditions can impact both speech and simulated driving performance. The results also shed some light on the effects of age on speech and driving tasks, although the degree of interference from divided attention did not differ by age.

Endocytic Markers Associated with the Internalization and Processing of Aspergillus fumigatus Conidia by BEAS-2B Cells.

Aspergillus fumigatus is a ubiquitous mold that produces small airborne conidia capable of traversing deep into the respiratory system. Recognition, processing, and clearance of A. fumigatus conidia by bronchial airway epithelial cells are thought to be relevant to host defense and immune signaling. Using z-stack confocal microscopy, we observed that only 10 to 20% of adherent conidia from the AF293 clinical isolate are internalized by BEAS-2B cells 6 h postchallenge and not prior. Similar percentages of internalization were observed for the CEA10 clinical isolate. A large subset of both AF293 and CEA10 conidia are rendered metabolically inactive without internalization at 3 h postchallenge by BEAS-2B cells. A significantly larger percentage of CEA10 conidia are metabolically active at 9 and 12 h postchallenge in comparison to the AF293 isolate, demonstrating heterogeneity among clinical isolates. We identified 7 host markers (caveolin, flotillin-2, RAB5C, RAB8B, RAB7A, 2xFYVE, and FAPP1) that consistently localized around internalized conidia 9 h postchallenge. Transient gene silencing of RAB5C, PIK3C3, and flotillin-2 resulted in a larger population of metabolically active conidia. Our findings emphasize the abundance of both host phosphatidylinositol 3-phosphate (PI3P) and PI4P around internalized conidia, as well as the importance of class III PI3P kinase for conidial processing. Therapeutic development focused on RAB5C-, PIK3C3-, and flotillin-2-mediated pathways may provide novel opportunities to modulate conidial processing and internalization. Determination of how contacted, external conidia are processed by airway epithelial cells may also provide a novel avenue to generate host-targeted therapeutics.IMPORTANCE Conidia from the fungus Aspergillus fumigatus are notorious for their ability to stay airborne. This characteristic is believed to allow conidia to penetrate into the cleanest environments. Several hundred conidia are thought to be inhaled each day by a given individual and then expelled by mucociliary clearance. Given that airway epithelial cells make up a significant portion of the pulmonary-air interface, we set out to determine the percentage of conidia that are actually internalized after initial contact with airway epithelial cells. We determined this through an in vitro assay using an immortalized bronchial airway epithelial cell line known as BEAS-2B. Our results suggest a small fraction of conidia are internalized by BEAS-2B cells, while the majority stay adherent to the surface of cells or are washed away during sample processing. Internalization of conidia was observed at 6 h postchallenge and not prior. Our data also indicate conidia are rendered metabolically inactive within 3 h of challenge, suggesting BEAS-2B cells process a large number of conidia without internalization in this early time frame. We have also identified several host endocytosis markers that localize around internalized conidia as well as contribute to the processing of conidia. Understanding how these host endocytosis markers affect the processing of internal and/or external conidia may provide a novel avenue for therapeutic development.

Pathways on demand: automated reconstruction of human signaling networks.

Signaling pathways are a cornerstone of systems biology. Several databases store high-quality representations of these pathways that are amenable for automated analyses. Despite painstaking and manual curation, these databases remain incomplete. We present PATHLINKER, a new computational method to reconstruct the interactions in a signaling pathway of interest. PATHLINKER efficiently computes multiple short paths from the receptors to transcriptional regulators (TRs) in a pathway within a background protein interaction network. We use PATHLINKER to accurately reconstruct a comprehensive set of signaling pathways from the NetPath and KEGG databases. We show that PATHLINKER has higher precision and recall than several state-of-the-art algorithms, while also ensuring that the resulting network connects receptor proteins to TRs. PATHLINKER's reconstruction of the Wnt pathway identified CFTR, an ABC class chloride ion channel transporter, as a novel intermediary that facilitates the signaling of Ryk to Dab2, which are known components of Wnt/ß-catenin signaling. In HEK293 cells, we show that the Ryk-CFTR-Dab2 path is a novel amplifier of ß-catenin signaling specifically in response to Wnt 1, 2, 3, and 3a of the 11 Wnts tested. PATHLINKER captures the structure of signaling pathways as represented in pathway databases better than existing methods. PATHLINKER's success in reconstructing pathways from NetPath and KEGG databases point to its applicability for complementing manual curation of these databases. PATHLINKER may serve as a promising approach for prioritizing proteins and interactions for experimental study, as illustrated by its discovery of a novel pathway in Wnt/ß-catenin signaling. Our supplementary website at http://bioinformatics.cs.vt.edu/~murali/supplements/2016-sys-bio-applications-pathlinker/ provides links to the PATHLINKER software, input datasets, PATHLINKER reconstructions of NetPath pathways, and links to interactive visualizations of these reconstructions on GraphSpace.

Corrigendum: Pathway on demand: automated reconstruction of human signaling networks.

[This corrects the article DOI: 10.1038/npjsba.2016.2.].