Developing type 1 diabetes resources: a qualitative study to identify resources needed to upskill and support community sport coaches

IntroductionCommunity sport coaches in Western Australia lack an understanding, the confidence, and knowledge in supporting young people with Type 1 diabetes (T1D). This study aims to identify what T1D educational resources are required to upskill coaches in Western Australia.MethodsSemi-structured online interviews were conducted with i) young people living with T1D, ii) parents of young people living with T1D and iii) community sport coaches. The questions explored i) past experiences of T1D management in community sport ii) the T1D information coaches should be expected to know about and iii) the format of resources to be developed. Thematic analysis of interview transcripts was performed, and the themes identified were used to guide resource development.ResultsThirty-two participants (16 young people living with T1D, 8 parents, 8 coaches) were interviewed. From the interviews, young people wanted coaches to have a better understanding of what T1D is and the effect it has on their sporting performance, parents wanted a resource that explains T1D to coaches, and sports coaches wanted to know the actions to best support a player living with T1D. All groups identified that signs and symptoms of hypoglycaemia and hyperglycaemia needed to be a key component of the resource. Sports coaches wanted a resource that is simple, quick to read and available in a variety of different formats.ConclusionThe interviews resulted in valuable information gained from all groups and have reinforced the need for the development of specific resources to increase community knowledge and provide support for players with T1D, parents and sport coaches

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Multiethnic Meta-Analysis Identifies Ancestry-Specific and Cross-Ancestry Loci for Pulmonary Function

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of lung function and clinical relevance of implicated loci

Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of l

Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney.

Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation

The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

To dissect the genetic architecture of blood pressure and assess effects on target-organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure loci, of which 17 were novel and 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target-organ damage in multiple tissues, with minor effects in the kidney. Our findings expand current knowledge of blood pressure pathways and highlight tissues beyond the classic renal system in blood pressure regulation

A Novel Mobile Health App to Educate and Empower Young People With Type 1 Diabetes to Exercise Safely: Prospective Single-Arm Mixed Methods Pilot Study

BackgroundEmpowering young people with type 1 diabetes (T1D) to manage their blood glucose levels during exercise is a complex challenge faced by health care professionals due to the unpredictable nature of exercise and its effect on blood glucose levels. Mobile health (mHealth) apps would be useful as a decision-support aid to effectively contextualize a blood glucose result and take appropriate action to optimize glucose levels during and after exercise. A novel mHealth app acT1ve was recently developed, based on expert consensus exercise guidelines, to provide real-time support for young people with T1D during exercise. ObjectiveOur aim was to pilot acT1ve in a free-living setting to assess its acceptability and functionality, and gather feedback on the user experience before testing it in a larger clinical trial. MethodsA prospective single-arm mixed method design was used. Ten participants with T1D (mean age 17.7 years, SD 4.2 years; mean HbA1c, 54 mmol/mol, SD 5.5 mmol/mol [7.1%, SD 0.5%]) had acT1ve installed on their phones, and were asked to use the app to guide their exercise management for 6 weeks. At the end of 6 weeks, participants completed both a semistructured interview and the user Mobile Application Rating Scale (uMARS). All semistructured interviews were transcribed. Thematic analysis was conducted whereby interview transcripts were independently analyzed by 2 researchers to uncover important and relevant themes. The uMARS was scored for 4 quality subscales (engagement, functionality, esthetics, and information), and a total quality score was obtained from the weighted average of the 4 subscales. Scores for the 4 objective subscales were determined by the mean score of each of its individual questions. The perceived impact and subjective quality of acT1ve for each participant were calculated by averaging the scores of their related questions, but were not considered in the total quality score. All scores have a maximal possible value of 5, and they are presented as medians, IQRs, and ranges. ResultsThe main themes arising from the interview analysis were “increased knowledge,” “increased confidence to exercise,” and “suitability” for people who were less engaged in exercise. The uMARS scores for acT1ve were high (out of 5) for its total quality (median 4.3, IQR 4.2-4.6), engagement (median 3.9, IQR 3.6-4.2), functionality (median 4.8, IQR 4.5-4.8), information (median 4.6, IQR 4.5-4.8), esthetics (median 4.3, IQR 4.0-4.7), subjective quality (median 4.0, IQR 3.8-4.2), and perceived impact (median 4.3, IQR 3.6-4.5). ConclusionsThe acT1ve app is functional and acceptable, with a high user satisfaction. The efficacy and safety of this app will be tested in a randomized controlled trial in the next phase of this study. Trial RegistrationAustralian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12619001414101; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=37837

Targeted Next-Generation Sequencing Improves the Prognostication of Patients with Disseminated Appendiceal Mucinous Neoplasms (Pseudomyxoma Peritonei)

BACKGROUND: Appendiceal mucinous neoplasms (AMNs) with disseminated disease (pseudomyxoma peritonei) are heterogeneous tumors with variable clinicopathologic behavior. Despite the development of prognostic systems, objective biomarkers are needed to stratify patients. With the advent of next-generation sequencing (NGS), it remains unclear if molecular testing can improve the evaluation of disseminated AMN patients. METHODS: Targeted NGS was performed for 183 patients and correlated with clinicopathologic features to include American Joint Committee on Cancer/World Health Organization (AJCC/WHO) histologic grade, peritoneal cancer index (PCI), completeness of cytoreduction (CC) score, and overall survival (OS). RESULTS: Genomic alterations were identified for 179 (98%) disseminated AMNs. Excluding mitogen-activated protein kinase genes and GNAS due to their ubiquitous nature, collective genomic alterations in TP53, SMAD4, CDKN2A, and the mTOR genes were associated with older mean age, higher AJCC/WHO histologic grade, lymphovascular invasion, perineural invasion, regional lymph node metastasis, and lower mean PCI (p \u3c 0.040). Patients harboring TP53, SMAD4, ATM, CDKN2A, and/or mTOR gene alterations were found to have lower OS rates of 55% at 5 years and 14% at 10 years, compared with 88% at 5 years and 88% at 10 years for patients without the aforementioned alterations (p \u3c 0.001). Based on univariate and multivariate analyses, genomic alterations in TP53, SMAD4, ATM, CDKN2A, and/or the mTOR genes in disseminated AMNs were a negative prognostic factor for OS and independent of AJCC/WHO histologic grade, PCI, CC score, and hyperthermic intraperitoneal chemotherapy treatment (p = 0.006). CONCLUSIONS: Targeted NGS improves the prognostic assessment of patients with disseminated AMNs and identifies patients who may require increased surveillance and/or aggressive management

Core feeding areas (50% contours of foraging locations) of black-legged kittiwakes from St. Paul and St. George Islands during trips to marine habitats.

<p>Trips to the shelf (A), and to the basin (B). Patterns: red  =  St. Paul; black  =  St. George; Years: 2008 =  dots, 2009  =  crossed lines, 2010  =  diagonal lines.</p