Glycemic traits are used to diagnose and monitor type 2 diabetes, and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here, we aggregated genome-wide association studies in up to 281,416 individuals without diabetes (30% non-European ancestry) with fasting glucose, 2h-glucose post-challenge, glycated hemoglobin, and fasting insulin data. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P <5x10 -8 ), 80% with no significant evidence of between-ancestry heterogeneity. Analyses restricted to European ancestry individuals with equivalent sample size would have led to 24 fewer new loci. Compared to single-ancestry, equivalent sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase understanding of diabetes pathophysiology by use of trans-ancestry studies for improved power and resolution.

BackgroundOntario, the most populous province in Canada, has a universal healthcare system that routinely collects health administrative data on its 13 million legal residents that is used for health research. Record linkage has become a vital tool for this research by enriching this data with the Immigration, Refugees and Citizenship Canada Permanent Resident (IRCC-PR) database and the Office of the Registrar General’s Vital Statistics-Death (ORG-VSD) registry. Our objectives were to estimate linkage rates and compare characteristics of individuals in the linked versus unlinked files.MethodsWe used both deterministic and probabilistic linkage methods to link the IRCC-PR database (1985–2012) and ORG-VSD registry (1990–2012) to the Ontario’s Registered Persons Database. Linkage rates were estimated and standardized differences were used to assess differences in socio-demographic and other characteristics between the linked and unlinked records.ResultsThe overall linkage rates for the IRCC-PR database and ORG-VSD registry were 86.4 and 96.2 %, respectively. The majority (68.2 %) of the record linkages in IRCC-PR were achieved after three deterministic passes, 18.2 % were linked probabilistically, and 13.6 % were unlinked. Similarly the majority (79.8 %) of the record linkages in the ORG-VSD were linked using deterministic record linkage, 16.3 % were linked after probabilistic and manual review, and 3.9 % were unlinked. Unlinked and linked files were similar for most characteristics, such as age and marital status for IRCC-PR and sex and most causes of death for ORG-VSD. However, lower linkage rates were observed among people born in East Asia (78 %) in the IRCC-PR database and certain causes of death in the ORG-VSD registry, namely perinatal conditions (61.3 %) and congenital anomalies (81.3 %).ConclusionsThe linkages of immigration and vital statistics data to existing population-based healthcare data in Ontario, Canada will enable many novel cross-sectional and longitudinal studies to be conducted. Analytic techniques to account for sub-optimal linkage rates may be required in studies of certain ethnic groups or certain causes of death among children and infants.Electronic supplementary materialThe online version of this article (doi:10.1186/s12911-016-0375-3) contains supplementary material, which is available to authorized users.

Diabetes is a pathological condition characterized by relative insulin deficiency, persistent hyperglycemia, and, consequently, diffuse micro-and macrovascular disease. One therapeutic strategy is to amplify insulin-secretion capacity by increasing the number of the insulin-producing β cells without triggering a generalized proliferative response. Here, we present the development of a small-molecule screening platform for the identification of molecules that increase β-cell replication. Using this platform, we identify a class of compounds [adenosine kinase inhibitors (ADK-Is)] that promote replication of primary β cells in three species (mouse, rat, and pig). Furthermore, the replication effect of ADK-Is is cell type-selective: treatment of islet cell cultures with ADK-Is increases replication of β cells but not that of α cells, PP cells, or fibroblasts. Short-term in vivo treatment with an ADK-I also increases β-cell replication but not exocrine cell or hepatocyte replication. Therefore, we propose ADK inhibition as a strategy for the treatment of diabetes.

Population-based surveillance of diabetes in children is possible using administrative data. This will facilitate further study of trends in incidence but also in use of health services and outcomes. Further work to differentiate type 1 and 2 diabetes will be important.

36Glioblastoma Multiforme (GBM) is a rapidly dividing tumour associated with a poor prognosis.1,2 The current standard of care for newly diagnosed GBM is surgical resection followed by radiotherapy with concurrent temozolomide (RT/TMZ) and then maintenance temozolomide for at least six months. Contrast-based imaging studies, computerized tomography (CT) or magnetic resonance (MR), may reveal increased contrast-enhancement and peritumoural edema following radiotherapy, with or without the use of concurrent temozolomide. Although in some cases these changes reflect tumour growth due to the treatment resistant nature of GBM , we ABSTRACT: Purpose: Pseudoprogression (psPD) is now recognised following radiotherapy with concurrent temozolomide (RT/TMZ) for glioblastoma multiforme (GBM). The aim of this study was to determine the incidence of psPD following RT/TMZ and the effect of psPD on prognosis. Materials/Methods: All patients receiving RT/TMZ for newly diagnosed GBM were identified from a prospective database. Clinical and radiographic data were retrospectively reviewed. Early progression was defined as radiological progression (RECIST criteria) during or within eight weeks of completing RT/TMZ. Pseudoprogression was defined as early progression with subsequent disease stabilization, without salvage therapy, for at least six months from completion of RT/TMZ. The primary outcome was overall survival (Kaplan-Meier) and log rank analysis was used to compare groups. Results: Out of 111 patients analyzed, 104 were evaluable for radiological response. Median age was 58 years and median follow-up 55 weeks. Early progression was confirmed in 26% and within this group 32% had psPD. Median survival for the whole cohort was 56.7 weeks [95% CI (51.0, 71.3)]. Median survival for patients with psPD was significantly higher than for patients with true early progression (124.9 weeks versus 36.0 weeks, p=0.0286). Conclusions: Approximately one third of patients with early progression were found to have psPD which was associated with a favourable prognosis. Maintenance TMZ should not be abandoned on the basis of seemingly discouraging imaging features identified within the first three months after RT/TMZ. RÉSUMÉ: Pseudoprogression après la chimioradiothérapie dans le traitement du glioblastome multiforme. Objectif : La pseudoprogression (psPD), qui survient après le traitement par radiothérapie associée à l'administration de témozolomide (RT/TMZ) pour traiter le glioblastome multiforme (GBM), est maintenant bien connue. Le but de cette étude était de déterminer l'incidence de la psPD après le traitement par la RT/TMZ et ses conséquences sur le pronostic. Matériel et méthodes : Tous les patients traités par RT/TMZ pour un GBM nouvellement diagnostiqué ont été identifiés dans une banque de données prospective. Les données cliniques et radiologiques ont été révisées rétrospectivement. Une progression précoce était définie comme une progression radiologique (critères RECIST) pendant ou au cours des 8 semaines suivant la fin du traitem...

Mental health care use for children and youth is increasing over time in all sectors, but appears to be increasing at a greater rate in the acute care sector. Further research is required to understand whether the observed differences reflect difficulty with access to outpatient care.

Under universal insurance there are differences in access to, and outcomes of, primary care related to local physician supply after controlling for neighborhood income. The most pronounced effect is on primary and ED care use, but there are implications for acute and chronic disease control. Physician distribution is a critical issue to address in policies to improve access to care.

Brachytherapy (BT) is an essential component of radical treatment for cervix cancer. Uterine perforation is a potential complication of intrauterine applicator (tandem) insertion. Postprocedure pelvic computed tomography (CT) scans are routinely performed at this center. The objective of this study was to prospectively compare radiation oncologists' (RO) clinical impression of satisfactory tandem placement with actual tandem placement as determined from pelvic CT. Patients with cervix cancer undergoing low-dose rate BT from April 2003 to December 2005 were prospectively identified. After tandem placement, patients were brought to the radiotherapy department for pelvic imaging (plain films and CT). Prior to viewing imaging, the RO specified whether they were concerned vs not concerned about uterine perforation. The CT was then reviewed to determine actual tandem placement (perforation vs no perforation). One hundred twenty-four sequential tandem insertions were performed in 114 patients and eligible for analysis. The incidence of CT detected uterine perforation was 13.7% (17/124). Physician concern, age greater than or equal to 60, and tumor size were significant predictors of uterine perforation (P < 0.0001, P= 0.0019, and P= 0.0016, respectively). The overall sensitivity and specificity for physician concern was 52.9% and 84.1%, respectively. CT detected perforation in 8.2% (8/98) of insertions where the RO was clinically confident of correct tandem placement. Pelvic CT was a useful modality to accompany clinical assessment in identifying uterine perforation in cervix BT. As a low but potentially clinical significant number of perforations identified on CT were not suspected clinically, we recommend acquiring pelvic imaging in all patients following tandem insertion to ensure intrauterine tandem positioning.