Performance of a computable phenotype for identification of patients with diabetes within PCORnet: The Patient-Centered Clinical Research Network

Purpose: PCORnet, the National Patient-Centered Clinical Research Network, represents an innovative system for the conduct of observational and pragmatic studies. We describe the identification and validation of a retrospective cohort of patients with type 2 diabetes (T2DM) from four PCORnet sites. Methods: We adapted existing computable phenotypes (CP) for the identification of patients with T2DM and evaluated their performance across four PCORnet sites (2012-2016). Patients entered the cohort on the earliest date they met one of three CP categories: (CP1) coded T2DM diagnosis (ICD-9/ICD-10) and an antidiabetic prescription, (CP2) diagnosis and glycosylated hemoglobin (HbA1c) ≥6.5%, or (CP3) an antidiabetic prescription and HbA1c ≥6.5%. We required evidence of health care utilization in each of the 2 prior years for each patient, as we also developed an incident T2DM CP to identify the subset of patients without documentation of T2DM in the 365 days before t 0 . Among a systematic sample of patients, we calculated the positive predictive value (PPV) for the T2DM CP and incident-T2DM CP using electronic health record (EHR) review as reference. Results: The CP identified 50 657 patients with T2DM. The PPV of patients randomly selected for validation was 96.2% (n = 1572; CI:95.1-97.0) and was consistently high across sites. The PPV for the incident-T2DM CP was 5.8% (CI:4.5-7.5). Conclusions: The T2DM CP accurately and efficiently identified patients with T2DM across multiple sites that participate in PCORnet, although the incident T2DM CP requires further study. PCORnet is a valuable data source for future epidemiological and comparative effectiveness research among patients with T2DM

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

Galaxy Clusters Associated with Short GRBs. II. Predictions for the Rate of Short GRBs in Field and Cluster Early-Type Galaxies

We determine the relative rates of short GRBs in cluster and field early-type galaxies as a function of the age probability distribution of their progenitors, P(\tau) \propto \tau^n. This analysis takes advantage of the difference in the growth of stellar mass in clusters and in the field, which arises from the combined effects of the galaxy stellar mass function, the early-type fraction, and the dependence of star formation history on mass and environment. This approach complements the use of the early- to late-type host galaxy ratio, with the added benefit that the star formation histories of early-type galaxies are simpler than those of late-type galaxies, and any systematic differences between progenitors in early- and late-type galaxies are removed. We find that the ratio varies from R(cluster)/R(field) ~ 0.5 for n = -2 to ~ 3 for n = 2. Current observations indicate a ratio of about 2, corresponding to n ~ 0 - 1. This is similar to the value inferred from the ratio of short GRBs in early- and late-type hosts, but it differs from the value of n ~ -1 for NS binaries in the Milky Way. We stress that this general approach can be easily modified with improved knowledge of the effects of environment and mass on the build-up of stellar mass, as well as the effect of globular clusters on the short GRB rate. It can also be used to assess the age distribution of Type Ia supernova progenitors.Comment: ApJ accepted versio

Stonefly (Plecoptera) fauna in a mountainous area of Central Brazil: composition and adult phenology

A survey of the stonefly (Plecoptera) fauna of streams of the Almas River basin, Pirenópolis, Goiás State, Central Brazil, is presented as well as data of some factors that could affeet the temporal distribution of the adults. For checking adult phenology, light sources were used in three stations from June 1993 to Jully 1994. The sampled individuais were identified to species or morphospecies, as possible. In this study, 301 individuais belonging to the perlid genera Anacroneuria Klapálek, 1909, Kempnyia Klapálek, 1916 and Macrogynoplax Enderlein, 1909 were collected. Adults of most species were collected along the studied period, except for those of Kempnyia that were restricted to the warm-rainy season, the same pattern for this genus in southeastern Brazil. Although adults of most species were collected along most of the studied period, the largest number of adults was collected in the months with larger mean temperatures, showing a clear seasonality in abundance

Multimodal somatostatin receptor theranostics using [⁶⁴Cu]Cu-/[¹⁷⁷Lu]Lu-DOTA-(Tyr³)octreotate and AN-238 in a mouse pheochromocytoma model.

Pheochromocytomas and extra-adrenal paragangliomas (PHEO/PGLs) are rare catecholamine-producing chromaffin cell tumors. For metastatic disease, no effective therapy is available. Overexpression of somatostatin type 2 receptors (SSTR2) in PHEO/PGLs promotes interest in applying therapies using somatostatin analogs linked to radionuclides and/or cytotoxic compounds, such as [(177)Lu]Lu-DOTA-(Tyr(3))octreotate (DOTATATE) and AN-238. Systematic evaluation of such therapies for the treatment of PHEO/PGLs requires sophisticated animal models. In this study, the mouse pheochromocytoma (MPC)-mCherry allograft model showed high tumor densities of murine SSTR2 (mSSTR2) and high tumor uptake of [(64)Cu]Cu-DOTATATE. Using tumor sections, we assessed mSSTR2-specific binding of DOTATATE, AN-238, and somatostatin-14. Therapeutic studies showed substantial reduction of tumor growth and tumor-related renal monoamine excretion in tumor-bearing mice after treatment with [(177)Lu]Lu-DOTATATE compared to AN-238 and doxorubicin. Analyses did not show agonist-dependent receptor downregulation after single mSSTR2-targeting therapies. This study demonstrates that the MPC-mCherry model is a uniquely powerful tool for the preclinical evaluation of SSTR2-targeting theranostic applications in vivo. Our findings highlight the therapeutic potential of somatostatin analogs, especially of [(177)Lu]Lu-DOTATATE, for the treatment of metastatic PHEO/PGLs. Repeated treatment cycles, fractionated combinations of SSTR2-targeting radionuclide and cytotoxic therapies, and other adjuvant compounds addressing additional mechanisms may further enhance therapeutic outcome

ExomeChip-based rare variant association study in restless legs syndrome.

Restless legs syndrome (RLS) is a common sleep-related movement disorder in populations of European descent and disease risk is strongly influenced by genetic factors. Common variants have been assessed extensively in several genome-wide association studies, but the contribution of rarer genetic variation has not been investigated at this scale. We therefore genotyped a case–control set of 9246 individuals for mainly rare and low frequency exonic variants using the Illumina ExomeChip. However, standard single variant and gene-level association tests were negative. This does not preclude a role of rare variants in RLS, but is likely due to the small sample size and the limited selection of rare genetic variation captured on the array. Therefore, exome or whole genome sequencing should be performed rather than increasing the sample size of ExomeChip studies in order to identify rare risk variants for RLS