Circulating extracellular vesicles during pregnancy in women with type 1 diabetes: a secondary analysis of the CONCEPTT trial.

BACKGROUND: Extracellular vesicles are membrane vesicles that are released into the extracellular environment and accumulate in the circulation in vascular disease. We aimed to quantify circulating extracellular vesicles in pregnant women with type 1 diabetes and to examine associations between extracellular vesicle levels, continuous glucose measures, and pregnancy outcomes. METHODS: We used plasma samples from the Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial study and quantified circulating extracellular vesicles by flow cytometry (n = 163). Relationships with clinical variables were assessed by repeated measures correlation. Logistic regression was used to assess associations between elevated extracellular vesicle levels and pregnancy outcomes. RESULTS: Platelet extracellular vesicle levels were inversely associated with glucose time above range and glycaemic variability measures (P < 0.05). A weak positive association was observed between endothelial extracellular vesicles and mean amplitude of glycemic excursion (P < 0.05). In a univariate logistic regression model, high baseline endothelial extracellular vesicles was associated with increased risk of neonatal intensive care unit (NICU) admission (OR: 2.06, 1.03-4.10), and respiratory distress requiring ventilation (OR: 4.98, 1.04-23.92). After adjusting for HbA1c and blood pressure the relationship for NICU admission persisted and an association with hyperbilirubinemia was seen (OR: 2.56, 1.10-5.94). Elevated platelet extracellular vesicles were associated with an increased risk of NICU admission (OR: 2.18, 1.04-4.57), and hyperbilirubinemia (OR: 2.61, 1.11-6.12) after adjusting for HbA1c and blood pressure. CONCLUSIONS: High levels of extracellular vesicles in early pregnancy were associated with adverse neonatal outcomes. Assessment of extracellular vesicles may represent a novel approach to personalized care in type 1 diabetes pregnancy

Prospective Evaluation of Pregnancy-Associated Plasma Protein-A and Outcomes in Patients With Acute Coronary Syndromes

ObjectivesThis study sought to investigate whether pregnancy-associated plasma protein-A (PAPP-A) is useful for risk assessment in non–ST-segment elevation acute coronary syndrome (NSTE-ACS).BackgroundPAPP-A is a high molecular weight, zinc-binding metalloproteinase that is associated with vulnerable plaque and may be a predictor of cardiovascular disease and mortality.MethodsWe measured PAPP-A at baseline in 3,782 patients with non NSTE-ACS randomized to ranolazine or placebo in the MERLIN–TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes) trial and followed for an average of 1 year. A cut point of 6.0 μIU/ml was chosen from pilot work in this cohort.ResultsPAPP-A >6.0 μIU/ml at presentation was associated with higher rates of cardiovascular death (CVD) or myocardial infarction (MI) at 30 days (7.4% vs. 3.7%, hazard ratio [HR]: 2.01; 95% confidence interval [CI]: 1.43 to 2.82; p < 0.001) and at 1 year (14.9% vs. 9.7%, HR: 1.63; 95% CI: 1.29 to 2.05; p < 0.001). PAPP-A was also associated with higher rates of CVD (HR: 1.94; 95% CI: 1.07 to 3.52, p = 0.027) and myocardial infarction (HR: 1.82; 95% CI: 1.22 to 2.71, p = 0.003) individually at 30 days. There was no difference in the risk associated with PAPP-A stratified by baseline cardiac troponin I [Accu-TnI >0.04 μg/l], p interaction = 0.87). After adjustment for cardiac troponin I, ST-segment deviation, age, sex, diabetes, smoking, hypertension, and coronary artery disease, PAPP-A was independently associated with CVD/myocardial infarction at 30 days (adjusted HR: 1.62, 95% CI: 1.15 to 2.29; p = 0.006) and 1 year (adjusted HR: 1.35, 95% CI: 1.07 to 1.71; p = 0.012). PAPP-A also improved the net reclassification for CVD/MI (p = 0.003). There was no significant interaction with ranolazine.ConclusionsPAPP-A was independently associated with recurrent cardiovascular events in patients with NSTE-ACS. This finding supports PAPP-A as a candidate prognostic marker in patients with ACS and supports investigation of its therapeutic implications

SkyMapper Southern Survey: First Data Release (DR1)

We present the first data release (DR1) of the SkyMapper Southern Survey, a hemispheric survey carried out with the SkyMapper Telescope at Siding Spring Observatory in Australia. Here, we present the survey strategy, data processing, catalogue construction and database schema. The DR1 dataset includes over 66,000 images from the Shallow Survey component, covering an area of 17,200 deg$^2$ in all six SkyMapper passbands $uvgriz$, while the full area covered by any passband exceeds 20,000 deg$^2$. The catalogues contain over 285 million unique astrophysical objects, complete to roughly 18 mag in all bands. We compare our $griz$ point-source photometry with PanSTARRS1 DR1 and note an RMS scatter of 2%. The internal reproducibility of SkyMapper photometry is on the order of 1%. Astrometric precision is better than 0.2 arcsec based on comparison with Gaia DR1. We describe the end-user database, through which data are presented to the world community, and provide some illustrative science queries.Comment: 31 pages, 19 figures, 10 tables, PASA, accepte

Transition probabilities for general birth-death processes with applications in ecology, genetics, and evolution

A birth-death process is a continuous-time Markov chain that counts the number of particles in a system over time. In the general process with $n$ current particles, a new particle is born with instantaneous rate $\lambda_n$ and a particle dies with instantaneous rate $\mu_n$. Currently no robust and efficient method exists to evaluate the finite-time transition probabilities in a general birth-death process with arbitrary birth and death rates. In this paper, we first revisit the theory of continued fractions to obtain expressions for the Laplace transforms of these transition probabilities and make explicit an important derivation connecting transition probabilities and continued fractions. We then develop an efficient algorithm for computing these probabilities that analyzes the error associated with approximations in the method. We demonstrate that this error-controlled method agrees with known solutions and outperforms previous approaches to computing these probabilities. Finally, we apply our novel method to several important problems in ecology, evolution, and genetics

111th Congress

Financial regulatory reform is being discussed in the 111th Congress, the continuation of a policy debate that began before the September 2008 financial disruption. This report reviews issues related to financial regulation. It provides brief descriptions of comprehensive reform bills in the 111th Congress that addresses these issues

The prognostic value of serum myoglobin in patients with non–ST-segment elevation acute coronary syndromes Results from the TIMI 11B and TACTICS-TIMI 18 studies

AbstractObjectivesThe goal of this study was to define the prognostic value of serum myoglobin in patients with non–ST-elevation acute coronary syndromes (ACS).BackgroundWhile myoglobin is useful for the early diagnosis of myocardial infarction (MI), its role in the early risk-stratification of patients with ACS has not been established.MethodsMyoglobin, creatine kinase-MB subfraction (CK-MB) and troponin I (cTnI) were measured at randomization in 616 patients from the Thrombolysis In Myocardial Ischemia/Infarction (TIMI) 11B study and 1,841 patients from the Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Therapy-Thrombolysis In Myocardial Ischemia/Infarction (TACTICS-TIMI) 18 study. The risks for death and nonfatal MI through six months of follow-up were compared between patients with and without myoglobin elevation (>110 μg/l) in each study and in a dataset combining all eligible patients from both studies (n = 2,457).ResultsIn a multivariate model adjusting for baseline characteristics, ST changes and CK-MB and cTnI levels, an elevated baseline myoglobin was associated with increased six-month mortality in TIMI 11B (adjusted odds ratio [OR] 2.9 [95% confidence interval {CI} 1.2 to 7.1]), TACTICS-TIMI 18 (adjusted OR 3.0 [95% CI 1.5 to 5.9]) and the combined dataset (adjusted OR 3.0 [95% CI 1.8 to 5.0]). In contrast, there was no significant association between myoglobin elevation and nonfatal MI (combined dataset adjusted OR 1.55, 95% CI 0.9 to 2.6). In TACTICS-TIMI 18, patients with versus those without myoglobin elevation were more likely to have an occluded culprit artery (28% vs. 10%; p < 0.0001) and visible thrombus (49% vs. 34%; p = 0.006) and less likely to have TIMI 3 flow (53% vs. 68%; p = 0.009).ConclusionsA serum concentration of myoglobin above the MI detection threshold (>110 μg/l) is associated with an increased risk of six-month mortality, independent of baseline clinical characteristics, electrocardiographic changes and elevation in CK-MB and cTnI. These findings suggest that myoglobin may be a useful addition to cardiac biomarker panels for early risk-stratification in ACS

Platelet‐Derived Growth Factor Stimulates Bone Fill and Rate of Attachment Level Gain: Results of a Large Multicenter Randomized Controlled Trial

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141430/1/jper2205.pd