A Rapidly Varying Red Supergiant X-Ray Binary in the Galactic Center

We analyzed multiwavelength observations of the previously identified Galactic center X-ray binary CXO 174528.79–290942.8 (XID 6592) and determine that the near-infrared counterpart is a red supergiant based on its spectrum and luminosity. Scutum X-1 is the only previously known X-ray binary with a red supergiant donor star and closely resembles XID 6592 in terms of X-ray luminosity (L X), absolute magnitude, and IR variability (L IR,var), supporting the conclusion that XID 6592 contains a red supergiant donor star. The XID 6592 infrared counterpart shows variability of ~0.5 mag in the Wide-field Infrared Survey Explorer-1 band (3.4 μm) on timescales of a few hours. Other infrared data sets also show large-amplitude variability from this source at earlier epochs but do not show significant variability in recent data. We do not expect red supergiants to vary by ~50% in luminosity over these short timescales, indicating that the variability should be powered by the compact object. However, the X-ray luminosity of this system is typically ~1000× less than the variable luminosity in the infrared and falls below the Chandra detection limit. While X-ray reprocessing can produce large-amplitude fast infrared variability, it typically requires LX >> LIR,var to do so, indicating that another process must be at work. We suggest that this system may be a supergiant fast X-ray transient (SFXT), and that a large (~1038 ergs s−1), fast (102-4 s) X-ray flare could explain the rapid IR variability and lack of a long-lasting X-ray outburst detection. SFXTs are normally associated with blue supergiant companions, so if confirmed, XID 6592 would be the first red supergiant SFXT, as well as the second X-ray red supergiant binary.A.M. acknowledges support from the Generalitat Valenciana through the grant BEST/2015/242 and from the Ministerio de Educación, Cultura y Deporte through the grant PRX15/00030

Insomnia as an Independent Predictor of Incident Cardiovascular Disease in HIV: Data from the Veterans Aging Cohort Study

Background: Insomnia is associated with increased cardiovascular disease (CVD) risk in the general population and is highly prevalent in people with HIV. The CVD risk conferred by insomnia in the HIV population is unknown. Methods: Using the Veterans Aging Cohort Study-Survey Cohort, insomnia symptoms were measured and dummy coded with the item, “Difficulty falling or staying asleep?” (5-point scale from no difficulty to bothers a lot). Incident CVD event ICD-9 codes (acute myocardial infarction, stroke, or coronary artery revascularization) were identified with VA and Medicare administrative data and VA fee-for-service data. Those with baseline CVD were excluded. Results: HIV-infected (N=3,108) veterans had a median follow-up time of 10.8 years, during which 267 CVD events occurred. Compared to HIV-infected veterans with no difficulty falling or staying asleep, HIV-infected veterans bothered a lot by insomnia symptoms had an increased risk of incident CVD after adjusting for demographics (HR=1.64, 95%CI=1.16-2.31, p=.005), CVD risk factors (HR=1.62, 95%CI=1.14-2.30, p=.007), additional potential confounders (hepatitis C infection, renal disease, anemia, alcohol use, cocaine use; HR=1.70, 95%CI=1.19-2.43, p=.003), and HIV-specific factors (HIV-1 RNA, CD4+ T-cell count, ART; HR=1.66, 95%CI=1.16-2.37, p=.005). Additional adjustment for non-benzodiazepine sleep medication (HR=1.62, 95%CI=1.13-2.32, p=.009) did not attenuate the association; however, it fell short of significance at p < .01 after adjustment for depressive symptoms (HR=1.51, 95%CI=0.98-2.32, p=.060) or antidepressant medication (HR=1.51, 95%CI=1.04-2.19, p=.031). Conclusion: Highly bothersome insomnia symptoms were significantly associated with incident CVD in HIV-infected veterans, suggesting that insomnia may be a novel, modifiable risk factor for CVD in HIV

Effects of BG9719 (CVT-124), an A1-Adenosine receptor antagonist, and furosemide on glomerular filtration rate and natriuresis in patients with congestive heart failure

AbstractOBJECTIVESTo determine the effects of furosemide and the selective A1adenosine receptor BG9719 on renal function in patients with congestive heart failure (CHF).BACKGROUNDStudies suggest that adenosine may affect renal function by various mechanisms, but the effects of blockade of this system in humans is unknown. In addition, the effects of a therapeutic dose of furosemide on glomerular filtration rate (GFR) and renal plasma flow (RPF) in heart failure patients are controversial.METHODSOn different days, 12 patients received placebo, BG9719 and furosemide. Glomerular filtration rate, RPF and sodium and water excretion were assessed immediately following drug administration.RESULTSGlomerular filtration rate was 84 ± 23 ml/min/1.73m2after receiving placebo, 82 ± 24 following BG9719 administration and a decreased (p < 0.005) 63 ± 18 following furosemide. Renal plasma flow was unchanged at 293 ± 124 ml/min/1.73m2on placebo, 334 ± 155 after receiving BG9719 and 374 ± 231 after receiving furosemide. Sodium excretion increased from 8 ± 8 mEq following placebo administration to 37 ± 26 mEq following BG9719 administration. In the six patients in whom it was measured, sodium excretion was 104 ± 78 mEq following furosemide administration.CONCLUSIONSNatriuresis is effectively induced by both furosemide and the adenosine A1antagonist BG9719 in patients with CHF. Doses of the two drugs used in this study did not cause equivalent sodium and water excretion but only furosemide decreased GFR. These data suggest that adenosine is an important determinant of renal function in patients with heart failure

Exenatide extended release in patients with type 1 diabetes with and without residual insulin production

AimsTo test whether a long- acting GLP- 1 receptor agonist would improve glucose control in patients with type 1 diabetes (T1D) and to determine whether the presence of residual beta cell function would affect the response. In addition, we sought to determine whether the drug would affect beta cell function.MethodsWe performed a randomized placebo- controlled trial of exenatide extended release (ER) in participants with T1D with and without detectable levels of C- peptide. Seventy- nine participants were randomized to exenatide ER 2 mcg weekly, or placebo, stratified by the presence or absence of detectable C- peptide levels. The primary outcome was the difference in glycated haemoglobin (HbA1c) levels at 24- weeks. Participants were followed for another 6 months off study drug.ResultsAt week 24, the time of the primary outcome, the least squares (LS) mean HbA1c level was 7.76% (95% confidence interval [CI] 7.42, 8.10) in the exenatide ER group versus 8.0% (95% CI 7.64, 8.35) in the placebo group (P = 0.08). At week 12 the LS mean HbA1c levels were 7.71% (95% CI 7.37, 8.05) in the exenatide ER group versus 8.05% (95% CI 7.7, 8.4) in the placebo group (P = 0.01). The improvement at week 12 was driven mainly by those with detectable levels of C- peptide. Those treated with exenatide ER lost weight at 12 and 24- weeks compared to those treated with placebo (P- <0.001 and P = 0.007). The total insulin dose was lower, but not when corrected for body weight, and was not affected by residual insulin production. Adverse events were more frequent with exenatide ER, but hypoglycaemia was not increased.ConclusionTreatment with exenatide ER may have short- term benefits in some individuals with T1D who are overweight or who have detectable levels of C- peptide, but short- term improvements were not sustained.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163873/1/dom14121_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163873/2/dom14121.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163873/3/dom14121-sup-0001-Supinfo.pd

Measures of insulin sensitivity, leptin, and adiponectin concentrations in cats in diabetic remission compared to healthy control cats

ObjectivesFirstly, to compare differences in insulin, adiponectin, leptin, and measures of insulin sensitivity between diabetic cats in remission and healthy control cats, and determine whether these are predictors of diabetic relapse. Secondly, to determine if these hormones are associated with serum metabolites known to differ between groups. Thirdly, if any of the hormonal or identified metabolites are associated with measures of insulin sensitivity.AnimalsTwenty cats in diabetic remission for a median of 101 days, and 21 healthy matched control cats.MethodsA casual blood glucose measured on admission to the clinic. Following a 24 h fast, a fasted blood glucose was measured, and blood sample taken for hormone (i.e., insulin, leptin, and adiponectin) and untargeted metabolomic (GC-MS and LC-MS) analysis. A simplified IVGGT (1 g glucose/kg) was performed 3 h later. Cats were monitored for diabetes relapse for at least 9 months (270 days).ResultsCats in diabetic remission had significantly higher serum glucose and insulin concentrations, and decreased insulin sensitivity as indicated by an increase in HOMA and decrease in QUICKI and Bennett indices. Leptin was significantly increased, but there was no difference in adiponectin (or body condition score). Several significant correlations were found between insulin sensitivity indices, leptin, and serum metabolites identified as significantly different between remission and control cats. No metabolites were significantly correlated with adiponectin. No predictors of relapse were identified in this study.Conclusion and clinical importanceInsulin resistance, an underlying factor in diabetic cats, persists in diabetic remission. Cats in remission should be managed to avoid further exacerbating insulin resistance

Long-term survival in people with transthyretin amyloid cardiomyopathy who took tafamidis: A Plain Language Summary

WHAT IS THIS PLAIN LANGUAGE SUMMARY ABOUT?: This summary presents the results from an ongoing, long-term extension study that followed an earlier study called ATTR-ACT. People who took part in this extension study and ATTR-ACT have a type of heart disease known as transthyretin amyloid cardiomyopathy (ATTR-CM for short), which causes heart failure and death. In ATTR-ACT, people took either a medicine called tafamidis or a placebo (a pill that looks like the study drug but does not contain any active ingredients) for up to 2½ years. So far, in the long-term extension study, people have continued taking tafamidis, or switched from taking a placebo to tafamidis, for another 2½ years. Researchers looked at how many people died in ATTR-ACT and the extension study. The long-term extension study is expected to end in 2027, so these are interim (not final) results. WHAT DID RESEARCHERS FIND OUT?: In the extension study of ATTR-ACT, the risk of dying was lower in people who took tafamidis continuously throughout ATTR-ACT and the extension study than in people who took placebo in ATTR-ACT and switched to tafamidis in the extension study. WHAT DO THE RESULTS MEAN?: Taking tafamidis increases how long people with ATTR-CM live. People with ATTR-CM who take tafamidis early and continuously are more likely to live longer than those who do not. These results highlight the importance of early detection and treatment in people with ATTR-CM. Clinical Trial Registration: NCT01994889 (ClinicalTrials.gov) Clinical Trial Registration: NCT02791230 (ClinicalTrials.gov)

HIV-2 Integrase Variation in Integrase Inhibitor-Naïve Adults in Senegal, West Africa

Antiretroviral therapy for HIV-2 infection is hampered by intrinsic resistance to many of the drugs used to treat HIV-1. Limited studies suggest that the integrase inhibitors (INIs) raltegravir and elvitegravir have potent activity against HIV-2 in culture and in infected patients. There is a paucity of data on genotypic variation in HIV-2 integrase that might confer intrinsic or transmitted INI resistance.We PCR amplified and analyzed 122 HIV-2 integrase consensus sequences from 39 HIV-2-infected, INI-naive adults in Senegal, West Africa. We assessed genetic variation and canonical mutations known to confer INI-resistance in HIV-1.No amino acid-altering mutations were detected at sites known to be pivotal for INI resistance in HIV-1 (integrase positions 143, 148 and 155). Polymorphisms at several other HIV-1 INI resistance-associated sites were detected at positions 72, 95, 125, 154, 165, 201, 203, and 263 of the HIV-2 integrase protein.Emerging genotypic and phenotypic data suggest that HIV-2 is susceptible to the new class of HIV integrase inhibitors. We hypothesize that intrinsic HIV-2 integrase variation at "secondary" HIV-1 INI-resistance sites may affect the genetic barrier to HIV-2 INI resistance. Further studies will be needed to assess INI efficacy as part of combination antiretroviral therapy in HIV-2-infected patients

Generalized Relativistic Meson Wave Function

We study the most general, relativistic, constituent $q{\overline q}$ meson wave function within a new covariant framework. We find that by including a tensor wave function component, a pure valence quark model is now capable of reproducing not only all static pion data ($f_\pi$, $\langle r_\pi^2 \rangle$) but also the distribution amplitude, form factor $(F_\pi(Q^2))$, and structure functions. Further, our generalized spin wave function provides a much better detailed description of meson properties than models using a simple relativistic extension of the $S=L=0$ nonrelativistic wave function.Comment: 17 pages, REXTeX 3.0 file, (uuencoded postscript files of 8 figures appended

Fall in C-peptide during first 2 years from diagnosis: Evidence of at least two distinct phases from composite type 1 diabetes trialnet data.

Interpretation of clinical trials to alter the decline in β-cell function after diagnosis of type 1 diabetes depends on a robust understanding of the natural history of disease. Combining data from the Type 1 Diabetes TrialNet studies, we describe the natural history of β-cell function from shortly after diagnosis through 2 years post study randomization, assess the degree of variability between patients, and investigate factors that may be related to C-peptide preservation or loss. We found that 93% of individuals have detectable C-peptide 2 years from diagnosis. In 11% of subjects, there was no significant fall from baseline by 2 years. There was a biphasic decline in C-peptide; the C-peptide slope was −0.0245 pmol/mL/month (95% CI −0.0271 to −0.0215) through the first 12 months and −0.0079 (−0.0113 to −0.0050) from 12 to 24 months (P \u3c 0.001). This pattern of fall in C-peptide over time has implications for understanding trial results in which effects of therapy are most pronounced early and raises the possibility that there are time-dependent differences in pathophysiology. The robust data on the C-peptide obtained under clinical trial conditions should be used in planning and interpretation of clinical trials