New Frontiers-class Uranus Orbiter: Exploring the feasibility of achieving multidisciplinary science with a mid-scale mission

n/

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

132 Assessment of Microvascular Obstruction after Acute Myocardial Infarction using Cardiac Magnetic Renonance (CMR) imaging

BackgroundInfarct size (IS) and presence of microvascular obstruction (MO) detected by cardiac magnetic resonance imaging (CMR) are of prognostic relevance in ST-elevation myocardial infarction (STEMI) patients. We sought to evaluate different cardiovascular magnetic resonance techniques for detection of MO to predict LV remodeling, in patients with first AMI who were treated within 12 hours with primary stenting.MethodsForty-three patients with first STEMI underwent cine CMR at 4 days and 6 months after AMI to calculate LV volumes and ejection fraction (LVEF). Presence of MO was qualitatively evaluated at baseline 1) using a classic first pass perfusion sequence (FP-MO); single shot SR GE at 1‘09±0’07 min, 2) using a 2D segmented IR GE pulse sequence (DHE-MO) at 8‘±1’30 min after contrast administration. CNR's were calculated from the SNR of infarcted myocardium and the MO region.ResultsMO was detected by both methods in 24% of patients (n= 11). DHE-MO was the strongest predictor of change in LV end-diastolic and end-systolic volumes over time (p<0.01), whereas FP-MO and DHE-MO had a comparable predicted value of change in LVEF (β=-3.1, p=0.03 and β=-2.8, p=0.04). CNR corrected for spatial resolution was significantly higher for detection of DHE-MO, compared to first pass defect (104±51 vs 8±4, p<0.001).ConclusionsDHE-MO is the best prognostic marker of LV remodeling, as determined by CMR within the first week of acute STEMI patients

A revised position for the primary strand of the Pleistocene-Holocene San Andreas fault in southern California.

The San Andreas fault has the highest calculated time-dependent probability for large-magnitude earthquakes in southern California. However, where the fault is multistranded east of the Los Angeles metropolitan area, it has been uncertain which strand has the fastest slip rate and, therefore, which has the highest probability of a destructive earthquake. Reconstruction of offset Pleistocene-Holocene landforms dated using the uranium-thorium soil carbonate and beryllium-10 surface exposure techniques indicates slip rates of 24.1 ± 3 millimeter per year for the San Andreas fault, with 21.6 ± 2 and 2.5 ± 1 millimeters per year for the Mission Creek and Banning strands, respectively. These data establish the Mission Creek strand as the primary fault bounding the Pacific and North American plates at this latitude and imply that 6 to 9 meters of elastic strain has accumulated along the fault since the most recent surface-rupturing earthquake, highlighting the potential for large earthquakes along this strand

007 Predictors of Infarct Size and Microvascular Obstruction Assessed by Cardiac Magnetic Resonance Imaging in patients with Acute ST elevation MI

BackgroundTime-to-reperfusion, electrocardiographic and angiographic parameters are of prognostic relevance in ST-elevation myocardial infarction (STEMI) patients. We sought to evaluate predictors of Infarct size (IS) and presence of microvascular obstruction (MO) using delayed hyper-enhancement magnetic resonance imaging (CMR).Methods and resultsWe analyzed 128 consecutive STEMI patients reperfused by primary PCI within 12 hours after symptom onset. IS and MO were assessed by delayed hyper-enhancement MRI as percentage of LV mass, 4±2 days after acute MI. Reperfusion times, TIMI-flow grades pre and post PCI, 90 min ST-segment resolution, cardiovascular risk factors, Killip-class, and infarct location were assessed. In patients with TIMI flow 0-1 before PCI, IS was significantly higher compared to patients with TIMI-flow 2-3 (22±12% versus 16±15%; p<0.01). Similarly, the extent of MO occurrence was affected by the pre PCI TIMI flow. A trend toward higher final IS and MO was noted in post PCI TIMI flow. Patients with TIMI flow 0 to <3 IS was 28±11% versus 20±12% in TIMI-flow =3 (p=0.067). The ST-segment resolution correlated inversely with final IS and presence of MO (IS r=-0.34, p<0.01; MO r=-0.31, p<0.01). IS was significantly higher in anterior AMI versus inferior AMI (24±16% versus 17±12%; p<0.01 as well as MO (9.8±7.8%vs. MO 4.8±3.7%; p=0.01). In a multivariable model the strongest predictors of IS and MO were pre-PCI TIMI-flow, infarct location, admission Killip class, and 90 minute ST-segment resolution (p<0.05 for all).ConclusionsThe pre-PCI TIMI flow, infarct location, Killip class and ST-segment resolution are the strongest predictors of IS and extent of MO as assed by delayed Hyper-enhancement MRI. CMR allow for strong evaluation in STEMI patients, giving important information regarding prognostic

Analyse des quatorze actions nationales pour le déterminant de santé activités physiques et sportives en France de 2001 à 2006

International audienc