Pioneer Venus 12.5 km Anomaly Workshop Report, volume 1

A workshop was convened at Ames Research Center on September 28 and 29, 1993, to address the unexplained electrical anomalies experienced in December 1978 by the four Pioneer Venus probes below a Venus altitude of 12.5 km. These anomalies caused the loss of valuable data in the deep atmosphere, and, if their cause were to remain unexplained, could reoccur on future Venus missions. The workshop participants reviewed the evidence and studied all identified mechanisms that could consistently account for all observed anomalies. Both hardware problems and atmospheric interactions were considered. Based on a workshop recommendation, subsequent testing identified the cause as being an insulation failure of the external harness. All anomalous events are now explained

Incidence and predictors of left ventricular thrombus formation following acute ST-segment elevation myocardial infarction : a serial cardiac MRI study

Aims: Left ventricular (LV) thrombus is a complication of acute ST-segment elevation myocardial infarction (STEMI). We determined the incidence and predictors of LV thrombus formation using serial cardiac magnetic resonance (CMR) and two-dimensional echocardiography studies. Methods and results: Two hundred and ten patients underwent CMR (median 4 days [IQR 3-7]) and transthoracic echocardiography (median 4 days [IQR 3-7]) early after STEMI presentation with serial follow-up CMR (median 55 days [IQR 46-64]) and echocardiography studies (median 54 days [IQR 45-64]) performed subsequently. The incidence of LV thrombus was 12.3% (26/210) by CMR and 6.2% (13/210) by two-dimensional echocardiography. Echocardiography had 50% sensitivity and 100% specificity for LV thrombus detection compared to CMR. LV thrombus was found in 23.6% of patients with anterior STEMI (22/93). Ischaemic stroke occurred in 1.4% of patients (3/210). Patients with LV thrombus had lower baseline LV ejection fraction (LVEF) (34.9% vs 47.4%, p < 0.001). Microvascular obstruction was more common in patients with LV thrombus (77% vs 39%, p < 0.001). Patients with LV thrombus had increased LV dimensions with larger LV end-diastolic (19 ml [IQR 9-44] vs 6 ml [IQR -4-18], p < 0.001) and end-systolic volumes (10 ml [IQR 0–22] vs -4 ml [IQR -12-4], p < 0.001). Conclusion: CMR increases the detection of LV thrombi which standard echocardiography may underestimate. Serial studies post-STEMI may improve detection of LV thrombus, which is more prevalent in patients with anterior infarction, moderate LV dysfunction and adverse LV remodelling. This subgroup of patients may represent a high-risk group for targeted serial screening with CMR

Reperfusion after Fibrinolytic Therapy (RAFT) : an open-label, multi-centre, randomised controlled trial of bivalirudin versus heparin in rescue percutaneous coronary intervention

Background The safety and efficacy profile of bivalirudin has not been examined in a randomised controlled trial of patients undergoing rescue PCI. Objectives We conducted an open-label, multi-centre, randomised controlled trial to compare bivalirudin with heparin ± glycoprotein IIb/IIIa inhibitors (GPIs) in patients undergoing rescue PCI. Methods Between 2010–2015, we randomly assigned 83 patients undergoing rescue PCI to bivalirudin (n = 42) or heparin ± GPIs (n = 41). The primary safety endpoint was any ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) bleeding at 90 days. The primary efficacy endpoint was infarct size measured by peak troponin levels as a multiple of the local upper reference limit (Tn/URL). Secondary endpoints included periprocedural change in haemoglobin adjusted for red cells transfused, TIMI (Thrombolysis in Myocardial Infarction) bleeding, ST-segment recovery and infarct size determined by the Selvester QRS score. Results The trial was terminated due to slow recruitment and futility after an interim analysis of 83 patients. The primary safety endpoint occurred in 6 (14%) patients in the bivalirudin group (4.8% GPIs) and 3 (7.3%) in the heparin ± GPIs group (54% GPIs) (risk ratio, 1.95, 95% confidence interval [CI], 0.52–7.3, P = 0.48). Infarct size was similar between the two groups (mean Tn/URL, 730 [±675] for bivalirudin, versus 984 [±1585] for heparin ± GPIs, difference, 254, 95% CI, -283-794, P = 0.86). There was a smaller decrease in the periprocedural haemoglobin level with bivalirudin than heparin ± GPIs (-7.5% [±15] versus -14% [±17], difference, -6.5%, 95% CI, -0.83–14, P = 0.0067). The rate of complete (≥70%) ST-segment recovery post-PCI was higher in patients randomised to heparin ± GPIs compared with bivalirudin. Conclusions Whether bivalirudin compared with heparin ± GPI reduces bleeding in rescue PCI could not be determined. Slow recruitment and futility in the context of lower-than-expected bleeding event rates led to the termination of this trial (ANZCTR.org.au, ACTRN12610000152022)

The underutilisation of dual antiplatelet therapy in acute coronary syndrome

Background Despite guideline recommendation of dual antiplatelet therapy (DAPT) in treating ACS, DAPT is underutilized. Our objective was to determine independent predictors of DAPT non-prescription in ACS and describe pattern of DAPT prescription over time. Methods Patients presenting to 41 Australian hospitals with an ACS diagnosis between 2009 and 2016 were stratified according to discharge prescription with DAPT and single antiplatelet therapy (SAPT) or no antiplatelet therapy. Multiple stepwise logistic regression, accounting for within hospital clustering, was used to determine the independent predictors of DAPT non-prescription, defined as discharge with SAPT alone or no antiplatelet agent. Results 8939 patients survived to discharge with an ACS diagnosis. Of these, 6294 (70.4%) patients were discharged on DAPT, 2154 (24.1%) on SAPT and 491 (5.5%) on no antiplatelet agent. Independent predictors of DAPT non-prescription in the overall cohort were: in-hospital CABG (OR 0.09, 95%CI 0.05–0.14), discharge with warfarin (0.10 (0.07–0.14)), in hospital major bleeding (0.48 (0.34–0.67), diagnosis of unstable angina (0.35, (0.27–0.45)), non-ST-elevation myocardial infarction (0.67 (0.57–0.78)) [both vs. ST-segment elevation myocardial infarction], in hospital atrial arrhythmia (0.72 (0.60–0.86)), history of hypertension (0.83 (0.73–0.94)) and GRACE high risk (0.83 (0.71–0.98)). There was an increase in prescription of DAPT and a shift towards ticagrelor over clopidogrel for ACS from 2013 to 2016 (p\ua

Management and 1-year outcomes of patients with newly diagnosed atrial fibrillation and chronic kidney disease: Results from the prospective garfield-af registry

Background-—Using data from the GARFIELD-AF (Global Anticoagulant Registry in the FIELD–Atrial Fibrillation), we evaluated the impact of chronic kidney disease (CKD) stage on clinical outcomes in patients with newly diagnosed atrial fibrillation (AF). Methods and Results-—GARFIELD-AF is a prospective registry of patients from 35 countries, including patients from Asia (China, India, Japan, Singapore, South Korea, and Thailand). Consecutive patients enrolled (2013–2016) were classified with no, mild, or moderate-to-severe CKD, based on the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative guidelines. Data on CKD status and outcomes were available for 33 024 of 34 854 patients (including 9491 patients from Asia); 10.9% (n=3613) had moderate-to-severe CKD, 16.9% (n=5595) mild CKD, and 72.1% (n=23 816) no CKD. The use of oral anticoagulants was influenced by stroke risk (ie, post hoc assessment of CHA2DS2-VASc score), but not by CKD stage. The quality of anticoagulant control with vitamin K antagonists did not differ with CKD stage. After adjusting for baseline characteristics and antithrombotic use, both mild and moderate-to-severe CKD were independent risk factors for all-cause mortality. Moderate-to-severe CKD was independently associated with a higher risk of stroke/systemic embolism, major bleeding, new-onset acute coronary syndrome, and new or worsening heart failure. The impact of moderate-to-severe CKD on mortality was significantly greater in patients from Asia than the rest of the world (P=0.001). Conclusions-—In GARFIELD-AF, moderate-to-severe CKD was independently associated with stroke/systemic embolism, major bleeding, and mortality. The effect of moderate-to-severe CKD on mortality was even greater in patients from Asia than the rest of the world

Somatic mutations affect key pathways in lung adenocarcinoma

Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well- classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers - including NF1, APC, RB1 and ATM - and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.National Human Genome Research InstituteWe thank A. Lash, M.F. Zakowski, M.G. Kris and V. Rusch for intellectual contributions, and many members of the Baylor Human Genome Sequencing Center, the Broad Institute of Harvard and MIT, and the Genome Center at Washington University for support. This work was funded by grants from the National Human Genome Research Institute to E.S.L., R.A.G. and R.K.W.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62885/1/nature07423.pd

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Potential for octylphenol to biodegrade in some English rivers

To study octylphenol biodegradation, samples of river water and sediments were taken from the Aire and Calderr vers in the United Kingdom, running through urban/industrial areas, as well as the Thames River running through a more rural area. Using laboratory microcosms, half-lives of 7 to 50 d were obtained for the water samples, with most curves fitting a zero-order reaction. The Calder River was sampled at four separate points along a 45-km length, encompassing rural to increasingly urban/industrial reaches. Little degradation was observed in the sample from the upland/rural reach, while half-lives of 8 to 13 d were seen in the more urban/industrial reaches. Mineralization of the phenyl ring, detected by evolution of 14CO2 from ring-labeled octylphenol, was only observed in water from the Calder River sample. Degradation rate was similar for a range of concentrations from 0.3 to 100 μ,g/L when tested with river water from the Thames River. No degradation was observed over 83 d when bed sediments were spiked with octylphenol and incubated under anaerobic conditions

Development and preliminary testing of the Cardiac Rehabilitation Enrolment Obstacles (CREO) scale: implications for service development

Background: In spite of the benefit in participating in cardiac rehabilitation (CR) programs, low participation rates are well documented. Participation rates are potentially lower in people who have undergone percutaneous coronary interventions (PCI). Assessment of the barriers to CR participation in PCI patients could provide vital information for the development of alternate strategies for coronary risk factor modification. Aim: The aim of this study was to develop and evaluate the psychometric properties of a scale to assess obstacles to cardiac rehabilitation enrolment in patients following PCI. Methods: Item generation for the 15 items of this scale was based on a comprehensive review of the literature and data collected from telephone interviews of CR coordinators related to cardiac rehabilitation enrolment obstacles (CREO). Content validity of the scale was undertaken using a reference group comprising of clinicians and patients. Construct validity was undertaken using a factor analysis. Data for the CREO scale was collected from December 2004 to March 2005 from 114 PCI patients recruited from a cardiology database in a Sydney metropolitan hospital. Results: Factor analysis revealed a two-factor structure: patient-related obstacles and health service-related obstacles, which accounted for 58% of cumulative explained variance. The scale showed good internal consistency (Cronbach\u27s alpha = 0.89) and satisfactory divergent validity. Conclusion: This scale can be used as a useful tool for the early identification of patients who would not normally enrol into CR and offer them alternate strategies for health-related lifestyle modification

Persistence of coronary risk factor status in participants 12-18 months following percutaneous coronary intervention

Background: Percutaneous coronary intervention (PCI) is a widely performed revascularization technique for coronary heart disease; however, there is limited research investigating the risk factor status of patients 1 year after the procedure. Objective: This cross-sectional study was conducted to investigate the self-reported risk factor status by patients who had undergone a PCI at a major teaching hospital in Sydney, Australia.Subjects: Two hundred seventy participants who underwent PCI between April 2003 and March 2004 and who met the inclusion criteria were followed up 1 year after the PCI. Methods: After obtaining informed consent, a follow-up self-administered questionnaire was mailed to participants. Information was collected relating to the following coronary risk factors: smoking, and physical activity status, blood pressure and cholesterol levels, body mass index, depression, anxiety, and stress levels. Results: Two hundred two participants (75%) returned a completed questionnaire. Approximately one third of participants had at least two modifiable risk factors. The most common cardiovascular risk factors identified were physical inactivity, increased body mass index, high blood pressure, and high cholesterol. Approximately half the women (46%) and a quarter of the men had at least two modifiable risk factors. Only a minority (11%) of the participants continued to smoke at 1-year follow up. Participating in physical activity for a total time of 150 minutes or more per week was reported by only 42% of the participants. Depression and anxiety were present in 25% and stress in 17% of the participants. A third of the participants (n = 64) erroneously believed that they had no heart problems. Conclusions: The findings reveal inadequate management of modifiable risk factors among post-PCI participants 12 to 18 months after revascularization, which highlights a need for tailored secondary prevention interventions to address factors contributing to cardiovascular risk. The evidence obtained from this study will inform the development of an intervention to address cardiovascular risk factor modification