After methane, ethane is the most abundant hydrocarbon in the remote atmosphere. It is a precursor to tropospheric ozone and it influences the atmosphere's oxidative capacity through its reaction ...with the hydroxyl radical, ethane's primary atmospheric sink. Here we present the longest continuous record of global atmospheric ethane levels. We show that global ethane emission rates decreased from 14.3 to 11.3 teragrams per year, or by 21 per cent, from 1984 to 2010. We attribute this to decreasing fugitive emissions from ethane's fossil fuel source--most probably decreased venting and flaring of natural gas in oil fields--rather than a decline in its other major sources, biofuel use and biomass burning. Ethane's major emission sources are shared with methane, and recent studies have disagreed on whether reduced fossil fuel or microbial emissions have caused methane's atmospheric growth rate to slow. Our findings suggest that reduced fugitive fossil fuel emissions account for at least 10-21 teragrams per year (30-70 per cent) of the decrease in methane's global emissions, significantly contributing to methane's slowing atmospheric growth rate since the mid-1980s.
FTIR/smog chamber experiments and ab initio quantum calculations were performed to investigate the atmospheric chemistry of (CF3)2CFCN, a proposed replacement compound for the industrially important ...sulfur hexafluoride, SF6. The present study determined k(Cl + (CF3)2CFCN) = (2.33 ± 0.87) × 10–17, k(OH + (CF3)2CFCN) = (1.45 ± 0.25) × 10–15, and k(O3 + (CF3)2CFCN) ≤ 6 × 10–24 cm3 molecule–1 s–1, respectively, in 700 Torr of N2 or air diluent at 296 ± 2 K. The main atmospheric sink for (CF3)2CFCN was determined to be reaction with OH radicals. Quantum chemistry calculations, supported by experimental evidence, shows that the (CF3)2CFCN + OH reaction proceeds via OH addition to −C(N), followed by O2 addition to −C(OH)N·, internal H-shift, and OH regeneration. The sole atmospheric degradation products of (CF3)2CFCN appear to be NO, COF2, and CF3C(O)F. The atmospheric lifetime of (CF3)2CFCN is approximately 22 years. The integrated cross section (650–1500 cm–1) for (CF3)2CFCN is (2.22 ± 0.11) × 10–16 cm2 molecule–1 cm–1 which results in a radiative efficiency of 0.217 W m–2 ppb–1. The 100-year Global Warming Potential (GWP) for (CF3)2CFCN was calculated as 1490, a factor of 15 less than that of SF6.
Objectives This study sought to test the hypothesis that semiautomated calculation of left ventricular global longitudinal strain (GLS) can identify high-risk subjects among patients with myocardial ...infarctions (MIs) with left ventricular ejection fractions (LVEFs) >40%. Background LVEF is a key determinant in decision making after acute MI, yet it is relatively indiscriminant within the normal range. Novel echocardiographic deformation parameters may be of particular clinical relevance in patients with relatively preserved LVEFs. Methods Patients with MIs and LVEFs >40% within 48 h of admission for coronary angiography were prospectively included. All patients underwent echocardiography with semiautomated measurement of GLS. The primary composite endpoint (all-cause mortality and hospitalization for heart failure) was analyzed using Cox regression analyses. The secondary endpoints were cardiac death and heart failure hospitalization. Results A total of 849 patients (mean age 61.9 ± 12.0 years, 73% men) were included, and 57 (6.7%) reached the primary endpoint (median follow-up 30 months). Significant prognostic value was found for GLS (hazard ratio HR: 1.20; 95% confidence interval CI: 1.10 to 1.32; p < 0.001). GLS > −14% was associated with a 3-fold increase in risk for the combined endpoint (HR: 3.21; 95% CI: 1.82 to 5.67; p < 0.001). After adjustment for other variables, GLS remained independently related to the combined endpoint (HR: 1.14; 95% CI: 1.04 to 1.26; p = 0.007). For the secondary endpoints, GLS > −14% was significantly associated with cardiovascular death (HR: 12.7; 95% CI: 3.0 to 54.6; p < 0.001) and heart failure hospitalization (HR: 5.31; 95% CI: 1.50 to 18.82; p < 0.001). Conclusions Assessment of GLS using a semiautomated algorithm provides important prognostic information in patients with LVEFs >40% above and beyond traditional indexes of high-risk MI.
Recent developments have set the stage for immunotherapy as a supplement to conventional cancer treatment. Consequently, a significant effort is required to further improve efficacy and specificity, ...particularly the identification of optimal therapeutic targets for clinical testing. Cancer/testis antigens are immunogenic, highly cancer-specific, and frequently expressed in various types of cancer, which make them promising candidate targets for cancer immunotherapy, including cancer vaccination and adoptive T-cell transfer with chimeric T-cell receptors. Our current understanding of tumor immunology and immune escape suggests that targeting oncogenic antigens may be beneficial, meaning that identification of cancer/testis antigens with oncogenic properties is of high priority. Recent work from our lab and others provide evidence that many cancer/testis antigens, in fact, have oncogenic functions, including support of growth, survival and metastasis. This novel insight into the function of cancer/testis antigens has the potential to deliver more effective cancer vaccines. Moreover, immune targeting of oncogenic cancer/testis antigens in combination with conventional cytotoxic therapies or novel immunotherapies such as checkpoint blockade or adoptive transfer, represents a highly synergistic approach with the potential to improve patient survival.
The smog chamber/Fourier-transform infrared spectroscopy (FTIR) technique was used to measure the rate coefficients k(Cl + CF3CHClOCHF2, isoflurane) = (4.5 ± 0.8) × 10–15, k(Cl + CF3CHFOCHF2, ...desflurane) = (1.0 ± 0.3) × 10–15, k(Cl + (CF3)2CHOCH2F, sevoflurane) = (1.1 ± 0.1) × 10–13, and k(OH + (CF3)2CHOCH2F) = (3.5 ± 0.7) × 10–14 cm3 molecule–1 in 700 Torr of N2/air diluent at 295 ± 2 K. An upper limit of 6 × 10–17 cm3 molecule–1 was established for k(Cl + (CF3)2CHOC(O)F). The laser photolysis/laser-induced fluorescence (LP/LIF) technique was employed to determine hydroxyl radical rate coefficients as a function of temperature (241–298 K): k(OH + CF3CHFOCHF2) = (7.05 ± 1.80) × 10–13 exp−(1551 ± 72)/T cm3 molecule–1; k(296 ± 1 K) = (3.73 ± 0.08) × 10–15 cm3 molecule–1, and k(OH + (CF3)2CHOCH2F) = (9.98 ± 3.24) × 10–13 exp−(969 ± 82)/T cm3 molecule–1; k(298 ± 1 K) = (3.94 ± 0.30) × 10–14 cm3 molecule–1. The rate coefficient of k(OH + CF3CHClOCHF2, 296 ± 1 K) = (1.45 ± 0.16) × 10–14 cm3 molecule–1 was also determined. Chlorine atoms react with CF3CHFOCHF2 via H-abstraction to give CF3CFOCHF2 and CF3CHFOCF2 radicals in yields of approximately 83% and 17%. The major atmospheric fate of the CF3C(O)FOCHF2 alkoxy radical is decomposition via elimination of CF3 to give FC(O)OCHF2 and is unaffected by the method used to generate the CF3C(O)FOCHF2 radicals. CF3CHFOCF2 radicals add O2 and are converted by subsequent reactions into CF3CHFOCF2O alkoxy radicals, which decompose to give COF2 and CF3CHFO radicals. In 700 Torr of air 82% of CF3CHFO radicals undergo C–C scission to yield HC(O)F and CF3 radicals with the remaining 18% reacting with O2 to give CF3C(O)F. Atmospheric oxidation of (CF3)2CHOCH2F gives (CF3)2CHOC(O)F in a molar yield of 93 ± 6% with CF3C(O)CF3 and HCOF as minor products. The IR spectra of (CF3)2CHOC(O)F and FC(O)OCHF2 are reported for the first time. The atmospheric lifetimes of CF3CHClOCHF2, CF3CHFOCHF2, and (CF3)2CHOCH2F (sevoflurane) are estimated at 3.2, 14, and 1.1 years, respectively. The 100 year time horizon global warming potentials of isoflurane, desflurane, and sevoflurane are 510, 2540, and 130, respectively. The atmospheric degradation products of these anesthetics are not of environmental concern.
Past observations that patients suffering from Lutembacher's syndrome (mitral stenosis and atrial septal defect) are less symptomatic than patients with isolated mitral stenosis without increases in ...stroke or reductions in cardiac output inspired the concept of passive unloading the LA by percutaneously creating an artificial interatrial shunt could alleviate symptoms in HF. ...the AFR a bi-directional device is a new device that in small case series has shown promising results and is now being tested in a pilot study including 30 patients with HF and elevated LAP (PRELIEVE trial, NCT03030274). ...absolute pressure reduction as a surrogate marker of efficacy is sub-optimal. ...it is important to include clinical benefit and at best hard clinical endpoint in future trials.
The use of β-adrenergic receptor blocking agents in symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM) rests on clinical experience and observational cohort studies.
This study ...aimed to investigate the effects of metoprolol on left ventricular outflow tract (LVOT) obstruction, symptoms, and exercise capacity in patients with obstructive HCM.
This double-blind, placebo-controlled, randomized crossover trial enrolled 29 patients with obstructive HCM and New York Heart Association (NYHA) functional class II or higher symptoms from May 2018 to September 2020. Patients received metoprolol or placebo for 2 consecutive 2-week periods in random order. The effect parameters were LVOT gradients, NYHA functional class, Canadian Cardiovascular Society (CCS) angina class, Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), and cardiopulmonary exercise testing.
Compared with placebo, the LVOT gradient during metoprolol was lower at rest (25 mm Hg interquartile range (IQR): 15-58 mm Hg vs 72 mm Hg IQR: 28-87 mm Hg; P = 0.007), at peak exercise (28 mm Hg IQR: 18-40 mm Hg vs 62 mm Hg IQR: 31-113 mm Hg; P < 0.001), and postexercise (45 mm Hg IQR: 24-100 mm Hg vs 115 mm Hg IQR: 55-171 mm Hg; P < 0.0001). During metoprolol treatment, 14% of patients were in NYHA functional class III or higher compared with 38% of patients receiving placebo (P < 0.01). Similarly, no patients were in CCS class III or higher during metoprolol treatment compared with 10% during placebo treatment (P < 0.01). These findings were confirmed by higher KCCQ-OSS during metoprolol treatment (76.2 ± 16.2 vs 73.8 ± 19.5; P = 0.039). Measures of exercise capacity, peak oxygen consumption, and N-terminal pro-B-type natriuretic peptide did not differ between the study arms.
Compared with placebo, metoprolol reduced LVOT obstruction at rest and during exercise, provided symptom relief, and improved quality of life in patients with obstructive HCM. Maximum exercise capacity remained unchanged. (The Effect of Metoprolol in Patients with Hypertrophic Obstructive Cardiomyopathy TEMPO; NCT03532802).
Adoptive cell therapy may be based on isolation of tumor-specific T cells, e.g. autologous tumor infiltrating lymphocytes (TIL), in vitro activation and expansion and the reinfusion of these cells ...into patients upon chemotherapy induced lymphodepletion. Together with high-dose interleukin (IL)-2 this treatment has been given to patients with advanced malignant melanoma and impressive response rates but also significant IL-2 associated toxicity have been observed. Here we present data from a feasibility study at a Danish Translational Research Center using TIL adoptive transfer in combination with low-dose subcutaneous IL-2 injections.
This is a pilot trial (ClinicalTrials.gov identifier: NCT00937625) including patients with metastatic melanoma, PS ≤1, age <70, measurable and progressive disease and no involvement of the central nervous system. Six patients were treated with lymphodepleting chemotherapy, TIL infusion, and 14 days of subcutaneous low-dose IL-2 injections, 2 MIU/day.
Low-dose IL-2 considerably decreased the treatment related toxicity with no grade 3-4 IL-2 related adverse events. Objective clinical responses were seen in 2 of 6 treated patients with ongoing complete responses (30+ and 10+ months), 2 patients had stable disease (4 and 5 months) and 2 patients progressed shortly after treatment. Tumor-reactivity of the infused cells and peripheral lymphocytes before and after therapy were analyzed. Absolute number of tumor specific T cells in the infusion product tended to correlate with clinical response and also, an induction of peripheral tumor reactive T cells was observed for 1 patient in complete remission.
Complete and durable responses were induced after treatment with adoptive cell therapy in combination with low-dose IL-2 which significantly decreased toxicity of this therapy.
Aims
The goal of the study was to examine the prognostic impact, haemodynamic and clinical features associated with lung congestion in patients with chronic heart failure (HF).
Methods and results
HF ...patients (n = 186) and HF‐free controls (n = 21) underwent right heart catheterization, echocardiography, pulmonary function testing and chest radiography that was blindly scored for the presence and severity of lung oedema. Lung congestion correlated directly with pulmonary vascular resistance (PVR, P = 0.004) and inversely with pulmonary artery (PA) compliance (P < 0.001) and the diffusion limit for carbon monoxide (DLCO, P = 0.009). Compared with dry lung HF, wet lung HF patients (congestion score > median) had 25% lower PA compliance and 25–35% higher PVR, transpulmonary gradients and PA pressures (40 vs. 32 mmHg, P < 0.001) despite marginally higher PA wedge pressure (PAWP; 22 vs. 19 mmHg, P = 0.002). Wet lung HF patients displayed more right ventricular (RV) dilatation and dysfunction, more restrictive ventilation and greater reduction of DLCO. The strongest correlates of lung congestion were NT‐proBNP, haemoglobin, albumin, and glomerular filtration, all surpassing PAWP. After a median of 333 days (interquartile range 80–875), 59 patients (32%) died. Lung congestion was associated with reduced survival (P < 0.0001), even after adjusting for PAWP, NT‐proBNP, anaemia, CAD and renal dysfunction.
Conclusion
Interstitial lung oedema is associated with pulmonary vascular disease, RV overload and dysfunction and increased mortality in HF. These data reinforce the importance of aggressive decongestion in HF and suggest that novel agents aimed at reducing lung water may help to deter progression of pulmonary vascular disease and biventricular HF.
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