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Methane cold seep systems typically exhibit extensive buildups of authigenic carbonate minerals, resulting from local increases in alkalinity driven by methane oxidation. Here, we demonstrate that modern seep authigenic carbonates exhibit anomalously low clumped isotope values (Δ47), as much as ∼0.2‰ lower than expected values. In modern seeps, this range of disequilibrium translates into apparent temperatures that are always warmer than ambient temperatures, by up to 50 °C. We examine various mechanisms that may induce disequilibrium behaviour in modern seep carbonates, and suggest that the observed values result from several factors including kinetic isotopic effects during methane oxidation, mixing of inorganic carbon pools, pH effects and rapid precipitation. Ancient seep carbonates studied here also exhibit potential disequilibrium signals. Ultimately, these findings indicate the predominance of disequilibrium clumped isotope behaviour in modern cold seep carbonates that must be considered when characterizing environmental conditions in both modern and ancient cold seep settings.

Doxorubicin (Dox), a mainstay of adjuvant breast cancer treatment, is associated with cardiac toxicity in the form of left ventricular dysfunction (LVD), LV diastolic dysfunction, or LV systolic dysfunction. Study objectives were to evaluate the prevalence of LVD in long-term breast cancer survivors treated with Dox and determine if brain-type natriuretic peptide (BNP) may help identify patients at risk for LVD. Patients who participated in prospective clinical trials of adjuvant Dox-based chemotherapy for breast cancer with a baseline left ventricular (LV) ejection fraction evaluation from 1999 to 2006 were retrospectively identified from the St Vincent's University Hospital database. Patients were invited to undergo transthoracic echocardiography, BNP analysis, and cardiovascular (CV) risk factor assessment. LVDD was defined as left atrial volume index >34 mL/m(2) and/or lateral wall E prime <10 m/s, and LVSD as LVEF <50 %. Of 212 patients identified, 154 participated, 19 patients had died (no cardiac deaths), and 39 declined. Mean age was 60.7 [55:67] years. A majority of the patients (128, 83 %) had low CV risk (0/1 risk factors), 21 (13.6 %) had 2 RFs, and 5 (3.2 %) ≥3 RFs. BMI was 27.2 ± 4.9 kg/m(2). Median Dox dose was 240 mg/m(2) [225-298]; 92 patients (59.7 %) received ≤240 mg/m(2) and 62 (40.3 %) > 240 mg/m(2). Baseline LVEF was 68.2 ± 8 %. At follow-up of 10.8 ± 2.2 years, LVEF was 64.4 ± 6 %. Three (1.9 %) subjects had LVEF <50 % and one (0.7 %) had LVDD. Dox >240 mg/m2 was associated with any LVEF drop. BNP levels at follow-up were 20.3 pg/ml [9.9-36.5] and 21.1 pg/ml [9.8-37.7] in those without LVD and 61.5 pg/ml [50-68.4] in those with LVD (p = 0.04). Long-term prospective data describing the impact of Dox on cardiotoxicity are sparse. At over 10 years of follow-up, decreases in LVEF are common, and dose related, but LVD as defined is infrequent (2.6 %). Monitoring with BNP for subclinical LVD needs further evaluation.