Separation and measurement of Pa, Th, and U isotopes in Marine sediments by microwave-assisted digestion and multiple collector inductively coupled plasma mass spectrometry

This manuscript describes a new protocol for determination of Pa/Th/U in marine sediments. It is based on microwave-assisted digestion and represents an important reduction of working time over conventional hot-plate digestion methods, and the use of HClO(4) is avoided. Although Th and U are completely dissolved with a first microwave step, around 40% of (231)Pa remains undissolved, and a short hot-plate step with reverse aqua regia is required to achieve total digestion and spike equilibration. Next, the method involves a separation of these elements and a further purification of the Pa fraction using Dowex AG1-X8 resin. Separation with Bio-Rad and Sigma-Aldrich resins was compared; although both perform similarly for Th and U, Pa yields are higher with Bio-Rad. Finally, samples are measured using a Nu instruments multiple collector inductively coupled plasma mass spectrometer (MC-ICPMS). Overall chemical yields range around 50% for Pa, 60% for Th, and 70% for U

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Radionuclides as tools to study the role of the Arctic Sea Ice in the interception, transport and redistribution of particulate matter and chemical species

The Arctic Ocean is characterized by being covered by sea ice with a large degree of seasonal variability between summer and winter. Along the whole life cycle of sea ice, diverse physical and chemical processes determine the concentration of the sea-ice sediments (SIS) and the chemical species entrapped in it and their final fate. Initially, sea ice incorporates particles (SIS) and associated chemical species (metals, nutrients, contaminants, etc.) during its formation mainly in the continental shelves, while dissolved solutes are excluded. As sea ice drifts offshore to the central Arctic Basin, it intercepts chemical species from the atmosphere and, the sediments in the ice may also incorporate some chemical solute compounds from the surface waters by scavenging (although this is likely small). Eventually, transported components, chemical species and SIS, are released to the underlying water column during melting. Thus, sea ice becomes an important transpo rt and distribution agent. However, the efficiency of interception of atmospheric fluxes by sea ice, the origin of the entrapped SIS and transit times of sea ice in the Arctic, as well as the importance of the transport of chemical species and particulate matter (SIS) and its release in the ablation area are all poorly understood. In an attempt to address these questions, a suite of natural (7Be and 210Po-210Pb) and artificial (137Cs, 239,240Pu) radionuclides were analysed in samples from precipitation, sea ice, surface water, water beneath ice and sea-ice sediments collected during the ARK XXII/2 expedition in 2007. The distributions of 7Be and 210Pb showed enrichment in sea ice (129 ± 90 and 5.1 ± 2.9 Bq·m-3, respectively) with respect to surface water (7.1 ± 1.3 and 1.1 ± 0.36 Bq·m-3, respectively). Given that only 4% of the total amount of 210Pb in sea ice comes from seawater and that any 7Be (T1/2 = 53 days) trapped in sea ice during its formation has decayed during drift, the direct atmospheric flux appears as the most important source of both radionuclides in sea ice. From mass balance calculations we estimate that sea ice intercepts about 30% of the 7Be atmospheric flux. This figure may be extrapolated to other chemical species with atmospheric sources, such as metals, nutrients, and contaminants. Given that 7Be and 210Pb are intercepted and accumulated during sea ice transit and also scavenged by SIS, we can use both radionuclides to assess sea ice transit time. Using the 210Pb inventory in ice floes respect to the 210Pb atmospheric flux intercepted by sea ice and the 7Be/210Pbex activity ratio in SIS, we estimated transit times from less than 0.5 to 3 years along the Eurasian Basin. Results are consistent with information reported by satellite maps and back-trajectories analysis of the sampled sea ice floes. Indeed, the SIS presence indicates that the ice floes come from continental shelves, and their origin can be constrained using artificial radionuclides (137Cs and the 239,240Pu) in SIS. Data shows that most of the SIS in the Eurasian Basin originated from the Siberian shelves, in agreement with back-trajectory analyses and main drift patterns. The relevance of sea ice as a significant transport and source of radionuclides in melting areas, such as the Fram Strait, is reflected in the annual fluxes of dissolved 7Be and 210Pb carried by sea ice (67 ± 55 and 13 ± 7 Bq·m-2·y-1, respectively), which are comparable to atmospheric inputs in this region (113-131 and 10-18.3 Bq·m-2·y-1, for 7Be and 210Pb). In addition, the annual mass flux of SIS to the Fram Strait, assessed using a 7Be mass balance and the mean annual ice area efflux through the Fram Strait, is on average 240 (4.5 - 1700) ·106 tons. As a reference, the discharge of sediment load from Arctic rivers is of about 115·106 tons per year

Comparison of international normalized ratio audit parameters in patients enrolled in GARFIELD-AF and treated with vitamin K antagonists

Vitamin K antagonist (VKA) therapy for stroke prevention in atrial fibrillation (AF) requires monitoring of the international normalized ratio (INR). We evaluated the agreement between two INR audit parameters, frequency in range (FIR) and proportion of time in the therapeutic range (TTR), using data from a global population of patients with newly diagnosed non-valvular AF, the Global Anticoagulant Registry in the FIELD\u2013Atrial Fibrillation (GARFIELD-AF). Among 17\ua0168 patients with 1-year follow-up data available at the time of the analysis, 8445 received VKA therapy (\ub1antiplatelet therapy) at enrolment, and of these patients, 5066 with 653 INR readings and for whom both FIR and TTR could be calculated were included in the analysis. In total, 70\ua0905 INRs were analysed. At the patient level, TTR showed higher values than FIR (mean, 56\ub70% vs 49\ub78%; median, 59\ub77% vs 50\ub70%). Although patient-level FIR and TTR values were highly correlated (Pearson correlation coefficient [95% confidence interval; CI], 0\ub7860 [0\ub7852\u20130\ub7867]), estimates from individuals showed widespread disagreement and variability (Lin's concordance coefficient [95% CI], 0\ub7829 [0\ub7821\u20130\ub7837]). The difference between FIR and TTR explained 17\ub74% of the total variability of measurements. These results suggest that FIR and TTR are not equivalent and cannot be used interchangeably