BACKGROUND Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications. METHODS This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants. FINDINGS Between March 12, 2013, and May 10, 2016, we ; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043). INTERPRETATION Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding. FUNDING Bayer AG. Methods This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, i...

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Spectral hole burning has been performed on the Q y -region of the isolated reaction center of photosystem II, the D1-D2-cytochrome b559 complex (PSII RC), between 665 and 688 nm, at liquid He temperatures. The "effective" homogeneous line width Γ′ hom at 682 nm, in the red wing of the Q y -band, follows a T 1.3(0.1 power law between 1.2 and 4.2 K characteristic of glasses and extrapolates to Γ′ 0 ) (2πT 1 ) -1 for T f 0 with T 1 ) (4 ( 1) ns, the fluorescence lifetime of the pigments. At these low temperatures, the red-absorbing "trap" pigments are unable to transfer energy to other pigments. The spectral distribution of the traps has been determined from hole depth vs λ exc experiments. Their linear electron-phonon coupling strength was found to be rather weak, S ) 0.73 ( 0.05. For λ exc < 678 nm, "downhill" energy transfer takes place. Spectral distributions of pigments characterized by decay times of 200 and 12 ps have further been identified in this spectral region. The data have been used to reconstruct the fluorescence excitation and absorption spectra.

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Spectral hole-burning experiments have been performed at liquid He temperature on the Q y -band of isolated reaction center complexes of photosystem II (PS II RC) containing five (RC-5) and six (RC-6) chlorophyll a (Chl a) molecules. The aim was to investigate the nature of the redmost shoulder in the absorption spectrum of RC-5 and to identify distributions of “trap” pigments. The “effective” homogeneous line width was measured at 682 nm as a function of temperature between 1.2 and 4.2 K. It follows a T 1.3±0.1 power law in both complexes and extrapolates to the fluorescence lifetime-limited value, τfl = (4 ± 1) ns, for T → 0. These results indicate that the redmost absorbing pigments act as “traps” for the excitation energy. The spectral distribution of these traps was reconstructed from the hole depth measured as a function of excitation wavelength λexc and compared to that of RC-6 previously obtained by us (Groot, M. L.; et al. J. Phys. Chem. 1996, 100, 11488). The maximum of the RC-5 trap distribution lies at (682.9 ± 0.2) nm. We discovered a second distribution of fluorescing pigments centered at (673.4 ± 0.5) nm in both RC-5 and RC-6. The dependence of on the delay time t d between burning and probing, for the red- and blue-absorbing pigments, is constant for t d ≤ 1 s and increases linearly with log t d for longer delay times. The molecules absorbing at ∼674 nm, which can be chemically removed, are not free Chl a but are bound to a protein with the same mass as that of the RC complex.