The extreme Sr, Nd, Hf, and Pb isotopic compositions found in Pitcairn Island basalts have been labeled enriched mantle 1 (EM1), characterizing them as one of the isotopic mantle end members. The EM1 origin has been vigorously debated for over 25 years, with interpretations ranging from delaminated subcontinental lithosphere, to recycled lower continental crust, to recycled oceanic crust carrying ancient pelagic sediments, all of which may potentially generate the requisite radiogenic isotopic composition. Here we find that δMg ratios in Pitcairn EM1 basalts are significantly lower than in normal mantle and are the lowest values so far recorded in oceanic basalts. A global survey of Mg isotopic compositions of potentially recycled components shows that marine carbonates constitute the most common and typical reservoir invariably characterized by extremely low δMg values. We therefore infer that the subnormal δMg of the Pitcairn EM1 component originates from subducted marine carbonates. This, combined with previously published evidence showing exceptionally unradiogenic Pb as well as sulfur isotopes affected by mass-independent fractionation, suggests that the Pitcairn EM1 component is most likely derived from late Archean subducted carbonate-bearing sediments. However, the low Ca/Al ratios of Pitcairn lavas are inconsistent with experimental evidence showing high Ca/Al ratios in melts derived from carbonate-bearing mantle sources. We suggest that carbonate-silicate reactions in the late Archean subducted sediments exhausted the carbonates, but the isotopically light magnesium of the carbonate was incorporated in the silicates, which then entered the lower mantle and ultimately became the Pitcairn plume source.

Abstract-The transcranial magnetic stimulation (TMS) technology development becomes a painless, noninvasive, green treatment and detection method in recent years. However, because of the difference in efficiency of the stimulation system, the technology is not widely used. The focality of the magnetic field is one of the key issues that affect the efficiency of magnetic stimulation. If the focusing problem cannot be solved, the development of TMS technology will be restricted. Therefore, research of focusing has become a hot spot in recent years. In this paper, we mainly carry out three meaningful works. First, a hybrid algorithm is proposed based on a simplified particle swarm optimization algorithm (sPSO) and simulated annealing (SA) algorithm. The convergence of those algorithms is tested. The current through the coils is optimized and solved. Second, the influence of discharge circuit parameters on the magnetic field distribution in the head model is analyzed. Finally, five array coils are established, and the related parameters are configured by using the results of above research. The simulation results show that the hybrid algorithm can improve focality performance. The hybrid algorithm is made up of sPSO and SA. The proposed optimization algorithm and the study to the parameters of the discharge circuit are useful to enhance the focality of the TMS technology in the further development.

Purpose Establish a PPK model describing the PK characteristics of the active metabolite (M1) of LEF in JRA; examine the influence of demographic covariates on PK of M1 in JRA; determine appropriate pediatric dose adjustments. Methods: S1037: 24‐wk open‐label trial, subjects 6–17 yrs; LEF dosing based on 10 mg/d per 1.73 m2. Serial blood samples (5) collected on d 3, wks 4, 12, 26. S3503: 16‐wk double‐blind trial, subjects 3‐17 yrs; LEF dosing by body weight (WT): 5 mg qd <20 kg; 10 mg qd 20‐40 kg; 20 mg qd >40 kg. Single blood samples collected at wks 2, 4, 8, 12, 16. Bioanalysis for M1 by HPLC/UV, LOQ 0.1 μg/mL. Data pooled; population analysis by NONMEM; dose adjustments tested by simulation. Results: 73 subjects 3–17 yrs (S1037 n=27; S3503 n=46) provided 674 M1 observations. M1 disposition was well described by a one‐compartment model with first order input. CL/F was weakly correlated with body size (WT or BSA): CL/F=0.020[WT/40]0.43. V/F was strongly correlated with body size: V/F=5.8[WT/40]0.769. Inter‐subject variabilities in CL/F and V/F were 50.4% and 18.6% and similar to adults. In S3503 20 mg qd in subjects >40 kg achieved Css (36.7 μg/mL) comparable to adults (34 μg/mL). Css in pts <20 kg or 20–40 kg were low (12.6 μg/mL; 26.2 μg/mL, resp). Conclusions: To achieve a uniform range of Css within the JRA population and comparable to adults, LEF doses should be adjusted for WT: 10 mg qd 10–19.9 kg; 15 mg qd 20–40 kg (20 mg/10 mg alternate days); 20 mg qd >40 kg. Clinical Pharmacology & Therapeutics (2004) 75, P5–P5; doi:

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