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This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas' original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300-600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75-150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175-300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100-200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250-400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150-300 mg/day, and 6) in the US with ancestries other than from Asia or the original people fr

A series of (Co1-xNix)88Zr7B4Cu1 soft magnetic alloys, where X was varied from 0 to 1, were fabricated by a melt spinning process into thin ribbons of the material. This process was followed by an isothermal anneal to produce a nanocomposite alloy, i.e. nanocrystalline grains in a residual amorphous matrix. The alloy series was designed to investigate crystallization kinetics and limits to the compositional regime where a nanocomposite could be formed. The primary and secondary crystallization temperatures of each alloy were determined using Differential Scanning Calorimetry (DSC) from which the crystallization activation energies were calculated using the Kissinger Method. When X exceeded 0.75, the as-spun ribbons exhibited partial crystallization, resulting in reduced exothermic crystallization peaks. For lower Ni contents, the ribbons were amorphous in the as-spun state. The activation energy for crystallization decreased with increasing Ni content. Transmission Electron Microscopy (TEM) and Atom Probe Tomography (APT) revealed fine nanocrystallite and boron segregation to the grain boundaries with increasing Ni content. The previously suspected use of Cu clustering, which can act as heterogeneous nucleation sites, showed no clear correlation with observed spatial location of the crystallites. Chemical partitioning between species in the as-spun and primary crystallization heat treatments were correlated to the resulting changes in magnetic properties. As Ni content increased, the saturation magnetization and normalized magnetization for these samples decreased accordingly.

Nitin Chopra, Pradeep Doddamreddy, Hermanjeet Grewal, Pratap C KumarJackson Park Hospital, Chicago, IL, USAAbstract: With 200,000 annual deaths in the United States due to pulmonary embolism (PE), efficient and accurate diagnosis is mandatory. Since negative D-dimer values are only useful in ruling out PE, elevated values alone should not result in excessive testing. This study assessed the diagnostic and financial yield of the D-dimer in diagnosing PE. This retrospective review of 220 medical records of patients at a South Chicago Community Hospital explored the extent of the work-up following an elevated D-dimer for a suspected PE. Patients were randomly selected with no exclusion criteria. Five of the 118 (4.2%) patients with elevated D-dimer values were diagnosed with a PE. Tests ordered based on elevated D-dimer values were billed for more than $200,000. The current diagnostic approach has been medically and financially inefficient. Patients should not be worked-up for a PE based primarily on an elevated D-dimer value. Two prominent factors, independent of PE, that result in elevated D-dimer values and were pertinent to the studied population, are age and African-American origin. Implementing a scoring system, like the revised-Geneva scale, will establish a better index of suspicion to improve both the physician's diagnostic approach and the yield of the work-up.Keywords: pulmonary embolism, D-dimer, diagnosis, age, African-Americans, scoring