Metal and metalloid multi-elementary ICP-MS validation in whole blood, plasma, urine and hair. Reference values

Four multi-elementary metal and metalloid quantification methods using inductively coupled plasma mass spectrometry (ICP-MS) were developed and validated in human whole blood, plasma, urine and hair by means of a single preparation procedure for each sample. The ICP-MS measurements were performed using a Thermo Elemental X7CCT series and PlasmaLab software without a dynamic reaction cell. With this procedure 27-32 elements can be simultaneously quantified in biological matrices: Li, Be, B, Al, V, Cr, Mn, Co, Ni, Cu, Zn, Ga, Ge, As, Se, Rb, Sr, Mo, Pd, Ag, Cd, Sn, Sb, Te, Ba, W, Pt, Hg, Tl, Pb, Bi, U. Whole blood, plasma and urine samples (0.4 ml each) were diluted with purified water, acid, triton X100 and butanol. Rhodium was used as internal standard. The urine sample results were corrected for enzymatic creatinine determination. Twenty-five milligrams hair samples were acid mineralized after a decontamination procedure and diluted as previously described for biological fluids. To be validated, each element had to show linearity with a correlation coefficient higher than 0.99. The intra-assay and inter-assay inaccuracy, measured as the variation coefficient, were below 5 and 10% respectively. Global performance was assessed by a quality control program. Our laboratory is a registered participant of the Institut National de Santé Publique du Québec (Sainte-Foy, Canada) inter-laboratory comparison program for whole blood, urine, and beard hair of non-occupationally exposed individuals spiked with selected elements. In our study multi-element metal and metalloid analysis was assessed for 27 elements in whole blood, 27 elements in plasma, 30 elements in urine and 32 elements in hair, from 0 to 25, or 250 to 1000 ng/ml, depending on the element. Quantification limits ranged from 0.002 ng/ml (U) to 8.1 ng/ml (Al) for whole blood, from 0.002 ng/ml (U) to 7.7 ng/ml (Al) for plasma, from 0.001 ng/ml (U) to 2.2 ng/ml (Se) for urine, and from 0.2 pg/mg (Tl) to 0.5 ng/mg (B) for hair. Normal values were determined in whole blood (n=100), plasma (n=100), urine (n=100), and hair (n=45) of healthy volunteers, leading to approximately 10,000 analyses. All results are presented and discussed. Clinical toxicology and forensic toxicology applications are also reported. ICP-MS has made significant advances in the field of clinical biology, particularly in toxicological analysis. This is due to the use of extremely effective equipment that permits better clinical and forensic toxicological analysis of metal and metalloid status of each individual patient.     

Mitochondrial DNA error prophylaxis: assessing the causes of errors in the GEP'02-03 proficiency testing trial

A qualitative and quantitative analytical method was developed and validated for the determination of 49 licit and illicit drugs in oral fluid. Small oral fluid samples, volume 1mL, were collected from volunteers using a modified Omni-Sal device and the analytes were extracted from an oral fluid/buffer mixture using a single Bond Elut Certify solid phase extraction cartridge. Liquid chromatography-tandem mass spectrometry (LC-MS-MS) and gas chromatography-repetitive full scan mass spectrometry (GC-MS) were used in parallel to analyze the extracts for the targeted drugs. Extracts were analyzed by GC-MS in their underivatized form and as their pentafluoropropionyl derivatives. Deuterated internal standards were used for quantification of drugs of abuse by LC-MS-MS to minimize matrix effects. Methadone-d(9) and tumoxetine were used as the internal standards for quantification of non-derivatized and derivatized analytes respectively by GC-MS. Linearity was demonstrated over the range 5-200 ng/mL and limits of detection were less than 4 ng/mL for each drug analyzed. The method demonstrated acceptable recoveries for most of the analytes and good intra- and inter-day precision. Acquisition of data by repetitive full scan GC-MS allows the addition of further analytes to the target menu.     

Running against the status quo: Institutions for direct democracy referenda and allocations over time

Stylized institutions for direct democracy referenda are examined in a dynamic full information environment with myopic voters. Competitive-agenda (median-voter) processes are contrasted with monopolistic (controlled-agenda) processes by extending existing static analyses to a class of dynamic institutions not previously characterized, the status quo reversion rule. This highlights the dependence of the progression of real equilibrium allocations over time on institutional structure. By delineating the restrictions implied by each institutional form the model explains some persistent empirical regularities. In particular, a strict ceteris paribus ordering of the magnitudes of budgets by institutional form is derived for a wide portion of the parameter space.     

STR analysis of artificially degraded DNA-results of a collaborative European exercise

Degradation of human DNA extracted from forensic stains is, in most cases, the result of a natural process due to the exposure of the stain samples to the environment. Experiences with degraded DNA from casework samples show that every sample may exhibit different properties in this respect, and that it is difficult to systematically assess the performance of routinely used typing systems for the analysis of degraded DNA samples. Using a batch of artificially degraded DNA with an average fragment size of approx. 200 bp a collaborative exercise was carried out among 38 forensic laboratories from 17 European countries. The results were assessed according to correct allele detection, peak height and balance as well as the occurrence of artefacts. A number of common problems were identified based on these results such as strong peak imbalance in heterozygous genotypes for the larger short tandem repeat (STR) fragments after increased PCR cycle numbers, artefact signals and allelic drop-out. Based on the observations, strategies are discussed to overcome these problems. The strategies include careful balancing of the amount of template DNA and the PCR cycle numbers, the reaction volume and the amount of Taq polymerase. Furthermore, a careful evaluation of the results of the fragment analysis and of automated allele calling is necessary to identify the correct alleles and avoid artefacts.     

„Spielarten des Kapitalismus“ und institutionelle Komplementaritäten in der Makroökonomie — Eine empirische Analyse

Der Beitrag geht der Frage nach, wie national unterschiedliche politökonomische Institutionen die Leistungskraft entwickelter Marktwirtschaften beeinflussen und ob institutionelle Komplementaritäten in der Makroökonomie existieren. Der Ansatz der ?Spielarten des Kapitalismus“ behauptet, dass es diese Komplementaritäten gibt und sich die Länder entsprechend dem in den ökonomischen Sphären vorherrschenden Modus der Koordination in klare Gruppen unterscheiden lassen. In dem Artikel werden die Kernaussagen des Ansatzes einer Reihe von empirischen Tests unterzogen, die auf einer zusammenfassenden Analyse einer Reihe von Fallbeispielen beruht, Die empirischen Ergebnisse bestätigen die Annahmen in überzeugender Weise. Dieliberalen undkoordinierten Marktwirtschaften variieren systematisch entsprechend dem relativen Verhältnis zwischen marktförmiger und strategischer Koordination. Institutionelle Komplementaritäten finden sich in beiden Typen, und sie bringen gesamtwirtschaftliche Leistungszuwächse hervor. Abschließend werden die Muster des institutionellen Wandels in den entwickelten politischen Ökonomien analysiert und einige politische Implikationen der Befunde diskutiert.     

Toward an Empirical Approach to Evidentiary Ruling

This paper responds to criticisms/misconstruals of our measure of the maximum probative value of evidence (D. Davis & W. C. Follette, 2002), and our conclusions regarding the potentially prejudicial role of intuitive profiling evidence, including motive. We argue that R. D. Friedman and R. C. Park's (2003) criticisms and example cases are largely based on inappropriate violation of the presumption of innocence. Further, we address the merits of our absolute difference measure of probative value versus those of the Bayesian likelihood ratio championed by D. H. Kaye and J. J. Koehler (2003). We recommend methods for presentation of measures of evidence utility that convey complexities of interdependence between new and existing evidence. Finally, we propose a probable cause standard for admission of potentially prejudicial evidence, dictating that admissibility of such evidence should be contingent upon other substantial evidence of guilt.     

Polyclonal systemic immunoblast proliferation: an unusual hematologic entity presenting as a medical examiner case

A 43-year-old woman who was receiving oral antibiotics for several days for a superficial foot infection developed a persistent rash, fever, and lymphadenopathy, despite discontinuation of the antibiotic and administration of steroids for a presumed drug reaction. Hours after a subsequent visit to the emergency room for worsening symptoms, she died at home. At autopsy, there was a florid, systemic proliferation of polyclonal plasma cells and immunoblasts infiltrating nearly every organ and tissue of the body, most notably the lymph nodes and spleen. The polyclonal nature of the process was confirmed by immunofixation electrophoresis and immunohistochemistry. Cases of fatal polyclonal systemic immunoblast proliferations are extremely rare, and the trigger for such proliferations is not always known. We review the literature on this unusual entity and discuss the clinical and pathologic findings.