General unknown screening in hair by liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF-MS)

The retrospective investigation of the exposure to toxic substances by general unknown screening of hair is still a difficult task because of the large number of possible poisons, the low sample amount and the difficult sample matrix. In this study the use of liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) was tested as a promising technique for this purpose. In the optimized procedure, 20mg hair were decontaminated with water and acetone and two times extracted by 18h incubation with 0.5ml of a mixture of methanol/acetonitrile/H(2)O/ammonium formate at 37°C. A mixture of deuterated standards from different drug groups was added for quantification and method control. The united extracts were evaporated to a residue of 0.5ml and 5μl were injected without clean-up for LC-QTOF-MS measurement (instrument Agilent 6530) with positive electrospray ionization and in data dependent acquisition mode. For peak identification the accurate mass data base and spectral library of the authors was used which contains accurate mass CID spectra of more than 2500 and theoretically calculated accurate mass data of more than 7500 toxicologically relevant substances. Validation at the example of 24 illegal drugs, their metabolites and benzodiazepines resulted in limits of detection of 0.003-0.015ng/mg, and limits of quantification of 0.006-0.021ng/mg with good accuracy and intra- and interday reproducibility. The matrix effect by ion suppression/enhancement was 72-107% for basic drugs and 42-75% for benzodiazepines. Yields of the hair extraction above 90% were determined for 59 drugs or metabolites. The method was applied to hair samples from 30 drug fatalities and from 60 death cases with known therapeutic drug intake at life time. Altogether 212 substances were identified with a frequency per drug of 1-40 (mean 4.2) and per case of 2-33 (mean 10.2), between them 35 illegal drug related substances and 154 therapeutic drugs. Comparison with the data known from case histories and from the analysis of blood, urine and gastric content showed only a low agreement, with many unexpected drugs detected and many reported drugs not detected in hair. Basic drugs and metabolites such as opioides, cocaine, amphetamines, several groups of antidepressants, neuroleptics, beta-blockers or the metamizole metabolite noramidopyrine were found with high frequency whereas acidic and several neutral drugs such as cannabinoids, salicylic acid, furosemide, barbiturates, phenprocoumone or cardiac glycosides could not be detected with sufficient sensitivity, mainly because of the low ion yield of positive ESI for these compounds. The advantage of a comprehensive acquisition of all substances is paid by a lower sensitivity in comparison to targeted screening LC-MS/MS procedures. In conclusion, the procedure of sample preparation and LC-QTOF-MS analysis proved to be a robust and sensitive routine method in which the qualitative screening for a wide variety of toxic substances in hair is combined with the quantitative determination of selected illegal drugs.     

A New Approach to the Investigation of Sexual Offenses—Cytoskeleton Analysis Reveals the Origin of Cells Found on Forensic Swabs*

Abstract: There are forensic inquiries in which an identification of epithelial cell types would provide important probative evidence. In cancer diagnosis, this information is yielded by histological examination of cytokeratin (Ck). Therefore, we tested 19 antibodies against different Cks (Ck1, Ck2e, Ck4, Ck5‐6, Ck7, Ck8, Ck9, CK10, Ck13, Ck14, Ck15, Ck16, Ck17, Ck18, Ck19, Ck20, Ck903, PanCkAE1_3, and CAM5‐2) on histological sections of epidermis, buccal mucosa, vaginal mucosa, penis, urogenital tract, and rectum and could identify two antigens unique to buccal‐cell and vaginal‐cell (Ck4) and skin epithelial‐cell (Ck10) cytokeratin. Subsequently, we developed an immunocytological technique for distinguishing swabbed skin and mucosal cells up to at least 1 year after sampling. By the detection of the Ck4 and Ck10 mRNAs in biopsy and laser capture microdissection collected samples via quantitative real‐time polymerase chain reaction, we were able to confirm our immunological findings. Hence, this study offers techniques to discriminate between skin and mucosal cells (buccal and vaginal) in forensic casework.     

Environmental aspects in free trade agreements in the Asia-Pacific region

The trade and environment interface has become a topic of growing importance. Until the early 1990s, the General Agreement on Tariffs and Trade (GATT) and its successor, the World Trade Organisation (WTO), were the major forums to address the relationship between trade and the environment. Significant progress in this area has not yet been made. Since the 1990s, environmental issues have been addressed by the North American Free Trade Agreement (NAFTA) and in recent times by trans-regional and bilateral free trade agreements (FTAs) such as the Trans-Pacific Strategic Economic Partnership Agreement (SEP), the U.S.–Singapore FTA (USSFTA), the Canada–Chile FTA or the New Zealand–Thailand Closer Economic Partnership Agreement (CEP). Not only questions on the effectiveness of FTAs in global and regional environmental governance arise but also on the various actors involved in these negotiations. The question here is whether the integration of environmental issues in FTAs is a top-down approach, leaving the negotiations and implementation of environment cooperation frameworks in the hands of governments, or whether environmental arrangements are the result of a multi-stakeholder dialogue, consequently committing governments, the private sector and civil society to the objective of making trade and environmental policies mutually supportive. This article seeks to address these questions by analysing environmental issues and stakeholder participation in the Asia-Pacific Economic Cooperation (APEC), the Trans-Pacific SEP and the New Zealand–Thailand CEP.

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A sudden death with lung embolism after inadvertent infusion of zinc oxide shake lotion

A 74-year old woman in postoperative treatment after a colonic surgery died immediately after perfusion of about 1.5 mL of a white emulsion which was believed to contain 1% propofol via cardiac catheter into the right atrium. It was strongly suspected that a syringe with a zinc oxide shake lotion (consisting of 20% ZnO, 20% talc, 25% glycerol and 35% water) which was intended for external treatment had been mistaken for the propofol syringe. During autopsy, an anatomic cause of death could not be found. In order to exclude an intoxication and to determine the significance of the perfusion fluid in this context, toxicological and histological investigations were performed. Propofol and other drugs applied to the patient were found in therapeutic or sub-therapeutic range. However, in comparison to a control case, the zinc concentrations determined by AAS were about 200 times higher in lung tissue, 10 times higher in heart blood and 3–4 times higher in kidney and liver tissue. No increase was seen in venous blood. Histology showed a strong embolism of the lung tissue with birefingent sharp-edged crystals, which were identified as the talcum, and an amorphous component (ZnO). The same embolism was seen to a medium extent also in the brain sections and to a low extent in heart, liver, pancreas and kidney. Pulmonary embolism by talcum and zinc oxide was established as the cause of death which occurred by syringe swap due to insufficient security precautions in the drug administration. The results are discussed in context of pulmonary microembolism cases frequently described for drug addicts after injection of crashed talcum containing tablets.     

Die argumentative Logik der Tabakmandate des Alten Bern: Eine historische Policy‐Analyse

Zusammenfassung: Die Analyse dynamischer sozialer Phänomene stellt sowohl für die Sozial‐ als auch die Geisteswissenschaften eine Herausforderung dar. Ziel dieses Artikels ist es, einen auf Dunn (2004) aufbauenden Analyseraster auf seine Durchführbarkeit anhand einer Analyse von Policy‐Argumenten in historischen Dokumenten zu testen. Ein Längsschnittvergleich von Struktur und Form der Policy‐Argumente in den Tabakmandaten der Stadt Bern von 1659 bis 1723 zeigt einen Wandel der Tabakpolitik des Alten Berns in der Ortung der gesellschaftlichen Probleme, ihrer Ursachen, den damit festgelegten Massnahmen und derer Legitimation auf. Insgesamt impliziert dieses Resultat, dass unsere Methode für die Analyse historischer Policy‐Argumente geeignet ist.     

The jury is still in: Florida's Birth-Related Neurological Injury Compensation Plan after a decade

Florida's Birth-Related Neurological Injury Compensation Plan (NICA) is the most significant experiment with compensation for medical injury yet undertaken in the United States. As NICA enters its second decade of operation, maintaining the scheme's jurisdictional integrity has emerged as a key challenge for policy makers in Florida. We explore the relationship that has emerged between NICA and the tort system as competing avenues for families to obtain compensation for severe birth-related neurological injury. By linking NICA claims data with data on malpractice claims filed in Florida, we found a lively persistence of "bad baby" litigation despite NICA's implementation. Many families pursued claims in both fora. An explanation for these results can be traced to key features of the plan's design--primarily, the way in which "exclusive" jurisdiction over injuries is determined and the restrictive nature of the compensation criteria used. Our findings may help efforts to consolidate NICA's role in injury compensation and inform future design of alternative compensation systems.     

Kompensationsmöglichkeiten föderaler Vollzugsdefizite. Das Beispiel der kantonalen Alkoholpräventionspolitiken

The implementation of public policies in Switzerland is highly federal and decentralized with the main competencies at the sub‐national level of the member states, i.e. the cantons. Comparing alcohol prevention policies in the Swiss cantons, the present article supports the thesis of considerable differences in the cantonal provision of respective outputs. At the same time we can find cooperative implementation strategies compensating the resulting performance deficits. However, this so‐called “secondary harmonization” only is applied by about half of the cantons. We identify three reasons for that fact: First, only those cantons engage in horizontal cooperation that, on the one hand, have an actual interest in improving their policy performance, and, on the other hand, can afford it resource‐wise. Second, today's paradigm of the “lean state” leads to competitive rather than cooperative implementation strategies. Third, the federal administration neither encourages horizontal cooperation, nor do we find a vertical cooperation between the higher and the lower federal level on an equal basis.     

Die Evaluation öffentlicher Politiken mit föderalistischen Vollzugsarrangements. Eine konzeptionelle Erweiterung des Stufenmodells und eine praktische Anwendung

Der vorliegende Artikel leistet einen Beitrag zur Konzipierung von Wirkungsmodellen für die Evaluation von öffentlichen Politiken mit föderalistischen Vollzugsarrangements. Das Phasenmodell des Policy‐Zyklus erfasst die Prinzipal‐Agent‐Probleme des Vollzugsföderalismus nur unzureichend. Es ist aus diesem Grund sinnvoll, in der Genesephase eine Zusatzschlaufe vorzusehen, die dem Umstand Rechnung trägt, dass in der Schweiz die Kantone beim Vollzug von Bundesgesetzen nicht nur Umsetzungs‐, sondern auch Programmierungskompetenzen haben. Diese Zusatzschlaufe impliziert allerdings beim häufig verwendeten Stufenmodell von Knoepfel und Bussmann (1997) für die Evaluierung öffentlicher Politik das Problem, dass es zu einer Vermischung der Evaluationsgegenstände auf Bundes‐ und Kantonsebene kommt. Diesem Umstand begegnen wir mit der Erweiterung des Stufenmodells, indem wir die beiden föderalen Ebenen getrennt betrachten und die Evaluationsgegenstände nicht generell, sondern entsprechend der Staatsebene definieren. Das Modell wird mit einer Anwendung aus der Evaluation des Krankenversicherungsgesetzes illustriert.