Off-label drug promotion and the ephemeral line between marketing and education

Fueled by massive settlements and concerns about pharmaceutical company influence over medical practice, the fight over off-label promotion has become a rancorous one with little middle ground. For some, off-label restrictions are both bad law and bad medicine, violating the First Amendment while denying physicians access to crucial information. For others, the battle pits the very soul of the FDA against the excesses of a profit-driven marketplace. Far from ameliorating concerns over manufacturer influence, the New Model proposed by Bennett et al. would exacerbate them. The Model would limit FDA authority to core communications proposing immediate commercial transactions, giving manufacturers unfettered discretion over scientific exchanges and nearly free rein over truthful quasi-commercial communications. Most problematically, the New Model relies on the longstanding assumption that truly educational and scientific activities can be distinguished from simple product promotion – a dichotomy that exists not only in federal law and professional association codes, but also underlies the jurisdiction of the federal agencies overseeing the pharmaceutical sector. Experience invites skepticism that these activities can be cleanly separated, suggesting that the New Model may simply perpetuate abusive behaviors without offering concomitant benefits to physicians or patients.     

Viele Tocquevilles? — Neuere Interpretationen eines Klassikers

Ohne Zusammenfassung     

Exploring Drivers of Innovative Technology Adoption Intention: The Case of Plug‐In Vehicles

How individuals respond to innovative technologies depends on how motivated they are by an array of internal and external factors and the informational and cost barriers they face. To better understand technology adoption decision making we (i) assess changes in intent to purchase plug‐in vehicles in response to reductions in their price and (ii) identify motivators that incline new car buyers toward plug‐ins under status quo and reduced vehicle cost scenarios. We find that individuals already inclined toward alternative vehicles have a higher interest in plug‐ins under a reduced‐cost scenario than individuals who favor conventional vehicles. We also find that individuals who shift their vehicle preference from conventional gasoline to plug‐in vehicles are motivated by material factors and fears relating to the innovative technology, whereas those shifting preferences between less to more innovative technologies are likely to be motivated by a mix of material and nonmaterial factors.     

The role and example of Chilean and Argentinian Mothers in democratisation

This paper explores the development issue of democratisation from a gendered perspective, emphasising the need to look for the building blocks of democracy within civil society sectors where women play a key role. Chilean and Argentinian women prove an important example for sustainable political development through their roles as Mothers, particularly in the 1980s in the movements to protest against political disappearances. The author seeks to demonstrate how these women's practical endeavours have made them an indispensable ingredient in the achievement of real democratic development at the grassroots level, and how they serve as a model for policymakers in developing countries elsewhere.     

Appearing moderate or radical? Radical left party success and the two-dimensional political space

Abstract

Challenger parties’ electoral successes have attracted increasing scholarly attention. Based on the example of West European radical left parties, this article investigates whether and how centripetal and centrifugal positional movements on different conflict dimensions influence the election results of these parties. Depending on parties’ issue-linkages, these strategies will have a different effect for the economic and the non-economic issue dimension. Due to radical left parties’ long-term commitment and a strong party-issue linkage on economic issues, more moderate positions will play to their electoral advantage. In contrast, far-left parties compete with social democratic and green-libertarian parties for party-issue linkages on the non-economic issue dimension. Here, they benefit from promoting centrifugal strategies. Based on time-series cross-section analyses for 25 West European far-left parties between 1990 and 2017, the empirical results show that the success of radical left parties’ positional strategies varies with the conflict dimension in question and that this effect is only partly moderated by the positions of competing mainstream left parties.     

LC-MS/MS analysis of pholedrine in a fatal intoxication case

Pholedrine (4'-hydroxymethamphetamine) is a cardiovascular agent exerting hypertensive and adrenergic effects. High doses may cause a drop in the peripheral circulation blood flow and increase blood pressure, heart rate and body temperature up to a state of central respiratory paralysis. A 15-year-old girl who suffered from heavy agitation and hallucinations was admitted to the intensive care unit in a comatose state. The clinical findings included a maximum heart rate of 170 bpm and a body temperature of 43.8 degrees C. Resuscitation measures were in vain and abandoned after approximately 2h. A toxicological emergency analysis using GC/MS revealed a considerable amount of pholedrine in blood and urine. A method for determining pholedrine in human body fluids utilizing high-performance liquid chromatography (HPLC)/tandem mass spectrometry (LC-MS/MS) with a turbo ion-spray source was developed, using D11-methamphetamine and D5-methylenedioxymethamphetamine as internal standards. Samples were prepared by SPE extraction using SPEC-C18AR/MP3((R)) columns, which yielded the best extraction recovery (67%). Chromatographic separation was achieved at pH 5 on an RP-18 stationary phase applying gradient elution from 50 to 70% of B (methanol/acetonitrile 3/1 (v/v), 0.02% acetic acid) in A (5mM ammonium acetate/acetonitrile 95/5 (v/v), 0.02% acetic acid). Supra-pure acetic acid was added to the post-column effluent with a flow rate of 0.2 microl/min to optimize ionization. Detection was carried out in the positive ionization, multiple reaction monitoring (MRM) mode. The chromatograms showed no interference from other substances. The limit of detection (LOD, S/N=3) of pholedrine was 0.8 ng/ml and its lower limit of quantification (LLOQ, S/N=10) 3ng/ml. The calibration curve was linear (r=0.999) in the range 1-100 ng/ml. Samples with higher concentrations were diluted to suit the working range. The intra-day R.S.D. between 5 and 80 ng/ml were 3.8-8.7% and the inter-day R.S.D. between 5 and 100 ng/ml were 6.7-10.7%. The pholedrine concentrations in blood and urine collected when the girl was still alive were 16.1 microg/ml (R.S.D. 10.5%) and 1120 microg/ml (R.S.D. 8%), respectively. In post-mortem samples, they were 23.0 microg/ml (R.S.D. 5.1%) in heart blood and 27.3 microg/g (R.S.D. 6.6%) in the liver.     

Mitochondrial diversity of a northeast German population sample

Mitochondrial DNA sequences of the hypervariable regions HV I and HV II were analyzed in 300 unrelated individuals born and living in the northeast corner of Germany (Western Pomerania) to generate a database for forensic identification purposes in this region. Sequence polymorphism were detected using PCR and direct sequencing analysis. A total of 242 different haplotypes were found as determined by 147 variable positions. The most frequent haplotype (263G, 315.1C) was found in 10 individuals and is also the most common sequence in Europe. Three other haplotypes were shared by 5 individuals, 2 sequences by 4, 8 haplotypes by 3, 15 sequences by 2 persons, and 213 sequences were unique. The genetic diversity was estimated to be 0.99 and the probability of two random individuals showing identical mitochondrial DNA (mtDNA) haplotypes is 0.6%. A comparison with other studies from Germany showed only little differences in the distribution of haplogroups. Nevertheless, one frequent haplotype in northeast Germany (five unrelated individuals) could only rarely be found in other German and European regions. Our results may indicate that despite a high admixture proportion in the German population some regions could demonstrate certain characteristic features.     

Political Appointments, Civil Service Systems, and Bureaucratic Competence: Organizational Balancing and Executive Branch Revenue Forecasts in the American States

Scholarship on executive politics provides conflicting views about whether staffing administrative agencies through politicized or (politically) autonomous means is the best method for maximizing bureaucratic competence. We offer a theoretical account which maintains that obtaining a proper balance between both types of personnel systems across the supervisory and subordinate levels of an organization will best foster bureaucratic competence. We evaluate our organizational balancing thesis using data on executive branch general revenue fund forecasts in the American states from 1987 to 2002. States with a combination of politically appointed agency executives and merit-selected subordinates generally provide more accurate revenue forecasts than states that possess uniformly politicized personnel selection systems. Conversely, states with a combination of department head–appointed executives and subordinates chosen from an at-will system (i.e., nonmerit) produce more accurate forecasts than states with uniformly autonomous personnel selection systems. Our statistical findings underscore the positive consequences associated with balancing politicized and autonomous means of selecting personnel within hierarchies of political organizations.     

Women’s Participation in Peace Negotiations and the Durability of Peace

There is an emerging consensus that women’s participation in peace negotiations contributes to the quality and durability of peace after civil war. However, to date, this proposition has remained empirically untested. Moreover, how women’s participation may contribute to durable peace has not been systematically explored. This article uses a mixed method design to examine this proposition. Our statistical analysis demonstrates a robust correlation between peace agreements signed by female delegates and durable peace. We further find that agreements signed by women show a significantly higher number of peace agreement provisions aimed at political reform, and higher implementation rates for provisions. We argue that linkages between women signatories and women civil society groups explain the observed positive impact of women’s direct participation in peace negotiations. Collaboration and knowledge building among diverse women groups contributes to better content of peace agreements and higher implementation rates of agreement provisions. We substantiate this argument with qualitative case study evidence and demonstrate how collaboration between female delegates and women civil society groups positively impacts peace processes. Our findings support the assumption that women’s participation in peace negotiations increases the durability and the quality of peace.