Olanzapine and pulmonary embolism, a rare association: a case report

Venous thromboembolism is a very common pathological process for which there are many well known (and less well-known) predisposing factors. Likewise, olanzapine is a commonly used anti-psychotic medication

Genetic Networks Controlling Structural Outcome of Glucosinolate Activation across Development

Most phenotypic variation present in natural populations is under polygenic control, largely determined by genetic variation at quantitative trait loci (QTLs). These genetic loci frequently interact with the environment, development, and each other, yet the importance of these interactions on the underlying genetic architecture of quantitative traits is not well characterized. To better study how epistasis and development may influence quantitative traits, we studied genetic variation in Arabidopsis glucosinolate activation using the moderately sized Bayreuth×Shahdara recombinant inbred population, in terms of number of lines. We identified QTLs for glucosinolate activation at three different developmental stages. Numerous QTLs showed developmental dependency, as well as a large epistatic network, centered on the previously cloned large-effect glucosinolate activation QTL, ESP. Analysis of Heterogeneous Inbred Families validated seven loci and all of the QTL×DPG (days post-germination) interactions tested, but was complicated by the extensive epistasis. A comparison of transcript accumulation data within 211 of these RILs showed an extensive overlap of gene expression QTLs for structural specifiers and their homologs with the identified glucosinolate activation loci. Finally, we were able to show that two of the QTLs are the result of whole-genome duplications of a glucosinolate activation gene cluster. These data reveal complex age-dependent regulation of structural outcomes and suggest that transcriptional regulation is associated with a significant portion of the underlying ontogenic variation and epistatic interactions in glucosinolate activation

Genetic loci associated with heart rate variability and their effects on cardiac disease risk

Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74 < r(g) < -0.55) and blood pressure (-0.35 < r(g) < -0.20). These findings provide clinically relevant biological insight into heritable variation in vagal heart rhythm regulation, with a key role for genetic variants (GNG11, RGS6) that influence G-protein heterotrimer action in GIRK-channel induced pacemaker membrane hyperpolarization

NAFTA as an agricultural "policy option" for Mexico : a case study within a two-level framework

NAFTA AS AN AGRICULTURAL 'POLICY OPTION' FOR MEXICO: A CASE STUDY WITHIN A TWO- LEVEL FRAMEWORK The main focus of the thesis was the agricultural negotiation process between Mexico and the United States within the NAFTA process. I wanted to investigate to what extent this process led to changes in Mexican agricultural policy. Furthermore I wanted to find out whose interests were taken into consideration when Mexico negotiated agriculture in NAFTA. If so, was this done at the expense of any other groups interests? The Mexican Government did make several radical changes to their agricultural policies during the NAFTA process, and in 1992 they transformed the ejido (small collective farm systems) as it was defined in Article 27 of the Mexican Constitution. These changes coincided with the NAFTA process. My contrafactual question was then: whether the agricultural policy changes would have been pursued by the Mexican Government without the impetus NAFTA provided? To find out whose interests were pursued in the process I had to investigate the dual character of NAFTA, and look at the agricultural negotiations within NAFTA as a process taking place at two levers. Thus I chose Robert D. Putnam's (1988) two-level framework to be my analytical tool, as this framework captures the dynamic and complexity of negotiations at two-levels: the national as well as the international negotiations. My main interest was the interaction between the different actors in the negotiation process in Mexico, and more specifically if NAFTA was deliberately used by the chief negotiators of Mexico to change the country's agricultural policy. I investigated both the role of the chief negotiators, their strategies and the participation and influence of the Mexican domestic constituency. A phenomenon most distinctive of the two-level game approach is what Putnam calls synergy. Putnam defines a synergistic linkage as an international deal that creates "a policy option...that was previously beyond domestic control." The most radical method of altering domestic constraints is to implement a broad program of social or institutional reforms. Statesmen may in this way attempt to gain approval for an important domestic measure by linking it to an attractive international agreement, or vice versa. According to Putnam economic interdependence multiplies the opportunities for altering domestic coalitions and ultimate policy. I found clear indications that NAFTA was used as a 'policy option' to instigate changes in the agricultural policies of Mexico. The international negotiations allowed the Mexican chief negotiator to shift the balance of power at Level 2 in favour of a policy he preferred for exogenous reasons. Furthermore President Salinas seemed more interested in disrupting traditional links to peasants and labour than to capital, and the NAFTA process was an important moment by which to act on behalf of large business interests and to encourage their involvement in the process itself. Thus, the Mexican chief negotiator benefited from the support of private interests, who, for their part, enjoyed the accommodating attitude of the Mexican negotiators. With joint efforts towards NAFTA this coalition managed to make corrections to the agricultural policies of Mexico. Furthermore the agricultural reforms undertaken in Mexico could also be seen as a result of the disciplines imposed by NAFTA. To fully grasp the particular state-society relations in Mexico I complemented Putnam's approach with a further discussion on the Mexican state's autonomy and how a state's embeddedness within particular groups in society may affect its course of action. The connection between the private and public interests in Mexico resembles the type of embedded autonomy as perceived by Peter B. Evans (1995). The notion of embedded autonomy, where the state connects to industrial capital and private interests, sharing the idea of a joint project of transformation, proved to be a useful supplement in the understanding of the intrastate division and economic restructuring of Mexico before and during the NAFTA process. Furthermore describing the intention of the coalition between the Mexican Government and the private interests as a 'joint process of transformation' seemed apt. My case study took as its subject parties negotiating within asymmetric power relations, and I assumed there was a great variation in bargaining leverage between Mexico and the United States, to Mexico's disadvantage. In my case the more dependent of the two was Mexico. This complies with Putnam's hypothesis on autonomy where the stronger the state is in terms of autonomy from domestic pressure, the weaker its relative bargaining position internationally. Although Putnam's hypothesis did not fully capture the nuance in Mexico's particular type of state autonomy (i.e. discussion on 'embedded autonomy'), I still found clear indications that Mexico's traditionally authoritarian structures and lack of popular mandate left the Salinas administration weakened in the international negotiations compared to the U.S. Putnam's focus on actor's motives, interests and tactics is somehow done at the expense of capturing the power relation between the negotiating parties. Therefore I tried to complement his approach with the theoretical approach of Bacharach and Lawler (1981), which places tactical action in the context of the power relation. I found, with certain modifications and complementations, that Putnam's two-level framework was the most fruitful analytical tool for my case study. The international power structures were hard to measure, but it should be no surprise if sharing borders with the world's greatest power and fiercest promoter of free trade to the world market economy, would effect the policies, attitudes and beliefs of its neighbour: Mexico. The world's greatest power, the U.S. (Strange 1988), was also Mexico's negotiating partner in the agricultural negotiations in NAFTA

Active galactic nuclei as scaled-up Galactic black holes

A long-standing question is whether active galactic nuclei (AGN) vary like Galactic black hole systems when appropriately scaled up by mass1,2,3. If so, we can then determine how AGN should behave on cosmological timescales by studying the brighter and much faster varying Galactic systems. As x-ray emission is produced very close to the black holes, it provides one of the best diagnostics of their behaviour. A characteristic timescale—which potentially could tell us about the mass of the black hole—is found in the x-ray variations from both AGN and Galactic black holes1,2,3,4,5,6, but whether it is physically meaningful to compare the two has been questioned7. Here we report that, after correcting for variations in the accretion rate, the timescales can be physically linked, revealing that the accretion process is exactly the same for small and large black holes. Strong support for this linkage comes, perhaps surprisingly, from the permitted optical emission lines in AGN whose widths (in both broad-line AGN and narrow-emission-line Seyfert 1 galaxies) correlate strongly with the characteristic x-ray timescale, exactly as expected from the AGN black hole masses and accretion rates. So AGN really are just scaled-up Galactic black holes