Identification of eight novel coagulation factor XIII subunit A mutations: implied consequences for structure and function

Severe hereditary coagulation factor XIII deficiency is a rare homozygous bleeding disorder affecting one person in every two million individuals. In contrast, heterozygous factor XIII deficiency is more common, but usually not associated with severe hemorrhage such as intracranial bleeding or hemarthrosis. In most cases, the disease is caused by F13A gene mutations. Causative mutations associated with the F13B gene are rarer.

Prevalence, predictors, and consequences of long-term refusal of antipsychotic treatment in first-episode psychosis

Studies investigating medication adherence in psychosis are limited by the need of a certain degree of medication adherence and the inclusion of mostly multiple-episode patients. By contrast, noninformed consent, epidemiological studies in first-episode psychosis (FEP) allow the assessment of an important subgroup of patients who persistently refuse antipsychotic medication and thereby never receive an adequate antipsychotic trial. The present study aims to assess the prevalence and predictors of such a "medication refusal" subgroup and its association with illness outcome.

Clinical and biochemical consequences of p450 oxidoreductase deficiency

Patients with P450 oxidoreductase (POR) deficiency typically present with adrenal insufficiency, genital anomalies and bony malformations resembling the Antley-Bixler craniosynostosis syndrome. Since our first report in 2004, more than 40 POR mutations have been identified in over 65 patients. POR is the obligate electron donor to all microsomal P450 enzymes, including the steroidogenic enzymes CYP17A1, CYP21A2 and CYP19A1. POR deficiency may cause disordered sexual development manifested as genital undervirilization in 46, XY newborns as well as overvirilization in those who are 46, XX. This may be explained by impaired aromatization of fetal androgens that may cause maternal virilization and low urinary estriol levels during pregnancy. In addition, the alternate 'backdoor' pathway of androgen biosynthesis, which leads to dihydrotestosterone production bypassing androstenedione and testosterone, may also play a role. Functional assays studying the effects of POR mutations on steroidogenesis showed that several POR variants impaired CYP17A1, CYP21A2 and CYP19A1 activities to different degrees, indicating that each POR variant must be studied separately for each potential target P450 enzyme. POR variants may also affect skeletal development and drug metabolism. As most drugs are metabolized by hepatic microsomal P450 enzymes, studies of the impact of POR mutations on drug-metabolizing P450s are particularly important.

European Union Trade Policy after Enlargement: Larger Crowds, Shifting Priorities and Informal Decision-Making

The article focuses on the effects of Eastern enlargement on EU trade policy-making. On interest constellation, the article makes a case that protectionist forces have been strengthened relative to liberal forces. This slight protectionist turn is mostly witnessed in the area of anti-dumping and with respect to the Doha trade round. On preference aggregation, guided by a principal–agent framework, it is argued that the growth in the number of actors (principals and interest groups) has not constrained the role of the European Commission (agent). However, it has led to an increase in informal processes and has empowered large trading nations vis-a`-vis smaller and less ‘comitology-experienced’ member states.

A "Beyond WTO" Scenario for Swiss Agriculture: Consequences for Income Generation and the Provision of Public Goods

The conclusion of the Doha Round negotiations is likely to influence Swiss agricultural policy substantially. The same goes for a free trade agreement in agriculture and food with the European Communities. Even though neither of them will bring about duty-free and quota-free market access, or restrict domestic support measures to green box compatible support, both would represent a big step in that direction. There is no empirical evidence on the effect of such a counterfactual scenario for Swiss agriculture. We therefore use a normative mathematical programming model to illustrate possible effects for agricultural production and the corresponding agricultural income. Moreover, we discuss the results with respect to the provision of public goods under the assumption of continuing green box-compatible direct payments. The aim of our article is to bring more transparency into the discussion on the effects of freer and less distorted trade on the income generation by a multifunctional agriculture. The article will be organized as follows. In the first Section we specify the background of our study. In the second section, we focus on the problem statement and our research questions. In Section 3, we describe in detail a counterfactual scenario of “duty-free, quota-free and price support-free” agriculture from an economic as well as a legal perspective. Our methodology and the results are presented in Section 4 and 5 respectively. In Section 6, we discuss our results with respect to economic and legal aspects of multifunctional agriculture.