The implementation §1,2 & 3 of article 8 of the sustainable use of pesticide directive in Sweden

contribution to session 1Inspection at regular intervals – Inspection of new equipment (according article 8/1 and 8/2

Consequences of including inspection of sprayers in use in the new Regulation on official controls

Inspection of sprayers in use in its current form cannot be carried out under the control regulation because:Neither size of sprayer inspections nor the use of pesticides is large enough to support the administrative structure of the regulation of official controls. Too high costs need to be transferred to the customer.It is unclear if the control regulation allows free pricing.The fee for an inspection of sprayers in use regulated by the control regulation would affect the number of sprayers and thereby diminish the market.The possibilities to implement inspection of sprayers in use outside a workshop decreases. The demand that inspections should be free from any conflicts of interest may make repairs and advisory services impossible.The control regulation does not provide any guidance as to how inspection of sprayers in use should be done in practice. The administrative control adds no positive value to the business. Planned improvements in quality assurance will be impossible.This official proposal creates difficulties to give straight answers to companies that want to expand their business. Since an expansion is necessary to provide access to inspections for all plant protection users, straight answers is crucial to implement mandatory inspections.If inspection of sprayers, despite our arguments, should be included in the regulation on official controls, the decision should be based on an impact assessment including a cost-benefit analysis, and whether there are alternative ways to achieve the benefits. Our assessment is that the cost of the regulation for corporate profitability, the environment and working conditions for all personal and, above all, increased administration at all stages is not offset by improvements

Stable isotopic labeling in proteomics

Labeling of proteins and peptides with stable heavy isotopes (deuterium, carbon-13, nitrogen-15, and oxygen-18) is widely used in quantitative proteomics. These are either incorporated metabolically in cells and small organisms, or postmetabolically in proteins and peptides by chemical or enzymatic reactions. Only upon measurement with mass spectrometers holding sufficient resolution, light, and heavy labeled peptide ions or reporter peptide fragment ions segregate and their intensity values are subsequently used for quantification. Targeted use of these labels or mass tags further leads to specific monitoring of diverse aspects of dynamic proteomes. In this review article, commonly used isotope labeling strategies are described, both for quantitative differential protein profiling and for targeted analysis of protein modifications

Oral direct thrombin inhibitor AZD0837 for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation: a randomized dose-guiding, safety, and tolerability study of four doses of AZD0837 vs. vitamin K antagonists

Aims Oral anticoagulation with vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF) is effective but has significant limitations. AZD0837, a new oral anticoagulant, is a prodrug converted to a selective and reversible direct thrombin inhibitor (AR-H067637). We report from a Phase II randomized, dose-guiding study (NCT00684307) to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of extended-release AZD0837 in patients with AF. Methods and results Atrial fibrillation patients (n = 955) with >= 1 additional risk factor for stroke were randomized to receive AZD0837 (150, 300, or 450 mg once daily or 200 mg twice daily) or VKA (international normalized ratio 2-3, target 2.5) for 3-9 months. Approximately 30% of patients were naive to VKA treatment. Total bleeding events were similar or lower in all AZD0837 groups (5.3-14.7%, mean exposure 138-145 days) vs. VKA (14.5%, mean exposure 161 days), with fewer clinically relevant bleeding events on AZD0837 150 and 300 mg once daily. Adverse events were similar between treatment groups; with AZD0837, the most common were gastrointestinal disorders (e.g. diarrhoea, flatulence, or nausea). D-Dimer, used as a biomarker of thrombogenesis, decreased in all groups in VKA-naive subjects with treatment, whereas in VKA pre-treated patients, D-dinner levels started tow and remained low in all groups. As expected, only a few strokes or systemic embolic events occurred. In the AZD0837 groups, mean S-creatinine increased by similar to 10% from baseline and returned to baseline following treatment cessation. The frequency of serum alanine aminotransferase >= 3 x upper limit of normal was similar for AZD0837 and VKA. Conclusion AZD0837 was generally well tolerated at all doses tested. AZD0837 treatment at an exposure corresponding to the 300 mg od dose in this study provides similar suppression of thrombogenesis at a potentially lower bleeding risk compared with dose-adjusted VKA

Oxidative protein folding by an endoplasmic reticulum-localized peroxiredoxin

Endoplasmic reticulum (ER) oxidation 1 (ERO1) transfers disulfides to protein disulfide isomerase (PDI) and is essential for oxidative protein folding in simple eukaryotes such as yeast and worms. Surprisingly, ERO1-deficient mammalian cells exhibit only a modest delay in disulfide bond formation. To identify ERO1-independent pathways to disulfide bond formation, we purified PDI oxidants with a trapping mutant of PDI. Peroxiredoxin IV (PRDX4) stood out in this list, as the related cytosolic peroxiredoxins are known to form disulfides in the presence of hydroperoxides. Mouse embryo fibroblasts lacking ERO1 were intolerant of PRDX4 knockdown. Introduction of wild-type mammalian PRDX4 into the ER rescued the temperature-sensitive phenotype of an ero1 yeast mutation. In the presence of an H2O2-generating system, purified PRDX4 oxidized PDI and reconstituted oxidative folding of RNase A. These observations implicate ER-localized PRDX4 in a previously unanticipated, parallel, ERO1-independent pathway that couples hydroperoxide production to oxidative protein folding in mammalian cells.EMBO [ALTF649-2008]; Fundacao para a Ciencia e Tecnologia, Portugal [SFRH/BSAB/922/2009, PTDC/QUI/73027/2006, IBB/CBME LA]; NIH [DK47119, DK075311, ES08681]; 100 Women In Hedge Funds Foundation; [NS050276]; [CA016087]; Medical Research Council [G0600717B]info:eu-repo/semantics/publishedVersio

Anticoagulation for non-valvular atrial aibrillation – towards a new beginning with ximelagatran

OBJECTIVES: Ximelagatran is a novel oral direct thrombin inhibitor. It has favorable pharmacodynamic properties, with a broad therapeutic range without the need for anticoagulation monitoring. We aimed to discover whether ximelagatran offers a genuine future replacement to warfarin for patients in persistent atrial fibrillation (AF). MATERIALS AND METHODS: We provide an evidence-based review of the relative merits and disadvantages of warfarin and aspirin. We subsequently present an overview of the evidence for the utility of ximelagatran in the treatment of AF. RESULTS: Adjusted dose warfarin is recommended over aspirin for patients in AF at high risk of future stroke. Some of this benefit is partially offset by the higher bleeding risks associated with warfarin therapy. The SPORTIF III and V studies have shown that ximelagatran is not inferior to warfarin in the prevention of all strokes in patients with AF (both persistent and paroxysmal). This benefit was partially offset by the finding of a significant elevation of liver transaminases (>3 × normal) in 6% of patients. CONCLUSIONS: Current data would suggest that ximelagatran might represent a future alternative to warfarin. The lack of need for anticoagulant monitoring has been partially offset by a need for regular monitoring of liver function. Further data from randomized clinical trials is clearly needed

Paediatric and adult congenital cardiology education and training in Europe

Background: Limited data exist on training of European paediatric and adult congenital cardiologists. Methods: A structured and approved questionnaire was circulated to national delegates of Association for European Paediatric and Congenital Cardiology in 33 European countries. Results: Delegates from 30 countries (91%) responded. Paediatric cardiology was not recognised as a distinct speciality by the respective ministry of Health in seven countries (23%). Twenty countries (67%) have formally accredited paediatric cardiology training programmes, seven (23%) have substantial informal (not accredited or certified) training, and three (10%) have very limited or no programme. Twenty-two countries have a curriculum. Twelve countries have a national training director. There was one paediatric cardiology centre per 2.66 million population (range 0.87-9.64 million), one cardiac surgical centre per 4.73 million population (range 1.63-10.72 million), and one training centre per 4.29 million population (range 1.63-10.72 million population). The median number of paediatric cardiology fellows per training programme was 4 (range 1-17), and duration of training was 3 years (range 2-5 years). An exit examination in paediatric cardiology was conducted in 16 countries (53%) and certification provided by 20 countries (67%). Paediatric cardiologist number is affected by gross domestic product (R-2 = 0.41). Conclusion: Training varies markedly across European countries. Although formal fellowship programmes exist in many countries, several countries have informal training or no training. Only a minority of countries provide both exit examination and certification. Harmonisation of training and standardisation of exit examination and certification could reduce variation in training thereby promoting high-quality care by European congenital cardiologists.Developmen

Mandatory ethics consultation policy

OBJECTIVE: To describe ethics consultations at a single institution that has a mandatory ethics consultation policy. PATIENTS AND METHODS: We retrospectively reviewed the medical records of all adult patients who were admitted to the intensive care unit at Columbia University Medical Center and had an ethics consultation between August 1, 2006, and July 31, 2007. All mandatory and nonmandatory ethics consultations were reviewed. Patient diagnosis, prognosis, presence of do-not-resuscitate order, presence of written advance directives, reason for the ethics consultation, and survival data were collected. The number of ethics consultations hospital-wide from January 1, 2000, to December 31, 2007, was collected. RESULTS: The total number of mandatory and nonmandatory ethics consultations requested was 168. Of these consultations, 108 (64%) were considered mandatory, and 60 (36%) were considered nonmandatory. Between January 1, 2000, and December 31, 2007, the total number of ethics consultations increased 84%. CONCLUSION: The increase in the total number of ethics consultations is interpreted as a positive outcome of the mandatory policy. The mandatory ethics consultation policy has possibly increased exposure to ethics consultant-physician interactions, increased learning for physicians, and raised awareness among physicians and nurses of potential ethics assistance.link_to_OA_fulltex