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- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
- 2008
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In: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
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Research review (peer-reviewed)abstract
- Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.
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| 3. |
- Drueke, Tilman B., et al.
(author)
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Normalization of hemoglobin level in patients with chronic kidney disease and anemia
- 2006
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In: New England Journal of Medicine. - 0028-4793. ; 355:20, s. 2071-2084
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Journal article (peer-reviewed)abstract
- Background: Whether correction of anemia in patients with stage 3 or 4 chronic kidney disease improves cardiovascular outcomes is not established. Methods: We randomly assigned 603 patients with an estimated glomerular filtration rate (GFR) of 15.0 to 35.0 ml per minute per 1.73 m(sup 2) of body-surface area and mild-to-moderate anemia (hemoglobin level, 11.0 to 12.5 g per deciliter) to a target hemoglobin value in the normal range (13.0 to 15.0 g per deciliter, group 1) or the subnormal range (10.5 to 11.5 g per deciliter, group 2). Subcutaneous erythropoietin (epoetin beta) was initiated at randomization (group 1) or only after the hemoglobin level fell below 10.5 g per deciliter (group 2). The primary end point was a composite of eight cardiovascular events; secondary end points included left ventricular mass index, quality-of-life scores, and the progression of chronic kidney disease. Results: During the 3-year study, complete correction of anemia did not affect the likelihood of a first cardiovascular event (58 events in group 1 vs. 47 events in group 2; hazard ratio, 0.78; 95% confidence interval, 0.53 to 1.14; P=0.20). Left ventricular mass index remained stable in both groups. The mean estimated GFR was 24.9 ml per minute in group 1 and 24.2 ml per minute in group 2 at baseline and decreased by 3.6 and 3.1 ml per minute per year, respectively (P=0.40). Dialysis was required in more patients in group 1 than in group 2 (127 vs. 111, P=0.03). General health and physical function improved significantly (P=0.003 and P<0.001, respectively, in group 1, as compared with group 2). There was no significant difference in the combined incidence of adverse events between the two groups, but hypertensive episodes and headaches were more prevalent in group 1. Conclusions: In patients with chronic kidney disease, early complete correction of anemia does not reduce the risk of cardiovascular events.
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| 4. |
- Eckardt, Kai-Uwe, et al.
(author)
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Left Ventricular Geometry Predicts Cardiovascular Outcomes Associated with Anemia Correction in CKD
- 2009
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In: Journal of the American Society of Nephrology. - 1046-6673. ; 20:12, s. 2651-2660
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Journal article (peer-reviewed)abstract
- Partial correction of anemia in patients with chronic kidney disease (CKD) reduces left ventricular hypertrophy (LVH), which is a risk factor for cardiovascular (CV) morbidity, but complete correction of anemia does not improve CV outcomes. Whether LV geometry associates with CV events in patients who are treated to different hemoglobin (Hb) targets is unknown. One of the larger trials to study the effects of complete correction of anemia in stages 3 to 4 CKD was the Cardiovascular Risk Reduction by Early Anemia Treatment with Epoetin Beta (CREATE) trial. Here, we analyzed echocardiographic data from CREATE to determine the prevalence, dynamics, and prognostic implications of abnormal LV geometry in patients who were treated to different Hb targets. The prevalence of LVH at baseline was 47%, with eccentric LVH more frequent than concentric. During the study, LVH prevalence and mean left ventricular mass index did not change significantly, but LV geometry fluctuated considerably within 2 yr in both groups. CV event-free survival was significantly worse in the presence of concentric LVH and eccentric LVH compared with the absence of LVH (P = 0.0009 and P <= 0.0001, respectively). Treatment to the higher Hb target associated with reduced event-free survival in the subgroup with eccentric LVH at baseline (P = 0.034). In conclusion, LVH is common and associates with poor outcomes among patients with stages 3 to 4 CKD, although both progression and regression of abnormal LV geometry occur. Complete anemia correction may aggravate the adverse prognosis of eccentric LVH.
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| 5. |
- Flammini, Francesco, Senior Lecturer, 1978-, et al.
(author)
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DETECT : A novel framework for the detection of attacks to critical infrastructures
- 2009
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In: Safety, Reliability and Risk Analysis. - : Taylor & Francis. - 9780415485135 ; , s. 105-112
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Conference paper (peer-reviewed)abstract
- Critical Infrastructure Protection (CIP) against potential threats has become a major issue in modern society. CIP involves a set of multidisciplinary activities and requires the adoption of proper protection mechanisms, usually supervised by centralized monitoring systems. This paper presents the motivation, the working principles and the software architecture of DETECT (DEcision Triggering Event Composer & Tracker), a new framework aimed at the automatic and early detection of threats against critical infrastructures. The framework is based on the fact that non trivial attack scenarios are made up by a set of basic steps which have to be executed in a predictable sequence (with possible variants). Such scenarios are identified during Vulnerability Assessment which is a fundamental phase of the Risk Analysis for critical infrastructures. DETECT operates by performing a model-based logical, spatial and temporal correlation of basic events detected by the sensorial subsystem (possibly including intelligent video-surveillance, wireless sensor networks, etc.). In order to achieve this aim, DETECT is based on a detection engine which is able to reason about heterogeneous data, implementing a centralized application of "data fusion". The framework can be interfaced with or integrated in existing monitoring systems as a decision support tool or even to automatically trigger adequate countermeasures.
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| 7. |
- Legler, Tobias J., et al.
(author)
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Workshop report on the extraction of foetal DNA from maternal plasma
- 2007
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In: Prenatal Diagnosis. - : Wiley. - 1097-0223 .- 0197-3851. ; 27:9, s. 824-829
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Journal article (peer-reviewed)abstract
- Objective Cell free foetal DNA (cff DNA) extracted from maternal plasma is now recognized as a potential source for prenatal diagnosis but the methodology is currently not well standardized. To evaluate different manual and automated DNA extraction methods with a view to developing standards, an International Workshop was performed. Methods Three plasma pools from RhD-negative pregnant women, a DNA standard, real-time-PCR protocol, primers and probes for RHD were sent to 12 laboratories and also to one company (Qiagen, Hilden, Germany). In pre-tests, pool 3 showed a low cff DNA concentration, pool I showed a higher concentration and pool 2 an intermediate concentration. Results The QIAamp DSP Virus Kit, the High Pure PCR Template Preparation Kit, an in-house protocol using the QIAamp DNA Blood Mini Kit, the CST genomic DNA purification kit, the Magna Pure LC, the MDx, the M48, the EZl and an in-house protocol using magnetic beads for manual and automated extraction were the methods that were able to reliably detect foetal RHD. The best results were obtained with the QIAamp DSP Virus Kit. The QIAamp DNA Blood Mini Kit showed very comparable results in laboratories that followed the manufacturer's protocol and started with >= 500 mu L plasma. One participant using the QIAamp DNA Blood Midi Kit failed to detect reliably RHD in pool 3. Conclusions This workshop initiated a standardization process for extraction of cff DNA in maternal plasma. The highest yield was obtained by the QIAamp DSP Virus Kit, a result that will be evaluated in more detail in future studies. Copyright (c) 2007 John Wiley & Sons, Ltd.
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| 8. |
- Olatunji, Bunmi O., et al.
(author)
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Confirming the Three-Factor Structure of the Disgust Scale-Revised in Eight Countries
- 2009
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In: Journal of Cross-Cultural Psychology. - : SAGE Publications. - 0022-0221 .- 1552-5422. ; 40:2, s. 234-255
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Journal article (peer-reviewed)abstract
- The current study evaluates the factor structure of the Disgust Scale–Revised (DS-R) in eightcountries: Australia, Brazil, Germany, Italy, Japan, the Netherlands, Sweden, and the UnitedStates (N = 2,606). Confirmatory factor analysis is used to compare two different models of the DS-R and to investigate the invariance of the factor structure of the DS-R across countries and gender. A three-factor solution consisting of three different but interrelated disgust factors (a 12-item core disgust factor, an 8-item animal-reminder disgust factor, and a 5-item contamination disgust factor) best accounted for the data in all countries except the Netherlands. Relative to the United States, the three-factor solution is invariant in Australia, Brazil, and Japan but not in Germany, Italy, the Netherlands, and Sweden. The three-factor solution is also invariant across gender in most countries. The implications of these cross-cultural findings for promoting a morevalid and reliable assessment of disgust dimensions, as assessed by the DS-R, are discussed.
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| 10. |
- Pertl, Leonhard, et al.
(author)
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Exports and Productivity : Comparable Evidence for 14 Countries
- 2007
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In: Policy Research Working Papers. - New York : World Bank. - 1813-9450.
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Reports (peer-reviewed)abstract
- The authors use comparable micro level panel data for 14 countries and a set of identically specified empirical models to investigate the relationship between exports and productivity. The overall results are in line with the big picture that is by now familiar from the literature: Exporters are more productive than non-exporters when observed and unobserved heterogeneity are controlled for, and these exporter productivity premia tend to increase with the share of exports in total sales; there is strong evidence in favour of self-selection of more productive firms into export markets, but nearly no evidence in favour of the learning-by-exporting hypothesis. The authors document that the exporter premia differ considerably across countries in identically specified empirical models. In a meta-analysis of their results the authors find that countries that are more open and have more effective government report higher productivity premia. However, the level of development per se does not appear to be an explanation for the observed cross-country differences.
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