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Detection of diphtheria antitoxin by four different methods

ObjectiveTo investigate the reliability of the different methods used in Norway and Russia for detection of diphtheria antitoxin.MethodsOne hundred and twenty-two sera were selected among Russian serum samples previously collected for seroepidemiologic studies of diphtheria antitoxin. The sera were selected to cover the total antitoxin range and were analyzed by four different antidiphtheria toxin assays: an in vitro toxin neutralization test using Vero cells (in vitro NT), an in vivo neutralization test using rabbit skin inoculation (in vivo NT), an indirect enzyme immunoassay (EIA) and a passive hemagglutination assay (PHA). The results were expressed according to the international standard as: not protected (<0.01 IU/mL), relatively protected (0.01–0.1 IU/mL) or protected (≤0.1 IU/mL). The sensitivity, specificity and inter-rater agreement (K or Kw) of each method were related to the in vitro NT selected as the reference method.ResultsThe in vivo NT test corresponded very well with the in vitro NT in its ability to differentiate between protection/relative protection and no protection (sensitivity 97%, specificity 87% and K=0.84). The EIA test showed a high sensitivity (96%), but since many sera were categorized as protected rather than not protected, the specificity (30%) and inter-rater agreement (K=0.29) were low. The PHA test had a very high specificity (100%) but a low sensitivity (86%).ConclusionsThe agreement between the two neutralization tests was high. If none of the neutralization assays is routinely available, the PHA test can be used to predict the need for vaccination on an individual basis but should not be used for seroepidemiologic studies, since the protection rate for diphtheria would be falsely too low, due to the lower sensitivity. The indirect EIA test used in this study should not be used routinely

Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome

Background: Lipoprotein(a) concentration is associated with cardiovascular events. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, lowers lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C). Objectives: A pre-specified analysis of the placebo-controlled ODYSSEY Outcomes trial in patients with recent acute coronary syndrome (ACS) determined whether alirocumab-induced changes in lipoprotein(a) and LDL-C independently predicted major adverse cardiovascular events (MACE). Methods: One to 12 months after ACS, 18,924 patients on high-intensity statin therapy were randomized to alirocumab or placebo and followed for 2.8 years (median). Lipoprotein(a) was measured at randomization and 4 and 12 months thereafter. The primary MACE outcome was coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina. Results: Baseline lipoprotein(a) levels (median: 21.2 mg/dl; interquartile range [IQR]: 6.7 to 59.6 mg/dl) and LDL-C [corrected for cholesterol content in lipoprotein(a)] predicted MACE. Alirocumab reduced lipoprotein(a) by 5.0 mg/dl (IQR: 0 to 13.5 mg/dl), corrected LDL-C by 51.1 mg/dl (IQR: 33.7 to 67.2 mg/dl), and reduced the risk of MACE (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.78 to 0.93). Alirocumab-induced reductions of lipoprotein(a) and corrected LDL-C independently predicted lower risk of MACE, after adjustment for baseline concentrations of both lipoproteins and demographic and clinical characteristics. A 1-mg/dl reduction in lipoprotein(a) with alirocumab was associated with a HR of 0.994 (95% CI: 0.990 to 0.999; p = 0.0081). Conclusions: Baseline lipoprotein(a) and corrected LDL-C levels and their reductions by alirocumab predicted the risk of MACE after recent ACS. Lipoprotein(a) lowering by alirocumab is an independent contributor to MACE reduction, which suggests that lipoprotein(a) should be an independent treatment target after ACS. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402)

Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome

Lipoprotein(a) concentration is associated with cardiovascular events. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, lowers lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C). A pre-specified analysis of the placebo-controlled ODYSSEY Outcomes trial in patients with recent acute coronary syndrome (ACS) determined whether alirocumab-induced changes in lipoprotein(a) and LDL-C independently predicted major adverse cardiovascular events (MACE). One to 12 months after ACS, 18,924 patients on high-intensity statin therapy were randomized to alirocumab or placebo and followed for 2.8 years (median). Lipoprotein(a) was measured at randomization and 4 and 12 months thereafter. The primary MACE outcome was coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina. Baseline lipoprotein(a) levels (median: 21.2 mg/dl; interquartile range [IQR]: 6.7 to 59.6 mg/dl) and LDL-C [corrected for cholesterol content in lipoprotein(a)] predicted MACE. Alirocumab reduced lipoprotein(a) by 5.0 mg/dl (IQR: 0 to 13.5 mg/dl), corrected LDL-C by 51.1 mg/dl (IQR: 33.7 to 67.2 mg/dl), and reduced the risk of MACE (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.78 to 0.93). Alirocumab-induced reductions of lipoprotein(a) and corrected LDL-C independently predicted lower risk of MACE, after adjustment for baseline concentrations of both lipoproteins and demographic and clinical characteristics. A 1-mg/dl reduction in lipoprotein(a) with alirocumab was associated with a HR of 0.994 (95% CI: 0.990 to 0.999; p = 0.0081). Baseline lipoprotein(a) and corrected LDL-C levels and their reductions by alirocumab predicted the risk of MACE after recent ACS. Lipoprotein(a) lowering by alirocumab is an independent contributor to MACE reduction, which suggests that lipoprotein(a) should be an independent treatment target after ACS. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402

BacHBerry: BACterial Hosts for production of Bioactive phenolics from bERRY fruits

BACterial Hosts for production of Bioactive phenolics from bERRY fruits (BacHBerry) was a 3-year project funded by the Seventh Framework Programme (FP7) of the European Union that ran between November 2013 and October 2016. The overall aim of the project was to establish a sustainable and economically-feasible strategy for the production of novel high-value phenolic compounds isolated from berry fruits using bacterial platforms. The project aimed at covering all stages of the discovery and pre-commercialization process, including berry collection, screening and characterization of their bioactive components, identification and functional characterization of the corresponding biosynthetic pathways, and construction of Gram-positive bacterial cell factories producing phenolic compounds. Further activities included optimization of polyphenol extraction methods from bacterial cultures, scale-up of production by fermentation up to pilot scale, as well as societal and economic analyses of the processes. This review article summarizes some of the key findings obtained throughout the duration of the project

Network level framing in INSTANCE

Internet services like the world-wide web and applications like News-on-Demand have become very popular over the last years. The number of users, as well as the amount of multimedia data downloaded by each user from servers in the Internet, is rapidly increasing. In this context, the potentially (very) high number of concurrent users that retrieve data from servers represents a generic problem. In the Intermediate Storage Node Concept (INSTANCE) project, we develop a radically new architecture for Media-on-Demand servers that maximizes the number of concurrent clients a single server can support. Traditional bottlenecks, like copy operations, multiple copies of the same data element in main memory, and checksum calculations in communication protocols are avoided by applying three orthogonal techniques: zero-copy-one-copy memory architecture, integrated error management, and network level framing. In this paper, we describe the design of the network level framing concept, that enables us to reduce the server workload by reducing the number of operations performed by the communication system at transmission time.

Integrated Storage and Communication System Error Management in a Media-on-Demand Server

Internet services like the world-wide web and applications like News-on-Demand have become very popular in the last years. The number of users, as well as the amount of multimedia data downloaded by each user from servers in the Internet, is rapidly increasing. In this context, the potentially (very) high number of concurrent users that retrieve data from servers represents a generic problem. In the Intermediate Storage Node Concept (INSTANCE) project, we develop a radically new architecture for Media-on-Demand servers that maximizes the number of concurrent clients a single server can support. Traditional bottlenecks, like copy operations, multiple copies of the same data element in main memory, and checksum calculation in communication protocols are avoided by applying the three orthogonal techniques: zero-copy-one-copy memory architecture, network level framing, and integrated error management. In this paper, we describe design, implementation, and evaluation of the integrated error..