Semiquantitative interpretation of anticardiolipin and antiβ2glycoprotein I antibodies measured with various analytical platforms: communication from the ISTH SSC subcommittee on Lupus Anticoagulant/Antiphospholipid antibodies

Background Antiβ2glycoprotein I (aβ2GPI) and anticardiolipin (aCL) IgG/IgM show differences in positive/negative agreement and titers between solid phase platforms. Method specific semiquantitative categorization of titers could improve and harmonize the interpretation across platforms. Aim To evaluate the traditionally 40/80 units thresholds used for aCL and aβ2GPI for categorization into moderate/high positivity with different analytical systems, and to compare with alternative thresholds. Material and methods aCL and aβ2GPI thresholds were calculated for two automated systems (chemiluminescent immunoassay (CLIA) and multiplex flow immunoassay (MFI)) by ROC-curve analysis on 1108 patient samples, including patients with and without APS, and confirmed on a second population (n=279). Alternatively, regression analysis on diluted standard material was applied to identify thresholds. Thresholds were compared to 40/80 threshold measured by an enzyme linked immunosorbent assay (ELISA). Additionally, likelihood ratios (LR) were calculated. Results Threshold levels of 40/80 units show poor agreement between ELISA and automated platforms for classification into low/moderate/high positivity, especially for aCL/aβ2GPI IgG. Agreement for semiquantitative interpretation of aPL IgG between ELISA and CLIA/MFI improves with alternative thresholds. LR for aPL IgG increase for thrombotic and obstetric APS based on 40/80 thresholds for ELISA and adapted thresholds for the other systems, but not for IgM. Conclusion Use of 40/80 units as medium/high thresholds is acceptable for aCL/aβ2GPI IgG ELISA, but not for CLIA and MFI. Alternative semiquantitative thresholds for non-ELISA platforms can be determined by a clinical approach or by using monoclonal antibodies. Semiquantitative reporting of aPL IgM has less impact on increasing probability for APS

Energy efficiency considerations in integrated IT and optical network resilient infrastructures

The European Integrated Project GEYSERS - Generalised Architecture for Dynamic Infrastructure Services - is concentrating on infrastructures incorporating integrated optical network and IT resources in support of the Future Internet with special emphasis on cloud computing. More specifically GEYSERS proposes the concept of Virtual Infrastructures over one or more interconnected Physical Infrastructures comprising both network and IT resources. Taking into consideration the energy consumption levels associated with the ICT today and the expansion of the Internet in size and complexity, that incurring increased energy consumption of both IT and network resources, energy efficient infrastructure design becomes critical. To address this need, in the framework of GEYSERS, we propose energy efficient design of infrastructures incorporating integrated optical network and IT resources, supporting resilient end-to-end services. Our modeling results quantify significant energy savings of the proposed solution by jointly optimizing the allocation of both network and IT resources

Signal acquisition and analysis of ambulatory electromyographic recordings for the assessment of sleep bruxism: A scoping review

Background: Ambulatory electromyographic (EMG) devices are increasingly being used in sleep bruxism studies. EMG signal acquisition, analysis and scoring methods vary between studies. This may impact comparability of studies and the assessment of sleep bruxism in patients. Objectives: (a) To provide an overview of EMG signal acquisition and analysis methods of recordings from limited-channel ambulatory EMG devices for the assessment of sleep bruxism; and (b) to provide an overview of outcome measures used in sleep bruxism literature utilising such devices. Method: A scoping review of the literature was performed. Online databases PubMed and Semantics Scholar were searched for studies published in English until 7 October 2020. Data on five categories were extracted: recording hardware, recording logistics, signal acquisition, signal analysis and sleep bruxism outcomes. Results: Seventy-eight studies were included, published between 1977 and 2020. Recording hardware was generally well described. Reports of participant instructions in device handling and of dealing with failed recordings were often lacking. Basic elements of signal acquisition, for example amplifications factors, impedance and bandpass settings, and signal analysis, for example rectification, signal processing and additional filtering, were underreported. Extensive variability was found for thresholds used to characterise sleep bruxism events. Sleep bruxism outcomes varied, but typically represented frequency, duration and/or intensity of masticatory muscle activity (MMA). Conclusion: Adequate and standardised reporting of recording procedures is highly recommended. In future studies utilising ambulatory EMG devices, the focus may need to shift from the concept of scoring sleep bruxism events to that of scoring the whole spectrum of MMA

Preferences and skills of Indian public sector teachers

With a sample of 700 future public sector primary teachers in India, a Discrete Choice Experiment is used to measure job preferences, particularly regarding location. General skills are also tested. Urban origin teachers and women are more averse to remote locations than rural origin teachers and men respectively. Women would require a 26-73 percent increase in salary for moving to a remote location. The results suggest that existing caste and gender quotas can be detrimental for hiring skilled teachers willing to work in remote locations. The most preferred location is home, which supports decentralised hiring, although this could compromise skills

Regulation of the zebrafish goosecoid promoter by mesoderm inducing factors and Xwnt1

Goosecoid is a homeobox gene that is expressed as an immediate early response to mesoderm induction by activin. We have investigated the induction of the zebrafish goosecoid promoter by the mesoderm inducing factors activin and basic fibroblast growth factor (bFGF) in dissociated zebrafish blastula cells, as well as by different wnts in intact embryos. Activin induces promoter activity, while bFGF shows a cooperative effect with activin. We have identified two enhancer elements that are functional in the induction of the goosecoid promoter. A distal element confers activin responsiveness to a heterologous promoter in the absence of de novo protein synthesis, whereas a proximal element responds only to a combination of activin and bFGE Deletion experiments show that both elements are important for full induction by activin. Nuclear proteins that bind to these elements are expressed in blastula embryos, and competition experiments show that an octamer site in the activin responsive distal element is specifically bound, suggesting a role for an octamer binding factor in the regulation of goosecoid expression by activin. Experiments in intact embryos reveal that the proximal element contains sequences that respond to Xwnt1, but not to Xwnt5c. Furthermore, we show that the distal element is active in a confined dorsal domain in embryos and responds to overexpression of activin in vivo, as well as to dorsalization by lithium. The distal element is to our knowledge the first enhancer element identified that mediates the induction of a mesodermal gene by activin

DNA methylation dynamics during intestinal stem cell differentiation reveals enhancers driving gene expression in the villus

Background: DNA methylation is of pivotal importance during development. Previous genome-wide studies identified numerous differentially methylated regions upon differentiation of stem cells, many of them associated with transcriptional start sites. Results: We present the first genome-wide, single-base-resolution view into DNA methylation dynamics during differentiation of a mammalian epithelial stem cell: the mouse small intestinal Lgr5+ stem cell. Very little change was observed at transcriptional start sites and our data suggest that differentiation-related genes are already primed for expression in the stem cell. Genome-wide, only 50 differentially methylated regions were identified. Almost all of these loci represent enhancers driving gene expression in the differentiated part of the small intestine. Finally, we show that binding of the transcription factor Tcf4 correlates with hypo-methylation and demonstrate that Tcf4 is one of the factors contributing to formation of differentially methylated regions. Conclusions: Our results reveal limited DNA methylation dynamics during small intestine stem cell differentiation and an impact of transcription factor binding on shaping the DNA methylation landscape during differentiation of stem cells in vivo