Display of antigens on polyester inclusions lowers the antigen concentration required for a bovine tuberculosis skin test

The tuberculin skin test is the primary screening test for the diagnosis of bovine tuberculosis (TB), and use of this test has been very valuable in the control of this disease in many countries. However, the test lacks specificity when cattle have been exposed to environmental mycobacteria or vaccinated with Mycobacterium bovis bacille Calmette-Guérin (BCG). Recent studies showed that the use of three or four recombinant mycobacterial proteins, including 6-kDa early secretory antigenic target (ESAT6), 10-kDa culture filtrate protein (CFP10), Rv3615c, and Rv3020c, or a peptide cocktail derived from those proteins, in the skin test greatly enhanced test specificity, with minimal loss of test sensitivity. The proteins are present in members of the pathogenic Mycobacterium tuberculosis complex but are absent in or not expressed by the majority of environmental mycobacteria and the BCG vaccine strain. To produce a low-cost skin test reagent, the proteins were displayed at high density on polyester beads through translational fusion to a polyhydroxyalkanoate synthase that mediates the formation of antigen-displaying inclusions in recombinant Escherichia coli. Display of the proteins on the polyester beads greatly increased their immunogenicity, allowing for the use of very low concentrations of proteins (0.1 to 3 μg of mycobacterial protein/inoculum) in the skin test. Polyester beads simultaneously displaying all four proteins were produced in a single fermentation process. The polyester beads displaying three or four mycobacterial proteins were shown to have high sensitivity for detection of M. bovis-infected cattle and induced minimal responses in animals exposed to environmental mycobacteria or vaccinated with BCG.Full Tex

The End Justifies the Means? The Impact of the ECB's Unconventional Monetary Policy on Citizens' Trust

Since 2010, the European Central Bank (ECB) has established a range of unconventional monetary policies in the context of several crises, including cheap and long-term refinancing operations and several forms of asset purchases. This ECB action has been legally and politically challenged, raising the question as to how the public has perceived the ECB's mandate widening. This article assesses the legitimacy of the ECB's unconventional monetary policy through the lens of public trust using Eurobarometer data from 1999 to 2023. This approach follows the theoretical argument that the legitimacy of non-elected independent public institutions derives from the citizens' trust in the fulfilment of the institutions' tasks. Through panel regression analysis, this article first finds that trust in the ECB is commonly pooled with trust in other EU institutions, which makes a singular assessment of public support of the ECB and its policies difficult. Second, macroeconomic factors, which are partially influenced by ECB policies, but which are mostly dependent on national decision-making, are the key factors influencing citizens' trust in EU institutions, including the ECB. Thus, citizens' trust in the ECB or the lack thereof is not determined by the ECB's use of contested unconventional monetary policy, but rather by the macroeconomic performance of their respective national economy

The Effectiveness of Alcohol Screening and Brief Intervention in Emergency Departments: A Multicentre Pragmatic Cluster Randomized Controlled Trial

BACKGROUND: Alcohol misuse is common in people attending emergency departments (EDs) and there is some evidence of efficacy of alcohol screening and brief interventions (SBI). This study investigated the effectiveness of SBI approaches of different intensities delivered by ED staff in nine typical EDs in England: the SIPS ED trial. METHODS AND FINDINGS: Pragmatic multicentre cluster randomized controlled trial of SBI for hazardous and harmful drinkers presenting to ED. Nine EDs were randomized to three conditions: a patient information leaflet (PIL), 5 minutes of brief advice (BA), and referral to an alcohol health worker who provided 20 minutes of brief lifestyle counseling (BLC). The primary outcome measure was the Alcohol Use Disorders Identification Test (AUDIT) status at 6 months. Of 5899 patients aged 18 or more presenting to EDs, 3737 (63·3%) were eligible to participate and 1497 (40·1%) screened positive for hazardous or harmful drinking, of whom 1204 (80·4%) gave consent to participate in the trial. Follow up rates were 72% (n?=?863) at six, and 67% (n?=?810) at 12 months. There was no evidence of any differences between intervention conditions for AUDIT status or any other outcome measures at months 6 or 12 in an intention to treat analysis. At month 6, compared to the PIL group, the odds ratio of being AUDIT negative for brief advice was 1·103 (95% CI 0·328 to 3·715). The odds ratio comparing BLC to PIL was 1·247 (95% CI 0·315 to 4·939). A per protocol analysis confirmed these findings. CONCLUSIONS: SBI is difficult to implement in typical EDs. The results do not support widespread implementation of alcohol SBI in ED beyond screening followed by simple clinical feedback and alcohol information, which is likely to be easier and less expensive to implement than more complex interventions

Effects of Hierarchical Levels on Social Network Structures within Communities of Learning

Facilitating an interpersonal knowledge transfer among employees constitutes a key building block in setting up organizational training initiatives. With practitioners and researchers looking for innovative training methods, online Communities of Learning (CoL) have been promoted as a promising methodology to foster this kind of transfer. However, past research has only provided limited data from actual organizations and largely neglected characteristics that constitute a major obstacle to such collaborative processes, namely participants’ hierarchical levels. The current study addresses these shortcomings by providing empirical evidence from 25 CoL of an online training program, provided for 249 staff members of a global organization. Using social network analysis, we are able to show significant differences in participants’ network behaviour and position based on their hierarchical rank. This translates into higher in- and out-degree network ties, as well as centrality scores among participants from higher up the hierarchical ladder. Finally, based on a longitudinal analysis of all indicated network measures, our results indicate that the main trend develops predominately during the first half of the training program. By incorporating these insights into the implementation of future CoL, it is not only possible to anticipate participants’ behaviour. Our findings also allow to draw conclusions about how collaborative activities within CoL should be designed and facilitated, in order to provide participants with a valuable learning experience