Search

Vaccines work largely by generating long-lived plasma cells (LLPCs), but knowledge of how such cells are recruited is sparse. Although it is clear that LLPCs preferentially originate in germinal centers (GCs) and relocate to survival niches in bone marrow where they can persist for decades, the issues of the timing of LLPC recruitment and the basis of their retention remain uncertain. Here, using a genetic timestamping system in mice, we show that persistent PCs accrue in bone marrow at an approximately constant rate of one cell per hour over a period spanning several weeks after a single immunization with a model antigen. Affinity-based selection was evident in persisting PCs, reflecting a relative and dynamic rather than absolute affinity threshold as evidenced by the changing pattern of VHgene somatic mutations conveying increased affinity for antigen. We conclude that the life span of persistent, antigen-specific PCs is in part intrinsic, preprogrammed, and varied and that their final number is related to the duration of the response in a predictable way. This implies that modulating vaccines to extend the duration of the GC reaction will enhance antibody-mediated protective immunity.

Contains fulltext : 228242.pdf (Publisher’s version ) (Open Access) Drawing on the concept of a gale of creative destruction in a capitalistic economy, we argue that initiatives to assess the robustness of findings in the organizational literature should aim to simultaneously test competing ideas operating in the same theoretical space. In other words, replication efforts should seek not just to support or question the original findings, but also to replace them with revised, stronger theories with greater explanatory power. Achieving this will typically require adding new measures, conditions, and subject populations to research designs, in order to carry out conceptual tests of multiple theories in addition to directly replicating the original findings. To illustrate the value of the creative destruction approach for theory pruning in organizational scholarship, we describe recent replication initiatives re-examining culture and work morality, working parents’ reasoning about day care options, and gender discrimination in hiring decisions. Significance statement It is becoming increasingly clear that many, if not most, published research findings across scientific fields are not readily replicable when the same method is repeated. Although extremely valuable, failed replications risk leaving a theoretical void - reducing confidence the original theoretical prediction is true, but not replacing it with positive evidence in favor of an alternative theory. We introduce the creative destruction approach to replication, which combines theory pruning methods from the field of management with emerging best practices from the open science movement, with the aim of making replications as generative as possible. In effect, we advocate for a Replication 2.0 movement in which the goal shifts from checking on the reliability of past findings to actively engaging in competitive theory testing and theory building. Scientific transparency statement The materials, code, and data for this article are posted publicly on the Open Science Framework, with links provided in the article. 19 p.

Thermoelectric (TE) materials are increasingly promising for power generation in medium to high-temperature environments. Recent research on thermoelectric generators (TEGs) has determined the thermodynamic properties which impact the total efficiency and figure of merit (ZT) of these materials. A large Seebeck coefficient, high electrical conductivity and low thermal conductivity optimise ZT. This meta-study investigates silicides for potential TEG applications due to their high chemical stability and higher natural abundance than other TE materials. Data on the thermoelectric properties of CrSi2, FeSi2, Mg2Si and MnSi2, with a range of dopants, was sourced from a wide scope of literature and is analysed. The above thermodynamic properties contributing to ZT for each of these materials are graphed between 300 and 1000 K. It was found that chromium silicides are most effective at a temperature range of 600-800 K, and undoped magnesium silicides are most effective around 900 K. Oxide addition to β-FeSi2 produced relatively high ZT scores (ZT ≈ 0.5) among iron silicides. Rhenium substitution in manganese silicides produced a maximum figure of merit (1.05) at 900 K. Supersaturation via liquid quenching was determined to maintain high rhenium substitution and this technique may be the key to further improving the thermoelectric properties of other silicides.

Background Mass drug administration (MDA) of 20 mg/kg (maximum 1 g in adults) azithromycin for ocular Chlamydia trachomatis (CT) infection is a key component of the WHO trachoma elimination strategy. However, this dose may be suboptimal in Mycoplasma genitalium infection and may encourage emergence of antimicrobial resistance (AMR) to azithromycin. Objectives To determine the effect of MDA for trachoma elimination on M. genitalium prevalence, strain type and azithromycin resistance. Methods A secondary analysis of CT-negative vulvovaginal swabs from three outpatient antenatal clinics (Honiara, Solomon Islands) from patients recruited either pre-MDA, or 10 months post-MDA in two cross-sectional surveys was carried out. Swabs were tested for M. genitalium infection using Fast Track Diagnostics Urethritis Plus nucleic acid amplification assay. M. genitalium-positive samples were subsequently tested for azithromycin resistance by sequencing domain V of the 23S rRNA DNA region of M. genitalium and underwent phylogenetic analysis by dual locus sequence typing. Results M. genitalium prevalence was 11.9% (28/236) in women pre-MDA and 10.9% (28/256) 10 months post-MDA (p=0.7467). Self-reported receipt of azithromycin as part of MDA was 49.2% in women recruited post-MDA and 17.9% (5/28) in those who tested M. genitalium positive. Of samples sequenced (21/28 pre-MDA, 22/28 post-MDA), all showed a macrolide susceptible genotype. Strain typing showed that sequence types diverged into two lineages, with a suggestion of strain replacement post-MDA. Conclusion A single round of azithromycin MDA in an island population with high baseline M. genitalium prevalence did not appear to impact on either prevalence or azithromycin resistance, in contrast to reported decreased genital CT prevalence in the same population. This may be due to limitations such as sample size, including CT-negative samples only, and low MDA coverage. Further investigation of the impact of multiple rounds of MDA on M. genitalium azithromycin AMR in antibiotic experienced and naïve populations is warranted.

This thesis investigates ideological change in Melbourne's household water marketplace. Drawing from consumer culture theory, macromarketing, anti-consumption and social marketing literature, the research explored a paradigm shift that occurred in how individuals used and consumed water. Using a grounded theory approach, data collection involved historic secondary sources, newspaper articles, Google Trends, photographs, field notes as well as in-depth interviews with three groups of respondents. These respondents included seven experts from the water industry, three innovator consumers who used minimal mains water and 26 mainstream consumers who had made smaller but significant reductions in their water consumption. Analysis used constant comparing and contrasting, with a number of theories found to resonate with the developing frameworks. It emerged from the findings that the dominant social paradigm of the marketplace inhibited the use of alternative water sources to the mains water supply. However, severe drought was revealed to have provided a significant shock to the marketplace, which had shifted this paradigm. A metaphoric analysis enabled the research to uncover the innovators' cultural frames, and illustrated how the individual barriers the innovators had encountered, led to these respondents seeking to communicate solutions to the wider marketplace. Framing theory distilled how the innovators' alternative ideological frames resonated with collectives of mainstream consumers. From a macro perspective the findings illustrated how drought, law, education, public discourse and marketing, contributed to a reduction in the average household water consumption in Melbourne. The antecedents of the marketplace interplayed with one another to enable and reinforce this change in the dominant social paradigm. Contributing to transformative consumer research this study used theoretically driven research to solve practical problems.

Respiratory dysfunction is one of the leading causes of morbidity and mortality in the world and the rates of mortality continue to rise. Quantitative assessment of lung function in rodent models is an important tool in the development of future therapies. Commonly used techniques for assessing respiratory function including invasive plethysmography and forced oscillation. While these techniques provide valuable information, data collection can be fraught with artefacts and experimental variability due to the need for anesthesia and/or invasive instrumentation of the animal. In contrast, unrestrained whole-body plethysmography (UWBP) offers a precise, non-invasive, quantitative way by which to analyze respiratory parameters. This technique avoids the use of anesthesia and restraints, which is common to traditional plethysmography techniques. This video will demonstrate the UWBP procedure including the equipment set up, calibration and lung function recording. It will explain how to analyze the collected data, as well as identify experimental outliers and artefacts that results from animal movement. The respiratory parameters obtained using this technique include tidal volume, minute volume, inspiratory duty cycle, inspiratory flow rate and the ratio of inspiration time to expiration time. UWBP does not rely on specialized skills and is inexpensive to perform. A key feature of UWBP, and most appealing to potential users, is the ability to perform repeated measures of lung function on the same animal.

The dust disease in question, silicosis, cut a swathe through a generation of hardrock miners in Australia in the first quarter of this century. 2The problem reached a pitch at the end of the First World War as unions, State governments and employers, with varying degrees of enthusiasm, sought a solution to the depredations of silicosis. Ultimately the Commonwealth Government intervened to help tackle the problem. In 1921 it established an Industrial Hygiene Division (IHD) as part of its new Department of Health, initiating the Commonwealth's first foray into the field of occupational health.3 Although the Division was to cover the field of occupational health and safety in industry in general during the 1920s, there is little doubt that the initial reason for the establishment of the Division was to assist the States to tackle dust disease.