Autoantibody subclass predominance is not driven by aberrant class switching or impaired B cell development

A subset of autoimmune diseases is characterized by predominant pathogenic IgG4 autoantibodies (IgG4-AID). Why IgG4 predominates in these disorders is unknown. We hypothesized that dysregulated B cell maturation or aberrant class switching causes overrepresentation of IgG4+ B cells and plasma cells. Therefore, we compared the B cell compartment of patients from four different IgG4-AID with two IgG1-3-AID and healthy donors, using flow cytometry. Relative subset abundance at all maturation stages was normal, except for a, possibly treatment-related, reduction in immature and naïve CD5+ cells. IgG4+ B cell and plasma cell numbers were normal in IgG4-AID patients, however they had a (sub)class-independent 8-fold increase in circulating CD20-CD138+ cells. No autoreactivity was found in this subset. These results argue against aberrant B cell development and rather suggest the autoantibody subclass predominance to be antigen-driven. The similarities between IgG4-AID suggest that, despite displaying variable clinical phenotypes, they share a similar underlying immune profile.</p

Still dreaming: service users' employment, education & training goals

Background: Enabling service users to find and keep real jobs is a significant strand of UK mental health policy. An evidence-based approach to employment support is well documented, but is not widely implemented in the UK. Aim: To inform the development of vocational services in South Essex by ascertaining service users' employment, education and training goals. Method: Face-to-face interviews with a randomly selected sample of service users on enhanced CPA carried out by a team of service user researchers using an adapted version of a questionnaire developed for a previous similar survey. A postal survey of a further randomly selected sample of service users on enhanced CPA using a brief version of the questionnaire was also carried out. Results: Interviews were carried out with 82 service users. A further 159 returned a postal questionnaire. 42.7% had no regular day time activity. Only 15% were in paid work. 60.6% were definitely interested in finding work. Seventy-seven percent of respondents to the interviews who were interested in work were not currently receiving support to achieve this. The main help wanted was support in work, help with mental health problems and benefits advice. The main barriers identified were employers' attitudes and threat to benefits. Service user researchers reported benefits from undertaking the work. Conclusions: High numbers of mental health service users are interested in pursuing employment, education or training goals but currently lack the support they need to do so. Implementation of an evidence-based approach to employment support has the potential to enable service users to achieve their goals. Service users are well able to undertake research with considerable benefits for themselves and other stakeholders

Impact of pre-analytical and analytical variables associated with sample preparation on flow cytometric stainings obtained with EuroFlow panels

Objective interpretation of FC results may still be hampered by limited technical standardization. The EuroFlow consortium conducted a series of experiments to determine the impact of different variables on the relative distribution and the median fluorescence intensity (MFI) of markers stained on different cell populations, from both healthy donors and patients’ samples with distinct hematological malignancies. The use of different anticoagulants; the time interval between sample collection, preparation, and acquisition; pH of washing buffers; and the use of cell surface membrane-only (SM) vs. cell surface plus intracytoplasmic (SM+CY) staining protocols, were evaluated. Our results showed that only monocytes were represented at higher percentages in EDTA- vs. heparin-anticoagulated samples. Application of SM or SM+CY protocols resulted in slight differences in the percentage of neutrophils and debris determined only with particular antibody combinations. In turn, storage of samples for 24 h at RT was associated with greater percentage of debris and cell doublets when the plasma cell disorder panel was used. Furthermore, 24 h storage of stained cells at RT was selectively detrimental for MFI levels of CD19 and CD45 on mature B- and T-cells (but not on leukemic blasts, clonal B- and plasma cells, neutrophils, and NK cells). The obtained results showed that the variables evaluated might need to be tailored for sample and cell type(s) as well as to the specific markers compared; however, defining of well-balanced boundaries for storage time, staining-to-acquisition delay, and pH of washing buffer would be a valid recommendation for most applications and circumstances described herein.This research was funded by the EuroFlow Consortium which received support from the FP6-2004-LIFESCIHEALTH-5 program of the European Commission (grant LSHB-CT-2006-018708) as Specific Targeted Research Project (STREP). The EuroFlow Consortium is part of the European Scientific Foundation for Hemato-Oncology (ESLHO), a Scientific Working Group (SWG) of the European Hematology Association (EHA); the grant of the Polish National Center for Research and Development (no. STRATEGMED3/304586/5/NCBR/2017 Person ALL); and internal grant of the Medical University of Silesia (no. PCN-1-050/K/0/K); the grant of CIBER-ONC, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain and FONDOS FEDER (no. CB16/12/00400)

Reducing Legionella Colonization of Water Systems with Monochloramine

Monochloramine reduced colonization in building hot water systems

Differences between urban and rural hedges in England revealed by a citizen science project

Background: Hedges are oth ecologically and culturally important and are a distinctive feature of the British landscape. However the overall length of hedges across Great Britain is decreasing. Current challenges in studying hedges relate to the dominance of research on rural, as opposed to urban, hedges, and their variability and geographical breadth. To help address these challenges and to educate the public on the importance of hedge habitats for wildlife, in 2010 the Open Air Laboratories (OPAL) programme coordinated a hedge-focused citizen science survey. Results: Results from 2891 surveys were analysed. Woody plant species differed significantly between urban and rural areas. Beech, Holly, Ivy, Laurel, Privet and Yew were more commonly recorded in urban hedges whereas Blackthorn, Bramble, Dog Rose, Elder and Hawthorn were recorded more often in rural hedges. Urban and rural differences were shown for some groups of invertebrates. Ants, earwigs and shieldbugs were recorded more frequently in urban hedges whereas blowflies, caterpillars, harvestmen, other beetles, spiders and weevils were recorded more frequently in rural hedges. Spiders were the most frequently recorded invertebrate across all surveys. The presence of hard surfaces adjacent to the hedge was influential on hedge structure, number and diversity of plant species, amount of food available for wildlife and invertebrate number and diversity. In urban hedges with one adjacent hard surface, the food available for wildlife was significantly reduced and in rural hedges, one adjacent hard surface affected the diversity of invertebrates. Conclusions: This research highlights that urban hedges may be important habitats for wildlife and that hard surfaces may have an impact on both the number and diversity of plant species and the number and diversity of invertebrates. This study demonstrates that citizen science programmes that focus on hedge surveillance can work and have the added benefit of educating the public on the importance of hedgerow habitats