The V_H repertoire and clonal diversification of B cells in inflammatory myopathies

The contribution of antigen-driven B-cell adaptive immune responses within the inflamed muscle of inflammatory myopathies (IMs) is largely unknown. In this study, we investigated the immunoglobulin VH gene repertoire, somatic hypermutation, clonal diversification, and selection of infiltrating B cells in muscle biopsies from IM patients (dermatomyositis and polymyositis), to determine whether B cells and/or plasma cells contribute to the associated pathologies of these diseases. The data reveal that Ig V<sub>H</sub> gene repertoires of muscle-infiltrating B cells deviate from the normal VH gene repertoire in individual patients, and differ between different types of IMs. Analysis of somatic mutations revealed clonal diversification of muscle-infiltrating B cells and evidence for a chronic B-cell response within the inflamed muscle. We conclude that muscle-infiltrating B cells undergo selection, somatic hypermutation and clonal diversification in situ during antigen-driven immune responses in patients with IMs, providing insight into the contribution of B cells to the pathological mechanisms of these disorders

Letter to the Editor: Clotting Profiles and Coagulation Factors

We aimed to test the hypothesis that if a coagulation profile specimen clots then the patient's clotting profile must be normal

Effects of Friction on the Dynamic Behavior of Flexible Rocking Bodies

Flexible rocking bodies are freestanding structures that are free to deform and rock, potentially overturning, when subject to ground excitation. Prior research on the seismic behavior of this type of structure typically assumed sufficient friction at the ground surface to avoid sliding motion. However, experimental observations showed that this assumption was often violated and structures demonstrated non-negligible sliding during their responses. The overarching goal of this study is to evaluate the impact of sliding on the overturning response of flexible rocking bodies. To this end, a two-dimensional analytical model was developed in a Lagrangian formulation, which is presented in this paper. This model was subjected to one-cycle sine pulses of varying amplitude and frequency for several levels of base friction to quantify the impact of sliding on overturning. In general, the results highlight that sliding behavior reduces the overturning demand, however motion-to-motion variability was observed

The Effect Of Draw-Up Volume On The Accuracy Of Electrolyte Measurements From Neonatal Arterial Lines

Objectives: Contamination by infusate of blood samples withdrawn from arterial lines has been recognized but not well documented for neonates. The aim of this study was to investigate, using in vitro and in vivo studies, the effects of different draw-up volumes (withdrawn from the line prior to the sample being taken) on the concentration of sodium. Methods: In-vitro study: The tip of an umbilical artery catheter (dead space 0.6 mL), infused with half normal saline containing 1 unit/mL of heparin was placed in a beaker of normal saline. The line was flushed with 1 mL of this infusate just before each sample was taken. Volumes from 0.5 mL to 2.0 mL of infusate/normal saline were withdrawn in 0.1 mL increments from a three-way tap and discarded. A sample was then taken from the line into a blood gas syringe for analysis of the sodium concentration by the 860 Blood Gas Analyzer (Chiron Diagnostics, Bayer, Scoresby). Control samples were taken from the beaker. In-vivo study: A 22 gauge intravenous catheter was inserted into a vein of an adult male volunteer. The dead space was also 0.6 mL. The line was flushed with 5 mL of half-normal saline immediately before sampling. Draw-up volumes of 0.6, 0.9, 1.3, and 1.6 mL were withdrawn and discarded. 10 mL was used as a control. A 0.5-mL blood sample was then taken and the electrolyte concentrations analysed immediately. Results: In-vitro: A minimum draw-up volume of 1.3 mL was required before the sodium concentration was not significantly different from the control samples. In-vivo: A minimum draw-up volume of 1.6 mL was required before the sodium concentration was not significantly different from the control samples. There were similar trends in the effect of draw-up volume for glucose, calcium, potassium, chloride and lactate. Conclusion: A minimum volume of 1.6 mL should be withdrawn from neonatal arterial lines (dead space 0.6 mL) before taking blood for analysi

The importance of place and authenticity in adaptive reuse of heritage buildings

© 2020, Emerald Publishing Limited. Purpose: In adaptive reuse, the importance of place referred to as “genius loci,” whereas authenticity refers to the design, materials, setting and workmanship of a building or place. Genius loci and authenticity are crucial evolving interconnected concepts; however, the concepts are usually studied separately, and consequently, overlooked in adaptive reuse practice. This paper provides precise definitions and a holistic understanding of these terms and discusses complications related to the understanding of the concepts in the adaptive reuse of heritage buildings. Design/methodology/approach: Content analysis is an acknowledged way of analysing information related to a subject area and allows researchers to provide new insights and knowledge in a particular area. This paper applies a critical content analysis of published works related to genius loci and authenticity over time. Findings: The findings show the inter-relationship of genius loci and authenticity, and how these concepts can be considered in the adaptive reuse of heritage buildings, in theory and in practice. Consequently, a checklist is proposed to enable all interested parties engaged with the adaptive reuse of heritage buildings to identify and preserve genius loci and authenticity. Originality/value: Identity and values of heritage buildings are argued to be the strongest reasons for adaptation. Amongst a wide range of values associated with the adaptive reuse of heritage buildings, place and authenticity are perceived to be the most confusing terms and concepts. Whilst place and authenticity are defined by many authors, their meaning and usage are subjective, which is a challenge in recognising and preserving the values they embody. This study contributes to the greater understanding of these concepts, their meanings and application in adaptive reuse

Two Randomized Trials Provide No Consistent Evidence for Nonmusical Cognitive Benefits of Brief Preschool Music Enrichment

Young children regularly engage in musical activities, but the effects of early music education on children’s cognitive development are unknown. While some studies have found associations between musical training in childhood and later nonmusical cognitive outcomes, few randomized controlled trials (RCTs) have been employed to assess causal effects of music lessons on child cognition and no clear pattern of results has emerged. We conducted two RCTs  with preschool children investigating the cognitive effects of a brief series of music classes, as  compared to a similar but non-musical form of arts instruction (visual arts classes, Experiment 1) or to a no-treatment control (Experiment 2). Consistent with typical preschool arts enrichment programs, parents attended classes with their children, participating in a variety of developmentally appropriate arts activities. After six weeks of class, we assessed children’s skills  in four distinct cognitive areas in which older arts-trained students have been reported to excel: spatial-navigational reasoning, visual form analysis, numerical discrimination, and receptive vocabulary. We initially found that children from the music class showed greater spatial-navigational ability than did children from the visual arts class, while children from the visual arts class showed greater visual form analysis ability than children from the music class (Experiment 1). However, a partial replication attempt comparing music training to a no-treatment control failed to confirm these findings (Experiment 2), and the combined results of  the two experiments were negative: overall, children provided with music classes performed no better than those with visual arts or no classes on any assessment. Our findings underscore the need for replication in RCTs, and suggest caution in interpreting the positive findings from past studies of cognitive effects of music instruction.Psycholog

Techno-economic assessment of biogas-fed CHP hybrid systems in a real wastewater treatment plant

The integration of solid oxide fuel cell (SOFC) systems and micro gas turbines in a reference wastewater treatment plant is proposed. The main scope is to utilize the available biogas in a real wastewater treat- ment plant (WWTP) to feed both the SOFCs and micro gas turbines (MGTs) to produce electrical power while covering the digester thermal demand of the plant. To do so, two cases namely SOFC-WWTP (in which the SOFC system is the only CHP unit), and SOFC-MGT-WWTP (integration of both SOFCs and microturbine systems) are proposed. Results show that use of microturbines along with the SOFC systems can increase the share of electricity covered by self-generation within the WWTP by up to 15% while keeping stable the coverage of the thermal load. Also, the energy efficiency of the novel system (SOFC- MGT-WWTP) is calculated to be 7% more than that of the SOFC-WWTP. Economic analysis results reveal that using microturbines, the payback time for whole the system could be reduced about 4 years. Also, for the short term scenario, the levelized cost of electricity for the SOFC-MGT-WWTP system is found to be 0.118 $/kWh which is about 12% less than that for the SOFC-WWTP system. However, for the long term scenario, the difference becomes remarkably les

MHC-Linked Syngeneic Developmental Preference in Thymic Lobes Colonized with Bone Marrow Cells: A Mathematical model

Reconstitution of the T-cell compartment after bone marrow transplantation depends on successful colonization of the thymus by bone-marrow-derived progenitor cells. Recent studies compared the development of syngeneic and allogeneic bone-marrow-derived cells in cocultures with lymphoid-depleted fetal thymus explants, leading to the discovery of MHC-linked syngeneic developmental preference (SDP) in the thymus. To determine the nature of cell interactions among the bone marrow and thymic elements that might underlie SDP, we analyzed this phenomenon by mathematical modeling. The results indicate that syngeneic mature T cells, responsible for inducing this preference, probably interfere both with the seeding of allogeneic bone-marrow-derived thymocyte progenitors in the thymic stroma and with their subsequent proliferation. In addition, the possibility of augmented death among the developing allogeneic thymocytes cannot be ruled out

Immunoglobulin variable-region gene mutational lineage tree analysis: application to autoimmune diseases

Lineage trees have frequently been drawn to illustrate diversification, via somatic hypermutation (SHM), of immunoglobulin variable-region (IGV) genes. In order to extract more information from IGV sequences, we developed a novel mathematical method for analyzing the graphical properties of IgV gene lineage trees, allowing quantification of the differences between the dynamics of SHM and antigen-driven selection in different lymphoid tissues, species, and disease situations. Here, we investigated trees generated from published IGV sequence data from B cell clones participating in autoimmune responses in patients with Myasthenia Gravis (MG), Rheumatoid Arthritis (RA), and Sjögren's Syndrome (SS). At present, as no standards exist for cell sampling and sequence extraction methods, data obtained by different research groups from two studies of the same disease often vary considerably. Nevertheless, based on comparisons of data groups within individual studies, we show here that lineage trees from different individual patients are often similar and can be grouped together, as can trees from two different tissues in the same patient, and even from IgG- and IgA-expressing B cell clones. Additionally, lineage trees from most studies reflect the chronic character of autoimmune diseases