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Objectives: (1) To measure sound exposures of marching band and non-marching band students during a football game, (2) to compare these to sound level dose limits set by NIOSH, and (3) to assess the perceptions of marching band students about their hearing health risk from loud sound exposure and their use of hearing protection devices (HPDs). Methods: Personal noise dosimetry was completed on six marching band members and the band director during rehearsals and performances. Dosimetry measurements for two audience members were collected during the performances. Noise dose values were calculated using NIOSH criteria. One hundred twenty-three marching band members responded to a questionnaire analyzing perceptions of loud music exposure, the associated hearing health risks, and preventive behavior. Results: Noise dose values exceeded the NIOSH recommended limits among all six marching band members during rehearsals and performances. Higher sound levels were recorded during performances compared to rehearsals. The audience members were not exposed to hazardous levels. Most marching band members reported low concern for health effects from high sound exposure and minimal use of HPDs. Conclusion: High sound exposure and low concern regarding hearing health among marching band members reflect the need for comprehensive hearing conservation programs for this population.

Many animals have large visual fields, and sensory circuits may sample those regions of visual space most relevant to behaviours such as gaze stabilisation and hunting. Despite this, relatively small displays are often used in vision neuroscience. To sample stimulus locations across most of the visual field, we built a spherical stimulus arena with 14,848 independently controllable LEDs. We measured the optokinetic response gain of immobilised zebrafish larvae to stimuli of different steradian size and visual field locations. We find that the two eyes are less yoked than previously thought and that spatial frequency tuning is similar across visual field positions. However, zebrafish react most strongly to lateral, nearly equatorial stimuli, consistent with previously reported spatial densities of red, green, and blue photoreceptors. Upside-down experiments suggest further extra-retinal processing. Our results demonstrate that motion vision circuits in zebrafish are anisotropic, and preferentially monitor areas with putative behavioural relevance.

The pace of the global decarbonization process is widely believed to hinge on the rate of cost improvements for clean energy technologies, in particular renewable power and energy storage. This paper adopts the classical learning-by-doing framework of Wright (1936), which predicts that cost will fall as a function of the cumulative volume of past deployments. We first examine the learning curves for solar photovoltaic modules, wind turbines and electrolyzers. These estimates then become the basis for estimating the dynamics of the life-cycle cost of generating the corresponding clean energy, i.e., electricity from solar and wind power as well as hydrogen. Our calculations point to significant and sustained learning curves, which, in some contexts, predict a much more rapid cost decline than suggested by the traditional 80% learning curve. Finally, we argue that the observed learning curves for individual clean energy technologies reinforce each other in advancing the transition to a decarbonized energy economy.

Rationale Tuberculosis diagnosis in children remains challenging. Microbiological confirmation of tuberculosis disease is often lacking, and standard immunodiagnostic including the tuberculin skin test and interferon-γ release assay for tuberculosis infection has limited sensitivity. Recent research suggests that inclusion of novel Mycobacterium tuberculosis antigens has the potential to improve standard immunodiagnostic tests for tuberculosis. Objective To identify optimal antigen–cytokine combinations using novel Mycobacterium tuberculosis antigens and cytokine read-outs by machine learning algorithms to improve immunodiagnostic assays for tuberculosis. Methods A total of 80 children undergoing investigation of tuberculosis were included (15 confirmed tuberculosis disease, five unconfirmed tuberculosis disease, 28 tuberculosis infection and 32 unlikely tuberculosis). Whole blood was stimulated with 10 novel Mycobacterium tuberculosis antigens and a fusion protein of early secretory antigenic target (ESAT)-6 and culture filtrate protein (CFP) 10. Cytokines were measured using xMAP multiplex assays. Machine learning algorithms defined a discriminative classifier with performance measured using area under the receiver operating characteristics. Measurements and main results We found the following four antigen–cytokine pairs had a higher weight in the discriminative classifier compared to the standard ESAT-6/CFP-10-induced interferon-γ: Rv2346/47c- and Rv3614/15c-induced interferon-gamma inducible protein-10; Rv2031c-induced granulocyte-macrophage colony-stimulating factor and ESAT-6/CFP-10-induced tumor necrosis factor-α. A combination of the 10 best antigen–cytokine pairs resulted in area under the curve of 0.92 ± 0.04. Conclusion We exploited the use of machine learning algorithms as a key tool to evaluate large immunological datasets. This identified several antigen–cytokine pairs with the potential to improve immunodiagnostic tests for tuberculosis in children.

Introduction Congenital heart surgery with cardiopulmonary bypass (CPB) initiates an immune response which frequently leads to organ dysfunction and a systemic inflammatory response. Complications associated with exacerbated immune responses may severely impact the postoperative recovery. The objective was to describe the characteristics of monocyte subpopulations and neutrophils at the level of pattern recognition receptors (PRR) and the cytokine response after CPB in infants. Methods An observational cohort study was conducted between June 2016 and June 2017 of infants Results Samples from 21 infants (median age 7.4 months) were analyzed by flow cytometry and from 11 infants, cytokine concentrations were measured. Classical and intermediate monocytes showed first receptor upregulation with an increase in CD64 expression four hours post CPB. CD64–expression on intermediate monocytes almost tripled 48 h post CPB (p TLR4 expression on intermediate monocytes correlated with vasoactive-inotropic score (rs = 0.642, p = 0.0017), duration of ventilation (rs = 0.485, p = 0.0259), highest serum creatinine (rs = 0.547, p = 0.0102), postsurgical transfusion (total volume per kg bodyweight) (rs = 0.469, p = 0.0321) and lowest mean arterial pressure (rs = -0.530, p = 0.0135). Concentrations of IL-10, MIP-1β, IL-8, G–CSF and IL-6 increased one hour post CPB. Methylprednisolone administration in six patients had no significant influence on the studied surface receptors but led to lower IL-8 and higher IL-10 plasma concentrations. Conclusions Congenital heart surgery with CPB induces a systemic inflammatory process including cytokine response and changes in PRR expression. Intermediate monocytes feature specific inflammatory characteristics in the 48 h after pediatric CPB and TLR4 correlates with poorer clinical course, which might provide a potential diagnostic or even therapeutic target.

Many animals have large visual fields, and sensory circuits may sample those regions of visual space most relevant to behaviours such as gaze stabilisation and hunting. Despite this, relatively small displays are often used in vision neuroscience. To sample stimulus locations across most of the visual field, we built a spherical stimulus arena with 14,848 independently controllable LEDs, measured the optokinetic response gain of immobilised zebrafish larvae, and related behaviour to previously published retinal photoreceptor densities. We measured tuning to steradian stimulus size and spatial frequency, and show it to be independent of visual field position. However, zebrafish react most strongly and consistently to lateral, nearly equatorial stimuli, consistent with previously reported higher spatial densities in the central retina of red, green and blue photoreceptors. Upside-down experiments suggest further extra-retinal processing. Our results demonstrate that motion vision circuits in zebrafish are anisotropic, and preferentially monitor areas with putative behavioural relevance.Author summaryThe visual system of larval zebrafish mirrors many features present in the visual system of other vertebrates, including its ability to mediate optomotor and optokinetic behaviour. Although the presence of such behaviours and some of the underlying neural correlates have been firmly established, previous experiments did not consider the large visual field of zebrafish, which covers more than 160° for each eye. Given that different parts of the visual field likely carry unequal amount of behaviourally relevant information for the animal, this raises the question whether optic flow is integrated across the entire visual field or just parts of it, and how this shapes behaviour such as the optokinetic response. We constructed a spherical LED arena to present visual stimuli almost anywhere across their visual field, while tracking horizontal eye movements. By displaying moving gratings on this LED arena, we demonstrate that the optokinetic response, one of the most prominent visually induced behaviours of zebrafish, indeed strongly depends on stimulus location and stimulus size, as well as on other parameters such as the spatial and temporal frequency of the gratings. This location dependence is consistent with areas of high retinal photoreceptor densities, though evidence suggests further extraretinal processing.

Background: Current immunodiagnostic tests for tuberculosis (TB) are based on the detection of an immune response toward mycobacterial antigens injected into the skin or following an in-vitro simulation in interferon gamma-release assays. Both tests have limited sensitivity and are unable to differentiate between tuberculosis infection (LTBI) and active tuberculosis disease (aTB). To overcome this, the use of novel Mycobacterium tuberculosis (M. tuberculosis) stage-specific antigens for the diagnosis of LTBI and aTB has gained interest in recent years. This review summarizes current evidence on novel antigens used for the immunodiagnosis of tuberculosis and discrimination of LTBI and aTB. In addition, results on measured biomarkers after stimulation with novel M. tuberculosis antigens were also reviewed. Methods: A systematic literature review was performed in Pubmed, EMBASE and web of science searching articles from 2000 up until December 2017. Only articles reporting studies in humans using novel antigens were included. Results: Of 1,533 articles screened 34 were included in the final analysis. A wide range of novel antigens expressed during different stages and types of LTBI and aTB have been assessed. M. tuberculosis antigens Rv0081, Rv1733c, Rv1737c, Rv2029c, Rv2031 and Rv2628, all encoded by the dormancy of survival regulon, were among the most widely studied antigens and showed the most promising results. These antigens have been shown to have best potential for differentiating LTBI from aTB. In addition, several studies have shown that the inclusion of cytokines other than IFN-γ can improve sensitivity. Conclusion: There is limited evidence that the inclusion of novel antigens as well as the measurement of other biomarkers than IFN-γ may improve sensitivity and may lead to a discrimination of LTBI from aTB.

The impact of the introduction and advancement in communication technology in recent years on exposure level of the population is largely unknown. The main aim of this study is to systematically review literature on the distribution of radiofrequency electromagnetic field (RF-EMF) exposure in the everyday environment in Europe and summarize key characteristics of various types of RF-EMF studies conducted in the European countries. We systematically searched the ISI Web of Science for relevant literature published between 1 January 2000 and 30 April 2015, which assessed RF-EMF exposure levels by any of the methods: spot measurements, personal measurement with trained researchers and personal measurement with volunteers. Twenty-one published studies met our eligibility criteria of which 10 were spot measurements studies, 5 were personal measurement studies with trained researchers (microenvironmental), 5 were personal measurement studies with volunteers and 1 was a mixed methods study combining data collected by volunteers and trained researchers. RF-EMF data included in the studies were collected between 2005 and 2013. The mean total RF-EMF exposure for spot measurements in European "Homes" and "Outdoor" microenvironments was 0.29 and 0.54 V/m, respectively. In the personal measurements studies with trained researchers, the mean total RF-EMF exposure was 0.24 V/m in "Home" and 0.76 V/m in "Outdoor". In the personal measurement studies with volunteers, the population weighted mean total RF-EMF exposure was 0.16 V/m in "Homes" and 0.20 V/m in "Outdoor". Among all European microenvironments in "Transportation", the highest mean total RF-EMF 1.96 V/m was found in trains of Belgium during 2007 where more than 95% of exposure was contributed by uplink. Typical RF-EMF exposure levels are substantially below regulatory limits. We found considerable differences between studies according to the type of measurements procedures, which precludes cross-country comparison or evaluating temporal trends. A comparable RF-EMF monitoring concept is needed to accurately identify typical RF-EMF exposure levels in the everyday environment.

Previous studies of thelurchermutation in GluR1 channels concluded that its main effect is to create constitutively active channels (Kohda et al., 2000; Taverna et al., 2000). GluR1Lc channels also exhibit slowed kinetics and a shift in their apparent affinity for glutamate (Kohda et al., 2000; Taverna et al., 2000). Here, we have undertaken a kinetic analysis of GluR1Lc channels to quantify the effects oflurcherand to determine the relative contribution of these effects to thelurcherphenotype. Analysis of GluR1Lc leak current demonstrated that the 2,3-dioxo-6-nitro-1,2,3,4-tetrahydro[f]quinoxaline-7-sulfonamide (NBQX)-sensitive portion of the leak current corresponded to a current generated by glutamate concentrations similar to the levels of contaminating glutamate measured in our normal external solutions. This result, and the small size of the leak current relative to the currents evoked by saturating glutamate, indicates that GluR1Lc channels exhibit little or no constitutive activity. Our results indicate that the primary effect of thelurchermutation is to increase the affinity of GluR1 for glutamate and reduce the desensitization of GluR1 at nanomolar concentrations. We also found that the mutation makes both the rate and extent of GluR1Lc channel desensitization depend strongly on subunit occupancy. We conclude that the poor survival of GluR1Lc-transfected cells, and presumably cerebellar neurons inlurchermice, results because channels carrying thelurchermutation open and do not desensitize at ambient levels of glutamate.

International audience; BACKGROUND: Recurrent bacterial and fungal infections, eczema, and increased serum IgE levels characterize patients with the hyper-IgE syndrome (HIES). Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. However, glycosylation defects have not been described in patients with HIES. One crucial enzyme in the glycosylation pathway is phosphoglucomutase 3 (PGM3), which catalyzes a key step in the synthesis of uridine diphosphate N-acetylglucosamine, which is required for the biosynthesis of N-glycans. OBJECTIVE: We sought to elucidate the genetic cause in patients with HIES who do not carry mutations in STAT3 or DOCK8. METHODS: After establishing a linkage interval by means of SNPchip genotyping and homozygosity mapping in 2 families with HIES from Tunisia, mutational analysis was performed with selector-based, high-throughput sequencing. Protein expression was analyzed by means of Western blotting, and glycosylation was profiled by using mass spectrometry. RESULTS: Mutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families identified 2 homozygous mutations in PGM3 that segregated with disease status and followed recessive inheritance. The mutations predict amino acid changes in PGM3 (p.Glu340del and p.Leu83Ser). A third homozygous mutation (p.Asp502Tyr) and the p.Leu83Ser variant were identified in 2 other affected families, respectively. These hypomorphic mutations have an effect on the biosynthetic reactions involving uridine diphosphate N-acetylglucosamine. Glycomic analysis revealed an aberrant glycosylation pattern in leukocytes demonstrated by a reduced level of tri-antennary and tetra-antennary N-glycans. T-cell proliferation and differentiation were impaired in patients. Most patients had developmental delay, and many had psychomotor retardation. CONCLUSION: Impairment of PGM3 function leads to a novel primary (inborn) error of development and immunity because biallelic hypomorphic mutations are associated with impaired glycosylation and a hyper-IgE-like phenotype.

Report describing the role of phosphates in the overall economy of the yeast cell. This report includes research methods, results, and a discussion of these results.

Magnesium was determined on aliquots of the same serum by atomic absorption and flame emission spectrophotometry, by Titan Yellow and Magon photometry, and by 8-hydroxy-quinoline and 8-hydroxy-quinoline-sulfonate fluorometry. Comparison is presented of reproducibility of results by the various methods and of the normal values obtained.