Neutrophils from p40phox−/− mice exhibit severe defects in NADPH oxidase regulation and oxidant-dependent bacterial killing

The generation of reactive oxygen species (ROS) by the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex plays a critical role in the antimicrobial functions of the phagocytic cells of the immune system. The catalytic core of this oxidase consists of a complex between gp91phox, p22phox, p47phox, p67phox, p40phox, and rac-2. Mutations in each of the phox components, except p40phox, have been described in cases of chronic granulomatous disease (CGD), defining their essential role in oxidase function. We sought to establish the role of p40phox by investigating the NADPH oxidase responses of neutrophils isolated from p40phox−/− mice. In the absence of p40phox, the expression of p67phox is reduced by ∼55% and oxidase responses to tumor necrosis factor α/fibrinogen, immunoglobulin G latex beads, Staphylococcus aureus, formyl-methionyl-leucyl-phenylalanine, and zymosan were reduced by ∼97, 85, 84, 75, and 30%, respectively. The defect in ROS production by p40phox−/− neutrophils in response to S. aureus translated into a severe, CGD-like defect in the killing of this organism both in vitro and in vivo, defining p40phox as an essential component in bacterial killing

Investigation of a Neuronal Nitric Oxide Synthase Gene (NOS1) Polymorphism in a Multiple Sclerosis Population

Multiple Sclerosis (MS) is a chronic neurological disease characterized by demyelination associated with infiltrating white blood cells in the central nervous system (CNS). Nitric oxide synthases (NOS) are a family of enzymes that control the production of nitric oxide. It is possible that neuronal NOS could be involved in MS pathophysiology and hence the nNOS gene is a potential candidate for involvement in disease susceptibility. The aim of this study was to determine whether allelic variation at the nNOS gene locus is associated with MS in an Australian cohort. DNA samples obtained from a Caucasian Australian population affected with MS and an unaffected control population, matched for gender, age and ethnicity, were genotyped for a microsatellite polymorphism in the promoter region of the nNOS gene. Allele frequencies were compared using chi-squared based statistical analyses with significance tested by Monte Carlo simulation. Allelic analysis of MS cases and controls produced a chi-squared value of 5.63 with simulated P=0.96 (OR(max)=1.41, 95% CI: 0.926-2.15). Similarly, a Mann-Whitney U analysis gave a non-significant P-value of 0.377 for allele distribution. No differences in allele frequencies were observed for gender or clinical course subtype (P>0.05). Statistical analysis indicated that there is no association of this nNOS variant and MS and hence the gene does not appear to play a genetically significant role in disease susceptibility

An agenda for creative practice in the new mobilities paradigm

Creative practices have made a standing contribution to mobilities research. We write this article as a collective of 25 scholars and practitioners to make a provocation: to further position creative mobilities research as a fundamental contribution and component in this field. The article explores how creative forms of research—whether in the form of artworks, exhibitions, performances, collaborations, and more—has been a foundational part of shaping the new mobilities paradigm, and continues to influence its methodological, epistemological, and ontological concerns. We tour through the interwoven history of art and mobilities research, outlining five central contributions that creativity brings. Through short vignettes of each author’s creative practice, we discuss how creativity has been key to the evolution and emergence of how mobilities research has expanded to global audiences of scholars, practitioners, and communities. The article concludes by highlighting the potency of the arts for lively and transdisciplinary pathways for future mobilities research in the uncertainties that lay ahead

Fatal Cases of Influenza A(H3N2) in Children: Insights from Whole Genome Sequence Analysis

During the Northern Hemisphere winter of 2003–2004 the emergence of a novel influenza antigenic variant, A/Fujian/411/2002-like(H3N2), was associated with an unusually high number of fatalities in children. Seventeen fatal cases in the UK were laboratory confirmed for Fujian/411-like viruses. To look for phylogenetic patterns and genetic markers that might be associated with increased virulence, sequencing and phylogenetic analysis of the whole genomes of 63 viruses isolated from fatal cases and non fatal “control” cases was undertaken. The analysis revealed the circulation of two main genetic groups, I and II, both of which contained viruses from fatal cases. No associated amino acid substitutions could be linked with an exclusive or higher occurrence in fatal cases. The Fujian/411-like viruses in genetic groups I and II completely displaced other A(H3N2) viruses, but they disappeared after 2004. This study shows that two A(H3N2) virus genotypes circulated exclusively during the winter of 2003–2004 in the UK and caused an unusually high number of deaths in children. Host factors related to immune state and differences in genetic background between patients may also play important roles in determining the outcome of an influenza infection

The first OSCE; Does students' experience of performing in public affect their results? Assessment and evaluation of admissions, knowledge, skills and attitudes

Background: Personal qualities have been shown to affect students' exam results. We studied the effect of experience, and level, of public performance in music, drama, dance, sport, and debate at the time of admission to medical school as a predictor of student achievement in their first objective structured clinical examination (OSCE). Methods: A single medical school cohort (n=265) sitting their first clinical exam in 2011 as third year students were studied. Pre-admission statements made at the time of application were coded for their stated achievements in the level of public performance; participation in each activity was scored 0-3, where 0 was no record, 1=leisure time activity, 2=activity at school or local level, 3=activity at district, regional or national level. These scores were correlated to OSCE results by linear regression and t-test. Comparison was made between the highest scoring students in each area, and students scoring zero by t-test. Results: There was a bell shaped distribution in public performance score in this cohort. There was no significant linear regression relationship between OSCE results and overall performance score, or between any subgroups. There was a significant difference between students with high scores in theatre, debate and vocal music areas, grouped together as verbal performance, and students scoring zero in these areas. (p<0.05, t-test) with an effect size of 0.4. Conclusions: We found modest effects from pre-admission experience of verbal performance on students' scores in the OSCE examination. As these data are taken from students' admission statements, we call into question the received wisdom that such statements are unreliable

Prioritizing sleep for healthy work schedules

Good sleep is advantageous to the quality of life. Sleep-related benefits are particularly helpful for the working class, since poor or inadequate amounts of sleep degrade work productivity and overall health. This review paper explores the essential role of sleep in healthy work schedules and primarily focuses on the timing of sleep in relation to the work period (that is, before, during and after work). Data from laboratory, field and modeling studies indicate that consistent amounts of sleep prior to work are fundamental to improved performance and alertness in the workplace. In addition, planned naps taken during work maintain appropriate levels of waking function for both daytime and night-time work. Clearly, sufficient sleep after work is vital in promoting recovery from fatigue. Recent data also suggest that the time interval between shifts should be adjusted according to the biological timing of sleep. Although sleep is more likely to be replaced by job and other activities in the real life, research shows that it is worthwhile to revise the work schedules in order to optimize sleep before, sometime during and after the work period. Therefore, we suggest establishing work-sleep balance, similar to work-life balance, as a principle for designing and improving work schedules