IL-17 can be protective or deleterious in murine pneumococcal pneumonia

Streptococcus pneumoniae is the major bacterial cause of community-acquired pneumonia, and the leading agent of childhood pneumonia deaths worldwide. Nasal colonization is an essential step prior to infection. The cytokine IL-17 protects against such colonization and vaccines that enhance IL-17 responses to pneumococcal colonization are being developed. The role of IL-17 in host defence against pneumonia is not known. To address this issue, we have utilized a murine model of pneumococcal pneumonia in which the gene for the IL-17 cytokine family receptor, Il17ra, has been inactivated. Using this model, we show that IL-17 produced predominantly from γδ T cells protects mice against death from the invasive TIGR4 strain (serotype 4) which expresses a relatively thin capsule. However, in pneumonia produced by two heavily encapsulated strains with low invasive potential (serotypes 3 and 6B), IL-17 significantly enhanced mortality. Neutrophil uptake and killing of the serotype 3 strain was significantly impaired compared to the serotype 4 strain and depletion of neutrophils with antibody enhanced survival of mice infected with the highly encapsulated SRL1 strain. These data strongly suggest that IL-17 mediated neutrophil recruitment to the lungs clears infection from the invasive TIGR4 strain but that lung neutrophils exacerbate disease caused by the highly encapsulated pneumococcal strains. Thus, whilst augmenting IL-17 immune responses against pneumococci may decrease nasal colonization, this may worsen outcome during pneumonia caused by some strains

Symmetry Protected Topological phases and Generalized Cohomology

We discuss the classification of SPT phases in condensed matter systems. We review Kitaev's argument that SPT phases are classified by a generalized cohomology theory, valued in the spectrum of gapped physical systems. We propose a concrete description of that spectrum and of the corresponding cohomology theory. We compare our proposal to pre-existing constructions in the literature.Comment: 27 pages, 10 figures. v2: citation updat

Density Deconvolution with Normalizing Flows

Density deconvolution is the task of estimating a probability density function given only noise-corrupted samples. We can fit a Gaussian mixture model to the underlying density by maximum likelihood if the noise is normally distributed, but would like to exploit the superior density estimation performance of normalizing flows and allow for arbitrary noise distributions. Since both adjustments lead to an intractable likelihood, we resort to amortized variational inference. We demonstrate some problems involved in this approach, however, experiments on real data demonstrate that flows can already out-perform Gaussian mixtures for density deconvolution.Comment: Appearing at the second workshop on Invertible Neural Networks, Normalizing Flows, and Explicit Likelihood Models (ICML 2020), Virtual Conference. 8 pages, 6 figures, 5 table

Diffuse Intramuscular Lipomatosis of a Lower Limb

Patient. A 40-year-old man presented with a swelling of the left thigh which had been increasing in size over 10 months. Surgery confirmed a diagnosis of lipoma. After 6 months, another swelling appeared, this time in the left calf. Ultrasound-guided biopsies revealed that the tissue showed appearances consistent with intramuscular lipoma. No further surgery was performed and the man is to be reviewed regularly, with possible debulking if necessary

The varieties of vitality: A cross-cultural lexical analysis

Vitality has been underappreciated and underexplored by academia at large. This oversight is potentially explained by the Western-centric nature of most fields, with vitality having been comparatively neglected in the West relative to elsewhere. One explanation for this lacuna is that vitality is not easily pigeonholed within the ontological categories dominant in the West, such as mind and body. This paper therefore aims to learn from cultures that have cultivated a greater understanding of vitality, doing so by engaging with relevant ‘untranslatable’ words (i.e., those without exact equivalent in English), thus enriching our conceptual map of this topic. Over 200 relevant terms were located and analyzed using an adapted form of grounded theory. Three themes were identified, each with four subthemes: spirit (life force, channels, soul, and transcendence); energy (fortitude, channeling, willpower, and recharging); and heart (desire, passion, affection, and satisfaction). The paper thus refines our understanding of this important topic and provides a foundation for future research.

A novel methodology for recording wing beat frequencies of untethered male and female Aedes aegypti

Aedes aegypti is a vector of many significant arboviruses worldwide including dengue, Zika, chikungunya and yellow fever viruses. With vector control methodology pivoting towards rearing and releasing large numbers of insects for either population suppression or virus-blocking, economical remote (sentinel) surveillance methods for release tracking become increasingly necessary. Recent steps in this direction include advances in optical sensors that identify and classify insects based on their wing beat frequency (WBF). As these traps are being developed, there is a strong need to better understand the environmental and biological factors influencing mosquito WBFs. Here, we developed new untethered-subject methodology to detect changes in WBFs of male and female Ae. aegypti. This new methodology involves directing an ultrasonic transducer at a free-flying subject and measuring the Doppler shift of the reflected ultrasonic continuous wave signal. This system’s utility was assessed by determining its ability to confirm previous reports on the effect of temperature, body size and age on the WBFs generated from acoustic or optical-based experiments. The presented ultrasonic method successfully detected expected trends for each factor for both male and female Ae. aegypti without the need for subject manipulation and potential impediment of natural flight dynamics due to tethering. As a result, this ultrasonic methodology provides a new method for understanding the environmental and physiological determinants of male and female WBFs which can inform the design of remote mosquito surveillance systems

Process, outcome and experience of transition from child to adult mental healthcare : multiperspective study

Background Many adolescents with mental health problems experience transition of care from child and adolescent mental health services (CAMHS) to adult mental health services (AMHS). Aims As part of the TRACK study we evaluated the process, outcomes and user and carer experience of transition from CAMHS to AMHS. Method We identified a cohort of service users crossing the CAMHS/AMHS boundary over 1 year across six mental health trusts in England. We tracked their journey to determine predictors of optimal transition and conducted qualitative interviews with a subsample of users, their carers and clinicians on how transition was experienced. Results Of 154 individuals who crossed the transition boundary in 1 year, 90 were actual referrals (i.e. they made a transition to AMHS), and 64 were potential referrals (i.e. were either not referred to AMHS or not accepted by AMHS). Individuals with a history of severe mental illness, being on medication or having been admitted were more likely to make a transition than those with neurodevelopmental disorders, emotional/neurotic disorders and emerging personality disorder. Optimal transition, defined as adequate transition planning, good information transfer across teams, joint working between teams and continuity of care following transition, was experienced by less than 5% of those who made a transition. Following transition, most service users stayed engaged with AMHS and reported improvement in their mental health. Conclusions For the vast majority of service users, transition from CAMHS to AMHS is poorly planned, poorly executed and poorly experienced. The transition process accentuates pre-existing barriers between CAMHS and AMH

Beyond a single story: The heterogeneity of human flourishing in 22 countries

Contemporary cross-cultural research on flourishing and development has been limited by a focus on Western populations and typically Western priorities, and by attention to only a few indicators of flourishing, such as life satisfaction, life expectancy, or GDP per capita. This paper highlights some significant challenges for robust cross-national and cross-cultural research on the domains and drivers of flourishing. Using data from the recently proposed Global Comparison Framework and the Gallup World Poll, we explore the within- and between-country heterogeneity of flourishing and its determinants across the 22 countries which are the subject of the Global Flourishing Study. Sources of heterogeneity considered include potential tradeoffs among domains of flourishing; the effects of cultural differences on the conceptualization and actualization of flourishing; and the cultural specificity of core analytical concepts, including “life evaluation” and “nation.

Apoptosis-Specific Protein (ASP) Identified in Apoptotic Xenopus Thymus Tumor Cells

A novel apoptosis-specific protein (ASP) has recently been identified in the cytoplasm of apoptotic mammalian cells. This paper investigates whether ASP is found in Xenopus thymus tumor-derived lymphoid cell lines undergoing apoptosis and also in apoptotic, nontransformed splenocytes. Cultured Xenopus tumor lymphoid cells induced to undergo, apoptosis by serum deprivation or treatment with the calcium ionophore, ionomycin, displayed altered morphology typical of apoptotic cells, as judged by flow cytometric light-scatter characteristics and by fluorescence microscopy of acridine-orange-stained cells. Flow cytometry of permeabilized cells and fluorescence microscopy of acetone-fixed cytospins revealed that apoptotic Xenopus tumor cells, especially those displaying loss or condensation of DNA, displayed increased expression of epitopes recognized by a rabbit polyclonal antibody against ASP. Flow cytometry confirmed that ASP is also expressed in splenocytes induced to apoptose by culture in ionomycin or following concanavalin A stimulation. No increased expression of ASP was seen when lymphoid tumor cells or splenocytes were induced into necrosis by overdose with the antifungal agent amphotericin B. Western blotting with antibody against ASP identified the emergence of several protein bands in cell lysates from apoptotic, but not necrotic, Xenopus tumor cells. The new and simple methodology for identifying apoptotic cells described here is likely to be of value to those studying immune system development and associated programmed cell death in Xenopus