Inflammatory cytokines IL-1β and TNF-α regulate p75NTR expression in CNS neurons and astrocytes by distinct cell-type-specific signalling mechanisms

The p75NTR (where NTR is neurotrophin receptor) can mediate many distinct cellular functions, including cell survival and apoptosis, axonal growth and cell proliferation, depending on the cellular context. This multifunctional receptor is widely expressed in the CNS (central nervous system) during development, but its expression is restricted in the adult brain. However, p75NTR is induced by a variety of pathophysiological insults, including seizures, lesions and degenerative disease. We have demonstrated previously that p75NTR is induced by seizures in neurons, where it induces apoptosis, and in astrocytes, where it may regulate proliferation. In the present study, we have investigated whether the inflammatory cytokines IL (interleukin)-1β and TNF-α (tumour necrosis factor-α), that are commonly elevated in these pathological conditions, mediate the regulation of p75NTR in neurons and astrocytes. We have further analysed the signal transduction pathways by which these cytokines induce p75NTR expression in the different cell types, specifically investigating the roles of the NF-κB (nuclear factor κB) and p38 MAPK (mitogen-activated protein kinase) pathways. We have demonstrated that both cytokines regulate p75NTR expression; however, the mechanisms governing this regulation are cytokine- and cell-type specific. The distinct mechanisms of cytokine-mediated p75NTR regulation that we demonstrate in the present study may facilitate therapeutic intervention in regulation of this receptor in a cell-selective manner

Resuscitation of Drowned Persons during the COVID-19 Pandemic: A Consensus Statement

Importance: Resuscitation is a niche example of how the COVID-19 pandemic has affected society in the long term. Those trained in cardiopulmonary resuscitation (CPR) face the dilemma that attempting to save a life may result in their own harm. This is most of all a problem for drowning, where hypoxia is the cause of cardiac arrest and ventilation is the essential first step in reversing the situation. Objective: To develop recommendations for water rescue organizations in providing their rescuers with safe drowning resuscitation procedures during the COVID-19 pandemic. Evidence Review: Two consecutive modified Delphi procedures involving 56 participants from 17 countries with expertise in drowning prevention research, resuscitation, and programming were performed from March 28, 2020, to March 29, 2021. In parallel, PubMed and Google Scholar were searched to identify new emerging evidence relevant to each core element, acknowledge previous studies relevant in the new context, and identify knowledge gaps. Findings: Seven core elements, each with their own specific recommendations, were identified in the initial consensus procedure and were grouped into 4 categories: (1) prevention and mitigation of the risks of becoming infected, (2) resuscitation of drowned persons during the COVID-19 pandemic, (3) organizational responsibilities, and (4) organizations unable to meet the recommended guidelines. The common measures of infection risk mitigation, personal protective equipment, and vaccination are the base of the recommendations. Measures to increase drowning prevention efforts reduce the root cause of the dilemma. Additional infection risk mitigation measures include screening all people entering aquatic facilities, defining criteria for futile resuscitation, and avoiding contact with drowned persons by rescuers with a high-risk profile. Ventilation techniques must balance required skill level, oxygen delivery, infection risk, and costs of equipment and training. Bag-mask ventilation with a high-efficiency particulate air filter by 2 trained rescuers is advised. Major implications for the methods, facilities, and environment of CPR training have been identified, including nonpractical skills to avoid being infected or to infect others. Most of all, the organization is responsible for informing their members about the impact of the COVID-19 pandemic and taking measures that maximize rescuer safety. Research is urgently needed to better understand, develop, and implement strategies to reduce infection transmission during drowning resuscitation. Conclusions and Relevance: This consensus document provides an overview of recommendations for water rescue organizations to improve the safety of their rescuers during the COVID-19 pandemic and balances the competing interests between a potentially lifesaving intervention and risk to the rescuer. The consensus-based recommendations can also serve as an example for other volunteer organizations and altruistic laypeople who may provide resuscitation.. © 2022 American Medical Association. All rights reserved

The Canada-UK Deep Submillimetre Survey: The Survey of the 14-hour field

We have used SCUBA to survey an area of 50 square arcmin, detecting 19 sources down to a 3sigma sensitivity limit of 3.5 mJy at 850 microns. We have used Monte-Carlo simulations to assess the effect of source confusion and noise on the SCUBA fluxes and positions, finding that the fluxes of sources in the SCUBA surveys are significantly biased upwards and that the fraction of the 850 micron background that has been resolved by SCUBA has been overestimated. The radio/submillmetre flux ratios imply that the dust in these galaxies is being heated by young stars rather than AGN. We have used simple evolution models based on our parallel SCUBA survey of the local universe to address the major questions about the SCUBA sources: (1) what fraction of the star formation at high redshift is hidden by dust? (2) Does the submillimetre luminosity density reach a maximum at some redshift? (3) If the SCUBA sources are proto-ellipticals, when exactly did ellipticals form? However, we show that the observations are not yet good enough for definitive answers to these questions. There are, for example, acceptable models in which 10 times as much high-redshift star formation is hidden by dust as is seen at optical wavelengths, but also acceptable ones in which the amount of hidden star formation is less than that seen optically. There are acceptable models in which very little star formation occurred before a redshift of three (as might be expected in models of hierarchical galaxy formation), but also ones in which 30% of the stars have formed by this redshift. The key to answering these questions are measurements of the dust temperatures and redshifts of the SCUBA sources.Comment: 41 pages (latex), 17 postscript figures, to appear in the November issue of the Astronomical Journa

International lease accounting reform and economic consequences: the views of UK users and preparers

In response to perceived difficulties with extant lease-accounting standards in operation worldwide, the G4+1 issued a discussion paper which proposes that all leases should be recognized on the balance sheet [ASB (1999). Leases: Implementation of a new approach, discussion paper. London: Accounting Standards Board]. Leasing is now on the active agenda of the IASB. A major difficulty faced by standard setters lies in overcoming the preparer/user lobbying imbalance and obtaining ex ante evidence on the likely impact of regulatory reform. This paper contributes to the ongoing international debate by conducting a questionnaire survey of U.K. users and preparers to assess their views on proposals for lease-accounting reform and on the potential economic consequences of their adoption. The results, based on 132 responses, indicate that both groups accept that there are deficiencies in the current rules, but they do not agree on the way forward and believe that the proposals would lead to significant economic consequences for key parties. The impact on respondents' views of familiarity with the proposals, level of lease usage, and company size, is also examined

Herschel-ATLAS: Far-infrared properties of radio-loud and radio-quiet quasars

This is pre-copyedited, author-produced pdf of an article accepted for publication in Monthly Notices of the Royal Astronomical Society following peer review. The version of record, E. Kalfountzou, et al., ‘Herschel-ATLAS: Far-infrared properties of radio-loud and radio-quiet quasars’, MNRAS, Vol 42(2): 1181-1196, first published online June 11, 2014, is available online via doi: 10.1093/mnras/stu782 Published by Oxford University Press on behalf of the Royal Astronomical Society.We have constructed a sample of radio-loud and radio-quiet quasars from the Faint Images Radio Sky at Twenty-one centimetres and the Sloan Digital Sky Survey Data Release 7, over the Herschel-ATLAS Phase 1 area (9h, 12h and 14 h . 5 ). Using a stacking analysis, we find a significant correlation between the far-infrared (FIR) luminosity and 1.4-GHz luminosity for radio-loud quasars. Partial correlation analysis confirms the intrinsic correlation after removing the redshift contribution, while for radio-quiet quasars, no partial correlation is found. Using a single-temperature grey-body model, we find a general trend of lower dust temperatures in case of radio-loud quasars compared to radio-quiet quasars. Also, radio-loud quasars are found to have almost constant mean values of dust mass along redshift and optical luminosity bins. In addition, we find that radio-loud quasars at lower optical luminosities tend to have on average higher FIR and 250-μm luminosity with respect to radio-quiet quasars with the same optical luminosites. Even if we use a two-temperature grey-body model to describe the FIR data, the FIR luminosity excess remains at lower optical luminosities. These results suggest that powerful radio jets are associated with star formation especially at lower accretion ratesPeer reviewe

Pneumococcal carriage in children in Ulaanbaatar, Mongolia before and one year after the introduction of the 13-valent pneumococcal conjugate vaccine.

BACKGROUND: Nasopharyngeal carriage of Streptococcus pneumoniae precedes disease, is the source of pneumococcal community spread, and the mechanism for herd protection provided by pneumococcal conjugate vaccines (PCVs). There are few PCV impact studies in low- and middle-income countries, particularly in Asia. In 2016, Mongolia introduced the 13-valent PCV (PCV13) in a phased manner using a 2 + 1 schedule, with catch-up. We aimed to assess the impact of PCV13 introduction on nasopharyngeal pneumococcal carriage and density in children in Mongolia. METHODS: We conducted two cross-sectional carriage surveys (pre- and one year post-PCV) at community health clinics in two districts of the capital city, Ulaanbaatar in both May-July 2015 and 2017. The study analysis included 961 children too young to be vaccinated (5-8 weeks old) and 989 children eligible for vaccination (12-23 months old). Pneumococci were detected by quantitative real-time PCR and molecular serotyping performed using DNA microarray. FINDINGS: One year post-PCV introduction, PCV13 serotype carriage reduced by 52% in 12-23 month olds (adjusted prevalence ratio [aPR] 0.48 [95% confidence interval [CI] 0.39-0.59]), with evidence of non-PCV13 serotype replacement (aPR 1.55 [95% CI 1.30-1.85]), compared with the pre-PCV period. In 5-8 week olds, PCV13 serotype carriage reduced by 51% (aPR 0.49 [95% CI 0.33-0.73]) with no significant change in non-PCV13 serotype carriage (aPR 1.10 [95% CI 0.83-1.46]). An increase was observed in both PCV13 and non-PCV13 pneumococcal density post-PCV introduction. Antimicrobial resistance (AMR) genes were common, with 82.3% of samples containing at least one of the 10 AMR genes assessed. CONCLUSION: This study demonstrates substantive PCV13 impact on pneumococcal carriage one year post-vaccine introduction in Mongolia. The reductions in PCV13 serotype carriage are likely to result in reductions in pneumococcal disease including indirect effects. Increases in non-PCV13 serotypes require further monitoring

Assessing the homogenization of urban land management with an application to US residential lawn care.

Changes in land use, land cover, and land management present some of the greatest potential global environmental challenges of the 21st century. Urbanization, one of the principal drivers of these transformations, is commonly thought to be generating land changes that are increasingly similar. An implication of this multiscale homogenization hypothesis is that the ecosystem structure and function and human behaviors associated with urbanization should be more similar in certain kinds of urbanized locations across biogeophysical gradients than across urbanization gradients in places with similar biogeophysical characteristics. This paper introduces an analytical framework for testing this hypothesis, and applies the framework to the case of residential lawn care. This set of land management behaviors are often assumed--not demonstrated--to exhibit homogeneity. Multivariate analyses are conducted on telephone survey responses from a geographically stratified random sample of homeowners (n = 9,480), equally distributed across six US metropolitan areas. Two behaviors are examined: lawn fertilizing and irrigating. Limited support for strong homogenization is found at two scales (i.e., multi- and single-city; 2 of 36 cases), but significant support is found for homogenization at only one scale (22 cases) or at neither scale (12 cases). These results suggest that US lawn care behaviors are more differentiated in practice than in theory. Thus, even if the biophysical outcomes of urbanization are homogenizing, managing the associated sustainability implications may require a multiscale, differentiated approach because the underlying social practices appear relatively varied. The analytical approach introduced here should also be productive for other facets of urban-ecological homogenization

Non-perturbative Euler-Heisenberg Lagrangian and Paraelectricity in Magnetized Massless QED

In this paper we calculate the non-perturbative Euler-Heisenberg Lagrangian for massless QED in a strong magnetic field $H$, where the breaking of the chiral symmetry is dynamically catalyzed by the external magnetic field via the formation of an electro-positron condensate. This chiral condensate leads to the generation of dynamical parameters that have to be found as solutions of non-perturbative Schwinger-Dyson equations. Since the electron-positron pairing mechanism leading to the breaking of the chiral symmetry is mainly dominated by the contributions from the infrared region of momenta much smaller than $\sqrt{eH}$, the magnetic field introduces a dynamical ultraviolet cutoff in the theory that also enters in the non-perturbative Euler-Heisenberg action. Using this action, we show that the system exhibits a significant paraelectricity in the direction parallel to the magnetic field. The nonperturbative nature of this effect is reflected in the non-analytic dependence of the obtained electric susceptibility on the fine-structure constant. The strong paraelectricity in the field direction is linked to the orientation of the electric dipole moments of the pairs that form the chiral condensate. The large electric susceptibility can be used to detect the realization of the magnetic catalysis of chiral symmetry breaking in physical systems.Comment: 18 pages, to be published in NP