Increase in airway neutrophils after oral but not inhaled corticosteroid therapy in mild asthma

SummaryBackground: Neutrophils, in addition to eosinophils, are prominent in the airways of patients with severe asthma who are usually on long-term oral and inhaled corticosteroid treatment. We determined whether inhaled or oral corticosteroid therapy can induce airway neutrophilia.Methods: We performed two separate placebo-controlled studies in which patients with mild asthma were treated with either prednisolone (30mg per day for 7 days; n=9) or placebo tablets (n=8), or with either inhaled budesonide (800μg twice daily for 4 weeks; n=6) or inhaled placebo (n=6). Fiberoptic bronchoscopy was performed before treatment and at day 7 of oral treatment, and at day 28 of inhaled therapy. Bronchial sections were immunostained with an antibody to major basic protein for eosinophils, and with an antibody to neutrophil elastase for neutrophils. Induced sputum was obtained in the prednisolone study.Results: Neutrophils in airway submucosa increased after prednisolone from median 76 to 140/mm2 (P=0.05); this change was higher than that after placebo (P=0.04). Eosinophils decreased from 24 to 9/mm2 (P=0.03), but this was not significantly different from placebo. Eosinophils and neutrophils, and levels of IL-8 and myeloperoxidase in induced sputum did not change after prednisolone. There was no change in neutrophil counts after budesonide, but the reduction in eosinophils was greater than placebo (P=0.05). Budesonide improved bronchial responsiveness, but prednisolone did not.Conclusion: Corticosteroid therapy by the oral but not inhaled route can induce neutrophil recruitment into the airways of patients with mild asthma. This could explain the increase in airway neutrophils observed in severe asthmatics treated with oral corticosteroids

STAT6 expression in T cells, alveolar macrophages and bronchial biopsies of normal and asthmatic subjects

<p>Abstract</p> <p>Background</p> <p>Asthma is characterised by increased numbers of Th2-like cells in the airways and IgE secretion. Generation of Th2 cells requires interleukin (IL)-4 and IL-13 acting through their specific receptors and activating the transcription factor, signal transducer and activator of transcription 6 (STAT6). STAT6 knockout mice fail to produce IgE, airway hyperresponsiveness and bronchoalveolar lavage eosinophilia after allergen sensitisation, suggesting a critical role for STAT6 in allergic responses.</p> <p>Methods</p> <p>We have investigated the expression of STAT6 in peripheral blood T-lymphocytes, alveolar macrophages and bronchial biopsies from 17 normal subjects and 18 mild-moderate steroid-naïve stable asthmatic patients.</p> <p>Results</p> <p>STAT6 expression was variable and was detected in T-lymphocytes, macrophages and bronchial epithelial cells from all subjects with no difference between normal and stable asthmatic subjects.</p> <p>Conclusions</p> <p>STAT6 expression in different cells suggests that it may be important in regulating the expression of not only Th2-like cytokines in T cells of man, but may also regulate STAT-inducible genes in alveolar macrophages and airway epithelial cells.</p

Instances and connectors : issues for a second generation process language

This work is supported by UK EPSRC grants GR/L34433 and GR/L32699Over the past decade a variety of process languages have been defined, used and evaluated. It is now possible to consider second generation languages based on this experience. Rather than develop a second generation wish list this position paper explores two issues: instances and connectors. Instances relate to the relationship between a process model as a description and the, possibly multiple, enacting instances which are created from it. Connectors refers to the issue of concurrency control and achieving a higher level of abstraction in how parts of a model interact. We believe that these issues are key to developing systems which can effectively support business processes, and that they have not received sufficient attention within the process modelling community. Through exploring these issues we also illustrate our approach to designing a second generation process language.Postprin

When and where to transfer for Bayesian network parameter learning

This work is supported by the European Research Council (ERC-2013-AdG339182-BAYES-KNOWLEDGE) and the European Union’s Horizon 2020 research and innovation programme under grant agreement No 640891. YZ is supported by China Scholarship Council (CSC)/Queen Mary Joint PhD scholarships and National Natural Science Foundation of China (61273322, 71471174)

Hologenome analysis of two marine sponges with different microbiomes

Background: Sponges (Porifera) harbor distinct microbial consortia within their mesohyl interior. We herein analysed the hologenomes of Stylissa carteri and Xestospongia testudinaria, which notably differ in their microbiome content. Results: Our analysis revealed that S. carteri has an expanded repertoire of immunological domains, specifically Scavenger Receptor Cysteine-Rich (SRCR) like domains, compared to X. testudinaria. On the microbial side, metatranscriptome analyses revealed an overrepresentation of potential symbiosis-related domains in X. testudinaria. Conclusions: Our findings provide genomic insights into the molecular mechanisms underlying host-symbiont coevolution and may serve as a roadmap for future hologenome analyses

Neural Correlates of Auditory Perceptual Awareness under Informational Masking

Our ability to detect target sounds in complex acoustic backgrounds is often limited not by the ear's resolution, but by the brain's information-processing capacity. The neural mechanisms and loci of this “informational masking” are unknown. We combined magnetoencephalography with simultaneous behavioral measures in humans to investigate neural correlates of informational masking and auditory perceptual awareness in the auditory cortex. Cortical responses were sorted according to whether or not target sounds were detected by the listener in a complex, randomly varying multi-tone background known to produce informational masking. Detected target sounds elicited a prominent, long-latency response (50–250 ms), whereas undetected targets did not. In contrast, both detected and undetected targets produced equally robust auditory middle-latency, steady-state responses, presumably from the primary auditory cortex. These findings indicate that neural correlates of auditory awareness in informational masking emerge between early and late stages of processing within the auditory cortex

"Who's ready for the cave?" Thailand's Tham Luang Rescue Museum as teaching case study

This article demonstrates how a teaching case study approach can benefit museum studies courses. It takes as its focus the widely reported rescue of a boys’ football team from a flooded cave in Thailand (2018). The success of this multinational effort led to immediate calls for the establishment of a “living museum” dedicated to remembering what became known as the “Tham Luang cave rescue.” Discussion of the potential form and function of this envisaged museum plus its wider ramifications formed a key component of a newly validated international MA program taught in the UK and China by local academics and practitioners. Issues addressed include collections management, interpretation and display as well as ethical considerations relating to funding and forward planning. These were debated through groupwork, student presentations and report writing. The article reflects on this experience and the lessons it has for studying museums. It advocates the use of other topical events as the basis for similar teaching case studies on the grounds that this best equips students with the knowledge and skills required in the workplace

Panchromatic Observations of the Textbook GRB 110205A: Constraining Physical Mechanisms of Prompt Emission and Afterglow

We present a comprehensive analysis of a bright, long-duration ( T 90 ~ 257 s) GRB 110205A at redshift z = 2.22. The optical prompt emission was detected by Swift /UVOT, ROTSE-IIIb, and BOOTES telescopes when the gamma-ray burst (GRB) was still radiating in the γ-ray band, with optical light curve showing correlation with γ-ray data. Nearly 200 s of observations were obtained simultaneously from optical, X-ray, to γ-ray (1 eV to 5 MeV), which makes it one of the exceptional cases to study the broadband spectral energy distribution during the prompt emission phase. In particular, we clearly identify, for the first time, an interesting two-break energy spectrum, roughly consistent with the standard synchrotron emission model in the fast cooling regime. Shortly after prompt emission (~1100 s), a bright ( R = 14.0) optical emission hump with very steep rise (α ~ 5.5) was observed, which we interpret as the reverse shock (RS) emission. It is the first time that the rising phase of an RS component has been closely observed. The full optical and X-ray afterglow light curves can be interpreted within the standard reverse shock (RS) + forward shock (FS) model. In general, the high-quality prompt and afterglow data allow us to apply the standard fireball model to extract valuable information, including the radiation mechanism (synchrotron), radius of prompt emission ( R GRB ~ 3 × 10 13 cm), initial Lorentz factor of the outflow (Γ 0 ~ 250), the composition of the ejecta (mildly magnetized), the collimation angle, and the total energy budget.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98559/1/0004-637X_751_2_90.pd

Evidence for a Novel Marine Harmful Algal Bloom: Cyanotoxin (Microcystin) Transfer from Land to Sea Otters

“Super-blooms” of cyanobacteria that produce potent and environmentally persistent biotoxins (microcystins) are an emerging global health issue in freshwater habitats. Monitoring of the marine environment for secondary impacts has been minimal, although microcystin-contaminated freshwater is known to be entering marine ecosystems. Here we confirm deaths of marine mammals from microcystin intoxication and provide evidence implicating land-sea flow with trophic transfer through marine invertebrates as the most likely route of exposure. This hypothesis was evaluated through environmental detection of potential freshwater and marine microcystin sources, sea otter necropsy with biochemical analysis of tissues and evaluation of bioaccumulation of freshwater microcystins by marine invertebrates. Ocean discharge of freshwater microcystins was confirmed for three nutrient-impaired rivers flowing into the Monterey Bay National Marine Sanctuary, and microcystin concentrations up to 2,900 ppm (2.9 million ppb) were detected in a freshwater lake and downstream tributaries to within 1 km of the ocean. Deaths of 21 southern sea otters, a federally listed threatened species, were linked to microcystin intoxication. Finally, farmed and free-living marine clams, mussels and oysters of species that are often consumed by sea otters and humans exhibited significant biomagnification (to 107 times ambient water levels) and slow depuration of freshwater cyanotoxins, suggesting a potentially serious environmental and public health threat that extends from the lowest trophic levels of nutrient-impaired freshwater habitat to apex marine predators. Microcystin-poisoned sea otters were commonly recovered near river mouths and harbors and contaminated marine bivalves were implicated as the most likely source of this potent hepatotoxin for wild otters. This is the first report of deaths of marine mammals due to cyanotoxins and confirms the existence of a novel class of marine “harmful algal bloom” in the Pacific coastal environment; that of hepatotoxic shellfish poisoning (HSP), suggesting that animals and humans are at risk from microcystin poisoning when consuming shellfish harvested at the land-sea interface

Mortality Among Adults With Cancer Undergoing Chemotherapy or Immunotherapy and Infected With COVID-19

Importance: Large cohorts of patients with active cancers and COVID-19 infection are needed to provide evidence of the association of recent cancer treatment and cancer type with COVID-19 mortality. // Objective: To evaluate whether systemic anticancer treatments (SACTs), tumor subtypes, patient demographic characteristics (age and sex), and comorbidities are associated with COVID-19 mortality. // Design, Setting, and Participants: The UK Coronavirus Cancer Monitoring Project (UKCCMP) is a prospective cohort study conducted at 69 UK cancer hospitals among adult patients (≥18 years) with an active cancer and a clinical diagnosis of COVID-19. Patients registered from March 18 to August 1, 2020, were included in this analysis. // Exposures: SACT, tumor subtype, patient demographic characteristics (eg, age, sex, body mass index, race and ethnicity, smoking history), and comorbidities were investigated. // Main Outcomes and Measures: The primary end point was all-cause mortality within the primary hospitalization. // Results: Overall, 2515 of 2786 patients registered during the study period were included; 1464 (58%) were men; and the median (IQR) age was 72 (62-80) years. The mortality rate was 38% (966 patients). The data suggest an association between higher mortality in patients with hematological malignant neoplasms irrespective of recent SACT, particularly in those with acute leukemias or myelodysplastic syndrome (OR, 2.16; 95% CI, 1.30-3.60) and myeloma or plasmacytoma (OR, 1.53; 95% CI, 1.04-2.26). Lung cancer was also significantly associated with higher COVID-19–related mortality (OR, 1.58; 95% CI, 1.11-2.25). No association between higher mortality and receiving chemotherapy in the 4 weeks before COVID-19 diagnosis was observed after correcting for the crucial confounders of age, sex, and comorbidities. An association between lower mortality and receiving immunotherapy in the 4 weeks before COVID-19 diagnosis was observed (immunotherapy vs no cancer therapy: OR, 0.52; 95% CI, 0.31-0.86). // Conclusions and Relevance: The findings of this study of patients with active cancer suggest that recent SACT is not associated with inferior outcomes from COVID-19 infection. This has relevance for the care of patients with cancer requiring treatment, particularly in countries experiencing an increase in COVID-19 case numbers. Important differences in outcomes among patients with hematological and lung cancers were observed