Intra-epithelial neutrophils in paediatric severe asthma are associated with better lung function

BACKGROUND: Neutrophils and IL-17A have been linked mechanistically in models of allergic airways disease and have been associated with asthma severity. However, their role in paediatric asthma is unknown. OBJECTIVES: To investigate the role of neutrophils and the IL-17A pathway in mediating paediatric severe therapy resistant asthma (STRA). METHODS: Children with STRA (n=51, age 12.6 (6 -16.3) years) and non-asthmatic controls (n=15, age 4.75 (1.6-16) years) underwent clinically indicated fiberoptic bronchoscopy, bronchoalveolar lavage (BAL), endobronchial brushings and biopsy. Neutrophils, IL-17A and IL-17RA expressing cells and levels of IL-17A and IL-22 were quantified in BAL and biopsies and related to clinical features. Primary bronchial epithelial cells (PBECs) were stimulated with IL-17A and/or IL-22, with and without Budesonide. RESULTS: Children with STRA had increased intra-epithelial neutrophils, which positively correlated with FEV1 %predicted (r=0.43, p=0.008). Neutrophil-high patients also had better symptom control, despite lower dose maintenance inhaled steroids. Submucosal neutrophils were not increased in STRA. Submucosal and epithelial IL-17A positive cells and BAL IL-17A and IL-22 levels were similar in STRA and controls. However, there were significantly more IL-17RA positive cells in the submucosa and epithelium in children with STRA compared to controls (p=0.001). Stimulation of PBECs with IL-17A enhanced mRNA expression of IL-17RA and increased release of IL-8, even in the presence of Budesonide. CONCLUSIONS: A proportion of children with STRA exhibit increased intra-epithelial airway neutrophilia that correlated with better lung function. STRA was additionally characterised by increased airway IL-17RA expression. These data suggest a potential beneficial rather than adverse role for neutrophils in paediatric severe asthma pathophysiology

Phosphorylation of β-catenin at Serine552 correlates with invasion and recurrence of non-functioning pituitary neuroendocrine tumours.

Non-functioning pituitary tumours (NF-PitNETs) are common intracranial benign neoplasms that can exhibit aggressive behaviour by invading neighbouring structures and, in some cases, have multiple recurrences. Despite resulting in severe co-morbidities, no predictive biomarkers of recurrence have been identified for NF-PitNETs. In this study we have used high-throughput mass spectrometry-based analysis to examine the phosphorylation pattern of different subsets of NF-PitNETs. Based on histopathological, radiological, surgical and clinical features, we have grouped NF-PitNETs into non-invasive, invasive, and recurrent disease groups. Tumour recurrence was determined based on regular clinical and radiological data of patients for a mean follow-up of 10 years (SD ± 5.4 years). Phosphoproteomic analyses identified a unique phosphopeptide enrichment pattern which correlates with disease recurrence. Candidate phosphorylated proteins were validated in a large cohort of NF-PitNET patients by western blot and immunohistochemistry. We identified a cluster of 22 phosphopeptides upregulated in recurrent NF-PitNETs compared to non-invasive and invasive subgroups. We reveal significant phosphorylation of the β-catenin at Ser552 in recurrent and invasive NF-PitNETs, compared to non-invasive/non-recurrent NF-PitNET subgroup. Moreover, β-catenin pSer552 correlates with the recurrence free survival among 200 patients with NF-PitNET. Together, our results suggest that the phosphorylation status of β-catenin at Ser552 could act as potential biomarker of tumour recurrence in NF-PitNETs

False-negative RT-PCR for COVID-19 and a diagnostic risk score: a retrospective cohort study among patients admitted to hospital

OBJECTIVE: To describe the characteristics and outcomes of patients with a clinical diagnosis of COVID-19 and false-negative SARS-CoV-2 reverse transcription-PCR (RT-PCR), and develop and internally validate a diagnostic risk score to predict risk of COVID-19 (including RT-PCR-negative COVID-19) among medical admissions. DESIGN: Retrospective cohort study. SETTING: Two hospitals within an acute NHS Trust in London, UK. PARTICIPANTS: All patients admitted to medical wards between 2 March and 3 May 2020. OUTCOMES: Main outcomes were diagnosis of COVID-19, SARS-CoV-2 RT-PCR results, sensitivity of SARS-CoV-2 RT-PCR and mortality during hospital admission. For the diagnostic risk score, we report discrimination, calibration and diagnostic accuracy of the model and simplified risk score and internal validation. RESULTS: 4008 patients were admitted between 2 March and 3 May 2020. 1792 patients (44.8%) were diagnosed with COVID-19, of whom 1391 were SARS-CoV-2 RT-PCR positive and 283 had only negative RT-PCRs. Compared with a clinical reference standard, sensitivity of RT-PCR in hospital patients was 83.1% (95% CI 81.2%-84.8%). Broadly, patients with false-negative RT-PCR COVID-19 and those confirmed by positive PCR had similar demographic and clinical characteristics but lower risk of intensive care unit admission and lower in-hospital mortality (adjusted OR 0.41, 95% CI 0.27-0.61). A simple diagnostic risk score comprising of age, sex, ethnicity, cough, fever or shortness of breath, National Early Warning Score 2, C reactive protein and chest radiograph appearance had moderate discrimination (area under the receiver-operator curve 0.83, 95% CI 0.82 to 0.85), good calibration and was internally validated. CONCLUSION: RT-PCR-negative COVID-19 is common and is associated with lower mortality despite similar presentation. Diagnostic risk scores could potentially help triage patients requiring admission but need external validation

Discrimination in the University in India

Despite changes to the status of women in India, the strong patriarchal traditions continue to shape the way that women take their place in Indian society. There are more opportunities for women in India today, inclusive of political, financial and working opportunities, but it is difficult not to notice that India is still a male dominated society

What we talk about when we talk about "global mindset": managerial cognition in multinational corporations

Recent developments in the global economy and in multinational corporations have placed significant emphasis on the cognitive orientations of managers, giving rise to a number of concepts such as “global mindset” that are presumed to be associated with the effective management of multinational corporations (MNCs). This paper reviews the literature on global mindset and clarifies some of the conceptual confusion surrounding the construct. We identify common themes across writers, suggesting that the majority of studies fall into one of three research perspectives: cultural, strategic, and multidimensional. We also identify two constructs from the social sciences that underlie the perspectives found in the literature: cosmopolitanism and cognitive complexity and use these two constructs to develop an integrative theoretical framework of global mindset. We then provide a critical assessment of the field of global mindset and suggest directions for future theoretical and empirical research

Testing the efficacy of voluntary urban greenhouse gas emissions inventories

Drawing from an original dataset of urban metropolitan carbon footprints, we explore the correlations between national level climate change commitments and subnational level inventories. We ask: Does voluntary reporting allow a city to perform better than national average? Does ambitiousness in commitment have an impact on performance in footprint reduction? Does having long-term commitments affect performance in footprint reduction? Do binding national level commitments (such as those under the Kyoto Protocol) affect performance at the city level in terms of footprint reduction? To provide answers, we synthesize data from the largest repository of voluntary sub-national commitments and actions towards footprint reduction and greenhouse gas inventories from around the world, the Carbonn platform. More than 500 cities report at least one action, commitment or inventory to this database. We find, using a subset of this database, perhaps counter intuitively that cities with more ambitious commitments do not necessarily have steeper reductions in emissions. Our data also suggest that having long-term self-reported goals does not make the cities perform better in terms of footprint reduction. This appears to be true for both government and community commitments reported. Lastly, and positively, our data did reveal a statistically significant effect for cities belonging to countries that had committed to the Kyoto Protocol, suggesting the necessity of binding national (and supranational) climate targets

A survey of performance enhancement of transmission control protocol (TCP) in wireless ad hoc networks

This Article is provided by the Brunel Open Access Publishing Fund - Copyright @ 2011 Springer OpenTransmission control protocol (TCP), which provides reliable end-to-end data delivery, performs well in traditional wired network environments, while in wireless ad hoc networks, it does not perform well. Compared to wired networks, wireless ad hoc networks have some specific characteristics such as node mobility and a shared medium. Owing to these specific characteristics of wireless ad hoc networks, TCP faces particular problems with, for example, route failure, channel contention and high bit error rates. These factors are responsible for the performance degradation of TCP in wireless ad hoc networks. The research community has produced a wide range of proposals to improve the performance of TCP in wireless ad hoc networks. This article presents a survey of these proposals (approaches). A classification of TCP improvement proposals for wireless ad hoc networks is presented, which makes it easy to compare the proposals falling under the same category. Tables which summarize the approaches for quick overview are provided. Possible directions for further improvements in this area are suggested in the conclusions. The aim of the article is to enable the reader to quickly acquire an overview of the state of TCP in wireless ad hoc networks.This study is partly funded by Kohat University of Science & Technology (KUST), Pakistan, and the Higher Education Commission, Pakistan

Renal Cell Carcinoma with Unusual Metastasis to the Small Intestine Manifesting as Extensive Polyposis: Successful Management with Intraoperative Therapeutic Endoscopy

We present here a rare clinical case of a 53-year-old gentleman with metastasis from renal cell carcinoma (RCC) to the small intestine presenting with extensive polyposis and massive gastrointestinal bleeding which was successfully managed with intraoperative endoscopic polypectomy and segmental small bowel resection. The patient presented with melena 2 weeks after right nephrectomy for RCC. Capsule endoscopy found extensive polyposis throughout the small bowel, and the histological features confirmed the diagnosis of metastatic RCC. The patient eventually underwent laparotomy with intraoperative endoscopy of the entire small bowel. Most of the polyps were removed by snare polypectomy. Three segments of the small bowel with extensive transmural involvement had to be resected with primary anastomosis. In the 2 months following his surgery, the patient had no further evidence of gastrointestinal bleeding. The decision of meticulously removing close to 100 polyps by intraoperative endoscopy prevented the patient from requiring total small bowel resection and lifelong dependence on parenteral nutrition. In conclusion, gastrointestinal bleeding in a patient with known RCC should always trigger full gastrointestinal work-up including capsule endoscopy and, if necessary, double balloon enteroscopy

Aspirin use and survival after the diagnosis of breast cancer:a population-based cohort study

Background: Aspirin use has been associated with a reduced cancer incidence and fewer deaths from cancer. This study examined whether women with breast cancer prescribed aspirin postdiagnosis had improved survival.Methods:An observational, population cohort study was undertaken using data linkage of cancer registry, dispensed prescriptions and death records in Tayside, Scotland. All community prescriptions for aspirin in women with breast cancer were extracted and use postdiagnosis for each individual examined using Cox's proportional hazard models. The main outcome measures were all-cause mortality and breast cancer-specific mortality.Results:Four thousand six hundred and twenty-seven patients diagnosed with breast cancer between 1 January 1998 and 31 December 2008 were followed up until 28 February 2010. Median age at diagnosis was 62 (IQR 52-74). One thousand eight hundred and two (39%) deaths were recorded, with 815 (18%) attributed to breast cancer. One thousand and thirty-five (22%) patients were prescribed aspirin postdiagnosis. Such aspirin use was associated with lower risk of all-cause mortality (HR=0.53, 95% CI=0.45-0.63, P<0.001) and breast cancer-specific mortality (HR=0.42, 95% CI=0.31-0.55, P<0.001) after adjusting for age, socioeconomic status, TNM stage, tumour grade, oestrogen receptor status, surgery, radiotherapy, chemotherapy, adjuvant endocrine therapy and aspirin use prediagnosis. Conclusions:Aspirin use postdiagnosis of breast cancer may reduce both all-cause and breast cancer-specific mortality. Further investigation seeking a causal relationship and which subgroups of patients benefit most await ongoing randomised controlled trials.Publisher PDFPeer reviewe

Two-pion Bose-Einstein correlations in central Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76 TeV

The first measurement of two-pion Bose-Einstein correlations in central Pb-Pb collisions at $\sqrt{s_{\rm NN}} = 2.76$ TeV at the Large Hadron Collider is presented. We observe a growing trend with energy now not only for the longitudinal and the outward but also for the sideward pion source radius. The pion homogeneity volume and the decoupling time are significantly larger than those measured at RHIC.Comment: 17 pages, 5 captioned figures, 1 table, authors from page 12, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/388