Analysis of Damping in Soil as Applied to Machine Foundations

The parameters needed for the design of machine foundations are usually evaluated from the model block resonance test conducted at a given site. Sometimes it may not be possible to attain complete resonance and the test results may be limited to the ascending part of the response. In this paper the possible effect of damping on the values of the design parameters evaluated from the ascending part of response is examined and the nature of damping which gives realistic values of design parameters is presented

If it's 'only' asthma, why are children still dying?

Outcomes for children with asthma in the UK continue to lag behind other European countries. Mortality remains unacceptably high and in contrast to adults with asthma, most deaths occur in the 1 in 20 children with asthma who have severe asthma. Despite evidence that children with asthma have better outcomes with subspecialist care, many children with severe asthma are not referred onwards and barriers exist at every level of the UK healthcare system. The National Review of Asthma Deaths (NRAD) recommended that specialist review should be requested if there had been three or more courses of oral steroids, two or more visits to accident and emergency or an admission to hospital. This review reports the results of a recent interview study of 126 healthcare professionals. More than half of general practitioners (n=49) reported adopting a higher threshold than this. General paediatricians (n=47) set a higher bar still. Their median thresholds for referral to a subspecialist asthma clinic were 4 courses of oral steroids, 3 hospital admissions and 30 days off school in the previous year. This review offers a simple working definition of severe asthma based on current national and international guidelines and provides an example of the recently adopted referral criteria t

The immune landscape of SARS-CoV-2-associated Multisystem Inflammatory Syndrome in Children (MIS-C) from acute disease to recovery.

Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening disease occurring several weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Deep immune profiling showed acute MIS-C patients had highly activated neutrophils, classical monocytes and memory CD8+ T-cells; increased frequencies of B-cell plasmablasts and double-negative B-cells. Post treatment samples from the same patients, taken during symptom resolution, identified recovery-associated immune features including increased monocyte CD163 levels, emergence of a new population of immature neutrophils and, in some patients, transiently increased plasma arginase. Plasma profiling identified multiple features shared by MIS-C, Kawasaki Disease and COVID-19 and that therapeutic inhibition of IL6 may be preferable to IL1 or TNF-α . We identified several potential mechanisms of action for IVIG, the most commonly used drug to treat MIS-C. Finally, we showed systemic complement activation with high plasma C5b-9 levels is common in MIS-C suggesting complement inhibitors could be used to treat the disease

IL-1β, IL-4 and IL-12 control the fate of group 2 innate lymphoid cells in human airway inflammation in the lungs

Group 2 innate lymphoid cells (ILC2s) secrete type 2 cytokines, which protect against parasites but can also contribute to a variety of inflammatory airway diseases. We report here that interleukin 1β (IL-1β) directly activated human ILC2s and that IL-12 induced the conversion of these activated ILC2s into interferon-γ (IFN-γ)-producing ILC1s, which was reversed by IL-4. The plasticity of ILCs was manifested in diseased tissues of patients with severe chronic obstructive pulmonary disease (COPD) or chronic rhinosinusitis with nasal polyps (CRSwNP), which displayed IL-12 or IL-4 signatures and the accumulation of ILC1s or ILC2s, respectively. Eosinophils were a major cellular source of IL-4, which revealed cross-talk between IL-5-producing ILC2s and IL-4-producing eosinophils. We propose that IL-12 and IL-4 govern ILC2 functional identity and that their imbalance results in the perpetuation of type 1 or type 2 inflammatio

Development of Core Outcome Measures sets for paediatric and adult Severe Asthma (COMSA).

BACKGROUND: Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) working group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies. METHODS: COMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult, and paediatric clinicians, pharmaceutical representatives and health regulators from across Europe. Evidence included a systematic review of development, validity, and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients' and carers' views about outcome measures. It was discussed using a modified GRADE Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria. RESULTS: Both adult and paediatric COM sets include forced expiratory volume in 1 s (FEV1) as z scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire, and Asthma Control Test (ACT) or Childhood-ACT while the adult COM includes the Severe Asthma Questionnaire and the Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately). CONCLUSIONS: This patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma