Singular inextensible limit in the vibrations of post-buckled rods: Analytical derivation and role of boundary conditions

In-plane vibrations of an elastic rod clamped at both extremities are studied. The rod is modeled as an extensible planar Kirchhoff elastic rod under large displacements and rotations. Equilibrium configurations and vibrations around these configurations are computed analytically in the incipient post-buckling regime. Of particular interest is the variation of the first mode frequency as the load is increased through the buckling threshold. The loading type is found to have a crucial importance as the first mode frequency is shown to behave singularly in the zero thickness limit in the case of prescribed axial displacement, whereas a regular behavior is found in the case of prescribed axial load.This publication is based in part upon work supported by Award no. KUK-C1-013-04, made by King Abdullah University of Science and Technology (KAUST) (A.G.). A.G. is a Wolfson/Royal Society Merit Award holder. Support from the Royal Society, through the International Exchanges Scheme (Grant IE120203), is also acknowledge

The paediatric journey to and through the emergencydepartment: the parent’s experience

Parenthood will inevitably include caring for a child suffering from a mild to moderate illness requiring access to health care. Most childhood illnesses can be managed in the community, and a variety of primary care services are available with patients being encouraged to attend the one most suitable for their needs. Yet the number of children visiting the emergency department with non-urgent illness continues to rise annually, with paediatric attendance representing over 25% of the total workload.This study investigated why parents chose to bring their child to the emergency department and explored the journey through parents experiences when making this decision. The research question was ‘What are the concerns, expectations and experiences of parents who choose to bring their child to the emergency department with mild or moderate acute illness?’Parents of children aged 0-16 years presenting with non-urgent conditions were approached over an 18-month period to participate. Prior to discharge, focused interviews were used to explore the antecedent decision-making factors leading up to attendance and parents experience of urgent care were explored.Parents often experience complex journeys prior to attending the emergency department following multiple health care contacts and referrals from other providers. The findings challenge assumptions that have led to the criticism of parents for overuse of the health service and, instead, highlight the culpability of health care professionals and health systems in generating increased demand for urgent care.For most parents, attending the emergency department was a considered decision. Interaction with professionals had a significant effect on their experience. Health care professionals were powerful agents controlling resources and knowledge, but they were influenced by pressures and targets within the health service. The NHS is a complicated system that parents tried to navigate, but they were thwarted by its complexity and conflicting messages. When their child was unwell parents wanted a service that was simple to access, and that would offer a standard of care that would reassure and empower them to continue to care for their child

Primary nodal anthracosis identified by EBUS-TBNA as a cause of FDG PET/CT positive mediastinal lymphadenopathy.

Isolated mediastinal lymphadenopathy can result from a number of potentially serious aetiologies. Traditionally those presenting with mediastinal lymphadenopathy would undergo mediastinoscopy to elucidate a final diagnosis or receive empirical treatment. There is now increased utilization of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), in this setting. Five cases of mediastinal lymphadenopathy are presented here in which lymph node anthracosis was identified as the primary diagnosis using EBUS-TBNA. They were female, non-smokers presenting with non-specific symptoms, who retrospectively reported cooking over wood fires. Four were from South Asia. Three were investigated by F-18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scanning and increased signal was identified in the anthracotic nodes sampled. With expansion of PET/CT and EBUS-TBNA services it is likely that primary nodal anthracosis will be encountered more frequently and should be considered in the differential diagnosis of those with PET/CT positive lymphadenopathy. It may mimic pathologies including tuberculosis and malignancy, thus accurate sampling and follow-up are essential

Subcellular Epithelial HMGB1 Expression Is Associated with Colorectal Neoplastic Progression, Male Sex, Mismatch Repair Protein Expression, Lymph Node Positivity, and an 'Immune Cold' Phenotype Associated with Poor Survival.

New treatment targets are needed for colorectal cancer (CRC). We define expression of High Mobility Group Box 1 (HMGB1) protein throughout colorectal neoplastic progression and examine the biological consequences of aberrant expression. HMGB1 is a ubiquitously expressed nuclear protein that shuttles to the cytoplasm under cellular stress. HMGB1 impacts cellular responses, acting as a cytokine when secreted. A total of 846 human tissue samples were retrieved; 6242 immunohistochemically stained sections were reviewed. Subcellular epithelial HMGB1 expression was assessed in a CRC Tissue Microarray (n = 650), normal colonic epithelium (n = 75), adenomatous polyps (n = 52), and CRC polyps (CaP, n = 69). Stromal lymphocyte phenotype was assessed in the CRC microarray and a subgroup of CaP. Normal colonic epithelium has strong nuclear and absent cytoplasmic HMGB1. With progression to CRC, there is an emergence of strong cytoplasmic HMGB1 (p < 0.001), pronounced at the leading cancer edge within CaP (p < 0.001), and reduction in nuclear HMGB1 (p < 0.001). In CRC, absent nuclear HMGB1 is associated with mismatch repair proteins (p = 0.001). Stronger cytoplasmic HMGB1 is associated with lymph node positivity (p < 0.001) and male sex (p = 0.009). Stronger nuclear (p = 0.011) and cytoplasmic (p = 0.002) HMGB1 is associated with greater CD4+ T-cell density, stronger nuclear HMGB1 is associated with greater FOXP3+ (p < 0.001) and ICOS+ (p = 0.018) lymphocyte density, and stronger nuclear HMGB1 is associated with reduced CD8+ T-cell density (p = 0.022). HMGB1 does not directly impact survival but is associated with an 'immune cold' tumour microenvironment which is associated with poor survival (p < 0.001). HMGB1 may represent a new treatment target for CRC

Open-label add-on treatment trial of minocycline in fragile X syndrome

<p>Abstract</p> <p>Background</p> <p>Fragile X syndrome (FXS) is a disorder characterized by a variety of disabilities, including cognitive deficits, attention-deficit/hyperactivity disorder, autism, and other socio-emotional problems. It is hypothesized that the absence of the fragile X mental retardation protein (FMRP) leads to higher levels of matrix metallo-proteinase-9 activity (MMP-9) in the brain. Minocycline inhibits MMP-9 activity, and alleviates behavioural and synapse abnormalities in <it>fmr1 </it>knockout mice, an established model for FXS. This open-label add-on pilot trial was conducted to evaluate safety and efficacy of minocycline in treating behavioural abnormalities that occur in humans with FXS.</p> <p>Methods</p> <p>Twenty individuals with FXS, ages 13-32, were randomly assigned to receive 100 mg or 200 mg of minocycline daily. Behavioural evaluations were made prior to treatment (baseline) and again 8 weeks after daily minocycline treatment. The primary outcome measure was the Aberrant Behaviour Checklist-Community Edition (ABC-C) Irritability Subscale, and the secondary outcome measures were the other ABC-C subscales, clinical global improvement scale (CGI), and the visual analog scale for behaviour (VAS). Side effects were assessed using an adverse events checklist, a complete blood count (CBC), hepatic and renal function tests, and antinuclear antibody screen (ANA), done at baseline and at 8 weeks.</p> <p>Results</p> <p>The ABC-C Irritability Subscale scores showed significant improvement (p < 0.001), as did the VAS (p = 0.003) and the CGI (p < 0.001). The only significant treatment-related side effects were minor diarrhea (n = 3) and seroconversion to a positive ANA (n = 2).</p> <p>Conclusions</p> <p>Results from this study demonstrate that minocycline provides significant functional benefits to FXS patients and that it is well-tolerated. These findings are consistent with the <it>fmr1 </it>knockout mouse model results, suggesting that minocycline modifies underlying neural defects that account for behavioural abnormalities. A placebo-controlled trial of minocycline in FXS is warranted.</p> <p>Trial registration</p> <p>ClinicalTrials.gov Open-Label Trial NCT00858689.</p

A review of RCTs in four medical journals to assess the use of imputation to overcome missing data in quality of life outcomes

Background: Randomised controlled trials (RCTs) are perceived as the gold-standard method for evaluating healthcare interventions, and increasingly include quality of life (QoL) measures. The observed results are susceptible to bias if a substantial proportion of outcome data are missing. The review aimed to determine whether imputation was used to deal with missing QoL outcomes. Methods: A random selection of 285 RCTs published during 2005/6 in the British Medical Journal, Lancet, New England Journal of Medicine and Journal of American Medical Association were identified. Results: QoL outcomes were reported in 61 (21%) trials. Six (10%) reported having no missing data, 20 (33%) reported ≤ 10% missing, eleven (18%) 11%–20% missing, and eleven (18%) reported >20% missing. Missingness was unclear in 13 (21%). Missing data were imputed in 19 (31%) of the 61 trials. Imputation was part of the primary analysis in 13 trials, but a sensitivity analysis in six. Last value carried forward was used in 12 trials and multiple imputation in two. Following imputation, the most common analysis method was analysis of covariance (10 trials). Conclusion: The majority of studies did not impute missing data and carried out a complete-case analysis. For those studies that did impute missing data, researchers tended to prefer simpler methods of imputation, despite more sophisticated methods being available.The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Government Health Directorate. Shona Fielding is also currently funded by the Chief Scientist Office on a Research Training Fellowship (CZF/1/31)

A review of RCTs in four medical journals to assess the use of imputation to overcome missing data in quality of life outcomes

Peer reviewedPublisher PD

On the number of excursion sets of planar Gaussian fields

37 pages, 14 figures37 pages, 14 figures37 pages, 14 figure