The Adiabatic Invariance of the Action Variable in Classical Dynamics

We consider one-dimensional classical time-dependent Hamiltonian systems with quasi-periodic orbits. It is well-known that such systems possess an adiabatic invariant which coincides with the action variable of the Hamiltonian formalism. We present a new proof of the adiabatic invariance of this quantity and illustrate our arguments by means of explicit calculations for the harmonic oscillator. The new proof makes essential use of the Hamiltonian formalism. The key step is the introduction of a slowly-varying quantity closely related to the action variable. This new quantity arises naturally within the Hamiltonian framework as follows: a canonical transformation is first performed to convert the system to action-angle coordinates; then the new quantity is constructed as an action integral (effectively a new action variable) using the new coordinates. The integration required for this construction provides, in a natural way, the averaging procedure introduced in other proofs, though here it is an average in phase space rather than over time.Comment: 8 page

Interstitial lung disease incidence and mortality in the United Kingdom and the European Union: an observational study, 2001-2017

Objective: To compare the trends in age-standardised incidence and mortality from interstitial lung diseases (ILD) in the United Kingdom (UK) and the European Union (EU). Design: Observational study using data obtained from the Global Burden of Disease Study. Setting and Participants: Residents of the UK and of the twenty-seven EU countries. Main outcome measures: ILD age-standardised incidence rates per 100 000 (ASIR), age-standardised death rates per 100 000 (ASDR), and mortality-to-incidence ratio (MIRs) are presented for males and females separately for each country, for the years 2001–2017. Trends were analysed using Joinpoint regression analysis. Results: For men, in 2017, the median incidence of ILD was 7.22 (IQR 5.57–8.96) per 100 000 population. For women, in 2017, the median incidence of ILD was 4.34 (IQR 3.36–6.29) per 100 000 population. For men, in 2017, the median ASDR attributed to ILD was 2.04 (IQR 1.13–2.71) per 100 000 population. For women, the median ASDR in 2017 for ILD was 1.02 (0.68–1.37) per 100 000 population. There was an overall increase in ASDR during the observation period with a median change of +20.42% (IQR 5.44–31.40) for men and an increase of +15.44% (IQR −1.01–31.52) for women. Despite increases in mortality over the entire observation period, there were decreasing mortality trends in the majority of countries at the end of the observation period (75% for men and 86% for women). Conclusion: Over the past two decades, there have been increases in the incidence and mortality of interstitial lung diseases in Europe. The most recent trends, however, demonstrate decreases in mortality from ILD in the majority of European countries for both men and women. These data support the ongoing improvements in the diagnosis and management of ILD

Neurophysiology

Contains reports on eight research projects.Bell Telephone Laboratories, Inc.Teagle Foundation, Inc.National Science Foundation (Grant GP-2495)National Institutes of Health (Grants MH-04737-04)National Institutes of Health (NB-04985-01)U. S. Air Force. Aeronautical Systems Division (Contract AF 33(615)-1747)U. S. Air Force. Cambridge Research Laboratories (Contract AF19(628)-3807)U. S. Air Force. Electronic Systems Division (Contract AF19(628)-4147)National Aeronautics and Space Administration (Grant NsG-496

Relationship of CD146 expression to secretion of interleukin (IL)-17, IL-22 and interferon-γ by CD4(+) T cells in patients with inflammatory arthritis.

Expression of the adhesion molecule, CD146/MCAM/MelCAM, on T cells has been associated with recent activation, memory subsets and T helper type 17 (Th17) effector function, and is elevated in inflammatory arthritis. Th17 cells have been implicated in the pathogenesis of rheumatoid arthritis (RA) and spondyloarthritides (SpA). Here, we compared the expression of CD146 on CD4(+) T cells between healthy donors (HD) and patients with RA and SpA [ankylosing spondylitis (AS) or psoriatic arthritis (PsA)] and examined correlations with surface markers and cytokine secretion. Peripheral blood mononuclear cells (PBMC) were obtained from patients and controls, and synovial fluid mononuclear cells (SFMC) from patients. Cytokine production [elicited by phorbol myristate acetate (PMA)/ionomycin] and surface phenotypes were evaluated by flow cytometry. CD146(+) CD4(+) and interleukin (IL)-17(+) CD4(+) T cell frequencies were increased in PBMC of PsA patients, compared with HD, and in SFMC compared with PBMC. CD146(+) CD4(+) T cells were enriched for secretion of IL-17 [alone or with IL-22 or interferon (IFN)-γ] and for some putative Th17-associated surface markers (CD161 and CCR6), but not others (CD26 and IL-23 receptor). CD4(+) T cells producing IL-22 or IFN-γ without IL-17 were also present in the CD146(+) subset, although their enrichment was less marked. Moreover, a majority of cells secreting these cytokines lacked CD146. Thus, CD146 is not a sensitive or specific marker of Th17 cells, but rather correlates with heterogeneous cytokine secretion by subsets of CD4(+) helper T cells.This is the final version. It was first published by Wiley at http://onlinelibrary.wiley.com/doi/10.1111/cei.12434/abstract

Spatial Models of Abundance and Habitat Preferences of Commerson’s and Peale’s Dolphin in Southern Patagonian Waters

Funding: This research was possible with the support of the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Funding for travel to and accommodation for NAD in Aberdeen, Scotland was provided by CONICET and Cetacean Society International. The work of NAD was part of a postdoctoral fellowship funded by CONICET. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS)

Background: Amyotrophic lateral sclerosis (ALS), a common late-onset neurodegenerative disease, is associated with fronto-temporal dementia (FTD) in 3-10% of patients. A mutation in CHMP2B was recently identified in a Danish pedigree with autosomal dominant FTD. Subsequently, two unrelated patients with familial ALS, one of whom also showed features of FTD, were shown to carry missense mutations in CHMP2B. The initial aim of this study was to determine whether mutations in CHMP2B contribute more broadly to ALS pathogenesis. Methodology/Principal Findings: Sequencing of CHMP2B in 433 ALS cases from the North of England identified 4 cases carrying 3 missense mutations, including one novel mutation, p. Thr104Asn, none of which were present in 500 neurologically normal controls. Analysis of clinical and neuropathological data of these 4 cases showed a phenotype consistent with the lower motor neuron predominant (progressive muscular atrophy (PMA)) variant of ALS. Only one had a recognised family history of ALS and none had clinically apparent dementia. Microarray analysis of motor neurons from CHMP2B cases, compared to controls, showed a distinct gene expression signature with significant differential expression predicting disassembly of cell structure; increased calcium concentration in the ER lumen; decrease in the availability of ATP; down-regulation of the classical and p38 MAPK signalling pathways, reduction in autophagy initiation and a global repression of translation. Transfection of mutant CHMP2B into HEK-293 and COS-7 cells resulted in the formation of large cytoplasmic vacuoles, aberrant lysosomal localisation demonstrated by CD63 staining and impairment of autophagy indicated by increased levels of LC3-II protein. These changes were absent in control cells transfected with wild-type CHMP2B. Conclusions/Significance: We conclude that in a population drawn from North of England pathogenic CHMP2B mutations are found in approximately 1% of cases of ALS and 10% of those with lower motor neuron predominant ALS. We provide a body of evidence indicating the likely pathogenicity of the reported gene alterations. However, absolute confirmation of pathogenicity requires further evidence, including documentation of familial transmission in ALS pedigrees which might be most fruitfully explored in cases with a LMN predominant phenotype

Parenting ‘gifted and talented’ children in urban areas: Parents' voices

This is the author's accepted manuscript. The final published article is available from the link below. Copyright © 2014 by SAGE Publications.International evidence demonstrates the importance of engaging parents in the education of their ‘high-potential’ children, yet limited research has focused on the involvement of parents from differing economic strata/backgrounds. The current study explored the dilemmas of parenting academically high-ability children from economically deprived urban areas in the UK. Data were gathered from a sample of parents whose children attended a university-based sustained intervention programme for designated ‘gifted’ pupils aged 12–16. Parental perceptions were sought in relation to (a) the usefulness/impact of the intervention programme, (b) parents’ aspirations for their children growing up in economically deprived urban areas and (c) parents’ views on the support provided by the extended family, peer groups and the wider community. The findings have significant implications for both policy and practice and, more specifically, for engaging parents in intervention programmes offered by universities and schools to children in order to increase their access to higher education and for enhancing their life chances

Failure or relapse predictors for the STREAM Stage 1 short regimen for RR-TB

BACKGROUND: STREAM (Standardised Treatment Regimens of Anti-tuberculosis drugs for Multidrug-Resistant Tuberculosis) Stage 1 demonstrated non-inferior efficacy of a short regimen for rifampicin-resistant TB (RR-TB) compared to a long regimen as recommended by the WHO. The present paper analyses factors associated with a definite or probable failure or relapse (FoR) event in participants receiving the Short regimen.METHODS: This analysis is restricted to 253 participants allocated to the Short regimen and is based on the protocol-defined modified intention to treat (mITT) population. Multivariable Cox regression models were built using backwards elimination with an exit probability of P = 0.157, equivalent to the Akaike Information Criterion, to identify factors independently associated with a definite or probable FoR event.RESULTS: Four baseline factors were identified as being significantly associated with the risk of definite or probable FoR (male sex, a heavily positive baseline smear grade, HIV co-infection and the presence of costophrenic obliteration). There was evidence of association of culture positivity at Week 8 and FoR in a second model and Week 16 smear positivity, presence of diabetes and of smoking in a third model.CONCLUSION: The factors associated with FoR outcomes identified in this analysis should be considered when determining the optimal shortened treatment regimen