Daily activity during stability and exacerbation of chronic obstructive pulmonary disease

BACKGROUND: During most COPD exacerbations, patients continue to live in the community but there is little information on changes in activity during exacerbations due to the difficulties of obtaining recent, prospective baseline data. METHODS: Patients recorded on daily diary cards any worsening in respiratory symptoms, peak expiratory flow (PEF) and the number of steps taken per day measured with a Yamax Digi-walker pedometer. Exacerbations were defined by increased respiratory symptoms and the number of exacerbations experienced in the 12 months preceding the recording of daily step count used to divide patients into frequent (> = 2/year) or infrequent exacerbators. RESULTS: The 73 COPD patients (88% male) had a mean (+/-SD) age 71(+/-8) years and FEV1 53(+/-16)% predicted. They recorded pedometer data on a median 198 days (IQR 134-353). At exacerbation onset, symptom count rose by 1.9(+/-1.3) and PEF fell by 7(+/-13) l/min. Mean daily step count fell from 4154(+/-2586) steps/day during a preceding baseline week to 3673(+/-2258) step/day during the initial 7 days of exacerbation (p = 0.045). Patients with larger falls in activity at exacerbation took longer to recover to stable level (rho = -0.56; p < 0.001). Recovery in daily step count was faster (median 3.5 days) than for exacerbation symptoms (median 11 days; p < 0.001). Recovery in step count was also faster in untreated compared to treated exacerbation (p = 0.030).Daily step count fell faster over time in the 40 frequent exacerbators, by 708 steps/year, compared to 338 steps/year in 33 infrequent exacerbators (p = 0.002). CONCLUSIONS: COPD exacerbations reduced physical activity and frequent exacerbations accelerate decline in activity over time

Correction: How Long Is Too Long in Contemporary Peer Review? Perspectives from Authors Publishing in Conservation Biology Journals.

<p>Correction: How Long Is Too Long in Contemporary Peer Review? Perspectives from Authors Publishing in Conservation Biology Journals</p

Inflammatory thresholds and the species-specific effects of colonising bacteria in stable chronic obstructive pulmonary disease

There has been increasing interest in the use of newer, culture-independent techniques to study the airway microbiome of COPD patients. We investigated the relationships between the three common potentially pathogenic microorganisms (PPMs) Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis, as detected by quantitative PCR (qPCR), and inflammation and health status in stable patients in the London COPD cohort

Detection of catalytic intermediates at an electrode surface during carbon dioxide reduction by an earth-abundant catalyst

The electrocatalytic reduction of CO2 offers a sustainable route to the many carbon fuels and feedstocks that society relies on. [fac-Mn(bpy)(CO)3Br] (bpy, 2,2-bipyridine) is one of the most promising and intensely studied CO2 reduction electrocatalysts. However, the catalytic mechanism remains experimentally unproven and many key intermediates of the prototypical catalyst have not been observed. Here we report the use of vibrational sum-frequency generation spectroscopy to study the catalytic intermediates during CO2 reduction in situ at the electrode surface. We explore the complex applied-potential and acid-dependent mechanistic pathways and provide evidence of the theoretically derived mechanisms. Demonstrating the ability to detect the key species that are only transiently present at the electrode surface is important as the need for an improved mechanistic understanding is a common theme throughout the field of molecular electrocatalysis

The effect of Ku on telomere replication time is mediated by telomere length but is independent of histone tail acetylation

Peer reviewedPublisher PD

RNA sequencing and lipidomics uncovers novel pathomechanisms in recessive X-linked ichthyosis

Recessive X-linked ichthyosis (RXLI), a genetic disorder caused by deletion or point mutations of the steroid sulfatase (STS) gene, is the second most common form of ichthyosis. It is a disorder of keratinocyte cholesterol sulfate retention and the mechanism of extracutaneous phenotypes such as corneal opacities and attention deficit hyperactivity disorder are poorly understood. To understand the pathomechanisms of RXLI, the transcriptome of differentiated primary keratinocytes with STS knockdown was sequenced. The results were validated in a stable knockdown model of STS, to confirm STS specificity, and in RXLI skin. The results show that there was significantly reduced expression of genes related to epidermal differentiation and lipid metabolism, including ceramide and sphingolipid synthesis. In addition, there was significant downregulation of aldehyde dehydrogenase family members and the oxytocin receptor which have been linked to corneal transparency and behavioural disorders respectively, both of which are extracutaneous phenotypes of RXLI. These data provide a greater understanding of the causative mechanisms of RXLI’s cutaneous phenotype, and show that the keratinocyte transcriptome and lipidomics can give novel insights into the phenotype of patients with RXLI

The Ctf18 RFC-like complex positions yeast telomeres but does not specify their replication time

Peer reviewedPreprin

The need for speed in a crisis discipline: Perspectives on peer-review duration and implications for conservation science

Scholarly peer review relies on rigorous yet fair assessments of articles by qualified referees in a timely manner. We considered the extent to which a prolonged peer-review process can delay the dissemination of results in a conservation context by combining insight from a survey with our own perspectives. A survey of authors who published peer-reviewed articles in biodiversity and conservation in 2012 and 2013 yielded 461 responses from participants in 119 countries. Approximately 44% of respondents thought that slow review times might hamper conservation, while only ~5% provided specific examples of how slow reviews had actually impeded conservation actions or policy formation. When queried about the value of expediting the review process for studies of high policy or conservation relevance, ca. 1/3 of respondents thought it was a worthwhile idea in principle, though mechanics of implementing such practices are unclear. Author self-identification of potentially important papers could lead to requesting a rapid review provided that a paper meets certain criteria-an approach already used by some generalist journals. Given the urgency of many conservation-oriented initiatives, we encourage the entire editor - ial team (staff, editors, referees, authors) to make a concerted effort towards improving the speed of the peer-review process while maintaining quality. Such efforts would reflect the notion that timeliness is a key component of scientific relevance to practitioners and policy makers in a crisis discipline. We conclude that there is a 'need for speed' and advocate that rapid, rigorous and thorough peer review can be accomplished and can provide collective benefits to the scientific community and global biodiversity