Is mitochondrial dysfunction a driving mechanism linking COPD to nonsmall cell lung carcinoma?

© ERS 2017. Chronic obstructive pulmonary disease (COPD) patients are at increased risk of developing nonsmall cell lung carcinoma, irrespective of their smoking history. Although the mechanisms behind this observation are not clear, established drivers of carcinogenesis in COPD include oxidative stress and sustained chronic inflammation. Mitochondria are critical in these two processes and recent evidence links increased oxidative stress in COPD patients to mitochondrial damage. We therefore postulate that mitochondrial damage in COPD patients leads to increased oxidative stress and chronic inflammation, thereby increasing the risk of carcinogenesis. The functional state of the mitochondrion is dependent on the balance between its biogenesis and degradation (mitophagy). Dysfunctional mitochondria are a source of oxidative stress and inflammasome activation. In COPD, there is impaired translocation of the ubiquitin-related degradation molecule Parkin following activation of the Pink1 mitophagy pathway, resulting in excessive dysfunctional mitochondria. We hypothesise that deranged pathways in mitochondrial biogenesis and mitophagy in COPD can account for the increased risk in carcinogenesis. To test this hypothesis, animal models exposed to cigarette smoke and developing emphysema and lung cancer should be developed. In the future, the use of mitochondria-based antioxidants should be studied as an adjunct with the aim of reducing the risk of COPD-associated cancer

Using technology to deliver cancer follow-up : a systematic review

Peer reviewedPublisher PD

Increased Oxidative Burden Associated with Traffic Component of Ambient Particulate Matter at Roadside and Urban Background Schools Sites in London

As the incidence of respiratory and allergic symptoms has been reported to be increased in children attending schools in close proximity to busy roads, it was hypothesised that PM from roadside schools would display enhanced oxidative potential (OP). Two consecutive one-week air quality monitoring campaigns were conducted at seven school sampling sites, reflecting roadside and urban background in London. Chemical characteristics of size fractionated particulate matter (PM) samples were related to the capacity to drive biological oxidation reactions in a synthetic respiratory tract lining fluid. Contrary to hypothesised contrasts in particulate OP between school site types, no robust size-fractionated differences in OP were identified due high temporal variability in concentrations of PM components over the one-week sampling campaigns. For OP assessed both by ascorbate (OPAA m−3) and glutathione (OPGSH m−3) depletion, the highest OP per cubic metre of air was in the largest size fraction, PM1.9–10.2. However, when expressed per unit mass of particles OPAA µg−1 showed no significant dependence upon particle size, while OPGSH µg−1 had a tendency to increase with increasing particle size, paralleling increased concentrations of Fe, Ba and Cu. The two OP metrics were not significantly correlated with one another, suggesting that the glutathione and ascorbate depletion assays respond to different components of the particles. Ascorbate depletion per unit mass did not show the same dependence as for GSH and it is possible that other trace metals (Zn, Ni, V) or organic components which are enriched in the finer particle fractions, or the greater surface area of smaller particles, counter-balance the redox activity of Fe, Ba and Cu in the coarse particles. Further work with longer-term sampling and a larger suite of analytes is advised in order to better elucidate the determinants of oxidative potential, and to fuller explore the contrasts between site types.\ud \u

Semi-analytical approach to magnetized temperature autocorrelations

The cosmic microwave background (CMB) temperature autocorrelations, induced by a magnetized adiabatic mode of curvature inhomogeneities, are computed with semi-analytical methods. As suggested by the latest CMB data, a nearly scale-invariant spectrum for the adiabatic mode is consistently assumed. In this situation, the effects of a fully inhomogeneous magnetic field are scrutinized and constrained with particular attention to harmonics which are relevant for the region of Doppler oscillations. Depending on the parameters of the stochastic magnetic field a hump may replace the second peak of the angular power spectrum. Detectable effects on the Doppler region are then expected only if the magnetic power spectra have quasi-flat slopes and typical amplitude (smoothed over a comoving scale of Mpc size and redshifted to the epoch of gravitational collapse of the protogalaxy) exceeding 0.1 nG. If the magnetic energy spectra are bluer (i.e. steeper in frequency) the allowed value of the smoothed amplitude becomes, comparatively, larger (in the range of 20 nG). The implications of this investigation for the origin of large-scale magnetic fields in the Universe are discussed. Connections with forthcoming experimental observations of CMB temperature fluctuations are also suggested and partially explored.Comment: 40 pages, 13 figure

Binary and Millisecond Pulsars at the New Millennium

We review the properties and applications of binary and millisecond pulsars. Our knowledge of these exciting objects has greatly increased in recent years, mainly due to successful surveys which have brought the known pulsar population to over 1300. There are now 56 binary and millisecond pulsars in the Galactic disk and a further 47 in globular clusters. This review is concerned primarily with the results and spin-offs from these surveys which are of particular interest to the relativity community.Comment: 59 pages, 26 figures, 5 tables. Accepted for publication in Living Reviews in Relativity (http://www.livingreviews.org

Spectroscopic Evidence for an Oxazolone Structure in Anionic b-Type Peptide Fragments

Infrared spectra of anionic b-type fragments generated by collision induced dissociation (CID) from deprotonated peptides are reported. Spectra of the b2 fragments of deprotonated AlaAlaAla and AlaTyrAla have been recorded over the 800–1800 cm–1 spectral range by multiple-photon dissociation (MPD) spectroscopy using an FTICR mass spectrometer in combination with the free electron laser FELIX. Structural characterization of the b-type fragments is accomplished by comparison with density functional theory calculated spectra at the B3LYP/6-31++G(d,p) level for different isomeric structures. Although diketopiperazine structures represent the energetically lowest isomers, the IR spectra suggest an oxazolone structure for the b2 fragments of both peptides. Deprotonation is shown to occur on the oxazolone α-carbon, which leads to a conjugated structure in which the negative charge is practically delocalized over the entire oxazolone ring, providing enhanced gas-phase stability

2.5PN kick from black-hole binaries in circular orbit: Nonspinning case

Using the Multipolar post-Minskowskian formalism, we compute the linear momentum flux from black-hole binaries in circular orbits and having no spins. The total linear momentum flux contains various types of instantaneous (which are functions of the retarded time) and hereditary (which depends on the dynamics of the binary in the past) terms both of which are analytically computed. In addition to the inspiral contribution, we use a simple model of plunge to compute the kick or recoil accumulated during this phase.Comment: To appear in Proceedings of "Relativity and Gravitation - 100 Years after Einstein in Prague" Ed. J. Bicak (2013

Analysis of dental care of children receiving comprehensive care under general anaesthesia at a teaching hospital in England

Objectives: This study aimed to analyse the characteristics of comprehensive dental care provided under general anaesthesia (CDGA) and to review the additional treatment required by children over the 6 years subsequent to CDGA. Method: Information collected from hospital records for the 6-year period following the first CDGA included the types of dental treatment performed at CDGA, the return rates for follow-up appointments, further treatment required subsequent to CDGA and the types of dental treatment performed at repeat DGA. Results: The study population consisted of 263 children, of whom 129 had a significant medical history, with mean age of 6.7 years. The results revealed that the waiting time for CDGA was significantly shorter in children who had a significant medical history, with 49 % being admitted for CDGA within 3 months of pre-GA assessment, as compared to 29 % of healthy children. 67 % of children had follow-up care recorded, with a slightly higher proportion of children with significant medical history returning for follow-up [70 % (90/129)] compared with 65 % (87/134) of healthy children. Re-treatment rates were 34 % (88/263), the majority of cases being treated under local analgesia (42/88). 34 of 263 children had repeat DGA (12.9 %). Of these 71 % (24/34) were children with significant medical history. The mean age at repeat DGA was 9 years. In 25 of 34 children (74 %), repeat DGA was due to trauma, oral pathology, supernumerary removal, hypomineralized teeth or new caries of previously sound or un-erupted teeth at CDGA. The ratio of extraction over restoration (excluding fissure sealants) performed at repeat DGA was 2.8, compared with the ratio of 1.3 in the initial CDGA. Conclusions: There was a higher ratio of extraction over restorations at the repeat DGA. This suggests that the prescribed treatments at repeat DGA were more aggressive as compared to the initial CDGA in 1997. The majority of the treatment required at repeat DGA was to treat new disease

Leadership and decision-making practices in public versus private universities in Pakistan

The goal of this study is to examine differences in leadership and decision-making practices in public and private universities in Pakistan, with a focus on transformational leadership (TL) and participative decision-making (PDM). We conducted semi-structured interviews with 46 deans and heads of department from two public and two private universities in Pakistan. Our findings indicate that leadership and decision-making practices are different in public and private universities. While differences were observed in all six types of TL-behaviour, the following three approaches emerged to be crucial in both public and private universities: (1) articulating a vision, (2) fostering the acceptance of group goals, and (3) high-performance expectations. In terms of PDM, deans and heads of department in public and private universities adopt a collaborative approach. However, on a practical level this approach is limited to teacher- and student-related matters. Overall, our findings suggest that the leadership and decision-making practices in Pakistani public and private universities are transformational and participative in nature