Coagulation and anticoagulation in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is an incurable, progressive interstitial lung disease with a prognosis that is worse than that of many cancers. Epidemiological studies have demonstrated a link between IPF and thrombotic vascular events. Coagulation and fibrinolytic systems play central roles in wound healing and repair, processes hypothesised to be abnormal within the IPF lung. Animal models of pulmonary fibrosis have demonstrated an imbalance between thrombosis and fibrinolysis within the alveolar compartment, a finding that is also observed in IPF patients. A systemic prothrombotic state also occurs in IPF and is associated with increased mortality, but trials of anticoagulation in IPF have provided conflicting results. Differences in methodology, intervention and study populations may contribute to the inconsistent trial outcomes. The new oral anticoagulants have properties that may prove advantageous in targeting both thrombotic risk and progression of lung fibrosis

Helmet-mounted pilot night vision systems: Human factors issues

Helmet-mounted displays of infrared imagery (forward-looking infrared (FLIR)) allow helicopter pilots to perform low level missions at night and in low visibility. However, pilots experience high visual and cognitive workload during these missions, and their performance capabilities may be reduced. Human factors problems inherent in existing systems stem from three primary sources: the nature of thermal imagery; the characteristics of specific FLIR systems; and the difficulty of using FLIR system for flying and/or visually acquiring and tracking objects in the environment. The pilot night vision system (PNVS) in the Apache AH-64 provides a monochrome, 30 by 40 deg helmet-mounted display of infrared imagery. Thermal imagery is inferior to television imagery in both resolution and contrast ratio. Gray shades represent temperatures differences rather than brightness variability, and images undergo significant changes over time. The limited field of view, displacement of the sensor from the pilot's eye position, and monocular presentation of a bright FLIR image (while the other eye remains dark-adapted) are all potential sources of disorientation, limitations in depth and distance estimation, sensations of apparent motion, and difficulties in target and obstacle detection. Insufficient information about human perceptual and performance limitations restrains the ability of human factors specialists to provide significantly improved specifications, training programs, or alternative designs. Additional research is required to determine the most critical problem areas and to propose solutions that consider the human as well as the development of technology

Increased platelet reactivity in idiopathic pulmonary fibrosis is mediated by a plasma factor

Introduction Idiopathic Pulmonary Fibrosis (IPF) is a progressive, incurable fibrotic interstitial lung disease with a prognosis worse than many cancers. Its pathogenesis is poorly understood. Activated platelets can release pro-fibrotic mediators that have the potential to contribute to lung fibrosis. We determine platelet reactivity in subjects with IPF compared to age-matched controls. Methods Whole blood flow cytometry was used to measure platelet-monocyte aggregate formation, platelet P-selectin expression and platelet fibrinogen binding at basal levels and following stimulation with platelet agonists. A plasma swap approach was used to assess the effect of IPF plasma on control platelets. Results Subjects with IPF showed greater platelet reactivity than controls. Platelet P-selectin expression was significantly greater in IPF patients than controls following stimulation with 0.1 µM ADP (1.9% positive ±0.5 (mean ± SEM) versus 0.7%±0.1; p = 0.03), 1 µM ADP (9.8%±1.3 versus 3.3%±0.8; p<0.01) and 10 µM ADP (41.3%±4.2 versus 22.5%±2.6; p<0.01). Platelet fibrinogen binding was also increased, and platelet activation resulted in increased platelet-monocyte aggregate formation in IPF patients. Re-suspension of control platelets in plasma taken from subjects with IPF resulted in increased platelet activation compared to control plasma. Conclusions IPF patients exhibit increased platelet reactivity compared with controls. This hyperactivity may result from the plasma environment since control platelets exhibit increased activation when exposed to IPF plasma

Personal and social correlates of types of drug abuse in Dublin.

Significant differences were found between opioid takers and non-takers among referrals to Jervis Street Drug Advisory and Treatment Centre, Dublin, for the following variables: Sex, Age, Employment Status, Prior Court Appearance, Solitary drug taking. First drug taken abroad. Injection history. Physical complications associated with drug taking, and Maternal psychiatric status (for referrals aged under 21). Further analysis indicated 6 types of abuse associated with particular personal and social circumstances: (1) Minor tranquillisers, (2) Barbiturates only or with minor tranquillisers, (3) Opioids only or mainly, (4) Cannabis and/or L.S.D. only, (5) Poly-abuse excluding opioids, and (6) Poly-abuse including opioids.In broad social terms, these 6 groups may be seen as representing psychiatric or personal inadequacy-groups (1), (2) and (3), subcultural deviance-(5) and (6), and subcultural hedonism in the context of poor family relationships-(4). Groups most at risk were considered to be in the following order-(2), (3), (6),(1). Finally, cluster analyses, using unweighted and weighted variables, were employed to test the significance of distinctions based on types (3), (4), (5) and (6). In general, similar groups were obtained

Monopole clusters in Abelian projected gauge theories

We show that the monopole currents which one obtains in the maximally Abelian gauge of SU(2) fall into two quite distinct classes (when the volume is large enough). In each field configuration there is precisely one cluster that permeates the whole lattice volume. It has a current density and a magnetic screening mass that scale and it produces the whole of the string tension. The remaining clusters have a number density that follows an approximate power law proportional to the inverse cube of l where l is the length of the monopole world line in lattice units. These clusters are localised in space-time with radii which vary as the square root of l. In terms of the radius r these `lumps' have a scale-invariant distribution proportional to (dr/r . 1/{r^4}). Moreover they appear not to contribute at all to the string tension. The fact that they are scale-invariant at small distances would seem to rule out an instanton origin.Comment: LaTeX, 31 pages, 11 PostScript figures. Typo in Table 2 correcte

Bleomycin increases neutrophil adhesion to human vascular endothelial cells independently of upregulation of ICAM-1 and E-selectin

© 2016 Taylor & Francis. Aim of the Study: Bleomycin-induced lung disease is a serious complication of therapy characterized by alveolar injury, cytokine release, inflammatory cell recruitment, and eventually pulmonary fibrosis. The mechanisms underlying bleomycin-induced pulmonary fibrosis may be relevant to other progressive scarring diseases of the lungs. Pulmonary vascular endothelial cells are critically involved in immune cell extravasation at sites of injury through adhesion molecule expression and cytokine release. We sought to determine the effects of bleomycin on adhesion molecule expression and cytokine release by pulmonary vascular endothelial cells, and their functional relevance to inflammatory cell recruitment. Materials and Methods: The effects of pharmacologically relevant concentrations of bleomycin on adhesion molecule expression and cytokine release by human vascular endothelial cells in vitro were studied by flow cytometry, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay. A flow chamber model was used to assess the functional consequences on adhesion of flowing human neutrophils to endothelial cell monolayers. Results: Bleomycin increased intercellular adhesion molecule 1 (ICAM-1; CD54), vascular cell adhesion molecule (VCAM-1; CD106), and E-selectin (CD62E) expression, and increased monocyte chemoattractant protein (MCP-1) and interleukin (IL-8) release by endothelial cells. Increases in protein expression were accompanied by increased mRNA transcription. In contrast, there was no direct effect of bleomycin on the profibrotic cytokines transforming growth factor-beta (TGF-β), platelet-derived growth factor-BB (PDGF-BB), or endothelin-1. Under flow conditions, endothelial cells exposed to bleomycin supported increased neutrophil adhesion which was independent of ICAM-1 or E-selectin. Conclusion: Our findings demonstrate that bleomycin promotes endothelial-mediated inflammation and neutrophil adhesion. These mechanisms may contribute to the development of pulmonary fibrosis by supporting immune cell recruitment in the lungs

Irish drug abusers II: their psychological characteristics.

This is the second in a series of 3 articles based on a study of a cohort of Irish drug abusers. This article attempts to identify the psychological traits of drug abusers within the cohort. The cohort consists of 100 drug abusers who attend a drug advisory and treatment centre in Dublin for the first time between November 1977 and February 1979. Three psychosocial, scales (GEFT, NSQ, and PFS) were administered to each subject. Overall, the results indicate that subjects who participated in the study, while of average or above average intelligence, were poorly psychologically adjusted, characterised by a poor sense of identity, a high level of suggestibility and a tendency towards emotional dependence. Their overall level of intelligence was within or above the normal range

Connectome analysis for pre-operative brain mapping in neurosurgery.

OBJECT: Brain mapping has entered a new era focusing on complex network connectivity. Central to this is the search for the connectome or the brains 'wiring diagram'. Graph theory analysis of the connectome allows understanding of the importance of regions to network function, and the consequences of their impairment or excision. Our goal was to apply connectome analysis in patients with brain tumours to characterise overall network topology and individual patterns of connectivity alterations. METHODS: Resting-state functional MRI data were acquired using multi-echo, echo planar imaging pre-operatively from five participants each with a right temporal-parietal-occipital glioblastoma. Complex networks analysis was initiated by parcellating the brain into anatomically regions amongst which connections were identified by retaining the most significant correlations between the respective wavelet decomposed time-series. RESULTS: Key characteristics of complex networks described in healthy controls were preserved in these patients, including ubiquitous small world organization. An exponentially truncated power law fit to the degree distribution predicted findings of general network robustness to injury but with a core of hubs exhibiting disproportionate vulnerability. Tumours produced a consistent reduction in local and long-range connectivity with distinct patterns of connection loss depending on lesion location. CONCLUSIONS: Connectome analysis is a feasible and novel approach to brain mapping in individual patients with brain tumours. Applications to pre-surgical planning include identifying regions critical to network function that should be preserved and visualising connections at risk from tumour resection. In the future one could use such data to model functional plasticity and recovery of cognitive deficits.S. J. P. received funding for this study through a National Institute for Health Research (NIHR) (UK) – Clinician Scientist Award (Ref: NIHR/CS/009/011). M. G. H. is funded by the Wellcome Trust Neuroscience in Psychiatry Network with additional support from the National Institute for Health Research Cambridge Biomedical Research Centre. This paper presents independent research funded by the NIHR.This is the final version of the article. It first appeared from Taylor & Francis via http://dx.doi.org/10.1080/02688697.2016.120880